Neuroanatomy

NEUROANATOMY
NINTH EDITION
ANDRE PARENT
CARPENTER’S
HUMAN
NEUROANATOMY Ninth Edition
CARPENTER’S
HUMAN
NEUROANATOMY Ninth Edition
Andre Parent, Ph.D.

Departement d'Anatomie
Faculte de Medecine
Universite Laval
Quebec, Canada
Williams & Wilkins

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Printed in the United States of America
First Edition 194.1
- -
Library of Congress Cataloging in Publication Data
Parent , Andre, 1944-

—
Human neuroanatomay / Andre Parent. 9th ed .
p. cm.
Rev. ed . of : Human neuroanatomy / Malcolm B. Carpenter, Jerome
Sutin. 8th ed . cl 983.
Includes bibliographical references and index.
ISBN 0-683-06752-4
1. Neuroanatomv. I . Carpenter, Malcolm B. Human neuroanatomv .
II. Title.
IDNLM: 1 . Nervous System —anatomy & histology. WL 101 P228h
19951
—
QM 451.T7 1995
611 '.8 dc20
DNLM / DLC
for Library of Congress 94-40506
CIP
96
1 2345678910
To my late father , Lucien Parent , who, with very little means , taught me
that knowledge is our destiny .
Et quant a la cognoissance des faicts de nature, je veux que lu t‘ y adonne curieusement: qu' il // ' y ait
mer , riviere , n y fontaine , dont tu ne cognoisse les poissons; tous les oiseaux de I' air , tous les arbres , les
arbustes et fructices des forets . . . Par frequente anatomies , acquiers toy parfaicte cognoissance. . .. Je
voye un abysme de science . . . Mais science sans conscience n’est que ruine de 1' ame.
Francois Rabelais, 1554

And as for knowledge of the facts of nature , I want you to devote yourself with curiosity: let there be no
sea , river nor fountain of which you do not know its fish; all the birds in the air , all the trees , all the
shrubs and fruits of the forests . . . By frequent dissections , acquire perfect knowledge . . . I feel a well of
science . . . But science without conscience is nothing but ruin of the soul .
Franqois Rabelais, 1554
vi
Preface
In the midst of the Decade of the Brain , attempts dated with the addition of more than 500 new
to summarize the current state of knowledge references. Most of the references to classic
about the anatomical and functional organi- studies have been retained , however, largely
zation of the nervous system has become a gi - because of their historical importance and
gantic task. Several thousand researchers also because they can no longer be found in
around the world are currently applying ever any current textbook. Thus, Human Neu -
more powerful neurobiological tools to un- roanatomy represents a unique repository of
ravel the complexities of the brain . The ap- over 3000 references to both historically sig-
proach is frankly multidisciplinary, involving nificant contributions and recent break -
techniques that range from genetics and mol- throughs in the neurosciences. Furthermore,
ecular biology to behavioral analyses and the chapters have been regrouped in distinct
neuropathology. Initiatives combining neuro- sections with new subheadings that empha -
sciences and informatics, such as The Human size the content and major conclusion of each
Brain Project , have helped to acquire, store, section . Over 180 new or revised illustrations
manipulate, analyze, integrate and , above all, have been added , many in the form of com -
share data derived from brain and behavioral puter-generated diagrams or drawings,
experiments. The joint effort of neuroscien - which students have found very useful in the
tists throughout the world has yielded a past. New sections on the molecular aspect of
wealth of knowledge whose detailed cover- neuronal and glial functions have also been
age would be well beyond the scope of this added as this type of information is essential
book. This knowledge has given rise to novel to understand properly the various basic neu -
concepts about neural organization and func- ronal functions in both normal and pathologi-
tion, and has also opened new therapeutic av- cal conditions. Information concerning the lo-
enues for some of the most devastating afflic- calization and roles of neurotransmitters and
tions of the brain and spinal cord . In the their highly specific receptors in the nervous
nervous system , however, structural organi- system has been given a high priority in this
zation is central to most functional concepts, book because a proper knowledge of chemi -
and this is what this book is all about. cal anatomy has become essential to under-
The Ninth Edition of Human Neuroanatomy stand the current views about neural func-
is an attempt to provide medical students, as tions. Finally, an effort was made to add as
well as graduate students in neuroscience many clinical notes and functional correla -
and neurology / neurosurgery residents, with tions as possible to emphasize the importance
a general guide to the structural and func- of a proper knowledge of neuroanatomy. In
tional organization of the nervous system . this context, particular attention was paid to
The book describes the major neuronal sys- neuropathological studies of normal aging
tems that compose the brain, spinal cord , and versus neurodegenerative diseases, such as
peripheral nervous system in the light of the Alzheimer's, Hutington's, and Parkinson 's
most recent concepts about neural organiza- diseases, because these investigations have
tion . In contrast to most other neuroscience shed new light on how the nervous system
texts, where there is a clear tendency toward works in both health and disease.
reductionism, 1 have tried as much as possi- I am immensely indebted to the previous
ble to provide more general and systematic authors who have contributed to Human
views of the organization of the nervous sys- Neuroanatomy since its inception in May of
tem so as to maximally help those students 1943. Among those are Professors Adolph
with clinical concerns. Elwyn, Oliver S. Strong, Raymond Truex,
There have been major changes in both the Jerome Sutin, and, above all, Malcom B. Car-
format and content of the book over the pre- penter, Professor and Chairman Emeritus,
vious edition published 12 years ago. Each Department of Anatomy, F. Edward Hebert
chapter has been entirely revised and up- School of Medicine, Services University of
vii
Health Science, Bethesda , Maryland . Despite mers and are still reproduced in the present
a ve ry active career in both research and edition of Human Neuroanatomy. The same
teaching, Dr. Carpenter has contributed sig- applies to the beautiful drawings made by
nificantly to Human Neuroanatomy , which has Mr. Robert J . Desmarest who worked for
become the most important reference book in many years in close collaboration with Dr.
the field under his expert guidance. M B. Carpenter. Most of the new illustrations
1 also want to express my deep gratitude for this edition were prepared by Mrs. Louise
to several colleagues from various American Bertrand of the Neurobiology Research Cen -
and Canadian Universities, including a fair ter at Laval University. Her skill, talent , and
number of neuroscientists from the Neurobi- total devotion to her work are greatly ac-
ology Research Center at Laval University , knowledged .
who have generously supplied illustrations Thanks are also due to the unfailing sup-
for this edition . Their names and specific con- port of Mrs. Carole Ernond who was respon-
tributions are indicated in appropriate sec- sible for many aspects of the production of
tions of the text . Thanks are also due to my this book, including the preparation of photo-
graduate students: Ali Charara , Pierre-Yves graphic illustrations, proof reading and text
Cote, Luc De Bellefeuille, Celine Desjardins, scanning. I also acknowledge the secretarial
Lili- Naz Hazrati, Brigitte Lavoie, and Abbas help of Mrs. Suzanne Bilodeau and of my
Sadikot, from whom 1 borrowed various pho- wife, Doris Parent . Finally, I express my deep
tomicrographs and drawings. gratitude to Williams & Wilkins and espe-
Many of the superb illustrations from Pro- cially to Pat Coryell and Linda Napora , for
fessor Fred A. Metier's Neuroanatomy , pub- their patience, support, and expert handling
lished in 1948, were made by Mr. Ivan Sum- of this vast project.
viii
Contents
Section I Regional Anatomy , Development, and
Blood Supply of the Neuraxis
1 Meninges and Cerebrospinal Fluid 3

Meninges 3
Cerebrospinal Fluid 14
Barriers Related to the Brain 16
Circumventricular Organs 21
2 Regional Anatomy of the Brain 25

Subdivisions of the Brain 25
Cerebral Hemispheres 25
Basal Ganglia 41
Lateral Ventricles 42
Brainstem 45
Diencephalon 50
Cerebellum 52
Brain Imaging 54
3 Development of the Nervous System 65

Determination and Differentiation 65
Formation of Neural Tube 65
Neural Crest 67
Histogenesis of Neural Tube 69
Neurons 69
Glial Cells 73
Spinal Cord 73
Brain 77
Congenital Anomalies .90
4 Blood Supply of the Central Nervous System 93

Blood Supply of the Spinal Cord 94
Blood Supply of the Brain 98
Basal Ganglia. Internal Capsule and Diencephalon 112
Vertebral Basilar System 113
Arteries of the Dura Mater 119
Cerebral Veins and Venous Sinuses 120
Section II Neurohistology and Neurocytology

5 Neurons 131
Neurons as Signaling Unit 131
Neurobiological Tools 134
Neuronal Diversity 144
Neuronal Cytoskeleton 146
Nerve Cell Body 148
Synthesis of Neuronal Proteins 157
Signaling Molecules 159
Axons 162
Synapses 172
Axoplasmic Transport 181
ix
Degeneration of Nerve Fibers 183
Regeneration and Plasticity 186
6 Neuroglia 199
Changing Concept of Neuroglia .. . . 199
General Features and Cell Lineage 200
Astrocytes 203
Oligodendrocytes 211
Microglia 214
Ependyma 218
Choroid Epithelium 224
Section III Peripheral Nervous System

7 Receptors and Effectors 235
Sensory Receptors 235
Receptors' Diversities 237
Sensory Receptors and Sensory Modalities 252
Effectors 255
8 Spinal Nerves and Peripheral Innervation 262

Peripheral Nervous System 262
Segmental Innervation 268
Peripheral Innervation 273
Functional Considerations 287
9 Autonomic Nervous System 293

Tripartite Integrated System 293
Pre- and Postganglionic Neurons ... 296
Sympathetic System 299
Parasympathetic System 301
Enteric System 302
Visceral Afferent Fibers 303
Structure of Autonomic Ganglia ... 304
Chemical Anatomy 306
Denervation Sensitization 311
Central Autonomic Pathways 314
Section IV Spinal Cord

10 Spinal Cord: Regional Anatomy and Internal Structure .. 325
Topographic Organization 325
Internal Structure 329
Primary Afferent Fibers 351
Chemoarchitecture 352
Functional Considerations , 359
11 Spinal Cord: Fiber Tracts 368

Ascending Spinal Tracts 368
Descending Spinal Tracts 383
Intrinsic Spinal Fibers 400
Upper and Lower Motor Neurons 402
Spinal Cord Lesions 405
Section V Brainstem and Cerebellum

12 Medulla 421
Spinomedullary Transition 421
x
Inferior Olivary Complex 432
Medullary Reticular Formation 434
Ascending and Descending Tracts 436
Inferior Cerebellar Peduncle 437
Cranial Nerves of the Medulla 437
Corticobulbar Fibers 451
Chemical Anatomy 454
Medullary-Pontine Junction 461
13 Pons 469
Caudal Pons 469
Vestibulocochlear Nerve . 474
Facial Nerve 495
Abducens Nerve 498
Trigeminal Nerve 500
Rostral Pons-Isthmus Level 509
Reticular Formation 519
14 Midbrain 527
Caudal Midbrain 527
Rostral Midbrain 534
Midbrain Tegmentum. 549
Substantia Nigra 557
Crus Cerebri 572
15 Cerebellum 583
Regional Organization 583
Cerebellar Cortex 585
Cerebellar Nuclei 600
Somatotopic Organization 605
Cerebellar Connections .... 606
Functional Organization .... 616
Clinical Considerations 617
Section VI Forebrain
16 Thalamus 633
Regional Organization of the Diencephalon.. 633
Midbrain-Thalamic Junction 633
Epithalamus 635
Topographical Organization of the Thalamus 639
Nuclear Organization of the Thalamus 640
Chemical Anatomy of the Thalamus 673
Thalamic Radiations and Internal Capsule 682
Visual Pathways 685
17 Hypothalamus 706
Hypothalamic Nuclei 707
Hypothalamic Connections 715
Hypophysial Portal System ... 728
Hypophysiotrophic Agents .. 729
Functional Considerations ... 732
18 Limbic System 744

Limbic Lobe Versus Limbic System . 744
Olfactory System 748
Anterior Commissure 759
Hippocampal Formation 760
Xi
Amygdala 773
Substantia Innominata 786
19 Basal Ganglia 795

Nomenclature 795
Striatum 798
Globus Pallidus .828
Subthalamic Region 838
Ventral Striatopallidal Complex 844
20 Cerebral Cortex 864

Structure of the Cortex 864
Chemical Anatomy of the Cortex . 873
Cortical Areas 882
Sensory Areas of the Cortex 886
Motor Areas of the Cortex 909
Nonpyramidal Corticofugal Fibers 916
Association Fibers 918
Section VII Atlas of the Human Brain

Figure and Table Credit List 945
Index 947
xii
Section I
Regional Anatomy , Development,

and Blood Supply of the Neuraxis
1
Meninges and Cerebrospinal
Fluid
MENINGES 42). The erroneous macroscopic impression of
a subdural space results from an extraordi-
The brain and spinal cord , which together nary lack of cohesion within the dura-arach-
form the neuroaxis, are delicate semisolid noid interface layer. Subdural lesions are be-
structures requiring protection and support. lieved to form within a sheet of torn dural
Major protection is ensured by the skull for border cells and not within a preexistent tis-
the brain and by the vertebral column for the sue compartment (42).
spinal cord . Additionally, the brain and The meningeal layer gives rise to several
spinal cord are surrounded by three mem- septa which divide the cranial cavity into var-
branes or meninges: (a ) the thick dura mater ious compartments. The largest of these septa
externally, (b) the delicate arachnoid lining the is the sickle-shaped falx cerebri , which extends
inner surface of the dura , and (c) the thin pia in the midline from the crista galli to the in-
mater internally, which accurately follows ternal occipital protuberance ( Fig. 1.2). Poste-
every contour of the brain and spinal cord. riorly this septum is continuous with a trans-
The dura mater is also termed pachymeninx verse dural reflection from the superior crest
( thick membrane), whereas the arachnoid
and the pia mater, which have a similar struc-
ture, may be combined under the heading
of the petrous portion of the temporal bone
—
the tentorium cerebelli which covers the dor-
—
sal surface of the cerebellum. As illustrated in
pia-arachnoid or leptomeninges (slender Figures 1.2 and 1.3, the various dural reflec-
membranes). The space between the arach- tions divide the cranial cavity into (a ) a large,
noid and the pia mater, the subarachnoid paired supratentorial compartment which con-
space, is filled with cerebrospinal fluid (CSF). tains the cerebral hemispheres, and (b) a
The main supportive and protective func- smaller, single infratentorial compartment con-
tions of the meninges come from the dura taining the cerebellum and the brainstem .
mater and the CSF, which serve as a cushion The infratentorial compartment corresponds
between the brain and the rigid skull. to the posterior cranial fossa , whereas the
A proper knowledge of the topographic supratentorial compartment comprises an an-
organization of the meninges and their rela - terior cranial fossa for the frontal lobes and a
tionships to the brain and CSF is essential for middle cranial fossa for the temporal lobes. The
understanding the physiopathology of differ- occipital lobes lie on the superior surface of
ent clinical conditions such as head trauma, the tentorium cerebelli whose free borders
intracranial hemorrhages, central nervous form the tentorial incisure (or notch ), the only
system infection, and hydrocephalus. opening between the supratentorial and in-
fratentorial compartments ( Figs. 1.2 and 1.3).
Dura Mater The brainstem passes through the tentorial
The cranial dura consists of (a ) an outer notch (Fig. 1.4) where it can be severely com-
periosteal layer , which is rich in blood ves- pressed and damaged in cases of expanding
sels and nerves and is adherent to the inner brain lesions. The occipital lobes lie on the su -
surface of the cranium, and (b) an inner perior surface of the tentorium. A small mid -
meningeal layer that is closely attached to the sagittal septum below the tentorium forms
underlaying arachnoid. At certain sites, these the falx cerebelli ( Fig. 1.2) which partially sepa-
layers are separated and form large venous rates the cerebellar hemispheres. The di -
sinuses such as the superior sagittal sinus aphragma sellae roofs over the pituitary fossa
( Fig. 1.1, see Chapter 4). Cranial meninges in and is perforated by the infundibulum (see
humans do not include a subdural space (23, Chapter 2).
3
Superior sagittal
sinus
Transverse sinus
Sinus
confluens
Occipital sinus
Jugular bulb
Foramen magnum level

Figure 1.1. Postenor view of the dura surrounding the brain Prominent dural sinuses have been opened The pe-
riosteal layer of the dura has been cut at the margins of the foramen magnum
Falx cerebri
Tentorial notch
Tentorium
cerebelli
Anterior cranial
Transverse
sinus
Falx cerebelli
Sigmoid
Middle cranial fossa
sinus Labyrinth
Figure 1.2. Sagittal section of the head showing the falx cerebri, the tentorium cerebelli and the falx cerebelli
4
halx cerebri Anterior cranial
Internal carotid Optic chiasm

artery
Middle
meningeal
artery
Sigmoid
sinus
Tentorium
cerebelli
Posterior
cranial
fossa Rectus sinus
Transverse
sinus
Sinus confluens
.
Figure 1.3 Base of the skull with dura mater The falx cerebri has been removed and the tentorium cerebelli has
been cut away on the left to expose the posterior fossa .
6 Section I Regional Anatomy, Development, and Blood Supply of the Neuraxis
NN 2E and T7TTT Sulcus for inf . cerebral veins
Tentorium
N . 31
Atlas Vertebral artery

Post spinal artery
, First cervical nerve
First denticulate lig.
Dorsal root filaments
of second cervical nerve
Post. inf . cerebellar a .
Second denticulate lig.
Arachnoid
'
Dorsal root ganglion
Ligomentum flavum
^
Dura mater Trunk of fourth

cervical
nerve
Figure 1.4. Posterior view of the brainstem, upper cervical spinal cord and meninges
The major blood supply for the dura is lesion located anywhere in the anterior fossa
provided by the middle meningeal artery, a will produce pain radiating toward the fore-
branch of the maxillary artery, which enters head on the lesion side. The pain from a simi -
the skull via the foramen spinosum ( 28) ( Figs. lar lesion in the posterior fossa will be felt
1.3 and 4.4 ). The ophthalmic artery gives rise more diffusely in the occipital and neck re-
to anterior meningeal branches and the occip- gion.
ital and vertebral arteries provide posterior The innermost layer of the dura is com -
meningeal branches. Skull fractures lacerat- posed of flattened fibroblasts that are in
ing these meningeal arteries produce space close contact with the arachnoid, suggesting
occupying epidural hemorrhages between that the subdural space is a potential space
the skull and the dura that require prompt rather than an actual space (11 , 23, 42). The
surgical intervention. spinal dura is a continuation of the meningeal
The supratentorial dura is innervated by layer of the cranial dura ( Figs. 1.4 and 1.5).
branches of the trigeminal nerve ( N . V ), The periosteum of the vertebrae corresponds
whereas the infratentorial dura is supplied by to the outer ( periosteal ) layer of the cranial
branches of the upper cervical spinal nerves dura . Inner and outer surfaces of the spinal
and the vagus nerve ( N . X ). Stimulation of dura are covered by flattened fibroblasts,
the supratentorial dura by a space-occupying and the dense membrane is separated from
the periosteum by a narrow epidural space. jected into the epidural space via the sacral
The spinal epidural space contains areolar canal .
tissue and the internal vertebral venous The spinal dura extends as a closed tube
plexuses ( Fig. 4.3). This actual space is from the margins of the foramen magnum to
largest at the level of the second lumbar ver - the level of the second sacral vertebra ( Fig. 1.6).
tebra where it is nearly half the diameter of At the caudal termination of the dural sac the
the spinal canal. Clinically the epidural dura invests the filum terminale to form a thin
space is used to inject a local anesthetic to fibrous cord , the coccygeal ligament ( Fig. 1.6).
produce an extensive paravertebral nerve This ligament extends caudally to the coccyx
bloc known as epidural anesthesia . The where it becomes continuous with the perios-
epidural space can be distinguished because teum. The spinal cord ends at the lower border
it has a negative pressure. Caudal anesthesia , of the first lumbar vertebra . Extensions of the
used in obstetrics, is a form of epidural anes- dura passing laterally around the spinal nerve
thesia in which the anesthetic agent is in - roots form dural root sleeves ( Figs. 1.5 and 1.7).
Dorsal root
Spinal ganglia Ventral root

Dura mater
Arachnoid
Denticulate
ligament
[r Arachnoid
' traberculae
Dorsal root
Ventral root
Pia and dorsal

spinal vessels
Figure 1.5. Posterior view of port of the upper thoracic spinal cord. The dura and arachnoid have been split at the
midllne to expose the spinal cord and pial vessels. Above the intact dura covers the spinal cord and spinal nerve
roots.
Conus medullaris —
Lumbar cistern
Filum termmale
Dura mater
Cauda equina
Coccygeal ligament
Figure 1.6. Diagrammatic representation of the caudal part of the spinal cord and lumbar cistern A . Sagittal view of
the conus medullaris, lumbar cistern, and lumbosacral vertebrae B. Posterior view of the cauda equina and nerve
roots,
Pia Mater 29 ). The epipial layer is formed by a mesh-

work of collagenous fiber bundles continuous
This thin and translucent vascular mem- with the arachnoid trabeculae. The blood ves-
brane is composed of an inner membranous sels of the spinal cord lie within the epipial
layer, the intima pin , and a more superficial layer. Over the convex surface of the cerebral
epipial layer . The intima pia, adherent to un - cortex, the epipial layer is absent and the
derlying nervous tissue, follows its contours large cerebral vessels lie on the intima pia
closely and is composed of fine reticular and where they are anchored by fine arachnoid
elastic fibers. Where blood vessels enter and trabeculae. The pia mater is made up of lep-
leave the central nervous system , the intima tomeningeal cells virtually indistinguishable
pia is invaginated forming a perivascular from those of the arachnoid . Subpial astro-
space ( Fig. 1.12 ). The intima pia, like the cytes form a continuous sheath of underlying
arachnoid , is avascular and derives its nutri- cytoplasm; between the pia and subpial as-
ents by diffusion from the cerebrospinal fluid trocytic layer is an osmiophilic basement
and the underlying nervous tissue (11, 12, membrane separated from the plasma mem -
Dura mater
Epidural space and veins Subdural space
Pia mater / Arachnoid and post orach septum
,
Denticulate ligament \ / Subarachnoid space

Ligamentum flavum Dorsal root
Spinal ganglion Ventral root
Dorsal ramus
White ramus'
Ventral ramus
Gray ramus
Vertebral veins
Rami communicantes
Vertebral artery
Figure 1.7 . Spinal cord ond its meningeal coverings in cross-section Note the continuities of the pia mater with the
denticulate ligament, and of the dura mater with the epineurium of the spinal nerves
branes. The spinal cord is attached to the and above the pineal body, form the velum in -
dura mater by a series of (18 to 24 ) lateral flat- terpositum ( Fig. 2.29B ) . The internal cerebral
tened bands of epipial tissue known as the veins, branches of the posterior cerebral
denticulate ligaments ( Figs. 1.4, 1.5, and 1.7). In artery, and arteries to the choroid plexuses of
the region of the conus medullaris, epipial tis- the third and lateral ventricles, lie between
sue forms a covering of the filum terminale these two layers ( Figs. 4.26 and 4.27).
(Fig. 1.6).
In the region of the ventricles, the brain Arachnoid
wall is formed by a single layer of ependymal
cells, the outer surface of which is firmly ad - The arachnoid is a delicate nonvascular
herent to the pia mater. In the roof of the membrane between the dura and the pia
third ventricle ( Figs. 1.9, 1.10, and 2.29 B ) , in mater which passes over the sulci without
the lower part of the roof of the fourth ventri- following their contours ( Figs. 1.11 and 1.12).
cle ( Figs. 1.9 and 1.10), and on the medial This membrane also extends along the roots
wall of the inferior horn of the lateral ventri- of the cranial and spinal nerves. Arachnoid
cle (choroid fissure), the intima pia blends trabeculae extend from the arachnoid to the
with the ependymal layer to form the tela pia . The space between the arachnoid and the
choroidea ( Fig. 6.17). The tela choroidea an- pia mater, filled with cerebrospinal fluid
chors the choroid plexuses to the walls of the (CSF), is called the subarachnoid space ( Figs.
ventricles. It has a triangular shape in the roof 1.11 and 1.12 ). Most cranial nerves are sur-
of the third and fourth ventricles and is rounded by a subarachnoid space (11, 12, 47).
horseshoe-shaped in the lateral ventricles as A small subarachnoid space also surrounds
it follows the choroidal fissure ( Figs. 2.29 B, the spinal nerve roots in the root sleeves ( Fig.
18.12, and 18.13). The two layers of the pia 1.7). In the spinal regions, fewer arachnoid
mater in the transverse cerebral fissure, trabeculae are concentrated into several sub-
below the splenium of the corpus callosum arachnoid septa ; hence the spinal subarach -
Cerebral subarachnoid spaces Olfactory bulb and tract
Optic n. ond central

Cistern of optic chiasm ; retinal a.
^ Oculomotor a
Internol carotid a Ophthalmic ond
maxillary nn .
Lominoe ot Abducens n.
dura mater
Mandibular n.
Trigeminal Trochlear n.
ganglion and cave
Straw in
sup. petrosal
Interpeduncular
and pontine
cisterns
- NN . sn a Tzm
Superior
petrosal sinus
In tentorium NN. IX, XXI
Vertebral a.
N . XU
Arachnoid ar
subarachnoid
trabeculae Transverse
dural sinus
Anastomotic
vein ( of labbe )
.
Cisterna magna
(cerebellomedularis )
Figure 1.8 . Inferior view of the brain, cranial nerves, and meninges showing locations of subarachnoid cisterns .
noid space is a more continuous cavity and The largest cistern is found between the
the spinal arachnoid a more distinct mem- medulla and the cerebellum and is called the
brane ( Fig. 1.7). The arachnoid membrane is cerebellomedullary cistern (cisterna magna ).
made up of leptomeningeal cells with a wa - Other cisterns of considerable size are the pon-
tery cytoplasm which forms long, irregular
pseudopods that interdigitate with those of
tine cistern , the interpeduncular cistern , the chias
matic cistern , and the superior cistern ( Fig. 1.9).
-
adjacent cells. These cells form a protoplas- The superior cistern , surrounding the poste-
mic layer which may be several cells thick rior, superior, and lateral surfaces of the mid -
and exhibit great irregularity. When certain brain, is referred to clinically as the cisterna
substances are injected into the subarachnoid ambiens (47). This cistern is of great impor -
space, these cells may swell and participate in tance because it contains the great vein of
phagocytic activity by ingesting particles of Galen , and the posterior cerebral and superior
the foreign material. They may also become cerebellar arteries. Most of these cisterns can
detached and form free macrophages. be visualized by special radiographic tech-
The extent of the subarachnoid space sur- niques (such as pneumoencephalography or
rounding the brain shows local variations. computerized tomography). The lumbar cistern
Over the convexity of the cerebral hemi- extends from the conus medullaris (lower bor-
sphere this space is narrow , except in the der of the first lumbar vertebra ) to about the
depths of the sulci. At the base of the brain level of the second sacral vertebra ( Fig. 1.6). It
and around the brainstem the pia and the contains the filum terminale and nerve roots of
arachnoid often are widely separated, creat - the cauda equina. It is from this cistern that
ing subarachnoid cisternae ( Figs. 1.8 and 1.9 ). CSF is withdrawn in a lumbar spinal tap.
Cerebral subarachnoid space
Choroid plexus
Third ventricle
Superior
cistern
Choroid plexus
Pontine cistern Cerebellomedullary cistern
Spinal subarachnoid space
Figure 1.9. Subarachnoid cisterns as seen in a midsagittal view The superior cistern is referred to clinically as the cis-
terna ombiens. The choroid plexus in the roof of the third ventricle and in the fourth ventricle is shown in red
In regions adjacent to the superior sagittal sagittal sinus, they are also found along the
sinus ( Figs. 1.1, 4.22, and 4.25), the cerebral other intracranial venous sinuses. Arachnoid
pia -arachnoid gives rise to tufted prolonga - villi also have been described in the spinal
tions termed arachnoid granulations which arachnoid and along the optic nerves. In both
protrude through the meningeal layer of the the spinal and cerebral arachnoid , cell clus-
dura into the superior sagittal sinus ( Figs. ters are sometimes formed which become at-
1.10 and 1.11 ). These granulations are vari - tached to the dura . These growths may be-
able in number and location and each con - come calcified or, under abnormal conditions,
sists of numerous arachnoid villi. These villi form the sites where tumors arise.
have a thin outer limiting membrane beneath Arachnoid granulations and villi are the
which are bundles of collagenous and elastic major site of fluid transfer from the subarach -
fibers. Cells similar to those of the pia -arach - noid space to the venous system . In the up-
noid are scattered among the fibers, and right position, venous pressure is less than
small oval epithelial cells cap the surface of the hydrostatic pressure of the CSF so that
the villi. Arachnoid granulations frequently fluid moves from the subarachnoid space to
are surrounded by a venous lacuna along the the venous dural sinuses. When venous pres-
margin of the superior sagittal sinus. With sure exceeds CSF pressure, the valves close
advancing age the arachnoid granulations be- and blood cannot enter the CSF. Arachnoid
come larger and more numerous and tend to granulations appear to function as passive,
become calcified . Although arachnoid villi pressure-dependent, one-way-flow valves
are most numerous in relation to the superior whose membranes are readily permeable to
Figure 1.10 . Sagittal view of the brain and spinal cord to illustrate the circulation ot the cerebrospinal fluid The direc-
tion of the CSF flow is indicated by arrows
metabolites, Prussian blue reagents, and even ceeds venous pressure, the microvilli disap-
large molecular weight substances. These pear, the cells are stretched and CSF flows
valves are spongy tissue containing a series into the venous sinuses. Bulk volume flow of
of interconnecting tubes approximately 6 pm CSF occurs through the arachnoid tubular
in diameter. The tubes remain open only system and between stretched endothelial
when the CSF flows from the subarachnoid cells. Flow of CSF into the venous sinuses is
space into venous blood under a pressure proportional to the increase in CSF pressure
head ( 18, 19, 22 ). When the pressure of ve- but does not begin until it exceeds venous
nous blood exceeds that of the CSF, the tubes pressure by 3-6 cm of water.
collapse ( 51 ). The surface of an arachnoid vil -
lus has a layer of overlapping endothelial Pia - Glia and the Perivascular Spaces
cells. In the absence of pressure differences
between the CSF and venous blood , the The intima pia or pia -glia is regarded
membranes of these cells are folded and have as the external limiting membrane of the cen-
numerous microvilli. When CSF pressure ex- tral nervous system (CNS) whereas the
Dura mater Superior sagittal sinus Arachnoid

granulation
Arachnoid and
,
^ trabecula
Aj— Subarachnoid space
Pia mater
Glial membrane
Cerebral cortex
1: I
^— Falx cerebri
Figure 1.11 . Meningeal-cortical relationships Arachnoid granulations may penetrate dural sinuses or terminate in a
lateral lacuna of a sinus. The pia is firmly anchored to cortex by the glial membrane
Dura mater
Subdural space
Arachnoid Subarachnoid
space
Arachnoid
trabeculae
Artery
Pia mater
Perivascular
space
Cerebral cortex
Figure 1.12. Meninges showing relationship of the membranes to the subarachnoid and perivascular spaces
ependyma can be considered as the internal which leads to the formation of over 400 ml
limiting membrane. It has been suggested per day (11, 12). These data suggest a CSF
that the intima pia arises from ectoderm ( 29). turnover rate of 0.25% per minute (9, 10).
The arachnoid membrane which represents The CSF is formed at a hydrostatic pres-
the principal physiologic barrier that protects sure head of 15 ml of FLO which is sufficient
the CNS and separates it from the surround - to drive it through the ventricular system and
ing connective tissue also has been consid
ered to be of ectodermal origin (11 , 12). The
- into the arachnoid spaces surrounding the
brain and spinal cord. Pulsation of the
parenchyma of the CNS, the glia , the choroid plexus also probably contributes to
ependyma , and the leptomeninges arise from the movement of CSF within the ventricular
ectoderm, while the blood vascular system system . These pulsations reflect the presence
and the dura mater are of mesodermal origin . of several arteries in the choroid plexus and
As blood vessels enter and leave the nervous are not due to some intrinsic pulsatile charac-
tissue, they carry with them arachnoid and teristic of the plexus itself .
pia -glia which form a cuff around the vessel. The CSF formed in the lateral ventricles
The space between the blood vessel and its enter the third ventricles through the inter-
“adventitial sheath" has been called the Vir- ventricular foramen (of Monro) and then
chow- Robin space. It was suggested that these pass via the cerebral aqueduct (of Sylvius)
spaces might permit the flow of cerebrospinal into the fourth ventricle ( Fig. 1.10). The fluid
fluid from the subarachnoid spaces into the enters the cerebellomedullary cistern via a
depths of the tissue. Electron microscopic median aperture ( foramen of Magendie) lev
studies indicate that as blood vessels pene- cated in the posterior medullary velum, and
trate neural tissue from the subarachnoid two lateral apertures ( foramina of Luschka ) in
space, reflections of the intima pia and arach- the lateral recesses of the fourth ventricle
noid which form the "adventitial sheath" are ( Figs. 1.10 and 2.21 ). The fluid then circulates
carried with it . In the CNS, however, these in the subarachnoid spaces surrounding both
two layers become continuous and there is no the brain and the spinal cord . The bulk of the
real space between them . When the smallest CSF is passively returned to the venous sys-
veins and capillaries are reached , no adventi- tem via the arachnoid villi ( Fig. 1.10). The hy-
tial elements surround them . Only processes drodynamic permeability of the arachnoid
of astrocytes surround the basement mem- villi is large compared with that of the pe-
branes of the capillary endothelium . ripheral capillaries. Large protein molecules
leave the CSF by passage through the arach-
CEREBROSPINAL FLUID noid villi at roughly the same rate as smaller
molecules.
The CSF is a clear, colorless liquid that fills The composition and pressure of the CSF
the ventricles of the brain and subarachnoid may vary in different pathologic conditions,
spaces. Approximately 70% of the CSF is pro- thus the analysis of this liquid can give us im -
duced by secretion at the choroid plexus lo- portant clues to establish a diagnosis (15).
cated in the walls of the lateral ventricles and Under normal conditions, the CSF is clear,
in the roof of the third and fourth ventricles mostly devoid of blood cells, and contains
( Figs. 1.10, 2.21, and 2.29). The remaining 30% only small amounts of protein, glucose, and
of the CSF is derived from the capillary bed potassium , but relatively large amounts of
of the brain and metabolic water production sodium chloride. In acute bacterial meningi-
(36, 40, 41 ). Estimates of metabolic water pro- tis, however, the white blood cell count may
duction, based on the assumption of com- reach 5000 / ml and cultures of CSF may be
plete oxidation of glucose for a 1500 g human used to identify the infectious agent. Usually,
brain, suggest a net contribution of about cell number increases only moderately in
12% of the total CSF. Approximately 18% cases of viral infections or in response to cere-
of the CSF is derived from extrachoroidal bral infarction, brain tumor, or other cerebral
sources, presumably as a capillary ultrafil - tissue damage. The concentration of glucose
trate. In humans, the total volume of CSF has in the CSF is decreased in acute bacterial in-
been estimated to be about 140 ml, of which fection, but rarely in viral infection. An in-
23 ml are contained within the ventricles. The crease in the protein content of the CSF may
net production of CSF in humans appears to be found in several pathologies of the CNS,
be between 0.35 and 0.37 ml per minute probably because of changes in the vascular
permeability. For instance, protein content there is often an accumulation of CSF within
greater than 500 mg / dl is often indicative of a the subarachnoid spaces, a condition referred
tumor or other compressive lesion blocking to as external hydrocephalus. Obstruction of
the spinal subarachnoidal space. In multiple the CSF flow through the tentorial notch
sclerosis, a slowly progressive CNS disease around the midbrain results in a combination
characterized by disseminated patches of de- of internal ( intraventricular ) hydrocephalus and
myelination in the brain and spinal cord , the subtentorial external In/ drocephalus . This path -
y-globulins increase to more than 13% of the ologic condition is known as communicating
total protein content in the CSF (15). hydrocephalus. Hydrocephalus resulting from
The CSF serves to support and cushion the a tumor obstructing the CSF flow can usu -
CNS against trauma. The buoyancy of CSF is ally be treated by surgical removal of the
indicated by the fact that a brain weighing causative factor . In the other cases, the over-
1500 g in air weighs only 50 g when im- flow of CSF can be diverted to a new site of
mersed in CSF ( 25). Buoyancy reduces the absorption by means of ventricular-atrial,
momentum and acceleration of the brain ventricular- peritoneal, or lumbar- peritoneal
when the cranium is suddenly displaced , surgical shunts.
thereby reducing concussive damage (31 ). Be- The CSF also removes waste products of
cause the brain is nearly incompressible neuronal metabolism, drugs, and other sub-
within the skull, the combined volumes of stances which diffuse into the brain from the
brain, CSF, and intracranial blood must be blood . As the CSF streams over the ventricu-
maintained at a constant level. The volume of lar and pial surfaces of the brain, it drains
any of these components can be increased away solutes and carries them through the
only at the expense of one or both of the oth - arachnoid villi into venous blood . Addition-
ers. For instance, any space-occupying lesion ally, some drugs, such as penicillin, and cer-
such as a tumor or hematoma usually results tain neurotransmitters, like serotonin and
in an increase in intracranial pressure that norepinephrine and their metabolites, are
may severely damage the brain . Brain tumors rapidly removed from the CSF by the choroid
and hematomas usually cause an increase in plexus (1 ). The 30% of the CSF derived from
CSF pressure, which can be used as a guide extrachoroidal sources may contribute to the
to intracranial pressure. The normal CSF bulk volume movement within normal brain
pressure measured at the lumbar cistern is parenchyma. The CSF also plays an impor-
about 100-150 mm of ICO in the recumbent tant role in integrating brain and peripheral
position, and varies between 200 and 300 mm endocrine functions in that hormones or hor-
1 FO in the sitting position. An excessive mone-releasing factors from the hypothala -
amount of CSF can , itself , markedly elevate mus are secreted into the extracellular space
the intracranial pressure, if not compensated or directly into the CSF. These hormones,
by increased absorption or decreased forma- which include hormone-releasing factors, are
tion. This pathologic condition, known as liy- carried via CSF to the median eminence in
drocephalus , is encountered frequently in in- the floor of the third ventricle, from which
fants. It is also observed in adults pursuant to site they are transported by specialized
tumors, vascular lesions, and other patho- ependymal cells ( i.e., tanycytes) into the hy-
logic conditions. Hydrocephalus is character- pophysial portal system ( Figs. 17.18 and
ized by an enlargement of the ventricles, a 17.19). The CSF also influences the microenvi -
thinning of neural tissue, and changes in the ronment of neurons and glial cells because
morphology of the skull . Such increases in there is no diffusion barrier between CSF at
CSF may result from an overproduction of either the ependymal lining of the ventricles
fluid , an obstruction to its flow, or inadequate or at the pia-glial membrane. Changes in CSF
absorption. In most instances, hydrocephalus calcium, potassium, and magnesium ion con-
results from obstruction within the ventricu- centrations may affect blood pressure, heart
lar system , particularly the cerebral aqueduct. rate, vasomotor reflexes, respiration, muscle
Removal of the choroid plexus from one lat- tone, and the emotional state of animals (24).
eral ventricle usually causes the ventricle to The CSF has been regarded as an ultrafil -
collapse, while obstruction of one interven- trate of the blood plasma because of their re-
tricular foramen results in dilatation of the ip- semblance, except for huge differences in
silateral ventricle. protein concentration ( plasma , 6500 mg / 100
In cases of senile atrophy of the brain, g; CSF, 25 mg / 100 g ). The characteristic dis-
tribution of the number of ions and nonelec- -

inhibition of the enzyme Na ' K ' -ATPase
trolytes in CSF and plasma , however, is such which catalyzes the Na ' pump.
that the CSF cannot be described as a simple
filtrate or dialysate of the blood plasma . In BARRIERS RELATED TO THE BRAIN
general the CSF has higher Na ', Cl , and
Mg2' concentrations, and lower K +, Ca 2 + , The functional capacity of all neurons of
and glucose concentrations than would be ex - the brain and spinal cord is dependent upon
pected in a plasma dialysate. Finally, the os- the nature of the chemical milieu which sur-
motic pressure relationships are not sufficient rounds them . To maintain the physiochemi-
to produce a virtually protein-free fluid from cal composition of the microenvironment of
the blood plasma (11, 12). neurons, axons, and glia within the narrow
The choroid plexus is a villous structure limits of neuron survival requires a unique
extending from the ventricular surface like regulatory mechanism . The system that regu -
coral fronds into the CSF. The plexus consists lates the transport of chemical substances be-
of a single layer of cuboidal epithelium with tween arterial blood , the CSF, and brain tis-
basal infoldings on the choroidal stroma and sue is the blood -brain barrier, a series of
apical microvilli in contact with the CSF (45). regulatory interfaces between blood and the
The cuboidal epithelial cells of the plexus rest nervous system . The blood - brain barrier sep-
on a basement membrane enclosing an exten- arates the two major compartments of the
sive capillary network embedded in a con - CNS, the brain and the CSF, from a third
nective tissue stroma ( Fig. 1.16). The choroid compartment , the blood . The sites of the bar-
plexus regulates a large part of the produc- rier are the interfaces between the blood and
tion, as well as, the composition of the CSF. A these two compartments of the CNS. These
Na '- K' exchange pump, catalyzed by Na + - interfaces regulate diffusion at cerebral capil -
K * - ATPase, drives Na + toward the ventricu - laries and the exchange of metabolites and
lar surface of the plexus and K ' in the oppo- metabolic products between blood and brain .
site direction. Thus, the concentration of K ' is Two separate barriers, a blood -CSF barrier and
lower and the concentration of Na ’ is higher a blood -brain barrier , have been distinguished
in the choroidal secretion than in serum or in to explain why intravascular substances enter
an ultrafiltrate of the plasma ( 30, 45). These the CSF and the brain at different rates (11,
data suggest that K + is transported out of the 12 ). When substances such as glucose or urea
CSF, while Na ' is actively transported into it. are injected intravascularly, they diffuse
The choroid plexus also plays a role in the rapidly and come to equilibrium with extra -
regulation of Mg2 + and Ca:’ in the CSF. Fluid cellular or interstitial fluids of most tissues.
secreted by the choroid plexus contains a The observation that the transport of sub-
higher concentration of Mg2' and a lower stances from the blood to the CSF requires
concentration of Ca 2' than does an ultrafil - hours instead of minutes gave rise to the con-
trate of the plasma . Considerable controversy cept of the blood -CSF barrier. Injections of
concerns the manner in which water, the certain dyes, such as trypan blue, into the
largest constituent of the CSF, moves across blood , stains most body tissue quickly, but
the choroidal epithelium . The hypothesis, does not enter the CSF. Early studies indi-
based upon hydrostatic pressure, is sup- cated important differences between CSF and
ported by data indicating that modifications the interstitial fluid of most body tissues and
of choroidal blood flow can increase or de- further established that this barrier is not ab-
crease the CSF secretion rate (50). Approxi- solute, but selectively permeable. The kinetic
mately 25% of the volume of blood flowing to aspects of the passage of substances from
the choroid plexus normally is secreted as blood into brain are included under the term
CSF. The other theory concerning the water blood -brain barrier, by analogy with the
content of the CSF, suggests that water moves blood-CSF barrier. The concept of the restric-
across the choroidal epithelium under a tion of the passage of dissolved substances
standing osmotic gradient established by the from blood to brain dates back to 1885, when
active transport of Na +. This hypothesis is Paul Ehrlich demonstrated that intravenous
based upon the observation that movement injections of many vital dyes stained practi-
of water into the CSF is quantitatively cou - cally all body tissues, except the brain (13).
pled to the active transport of Na + ( 48). Water These blood-brain and blood -CSF barriers
secretion is reduced proportionally to the differ greatly in surface area . The surface area
of the blood -brain barrier has been estimated CSF and the brain. Ferritin and the enzymatic
to be 5000 times greater than that of the marker horseradish peroxidase (HRP) in-
blood -CSF barrier ( 33). jected into CSF of the ventricles diffuse be-
Overall, the blood -brain barrier appears to tween ependymal cells and enter the extracel-
be principally in charge of transporting those lular space of the brain ( 4 ). Additionally,
substances that the brain consumes rapidly these tracers are found in pinocytotic vesicles
and in large quantities (e.g., glucose, amino within ependymal cells. Drugs injected into
acids, lactate, and ribonucleosides ). In con- the cerebral ventricles easily cross the
trast, the choroid plexus controls the transfer ependymal lining and produce immediate
—
of different micronutrients substances that
are essential to the brain but only needed in
pharmacologic and behavioral effects. A
schematic diagram of relationships between
relatively small amounts over extended peri- the blood -brain barrier, the blood -CSF bar-
ods (e.g., vitamin C, folates, deoxyribonucleo- rier, and the brain-CSF interface is shown in
sides, and vitamin B„ ) (45). Figure 1.14. Excellent reviews of the brain
The brain barriers develop at the time barriers consider this subject in depth ( 2, 3,
when blood vessels invade the brain , and evi- 16, 17, 37).
dence suggests that the adult barriers react
differently to the electrical charges of various Blood- Brain Barrier
vital dyes. The blood - brain barrier is more
permeable to basic ( positively charged ) dyes, It is important to realize that for any chem -
whereas the blood -CSF barrier is more per- ical compound the efficacy of the blood -brain
meable to acid ( negatively charged ) dyes. barrier is determined by two major sets of
Such interfaces are structural and functional factors: (a ) the morphologic and functional
entities which dynamically control the trans- characteristics of brain capillaries that are dif -
fer of chemical substances into and out of the ferent from those of the capillaries found
three fluid compartments of the brain (i.e., ex- elsewhere in the body, and ( b ) the biochemi -
tracellular or interstitial, intracellular, and cal and biophysical characteristics of the com-
CSF). pound , among which molecular size, lipid
The ependymal surfaces of the cerebral solubility, and existence of carrier-mediated
ventricles and the pia-glial membrane on the transport systems play the most crucial role.
surface of the brain do not impede the ex- The blood - brain barrier comprises three
change of substances between the CSF and major components: (a ) the endothelial cells
brain and do not constitute a subbarrier. The forming the wall of brain capillaries, ( b) the
walls of the cerebral ventricles and the spinal continuous and homogeneous basement
canal are lined by a single layer of epithelial membrane of these endothelial cells, and (c)
cells whose cilia beat synchronously to cause the multiple processes of the astrocytes cov -
local mixing of CSF. Ependymal cells are not ering much of the surface of brain capillaries
connected by tight junctions and do not hin- ( Fig. 1.13). These three elements are all that
der macromolecular exchange between the separate the plasma in blood vessels from the
BRAIN CAPILLARY GENERAL CAPILLARY
Pinocylosis
Basement membrane
Basement membrane
Transcellular
passage
Endothelial cell
Tight junction between
endothelial cells
Fenestration of
Endothelial cell endothelial cells
Foot process of Intercellular

cleft passage
astrocyte
Figure l . ) 3 . Differences between the structure of capillaries in the brain ( left) and those in the general circulation
(.right)
extracellular (i.e., interstitial) space within the found in the capillaries of skeletal and cardiac
CNS. muscles. Pinocytotic vesicles are rare in en-
In all parts of the body, the exchanges be- dothelial cells of cerebral capillaries or
tween blood and tissue take place in the cap- venules, but are occasionally seen in arteri-
illary bed. The brain is no exception to this oles. Additionally, endothelial cells of cere-
generalization, but there are some significant bral vessels do not contain contractile protein
differences. A capillary is distinguished from as seen in peripheral capillaries, and capillary
an arteriole and a venule by the absence of a permeability does not increase in response to
well-defined muscular coat. The wall of a histamine, serotonin, or norepinephrine (52).
capillary consists only of flattened endothe- The capillary endothelial cells in the central
lial cells resting on a basement membrane nervous system are metabolically active with
surrounded by a thin adventitial layer made respect to both oxidative and hydrolytic en-
up of cells and fibers. These latter cells, re- zymes. Enzymes within these cells regulate
ferred to as pericytes , are often enclosed the transport of amines and amino acids. An
within parts of the basement membrane (12). example of this regulation is seen in Parkin-
Capillaries within the CNS contain a continu- son's disease ( paralysis agitans) in which
ous inner layer of endothelial cells connected there is a deficiency of dopamine, a neuro-
by tight junctions ( Fig. 1.13). Similar capillar- transmitter synthesized in the substantia
ies are found in the retina, the iris, the inner nigra and conveyed by axons to specific por-
ear, and within the endoneurium of periph- tions of the striatum. Because dopamine can-
eral nerves. Tissue with capillaries of this not cross the blood -brain barrier, the precur-
type are derived totally or partially from neu - sor L-dopa is given to correct this metabolic
roectoderm (20). The morphologic and enzy- defect. L-dopa crosses the blood-brain barrier
matic properties of capillaries in tissue de- and is decarboxylated in the capillary en-
rived from neuroectoderm are controlled by dothelium to dopamine, a biogenic amine
specific angiogenic substances released by that is therapeutically effective ( Fig. 1.15). Al-
neural tissue. When iris tissue is transplanted though it has been suggested that active
to the brain it is vascularized with capillaries transport mechanisms exist across cerebral
that do not contain monoamine oxidase or capillaries, their precise role is difficult to dis-
dopa -decarboxylase. Embryonic brain tissue tinguish from that of the choroid plexus.
transplanted in the anterior chamber of the The blood -brain barrier in the central ner-
eye is vascularized from the iris, but the cap- vous system is not everywhere complete. In
illaries contain these brain enzymes. The tight certain regions of the brain, the continuous
junctions between endothelial cells of cere- capillary endothelia are replaced by capillar-
bral capillaries restrict intercellular diffusion ies with fenestrated endothelia . These regions
( Fig. 1.15). The presence of high-resistance with capillary fenestrations provide specific
tight junctions between adjacent brain en- sites for the transfer of proteins and solutes
dothelial cells, and the paucity of pinocytosis irrespective of molecular size and lipid solu-
or capillary fenestrations, means that circulat- bility. Regions of the brain devoid of a blood -
ing substances in the cerebral vascular sys- brain barrier include the pineal body (or
tem can enter the brain only via carrier medi- pineal gland ), the neurohypophysis, the area
ation or lipid mediation (33). The tight postrema, the subfornical organ, the or-
junctions that connect capillary endothelial ganum vasculosum of the lamina terminalis
cells form, in essence, a continuous cell layer (or supraoptic crest ), and the median emi-
that has the permeability properties of a nence of the hypothalamus. All of these re-
plasma membrane. The basement membrane gions are highly vascular, and many are
surrounds the endothelial cells and approxi- known or suspected of having a secretory
mately 85% of its surface is covered by glial function. The blood-brain barrier, except in
cells. The tight junctions between endothelial the special regions noted earlier, functions as
cells prevent the transfer of La(OH)3, mi- a differential filter that permits the selective
croperoxidase, HRP, and ferritin (5, 6, 38). exchange of many substances from blood to
The capillary surface area in 1 g of brain has the extracellular compartment (i.e., interstitial
been estimated to be 240 cm2 (8). fluid ). It appears to be impermeable to many
Cerebral blood vessels have neither a well- substances (e.g., vital dyes).
developed small pore system for diffusion It has been suggested that the blood -brain
nor a vesicular transport system such as that barrier in the fetus and newborn is immature
because blood -borne dyes stain these brains reach the brain in large amounts mostly be-
more extensively than adult brains. Electron cause of its large size ( in plasma , penicillin is
microscopic evidence indicates that tight bound to albumin) and low degree of lipid
junctions surrounding epithelial cells of the solubility. This is fortunate because penicillin
choroid plexus of the rat at early develop- is toxic to the nervous tissue. In meningitis,
mental stages do not differ qualitatively from however, the blood - brain barrier becomes
the adult ( 32 ). However, the water content of much less effective and the antibiotic enters
the cerebral cortex and white matter of the the brain in sufficient amounts to exert a ther -
brain of the rhesus monkey progressively di- apeutic effect. In cases of focal brain lesion
minishes during fetal development and post- such as tumor and abscess, the breakdown of
partum maturation ( 44 ). An expanded extra- the blood -brain barrier is often limited to the
cellular space in the brains of the newborn lesion site and this has important practical
appears to provide a greater volume for the implications. For instance, albumin labeled
distribution of extracellular markers (e.g., in- with radioactive iodine can be used as a
ulin ). This increased extracellular space ap- tracer to locate the lesion site, since this pro-
pears to account for the observation that try - tein will reach only the lesion area and not
pan blue, given intravenously, stains the the normal parts of the brain where the
brain of an immature animal. Although the blood-brain barrier has remained intact . The
dye enters the brain only at the nonbarrier accumulation of radioactivity in a restricted
sites, it extends further in the extracellular brain area can then be localized by external
space than in the mature brain . detectors or can serve to enhance computer -
Unconjugated bilirubin, a breakdown ized images of the brain .
product of hemoglobin, can stain the brain of Neurons and neuroglial cells comprise the
the newborn if severe jaundice results from intracellular fluid compartment of the brain
accelerated destruction of red cells, as occurs ( Fig. 1.14 ). Passage of substances into and out
in erythroblastosis fetalis associated with Rh of glial cells and neurons takes place from the
incompatibility. This condition , known as ker- extracellular space through cell membranes.
nicterus , results in a yellow staining of the Estimates of the total extracellular space be-
brain , especially the nuclei of the basal gan- tween neurons, neuroglia, and capillaries of
glia. Unconjugated bilirubin is very lipid -sol- the brain vary widely, but some data suggest
uble and crosses the lipoid membranes of that it equals approximately 18% of wet brain
capillary endothelia in both the adult and im- weight (14 ).
mature brain. In the adult, bilirubin is bound In some pathologic processes, increased
to serum albumin and does not enter the permeability of brain capillary endothelial
brain . The immature liver of the neonate can- cells may lead to important augmentation of
not conjugate large quantities of bilirubin and the volume of the extracellular fluid , a condi-
unconjugated bilirubin passes the blood - tion referred to as brain edema . Brain edema
brain barrier to stain the brain nuclei yellow. may be local, as in areas surrounding contu -
The mortality in kernicterus is high and in- sion, infarct, or tumor, or general, as in head
fants that survive have a high incidence of injury, lead encephalopathy, and meningitis.
motor disorders and mental retardation ( 26). Local brain edema may cause herniation of
Certain regions outside the CNS have brain tissue. For instance, the cingulate gyrus
neural tissue in direct contact with the extra - may be forced to protrude beneath the falx
cellular fluid . Regions without an intervening cerebri on one side, whereas the uncus of the
barrier include (a ) the terminals of peripheral temporal lobe may engage itself across the
nerves, ( b) sensory ganglia, (c) the olfactory tentorium cerebelli and the cerebellar tonsils
epithelium, and ( d ) the optic nerve where it through the foramen magnum . All these her -
penetrates the sclera. The absence of a barrier niations cause severe damage to the brain
at these sites represent loci where protein, in- tissue. Functional manifestations of more
cluding toxins and viruses, may enter the ex- generalized brain edema comprise focal neu -
tracellular space. In some diseases, the blood - rologic deficits, a slowing of the electroen -
brain barrier may break down and substances cephalogram , and impaired consciousness.
that are normally excluded may enter the Glucocorticoids and hypertonic solutions of
brain. This is the case with penicillin, an im- urea , mannitol , or glycerol are the most com -
portant antibiotic used to treat some forms of monly used compounds to treat brain
meningitis. Normally, penicillin does not edema .
CEREBRAL AND SPINAL ARTERIAL BLOOD
BLOOD- BRAIN- BARRIER BLOOD- CSF- BARRIER

( Vascular endothelium, basement (Vascular endothelium , basement
membrane , neuroglial membrane , membrane, choroid epithelium
and glial perivascular feet) of choroid plexuses)
Intracellular fluid Cerebrospinal fluid

compartment compartment
Neurons EH X_
_J i
'
Ventricles,
tl “
I
EXTRACELLULAR
COMPARTMENT
subarachnoid cisterns
and spaces of CNS
Neuroglia a i
l T
tl
BRAIN- CSF- INTERFACE
Post-capillary (Ependyma , basement membrane ,
Arachnoid villi
venules and veins and subependymal glial
I
Cerebral veins
membrane )
VENOUS BLOOD OF DURAL

SINUSES AND SPINAL VEINS
Figure 1.14. Blood- brain barrier, the blood- CSF barrier, and the brain -CSF interface that separate the brain and CSF
from the cerebral vascular compartment The blood-brain barrier is a series of interfaces between arterial blood, CSF.
and neural tissue that regulate the transport of chemical substances . Tight junctions between endothelial cells (Figs ,
1.13 and 1 15) of cerebral capillaries (the blood-brain barrier) and a paucity of pinocytosis restrict the passage of
solutes from the blood into the extracellular compartment (i. e . interstitial fluid) The blood-CSF bdrrier is formed by
tight junctions surrounding apical regions of the cuboidal epithelium of the choroid plexus The brain-CSF Interface,
.
consisting of the ependymal lining of the cerebral ventricles and the pia-glial membrane on the external surface of
the brain, does not impede the exchange of solutes between the CSF and the brain. The extracellular compartment
has been estimated to constitute about 18% of wet brain weight
Blood - Cerebrospinal Fluid Barrier drophilic solutes between blood and CSF is
not at the choroidal capillaries as they have
The epithelium and adnexa of the choroid fenestrated endothelia that permit exchange
plexuses of the lateral , third , and fourth ven- of solutes ( Fig . 1.16). The blood-CSF barrier is
tricles actively secrete CSF. Evidence that located at tight junctions which surround and
they are an effective barrier is attested to by connect the cuboidal epithelial cells on the
the relatively higher concentration of sodium surface of the choroid plexus. Protein tracers
and chloride ions in CSF than in the plasma . like Evans blue-albumin, injected intravascu-
In composition , the CSF is the same as that of larly , stain the stroma of the choroid plexus
the interstitial fluid of the brain . The barrier but do not enter the CSF . Similarly, HRP
to passive exchange of proteins and small hy - passes through pores of choroidal capillaries
Brain capillary
Adrenergic
axon
/ Blood
L-DOPA ^
\ / Norepinephnri .
J Dopamine
( 5 Hydroxytryptamin( >
-
Tight junction
Figure 1.15. Brain capillary demonstrating a tight junction between endothelial cells that constitute part of the
blood-brain barrier Endothelial cells of brain capillaries contain enzymes that regulate the specific transport of bio-
.
genic amines (norepinephrine, dopamine, and 5-hydroxytryptamine) and amino acids. Dopa passes the blood-brain
barrier ( f), is decarboxylated to dopamine in the capillary endothelium (2) and enters neural tissue (3). where it is de-
graded by monoamine oxidase Decarboxylation of L-dopa to dopamine (2) also occurs after its incorporation into
axonal varicosities of aminergic neurons
to fill the connective tissue stroma but does transported across the blood -CSF barrier in a
not pass beyond the tight junctions which selective and limited fashion.
surround the apical regions of epithelial cells
of the choroid plexus (6). The surface area of CIRCUMVENTRICULAR ORGANS
the blood -CSF barrier is only about 0.02% of
the surface area of the blood -brain barrier. The circumventricular organs are areas of
Despite great quantitative differences in sur- specialized tissue located at strategic posi -
face area , it is probable that some circulating tions in the midline ventricular system ( Fig.
substances enter the brain via the blood -CSF 1.17). Included under this designation are ( a )
barrier (33). Available evidence suggests that the subfornical organ, ( b) the organum vascu-
some circulating peptides (e.g., insulin ) and losum of the lamina terminalis ( or supraoptic
plasma proteins ( e.g., prealbumin ) may be se- crest ), (c ) the median eminence, (d ) the neu -
lectively transported into the CSF via the rohypophysis, ( e ) the pineal body, ( f ) the sub-
blood -CSF barrier. The ependymal surface of commissural organ , and (g ) the area
the cerebral ventricles and the pia -glial mem - postrema (27, 49 ). With the exception of the
brane on the surface of the brain do not im - area postrema, located along the caudal mar-
pede exchanges between the CSF and the gins of the fourth ventricle ( Figs. 1.17 and
brain. Molecules with a relatively high 12.11 ), all circumventricular organs are un -
plasma / CSF ratio ( compared with inulin ) are paired , occupy midline positions, and are re-
Apical
microvillus
Ventricular
Apical tight
junction
Basement
32. membrane
/ >
Stroma
/ /
-,V/A
5' .
Lateral intercellular space Fenestrated capillary

Figure 1.16 . Choroid plexus villus covered by a single layer of cuboidal epithelium with apical microvilli protruding
Into the ventricular CSF The base of these cells rests upon a basement membrane. Tight junctions connecting apical
regions of the epithelial cells constitute the blood-CSF barrier The underlying connective tissue stroma contains capil-
laries with fenestrations.
Subfornical organ Subcommissural organ
Pineal
Organum
Vasculosum
Median eminence postrema
Neurohypophysis
Figure 1.17. Midsagittal section of the human brain indicating the locations of the circumventricular organs All of
these structures, except the area postrema. are unpaired, situated in the midline, and related to diencephalic struc -
tures All. except the subcommissural organ are highly vascularized and lack a blood-brain barrier Neuropeptides
have limited transport across the blood-brain barrier, but can enter and leave the brain, via the CSF. in regions of the
circumventricular organs The organum vasculosum of the lamina terminalis (OVLT) resembles the median eminence,
but its function is not yet clarified This structure, particularly prominent in rodents, is also designated as the supraoptic
crest The median eminence serves as a neuroendocrine transducer and the final common pathway by which re-
leasing factors are discharged into the hypophysial portal system
lated to portions of the diencephalon . All of traced from the cerebral aqueduct through
these structures, except the subcommissural the fourth ventricle to the caudal end of the
organ, are highly vascularized and contain central canal of the spinal cord . The function
fenestrated capillary loops surrounded by of this structure is unknown. The area
perivascular connective tissue spaces. The postrema, located at the junction of fourth
circumventricular organs, with the exception ventricle and spinal canal, has a structure
of the subcommissural organ, lack a blood - similar to that of the subfornical organ ( Fig.
brain barrier. The absence of this barrier, 12.11 ). It is surrounded by fields of terminal
demonstrated by permeability to HRP, sug- fibers containing neurophysin, oxytocin, and
gests that these tissues are permeable to pro- vasopressin, although none of these peptides
teins and peptides. can be identified within the area postrema.
The neurohypophysis is a well -known target The area postrema is considered a chemore-
of various peptidergic neuroendocrine neu - ceptor that triggers vomiting in response to
rons. Fibers from the magnocellular hypo- circulating emetic substances ( i.e., apomor-
thalamic nuclei terminate in the neural lobe phine and digitalis glycosides).
of the hypophysis around fenestrated capil - Recent evidence of the widespread distrib-
laries. These terminal fibers contain neuro- ution of peptides in the CNS suggests that the
physin, vasopressin, and oxytocin, which are CSF may be a route by which these sub-
stored and released into the general circula - stances modulate neuronal function in differ-
tion from the neural lobe of the hypophysis. ent regions of the brain (21 ). Although neural
The organum vasculosum of the lamina termi- peptides have limited access to the CNS
nals (OVLT) appears to be a vascular outlet across the blood -brain barrier, hypothalamic
for luteinizing hormone releasing hormone hormones have been detected in high concen-
( LHRH ) and somatostatin, which inhibits the trations in the circumventricular organs. The
release of somatotropin (growth hormone) peptides which have been identified in the
( 49). The OVLT may serve not only as a neu- CSF include (a ) thyroid releasing hormone
rohemal outlet for hypothalamic peptides, (TRH ), ( b ) luteinizing hormone releasing hor-
but also as a hemoneural function whereby mone ( LHRH ), (c) somatostatin (SRIF), ( d )
certain peptides, proteins, and amines in the opioid peptides, (e) cholecystokinin (CCK ),
blood are sensed by neurons with receptor ( f ) angiotensin II, ( g ) substance P (SP), ( h )
properties. The median eminence , recognized adenohypophysial hormones, and (i ) neuro-
as a circumventricular organ, serves as a neu- hypophysial hormones. There is some evi-
roendocrine transducer that translates bio- dence that neural peptides in the CSF may be
electrical activity in the central nervous sys- altered by neurologic diseases. These data
-
tem into blood borne signals in the form of raise the interesting possibility that measure-
releasing factors ( 43). The final common path- ments of neural peptides in the CSF might
way of neuroendocrine control of the anterior provide a sensitive "marker" for the anatomic
pituitary by the hypothalamus is a pool of localization of pathologic processes in spe-
neurosecretory neurons whose axons termi - cific regions of the CNS ( 21 ).
nate upon fenestrated portal capillaries in the In nonmammalian vertebrates, the circum-
median eminence, and discharge releasing ventricular organs are highly developed and
factors into the hypophysial portal system comprise a multitude of small monoamin-
( Fig. 17.18). The subfornical organ , located be- ergic cells provided with a short clublike
tween the interventricular foramina, has con- process floating freely within the CSF of the
nections with the choroid plexus and its vas- third ventricle (34 ). In mammals, many of
cular permeability suggests that it may the circumventricular organs, particularly the
regulate body fluids ( 46, 49 ). The pineal body OVLT, SCO, and subfornical organ, are
( pineal gland or epiphysis) contains special - densely innervated by serotonin-containing
ized cells known as pinealocytes and pro- fibers originating in the raphe nuclei of the
duces the hormone melatonin under the midbrain (7, 35). Other serotoninergic fibers
influence of light deprivation . The subcommis- pierce the ependymal wall of the cerebral
sural organ (SCO) is located beneath the pos- ventricles and form a relatively dense and ex-
terior commissure at the junction of the third tended supraependymal plexus, as demon -
ventricle and the cerebral aqueduct ( Fig. strated in different mammals, including hu -
14.12). Cells of SCO are not highly vascular - mans (39). These recent findings led to the
ized , but secrete a mucopolysaccharide into suggestion that serotonin may act as a neuro-
the CSF which forms filaments that converge hormone in these circumventricular organs
as Reissner's fiber. This curious fiber can be and supraependymal fibers ( 7).
24 Section 1 Regional Anatomy, Development, and Blood Supply of the Neuraxis
References 18. Gomez DG , Chambers AA ,

DiBenedetto AT, Potts DG. The
tricular administration of f’H|5 -
h vd rox v t rv pta m i ne. N euroscience
1 . Baranv EH. Inhibition of hippurate
and probenecid of in vitro uptake of
spinal cerebrospinal fluid absorp-
tive pathways . Neuroradiology
-
1981;6:115 138.
36. Pollay M , Curl F. Secretion of cere-
-
iodipamide and o iodohippurate: a I 974a;8:61-66 .
'
brospinal fluid by the ventricular

composite uptake system for iodi-
pamide in choroid plexus, kidney
19. Gomez DG , Potts DG, Deonarine
J . Arachnoid granulations of sheep:
ependvma of the rabbit . Am J Phvs -
iol 1967;213:1031-1038.
cortex and anterior uvea of several structural and ultrastructural chan - -
37. Rapoport SI . Blood brain barrier in
species. Acta Physiol Scand 1972; ges with varying pressure differ- physiology and medicine. New
-
86:12 27. ences. Arch Neurol 1974b;30: York: Raven Press, 1976.
2. Bradbury' MWB. The concept of a 169-175.
blood - brain barrier . Neyv York: John 20. Hamilton WJ , Mossman , HW .
38. Reese TS, Karnovsky MJ . Fine struc -
Wiley & Sons, 1979. I luman embrvologv. Baltimore:
-
tural localization of a blood brain
barrier to exogenous peroxidase. )
3. Bradbury MWB. The structure and Williams & Wilkins, 1972. Cell Biol 1967;34:207-217.
-
function of the blood brain barrier . 21 . Jackson IMD. Neural peptides in the 39. Richards JG , Lorez HP, Colombo
Fed Proc 1984;43:186-190. cerebrospinal fluid . Adv Biochem VE, Guggenheim R , Kiss D, Wu JY.
4. Brightman MW . The distribution Psychopharmacol 1981;28:337-356. Demonstration of supra -ependvmal
within the brain of ferritin injected 22. Javatilaka ADP. An electron micro - -
5 HT nerve fibres in human brain
into cerebrospinal fluid compart - scopic study of sheep arach - and their immunohistochemical
ments. I . Ependymal distribution . J noid granulations J Anat 1%5;99: identification in rat brain . J Phvsiol
Cell Biol 1965;26:99-123. 635-649. ( Paris ) 1981;77:219-224.
5. Brightman MW, Reese TS. Junctions 23. Kawano N , Endo M , Saito M , Yada 40. Sahar A . Choroidal orgin of cere-
between intimately apposed cell K. Origin of the capsule of a chronic
brospinal fluid . Isr j Med Sci
membranes in the vertebrate brain. J
Cell Biol 1969;40:648-677.
—
subdural hematoma an electron
microscopy studv. No Shinkei Geka
1972;8:594-596 .
41 . Sato O, Bering EA . Extra - ventricu -
6 Brightman MW', Reese TS, Feder N . 1988;16:747-752.
lar formation of cerebrospinal fluid .
Assessment with the electronmicro - 24. Leusen I . Regulation of cere - Brain Nerve (Tokyo ) 1967;19:
scope of the permeability to peroxi - brospinal fluid composition with 883-885.
dase of cerebral endothelium and reference to breathing. Physiol Rev
epithelium in mice and sharks. In : 1972;52:1-56. 42. Schachenmayr W, Friede R . The ori -
gin of subdural membranes: I . Fine
Crone C, Lassen NA , eds. Capillary 25. Livingston RB. Mechanics of cere - structure of the dura -arachnoid in -
permeability. New York: Academic brospinal fluid . In : Ruch TC, Patton terface in man. Amer J Pathol
Press, 1970:468-476. HD, eds. Physiology and bio-
1978;92:53-68.
7. Calas A, Bossier O, Arluison M, physics. Ch . 47. Philadelphia : W .B.
Bouchaud C. Serotonin as a neuro- Saunders, 1964:935-940. 43. Scott DE, Krcbisch-Dudley G. Ultra -
structural analysis of the mam -
hormone in circumventricular or - 26. Merritt HH . A textbook of neurology.
malian median eminence. In:
gans and supraependvmal fibers. In: Philadelphia : Lea & Febiger, 1979.
Scott DE, Kozlovsky GP, Wiendl A , 27. Mestres P. Old and new concepts Knigge KM, Scott DE, Kobayashi H ,
eds. Brain -endocrine interaction . III . about circumventricular organs: an Ishii S, eds. Brain-endocrine interac-
Neural hormones and reproduction . overview . Scan Electron Micros tion II. Basel : Karger, 1975:29-39.
Basel: Karger, 1978:238-250. 1978;2:137-143. 44. Selzer ME, Myers RE, Holstein SB.
8. Crone C. The permeability of capil - 28. Mettler FA . Neuroanatomv. 2d ed . Maturational changes in brain water
laries in various organs as deter- St. Louis: CV. Mosby, 1948. and electrolytes in rhesus monkey
with some implications for electro-
mined bv use of the “ indicator dif - 29 . Millen JW , Woollam DHM . Obser - genesis. Brain Res 1972;45:193-204.
fusion '’ method . Acta Physiol Scand vations on the nature of the pia
-
1963;58:292 305. mater. Brain 1961;84:514-520. 45. Spector R, Johanson CE . The mam -
9. Cutler RWP, Lorenzo AV , Barlow 30. Miner LC, Reed DJ . Composition of malian choroid plexus. Sci Am
CF. Changes in blood -brain perme- fluid obtained from choroid plexus 1989;261:68-74.
ability during pharmacologically in - tissue isolated in a chamber in situ . J 46. Summy - Long JY , Keil LC, Severs
duced convulsions. Prog Brain Res Physiol ( Lond ) 1972;227:127-139. WB. Identification of vasopressin in
-
1967;29:367 384. 31 . Ommava AK , Corrao P, Letcher FS. the subfornical organ region: effects
10. Cutler RWP, Spertel RB. Cere
brospinal fluid : a selective review.
- Head injury in the chimpanzee.
I . Biodynamics of traumatic un -
of dehydration. Brain Res 1978;
140:241 - 250.
Ann Neurol 1982;11 : 1 -10. consciousness. J Neurosurg 1973;39: 47. Taverras |M , W'ood EH . Diag-
11 . Davson H . Physiology of the cere- 152-166. nostic neuroradiology. Baltimore:
brospinal fluid . Boston : Little, 32. Pappas GD, Tennyson JM . An elec - Williams & Wilkins, 1976.
48. Vates TS, Bonting SL, Oppelt WW .
Brown and Company , 1967. tron microscopic study of the pas-
-
12. Davson 11. The blood brain barrier: sage of colloidal particles from the
blood vessels of the ciliary processes
Na- K activated adenosine triphos -
phatase formation of cerebrospinal
review lecture. J Physiol ( Lond )
1976;255: 1-28. and choroid plexus of the rabbit. | fluid in the cat. Am J Physiol
-
13. Ehrlich P. Das sauerstoff bediirfnis -
Cell Biol 1962;15:227 239. 1964;206:1165-1172.
des organismus. Fine farbenalvtis- 33. Pardridge WM , Frank HJL, Corn - 49. Weindl A , Sofroniew MV . Relation
che studie. Berlin : Herschwald, ford EM , Braun I D, Crane PD, Old - of neuropeptides to mammalian cir -
1885:69-72. endorf WII . Neuropeptides and the cumventricular organs. In: Martin
14 . Fenstermacher |D, Rail DP. Physiol - blood brain barrier. Adv Biochem JB, Reichlin S, Bick KL, eds. Ad -
ogy and pharmacology of cere - Psychopharmacol 1981;28:321-328.
34 . Parent A . Anatomical organization
vances in biochemical psychophar -
macology . Vol 28. Neurosecretion
brospinal fluid In: Fenstermacher
) D, Rail DP, eds. Pharmacology of of monoamine- and acetyl - and brain peptides. New York:
Raven Press, 1981 ;303-320.
the cerebral circulation . Vol. 1. Ox - cholinesterase-containing neuronal
ford : Pergamon Press, 1973:35-79. systems in the vertebrate hypothala - 50. Welch K . Secretion of cerebrospinal
15. Fishman RA . Cerebrospinal fluid in mus. In : Morgane PJ , Panksepp J , fluid by choroid plexus of the rabit.
diseases of the nervous system. eds. Handbook of the hypothala - Am | Physiol 1963;205:617-624.
Philadelphia: W . B. Saunders, 1980. mus. Vol . I Anatomy of the hypo - 51. Welch K , Friedman J . The cere-
16. Ford Dl 1 Blood - brain barrier: a reg- thalamus. New York: Marcel brospinal fluid valves. Brain
.
ulatory mechanism. Ann Rev Neu -
ron 1976;2:1 42
17. Goldstein GW , Betz AL. The blood -
Dekker, 1979:511-554 .
35. Parent A , Descarries L, Beaudet A .
Organization of ascending serotonin
1960;83:454-469.
52. Westergaard E , Brightman , MW .
Transport of proteins across normal
brain barrier. SciAm 1986;255: systems in the adult rat brain . A ra - cerebral arterioles. J Comp Neurol
-
74 93. dioautographic study after intraven - 1973;152:17-44 .
2
Regional Anatomy of the Brain
SUBDIVISIONS OF THE BRAIN 2.9, 2.25, 2.27, and 2.30 ). The massive paired
cerebral hemispheres are derived from the telen-
The nervous system is composed of two cephalon , the most rostral cerebral vesicle. The
parts, the central nervous system (CNS) and brainstem proper consists of three distinct
the peripheral nervous system ( PNS). The pe -
ripheral nervous system consists of the spinal
parts: (a ) the mesencephalon , ( b) the meten -
cephalon , and ( c) the myelencephalon ( Fig. 2.1 ).
and cranial nerves, while the central nervous A fourth subdivision, the diencephalon , which
system is represented by the brain and spinal is considered by some authors as the most
cord . The autonomic nervous system , often rostral segment of the brainstem ( Figs. 2.25
considered as a separate functional entity, is and 2.26 ), acts as an anatomic and functional
part central and part peripheral. interface between the brainstem and the fore-
The human brain is a relatively small brain ( i.e., telencephalon ). The mesen -
structure weighing about 1400 g and consti - cephalon, or midbrain, is the shortest division
tuting about 2% of total body weight. The of the brainstem . The metencephalon ( pons )
brain is regarded as the organ solely con - and myelencephalon ( medulla ) together con -
cerned with thought , memory, and constitute the rhombencephalon or hindbrain . The
sciousness, but these are only a few of its cerebellum is a derivative of the meten-
complex and varied functions. All informa - cephalon that develops from ectodermal
tion we have concerning the world about us thickening about the rostral borders of the
is conv eyed centrally to the brain by an elabo- fourth ventricle, known as the rhombic lip
rate sensory system . Receptors of many kinds ( Figs. 2.27, 2.30, 2.31, 3.11 A , and 3.14 ).
act as transducers which change physical and
chemical stimuli in our environment into
CEREBRAL HEMISPHERES
nerve impulses which the brain can read and
give meaning to. The ability to discriminate The paired cerebral hemispheres consist of
between stimuli of the same and different a highly convoluted gray cortex ( pallium or
types forms one of the bases for learning. At- mantle), an underlying white matter of con -
tention , consciousness, emotional experience, siderable magnitude and a collection of
and sleep are all central neural functions. deeply located neuronal masses, known as
Such higher functions as memory, imagina - the basal ganglia ( 7, 13 ) ( Figs. 2.4-2.7, 2.9, and
tion, thought, and creative ability are poorly 2.10 ). The cerebral hemispheres are partially
understood , but must be related to complex separated from each other by the longitudinal
neuronal activity. The brain is also concerned fissure. This fissure in situ contains the falx
with all kinds of motor activity, with the reg- cerebri ( Fig. 1.2). In frontal and occipital re-
ulation of visceral , endocrine and somatic gions, the separation of the hemispheres is
functions, and with the receptive and expres- complete, but in the central region the fissure
sive use of symbols and signs that underlie extends only to fibers of the broad interhemi -
communication. While the gross features of spheric commissure, the corpus callosum
the human brain are not especially impres- .
( Figs. 2.4-2.7, 2.9, and 2.10) Each cerebral
sive, its versatility, potential capabilities, effi- hemisphere is subdivided into lobes, most of
ciency, and self - programming nature render which are named after the bones of the skull
it unique among all organs of the human overlying them ( Figs. 2.2-2.4 ). Although the
body . boundaries of the various lobes as seen in the
The brain consists of four subdivisions, the gross specimen are somewhat arbitrary, mul -
cerebral hemispheres, the brainstem, the di- tiple cortical areas in each lobe are histologi -
encephalon, and the cerebellum ( Figs. 2.1-2.4, cally distinctive. The gray cellular mantle of
25
\J
:•
O. '
:
o
MAJOR SUBDIVISIONS OF THE CENTRAL NERVOUS SYSTEM o:
MAJOR COMPONENTS EMBRYONIC SUBDIVISIONS ADULT CAVITIES Î J

DERIVATIVES <9.
:
-
Q.
Cerebral hemispheres >
Telencephalon ( Cortex , white matter, Lateral J
( Endbrain )
and basal ganglia ) ventricles Q
O
Cerebrum Prosencephalon 3
( Forebrain )
Diencephalon
Diencephalon (Thalamus, Third <
( Interbrain ) subthalamus and ventricle 9.
C
hypothalamus )
3
Brain :
Midbrain Cerebral D
( Encephalon ) Mesencephalon
( Midbrain )
( tectum , tegmentum aqueduct
and crura cerebri ) (of Sylvius)
Pons
Brainstem Rhombencephalon Mctencephalon and I
( Hindbrain ) ( Afterbrain ) Fourth Q
Cerebellum
ventricle cn
( Rhomboid T3
Myelencephalon Medulla oblongata fossa )
(Medula )
<
O
Spinal cord Neural tube Spinal cord Central canal

( Medulla spinalis) (Caudal portion )
c
2
Figure 2.1 . Principal subdivisions of fhe human central nervous system their embryonic origin and major derivatives
,
in adults, as well as the corresponding ventricular compartments

Central sulcus
Postcentral gyrus Precentral gyrus
Supramarginal gyrus
Superior
Frontal
Angular gyrus gyri
Middle
Inferior frontal
gyrus
Tentori
cerebelli
Maxillary sinus
Lateral sulcus
Inferior
Middle Superior Temporal gyri
Figure 2.2. Lateral view of the brain exposed in the skull to show topographic relationships
Central sulcus Postcentral sulcus

Precentral sulcus Sup. parietal lobule
Sup. frontal sulcus

Inf . parietal lobule
Parieto- occipital
Inf . frontal sulcus
sulcus
Lateral sulcus
Orbital gyri
Preoccipital notch
Medulla oblongata
a
1. Sup. frontal gyrus 7. Angular gyrus
2. Middle frontal gyrus a Lateral occipital gyrus
3.Inf. frontal gyrus 9. Sup. temporal gyrus
4.Precentral gyrus 10- Middle temporal gyrus
5.Postcentral gyrus 11 Inf. temporal gyrus
6. Supramarg. gyrus 12. Cerebellum
Figure 2.3. Lateral surface of the brain

Longitudinal cerebral fissure
Superior
frontal gyrus-
— Middle
frontal gyrus
Inferior
frontal gyrus
Precentral ,
sulcus -] Precentral
gyrus
Postcentral
gyrus J
Central
sulcus
Paracentral
lobule
Superior
parietal lobule
Parieto-occipital sulci
Figure 2.4. Superior view of tbe brain indicating the main sulci and gyri.
the cerebral cortex in humans is highly con - Lateral Surface

voluted . The crest of a single convolution is
referred to as a gyrus. Sulci ( fissures ) separate The two most important sulci for topo-
the various gyri, producing a pattern with graphic orientation on the lateral convexity of
more or less constant features. On the basis of the hemisphere are the lateral and central
the more constant sulci and gyri, the cere- sulci ( Figs. 2.2 and 2.3). The lateral sulcus be-
brum is divided into six so-called lobes: (a ) gins interiorly in the Sylvian fossa and ex-
frontal, ( b) temporal, (c) parietal, ( d ) occipital , tends posteriorly, separating the frontal and
(e) insular, and (f ) limbic. Neither the insula temporal lobes. Caudally this sulcus sepa -
nor the limbic lobe is a true lobe. The insula is rates portions of the parietal and temporal
a cortical area buried in the depths of the lat - lobes. The terminal ascending ramus of the
eral sulcus ( Figs. 2.8, 2.11, and 2.14 ) . The lim - sulcus extends into the inferior part of the
bic lobe is a highly heterogeneous entity on parietal lobe. Portions of the frontal, parietal,
the medial aspect of the hemisphere consist- and temporal lobes, adjacent to the lateral
ing of portions of the frontal, parietal, occipi - sulcus, which overlie the insular region, are
tal, and temporal lobes which surround the referred to as the opercular portions of these
upper part of the brainstem ( Fig. 18.1 ). lobes ( Fig. 2.8). The central sulcus is a promi-
/ Superior frontal gyrus
— Middle
frontal gyrus
, — Lateral
^ orbital gyrus
Gyrus rectus Inferior

li I frontal gyrus
Olfactory Ml / Lateral
bulb sulcus
Oculomotor ! Superior
nerve temporal gyrus
Middle
temporal gyrus I
j
Parahippocampal Optic nerve
gyrus
Pons -
Hypophysis
Nerves
VII and VIII Abducens
nerve
Inferior Nerve IX
olive
Nerve X
Nerve XII Nerve XI
Pyramid
Figure 2.5. Frontal view of the rostral aspect of the brain.
Paracentral lobule Callosal sulcus

Cingulate sulcus
( marginal branch ) Superior frontal gyrus
Cingulate sulcus
Precuneus
Cingulate gyrus
Parietooccipital
sulcus Corpus callosum
Septum
pellucidum
Cuneu
Calcarine
sulcus. ^\subcallosal
rea
Gyrus rectus
Anterior
commissure
Gyrus lingula
Fornix
Isthmus of gyrus cinguli
Uncus
Hippocampal sulcus i
Parahippocampal gyrus
Occipitotemporal gyrus
Collateral sulcus
Figure 2.6. Medial surface of the cerebral hemisphere with diencephalic structures removed.
Intraparietal sulcus ,Superior parietal lobule

-
Parieto occipital
Superior sulcus
occipital gyrus
Angular
gyrus
Transverse Calcarine
occipital sulcus
sulcus '
Lateral
Anterior occipital
occipital gyrus
sulcus '
Lingual
gyrus Cerebellar
hemisphere
Horizontal
fissure '
Tonsil
Figure 2.7. Posterior view of the cerebral hemispheres and cerebellum
Central sulcus
Parietal
operculum
^
Frontal operculum
Long insular
insular
Transverse
temporal
Limen insula
Superior temporal
gyrus
Temporal operculum
Figure 2.8 . Right cerebral hemisphere with the banks of the lateral sulcus drawn apart to expose the Insula
Longitudinal cerebral fissure

Olfactory sulcus Gyrus rectus
Olfactory bulb
Orbital gyri Olfactory tract
Optic chiasm
Inf. frontal gyrus
Lateral and medial

' eminences
Lateral sulcus
Oculomotor nerve - Uncus
Trochlear nerve r - .J Motor root ( NI).
Trigeminal nerve r. .- VCollateral sulcus
( sensory root )
Facial nerve
Obi. fasciculus
of pons Intermediate nerve
Flocculus
f* Vestibulocochlear
nerve
'Glossopharyngeal nerve
Lateral recess
(DC ventricle) Olive
Pyramidal decussotion
Vagus nerve
Hypoglossal nerve
^
' Accessory nerve
First cervical nerve Second cervical nerve
+: Mammillary body; cerebral peduncle

0 = Abducens nerve; pyramid of medulla
Figure 2.9 . Inferior surface of the brain showing the cranial nerves
nent sulcus running from the superior mar - lobe has four principal convolutions: (a ) a pre-
gin of the hemisphere downward and for - central gyrus that parallels the central sulcus,
ward toward the lateral sulcus ( Figs. 2.2 and and ( b) three horizontally oriented convolu -
2.3). Usually , this sulcus is bowed in two lo- tions, the superior , middle , and inferior frontal
cations, and superiorly it does not extend gyri ( Figs. 2.2 and 2.3). The anterior boundary
onto the medial surface of the hemisphere for of the precentral gyrus is the precentral sulcus.
any distance. The depths of the sulcus consti- The precentral gyrus and the anterior bank of
tute the boundary between the frontal and the central sulcus comprise the primary motor
parietal lobes. area , where all parts of the body are repre-
sented in a distorted but topographic manner
( Fig . 20.18) . Regions of the frontal lobe rostral
FRONTAL LOBE
to the primary motor area are referred to as
It is the largest of all the lobes of the brain , premotor and prefrontal areas. The broad mid -
comprising about one-third of the hemi- dle frontal gyrus often is divided by a shal-
spheric surface. Its large size represents one low horizontal sulcus into upper and lower
of the most characteristic morphologic fea - tiers ( Figs. 2.2 and 2.3). The inferior frontal
tures of the human brain. The frontal lobe ex- gyrus is divided by anterior and horizontal
tends rostrally from the central sulcus to the rami (limbs ) of the lateral sulcus into three
frontal pole; its inferior lateral boundary is parts: (a ) pars orbitalis , ( b) pars triangularis ,
the lateral sulcus. The convexity of the frontal and (c) pars opercularis . The pars triangularis
32 Section I Regional Anatomy. Development, and Blood Supply of the Neuraxis
Gyrus rectus
Frontal lobe
Optic tract . ( orbital surface )
Infundibulum
Rhinal sulcus Anterior

perforated
Inferior temporal
substance
gyrus .
- Amygdaloid
complex
Uncus
Parahippocampal — Hippocampal
gyrus \ formation
Occipitotemporal —
gyrus
Collateral
sulcus ' Choroid
plexus
Gyrus lingula
Lateral ventricle
( posterior horn )
Corpus callosum ( splenium )
Figure 2.10. Inferior surface of the brain following transection of the midbrain The inferior and posterior horns of the
left lateral ventricle have been opened and portions of the temporal and occipital lobes have been removed.
and opercularis in the dominant hemisphere 2.3 and 2.6 ). On the convexity of the hemi -
( usually the left in right - handed individuals ) sphere, the posterior boundary is arbitrarily
are referred to as Broca' s speech area , a region considered as an imaginary line projected
concerned with the motor mechanisms of from the superior limit of the parieto-occipi -
speech formulation. The inferior surface of tal sulcus to the small indentation on the infe-
the frontal lobe lies on the superior surface rior surface known as the preoccipital notch
of the orbital part of the frontal bone and is ( Fig. 2.3) . Three parts of the parietal lobe are
concave ( Figs. 2.4, 2.9, and 2.10 ). The olfactory distinguished: (a ) a postcentral gyrus running
bulb and tract lie in a sulcus near the medial parallel and caudal to the central sulcus, ( b ) a
margin of the hemisphere known as the olfac - superior parietal lobule , and (c) an inferior pari -
tory sulcus. The gyrus rectus lies medial to the etal lobule. The postcentral gyrus, usually not
olfactory sulcus and the medial orbital gyrus is continuous but broken into superior and infe-
located lateral to this sulcus. The orbital gyri rior segments, lies between the central and
occupy the concave lateral area . postcentral sulci. The posterior bank of the
central sulcus and the postcentral gyrus con-
PARIETAL LOBE stitute the primary somesthetic area , the cortical
region where impulses concerned with tactile
The boundaries of this lobe are not precise, and kinesthetic sense from superficial and
except for its anterior border on the lateral deep receptors converge and are somatotopi-
convexity formed by the central sulcus and cally represented . The majority of cortical
its posterior border on the medial aspect of neurons in the postcentral gyrus are con-
the hemisphere ( parieto-occipital sulcus ) ( Figs. cerned with fixed receptive fields on the con -
Corpus callosum
( anterior forceps)
Corpus callosum
( genu)
Insular cortex
Cingulum
Corpus
callosum - Transverse
(
temporal
( body ) gyrus Heschl )
Centrum Longitudinal
semiovale striae
Auditory radiation
- Tapetum
Corpus callosum Optic radiation

( splemum )
Figure 2.11. Dissection of the superior surface of the hemispheres exposing the corpus callosum, cingulum, longitudi-
nal striae, and the optic and auditory radiations.
Corona radiata Central sulcus
Posterior limb
of internal capsule
Anterior limb
internal capsule Optic radiation
Optic tract geniculate

Crus cerebri body
Middle cerebellar peduncle

Pyramid
Inferior olive
Pyramidal decussation \ \
Figure 2.12. Dissection demonstrating the continuity and relationships of the corona radiata, the internal capsule,
the crus cerebri, and the medullary pyramid.
.
34 Section I Regional Anatomy Development, and Blood Supply of the Neuraxis
tralateral side of the body that are place-spe- boundary of this lobe is the parieto-occipital
cific, modality-specific, and related to dis- sulcus on the medial aspect of the hemi-
criminative aspects of sensation. The intra- sphere ( Fig. 2.6). The lateral surface of the oc-
parietal sulcus , a horizontally oriented sulcus, cipital lobe is poorly delimited from the pari-
divides portions of the parietal lobe caudal to etal lobe and is composed of a number of
the postcentral gyrus into superior and infe- irregular lateral occipital gyri which are sepa-
rior parietal lobules ( Fig. 2.3). The inferior rated into groups by the lateral occipital sulcus.
parietal lobule consists of two gyri, the supra- ( Figs. 2.3 and 2.6 ) . On the medial aspect of the
marginal gyrus , arching along both banks of hemisphere, the occipital lobe is divided by
an ascending ramus of the lateral sulcus, and the calcarine sulcus into the cuneus and the lin-
the angular gyrus , which surrounds the as- gual gyrus ( Figs. 2.6 and 2.7). The calcarine
cending terminal part of the superior tempo- sulcus joints the parieto-occipital sulcus ros-
ral sulcus ( Figs. 2.2 and 2.3). The inferior pari- trally in a Y-shaped formation. The cortex on
etal lobule represents a cortical association both banks of the calcarine sulcus represents
area where various multisensory perceptions the primary visual cortex (i.e, the striate cor-
of a higher order from adjacent parietal tem- tex ). The visual cortex in each hemisphere re-
poral and occipital regions overlap. This receives impulses from the temporal half of the
gion is especially concerned with mnemonic ipsilateral retina and the nasal half of the con-
constellations that form the basis for under- tralateral retina, and is concerned with per-
standing and interpreting sensory signals. ception from the contralateral half of the vi-
This is one region of the cortex where differ- sual field.
ent disturbances occur as a consequence of le-
sions in the dominant and nondominant INSULA
hemisphere.
The insula is a cortical area that lies buried
TEMPORAL LOBE in the depths of the lateral sulcus; it can be
seen only when the temporal and frontal
This large lobe lies ventral to the lateral lobes are separated . This "lobe" is, in fact, a
sulcus and on its lateral surface displays triangular cortical area, the apex of which is
three obliquely oriented convolutions, the su - directed forward and downward to open into
perior , middle , and inferior temporal gyri ( Figs. the lateral fossa ( Figs. 2.8, 2.11, and 2.14). The
2.2 and 2.3). The superior temporal sulcus surface is covered by the gyri breves and
courses parallel to the lateral sulcus and its longus (short and long gyri) which course
ascending ramus terminates in the angular nearly parallel to the lateral sulcus. The rela-
gyrus. On the inner bank of the lateral sulcus, tionships of this region can be appreciated in
several short, oblique convolutions form the transverse and horizontal sections of the
transverse gyri of Heschl. These gyri consti- -
hemisphere ( Figs. 2.13 2.16). The opening
tute the primary auditory cortex in humans leading to the insular region is called the
( Figs. 2.8 and 2.11 ). The inferior surface of the limen insula. The temporal, frontal, and pari-
temporal lobe, which lies in the middle fossa etal opercular regions cover the insula .
of the skull, reveals part of the inferior tempo-
ral gyrus , the broad occipitotemporal gyrus , and Medial Surface
the parahippocampal gyrus ( Figs. 2.9 and 2.10).
The parahippocampal gyrus and its most me- Convolutions on the medial surface can be
dial protrusion, the uncus , are separated from studied in a hemisected brain. These convolu -
the occipitotemporal gyrus by the collateral tions are somewhat flatter than those on the
sulcus ( Fig. 2.6). The rostral part of the convexity. The most prominent structure on
parahippocampal gyrus, the uncus, and the the medial surface is the massive interhemi -
lateral olfactory stria constitute the pyriform spheric commissure, the corpus callosum ( Figs.
( pear-shaped ) lobe, parts of which constitute 2.6, 2.11, 2.20, 2.22, and 2.28). This structure,
the primary olfactory cortex ( Figs. 2.6, 2.7, and composed of millions of myelinated fibers,
2.10). reciprocally interconnects broad regions of
the two hemispheres. Different parts of the
OCCIPITAL LOBE corpus callosum are referred to as the ros-
trum , genu , body , and splenium ( Figs. 2.11 and
This small lobe rests on the tentorium 2.20). Fibers in this structure spread out as a
cerebelli ( Figs. 2.2 and 2.7). The rostral mass of radiations to nearly all parts of the
Column of fornix Corpus callosum

Caudate nucleus
( head ) —
Lateral ventricle
horn )
Internal capsule
( ant limb )—
Putamen
Extreme capsule
— — Globus pallidus
Claustrum
Thalamus
External capsule —
- Third ventricle
Internal capsule Posterior

( post limb ) - commissure
Pulvinar
Caudate nucleus
Hippocampal
formation
Superior colliculus '
Cerebellar vermis
Figure 2.13. Horizontal section through the cerebral hemispheres showing relationships of internal structures to the in
ternal capsule.
cortex. Callosal fibers, projecting to parts of sion and analytic functions are organized al -
the frontal and occipital lobes, form the so- most exclusively in the dominant hemi -
called anterior and posterior forceps , which are sphere. The nondominant hemisphere is con -
best appreciated in horizontal sections of the cerned with spatial concepts, recognition of
brain ( Fig. 2.11 ). The corpus callosum forms faces, and some musical ability. The callosal
the floor of the longitudinal fissure, as well as sulcus separates the corpus callosum from the
a good part of the roof of the lateral ventricle. cingulate gyrus. Posteriorly, this sulcus
It plays an important role in in ter hemispheric curves around the splenium to be continued
transfer of learned discriminations, sensory into the temporal lobe as the hippocampal sul -
experience, and memory. Although surgical cus ( Fig. 2.6). The cingulate gyrus, dorsal to the
section of the corpus callosum in humans callosal sulcus, encircles the corpus callosum
produces little disturbance of ordinary be- and consists of two tiers. The cingulate sale us ,
havior, temperament, or intellect, informa - dorsal to the cingulate gyrus, runs parallel to
tion received exclusively by the nondominant the callosal sulcus, but near the splenium
hemisphere ( usually the right ) cannot be turns dorsally as the marginal sulcus . The an -
communicated in speech or writing ( 4, 5). In terior portion of cortex dorsal to the cingulate
these same patients there was no impairment gyrus is the medial surface of the superior
of speech or writing when information was frontal gyrus. The paracentral lobule is formed
processed in the dominant hemisphere ( left ). by the precentral and postcentral gyri and is
These studies conclude that linguistic expres- notched in its middle portion by the central
Internal capsule lant. limb) Anterior commissure

Caudate nucleus
Frontal lobe
Putamen
Column of fornix
Insula
Third ventricle
Red nucleus
Crus cerebri
Substantia nigra — Lateral geniculate
Medial geniculate
body "
Hippocampal
formation
Cerebral aqueduct
Occipital lobe
Cerebellar vermis
Figure 2.14. Horizontal section through the cerebral hemispheres passing through the anterior commissure and the
crus cerebri.
sulcus ( Fig. 2.6). The paracentral sulcus forms The parahippocampal gyrus is directly con-
the rostral border of this lobule, while the tinuous with the cingulate gyrus by a narrow
marginal sulcus forms the caudal border. The strip of cortex, posterior and inferior to the
portion of the parietal lobe caudal to the splenium, known as the isthmus of the cingu -
paracentral lobule is known as the precuneus. late gyrus ( Fig. 2.6). The parahippocampal
This lobule lies immediately rostral to the gyrus, the most medial convolution of the
parieto-occipital sulcus previously discussed . temporal lobe, is bounded laterally by the rhi-
nal and collateral sulci and superiorly and me-
LIMBIC LOBE dially by the hippocampal sulcus ( Figs. 2.9 and
2.10). Rostrally, the parahippocampal gyrus
The limbic lobe consists of large cortical hooks around the hippocampal sulcus to
convolutions on the medial aspect of the form a medially protruding convolution, the
hemisphere which surround the rostral part uncus. The proximity of the uncus to the cere-
of the brainstem and the interhemispheric bral peduncle should be noted . There are dif -
commissure ( Fig. 18.1 ). As originally defined ferences of opinion concerning what should
by the French anatomist Paul Broca in 1878 be lumped together as the so-called "limbic
(1 ), the limbic lobe includes the subcallosal , lobe" ( 2 ). While all of these structures appear
cingulate , and parahippocampal gyri , as well as early in phylogenesis, physiologic evidence
primitive cortical derivatives, the hippocampal suggests that wide functional differences
formation and the dentate gyrus , which in the exist between various components and sepa-
course of development have become invagi - rate functions are expressed by distinctive
nated within the temporal lobe ( Fig. 2.10). neural mechanisms.
Cavum septum pellucidum

Corpus callosum
Column of fornix Lateral ventricle

/ Caudate nucleus
Globus pallidus
Internal capsule
Putamen
/ External capsule
/
[V
Lateral sulcus Claustrum
Extreme capsule
Insular cortex
Olfactory area
Uncus Anterior commissure
Amygdaloid complex
figure 2.15 . Frontal section of the brain passing through the columns of the fornix and the anterior commissure
Thalamus
Ant nuc group

Med nuc group
Vent tier nuc
r\ Corpus callosum
Fornix
\
Caudate nucleus
Internal capsule
Putamen
* 4
T
*
fl
m .
A*
%
I V,
-
It
Extreme capsule
1 Globus pallidus
/
External capsule \
Claustrum Amygdaloid complex
Mammillary body
Figure 2.16. Frontal section of the brain at the level of the mammillary bodies In this section, the main nuclear
groups of the thalamus are identified and portions of all components of fhe basal ganglia are present . The amyg-
daloid nuclear complex lies in the temporal lobe internal to the uncus and ventral to the lentiform nucleus.
Inferior Surface the semioval center (or centrum semiovale )

( Fig. 2.11 ).
The inferior surface of the hemisphere
consists of two parts: ( a ) a larger posterior
PROJECTION FIBERS
portion, representing the inferior surfaces of
the temporal and occipital lobes, and ( b) the Afferent and efferent fibers conveying im-
orbital surface of the frontal lobe ( Figs. 2.5, pulses to and from the entire cerebral cortex
2.9, and 2.10). The inferior surface of the oc - enter the white matter and are arranged as ra -
cipital lobe and the posterior part of the tem - diating bundles that converge toward the
poral lobe lie on the tentorium cerebelli ( Figs. brainstem ( Figs. 2.12 and 2.19 ). These radiat -
1.2 and 2.2), while rostral parts of the tempo- ing projection fibers are known as the corona
ral lobe lie in the middle cranial fossa . Gyri radiata. Near the upper part of the brainstem
present in this posterior part include (a ) the these fibers form a compact band known as
lingual gyrus, ( b ) the extensive occipitotem - the internal capsule , which is flanked medially
poral gyrus, and (c ) the parahippocampal and laterally by nuclear masses ( Figs. 2.13,
gyrus and uncus ( Fig. 2.10). Part of the infe- 2.15, 2.16, and 2.19 ). Three distinct parts of
rior temporal gyrus may be seen lateral to the the internal capsule are evident in horizontal
occipitotemporal gyrus. A small part of the sections of the hemispheres: ( a ) an anterior
isthmus lies medially posterior to the sple- limb, ( b ) a posterior limb, and (c ) a genu ( Fig.
nium of the corpus callosum ( Fig. 2.6). The 2.13). The anterior limb partially separates two
orbital surface of the frontal lobe has a deep, of the largest components of the basal gan-
straight sulcus medially, the olfactory sulcus, glia , the caudate nucleus, and the putamen
which contains both the olfactory bulb and ( Figs. 2.13, 2.14, and 2.15). Fibers in the ante-
tract ( Figs. 2.5, 2.9, and 2.10 ). The gyrus rectusrior limb of the internal capsule are directed
lies along the ventromedial margin of the horizontally, obliquely, laterally, and up-
hemisphere medial to the olfactory sulcus. wards toward the frontal lobe, and in hori-
The region lateral to the olfactory sulcus con- zontal sections of the hemisphere appear to
tains the orbital gyri whose convolutional be cut in the longitudinal axis of the fiber
patterns are variable ( Figs. 2.5 and 2.10 ). Pos- bundles ( Figs. 2.12, 2.13, 2.14, and 2.19 ). In
teriorly, the olfactory tract divides into medial horizontal sections, the anterior and posterior
and lateral olfactory striae ( Figs. 2.9 and 2.10). limbs of the internal capsule meet at an ob-
Caudal to this is the olfactory trigone and the tuse angle with the apex directed medially.
anterior perforated substance , a region studded The larger and longer posterior limb of the in -
with small openings through which numer- ternal capsule is flanked medially by the di -
ous small blood vessels pass to deep regions encephalon and laterally by a part of the
( Figs. 2.9, 2.10, 2.24, and 4.11 ). basal ganglia known as the lentiform nucleus
.
(Figs 2.13, 2.16, and 2.19). The region of junc -
White Matter tion between the anterior and posterior limbs
of the internal capsule is referred to as the
The massive white matter of the cerebral genu . Fibers in the posterior limb of the inter-
hemisphere forms the medullary core of the nal capsule course in nearly a vertical plane
cortical convolutions and contains basically toward the brainstem , and in horizontal sec-
three types of fibers in prodigious quantity. tions fibers appear to be cut transversely ( Fig.
Fibers within the white matter are classified 2.13). The most posterior component of the
as ( a ) protection fibers that convey impulses ei - posterior limb of the internal capsule contains
ther from the cortex to distant loci, or from fibers, radiating toward the calcarine sulcus,
distant loci to the cortex, ( b) association fibers known as the optic radiation ( Figs. 2.11, 2.12,
that interconnect various cortical regions of 2.19, and 2.36). Afferent fibers in the internal
the same hemisphere, and (c) commissural capsule arise mainly from the thalamus and
fibers that interconnect corresponding cortical project to nearly all regions of the cortex;
regions of the two hemispheres. The white these fibers are referred to as thalamocortical
matter extends from the cortex to the basal radiations ( Fig. 2.19). Efferent fibers in the in -
ganglia and the ventricular system. The com- ternal capsule arise from cells in various re-
mon central mass of the white matter, con- gions of the cerebral cortex and project to
taining commissural, association , and projec- specific nuclear masses in the brainstem and
tion fibers, has an oval appearance in spinal cord . These fibers are categorized as
horizontal sections of the brain and is termed corticothalamic, corticopontine, corticobul -
bar, and corticospinal. Cortical fibers project - ASSOCIATION FIBERS

ing to the brainstem and spinal cord traverse
the internal capsule and enter the crus cere- Association fibers are divided into long
bri , its equivalent at midbrain levels ( Figs. and short groups. Short association fibers arch
2.12, 2.14, 2.24, and 2.26). The continuity of through the floor of each sulcus to connect
projection fibers in the internal capsule, the adjacent convolutions and course trans-
crus cerebri, and the medullary pyramid is versely to the long axis of the sulci ( Fig. 2.17).
shown in Figure 2.12. Long association fibers , interconnecting cortical
Postcentral sulcus
Central sulcus
Supramarginal
gyrus
y Superior
Intraparietal frontal sulcus
gyrus -
Precentral
Angular SK. sulcus
gyrus -
Parieto-occipital j
gyrus
Insular cortex
Transverse
occipital Superior
Temporal
sulcus
Inferior | sulci
Postcentral sulcus
Figure 2.17 . Lateral view of the brain after removal of the cortical gray matter The medullary laminae and short as-
sociation fibers of major gyri are indicated
Superior longitudinal fasciculus
Arcuate fasciculus
Claustrum
Uncinate
fasciculus
Fronto-occipital fasciculus
Inferior longitudinal fasciculus
Figure 2.18 . Dissection of the lateral surface of the hemisphere revealing the long association fibers interconnecting
cortical regions in different lobes
regions in different lobes within the same and middle frontal gyri with anterior por-
hemisphere, form three main bundles: (a ) the tions of the temporal lobe ( Figs . 2.18 and
uncinate fasciculus, ( b ) the arcuate fasciculus, 2.19) . A deeply placed part of this fasciculus
and ( c ) the cingulum ( Figs. 2.18 and 2.20) . is thought to connect the frontal and occipital
The uncinate fasciculus is a compact bundle lobes ( i .e. , inferior occipitofrontal fasciculus).
between the limen insula which connects the The arcuate fasciculus sweeps dorsally around
orbital frontal gyri and parts of the inferior the insular region and its fan-shaped ends
Somatosensory Posterior limb i internal

radiation Anterior limbi capsule
Frontopontine
fibers
Uncinate
fasciculus
radiation
Anterior commissure
Auditory radiation
Lentiform nucleus (removed)
Figure 2.19. Dissection of the lateral aspect of the cerebral hemisphere to reveal the corona radiata and the optic
radiation. The lentiform nucleus (asterisk ) has been removed.
Cingulum
Paracentral lobule
Fornix
Corpus callosum
Parietooccipital
sulcus
Corpus
callosum
( rostrum)
Anterior commissure
Spiral fibers ot Uncus

Calcarine
sulcus hippocampus Fimbria of
fornix
Figure 2.20. Dissection of the medial surface of the left cerebral hemisphere exposing the cingulum. The dien-
cephalon has been removed.
connect the superior and middle frontal gyri distinguished in the gross specimen ( Fig.
with parts of the temporal lobe. A group of 18.12). A small anterior part of the commis-
superiorly situated fibers in this bundle, ex- sure interconnects olfactory structures on the
tending caudally into portions of the parietal two sides ( Fig. 18.8), while the larger poste-
and occipital lobe, is known as the superior rior part mainly interconnects regions of the
longitudinal fasciculus ( Fig. 2.18). middle and inferior temporal gyri.
The cingulum , the principal association
bundle on the medial aspect of the hemi- BASAL GANGLIA
sphere, lies in the white matter of the cingu -
late gyrus ( Fig. 2.20). This bundle contains Basal ganglia are large subcortical nuclear
fibers of variable length which connect re- masses derived mostly from the telen-
gions of the frontal and parietal lobes with cephalon ( Figs. 2.13-2.16). Structures com-
parahippocampal gyrus and adjacent tempo- posing the basal ganglia are the caudate nu -
ral cortical regions ( Figs. 2.11 and 2.20). The cleus , the putamen , the globus pallidus , and the
cortical area deep to the insula contains asso- amygdaloid nuclear complex. The caudate nu -
ciation fibers in the extreme and external cap- cleus and putamen constitute the striatum.
sules ( Figs. 2.13, 2.15, and 2.16). These cap- The term lentiform nucleus (lenticular nucleus)
sules are two thin layers of white matter refers to the putamen and the globus pal-
separated by a sheet of gray matter, known as lidus. The lentiform nucleus, with the size
the claustrum. All three of these structures and shape of a Brazil nut, appears in trans-
overlie the lateral aspect of the basal ganglia . verse sections as a wedge with the apex di-
rected medially. This nuclear mass lies be-
tween the internal and the external capsules.
COMMISSURAL FIBERS
A slightly curved vertical lamina of white
Commissural fibers are represented princi- matter divides the lentiform nucleus into an
pally by two structures: (a ) the corpus callo- outer portion, the putamen, and an inner por-
sum and (b) the anterior commissure. The tion, the globus pallidus.
corpus callosum is a broad, thick plate of dense
myelinated fibers that reciprocally intercon- Putamen
nect broad regions of the cortex in all lobes
with corresponding regions of the opposite This structure is the largest and most lat-
hemisphere ( Figs. 2.6, 2.11, and 2.20 ). These
eral component of the basal ganglia , lying be -
fibers traverse the floor of the hemispheric tween the external medullary lamina of the
fissure, form most of the roof of the lateral globus pallidus and the external capsule
ventricles, and fan out in a massive callosal -
( Figs. 2.13 2.16). It is traversed by numerous
radiation as they are distributed to various fascicles of myelinated fibers directed ventro-
cortical regions ( Fig. 2.22). As mentioned ear- medially toward the globus pallidus, but
lier, the various parts of the corpus callosum these are seen clearly only in stained sections.
The rostral part of the putamen is continuous
are designated as (a ) rostrum, (b) genu, (c)
with the head of the caudate nucleus ( Fig.
body, and (d ) splenium. The genu contains
fibers interconnecting rostral parts of the 19.5).
frontal lobes. Fibers from the remaining parts
of the frontal lobe and the parietal lobe tra- Globus Pallidus
verse the body of the corpus callosum. Fibers The globus pallidus forms the most medial
traversing the splenium relate regions of the part of the lentiform nucleus and consists of
temporal and occipital lobes. Fibers in the two segments separated by the internal
splenium of the corpus callosum, which medullary lamina of the globus pallidus
sweep interiorly along the lateral margin of ( Figs. 2.13, 2.15, and 2.16). The globus pal-
the posterior horn of the lateral ventricle and lidus appears pale and homogeneous in
separate the ventricle from the optic radia- freshly sectioned brains. Its medial border is
tion, form the tapetum ( Figs. 2.11 and 2.22). formed largely by the fibers of the posterior
The anterior commissure is a small compact limb of the internal capsule.
bundle which crosses the midline rostral to
the columns of the fornix, which is the major Caudate Nucleus
efferent bundle of the hippocampal forma-
tion ( Figs. 2.6, 2.14, 2.15, and 2.20). This com- The caudate nucleus is an elongated ,
missure consists of two parts that cannot be arched gray mass related throughout its ex -
tent to the lateral cerebral ventricle ( Figs. foramen, has a triangular shape in frontal sec-
2.13-2.16 and 19.5). It consists of an enlarged tion, and extends forward , laterally and ven -
rostral part, called the head of the caudate nu - trally, to end in a rounded termination in the
cleus, which protrudes into the anterior horn white matter of the frontal lobe ( Figs. 2.13,
of the lateral ventricle. The body of the cau - 2.15, and 2.21 ). The roof and rostral wall of
date nucleus lies dorsolateral to the thalamus this horn are formed by the corpus callosum,
near the lateral wall of the lateral ventricle. while its medial wall is the septum pellucidum
The tail of the caudate nucleus follows the which separates the ventricles of the two
curvature of the inferior horn of the lateral hemispheres ( Fig. 2.6 ). The lateral wall of the
ventricle and enters the temporal lobe ( Fig. ventricle is formed by the head of the caudate
2.13). The tail of the caudate nucleus termi - nucleus whose surface bulges convexly into
nates in the region of the amygdaloid nuclear the cavity ( Figs. 2.13-2.15 and 2.29A ).
complex ( Fig. 2.16).
Body of the Lateral Ventricle
Amygdaloid Nuclear Complex
The body of the lateral ventricle extends
The amygdaloid nuclear complex is a gray caudally from the interventricular foramen
mass in the dorsomedial part of the temporal to an ill -defined point near the splenium of
lobe which underlies the uncus ( Figs. 2.10, the corpus callosum . This narrow arched
2.15, and 2.16). This complex lies dorsal to the part of the ventricle continues until the ven -
hippocampal formation and rostral to the tip tricle begins to widen into the collateral
of the inferior horn of the lateral ventricle. trigone ( referred to by neuroradiologists as
The amygdaloid complex gives rise to fibers the atrium ). The collateral trigone composes
of the stria terminalis , which arch along the that part of the lateral ventricle near the
entire medial border of the caudate nucleus splenium of the corpus callosum where the
and are especially evident near the junction body of the lateral ventricle is confluent
of the caudate nucleus and thalamus ( Figs. with the temporal and occipital horns ( Fig.
2.25 and 2.29B ). The terminal vein lies near 2.21) .
the stria terminalis. Despite its close topo-
graphic relationship with the caudate nu - Inferior Horn
cleus, the amygdaloid complex appears to be
functionally more closely related to the so- The inferior horn portion of the lateral
called limbic system than to the basal ganglia. ventricle curves downward and forward
around the posterior aspect of the thalamus,
LATERAL VENTRICLES and extends rostrally into the medial part of
the temporal lobe to end approximately 3 cm
The ependyma -lined cavities of the cere- from the temporal pole ( Fig. 2.10 ). The roof
bral hemisphere constitute the lateral ventri- and lateral wall of this horn are formed by
cles. The arched-shaped lateral ventricles the tapetum ( Figs. 2.11 and 2.22 ) and the
contain cerebrospinal fluid and conform to optic radiation; the floor contains the collat -
the general shape of the hemispheres ( Fig. eral eminence caused by the deep collateral
2.21 ). The lateral ventricles can be divided sulcus ( Fig. 2.10 ). The inferior horn of the
into five parts: (a ) the anterior ( frontal ) horn, lateral ventricle contains the hippocampal for -
( b) the ventricular body, (c) the collateral mation in the medial wall of the horn which
(atrium ) trigone, (d ) the inferior ( temporal ) extends from the region of the splenium to
horn, and (e) the posterior (occipital) horn. the temporal tip of the ventricle ( Figs. 2.10,
Each lateral ventricle communicates with the 2.13, and 2.14 ). The hippocampal formation
slit-shaped , midline third ventricle by a short becomes folded into the ventricle along the
channel, known as the interventricular fora - hippocampal sulcus during development.
men (of Monro). These foramina serve as a Along the superior and medial surfaces of
basic reference point and are of great impor- the hippocampus is a flattened band of
tance in radiographic studies. fibers, known as the fimbria , which extends
from the region of the uncus toward the
Anterior Horn splenium of the corpus callosum . The fim -
bria continues under the corpus callosum
The anterior horn portion of the lateral and becomes the fornix ( Figs. 2.10, 2.20, 2.27,
ventricle lies rostral to the intraventricular and 2.28).
Body (lat . vent.)
III Ventricle
• x
\N
\
Uiti
Collateral trigone
%
Posterior horn Anterior horn (lat. vent.)
(lat. vent.) Interventricular foramen
Suprapineal recess Preoptic recess
Pineal recess ' j Infundibular recess
(/ Cerebral
aqueduct Inferior horn ( lat . vent . )
Lateral aperture
Median aperture (IV ventricle)
(IV ventricle)
A
Posterior horn
(lat . vent.) Inferior horn (lat. vent.)
Anterior horn (lat . vent. )

Lateral recess
(IV vent.)
IV Ventricle Interventricular
foramen
Cerebral aqueduct
f
Atrium (lat. vent.) Ill Ventricle

B
Figure 2.21. Ventricular system in lateral (A) and superior (B) views. Arrows indicate direction of CSF flow .
Callosal radiations Cingulate sulcus
Optic radiation
Lateral ventricle
Hippocampal formation
Collateral eminence
Collateral sulcus
Splemum of
Tapetum corpus callosum
Figure 2.22. Frontal section at the level of the splenium of the corpus callosum. Callosal fibers lateral to the ventricle
are known as the tapetum. The optic radiations lie lateral to the tapetum.
43
Posterior Posterior Horn

third ventricle
The posterior horn part of the lateral ven -
Pineal tricle extends from the collateral trigone into
recess the occipital lobe. This horn exhibits a high
degree of variability in appearance and is
Aqueduct often rudimentary. The occipital horn has fre-
quently the appearance of a small fingerlike
Fourth projection with a rounded tip. The roof and
ventricle lateral wall of this horn are formed by tapetal
fibers of the corpus callosum, whereas its
floor is the white matter of the occipital lobe
( Fig. 2.22). The calcar avis , a longitudinal
Cisterna
magna prominence, is produced by the deep pene-
tration of the calcarine sulcus.
Portions of the lateral ventricles contain
Spinal choroid plexus , formed by the invagination of
subarachnoid the ependymal roof plate into the ventricular
space
cavities. The choroid plexus develops at sites
Figure 2.23. Positive contrast ventriculography clearly
where the ependyma and the pia mater con -
outlining the fourth ventricle, cerebral aqueduct, and
taining blood vessels come together. This
the posterior part of the third ventricle. In this lateral view plexus is present in the body, collateral
radiopaque material also fills part of the cisterna magna trigone, and in the inferior horn of the lateral
and part of the spinal subarachnoid space. ventricle, and extends through the interven -
Optic nerve
Optic chiasm V
A ~
Anterior perforated substance
Infundibulum
Optic tract
Oculomotor nerve
Mammillary body
Crus cerebri
Trochlear nerve I Trigeminal nerve
Pons —
Facial nerve
Abducens nerve -
Vestibulocochlear nerve
Glossopharyngeal nerve
Vagus nerve
Hypoglossal nerve Spinal accessory nerve
1
/
Pyramidal decussation Ventral root C|
'
Figure 2.24. Anterior surface of the brainstem showing the emergence and entrance of most of the cranial nerves .
tricular foramen to lie in the roof of the third 2.24 ) . The ventral surface of the pons pro-
ventricle ( Fig. 2.29 ) . duces a convex protrusion covered by trans-
versely coursing fiber bundles which disap-
BRAINSTEM pear laterally in the substance of the
cerebellum . The medulla , caudal to the pons,
In the intact brain , only the anterior sur- reveals the large medullary pyramids medially
face of the brainstem can be seen throughout and the oval olivary eminences ventrolaterally .
its extent , because the cerebral hemispheres The transition from medulla to spinal cord is
and cerebellum overlap its lateral and poste- characterized by the disappearance of the
rior surfaces. On the anterior surface of the medullary pyramids, the development of the
brainstem , the medulla , pons, midbrain , and anterior median fissure of the spinal cord , a
part of the hypothalamus (a component of the conspicuous reduction in size, and the ap-
diencephalon ) can be identified ( Figs. 2.5, 2.9, pearance of paired spinal nerves.
and 2.24 ) . The diencephalon is surrounded by Removal of the cerebral hemispheres and
hemispheric structures on all sides except for cerebellum reveals the posterior and lateral
a small region of the hypothalamus between surfaces of the brainstem ( Figs. 2.25 and 2.26 ) .
the optic chiasm and the mammillary bodies. The expanded diencephalon appears as
The midbrain appears very small , but root paired oval nuclear masses on each side of a
fibers of the oculomotor nerve ( N . Ill ) can be vertical slitlike third ventricle ( Fig . 2.25 ) . The
seen emerging between two massive fibers thalamus and epithalamus , seen in the posterior
bundles, the crura cerebri ( Figs. 2.9, 2.10, and view of the brainstem, lie between the fibers
Stria medullans
Anterior tubercle
/
III
ventricle Stria terminals
Lamina affixa
Thalamus
Tenia
choroidea
Habenula
Pulvinar
Superior
Colliculus
Inferior Superior
Cerebellar
Middle peduncles
Facial
colliculus
Striae ~ Hypoglossal trigone

medullares
Area postrema
Cuneatus
-— Accessory nerve
Tuberculum
^ Gracilis Obex
Posterior median sulcus
Figure 2.25. Posterior surface of the brainstem and diencephalon with the cerebellum removed
Ant . tubercle of thalamus Thalamus

Fornix
Cerebral peduncle
Pulvinar
Ant commissure
Optic tract Lateral
geniculate
Optic chiasma body
Optic n Sup colliculus

and brachium
Medial geniculate
Hypophysis body
Oculomotor n Inf . colliculus
and brachium
Crus cerebri
Ophthalmic n Trochlear n
Maxillary n -• Sup cerebellar
peduncle
Mandibular n .
Motor root Middle
N V
_ cerebellar
Facial n peduncle
N intermedius
Vestibulocochlear n
Abducens n
Glossopharyngeal n
— Inf cerebellar
Pyramid peduncle
Vagus n
Inferior olive
-
Medulla oblongata
Hypoglossal n
- Cuneate tubercle
Spinal accessory n
— Gracilis tubercle
Figure 2.26. Lateral view of the brainstem and diencephalon with the cerebellum removed showing the sites of
emergence and entrance of most of the cranial nerves.
of the internal capsule and are flanked dorso - bellum ( Fig. 2.25). This discloses the rhom-
laterally by the body and tail of the caudate boid fossa, an unpaired symmetric ventricle
nucleus. Along the dorsomedial margin of that overlies the pons and medulla. The rhom -
the thalamus is the stria medullaris , a band of boid -shaped fourth ventricle is surrounded by
fibers coursing posteriorly toward the habe- three paired cerebellar peduncles, which re-
nula and the base of the pineal gland . late the three brainstem segments to the cere-
The dorsal aspect of the midbrain reveals bellum . The fourth ventricle contains several
the superior and inferior colliculi and their eminences which overlie nuclear masses, the
brachia , which relate these structures to partic- most evident of which are the facial colliculus
ular parts of the thalamus. The trochlear and the hypoglossal eminence. Caudal to the
nerve ( N . IV ) emerges from the dorsal part of fourth ventricle on the dorsal surface of the
the midbrain caudal to the inferior colliculus medulla are nuclear masses related to ascend -
( Figs. 2.25 and 2.26). The dorsal aspects of the ing spinal systems, namely, the cuneate and
hindbrain are revealed by removing the cere- gracilis tubercles ( Fig. 2.25).
Figure 2.27 . Midsagittal section of the brainstem and diencephalon Structures are identified in Figure 2 28
Structurally, the brainstem consists of Medulla

three distinctive parts: (a ) a roof plate dorsal
to the ventricular system , ( b ) a central core of The medulla (myelencephalon ), the most
cells and fibers beneath the ventricular sys- caudal basic subdivision of the brainstem, ex -
tem known as the tegmentum, and (c) a mas- tends from the level of the foramen magnum
sive collection of ventrally located fibers de- to the caudal border of the pons. The transi -
rived from cells of the cerebral cortex ( Figs. tion from spinal cord to medulla is gradual
2.27 and 2.28). The roof plate of the midbrain is and characterized by (a ) the obliteration of
represented by the tectum or quadrigeminal the anterior median fissure ventrally and the
plate , consisting of the superior and inferior decussation of the medullary pyramids, ( b )
colliculi. In the hindbrain, the roof plate is the appearance of the gracilis and cuneate tu -
more elaborate and comprises the cerebellum bercles dorsally, (c) the disappearance of
and the tela clwroidea. The tegmentum of the spinal nerves and the appearance of cranial
midbrain, pons, and medulla contains the nerves, and ( d ) the development of the fourth
brainstem reticular formation , a large collec- ventricle ( Figs. 2.23-2.26 ). The full develop-
tion of cells and intermingled fibers that sub- ment of the medullary pyramids, the appear -
serve multiple functions, as well as several ance of the inferior olivary eminence, the
more precisely delineated nuclei. The corti- widening of the fourth ventricle, and the
cally derived ventral fiber system forms the crus gradual increase in size of the restiform body,
cerebri at midbrain levels, one of the principal which is the larger component of the inferior
constituents of the ventral or basilar part of the cerebellar peduncle, give the medulla its
pons, and the medullary pyramids of the characteristic configuration ( Figs. 2.24 and
medulla ( Fig. 2.26 ). Both the reticular forma- 2.25). Cranial nerves associated with the
tion and the cortically derived ventral fiber medulla are ( a ) the hypoglossal ( N . XII )
system are continuous within the brainstem, whose fibers emerge through the preolivary
but undergo change and modification at vari- fissure located ventrolaterally between the
ous levels ( Fig. 2.12). pyramid and the inferior olivary complex, ( b )
Fornix Tenia thalami Habenular

commissure
Corpus Posterior
callosum commissure
Septum
pellucidum
Pineal
Interventricular
Thalamus
foramen Superior and inferior
Anterior colliculi
commissure
Cerebral aqueduct
Lamina
terminalis
Superior medullary
Supraoptic velum
recess
Optic chiasm— IV Ventricle
® III Ventricle Hypophysis
Mammillary body -1
N. Ill
Medulla
Figure 2.28 . Midsagittal section of the brainstem and diencephalon identifying some of the structures shown in Fig-
ure 2.27
the accessory ( N . XI ), the vagus ( N. X ), and cerebellomedullary (or inferior cerebellopontine )

the glossopharyngeal ( N. IX ) whose fibers cistern ( Figs. 1.8 and 1.9). These small lateral
emerge from the postolivary sulcus, and (c) recesses contain choroid plexus that pro-
the vestibulocochlear nerve ( N. VIII ) whose trudes through the foramina of Luschka into
separate components enter the brainstem at the subarachnoid space ( Figs. 2.9 and 2.21 ). A
the junction of the pons and medulla ( Fig. small median aperture in the caudal part of
2.26). Auditory fibers are located dorsally and the ventricle is known as the foramen of Ma -
partially arch over the lateral aspect of the in - gendie. Through these three apertures cere-
ferior cerebellar peduncle. brospinal fluid flows from the ventricular
system into the subarachnoid spaces (see
Fourth Ventricle Chapter 1 ). Using positive contrast ventricu -
lography the fourth ventricle, cisterna magna
The fourth ventricle is a broad , shallow, and cerebral aqueduct can be viewed in detail
rhomboid -shaped cavity overlying the pons ( Fig. 2.23).
and medulla that extends from the central The rhomboid fossa , which forms the floor
canal of the upper cervical spinal cord to the of the fourth ventricle, is divided by the me-
cerebral aqueduct of the midbrain ( Figs. 2.21 , dian sulcus into symmetric halves. The sulcus
2.23, and 2.25). Its roof is the cerebellum and limitans divides each half into a medial emi-
the superior and inferior medullary veli , which nence and a lateral region known as the
extend toward an apex within the cerebellum vestibular area ( Fig. 12.14 ). The vestibular nu -
known as the fastigium ( Figs. 2.21, 2.27, 2.28, clei lie beneath the vestibular area. The facial
and 2.33). The superior medullary velum colliculus and the hypoglossal trigone lie within
forms the roof of the pontine part of the ven - the medial eminence, with the latter near the
tricle, while the inferior medullary velum and caudal border of the ventricle. Transversely
the tela choroidea form the roof over the coursing fibers of the striae medullares run
medullary part of this ventricle. The choroid from the region of the lateral recess toward
plexus from the tela choroidea projects into the midline and disappear in the median sul-
the caudal part of the ventricle. The widest cus ( Fig. 2.25). These strands of myelinated
part of the fourth ventricle is immediately fibers lie rostral to the hypoglossal trigone.
caudal to the middle cerebellar peduncles . In this The vagal trigone lies lateral to the hypoglos-
region, there is a lateral recess on each side, sal trigone. The most caudal end of the rhom-
which extends over the surface of the inferior boid fossa resembles a pen and is called the
cerebellar peduncle to open into the lateral calamus scriptorius. The point of caudal junc-
tion of the walls of the fourth ventricle is cerebellar peduncle to reach nuclei in the dor -
known as the obex ( Fig. 2.25). Immediately solateral pontine tegmentum ( Fig. 2.26). The
rostral to the obex on each side of the fourth middle cerebellar peduncle consists of a large
ventricle is a slightly rounded eminence, the number of fibers, arising from the pontine
area postrema. nuclei, which project to the cerebellum; this is
the largest of the three cerebellar peduncles
Pons ( Figs . 2.25 and 2.26 ). Ventral to the root ot the
The pons ( metencephalon ), representing trigeminal nerve is the basilar pons while
the rostral part of the hindbrain, is well -de- dorsal to the root of this nerve is the middle
limited on the anterior surface of the brain- cerebellar peduncle.
stem ( Figs. 2.24, 2.26 and 2.27). The massive Midbrain
pontine protuberance covered by broad
bands of transversely oriented fibers is sepa - The midbrain ( mesencephalon ) is the
rated from the crus cerebri of the midbrain by smallest part of the brainstem ( Figs. 2.10,
the superior pontine sulcus and from the an - 2.25-2.27). It consists of (a ) the tectum , repre-
terior surface of the medulla by the inferior sented by the superior and inferior colliculi,
pontine sulcus. The predominantly trans- ( b) the tegmentum , ventral to the cerebral
verse fibers in the ventral part of the pons aqueduct, and ( c ) the massive crura cerebri
form the middle cerebellar peduncle ( Figs. 2.26 ( Figs. 2.24, 2.26, and 14.1 ). The tegmentum
and 2.32 ). An anterior median depression , the and crura cerebri are separated by a large
basilar sulcus , indicates the position occupied pigmented nuclear mass, the substantia nigra
by the basilar artery ( Figs. 2.24 and 4.11 ). ( Fig. 2.14 ). The superior colliculus and a re-
Transverse sections of the pons reveal its gion immediately rostral to it, known as the
basic organization ( Fig. 13.1 ). The pons con- pretectum , are important relays in the visual
sists of a massive ventral part composed of (a ) system . The inferior colliculus relays auditory
longitudinal descending fiber bundles, ( b ) impulses to thalamic nuclei that in turn pro-
pontine nuclei, (c) transversely oriented ject to specific cortical areas.
fibers projecting to the cerebellum , and ( d ) a Two cranial nerves are associated with the
smaller dorsal part, known as the teg- midbrain, the oculomotor ( N. Ill ) and the
mentum . The tegmental portion contains ag - trochlear ( N . IV ). The oculomotor nerve
gregations of cells and fibers which form a emerges from the interpeduncular fossa , be-
central core known as the pontine reticular tween the massive crura cerebri ( Figs. 2.9,
formation. The pontine tegmentum is contin - 2.10, and 2.26 ). The slender trochlear nerve
uous with the reticular formation of the exits from the dorsal surface of the brainstem,
medulla and midbrain. caudal to the inferior colliculus. Fibers of this
Cranial nerve nuclei, ascending sensory nerve cross in the superior medullary velum
systems and descending motor pathways are and course anteriorly around the brainstem
found within the tegmentum. Cranial nerves ( Figs. 2.25 and 2.26). The fibers of the superior
associated with the pons are the trigeminal cerebellar peduncle , seen on each side of the
( N . V ), abducens ( N . VI ), facial ( N . VII ), and upper part of the fourth ventricle ( Figs. 2.25
the two components of the vestibulocochlear and 2.26 ), decussate completely in the caudal
nerve ( N. VIII ). The abducens nucleus lies in midbrain tegmentum . Crossed fibers of this
the floor of the fourth ventricle and is par - peduncle traverse and surround a large nu -
tially encircled by fibers of the facial nerve clear mass in the tegmentum called the red
( N . VU ). Facial nerve fibers and cells of the nucleus ( Fig. 2.14 ).
abducens nucleus underlie the facial colliculus The crus cerebri on the ventral surface of
seen in the floor of the fourth ventricle ( Fig. the midbrain are collections of fibers originat-
2.25). Fibers of the abducens nerve emerge ing in broad areas of the cerebral cortex that
from the ventral surface of the brainstem at pass through the internal capsule ( Figs. 2.12
the junction of the pons and medulla ( Fig. and 2.24 ). These fibers project to ( a ) spinal
2.26 ). The facial and vestibulocochlear nerves cord ( i.e., corticospinal ), ( b) pontine nuclei
emerge and enter the lateral surface of the ( i .e., corticopontine ), and (c) specific regions
pons at the cerebellopontine angle , formed bv of the lower brainstem ( i.e., corticobulbar ). A
the junction of pons, medulla , and cerebellum large part of the corticobulbar fibers project to
( Figs. 2.26 and 13.6) . The trigeminal nerve ( N . parts of the reticular formation . The pig-
V ), consisting of motor and sensory fibers, mented substantia nigra , rich in dopamine
passes through rostral parts of the middle and other neurotransmitters, is the largest
single nuclear mass in the midbrain. It has ependyma and forms part of the floor of the
connections with parts of the basal ganglia , lateral ventricle. This strip is called the lamina
thalamus, and superior colliculus, and is con- affixa ( Fig. 2.25). The stria terminalis and the
sidered to subserve a motor function ( Fig. terminal vein lie dorsally at the junction of
2.14 ). thalamus and caudate nucleus. The stria
ntedullaris extends along the dorsomedial
margin of the thalamus near the roof of the
DIENCEPHALON third ventricle. The medial surfaces of thal-
The diencephalon is a paired structure on ami on each side of the third ventricle are
each side of the third ventricle ( Figs. 2.13, partially fused in about 80% of human brains.
2.16, and 2.25-2.28). The lateral ventricles, This place of fusion is called the interthalamic
corpus callosum, fornix, and velum interposi- adhesion or massa intermedia .
tum lie superior to the diencephalon ( Fig. Although most subdivisions of the thala -
2.29 ). Fibers of the posterior limb of the inter- mus are not evident in gross specimens, the
nal capsule and the body of the caudate nu - anterior tubercle of the thalamus is discernible
cleus constitute its lateral border. Caudally, rostrally as a distinct swelling ( Fig. 2.26). The
the diencephalon appears continuous with expanded posterior portion of the thalamus is
the tegmentum of the midbrain ; the posterior known as the pulvinar ( Figs. 2.13 and 2.25).
commissure is the junctional zone between The medial and lateral geniculate bodies , impor-
the diencephalon and mesencephalon ( Figs. tant relay nuclei concerned with audition and
2.13 and 2.28). The rostral boundary of the division , lie ventral to the pulvinar ( Fig. 2.26).
encephalon is near the interventricular fora - Together, these structures are referred to as
men , but portions of the hypothalamus ex - the metathalamus . The thalamus is divided
tend almost to the lamina terminalis ( Figs. 2.27 into anterior, lateral, medial, and ventral nu -
and 2.28). The diencephalon consists of four clear groups by a thin layer of myelinated
parts: (a ) the epithalamus, ( b) the thalamus, fibers, known as the internal medullary lamina
(c) the hypothalamus, and (d ) the subthala - of the thalamus, which can be seen grossly in
mus ( Figs. 2.27-2.29 ). transverse sections of the brain ( Figs. 2.16 and
2.29 ). Nuclear groups within the internal
Epithalamus medullary lamina are collectively referred to
as the intralaminar thalamic nuclei. The largest
The epithalamus forms the dorsal part of of the intralaminar nuclei is the centromedian
the diencephalon and consists of (a ) the nucleus ( Fig. 2.29 B ).
pineal body or gland ( epiphysis), ( b) the The thalamus is regarded as the neural
habenular nuclei, (c ) the stria medullares, and structure whose relationship with other parts
( d ) the tenia thalami. of the neuraxis provides the key to under-
standing the organization of the central ner-
Thalamus vous system . This part of the diencephalon is
concerned with (a ) distributing most of the
The thalamus represents the largest and afferent inputs to the cerebral cortex, (b) the
most central portion of the diencephalon. The control of the electrocortical activity of
thalamus appears as an oblique, egg-shaped the cerebral cortex, and ( c) the integration of
nuclear mass at the rostral end of the brain- motor functions by providing the relays
stem ( Figs. 2.13, 2.16, and 2.25-2.29 ). This nu - through which impulses from the basal gan -
clear complex lies between the interventricu - glia and cerebellum can reach the motor cor-
lar foramen and the posterior commissure, tex. Through influences that modify elec-
and extends from the third ventricle to the trocortical activities, the thalamus plays
medial border of the posterior limb of the in - important roles in arousal, consciousness,
ternal capsule. The thalamus lies dorsal to the and sleep mechanisms.
hypothalamic sulcus, a shallow groove on the
lateral wall of the third ventricle. The lateral Hypothalamus
and caudal parts of the thalamus overlie mid -
brain structures. The superior surface of the The hypothalamus portion of the dien-
thalamus is covered by a thin layer of fibers cephalon lies ventral to the hypothalamic sul-
known as the stratum zonale. A narrow lateral cus. I * *brms the inferior and lateral walls of
strip of the superior surface, adjacent to the the third ventricle ( Figs. 2.27-2.29 and 17.1 )
body of the caudate nucleus, is covered by and extends from the region of the optic chi-
Corpus callosum
Caudate nucleus Septum pellucidum
Column of fornix
Lenticular nucleus
— Internal capsule
Thalamus
Stria medullaris
Choroid plexus
Habenula
Fimbria of fornix
Inferior colliculus Superior colliculus

A Pineal body
Stria medullaris — Velum interpositus Corpus callosum

Fornix Choroid plexus
Caudate nucleus- Lateral ventricle
internal medullary Stria terminalis
lamina Thalamic nucleus
Internal capsule — — Lateral group
Globus pallidus
i
<•
— Dorsomedial
T — Centromedian
Putamen - — Ventral group
Subthalamic nucleus Mammillothalamic tract
Fornix Optic tract
III Ventricle Hypothalamus
B Optic chiasm Optic nerve
Figure 2.29 . A. Posterior view of the diencephalon and related structures B. Frontal section through the dien
cephalon and adjacent structures indicating some of the major nuclear groups of the thalamus. The hypothalamus
lies on both sides of the third ventricle below the hypothalamic sulcus,
asm to the caudal border of the mammillary stalk . It has a rostrocaudal extent of about 10
bodies. The gross structures visible on the mm . This subdivision of the diencephalon is
ventral surface include the optic chiasm , in - concerned with visceral, endocrine, and
fundibulum , tuber cinereum , and mammillary metabolic activity, as well as with tempera -
bodies ( Figs. 2.9, 2.10, 2.24, 2.27, and 2.28). The ture regulation, sleep, and emotion.
hypothalamus is divided into medial and lat -
eral nuclear groups by fibers of the fornix Subthalamus
which mainly end in the mammillary body.
Three rostrocaudal regions of the hypothala- The subthalamus portion of the dien-
mus are recognized: ( a ) a supraoptic region, cephalon is a transitional zone ventral to the
dorsal to the optic chiasm, (b) a tuberal re- thalamus and lateral to the hypothalamus. It
gion centrally, and (c) a mammillary region is bounded by the thalamus dorsally, the hy-
caudally ( Fig. 17.1 ). The hypothala pus is pothalamus medially, and the internal cap-
continuous with the pituitary gland ( hypoph- sule laterally ( Fig. 2.29 ). The largest discrete
ysis) through the infundibulum and pituitary nuclear mass is the subthalamic nucleus , a lens-
shaped structure on the inner aspect of the in- and 2.27). The superior surface is somewhat
ternal capsule ( Fig. 16.6 ). This region is tra- flattened , while the inferior surface is convex.
versed by many important fiber systems in A shallow anterior cerebellar incisure is present
their projection to thalamic nuclei . A small , superiorly. A deeper and narrower posterior
relatively clear area, known as the zona in- cerebellar incisure contains a fold of dura
certa, serves as an important landmark in dis- mater, the falx cerebelli ( Fig. 1.2).
tinguishing certain fiber bundles ( Fig. 16.6 ). The cerebellum consists of a midline por-
The subthalamic nucleus and pathways tra - tion, the vermis , and two lateral lobes or hemi -
versing this region are concerned with the in - spheres. This structure is essentially wedge-
tegration of somatic motor function . shaped , having a superior surface covered by
the tentorium , a posterior surface in the sub-
CEREBELLUM occipital region , and an inferior surface
which overlies the fourth ventricle. On the
The cerebellum overlies the posterior as- superior surface the distinction between ver-
pect of the pons and medulla and extends lat- mis and hemispheres is not sharp ( Fig. 2.30),
erally under the tentorium to fill the greater whereas on the inferior surface two deep
part of the posterior fossa ( Figs. 2.2, 2.7, 2.9 , sulci clearly separate the vermis from the
Anterior incisure
Anterior lobe
Primary fissure
Posterior -Culmen
quadrangular
lobule
Posterior
superior
fissure
Superior
semilunar
lobule
Horizontal fissure "
Posterior Inferior semilunar lobule
Declive incisure
Figure 2.30. Superior surface of cerebellum
Posterior incisure Folium

Superior semilunar
Inferior lobule
semilunar
lobule
Gracile lobule
Biventer lobule
Tonsil
Flocculus
Vallecula cerebelli
Figure 2.31. Posteroinferior view of the cerebellum.

hemispheres. Interiorly, a deep median fossa , lobule, and the culmen ( Fig. 2.33). In the
the vallecula cerebelli, is continuous with the hemisphere, the lingula has no correspond -
posterior incisure. The floor of this fossa is ing part, but the alar central lobule and the an-
formed by the inferior vermis ( Fig. 2.31 ). terior quadrangular lobule correspond to the
Structurally, the cerebellum consists of a central lobule and the culmen.
gray cortical mantle, the cerebellar cortex, a The posterior lobe of the cerebellum , be-
medullary core of white matter, and four tween the primary and posterolateral fis -
pairs of intrinsic nuclei . Three paired cerebel- sures, represents the largest subdivision of
lar peduncles connect the cerebellum with tlie cerebellum ( Figs . 2.33 and 15.1 ). Vermal
the three segments of the brainstem ( Figs. parts of the posterior lobe in sequence are (a )
2.25, 2.26, and 2.32 ). The cerebellar cortex the declive, (b) the folium and tuber , (c) the
consists of a large number of narrow leaflike pyramis , and ( d ) the uvula ( Fig. 2.33). The sim -
laminae known as cerebellar folia . Cerebellar ple lobule , between the primary and posterior
folia are nearly parallel with each other and superior fissures, corresponds to the declive
for the most part are oriented transversely. of the vermis ( Fig. 15.1 ) . The ansiform lobule is
Each lamina contains several secondary and that part of the cerebellar hemisphere be-
tertiary folia . Five transversely oriented fis- tween the posterior superior fissure and the
sures divide the cerebellum into lobes and gracile lobule. The horizontal fissure divides
lobules ( Fig. 15.1 ). These fissures, and the the ansiform lobule into the superior semilunar
various lobular subdivisions, can be identi - lobule (crus I ) and the inferior semilunar lobule
fied on the isolated cerebellum or in mid - ( crus II ). Vermal, counterparts of the ansi -
sagittal section ( Fig. 2.33). On the superior form lobule, are the folium and tuber. Be-
surface of the cerebellum two fissures can be tween the prepyramidal and posterolateral
identified: (a ) the primary and ( b) the posterior fissures are the pyramis and uvula in the ver-
superior fissures ( Fig. 2.30 ). The horizontal fis - mis, and the biventer lobule and the cerebellar
sure , one of the most distinctive, roughly di- tonsil in the hemisphere ( Figs. 2.32 and 2.33).
vides the cerebellum into superior and infe- The flocculonodular lobule lies rostral to the
rior halves. The prepyramidal and posterolateral posterolateral fissure and consists of the ver -
fissures are found on the inferior surface ( Fig. mal nodulus and the paired flocculi ( Fig.
2.33). 2.32). The nodulus lies immediately caudal to
The cerebellar vermis is the key to under- the inferior medullary velum ( Fig. 2.33).
standing the gross organization of the cere- In the midsagittal section , the relationships
bellum , but in this part there is no median of the cerebellum to the brainstem are evi-
raphe and the midline is difficult to establish . dent ( Fig. 2.27). The complex branching of
Portions of the cerebellum rostral to the pri - the medullary core, and the treelike appear -
mary fissure constitute the anterior lobe of the ance of the laminae and folia , have given
cerebellum ( Figs. 2.30 and 15.1 ). In the vermis, rise to the descriptive term , arbor vitae ( Figs.
the lobules consist of the lingula , the central 2.27, 2.28, and 2.33). The intrinsic nuclei of
Culmen
Central lobule
Lingula Superior medullary velum
^
Superior Superior cerebellar peduncle
semilunar
lobule
- Middle cerebellar
peduncle
Hori2ontal
fissure - Inferior
cerebellar
Inferior peduncle
semilunar
lobule
Paraflocculus
Biventer
lobule Tonsil Nodulus Flocculus
Figure 2.32. Inferior surface of cerebellum removed from brainstem by transection of cerebellar peduncles.
.
Figure 2.33 . Sagittally sectioned cerebel- Culmen

lum showing the lobules of the cerebellar
vermis. The primary fissure is the deepest of
all cerebellar fissure. (See Fig. 15.1.) Primary fissure
Central lobule /
Declive
Lingula Folium
V
- Tuber
Nodulus
H W Prepyramidal
' fissure
x
Pyramis
Flocculus \
Uvula
:
Middle cerebellar
peduncle Posterolateral fissure
the cerebellum can be seen only in sections. photon absorption coefficients that prevents
These nuclei are the dentate ( most lateral ), discrimination of different tissue densities by
the emboliform, the globose, and the fastigial conventional x-ray radiographic techniques.
(Figs. 15.17 and 15.11) ). The fastigial nuclei, Additionally, when an x-ray beam penetrates
commonly called the roof nuclei, lie in the the head, it superimposes the densities of all
roof of the fourth ventricle. structures in its path with the composite den-
Although the cerebellum is derived from sity recorded on the x-ray film . One of the x-
the metencephalon, this portion of the neu- ray techniques that is successfully used is
raxis functions in a suprasegmental manner. based upon the introduction of air (or various
Therefore, it is not considered part of the contrast media ) into the subarachnoid space
brainstem. It is concerned primarily with coat spinal cord level to produce an image of
ordination of somatic motor function, control
of muscle tone, and equilibrium. The cerebel-
the ventricular system termed a pneumoen -
cephalogram ( Fig. 2.23). In contrast to bone, air
lum receives input directly or indirectly from absorbs very little x-ray photons and appears
virtually all sensory receptors, including the dark in radiographs. Although useful for di-
organs of special sense, but this sensory infor- agnostic purpose, this method is painful and ,
mation does not enter the conscious sphere. in some cases, can be dangerous for the pa-
This structure functions as a special kind of tient. The same limitations apply to another
computer that automatically processes, orga- procedure which consists of injecting intra-
nizes, and integrates sensory input and pro- arterially or intravenously a radiopaque dye
vides prompt responses that contribute to to produce an image of the cerebral vascula-
smooth and effective control of somatic ture called an angiogram ( Figs. 4.3, 4.9, 4.15,
motor function. The output systems of the and 4.16). The blood vessels of the brain and
cerebellum arise largely from the cerebellar brainstem can be studied in detail from
nuclei and their influences upon motor func- carotid and vertebral angiograms, which first
tion are mediated through brainstem nuclei reveal the arteries and later the filling of the
at multiple levels. veins. Normal intracranial structures are not
readily visualized with cerebral angiography,
BRAIN IMAGING although some abnormalities can be inferred
from distortion in the appearance of the brain
Standard x -ray techniques for visualizing vasculature. This procedure, however, clearly
gross structures in and around the brain have reveals highly vascularized tumors and vas-
been used for many years for diagnostic pur- cular lesions such as aneurysms and arteri -
poses. However, under ordinary circum- ovenous malformations (see Chapter 4 ).
stances, the soft tissues within the cranium In the past decade, there was a true revo-
are so nearly homogeneous in radiodensity lution in the field of brain imaging. Three ex-
that the brain is almost completely invisible tremely powerful and noninvasive tech-
on plain x-ray films of the head . All living tis- niques, computerized tomography (CT ),
sue, except bone, fall within a narrow band of magnetic resonance imaging ( MR1), and
positron emission tomography ( PET) (3, 6, radiodensity by more than 2%, they can be
12 ), were developed to study the regional distinguished from each other in CT scans.
anatomy of the living brain with a high de- Although CT scans or computerized tomo-
gree of spatial resolution. grams can be taken in a horizontal plane par -
allel to the anatomic baseline of Reid (a line
Computerized Tomography joining the inferior orbital margin and the top
of the auditory meatus), such scans do not
A system theoretically capable of produc- permit visualization of all posterior fossa
ing a cross-sectional display of discontinu- structures ( Fig. 2.34 ). An example of a com -
ities of radiodensity within an irregular ob- puterized tomogram in the horizontal plane
ject , such as the head , was described bv and a corresponding section of the head and
Oldendorf ( 9-11 ). He used a 7- ray source and brain in the same plane are shown in Figures
a collimated scintillation counter to detect 2.35 and 2.36. To visualize the largest number
discontinuities in a rotating model . Computer- of intracranial structures, including those in
ized tomography , a technique capable of pre- the posterior fossa , computerized tomograms
senting an image of a cross section of the usually are taken in parallel planes at angles
brain or body, is a remarkable method for x- of 25-30 with reference to the orbitomeatal
'
ray examination of soft tissue. It was devel- baseline ( Fig. 2.34 ). Another advantage of
oped by Godfrey Hounsfield and Allan Cor- choosing such an angle is that the eye does
mack, who were awarded the Nobel Prize for not become involved and the whole brain
Physiology and Medicine in 1979 for the im - can be scanned with a minimum amount of
portance of their contribution . This system radiation.
utilizes scintillation counters as the primary Computerized x-ray tomography provides
detector, rather than x-ray film, and the infor- -
a pictorial cross section of the intracranial
mation is fed into a computer capable of di- contents and brain at multiple levels which
rect imaging. Using scintillation counters to cannot be obtained by any other radiologic
detect photon attenuation ( i.e., absorption co- technique. The method is entirely noninva -
efficients) instead of x- ray film increases the sive and has the capacity to reveal differential
sensitivity of the method by two orders of densities in the components of the brain (e.g.,
magnitude (6, 8). This procedure uses an x- gray and white matter ). Certain contrast
ray tube, which gives off a series of narrow, agents containing iodine can be used to en-
highly-collimated beams of radiation, and hance the contrast of tomograms, especially
photon detectors (sodium iodide crystals and when lesions or neoplasms show increased
photomultipliers) accurately aligned with the vascularity.
x-ray source to provide a detailed plot of the
x- ray absorption coefficients in the scanned Magnetic Resonance Imaging
cross section of the body. The x-ray beam and
the photon detectors scan the head in a linear Magnetic resonance imaging ( MRI ), previ-
fashion allowing 160 readings of photon ously called nuclear magnetic resonance
transmission. The scanning unit is then ro- ( NMR ), creates very detailed images of the
tated 1 ° around the head and the process is brain and other body organs without using x-
repeated ; 180 scans are taken, each with the rays. First developed to measure the atomic
apparatus rotated an additional 1 . This re- constituent of chemical samples, it was re-
sults in 28,800 readings of photon detectors cently combined with CT for spatial localiza -
which are processed by a computer capable tion of atomic nuclei, and this combination
of calculating 6400 absorption values for each has produced an imaging technique much
brain slice. From the computer calculations, a more powerful than CT itself . This method is
picture of the brain slice is constructed in the based on the resonance of certain atomic nu -
form of a matrix (80 x 80 ) of 6400 picture clei, such as hydrogen, when placed in a
points ( or pixels), each indicating an absorp- strong, static, and homogeneous magnetic
tion coefficient value. Considerably greater field . The magnetic field used is as much as
definition is supplied by newer instruments 60,000 times as strong as that of the earth and
using a 160 X 160 ( 25,600 pixels ) or 320 x 320 is produced by several powerful electromag-
(102,400 pixels ) matrix. Currently available nets supercooled by helium . To obtain an
CT equipment can produce scans that have a MRI signal, a brief pulse of radio waves at a
resolution of less than 1 mm. Hence, even given frequency is used to perturb the align-
though gray and white matter do not differ in ment of the spinning nuclei along the strong
Figure 2.34. Head and brain demonstrating tomographic planes. The zero degree plane (/4) corresponds to the or-
bitomeatal baseline which passes through the inferior margin of the orbit and the external auditory meatus. Tomo-
grams taken in parallel planes at an angle of 25” to the baseline ( B) provide more information about structures in the
posterior fossa.
Cingulate gyrus
Frontal lobe
Anterior horn of
lateral ventricle
Caudate nucleus
Anterior limb of
internal capsule
- Lateral sulcus
Circular sulcus
-<
Temporal lobe
— - Lentiform nucleus
Posterior limb of
internal capsule
^ Thalamus
^ - Glomus of
choroid plexus
\ Splenium of
corpus callosum
Occipital lobe
Falx cerebri
Figure 2.35. Computerized tomogram taken parallel to the zero degree plane through the thalamus internal cap-
sule and basal ganglia.
Falx cerebri
Cingulate gyrus
Genu corpus
callosum
Fornix
. Caudate nucleus
(head )
Anterior limb
internal capsule i
l Insula
Posterior limb
internal capsule
Putamen
Globus
Thalamus pallidus
Posterior III
commissure ventricle
Caudate nucleus ' Pulvinar
Fimbria
of fornix
Hippocampus
Choroid
plexus
Optic radiation
Tentorium cerebelli
Occipital horn
Calcarine sulcus Cerebellar vermis

Falx cerebri
Figure 2.36. Section of the head and brain in the same horizontal plane as the computerized tomogram shown in
Figure 2 35
magnetic field . When this pulse is turned off , magnetic qualities. Hydrogen largely reflects
the nuclei tend to return to their original ori- water content, which varies from one brain re -
entation , and in doing so release energy in gion to the other ( e.g., there is more water in
the form of faint radio waves that are used to gray than in white matter ). Therefore, by ma -
construct the images (6, 12 ). nipulating the radiofrequency signal to which
The radiofrequencies emitted are different the tissue is exposed , the relaxation time of
for each atom and the strength of the radio protons in water can be enhanced and a strik -
wave at each frequency is proportional to the ingly differentiated image of a section of the
number of atomic nuclei of each kind in the brain can be produced by MRI . In contrast to
sample. The rate at which a group of nuclei soft tissues, bones contain little free water so
return from an excited to a lower energy state that their image in MRI scans of the head is
is termed relaxation and is usually expressed usually faint and does not compromise the vi-
by its time constant (T). Two types of relax- sualization of brain structures. In fact, due to
ation are of particular importance: spin-lattice its ability to clearly distinguish between white
,
relaxation (T ) and spin-spin relaxation ( T2). and gray matter, the images obtained in a liv-
Relaxation times are influenced by local tis- ing brain with MRI reveal almost as many de-
sue conditions so that images emphasizing ei- tails as one can obtain with fixed and sec -
,
ther T or T, help in discriminating between tioned anatomic material ( Figs. 2.37-2.39).
normal tissues of various compositions and MRI can greatly facilitate clinical diagno-
pathologic processes. sis. The analysis of relaxation times, which
The hydrogen atom, whose nucleus com - varies and depends on local tissue conditions,
prises a single proton , is a particularly good enables clinicians to detect pathologic pro-
candidate for MRI scanning because of its cesses such as small infarctions, tumors, or
abundance in the body and its prominent the plaques of multiple sclerosis ( Fig. 2.40 ).
1- Optic nerve
2- Crus cerebris
3- Inferior colliculus
4- Vermis of cerebellum
5- Temporal Horn
6- Cerebral aqueduct
7- Occipital lobe
1 - Frontal lobe
2- Caudate nucleus
3- Internal capsule
4- External capsule
5- Tngone
6- Interhemispheric fissure
7- Frontal horn
8- Lentiform nucleus
9- Lateral fissure
10- Thalamus
11 - Third ventricle
12- Occipital lobe
Figure 2.37 . Magnetic resonance imaging (MRI) of two horizontal sections (or slices) of the brain parallel
to the orbit
omeatal line in a healthy human subject A . A ventral section passing through the midbrain B. A more dorsal section
, .
passing through the basal ganglia T - weighted images (TR 500 msec TE 30) carried out with 1 5 Tesla Philips gyroscan
unit .
1 - Caudate nucleus
2- Mammillary body
3- Amygdala
4- Interhemispheric fissure
5- Corpus callosum
6- Interventricular foramen
7- Third ventricle
8- Temporal horn
1 - Lateral fissure
2- Choroidal fissure
3- Hippocampal gyrus
4- Fornix
5- Thalamus
6- Crus cerebri
7- Pons
8- Medulla
9 - Spinal cord
Figure 2.38. MRI images of two frontal sections of the same subject as in Figure 2.37. A. A somewhat rostral section,
passing through the basal ganglia and rostral pole of the temporal lobe B A more caudal section showing the brain-
stem and the thalamus. T -weighted Images (TR 500 msec. TE 30) carried out with 1.5 Tesla Philips gyroscan unit.
.
1- Frontal lobe
2- Corpus callosum
3- Fornix
4 - Midbrain tegmentum
5- Pons
6- Medulla
7- Spinal cord
8- Gyrus cingulis
9- Massa intermedia
10 - Quadrigeminal plate
11 - Vermis of cerebellum
12- Fourth ventricule
1- Insula
2- Temporal horn
3- Temporal lobe
Figure 2.39. MRI images of two parasagittal sections of the same subject as in Figures 2 37 and 2.38 A. Section along
the midline showing the medial surface of the hemisphere and the entire brainstem B . A more lateral section depict -
ing the insula and part of the temporal lobe T - weighted images (TR 500 msec, TE 30) carried out with 1.5 Tesla Ftiilips
gyroscan unit
Research is under way to develop MRI scan- tope imaging and allows exploration of vari-
ners that detect other elements, such as ous functions of the living brain . In contrast
sodium or phosphorus, whose altered prop- to CT, which depends on transmission to-
erties could provide early warning signs of mography, PET images depict the distribu -
cerebral infarction or metabolic diseases. tion in the tissue of injected or inhaled iso-
However, sodium and phosphorus imaging topes that emit positrons ( positively charged
requires a magnetic field that is even stronger electrons). The most commonly used
than that used for hydrogen imaging. positron-emitting isotopes are "C, 13N, 1 'O,
and IKF. Any one of these radioisotopes can
Positron Emitting Tomography be bound to compounds of biologic interest,
such as water, glucose, neurotransmitters, or
Positron emitting tomography ( PET ) is a ligands that bind to particular receptors on
technique that combines CT with radioiso- neuronal membranes, so that it becomes pos-
sible to map the distribution of these various

compounds within the brain (3, 6 ).
These positron-emitting isotopes have rel -
atively short half -lives ( minutes to hours ) so
that they must be generated shortly before
their use. Hence, they are usually made on
site by accelerating protons in a small, low-
energy cyclotron at very high rates until they
collide into the stable nuclei of nitrogen, oxy-
gen, carbon, and fluorine. In their normal
state, these nuclei contain protons and neu -
trons in equal numbers and incorporation of
an extra proton produces an unstable isotope.
To regain stability, the proton is broken down
into a neutron and a positron. The neutron re-
mains within the nucleus because a stable nu -
cleus can accept extra neutrons. In contrast,
the positron is an unstable particle, which
tends to travel away from the site where it
was generated. Along its course, the positron
eventually collides with an electron and this
event leads to the annihilation of the two par-
ticles and the release of a burst of energy in
the form of two 7-rays. These rays are emit -
ted precisely at 180° from each other and are
simultaneously detected by crystal photo-
multipliers that surround the patient's head .
A computer records the precise location of
-
the site of 7 rav emission and uses this infor-
mation to construct the image.
One of the most interesting possibilities of
PET scanning is the mapping of regional
brain activities through the monitoring of
local variations in neuronal glucose metabo-
lism . It is possible to map glucose metabolism
by using 2-dcoxyglucose, an analogue of glu -
cose. This compound is readily taken up by
neurons and phosphorylated by hexokinase
in the same hnanner as glucose. Unlike glu -
cose, however, phosphorylated deoxyglucose
cannot be further metabolized nor can it exit
from neurons by traversing the cell mem -
brane. Therefore, 2-deoxyglucose accumu - Figure 2.40 . Spin-echo MRI images from patients with
lates within active neurons where it can be vi - multiple sclerosis A Axial (horizontal) section high in the
brain showing a single lesion ( arrow ) in a neurologically
sualized with PET scanning if , prior to its .
unimpaired patient with multiple sclerosis. B Axial (hori-
intravenous injection, the compound has zontal) section through the basal ganglia depicting mul-
been tagged with the positron -emitting iso- tiple lesions ( arrows ) in the brain of a moderately im-
tope of fluorine ( IKF). Assuming that the up- paired patient with long standing multiple sclerosis .
take of lsF-deoxyglucose into neurons is di-
rectly proportional to the degree of activity of
these neurons, active brain areas will appear orbitomeatal line. In this case, the isotope IKF-
more heavily labeled than inactive ones in deoxyglucose was used to measure glucose
PET images. metabolism in various brain areas in a nor-
Figure 2.41 A shows PET scans of 14 brain mal person at rest. The resolution ( 4-8 mm )
sections, each section being 14 mm apart of current PET scanners is modest by com -
from each other and aligned parallel to the parison to those of MRI and CT scanners. Yet,
UBC/TRIUHF PET PROGRAM
;>
CTiNua
m • %
A
UBC/TRIUHF PET PROGRAM
UM
i
©
Figure 2.41, Positron emission tomography (PET) images A. Fourteen interleaved PET axial slice images of regional
,
cerebral glucose metabolism, as measured by fluorodeoxyglucose ( sF -2-fluoro-2-deoxy-D-glucose). in a normal
human brain, with the highest brain slice at the top left and the lowest at bottom right. The slice thickness varies with
radius from 10-16 mm, and the in-plane resolution is 8-9 mm. B. Four PET axial slice images through the basal ganglia
showing regional cerebral glucose metabolism as measured with : 8F-deoxyglucose in the brains of a normal subject
and subjects suffering from Alzheimer ' s disease, the Guamanian ALS-Parklnson's-dementia complex, and dementia
associated with Parkinson' s disease.
despite this relatively poor spatial resolution, the Alzheimer's type and dementia present in
one can clearly see the contours of various patients suffering from the Guamanian amy-
gyri and sulci, as well as subcortical struc- otrophic lateral sclerosis-Parkinson's-demen-
tures such as the thalamus and the basal gan- tia complex or Parkinson's disease ( Fig .
glia , in these PET scans. PET scans can also 2.41 B ). The Guamanian syndrome is a corn-
reveal major disturbances in glucose metabo- plex disease characterized by motor deficien -
lism in certain diseases, such as dementia of cies resulting from a combined lesion of vari -
UBC / TRIUMF PET PROGRAM
ZmlKttaT
HUMM
!
153
Figure 2.42 . Positron emission tomography (PET) images. A. Fourteen interleaved PEt axial slice images of fluorodopa
(l8F-6-fluorodopa) uptake in the brain of a normal subject. Slice locations and thickness are similar to those in Figure
,
2.41 A B. Four PET axial slice images through the basal ganglia showing 8F-6-fluorodopa uptake in the brains of a nor-
mal subject, one suffering from early Parkinson's disease, an asymptomatic subject known to have ingested MPTP
neurotoxin, and one suffering from the Guamanian ALS-Parkinson ' s-dementia complex .
ous portions of the pyramidal motor tract world , this disease is particularly frequent on
and motoneurons at spinal cord level (amy- the island of Guam, from which it derives its
otrophic lateral sclerosis or ALS), together name.
with the cardinal signs of Parkinson's disease PET scan can also be used to probe the
(akinesia , rigidity, and tremor ) and an im - functional status of various neurotransmitter
pairment of higher mental functions (demen- systems in the living brain . This is the case
tia ). Although present in all parts of the with the neurotransmitter dopamine, which
is produced by neurons of the substantia ministered systemically it produces a marked

nigra at midbrain level and acts principally degeneration of dopaminergic cell bodies of
within the striatum at telencephalic level . the substantia nigra , which rapidly leads to
Areas of the brain containing high concentra - severe Parkinson's disease, as observed in
tions of dopamine can be visualized with PET young adults who injected themselves with
scans by using the isotope fluorodopa ( ISF- this drug on the street . This neurotoxin is cur -
-
dopa ). L dopa, the immediate metabolic pre- rently used to produced animal models of
cursor of dopamine, is preferred to dopamine Parkinson's disease in nonhuman primates.
because it crosses the blood brain barrier - In addition to neurotransmitters and their
much more easily than the neurotransmitter precursors, molecules that bind to specific
( Fig. 1.15). Figure 2.42 A displays PFT scans of neurotransmitter receptors on the surface of
14 brain sections (slices ) obtained with IKF
dopa . At the spatial resolution of these scans,
- neurons have been labeled with positron-
emitting isotopes and used successfully with
we can see that the most heavily labeled areas PET scans. For example, "C- N - methylspiper-
of the brain correspond to the basal ganglia one, a ligand that preferentially binds to
and particularly to the striatum , which can be dopaminergic receptors, has been used to
visualized on both sides of the brain on sec- map receptor locations in the living brain.
tions 6 to 9 from top to bottom . Additionally , subclinical impairment of the
Lesions of the nigrostriatal dopaminergic dopaminergic nigrostriatal system can be de-
system resulting in a marked depletion of tected with PET scan by combining the use of
striatal dopamine is believed to be the major IHF-dopa and "C-nomifensine. In such a case,
cause of Parkinson 's disease. A decrease in the kinetics of INF-dopa uptake gives an indi-
striatal dopamine concentration is readily de- cation of the dopamine storage capacity of
tected with PFT scans, as illustrated in Figure the striatum , whereas "C-nomifensine allows
2.42 B . This Figure shows four brain sections to assess the integrity of the dopamine re- up-
through the basal ganglia in a normal subject, take sites in the same structure. Because of its
one suffering from early Parkinson 's disease, ability to reveal the distribution of specific
an asymptomatic subject known to have in - neurotransmitters as well as metabolic sub-
gested the neurotoxin MPTP, and one suffer- strates, PET permits a more functional ap-
ing from the Guamanian ALS- Parkinson 's- proach to the anatomic study of the human
dementia complex. The compound MPTP brain . This cell-biologic approach may soon
(1- methyl - 4- pheny 1-1 , 2,3,6- tetrahyd ropy ri - lead to major revisions of our basic concepts
dine ) is a synthetic analogue of the narcotic of the anatomy and physiology of the ner-
analgesic meperidine ( Demerol). When ad - vous system.
References New York: Appleton -Centurv - primer . New York: Raven Press,
Crofts, 1970. 1991.
1 . Broca P. Anatomic compare? des 5. Gazzaniga MS, Sperry RW . 10. Oldendorf Wll Isolated living spot
circonvolutions cerebrates: le grand Language after section of the cere- detection of radiodensity disconti-
lobe limbique et la scissure lim -
bique dans la serie des mam -
bral commissures. Brain 19b7;90:
131-148.
—
nuities displaying the internal
structural pattern of a complex ob-
mi feres. Rev Anthropol ( Ser. 2 ) 6. Martin JH, Brust JCM , I lilal S. Imag- ject . IRE Trans Biomed Electron
1878;1 :384-498. ing the living brain. In : Kamiel FR , 1981;8:68-72.
2. Brodal A . Neurological anatomy in .
Schwartz jl I Jessell TM , eds. Princi - 11 . Oldendorf Wll. The quest for an
relation to clinical medicine. 3rd ed . ples of neural science. Ch. 22. Ams- image of brain : computerized to -
New York: Oxford University Press, -
terdam : Elsevier, 1991:309 324. mography in the perspective of past
1981 . 7. Mettler FA . Neuroanatomy . 2d ed . and future imaging methods. New
3. Brownell GL, Budinger TF, Lauter - St . Louis: C. V . Mosby , 1948. York: Raven Press, 1980.
bur PC McGecr PL . Positron to- 8. New PFJ , Scott WR. Computer to - 1 2 . Pykett ii NMR imaging in medi -
mography and nuclear magnetic re -
sonance imaging. Science 1982:215:
619-626.
mography of the brain and orbit
( FMI scanning ). Baltimore: Williams
& Wilkins, 1975.
.
.
cine Stf Am
^ -.
1982 46:78 88
13 Truex RC, Kellner CF . Detailed atlas
of the head and neck . New York:
4. Gazzaniga MS. The bisected brain 9. Oldendorf W , Oldendorf W Jr . MRI Oxford University Press, 1948.
3
Development of the
Nervous System
DETERMINATION AND DIFFERENTIATION FORMATION OF NEURAL TUBE
The central nervous system ( CNS) is a The fertilized ovum undergoes a period of
segmented entity whose complexity in- cell division until it reaches the uterus. At this
creases markedly as it develops. Part of this time, the spherical ball of cells develops a
complexity derives from the fact that the var- cavity, forming the blastula . A bilaminar
ious segments of the CNS do not develop at layer of cells, called the embryonic disk, de-
the same rate and that each segment acquires velops a few days after the blastula and be-
its adult form by going through a succession comes implanted into the uterine wall ( Fig.
of highly specific developmental events. The 3.1 ). During the third week of development,
development of the nervous system, like that the embryonic disk becomes trilaminar, and
of any other system or organ of the body, at this stage the three primary tissues of the
proceeds according to two fundamental se- embryo, ectoderm, endoderm, and meso-
—
quences determination and differentiation .
Determination refers to the event whereby a
derm , can be distinguished . Additionally, a
cord of mesodermal cells, the notochord , lies
certain cell population of the embryo gives directly beneath the most dorsal portion of
rise to cells of the nervous system ( neurons the ectoderm .
and glia ), whereas differentiation alludes to The interaction between the notochord
the cellular processes which ensures that the and its overlying ectoderm is of utmost im -
cells arising from the determined population portance because the notochord will induce
will be the source of subpopulations of neu- the ectoderm to form the hollow neural tube
rons and glial cells that are specific to each which will differentiate into the brain and
region of the CNS. The term differentiation spinal cord (13). The action by which the no-
thus applies to the complex mechanisms tochord instructs the ectoderm to become the
whereby neurons will proliferate and mi- neural tube is called priman/ embryonic induc -
grate to appropriate locations within the ner- tion or, more specifically , neural induction . The
vous system, and ultimately make highly cellular response by which the flat layer of ec-
specific connections with their targets. Neu- toderm cells is transformed into a hollow
ronal differentiation is, in fact, the result of tube is called neurulation . Early in develop-
elaborated interactions between the development, neural induction imposes a regional
ing neuron and its microenvironment, that is specificity along the rostrocaudal axis of the
between intrinsic ( genetic ) and extrinsic (epi- ectoderm ( or neuroectoderm ) and this speci-
genetic ) factors ( 5, 13, 21, 33). Such poorly ficity is irreversible. As a result, the major
understood interactions are currently the subdivisions of the CNS ( forebrain, midbrain,
subject of active researches in developmental hindbrain , and spinal cord ) are already speci -
neurobiology whose aim is to elucidate the fied in the neuroectoderm and this specifica -
molecular basis of neuronal development. tion appears to be irreversible (5, 21, 33).
The present chapter describes the major de- Neurulation is a highly complex and mul -
velopmental events that lead to the forma - tifactorial process resulting from forces both
tion of the nervous system in humans. A intrinsic and extrinsic to the neuroectoderm .
proper knowledge of these events will It is driven by changes in neuroectodermal
greatly facilitate the understanding of the cell shape, as well as other form-shaping
anatomical organization of the CNS and the events, in which microtubules, microfila -
comprehension of various malformations of ments, and other elements of the cytoskeleton
the CNS. are involved ( 50 ). The first stage of neurula-
65
Synctiotrophoblast
(lacunar)
Cytotrophoblast
Amniotic
cavity —
Mesoderm
Embryonic J Ectoderm-
disk I
Entoderm
Primitive
lining
amnion
yolk sac Mesoderm

Celom lining
entoderm
Embryonic disk
\
Amnion
I
cx
' Primitive streak
'V
Ectoderm
Entoderm Primitive
"
B yolk sac
entoderm
Figure 3.1. A. Embryonic disk in a blastocyst at the end of the second week of development : cytotrophoblasts are
green; mesoderm is yellow, ectoderm is blue; and endoderm is light red . B. Schematic diagram of the embryonic disk
viewed from the amniotic cavity. The appearance of the primitive streak indicates the start of gastrutalion.
tion is characterized by the formation of a neuroectodermal cells proliferate, the neural

thickened plate of neuroectoderm known as groove deepens, and the neural folds thicken,
the neural plate , which first appears late in the become more prominent, and ultimately fuse
third week of fetal life and contains about dorsally to form the neural tube. Closure of
125,000 cells. As much as 50% of the ectoderm the neural tube begins in the region of the
is included in this plate (13). Initially, the fourth somite ( i.e., future cervical region ) and
neural plate lies dorsally, rostral to the primi- proceeds in both cranial and caudal direc-
tive streak and Hensen's node (7, 20, 32,) ( Fig. tions. During the formation of the neural tube
3.2), and consists of a single layer of cells. This its lumen has temporary cranial and caudal
neuroectoderm undergoes rapid proliferation connections with the amniotic cavity via the
and becomes stratified . The growth rate near anterior ( rostral ) and posterior ( caudal ) neuro-
the margins of the plate exceeds that in the pores ( Fig. 3.2). The anterior neuropore which
midline, causing the formation of a neural represents the most rostral opening of the
groove , which is bounded on each side by an embryonic neural tube closes in embryos of
elevated neural fold ( Fig. 3.3). As the primitive 18 to 20 somites and the zone of closure ulti -
Anterior neuropore
Cut edge of amnion
Neural fold
Brain plate
Cardiogenic area
Neural plate Somite I
Neural groove
Node of Hensen
Neural tube —
Primitive streak Posterior

neuropore
-
A C
.
Figure 3.2. Early development of the human nervous system A Late presomite and early neural plate stage B. Early
somite and neural groove stage C. Eight-somite and early neural tube stage
mutely becomes the lamina terminalis The . time, continuous across the midline. Neural
posterior neuropore usually closes later when crest cells migrate laterally, then divide and
the embryo has reached the 25 to 26 somite become segmented into cell clusters between
stage. At early stages in the formation of the the neural tube and the somites ( Fig. 3.3).
neural tube, before closure is complete, ros- These clusters of neural crest cells give rise to
tral portions of the neural tube are enlarged the primary sensory neurons of the dorsal
and indicate the formation of primary brain root ganglia of spinal nerves. Similar cell
vesicles. Three primary brain vesicles are evi - clusters in the hindbrain give rise to sensory
dent by the time the neural tube is completely neurons which form cranial nerve ganglia
closed (19) ( Fig . 3.10 ). The brain is formed ( N . V, VII , VIII , IX, and X ), but these are not
from these primary vesicles. Caudal portions segmentally arranged ( Fig. 3.10 ). The neural
of the neural tube which remain relatively crest has a temporary existence as its cells mi -
small in diameter form the spinal cord . The grate widely in the body and undergo vari-
appearance of the neural folds heralds the ous differentiations in different tissues ( 30 ).
segmentation of bilateral strips of paraxial All of the sensory cells of the peripheral ner-
mesoderm into somites ( Figs. 3.2 and 3.3). vous system ( with a few exceptions), and
New somites continue to be formed in a cran- most of the peripheral cells of the autonomic
iocaudal sequence and at the end of the nervous system , are derived from the neural
fourth week 40 somites normally are present. crest . Thus, the neural crest gives rise to the
unipolar spinal ganglion cells and their
NEURAL CREST equivalent in the sensory ganglia of cranial
nerves V, VII , IX, and X . Some elements per-
The lateral margins of the neural plate are sisting as bipolar cells form the auditory
thinner and continuous with the general nerve. Other derivatives of the neural crest
body ectoderm . The thinned lateral margins include (a ) the neurolemmal sheath cells of
of the neural plate ( neural crest cells ) are ap- all peripheral nerves, ( b ) capsule cells in gan -
proximated as the neural folds meet and fuse. glia , (c) sympathetic ganglia , ( d ) chromaffin
Neural crest cells form a temporary interme- cells, and ( e) pigment cells (30 ).
diate layer between the neural tube and the Cells of the sympathetic ganglia and the
surface ectoderm ( Fig. 3.3). This temporary chromaffin cells of the adrenal medulla pro-
layer extends from the level of the mesen- duce high levels of specific amines such as
cephalon to the caudal somites and , is for a norepinephrine ( noradrenaline ) or epineph -
Ectoderm »
r T rr rnrT U rtteT^ Somatic mesoderm
NEURAL PLATE P < /
^ ^xx
panooooononnnnooannnD
A Splanchnic mesoderm
Entoderm Notochord Mesoderm
Paraxial mesoderm
*
>wjoaaa o <.
^
B <r
NEURAL GROOVE Neural folds Neural groove
7\ '
m Somatic mesoderm
> o m <
c Splanchnic mesoderm
Neural tube Neural crest

Somite
l
Paraxial mesoderm Intermediate mesoderm Lateral mesoderm

NEURAL TUBE
Dorsal root ganglion
Ependymal canal
Figure 3.3, Transverse sections of embryos at different ages to show development of the spinal cord A Neural plate
stage B. Early neural groove stage C. Late neural groove stage D. Early neural tube and neural crest stage E .
Neural tube and dorsal root ganglion stage
.
rine (adrenaline) Other cells that contain tion, but it cannot be assumed that these cells
high concentrations of amines are found are of neural crest origin ( 41 ).
throughout the gut and its associated glands. It is also important to realize that cells of
These have been termed APUD (amine pre- the neural crest, as well as any other neurons,
cursor uptake and decarboxylation ) cells. are influenced by the local environment dur-
APUD cells can be recognized with fluores- ing their migration . The target of the rnigrat -
cent histochemical techniques. Some of the ing crest cells plays a crucial role in their
polypeptide hormone-producing cells in the differentiation. For instance, analysis of
pancreas, stomach , and other parts of the gut sympathetic neurons developing in cell cul -
also show a fluorescent histochemical reac- ture show that neurons normally utilizing
norepinephrine as a neurotransmitter ( i .e., migrates toward the external limiting mem-

noradrenergic neurons) can be changed to brane and then moves back toward the inter-
neurons using acetylcholine (i.e., cholinergic nal limiting membrane. Deoxyribonucleic
neurons) under the influence of soluble fac- acid ( DNA ) replication occurs only when the
tors released by nonneuronal cells normally nucleus is near the external limiting mem-
present in the local environment ( 30). A simi - brane ( in the so-called synthetic zone). Once
lar switch in the expression of neurotransmit - DNA replication is complete, the nucleus
ter phenotype has been shown to occur dur- moves toward the lumen of the neural tube
ing the normal development of the sweat ( in the so-called mitotic zone) and the cell
glands in the rat ( 27). In this particular case, loses its contact with the external limiting
neurons that innervate developing sweat membrane. Cells undergo mitosis only when
glands are noradrenergic at the time of inner- the nucleus has reached the innermost zone,
vation, but as the glands and their innerva- and daughter cells remain attached by the
tion mature, cholinergic properties appear. terminal bars at the internal limiting mem-
The finding that targets can retrogradely brane. After division the cells elongate and
specify the transmitter phenotype of neurons their nuclei migrate toward the external limit-
that innervate them provides important ining membrane where further DNA synthesis
sight into the role that neuronal targets can occurs. After several divisions, the stem cells
play during development. For example, it is lose their ability to divide. The postmitotic
well-established that targets can determine cells then leave the germinal zone of the
the final number of surviving neurons during ependymal layer and migrate to their appro-
the development of the vertebrate CNS. Fur- -
priate position in the so called mantle layer.
thermore, targets can influence the morpho- The migrating cells are either immature neu -
logic phenotype of the neurons that survive. rons ( neuroblasts) or glial cells precursors
For instance, the size of sympathetic neuron ( glioblasts ). In contrast to most neuroblasts,
cell bodies and the extent of branching of the glioblasts retain their capability to divide.
their dendritic arbors is influenced by the size Having reached their appropriate position in
of the target that they innervate during devel - the mantle layer, the neuroblasts tend to send
opment ( 27). Likewise, peripheral targets of their processes into the outermost layer called
sensory neurons, such as skin or muscle, may the marginal layer ( 24 ) ( Fig. 3.5).
determine the nature and specificity of their
central connections as well as that of the neu - NEURONS
rotransmitter they contain.
The differentiation of neurons from primi-
tive neuroepithelial cells involves three
HISTOGENESIS OF NEURAL TUBE
phases: (a ) proliferation and generation of
The histogenetic changes whereby the specific classes of neurons, ( b) migration of
columnar neuroectoderm is converted to ner- cells to a specific position, and (c ) maturation
vous tissue occur in characteristic areas of the of cells and establishment of specific connec-
neural tube called germinal zones. In most re- tions. Neuroblasts arising from division of
gions of the CNS, these germinal zones are neuroepithelial cells in germinal zones mi-
located near the lumen of the central canal, grate into the mantle layer of the neural tube
which will later form the ventricular system and increase in number as neuroepithelial
of the brain. The recently closed neural tube cells continue to proliferate. These cells form
consists of only one type of cell, the undiffer- rounded apolar neuroblasts ( Fig. 3.6), which
entiated neuroepithelial cell or stem cell . In the further differentiate into bipolar neuroblasts
germinal zone, the neuroepithelial cells form with two cytoplasmic processes on opposite
a pseudostratified epithelium which extends sides of the cell body. One cytoplasmic
from the internal limiting membrane to the ex- process elongates to form a primitive axon ,
ternal limiting membrane ( Fig. 3.4 ). Each neu - whereas the other cytoplasmic process devel -
roepithelial cell is wedge-shaped and pos- ops numerous small outgrowths which ar-
sesses cytoplasmic processes which reach the borize and form the primitive dendrites. At this
internal limiting membrane and are attached stage, the cell becomes a multipolar neuroblast .
to adjacent cells by terminal bars. Nuclei of Further growth and differentiation results in
neuroepithelial cells that will divide undergo the formation of an adult nerve cell or neuron .
characteristic oscillatory movements (12, 49 ). The intense bursts of neuroblast proliferation
First, the nucleus of an actively dividing cell that occur early in neurogenesis result in an
EXTERNAL LIMITING MEMBRANE
Synthetic
zone
Intermediate
zone
Mitotic
zone
Newborn
INTERNAL LIMITING MEMBRANE neurons
( Ventricular surface)
Figure 3.4 . Characteristic oscillatory movement of the nuclei of the actively dividing cells in the germinal zone of the
primitive neural tube. At the beginning of the cycle, the cells have long cytoplasmic processes that span the entire
width of the germinal zone and their nuclei lie near the ventricular surface. The nuclei then migrate toward the exter -
nal limiting membrane, into the synthetic (or marginal) zone, where DNA synthesis occurs. The nuclei then migrate
back toward the ventricular surface, into the mitotic (or ventricular) zone, retract their processes from the outer sur -
face, and undergo mitosis. The daughter cells can either resume the mitotic activity and enter a second phase of the
cycle or stop dividing and migrate away from the ventricular surface
Root plate Posterior medion septum
Soimatic Mantle layer Posterior gray column

aft erent ( afferent )
Anterior groy column Motor

Marginal layer ( efferent ) neurons
Figure 3.5. Differentiating layers of the spinal cord A. Section through spinal cord of a 5- week human embryo B.
Cervical spinal cord of an 8- week human embryo C. Cervical spinal cord of a 10- week human embryo.
overproduction of neurons. Neurons, how - their target and establish proper connections,
ever, that are not properly located in the vari - This finding has lead Gerald Edelman to pro-
ous regions of the CNS, or those which have pose the interesting concept of "neuronal
not established appropriate connections, will Darwinism" based upon the survival of neu-
eventually die, so that the total number of rons which are successful in contacting their
neurons is reduced to the final normal popu- target ( 11 ) .
lation size. In fact, there appears to be a fierce Maturing neuroblasts do not establish
competition between neuroblasts to reach synapses randomly ( 23). Instead , they are at -
N Ependymal
/ Neuroepithelial \
Glioblast
Apolar neuroblast
i
i
l
I
* Oligodendrocyte
Bipolar neuroblast
I
y
Protoplasmic Fibrillar
astrocyte astrocyte
Multipolar
neuroblast Mesenchyme cell Microglia
Figure 3.6 . Histogenesis of neurons and neuroglial cells . Neuroblasts, glioblasts. and ependymal cells originate from
neuroepithelial cells. The origin of the oligodendrocyte is obscure, but both protoplasmic and fibrillar astrocytes are
derived from gliobasts. The microglia are considered to arise from mesenchyme.
tracted in a very specific manner to particular provide the mechanical force that pull an
groups of target cells. Many years ago, the el- axon forward through cycles of protrusion,
egant experiments conducted by Roger adhesion, and contraction of filopodia . It is
Sperry on the visual system of frogs, sala- likely that the physical substrate over which
manders, and goldfish (52 ), lead to the sug- an axon grows contributes mechanical and
gestion that chemical gradients or specific chemical cues, particularly molecules control-
chemical affinities enabled axons to establish ling cell adhesiveness, that guide the growth
synaptic contacts only with appropriate post- cone to its target . Proteins that promote the
synaptic neurons. The movement of axons is aggregation of neurons in specific portions
determined by expansions of the growing of the brain have been isolated (38) and cell
axons called growth cones . The growth cones surface proteins, such as N-acetyl- D-galac -
.
tosamine have been implicated in adhesion neurons to proliferate into the brain . These
between specific pre- and postsynaptic ele- axons, which normally do not invade the
ments (15). These molecules, called cell adhe- CNS, will do so, apparently by following
sion molecules (CAM ), or, in the present case, chemical tracks created by diffusion of NGF
nerve cell adhesion molecules ( N -CAM ), are (31 ). Recently, a specific receptor for NGF
sizable glycoproteins with molecular weights was identified in the nervous tissue and anti-
of 180-250 kD that contain large amounts of bodies against this receptor were produced.
the ionically charged sugar, sialic acid (10). Immunohistochemical mapping studies with
The various forms of N -CAM that character- these antibodies revealed the presence of
ize the different regions of the CNS appar- NGF receptors in several neuronal popula -
ently can be differentiated from one another tions of the adult human brain, such as the
by their sugar residues. Besides N -CAM , sub- cholinergic neurons of the basal forebrain.
strate adhesion molecules (SAM ) were also Antibodies against NGF itself were also pro-
studied intensively . These molecules, which duced and administration of these antibodies
include laminin, fibronectin, chodronectin , to newborn animals causes sympathetic gan -
and certain types of procollagen located in glia to atrophy Ummunosympathectomy ).
the extracellular matrix, play a key role in the The direction of growth cones and , hence,
migration of neuroblasts outside the CNS the establishment of neuronal connections, ap-
( e.g., neural crest cells), but their role within pears to be influenced by a wide variety of
the CNS is still uncertain ( 3). clues ranging from (a ) simple mechanical dif -
Experiments in developing amphibians, in ferences in the texture of the extracellular ma-
which an eye is transplanted into the spinal trix (e.g., adhesiveness), ( b) signals from recog-
cord , show that factors other than cell surface nition molecules on the cell membrane (e.g.,
recognition sites are also involved in the N-CAM ), and (c) molecular information pro-
specification of neural connections. Axons vided by a distant source via the production of
from the ectopic (spinal ) eye reach the optic a diffusible compound ( e.g., NGF). The final
tectum and form synapses only when the em- step in the making of a neuronal connection in-
bryo's own eyes are removed (14 ), suggesting volves a highly complex set of events that lead
that some afferent axons may mask cellular to the formation and stabilization of synapses.
recognition sites or render them ineffective. This set of events comprises two major series of
Among the various pathfinding mechanisms interactions between the outgrowing fiber and
which may explain how axons find their way its target . First, there is a matching of the size of
over such great distances are those involving the population of presynaptic neurons and
the presence of different growth factors. Of their target which is accomplished by cell
all the putative growth factors that have been death , synapse retraction, and competition for
identified up to now , the nerve growth factor growth substance. Second, there is a fine tun-
( NGF) is certainly the most well -character- ing of the connections that results from the
ized ( 31 ). NGF is a protein that is synthesized competition between various outgrowing
in target cells as part of a larger prohormone. fibers and the activity of both the pre- and
It has a molecular weight of 130 kD and con- postsynaptic elements. The influence of the ex-
tains three subunits: a , (i, and y . The biologic ternal environment on the developing brain is
activity of NGF depends on the (i subunit, crucial for the fine tuning, maintenance, and
which is a 26 kD dimer similar in amino acid strength regulation of neuronal connections.
sequence to insulin, another growth-enhanc- Although the structures of the brain are largely
ing hormone. Although its exact mode of ac- specified by genetic and developmental
tion is still not known, the presence of NGF processes, the pattern of interconnections be-
appears essential for the development and tween neurons is also influenced by experi-
maintenance of certain neuronal populations, ence. In fact , studies during the last decade re-
such as the sympathetic neurons and the sen- vealed that the brain is remarkably plastic; it
sory neurons of the dorsal root ganglia ( 31 ). can readily change its performance, and even
NGF can be taken up from the target cells by its strategies, as a result of experience. The in-
pinocytic activity of neuron terminals and fluence of experience on the brain is particu-
then carried back by axonal retrograde trans- larly important at early stages of development,
port to the cell body, where it acts by altering when the integrative action of the brain and
gene expression . When injected into the even its structural organization is dependent
brain, NGF will cause axons of sympathetic on its interaction with the environment.
GLIAL CELLS is a significant point because the maintenance

of specific neural pathways and reflexes, as
Some of the neuroepithelial cells differen- well as the storage of learned information, all
tiate into primitive glioblasts which form sup- require a metabolically stable and permanent
porting cells. The majority of glioblasts are set of neurons. Structural and functional fea-
generated after the production of neuroblasts tures of the neuroglial elements are presented
has ceased ( 28). Glioblasts become spindle- in Chapter 6.
shaped bipolar cells that extend the entire
thickness of the neural tube. Their large nu- SPINAL CORD
clei are placed close to the lumen and their
processes are attached to both the internal In the spinal cord continued cell prolifera -
and external limiting membranes of the tion produces an anterior and a posterior
neural tube. Some glioblasts retain this posi- thickening in the mantle layer. The anterior
tion and become transformed into ependymal thickening forms the larger basal plate, which
cells ( Fig. 3.6). During maturation most gives rise to the anterior (motor ) gray horn in
ependymal cells lose their attachment to the the adult spinal cord. The smaller posterior
external limiting membrane and their thickening constitutes the alar plate, from
processes extend only a short distance from which the future posterior (sensory ) gray
the central canal to become anchored in a horn of the spinal cord is formed. A longitu-
subependymal glial membrane (Fig. 6.13) . dinal groove, the sulcus limitans , marks the
Ependymal cells in the adult form the lining lateral junction of basal and alar plates ( Fig.
of the central canal of the spinal cord and the 3.5). The sulcus limitans extends the length of
ventricular surfaces of the brain. Epithelial the primitive spinal cord and continues into
cells of the choroid plexus (Fig. 6.15) are be- the brainstem and remains as a prominent
lieved to be modified ependymal cells. sulcus in the floor of the fourth ventricle in
Other glioblasts in the mantle layer lose the adult brain (Fig. 12.14 ). In transverse sec-
their attachments with the limiting membrane tions of the neural tube, the lumen is rhom-
and assume apolar or unipolar appearances. boid-shaped with relatively thin roof and floor
In later stages of development, these detached plates (Fig. 3.5). The roof and floor plates fur-
stem cells send out new processes and are nish only glioblastic elements at spinal cord
transformed ultimately into fibrous and pro- levels.
toplasmic astrocytes (Fig. 3.6). Smaller glial Neuroblasts of the basal plates become the
cells, the oligodendrocytes, are also thought efferent peripheral neurons. Their axons pen-
to be derived from glioblasts. These cells are etrate the marginal layer and the external
found mainly in the marginal layer and play a limiting membrane and emerge from the
role in developing myelin sheaths ( Fig. 6.9). spinal cord as ventral root fibers ( Figs. 3.7
In addition to the macroglia, the adult cen- and 3.9). Fibers of the ventral root pass di-
tral nervous system contains microglia , con- rectly to skeletal muscles or to autonomic
sidered by Del Rio-Hortega to be of mesoder- ganglia for the innervation of visceral struc -
mal origin ( 8). These cells do not appear in tures ( Figs. 3.9 and 10.23). Neuroblasts of the
the central nervous system until it is invaded basal plates also give rise to local circuit neu-
by blood vessels and their perivascular ad- rons. Cells of the alar plate have axons that
ventitia. Despite many descriptions of mi- remain within the central nervous system.
croglia in light microscopy, there is uncer- Part of these axons arch anteriorly, cross
tainty regarding their identification in the through the basal plate to the opposite side,
electron microscope (40). Microglia are con- and reach the marginal layer, where they as-
sidered to serve a phagocytic function and cend or descend for variable distances (Fig.
may be derived from blood histiocytes. In tis- 3.7). Some of these axons ascend as far as
sue culture, neurons develop better if they supraspinal levels (e.g., spinothalamic, spi-
are embedded in dense glia. Glial cells retain noreticular, and spinocerebellar pathways).
a certain degree of motility in the adult, Other axons remain on the same side and as-
whereas neurons are immobile beyond the cend or descend in the marginal layer. These
neuroblast stage. Glial cells also can divide neurons, whose processes are entirely con-
and increase in number, while neurons do fined to the central nervous system, consti-
not divide after birth and remain in perma - tute the central , or intermediate, cells . Those
nent interphase throughout life ( 1 ). The latter whose axons remain on the same side are
Ependymal cells
Marginal zone
:
Tn / Mantle zone
Dorsal root
1 va
m
Spinal ganglion
ib
.V
r £
/o. £ . • v 5
Anterior horn cell
Figure 3.7. Transverse section ot spinal cord and spinal ganglia ot a chick embryo The mantle zone becomes the
butterfly gray matter ot the adult spinal cord, while the marginal zone develops into the white matter containing as-
cending and descending fiber trocts: a indicates afferent fiber with collaterals; b represents a column cell that pro-
jects contralaterally Based upon silver impregnation
known as association cells , whereas those ( Figs. 3.5

and 10.7). As a consequence of all
whose axons cross to the opposite side are these changes, the size of the central canal is
commissural cells . greatly reduced and the embryonic neural
As development proceeds, the prolifera- tube is transformed into the spinal cord.
tion of the germinal cells gradually decreases The spinal cord has a long cylindrical
and ultimately stops altogether. As more and shape and is curved in the embryonic axis.
more stem cells are transformed into neuro- There is an acute ventral flexure, the ceroical
blasts, the germinal zone progressively di- flexure , at the junction of the spinal cord and
minishes in size and ultimately is reduced to hindbrain ( rhombencephalon ). Until the be-
a single layer of columnar ependymal cells. In ginning of the third month, the spinal cord ex -
certain places, as in the anterior commissure tends the entire length of the vertebral canal.
of the spinal cord , some of the ependymal After this time, the mesodermal elements
cells may retain their embryonic glioblast which have formed the cartilages and bones
character and extend the whole thickness of of the vertebral column grow more rapidly
the neural wall ( Fig. 3.7). On the other hand , than the spinal cord , so that at birth the most
the mantle layer progressively increases in caudal part of the spinal cord , the conus
size and becomes the gray matter of the medullaris , lies at the level of the third lumbar
spinal cord . It is surrounded by an expanding vertebra . The sites of emergence of spinal
marginal layer which contains the descend - nerves do not change, but there is a lengthen-
ing and ascending axons of the central cells. ing of root filaments between the interverte-
At a much later period, most of the axons be- bral foramina and the spinal cord which is
come myelinated and the marginal layer as- most marked for lumbar and sacral spinal
sumes the white, glistening appearance char- roots. The lengthening of root filaments is the
acteristic of the white matter of the adult result of the differential growth rate between
spinal cord . The expansion of the alar plates the vertebral column and the spinal cord . The
in a medial direction brings these plates into large number of nerve roots surrounding the
close apposition. The posterior median septum , fHum terminate ( Fig. 1.6) constitute the outdo
formed of glial processes and intima pia , equina . In the adult, the conus medullaris lies
marks the line of junction in the adult ( Figs. between the LI and L2 vertebrae, and the
3.5 and 10.6). In the floor plate region , an in- spinal cord occupies only the upper two-
vagination forms the anterior median fissure thirds of the vertebral canal ( Fig. 10.3).
Neuron Differentiation in Ganglia in the formation of myelin and may be con-

In the spinal ganglia, derived from the
sidered as a peripheral type of neuroglia , per -
haps most closely related to oligodendro-
neural crest, a similar differentiation takes cytes.
place. Many of the original polygonal or Besides the spinal ganglia , there are other
-
round cells become spindle shaped and bipo- peripheral aggregations of nerve cells known
lar with the development of two neurofibril- as autonomic or sympathetic ganglia ( Figs. 3.9
lar processes, one central and one peripheral and 9.2). Arising mainly from the neural
( Figs. 3.7 and 5.10). The central processes
crest, these cells form two ganglionic chains
enter the spinal cord as dorsal root fibers and on the anterolateral aspect of the vertebral
there bifurcate into ascending and descend - column ( vertebral sympathetic ganglia ). Oth-
ing arms which contribute collaterals to the ers migrate further to form the ganglia of the
mantle layer or gray matter ( Figs. 3.7 and mesenteric plexuses (collateral or preverte-
10.23). In human embryos with a crown - to- bral ganglia ), while some actually invade the
rump length of 25 mm, many of the neuro walls of the viscera , or settle close to them , as
blasts have attained the bipolar stage. A few the terminal or peripheral autonomic ganglia
neurons with greater amounts of cytoplasm ( Figs. 3.8 and 9.1 ). Here, too, differentiation
and distinct neurofilaments appear transi
tional in shape and are referred to as
- occurs in several directions. Some cells en-
large to form the multipolar sympathetic gan -
pseudounipolar cells ( Fig. 5.10 ). The cyto - glion cells, whose axons terminate in visceral
plasm of the cell body elongates, and the two effectors, smooth muscle, heart muscle, and
processes become approximated . Ultimately, glandular epithelium ( Fig. 5.10). Others, as in
the elongated cell cytoplasm forms the single the case of the spinal ganglia , give rise to
stem of a T-like structure, while the top of the satellite cells, which envelop the bodies of
T is formed by the thin central and thicker pe- one or several ganglion cells. Finally, some
ripheral processes (53). Many neurons are of differentiate into the chromaffin cells found
the unipolar type in spinal ganglia of human in the adrenal medulla , carotid bodies, and
100 mm fetuses, and most of the spinal gan - other portions of the body.
glia cells are true unipolar neurons in the
newborn human infant. An occasional bipo-
lar neuron , or those in transitional stages, Segmental Arrangement of Peripheral
may, at times, be observed in the adult dorsal Nerve Elements
root ganglia. It is interesting to note that a
large number of ganglionic neuroblasts may With the differentiation of the various
be produced initially. Embryonic dorsal root types of nerve cells in early stages of develop-
and sympathetic ganglia appear to have an ment, a neuronal mechanism adequate for
overabundance of neuroblasts when com- complete, if simple, reflex arcs is established .
pared to the number of fully differentiated Such arcs consist of afferent, intermediate,
ganglion cells present at birth. For example, and efferent neurons, and their peripheral ex-
total cell counts of the submandibular ganglia tensions. However, the synaptic junctions of
in a graded series of human fetuses showed a these cells, which make such reflex arcs func-
progressive reduction from 12,128 cells at 17 tional, are as yet unformed . In embryos of
weeks of gestation to 5,988 at full term (6). As about 10 mm , the various components of the
in the CNS, cell death appears to be a normal peripheral nervous system already are laid
event in the course of embryonic develop- down and may be recognized in a transverse
ment of peripheral ganglia . It is estimated section of any typical body segment ( Fig. 3.9).
that 25-75% of the original neuronal popu- The central processes of the spinal ganglion
lation in autonomic ganglia lies in neonatal cells form the dorsal wots , whereas the ventral
life ( 43). root is composed of axons from cells in the an -
Not all of the cells in the spinal ganglia dif - terior gray matter of the spinal cord ( mantle
ferentiate into neuroblasts. Some develop layer ). Distal to the ganglion, the ventral root
into capsule or satellite cells which form a cap- unites with the peripheral processes of the
sule around the bodies of the spinal ganglion spinal ganglion cells to form a mixed spinal
cells ( Fig. 5.2A ). Others wander out along nerve ( Figs. 3.9 and 8.1 ). Each spinal nerve con-
the course of the growing peripheral nerve fi - taining afferent and efferent fibers divides into
bers, envelop them, and ultimately become a dorsal and a ventral ramus and also sends a
Schwann cells. These cells play an active role fiber bundle known as the ramus communicans
Primordial spinal ganglion

Lateral vertebral
chain ganglion
Preaortic
ganglion. Adrenal medulla
Paraganglion
(gonad)
Mesonephros
Visceral
ganglion
Intestine
Figure 3.8 Neural crest cells differentiate to form the primordial spinal ganglia. Sympathetic neuroblasts migrate
,
ventrally where clusters of cells differentiate further to form sympathetic ganglia, preaortic ganglia, chromaffin cells
of the adrenal medulla and autonomic neurons of the alimentary tract .
Dorsal root
Spinal ganglia Spinal cord
/
Somatic afferent fiber

Dorsal ramus ( GSA )
Somatic efferent fiber

Ventral ramus ( GSE )
Visceral efferent fiber

(GVE. postganglionic )
Visceral efferent fiber

( GVE. preganglionic )
Ramus communicans Visceral afferent fiber

Sympathetic ( GVA )
ganglion
Figure 3.9 . Transverse section of 14-mm pig embryo The functional categories of spinal nerve fibers are indicated on
the right (Bielschowsky ' s silver stain).
to the vertebral sympathetic chain. The dorsal diffusely sensitive to acetylcholine. However,
ramus supplies the muscles and skin of the once the muscle fiber becomes innervated, its
back, whereas the larger ventral ramus goes sensitivity to the neurotransmitter is progres-
to the ventrolateral parts of the body wall. sively restricted to the end - plate region .
Four functional types of peripheral nerve These findings suggest that the restriction
fibers may be distinguished: general somatic of chemosensitivity, which occurs when
afferent (GSA ), general visceral afferent (GVA ), synapse formation has started , may be one
general somatic efferent (GSE ), and general vis - means of preventing other nerve axons from
ceral efferent (GVE ). The efferent innervation forming synapses on the muscle ( 22).
of visceral structures differs from that of the
somatic muscles by the fact that two neurons BRAIN
are always involved in the conduction of im -
pulses from the central nervous system to the As soon as the anterior neuropore is
effector organs ( Figs. 3.9 and 9.2). The fibers closed , the rostral cavity of the neural tube
of these two neurons are referred to as pre- shows three dilatations or brain vesicles.
and postganglionic fibers. The arrangement These three early subdivisions are the prosen -
of these various type of fibers that constitute cephalon or forebrain, the mesencephalon or
the peripheral nervous system are described midbrain, and the rhombencephalon or hind -
in detail in Chapters 8 and 9. brain ( Figs. 2.2 and 3.10A ). The constricted
As in the CNS, cell death is a normal region between the mesencephalon and
process during development of the periph - rhombencephalon is known as the isthmus.
eral nervous system. Somewhat later in de- The brain vesicles maintain many of the fun-
velopment, there is a change in synapses damental morphologic features seen in more
formed by motor neurons upon striated mus- caudal parts of the embryonic neural tube in
cle and by parasympathetic preganglionic that each has roof and floor plates and alar
axons upon postganglionic cells (43). In new- and basal plates. Although the walls of these
born animals, both muscle fibers and gan - vesicles are thin, the sulcus limitans is pre-
glion cells are innervated by several different sent at the junction of alar and basal plates in
axons, but in the adult each cell is usually in - caudal brain vesicles ( rhombencephalon and
nervated by a single axon (9). In the case of mesencephalon ). The large dilated cavities
ganglion cells, the number erf synaptic termi- within each brain vesicle are the forerunners
nals per cell may actually increase, but the of the ventricular system. They are destined
number of cells innervated by a single axon to undergo extensive alterations in size,
decreases. As we have seen , target structures shape, and extent as a consequence of cell
influence the outgrowing neurons and play a proliferation, growth, and various brain flex-
fundamental role in the establishment of ures. These ventricular cavities are continu -
synaptic contacts. Conversely, outgrowing ous with the central canal of the spinal cord .
neurons can markedly influence their targets The lateral margins of the prosencephalon
as exemplified by the effect of activity in mo- develop shallow depressions, the optic sulci,
toneurons on the properties of skeletal mus- which subsequently becomes evaginated to
cles. The motoneuron exerts its effect on form the optic vesicle ( Fig. 3.1OB and C ). Each
skeletal muscles by using acetylcholine as optic vesicle becomes modified to form an
a neurotransmitter. Acetylcholine acts upon optic cup which is joined to the prosen-
specific receptors normally confined to the cephalon by a hollow optic stalk.
end - plate region where their density exceeds Two prominent brain flexures appear at an
20,000 /|A!rr . The density of acetylcholine re- early embryonic stage. The cervical flexure de-
ceptors is much lower in other regions of the velops at the junction of rhombencephalon
muscle fiber. However, if motoneuron fibers and spinal cord , with its concavity directed
are sectioned and degenerate, acetylcholine ventrally. A second ventral flexure, the
receptors are no longer confined to the end - cephalic flexure , occurs at the junction of mes-
plate, but occur all over the muscle fiber. encephalon and rhombencephalon ( Fig. 3.1OB
These numerous extrajunctional receptors, and D ). Rapid changes in the brain occur in
which are the result of a synthesis of new re- the fourth and fifth week of development. In
ceptors and their insertion into the mem - the sixth week, a third impressive flexure
brane, will disappear if the muscle is reinner- with a dorsal concavity develops in the
vated . Likewise, embryonic muscles are first rhombencephalon and divides it into two
Prosencephalon
Rhombencephalon
(hindbrain )
Mesencephalon
Cervical
flexure Cephalic flexure
Mesencephalon
Rhombencephalon ( midbrain )
Optic vesicle
Telencephalon
Spinal cord ( forebroin )
T.A .
Cranial and
spinal ganglia B.
Interventriculor Lammo terminalis
foramen \
Third ventricle
Cerebral vesicle
Corpus striatum
Lot ventricle Metencephalon Isthmus rhombencepholi
Pontine flexure Mesencepholon
Optic vesicle
Future cerebral Mesen- Diencephalon

aqueduct cephalon
Hemispheric
sulcus
vesicle Telencephalon
Fourth ventricle ( cerebral hemisphere )
Myelencepholon Spinal cord D.

Central conal n
C.
Figure 3.10, Developing brain vesicles and ventricular system. A , B. Three-brain vesicle stage of a 4- week embryo . C
D . Five-brain vesicle stage of a 6- week human embryo. The prosencephalon, telencephalon, and spinal cord are
stippled. The diencephalon is shown in dark red, while the mesencephalon is blue . The derivatives of the rhomben-
cephalon (pons and medulla) are in light red and the isthmus is white.
segments, the metencephalon and the mi/ elen- underlying cavity ( fourth ventricle ) appears as
cephalon. This prominent pontine flexure cre- a shallow, diamond -shaped depression called
ates the transverse rhombencephalic sulcus on the rhomboid fossa (42, 55) ( Figs. 2.26, 3.1 IB, 3.14,
the dorsal surface of the brainstem (Figs. and 3.16 ). With continued growth, the lumen of
3.10D and 3.11 A ). A relatively shallow hemi- the midbrain will become narrowed to form
spheric sulcus on each side of the forebrain the cerebral aqueduct . Medial growth and ex-
divides the prosencephalon into a cephalic tel - pansion of the diencephalon also reduce the
encephalon , or endbrain , and a caudal part, the lumen of this segment of the brain to a thin
diencephalon . The optic stalks and optic vesi- vertical cleft, the third ventricle. A large open -
cles are attached to the diencephalon. It has ing ( interventricular foramen ) behind the lam-
been assumed that bending of the developing ina terminalis provides continuity between
neural tube results from differences in the the third ventricle and the cavity of the later-
rate of cell proliferation ( 50). In chick em- ally expanding cerebral hemisphere. The
bryos, cyclic adenosine monophosphate can primitive lateral ventricle within each cerebral
act as a stimulus for axial bending of the em - hemisphere will become altered extensively
bryo which is caused , at least in part , by cell by subsequent development ( Figs. 3.10 and
movement (48). 3.15). Five distinctive subdivisions of the de-
The basic pattern of the ventricular system veloping brain are established at this stage,
of the brain is evident in early stages of devel- and each subdivision undergoes elaborate,
opment ( Fig. 3.1 IB ) . The caudal roof of the and sometimes unique, development as
rhombencephalon is extremely thin and the growth continues ( Fig. 3.11 ). The five basic
Mesencephalon Diencephalon
Hemispheric sulcus
Isthmus
rhombencephali r.
Telencephalon
(cerebral hemisphere )
, d
m
Rhombic lip
( cerebellar plate )
Trans rhombencephalic
sulcus ^^^ ^ T
Myelencephalon
Olfactory lobe
Optic stalk
Metencephalon
Infundibulum
Roof of diencephalon Third ventricle

Epiphysis ( pineal body ) J
\»A Choroid plexus
Roof of mesencephalon^
Cerebral aqueduct ^
Corpus callosum
Ant . commissure
Cerebellum
Lamina terminalis
" Hypophysis
Choroid plexus
Mesencephalon ( tegmentum )
Fourth ventricle etencephalon
' 1. Basilar portion
2 . Tegmental portion
Central canal
Myelencephalon
Spinal cord
Figure 3. ) I. Developing brain vesicles and ventricular system A . Lateral view of cerebral vesicle and developing
brainstem in human embryo of 8 weeks. Arrows indicate directions of growth and expansion of cerebral hemisphere.
B. Sagittal section through the brainstem of a 12-week human fetus. The telencephalon is stippled, the diencephalon
is dark red. and the mesencephalon is blue . Rhombencephalic derivatives (metencephalon and myelencephalon)
are light red. while the isthmus is white.
subdivisions of the brain are (a ) the telen - first spinal nerve of the cervical cord to the
cephalon , ( b) the diencephalon , (c) the mesen - beginning of the pontine flexure ( Fig. 3.11 ).
cephalon , (d ) the metencephalon , and (e) the As the future medulla oblongata , it differs
myelencephalon ( Fig. 2.1 ). The development of from the spinal cord in that the walls ( alar
each subdivision is considered separately, portions of the neural tube in the rhomben -
even though the embryologic events de- cephalon ) are shifted laterally at higher levels
scribed occur simultaneously. by the expanding fourth ventricle and also by
the development of the cerebellum dorsal to
Myelencephalon the medulla and pons. As a result of the ex-
pansion of the roof plate, the alar plate is dis-
The medulla , the most caudal brain seg - placed laterally to the basal plate. The sulcus
ment, is derived from the myelencephalon . limitans continues to mark the boundary be-
This brain segment extends from levels of the tween these alar and the basal plates as can
be seen in both gross and microscopic speci- Derivatives of the alar plate form sensory
mens ( Figs. 3.12 and 12.14 ). Derivatives of the relay nuclei lateral to the sulcus limitans. The
basal plate form the motor nuclei of cranial most lateral of these nuclei are the auditory
nerves, and come to occupy positions in the and vestibular (special somatic afferent (SSA )
floor of the fourth ventricle medial to the sul - cranial nerve components), and those of the
cus limitans ( Fig. 3.12 ). The most medial cell trigeminal complex (general somatic afferent
column gives rise to general somatic efferent (GSA ) ). General and special visceral afferent
(GSE ) fibers that form the hypoglossal nerve (GVA and SVA ) cell columns, represented by
( N . XII ). The more laterally located cell the solitary nuclei, lie medial to the this
columns are associated with special (SVE ) group ( Fig. 3.13). Caudally, near the junction
and general efferent (GVE ) fibers. The SVE between the myelencephalon and the spinal
cell column issues fibers from the nucleus cord, cell groups of the alar lamina differenti-
ambiguous, that forms components of cranial ate into the nuclei gracilis and cuneatus (gen-
nerves IX, X, and XI ( Fig. 12.14 ). The GVE cell eral somatic afferent, GSA ). More rostrally,
column, also medial to the sulcus limitans, some cells derived from the alar lamina mi -
represented by the dorsal motor nucleus of grate ventrally from the inferior rhombic lip
vague nerve ( N. X ) and inferior salivatory nu- to form portions of the inferior olivary complex ,
cleus ( N. IX ), gives rise to preganglionic the largest cerebellar relay nucleus of the
parasympathetic fibers that are widely dis- medulla ( Fig. 12.11 ). Fibers forming the
tributed . medullary pyramids are cortically derived ,
rriTrir
Roofplate Fourth (IV) ventricle
Median sulcus
Rhombic lip
Alar plate' Sulcus limitans
Hypoglossal
( XII) nerve Sup ganglion of
Basal plate vagus ( X ) nerve
Figure 3.12. Medulla of a 5- week human embryo. Note the prominent sulcus limitans separating structures derived
from the basal and alar plates
Roof plate 4th ventricle
f- Rhombic lip
SSA and GSA cell columns
SVA and GVA cell columns
SVE and GVE cell columns
GSE cell column

Sulcus limitans Pontine nuclei
Figure 3.13. Caudal metencephalon showing the cell columns of the cranial nerve nuclei with respect to the sulcus
limitans , Cell groups derived from the alar plate are shown in blue, while those from the basal plate are red . Both the
superior rhombic lip (cerebellum) and the pontine nuclei develop from the alar plate. Cells of the pontine nuclei mi-
grate ventrally ( arrows). Dark blue, superior rhombic lip. special (SSA), general somatic afferent (GSA) cell columns,
and the pontine nuclei; blue stipple, special (SVA) and general visceral afferent (GVA) cell columns; red stipple, spe-
cial (SVE) and general visceral efferent (GVE) cell columns; red, general somatic efferent (GSE) cell column.
late in appearance and occupy ventromedial matic efferent (GSE ) cell column gives rise to
regions near the midline. fibers of the abducens nerve ( N . VI ). An inter-
In the region of the fourth ventricle, the mediate and interrupted cell column of typi -
roof plate consists of a single layer of ependy- cal motor neurons gives rise to special vis-
mal cells covered by a thin layer of pia mater. ceral efferent (SVE ) fibers that form cranial
These two layers form the tela choroidea , and nerves V and VII, and respectively innervate
prolongations project into the ventricle in the the musculature of the first and second
region of the transverse rhombencephalic sul - branchial arches. General visceral efferent
cus to form the choroid plexus ( Fig. 6.17). ( GVE ) cells contained in the superior saliva -
Openings in the roof plate appear ( 4 to 5 tory nucleus supply preganglionic parasym -
months) which establish continuity between pathetic innervation for the submandibular,
the fourth ventricle and the subarachnoid sublingual, and lacrimal glands. Cells of the
space surrounding the brainstem. Two lateral basal plate also contribute to the pontine
apertures (foramina of Luschka ) connect the reticular formation ( Fig. 3.13).
lateral recesses of the fourth ventricle with Ventromedial portions of the alar plate
the pontine cistern. A single median aperture form cell groups similar to those described
( foramen of Magendie ) in the lower roof con- for the medulla ( 28 ). These cell groups are
nects the fourth ventricle with the dorsal concerned with (a ) the vestibulocochlear
cerebellomedullary cistern . nerve (SSA ), ( b ) the trigeminal nuclear com -
.
plex (CSA ), and ( c ) the solitary nucleus (SVA
and GVA ). The pontine nuclei which form
Metencephalon
massive cell collections in the ventral portion
This rostral portion of the hindbrain, ex- of the pons originate from the alar plate of
tending from the pontine flexure to the both the metencephalon and myelencephalon
rhombencephalic isthmus, develops into two ( Fig. 3.13). Corticofugal fibers which develop
elaborate and distinctive components of the later end , in part , upon these nuclei. The pon -
—
neuraxis the pons and the cerebellum ( Figs.
3.13 and 3.14). The pons consists of two parts:
tine nuclei give rise to a massive collection of
fibers which cross the midline and enter the
(a ) a dorsal portion lying in the floor of the opposite cerebellar hemisphere. Fibers in this
fourth ventricle, referred to as the pontine bundle form the middle cerebellar peduncle
tegmentum , and ( b) a ventral portion in ( Figs. 2.26 and 2.33). The cerebellum is derived
which some cortical efferent fibers terminate mainly from the dorsolateral portions of the
while others continue to more caudal regions. alar plates which bend posteriorly and medi -
The pontine tegmentum is derived from the ally to form the rhombic lips ( Figs. 3.11 and
basal plate ( Fig. 3.13). A medial general so- 3.14). The rhombic lips are at first widely sep-
Midbrain
Cerebellar
Rhombic lip vermis
Midbrain
Cerebellar
Extraventricular
/k hemisphere
Intraventricular
w
Flocculus
Lateral recess
Nodulus
Alar plate
Sulcus limitans Roof plate
Basal plate Margin of IV ventricle
rhomboid fossa
Spinal cord
B
Figure 3.14 Developing cerebellum and hindbrain A. Posterior oblique view of human embryo at 6 weeks B . Poste -
rior view of human fetus at 4 months of gestation
arated from each other, and each lip projects germinal zone called the external granular
-
partly into the fourth ventricle ( intraventricu layer (17, 37, 45, 51). After their migration,
lar portion ) and partly on the surface of the these neuroblasts proliferate and produce the
metencephalon above the roof plate. Further three main types of interneurons of the cere-
deepening of the transverse rhombencephalic bellar cortex: the basket and stellate cells of
sulcus at the pontine flexure causes the cere - the molecular layer, and the granule cells of
bellar rudiments of both sides to fuse in the the granular layer. The production of in-
midline caudal to the roof of the mesen - terneurons of the molecular layer is com-
cephalon. Fusion of the rhombic lips forms pleted at birth, whereas that of the granule
the transverse cerebellar plate. At 3 months cells continues for periods ranging from 6
these cerebellar primordia have a dumbbell- months to 2 years after birth in primates. In
shaped appearance ( Fig. 3.14) in which the contrast to the basket and stellate cells, which
unpaired central part represents the vermis remain superficially located , the newly
and the two large lateral knobs represent the formed granule cells must migrate from the
hemispheres. Near the end of the fourth month external granular layer across the molecular
fissures begin to develop on the cerebellar and Purkinje cell layers to reach their final
surface. The first fissure to appear is the pos- destination in the granular layer. The guid-
terolateral ( prenodular ) fissure which sepa- ance for the migrating granule cells is pro-
rates the nodulus from other parts of the ver- vided by a particular type of glial process, the
mis and the flocculus from the rest of the radial glial fibers , which are extensions of
cerebellar hemisphere. The flocculonodular lobe Bergman astrocytes. These peculiar glial cells
( archicerebellum ) ,
phylogenetically the oldest are generated in the ventricular germinal
part of the cerebellum, has the most extensive zone. Their cell bodies are located just be-
connections with the vestibular system ( 29). neath the Purkinje cell layer and they send ra-
The portion of the cerebellar plate between dially oriented fibers to the pial surface. The
the posterolateral fissure and the isthmus Bergman glial fibers can be readily identified
represents the rudiment of the corpus cerebelli. by their content in glial fibrillary acidic pro-
The first fissure to become visible in the cor- tein (GFAP) against which specific antibodies
pus cerebelli is the primary fissure. The pri- have been raised (32). It is along these fibers
mary fissure is the deepest of all cerebellar that the migrating granule cells move until
fissures, and it separates the anterior and pos- they reach the granular layer (44, 45). Ab-
terior lobes ( Figs. 2.33 and 15.1 ). All parts of sence or aberrant orientation of the radial
the cerebellum rostral to the primary fissure glial fibers leads to degeneration of granule
constitute the paleocerebeUum (anterior lobe), cells and severe malfunctions of the cerebel-
whereas the neocerebellum ( posterior lobe) lies lum, as seen in the weaver mutant mice (46).
between the primary and posterolateral fis- After completion of the granule cell migra-
sures. The neocerebellum is subsequently dition, the network of radial glial fibers disap-
vided into lobules by three transverse fis- pear. The Bergman glia appear to transform
sures, the prepyramidal, the horizontal, and into astrocytes, ependymal cells, and , possi-
the posterior superior. bly, oligodendroglial cells (4). Although cells
Studies of the neurogenesis of the cerebel- of the transient external granular layer mi-
lar cortex have revealed developmental fea- grate inward , their axonal processes, which
tures that are general and apply to other cor- will become the parallel fibers , remain in the
tical structures, including the neocortex of the molecular layer where synaptic contacts are es-
cerebral hemispheres. Cerebellar primordia tablished with outgrowing dendrites of the
initially consist of a germinal zone at the sur- Purkinje cells.
face of the fourth ventricle (ependymal layer ) The cerebellar nuclei, which are also gener-
and a marginal zone at the pial surface. The ated relatively early, are considered to be de-
germinal zone gives rise first to the large rived from neuroblasts located close to the
Purkinje and Golgi-II cells that migrate out- ventricular surface of the cerebellum. The
ward from the ependymal layer to form the largest and most lateral of these nuclei, the
Purkinje cell layer. The Purkinje cells are the dentate nucleus , has a convoluted appearance
principal projection neurons of the cerebellar ( Fig. 15.17) which becomes evident during
cortex. The germinal zone of the fourth ven- the fifth month ( 29). The roof nuclei ( the fas-
tricle also produces neuroblasts that migrate tigial nuclei) develop near the midline and
to the pial surface where they form a second have profuse connections with the vestibular
nuclei. In some species, the globose and embo- through the deep layers. The inferior collicu-
li form nuclei are not clearly separated and are lus serves as a major relay complex in the au-
referred to as the interposed nuclei. Cranial ditory system, whereas the superior collicu -
and caudal portions of the thin metencephalic lus serves as a subcortical integrative center
roof plate persist in the adult as the superior for the visual system.
and inferior medullary veli ( Fig. 2.28). The exact origin and patterns of formation
of the midbrain reticular formation , the red nu-
Mesencephalon cleus , and the substantia nigra are still poorly
understood. As to the substantia nigra, how-
The mesencephalon is the smallest brain ever, recent evidence from the rat embryo
vesicle and ultimately forms the shortest divi- suggests that most of the nigral neurons orig-
sion of the brainstem. The alar and basal inate from a specific region of the basal plate
plates are separated by a well-defined sulcus located at the junction between the mesen -
limitans. The cavity of this vesicle is greatly cephalon and the isthmus of the meten-
reduced during development and ultimately cephalon (36). Cells of the pars compacta of
becomes the cerebral aqueduct. The portion the substantia nigra do not contain melanin
of the midbrain ventral to the aqueduct con- pigment at birth; appreciable pigmentation
sists of the midbrain tegmentum , dorsally, and does not develop until the fourth or fifth
the crus cerebri ventrally. These structures are year. In the rabbit, neurons of the substantia
separated by the substantia nigra ( Fig. 14.1 ). nigra have been found to contain dopamine
Motor neurons derived from the basal plates on the nineteenth day of gestation (54).
form the general somatic efferent (GSE) cell
columns that compose the oculomotor com- Diencephalon
plex ( N. Ill ) and what must be regarded as a
caudal appendage to it, the trochlear nuclei The prosencephalon comprises the dien-
( N. IV ). These cranial nerves, together with cephalon and the telencephalon, both subdi-
the abducens nerve, innervate the extraocular visions forming the entire central nervous
muscles derived from the preotic somites. A system rostral to the midbrain ( Figs. 3.1 and
smaller lateral cell group from the basal plate 3.10). The diencephalon develops from the
migrates dorsal to the somatic cell columns of thickened lateral walls of the caudal portion
cranial N. Ill to form the visceral component of the original prosencephalic vesicle. It is
(GVE ) of this nuclear complex. The marginal considered to be derived only from the alar
layer of each basal plate eventually is in- plates. The prosencephalon is caudally con-
vaded by massive collections of corticofugal tinuous with the mesencephalon, and at an
fibers which form the crus cerebri. These are early embryonic stage optic cups, formed
corticospinal, corticopontine, and corticobul- from the optic vesicles, are attached to the lat-
bar fibers largely destined for more caudal re- eral walls of the diencephalon. The cavity of
gions of the neuraxis. the prosencephalon becomes narrowed to
The alar plates of the mesencephalon pro- form the third ventricle. The posterior commis-
liferate and produce two longitudinal emi- sure is considered to mark the caudal limit of
nences separated by a median depression the diencephalon ( Fig. 2.13), whereas the in -
dorsal to the aqueduct. These eminences form terventricular foramen delineates its boundary
the quadrigeminal plate ( Fig. 3.16). A later de- with the telencephalon ( Fig. 3.15). The lamina
veloping transverse depression divides each terminalis , representing the membrane
longitudinal eminence into a superior and in - formed by the closure of the anterior ( rostral )
ferior colliculus ( Fig. 2.26). Neuroblasts form- neuropore, is a telencephalic derivative, but
ing the inferior colliculus produce a central its ventral part gives rise to a matrix in which
homogeneous cell mass surrounded by a nar- the optic chiasm ultimately develops.
row cortical rim. The superior colliculus is a The roof plate of the diencephalon be-
more complex stratified structure formed by comes very thin and rostral parts of it invagi -
waves of migrating neuroblasts. Its develop- nate to form the choroid plexus of the third
ment resembles that of the cerebral cortex in ventricle ( Figs. 3.11 and 3.15). Caudal por-
that cell migrations follow an "inside-out" se- tions of the roof plate thicken medially and
quence (12), which means that cells forming evaginate posteriorly to form the pineal gland .
the deeper layers appear first and those des- This gland which develops at about the sev-
tined for the superficial layers must pass enth week, functions as a neuroendocrine
Corpus callosum Lateral ventricle

and
Dentate gyrus of
hippocampus Choroid plexus
Pallium
Basal ganglia
Line ot fusion
\ mi o
Thalamus
Internal capsule
Amygdaloid N —
nuclear complex
Third ventricle
and
Hypothalamic
sulcus
A choroid plexus
Hypothalamus
B
Figure 3.15. Frontal sections through diencephalon, ventricular system, and choroid plexuses of the developing
brain. A . Invagination of choroid plexuses into lateral and third ventricles B. Choroid plexuses and secondary fusion of
telencephalon with diencephalon. The transverse cerebral fissure is indicated in both A and B by an asterisk .
transducer . It produces melatonin, a hormone ceives fibers of the stria medullaris and gives
which is secreted into the bloodstream with a rise to the fasciculus retroflexus , links the sep-
24- hour periodicity, providing the body with tal nuclei with the midbrain reticular forma -
a circulating "clock" which is under the dition .
rect control of lighting environment . Mela - The proliferative activity of the germinal
tonin appears to exert inhibitory effects on zone of the third ventricle is used to subdi-
gonadal and thyroid function . After puberty vide the diencephalon into five longitudinal
the gland has a tendency to calcify and be- zones: (a ) the hypothalamus, ( b) the subthala-
cause it lies in the midline dorsal to the poste- mus, (c) the pars ventralis thalami, ( d ) the
rior commissure, it serves as an important pars dorsalis thalami, and (e) the epithala-
landmark on x-ray films of the skull. The roof mus, comprising the pineal gland and the
plate of the diencephalon may form another habenular nuclei. Contemporaneously, the
evagination in the region of the interventricu - lateral walls of the third ventricle develop
lar foramen, known as the paraphysis . This ep- distinct longitudinal sulci on the surfaces fac-
ithelial sac may persist into adult life as a pa - ing the lumen . One of these depressions is the
raphysial cyst and produce intermittent hypothalamic sulcus which serves to divide the
blockages in the flow of cerebrospinal fluid . major part of the diencephalon into the thala -
Other epithalamic structures, considered to mus and hypothalamus ( Figs. 3.15 and 16.6).
be derived from the roof plate, or adjacent Some authors have suggested that the hypo-
parts of the alar plate, are the habenular nuclei thalamic sulcus may be the diencephalic
and habenular commissure. These structures lie equivalent of the sulcus limitans, but this is
dorsally, immediately rostral to the posterior uncertain since it does not mark either the di -
commissure. The habenular nuclei, which revision of alar and basal plates or the bound -
ary between sensory and motor regions. Ac- the lamina terminalis ( Figs. 3.10 and 3.11 ).
tive proliferation and cell differentiation pro- Each cerebral vesicle is in wide communica -
duces an expansion of thalamic regions dor- tion with the third ventricle via the interven-
sal to the hypothalamic sulcus which greatly tricular foramen ( Fig. 3.15) and expands up-
narrows the third ventricle. The thalamic nu - ward, forward , and backward . Through this
clear masses of each side approach the mid - caudal expansion, the telencephalic vesicles
line and fuse in an interthalamic adhesion in cover the diencephalon dorsally and laterally.
about 80% of human brains. Cell growth in The region where the cerebral vesicle is at -
the thalamus proceeds rapidly and results in tached to the roof of the diencephalon be -
the formation of thalamic nuclear groups, comes very thin. Here the single layer of
some of which are clearly separated by ependymal cells and the vascular mes-
medullary laminae ( Figs. 2.16 and 2.29B). The enchyme in the roof of the third ventricle be -
principal nuclear groups of the thalamus are come continuous with similar layers in the
the anterior, the medial, the ventral, and the lateral ventricle that form the choroid plexus.
dorsal nuclear groups. The medial and lateral The line of invagination which first appears
geniculate bodies ( metathalamus ) represent a at the level of the interventricular foramen is
caudal extension of the ventral nuclear group called the choroidal fissure. Thus, the choroid
which function in part as relay nuclei. In gen- plexus of the third and lateral ventricles is
eral, the dorsal nuclear group serves as asso - continuous through the interventricular
ciation nuclei. Thalamic nuclear groups read - foramina along the line of vesicle evagina -
ily detectable in gross specimens include the tion, the choroid fissure. A small horizontal
anterior and medial groups, as well as the cleft persists between the cerebral vesicle and
geniculate bodies and the pulvinar, which are the diencephalon ( Fig. 3.15). This narrow tri -
part of the posterior group. angular space dorsal to the thalamus is lined
The germinal zone that lies ventral to the with a double layer of pia mater and filled
hypothalamic sulcus ( Figs. 3.11 and 3.15) on with loose mesenchyme ( velum interpositum,
both sides of the third ventricle gives rise to Fig. 2.29B). This space represents the most
the hypothalamus. Cells in this region differ - rostral extension of the transverse cerebral fis-
entiate into a number of separate nuclear sure ( Fig. 3.15A and B ). The lower pial layer
groups which subserve visceral, endocrine, of this fissure, as observed in frontal section,
and regulatory functions. The most promi- forms the roof of the diencephalon and be -
nent nuclear group forms the mammillary comes invaginated as the choroid plexus of
body , a rounded protuberance on the ventral the third ventricle ( Figs. 2.29A and 3.15). The
surface of the hypothalamus ( Figs. 2.9 and adult cerebral hemisphere also is separated
2.10). A small evagination in the floor of the from the cerebellum by the transverse cere -
diencephalon caudal to the optic chiasm bral fissure. The tentorium cerebelli occupies
forms the primordium of the infundibulum , part of the transverse fissure and separates
which gives rise to the posterior lobe of the hy- the inferior surfaces of the hemispheres from
pophysis or neurohypophysis. The anterior lobe the superior surface of the cerebellum ( Fig.
of the hypophysis derives from an ectoder - 2.3).
mal diverticulum of the mouth cavity (sto- Immediately above the choroid fissure the
modeum ) known as Rathke' s pouch , which medial wall of the cerebral vesicle becomes
superiorly comes in contact with the in- thickened and forms the hippocampal ridge
fundibulum. Rathke's pouch loses its pharyn- ( Figs. 3.15 and 3.17). This ridge bulges into
geal attachment and differentiates into the the lateral ventricle as a longitudinal eleva-
anterior lobe of the hypophysis or adenohy- tion, the hippocampal formation . As the cerebral
pophysis ( Fig. 3.11 ). hemispheres expand , the hippocampal for-
Other hypothalamic derivatives include mation extends posteriorly and is finally car -
the subthalamic nucleus and the inner part of ried downward into the temporal lobe. The
the globus pallidus. These structures are de - medial surface of the hemisphere develops a
scribed in the next section. corresponding groove, the hippocampal fissure,
which runs parallel to the choroid fissure
Telencephalon throughout its extent. The hippocampal for-
mation and the dentate gyrus together consti-
This most rostral segment of the develop- tute the archipaUium , which is believed to be
ing brain is composed of the two evaginating the most phylogenetically ancient portion of
cerebral vesicles and their median connection , the cerebral cortex.
The walls of the primitive telencephalic subthalamic region that is closely connected
vesicle consist of germinal, mantle, and mar- with the globus pallidus, also is considered a
ginal layers, and represent only the alar hypothalamic derivative. More precisely, it is
plates. The mantle layer ventrolaterally un - generated in a germinal zone lying in the
dergoes relatively rapid thickening as a con- supramammillary recess of the third ventricle
sequence of cell proliferation, and creates a (34). The internal capsule, formed by fibers
cell mass that protrudes into the lumen of the projecting to and from the cerebral cortex,
vesicle. This thickened basal region is known has a complex development (18), but ulti-
as the striatal portion because it ultimately
gives rise to the striatum and other compo-
—
mately forms two major limbs an anterior
limb which partially separates the head of the
- caudate nucleus and the putamen, and a
nents of the basal ganglia ( Fig. 3.15). The thin
ner and more dorsal wall of the brain vesicle larger posterior limb between the thalamus
is referred to as the suprastriatal portion . This and the globus pallidus ( Fig. 2.13).
part of the cerebral hemisphere gives rise to The cerebral hemispheres grow and expand
the cerebral cortex. rapidly, first forward to form the frontal lobe
area, then laterally and upward to form the
BASAL GANGLIA AND INTERNAL CAPSULE future parietal lobe ( Figs. 3.11, 3.16, and 3.17).
Posterior and inferior expansions soon pro-
The thickened basal ganglia region ap- duce the occipital and temporal lobes. The ex-
pears in the telencephalon at the level of the pansions of the cerebral hemispheres cover
interventricular foramen ( Fig. 3.15). With the the diencephalon and posterior surface of the
expansion of the cerebral hemispheres back midbrain. The anterior, posterior, and infe-
over the diencephalon, part of the striatal rior expansions during development explain
ridge is carried in the wall of the lateral ven- the curved shape and the relations of several
tricle dorsal to the lateral border of the thala- internal telencephalic structures in the adult
mus and down into the roof of the inferior brain (e.g., lateral ventricle, choroid plexus,
horn of the lateral ventricle. Large numbers caudate nucleus, and fornix ). The cortex cov-
of developing corticofugal and corticopetal ering the lenticular nucleus remains as a fixed
fibers projecting from, and to, the developing area, the insula ( Fig. 3.18). This region be-
cerebral cortex incompletely divide the basal comes buried in the floor of the lateral sulcus
ganglia into a dorsomedial portion which by the subsequent overgrowth of adjacent
bulges into the lateral ventricle and a ventro- lobes ( Fig. 3.17).
lateral portion medial to the insular region.
The paraventricular striatal tissue medial to CEREBRAL CORTEX
these fibers forms the caudate nucleus which
throughout most of its extent is closely re- The suprastriatal portion of the early telen-
lated to the lateral ventricle ( Figs. 2.15 and cephalic vesicle appears to be composed of
2.29B). The amygdaloid nuclear complex arises three concentric zones during its smooth-sur-
from the same medial primordium. The por- faced (lissencephalic) stage. A germinal or ma-
tion of the basal ganglia lateral to these corti- trix zone surrounds the lateral ventricle. Most
cal fiber systems, which collectively form the of the cells of this zone migrate outwards to
internal capsule , constitutes the lentiform nu- become nerve and glial cells upon matura-
cleus ( Fig. 3.15). The lentiform nucleus is dition. However, some cells remain in this zone
vided into two parts: (a ) a larger lateral part to form the internal limiting membrane,
known as the putamen , and ( b) a smaller inner ependyma, and the subependymal glial layer.
part, the globus pallidus. The pale intermediate zone becomes the white
Although the basal ganglia are classically matter of the cerebral hemispheres. It has
regarded as subcortical telencephalic nuclei, many radiating fibers and is traversed by
some authors ( 25, 26, 47) consider parts, or neuroblasts and glioblasts migrating from the
all, of the globus pallidus to be derived from matrix zone to the more superficial layer. An
portions of the hypothalamus. Indeed , the en- outer cortical zone or plate represents the
topeduncular nucleus of the rat, considered prospective neopallium (isocortex ). This zone
homologous to the internal segment of the has two distinct layers. The deeper pyramidal
primate globus pallidus, was shown to arise layer has many cells and will form layers II to
from a germinal zone that is closely associ- VI of the adult six-layered cortex ( Fig. 20.1 ).
ated with the hypothalamic sulcus (35). The The marginal layer is composed mostly of
subthalamic nucleus , a small nucleus of the fibers and becomes the molecular ( plexiform )
Pineal body
Cerebral hemisphere
/
\ Midbrain
4
s
Insular fossa
9 Cerebellum
Rhomboid fossa
A B
Figure 3.16. Cerebral vesicle and brainstem in the 12- week human fetus A. Lateral view B . Posterior view
or most superficial layer (layer I ). In areas of after the completion of migration. This differ-
the olfactory cortex (allocortex ), the six layers entiation involves both the shape of the
are not present . In these regions, the migrat- perikaryon ( pyramidal versus nonpyramidal )
ing neuroblasts and glioblasts enter the corti- and its connections. The commitment of a
cal zone and form a thin nuclear layer close to neuron to differentiate into a certain morpho-
the surface. logic class appears to depend mostly on the
It is now well-established that the cortical order in which it is generated , rather than on
cell layers develop in an inverted fashion, so its final position within the cortex. In support
that cells in the deeper layers ( i.e., layer VI ) of this view is the evidence gathered in the
develop first ( 2, 45, 51). Hence, cells destined murine reeler mutant that suffers from an in -
to the superficial layers must migrate past herited neuronal migration disorder which
older cells to reach their final position . As in specifically affects the intracortical migration
the cerebellar cortex, the migration of neuro- of the pyramidal neurons. In this mutant, the
blasts is guided from an early stage by a sys- neuroblasts migrate to faulty positions but
tem of radial glial fibers that extends the nevertheless differentiate into neurons whose
width of the thickening telencephalon . The perikaryal shapes are characteristic of each
perikarya of the radial glial cells lie in layer ( 3). At birth the human neopallium has
the ventricular and subventricular zones. In assumed a stratified appearance as a result of
the human fetus, this process takes place, for neuron differentiation and laminae formation
the greater part , between 7 and 16 weeks ges- by the incoming and outgoing nerve fibers.
tational age. However, the presence of radial In the early weeks of gestation , the sur-
glial fibers has been noted in the human faces of the cerebral hemispheres are lis-
telencephalon beyond 16 weeks, raising sencephalic (smooth ). The developing com-
the possibility that migration does not end missures form conspicuous bundles on the
sharply at this time. In addition to the system cut medial surfaces ( Figs. 3.15 and 3.17). Dur-
of radial glial fibers, other organizing princi- ing the sixth and seventh months, the sur-
ples may be involved , such as the thalamo- faces of the hemispheres grow rapidly and
cortical afferents that already exist before develop convolutions (gyri ) separated by
the beginning of migration to the cortical shallow or deep furrows ( sulci ). As a result of
plate (3). such surface folds, two-thirds of the cerebral
In humans, the cortical zone becomes cortex becomes buried in the walls and floor
highly cellular due to massive neuroblast mi - of the sulci when the brain attains its adult
grations in the twelfth week. Differentiation size. Fetal sulci appear in an orderly se-
of neuroblasts into neuronal classes charac- quence: the phylogenetically older sulci ap-
teristic of each cortical layer is accomplished pear first, and more recently acquired sulci
Corpus x
De-
Insula Stria terminalis callosum
Lateral- Anterior
ventricle o
commissure
o
'
Hippocampus Lamina
Choroid \ terminalis
i?
fissure Olfactory 1'
Lateral Olfactory
olfactory tract bulb Thalamus bulb <9.
o
3
B 0.
A
>
Q
Occipital lobe Parietal Fornix and commissure Septum o
lobe of the fornix pellucidum 3
<
Thalamus
o
i
<
o
O
3
Hippocampus i
O
Temporal lobe Frontal Lamina
Rhinal sulcus -
terminalis Q
Olfactory bulb- Insula lobe 3
D
C
O
o
Insula Stria terminalis Corpus o
C/1
callosum r
Fornix — T3
r- Interventricular o
Midbrain - <
/ \ foramen o
Cuneus ' -
Calcarine
sulcus /
J
V i
*
III Ventricle t
Fossa of
lat sulcus
Rhinal-
sulcus
X Lamina
terminalis
c
><
co
E F
.
Figure 3.17 Development of human cerebral hemisphere A B. Lateral and medial surfaces of the hemisphere in a
.
fetus of 3 months C, D Lateral and medial surfaces of the hemisphere in a fetus at the beginning of the fifth month E
F. Lateral and medial surfaces of the hemisphere at the end of the seventh month
Parietal lobe
Inferior Superior
frontal sulcus frontal sulcus Central sulcus
.Intraparietal
^
sulcus
Lateral sulcus
- Occipital lobe
- Cerebellum
Frontal lobe / Temporal lobe Inferior temp sulcus

,
Insula & Sylvian fossa Superior temp sulcus
Figure 3.18 . Lateral view of the brain of a 7 -month human fetus Note the primitive sulcal pattern and the exposure
of the insular cortex
appear later ( Figs. 3.17E, F and 3.18). The connecting nonolfactory cortical areas of the
principal sulci and gyri that form the charac- two hemispheres, appears as a small bundle
teristic pattern of the human cerebral cortex rostral to the commissure of the fornix. The
all can be identified in the full-term infant . size of the corpus callosum parallels the rapid
growth and expansion of the neopallium . It
COMMISSURES first extends anteriorly to connect the frontal
lobes and then enlarges posteriorly as the
The medially placed lamina terminalis rep- parietal lobes develop. As the constituent
resents the cephalic end of the early neural fibers increase in number, the corpus callo-
tube and extends from the roof plate of the sum arches back over the thin roof of the di-
diencephalon to the optic chiasm ( Figs. 3.11 encephalon ( Fig. 3.17). The superior and ros-
and 3.17). This primitive midline telen- tral portions of the hippocampal formation
cephalic structure provides the only bridge undergo regressive changes in association
whereby nerve fibers can pass from one cere- with development of the corpus callosum,
bral hemisphere to the other. The first fibers but these parts persist in the adult as the in -
to cross between the two hemispheres ( com- dusiuw griseum or supracallosal gyrus ( Fig.
missural fibers ) are within the anterior commis- 18.11 ). The area between the corpus callosum
sure. This structure appears in the lower por- and the fornix becomes very thin and forms
tion of the lamina terminalis by the third the septum pellucidum. These commissures
month . It connects the olfactory bulb and por- and septum pellucidum develop within, and
tions of the temporal lobe of one side with the represent prolongations of , the embryonic
same structures of the opposite hemisphere lamina terminalis. The fibers of the optic chi-
( Figs. 18.8 and 18.12). The small commissure of asm cross in the junctional zone between the
the fornix ( psalterium ) is the second to appear lamina terminalis and the rostral wall of the
in the lamina terminalis close to the roof of diencephalon ( Figs. 2.29 and 3.17).
the diencephalon ( Fig. 3.17D ). Its fibers con
nect portions of the hippocampal formation
- After the neural tube has been formed , it
lies deep to the overlying ectoderm and is
with each other. surrounded on all sides by primitive meso-
The largest and most important commis- derm ( or mesenchyme ). This embryonic rela -
sure to cross in the lamina is the corpus callo- tionship is shown in Figure 3.9, where the
sum . The first fibers of the corpus callosum, more darkly stained mesenchyme is seen to
the left of the spinal nerve and neural tube. from the meninges, from the connective tis-
Recent evidence in birds suggests that much sue sheaths along peripheral nerves, or from
of this mesenchyme has most likely a neural glioblasts. An intervertebral disc may rupture
crest origin ( 30). From the surrounding mes- posteriorly into the vertebral canal and com-
enchyme the muscles, blood vessels, carti- press the spinal cord or spinal nerves. Also,
lage, bone, and connective tissue of the body fractures of the skull and vertebrae often
are derived . This mesenchyme thus gives rise compress the underlying brain or spinal cord .
to several supporting structures of the ner-
vous system (e.g., skull, vertebrae, meninges CONGENITAL ANOMALIES
( dura mater ), intervertebral discs, ligaments,
sheaths of peripheral nerves, blood vessels, A detailed discussion of malformations of
and microglia ). These mesodermal structures the developing neural tube or changes in
are of paramount importance, for they pro- brain development resulting from malnutri-
vide not only support, but protection and tion are beyond the scope of this textbook.
nourishment to the nervous system . Some malformations involving both the de-
Supporting tissues are, under some cir- veloping neural tube and the vertebral col -
cumstances, responsible for serious damage umn will serve as examples. Defects in the
to the nervous system . For example, an artery development and fusion of the dorsal arch of
may rupture with extensive hemorrhage, or one or more vertebrae produce a condition
the lumen of a vessel may be occluded sud - referred to as spina bifida . There are many
denly and produce anoxia in the area of its variations of such a condition, including
neural distribution. Tumors commonly arise some in which the meninges and / or the
Vertebral
body
Figure 3.19. One type of spinal malformation is called spina bifida. In this condition, there is a failure of closure of
the posterior arch of one or more vertebrae and in some types there is a failure of development of the neural
tube. A illustrates failure of closure of both neural tube and the vertebral arch. In B the neural tube develops nor -
mally, but the meninges and the subarachnoid space extend dorsally through the defect In the vertebrae to pro-
duce a meningocele . If the spinal cord forms part of the subcutaneous herniation ( arrow / ), it is called a meningocele.
C represents a minor defect in the vertebral arch in which a dermal sinus extends from the skin to the subarachnoid
space. This sinus may close secondarily . D represents spina bifida occulta, in which the meningeal herniation does not
extend far above the defect in the vertebral arch. Skin overlying the vertebral defect may contain a dense tuft of
hair . Nerves and neural tissue are in blue; the meninges are In red
spinal cord may be involved . For instance, an tissue to form a cyst , there may be no protru -
unclosed posterior arch of the vertebra may sion of the overlying skin ( Fig . 3. WD ) . This
result in herniation of the dura and arach- relatively asymptomatic condition is termed
noid membranes dorsally, forming a translu- spina bifida occulta and is often marked by a
cid cystlike expansion of the subarachnoid tuft of hair on the overlying skin . In some
space filled with cerebrospinal fluid . This cases, the caudal neuropore may not close
condition , which occurs most often in the completely , forming a channel or fibrous
lumbosacral region , is called a meningocele cord extending from a dimple on the surface
( Fig . 3.19 B ) . Meningocele is often associated of the skin to the meninges ( Fig . 3.19C) . This
with other congenital malformations, such as abnormality is referred to as congenital dermal
hydrocephalus that sometimes can be cured sinus . A more serious defect involves failure
only after the resection of the protruding of the neural groove to close and form the
meningeal sac . When the spinal cord is dis- neural tube . The neural tissue then remains
placed dorsally into the cyst, the condition exposed to the outside and the subsequent
is termed a meningomyelocele . Neurologic differentiation of neurons is arrested . This is
complications, such as motor , sensitive, termed spina bifida with myeloschisis , or sim -
and sphincteral deficits, often accompany ply rachischisis , a condition that is accompa -
meningomyelocele. If the meningeal sac does nied by severe neurologic deficits ( Fig .
'
not extend far enough into the subcutaneous 3.19A ) .
References radiography. J Comp Neurol 1964;122: XIV . Philadelphia : J .P. Lippincott ,
1 . Altman J . Proliferation and migra -

-
311 327.
13. Gilbert SF. Developmental biology .
1912:1-144.
23. Kuhlenbeck H. The central nervous
tion of undifferentiated precur- Sunderland , MA: Sinauer Associ - system of vertebrates. Vol. 5, Part I .
sor cells in the rat during postnatal ates, 1988. Derivatives of the prosencephalon :
gliogenesis. Exp Neurol 1966,16: 14 . Giorgi PP, van Der Loos II . Axons diencephalon and telencephalon .
263-278. from eyes grafted in Zenopus can Basel: Karger, 1977.
2. Angevine JB Jr, Sidman RL. Autora - grow into the spinal cord and reach
the optic tectum . Nature 1978;273:
26. Kuhlenbeck H , Haymaker W. The
derivatives of the hypothalamus in
diographic study of cell migration
during histogenesis of the cerebral
cortex in the mouse. Nature 1961;
- .
746 748
15. Gottlieb DI, Glaser L. Cellular
the human brain : their relation to
the extrapyramidal and autonomic-
192:766-768. recognition during neural develop- systems. Milit Surg 1949;105:26-52.
.
3. Barth 1X7 . Disorders of neuronal mi-
gration . Can J Neurol Sci 1987;
ment . Annu Rev Neurosci 1980;
3:303-318.
27. l andis SC. Target regulation of neu -
rotransmitter phenotype. Trends in
-
14:1 16. 16. Hamilton WJ , Boyd |D, Mossman
HW . Human embryology. Prenatal
Neurosci 1990;13:344-350.
4. Choi BH , Lapham LW . Evolution of 28. hangman J . Medical embryology
Bergman glia in developing human development of form and function . 4 th ed. Baltimore: Williams &
fetal cerebellum: a Golgi, elec- Ch . XII . Baltimore Williams & Wilkins, 1981 .
tronmicroscopic and immunofluo- Wilkins, 1962:313-388. 29. Larsell O, Jansen J. The comparative
rescence study. Brain Res 1980,190: 17. HanawayJ. Formation and differen - anatomy and histology of the cere-
369-383. tiation of the external granular layer bellum : the human cerebellum ,
5. Cowan WM. The development of ol the chick cerebellum . J Neurol Sci cerebellar connections and cerebel -
6.
-
the brain. Sd Am 1979;241:112 13
!
Crouse GS, Cucinotta AJ . Progres-
1967;131 : 1 -14.
18. Hewitt W . The development of
lar cortex. Minneapolis: University
of Minnesota Press, 1972.
sive neuronal differentiation in the the human internal capsule and 30. Le Douarin N . The Neural Crest
submandibular ganglia of a series of lentiform nucleus. J Anat 1961 ;95: Cambridge, UK: Cambridge Univer -
human fetuses. J Comp Neurol
1965;125:259-272.
- .
191 199
19. |lochstetter F. Beitrage zur Entvvick - 31 .
sal) Press, 1982.
Levi - Montalcini K , Calissano P. The
7. Davis CL. Description of a human lungsgeschichte des menschlichen nerve-growth factor. Sci Am
embrvo having 20 paired somites. Gehirns. Vol . 1. Vienna and Leipzig: 1979;240:68-77.
Contrib Embryol 1923;15:1-51. F. Deutcke, 1919. 32. Levitt P, Rakic P. Immunoperoxy -
-
8. Del Rio Llortega P. El Tercer ele- 20. Ingalls NW . A human embryo at the dase localization of glial fibrilary
mento de los centros nerviosus. I lis - beginning of segmentation with acidic protein in radial glial cells
togenesis y evolution normal: exoda special reference to the vascu - and astrocytes of the developing
v distribution regional de microglia . lar system . Contrib Embrvol 1920;!1: rhesus monkev brain. J Comp Neu -
Mem R Soc Espan Hist
1921;11 :213-268.
.
\ it 61-90.
21. Jacobson M . Developmental neuro- 33.
-
rol 1980;193:417 448.
Lund KD. Development and plastic-
9. Dennis J . Development of the neuro - biology. New' York : Plenum Press, ity of the brain. New York: Oxford
muscular junction : Inductive inter - 1978. University Press, 1978.
actions between cells. Annu Rev 22. Jessell TM. Neuronal survival and 34. Marchand R . 1 listogenesis of sub-
Neurosci 1981;4:43-68. synapse formation . In : Kandel thalamic nucleus. Neuroscience
10. -
Edelman GM . Cell adhesion mole-
cules in neural histogenesis. Annu
ER, Schwartz Jll, Jessell TM , eds.
Principles of neural science. Ch . 35.
1987;21:183-195.
Marchand R , Lajoie L, Blanche! C.
Rev Physiol 1986;48:417-430. 59. Am sterdam: Elsvier, 1991:929- I listogenesis at the level of the basal
11 . Edelman GM . Neural Darwinism. 944. forebrain: the en toped uncu la r
The theory of neuronal group selec- 23. Kalil RE. Synapse formation in nucleus. Neuroscience 1986, 17:
tion . New York : Basic Books, 1987. the developing brain. Sci Am 1989; 591 61 ) 7
12. Fujita S. Analysis of neuron differ- 261:76-85. 36. Marchand R , Poirier LJ . Isthmic ori -
entiation in the central nervous sys- 24. Keibel F, Mall FP. Manual of gin of neurons of the rat substantia
tem by tritiated thymidine auto- Human Embryology, Vol. II , Ch . nigra . Neuroscience 1983;9:373-381.
37. Miale IL, Sidman RL. An autoradi- nections in autonomic ganglia. viewpoint and recent advances. De-
ographic analysis of histogenesis in Physiol Rev 1978;58:821-862. velopment 1990;109:243-270.
the mouse cerebellum . Exp Neurol 44 . Rakic P. Neuron -glia relationship 51 . Sidman RL , Rakic P. Neuronal mi-
1961;4:277-296. during granule cell migration in de- gration , with special reference to de-
38. Moscona AA , Hausman RE. Biologi - veloping cerebellar cortex. A Golgi veloping human brain: a review.
cal and biochemical studies on em- and electron microscopic study in Brain Res 1973;62:1-35.
bryonic cell recognition . In: Lash Macacus rhesus. J Comp Neurol 52. Sperry RW. Chemoaffinitv in the or -
JW, Burger MB, eds. Cell and tissue -
1971;141:283 312. derly growth of nerve fiber patterns
interactions. New York: Raven 45. Rakic P. Neuronal - glial interaction and connections. Proc Natl Acad Sci
-
Press, 1977:173 186. during brain development . Trends ( USA ) 1963;50:703-710.
39. Payne F. General description of a 7 - in Neurosci 1981;4:184-187. 53. Tennyson VM . Electron microscopic
somite human embryo. Contrib Em - 46. Rakic P, Sidman RL. Weaver mutant study of the developing neuroblast
bryol 1924;16:115-124. mouse cerebellum: defective neu - of the dorsal root ganglion of the
40. Peters A , Palav SL, Webster H de F. ronal migration secondary to ab- rabbit embryo. J Comp Neurol
The fine structure of the nervous normality of Bergman glia . Proc 1965;124:267-318.
system: the neurons and supporting Natl Acad Sci ( USA ) 1973;70:24O- 54. Tennyson VM , Barrett RE, Cohen G ,
cells. Philadelphia : W . B. Saunders 244. Cote L, Heikkila R, Mytilineou C.
Co., 1976. 47. Richter E . Die Entwicklung des Correlation of anatomical and bio-
41 . Pictet RL , Rail LB, Phelps P, Rutter Globus Pallidus und des Corpus chemical development of the rabbit
WJ . The neural crest and the origin Subthalamicum. Berlin : Springer - neostriatum . In: Ford D, ed . Neuro-
of the insulin - producing and other Verlag, 1965. biological aspects of maturation and
-
gastrointestinal hormone producing 48. Robertson A, Gingle AR . Axial aging. Progress in brain research .
-
cells. Science 1976;191:191 192. bending in the early chick embryo Vol. 40. Amsterdam : Elsevier,
42 . Prentiss CW, Arey LB. A laboratory by a cyclic adenosine mono- 1 ^ 73: 203-217.
manual and textbook of embry - phosphate source. Science 1977,197: -
55. Tuchman Duplessis H , Auronx M ,
ology. Ch. XII . Philadelphia : 1078-1079. Haegel P. Illustrated human embry -
W . B. Saunders Company , 1920:321- 49. Sauer FC. Mitosis in the neural tube. ology. Vol. 3. Nervous system and
352. |Comp Neurol 1935;62:377-405. endocrine glands ( translated from
43. Purves D, Lichtman JW . Formation 50. Schoenvvolf GC, Smith JL. Mecha - French ). New York: Springer Ver- -
and maintenance of synaptic con - nisms of neurulation: traditional lag, 1974.
4
Blood Supply of the Central
Nervous System
Metabolically, the central nervous system brain areas deprived of glucose following the
is one of the most active systems of the body. occlusion of cerebral arteries ( 55 ).
Although the brain constitutes only about 2% The term stroke, or cerebrovascular accident ,
of the body weight , it requires 17% of the car- refers to the neurologic symptoms and signs,
diac output and 20 % of the oxygen utilized usually focal and acute, that result from dis -
by the body. Estimates of cerebral blood flow eases involving blood vessels. Strokes are ei -
based on the nitrous oxide method ( 39 ) indi - ther occlusive ( due to closure of a blood ves -
cate a normal blood flow of about 50 ml / 100 sel ) or hemorrhagic ( due to bleeding from a
g of brain tissue per minute. Thus, a brain of blood vessel ). The term ischemia refers to in -
average weight has a normal blood flow of sufficiency of blood supply. In cases of brief
about 750 ml / minute and a mean oxygen or temporary ischemia , neurologic symptoms
consumption of about 3.3 ml / 100 g of brain and signs may disappear rapidly , without
tissue per minute (about 46 ml / min for the leaving traces of tissue damage. Severe and
entire brain ) . prolonged ischemia , however, deprives brain
The brain is not a homogeneous organ and tissue not only of oxygen but also of glucose,
metabolic activity in various regions reflect and, moreover, prevents the removal of po-
the functional activity of distinct brain re- tentially toxic metabolites such as lactic acid
gions. This differential functional activity of (9 ). It usually leads to the death of neurons
neuronal systems under various conditions and glial cells in the ischemic zone, a condi -
can be demonstrated autoradiographically tion referred to as infarction. Diseases of the
and mapped quantitatively by injections of blood vessels are among the most frequent
2[ l 4C|-deoxyglucose ( 2- DG ) technique, which serious neurologic disorders, ranking third as
uses a glucose analogue, that passes the a cause of death in the adult population of the
-
blood brain barrier, is partially metabolized United Sates and probably first as a cause of
by functionally active neurons, and is chronic functional incapacity (9 ).
trapped in the neurons ( 37, 38, 53). This tech- Even brief interference with cerebral circu -
nique has revealed surprisingly detailed fea
tures of neuronal activity under controlled
- lation can cause neurologic or mental distur -
bances. Neural tissue deprived of an adequate
conditions, as illustrated in Chapter 20 ( Figs. blood supply undergoes necrosis. Impairment
20.24 and 20.25). of local or regional blood supply constitutes
Positron emission tomography ( PET ) pro- the most common cause of central nervous
vides images of brain functions in living indi- system lesions. Vascular lesions most com-
viduals, and the introduction of the PET scan monly result from arteriosclerosis of cerebral
technology has revolutionized the study of and cervical ( i.e., internal carotid artery ) ves-
human cognitive processes, as well as that of sels, which reduce blood flow and can lead to
psychiatric and neurologic diseases. One thrombosis. Vascular occlusions also may re-
powerful application of this noninvasive sult from emboli ( i.e., fragments of blood
method makes use of deoxyglucose to visual - clots, fat, and tumors or air bubbles ) (5, 12 ).
ize the metabolic activity of various cortical Hemorrhage into brain tissue, the brain ven -
regions and subcortical nuclei. By covalently tricles, or the meninges may result from vas-
bonding the positron-emitting isotope of flu - cular lesions. Probably the most common
orine-18 to deoxyglucose to make lsF-labeled cause of spontaneous hemorrhage into the
deoxyglucose, it is possible to assess glucose brain and subarachnoid space is rupture of
utilization in small regions of the brain . This cerebral aneurysms ( abnormal sacculations),
approach is very useful for detecting any most of which are of congenital origin . Neural
93
.
lesions resulting from interruptions of the root entry zone. At certain sites these spinal
blood supply often can be localized to specific arteries become so small that they appear dis-
cerebral arteries on the basis of characteristic continuous. These arteries and their small
sensory and motor deficits (8, 9). branches supply the posterior third of the
spinal cord (67).
BLOOD SUPPLY OF THE SPINAL CORD
Anterior Spinal Arteries
The spinal cord is supplied by (a ) branches
of the vertebral arteries that descend , and ( b ) The paired anterior spinal arteries unite to
multiple radicular arteries derived from seg- form a single descending midline vessel that
mental vessels (7) ( Fig. 4.1 ). As the vertebral ar- supplies midline rami to the lower medulla
teries ascend along the anterolateral surfaces and sulcal branches that enter the anterior
of the medulla , each gives rise to two paired median fissure of the spinal cord ( Figs. 4.1 A
descending vessels: (a ) the posterior spinal and 4.2). The continuity of the anterior spinal
artery , and ( b) the anterior spinal artery. artery is dependent upon anastomotic
branches that it receives from the anterior
Posterior Spinal Arteries radicular arteries (63). The anterior radicular
arteries join the anterior spinal artery by
Paired posterior spinal arteries descend on branching gently upward or sharply down -
the posterior surface of the spinal cord me- ward . Where two anterior radicular arteries
dial to the dorsal roots ( Fig. 4. IB ). These ves- reach the same level of the spinal cord , a dia -
sels receive variable contributions from the mond -shaped arterial configuration results.
posterior radicular arteries and form two lon- The anterior and posterior spinal arteries
gitudinal plexiform channels near the dorsal form anastomotic channels that extend the entire
Posterior cerebral Middle cerebellar

artery Superior cere- peduncle
bellar artery
Basilar artery 4th Ventricle
Posterior inferior
Anterior spinal — cerebellar artery
artery Posterior spinal
artery
Vertebral artery ;
Ascending cervical
artery
Ascending cervical
artery
J3 Intercostal Artery
T5j
Intercostal artery
T10
L3 Lumbar artery
L5
Lumbar artery
Filum terminate B
A
Figure 4.1. Arterial supply of the spinal cord. A. Anterior surface and arteries. B. Posterior surface and arteries Vulner-
able segments of the spinal cord are stippled Letters and numbers indicate most important radicular arteries
Posterior spinal vein
Posterolaterol Posterior spinol artery

spinal vein
Sulcal vein
—F
artery __
I Arterial vasocorona
Anterior Spinal Radicular arteries

artery - — posterior
vein — — anterior
Pia mater — \ Dorsal root

ganglion
Arachnoid
I
Spinal orteries
Dura mater —
Dorsal root sleeve
Internal vertebral venous plexus

Figure 4.2. Blood supply and venous drainage of the spinal cord shown with respect to the meninges and internal
structure
length of the spinal cord and receive branches course along the ventral surface of the spinal
from the radicular arteries. Branches of the root they accompany ( Fig. 4.2). Where the
vertebral arteries provide the principal blood epineurium blends with the dura mater, the
supply of virtually the entire cervical spinal radicular arteries enter the subarachnoid
cord . In the thoracic region, the anterior space. A single radicular artery may become
spinal artery narrows to such an extent that it either an anterior or posterior radicular
may not form a functional anastomosis if the artery, or divide to form both (67). Small
radicular arteries are occluded above or twigs leave the arteries to supply the dura
below . An arterial ring encircling the conus mater and the spinal roots they accompany.
medullaris communicates with the most cau - The anterior radicular arteries contributing
dal part of the anterior spinal artery. to the anterior spinal artery vary from 2 to 17,
but most commonly number between 6 and
Radicular Arteries 10 arteries. The cervical spinal cord receives
up to six anterior radicular arteries, while the
Radicular arteries are derived from seg - thoracic cord receives two to four and the
mental vessels ( i .e., ascending cervical, deep lumbar cord has one or two. One anterior
cervical, intercostal, lumbar, and sacral arter - radicular artery in the lumbar region, appre-
ies) that pass through the intervertebral ciably larger than all others, is known as the
foramina and divide into anterior and poste- artery of Adamkiewicz or the artery of the lum -
rior radicular arteries. These arteries provide bar enlargement ( 41 ). In 75% of cases, this
the principal blood supply of thoracic, lum- artery originates at the level of the vertebral
bar, sacral, and coccygeal spinal segments segments T9 to T12. This radicular artery
( Figs 4.1 and 4.2). Radicular arteries are most travels with a lower thoracic or upper lumbar
frequently on the left side in the thoracic and spinal root most frequently on the left side.
lumbar regions of the spinal cord, while cer- Thoracic spinal segments have the greatest
vical spinal cord segments are supplied length between radicular arteries, which
equally from both sides. Radicular arteries means that occlusion of one radicular artery
may seriously compromise its circulation (5, dependent upon the radicular branches of the
12, 32 ). Certain spinal regions which receive intercostal arteries. If one or more of the par-
their blood supply from more than one ent intercostal vessels are compromised by
source are particularly vulnerable if they are injury or ligature, spinal cord segments T1 to
suddenly deprived of blood from one of these T4 could not be adequately maintained by the
sources ( Fig. 4.1 ). The' upper thoracic (T1-T4 ) small sulcal branches of the anterior spinal
and ( first lumbar spinal segments are among artery ( Fig. 4.1 A ). For this reason, thoracic
^
the most vulnerable regions of the spinal segments T1 to T4, particularly T4, are con-
cord . The intercostal arteries do not intercon- sidered vulnerable areas in the distribution of
nect with other arteries in the same extensive the anterior spinal artery (70). The occlusion
fashion as the other extraspinal arteries in the of several intercostal arteries in a vulnerable
cervical and lumbosacral regions. Occlusion region can result in spinal cord infarction .
of one intercostal artery in a vulnerable re- This clinical picture may be seen in associa-
gion can result in a spinal cord infarction . tion with dissecting aneurysms of the aorta or
This clinical picture is seen with dissecting as a complication of surgery on the aorta
aneurysms of the aorta or as a result of where more than one intercostal artery has
surgery on the aorta where more than one in- been occluded (5, 12, 68). Spinal cord segment
tercostal artery may be occluded . Spinal cord LI is another vulnerable region. The posterior
segment LI is another vulnerable region, surface of the cord most susceptible to vascu -
where the anterior aspect of the cord is sus- lar insult is also in segments T1 to T4 ( Fig.
ceptible to vascular insult ( Fig. 4.1 ) (5, 12). 4.1 B ). Such vascular injuries may result in
The posterior radicular arteries , numbering necrosis of an entire segment and produce
between 10 and 23, divide on the posterolat- neurologic symptoms comparable to com-
eral surface of the spinal cord and join the plete cord transection .
paired posterior spinal arteries. Although
these vessels are more often on the left side, Spinal Veins
left predominance is not as evident as with
the anterior radicular arteries. Veins draining the spinal cord have a gen-
The anterior spinal artery gives rise to a eral distribution similar to that of spinal ar-
number of sulcal branches that enter the ante- teries. Anterior longitudinal venous trunks
rior median fissure and alternately pass to consist of anteromedian and anterolateral
the right or left, except for an occasional sul- veins ( Fig. 4.2 ). Sulcal veins entering the an-
cal artery that divides into right and left teromedian vein drain anteromedial portions
branches ( 23) ( Fig. 4.2). Central branches aris- of the spinal cord ; each sulcal vein drains re -
ing from the anterior spinal artery are numer- gions on both sides of the spinal cord. An -
ous and of larger caliber in the cervical and terolateral regions of the spinal cord drain
lumbar regions of the spinal cord ( 28). Sulcal into anterolateral veins and into the venous
branches of the anterior spinal artery supply vasocoronal . The anteromedian and anterolateral
the anterior horn , the lateral (intermediate) spinal veins are drained by 6 to 11 anterior
horn , the central gray matter, and the basal radicular veins that empty into the epidural
part of the posterior horn. Additionally, these venous plexus. One large radicular vein in
branches supply the anterior and lateral funi- the lumbar region is referred to as the vena
culi. Peripheral portions of the lateral funiculi radicularis magna (63); other smaller radicular
receive branches from the arterial vasocorona . veins are distributed along the spinal cord .
The posterior spinal arteries supply the pos- Posterior longitudinal venous trunks, con-
terior horns and the posterior funiculus sisting of a posteromedian vein and paired pos-
( Fig. 4.2). terolateral veins , drain the posterior funiculus,
The blood supply of the spinal cord may the posterior horns ( including their basal re-
be jeopardized in certain transitional regions gions), and the white matter in the lateral fu -
where its arterial supply is derived from niculi adjacent to the posterior horn ( Fig. 4.2).
more than one source. For example, the cer- The posterior longitudinal veins are drained
vical segments are supplied primarily by bv 5 to 10 posterior radicular veins that enter
branches of the vertebral artery and to a the epidural venous plexus. The longitudinal
lesser extent by small branches of the ascend - veins are connected with each other by coro-
ing cervical artery. The upper segments of the nal veins ( venous vasocorona ) that encircle
thoracic spinal cord , on the other hand , are the spinal cord .
The internal vertebral venous plexus valves in this spinal venous network, blood
(epidural venous plexus), located between flowing in these channels may pass directly
the dura mater and the vertebral periosteum into the systemic venous system . When intra -
( Fig. 4.3), consists of two or more anterior abdominal pressure is increased , venous
and posterior longitudinal venous channels blood from the pelvic plexus passes upward
that are interconnected at many levels from in the internal vertebral venous system ,
the clivus to the sacral region ( Fig. 4.23) (13). When the jugular veins are obstructed , blood
At each intervertebral space there are connec- leaves the skull via this plexus. The continu -
tions with thoracic, abdominal, and inter- ity of this venous plexus with the prostat -
costal veins, as well as with the external ver- ic plexus is believed to be a route whereby
tebral venous plexus. Since there are no neoplasms may metastasize (6). Epidural
Pedicle L3 -
^-Ascending
vertebral
L 3 -L 4 veins
disc
Emissary veins
Pedicle L4 ( vertebral body)
Pediculate
veins
L4 -L5
disc Intervertebral
foramen
Pedicle L 5 -
Anterior internal
vertebral veins -
•^ Presacral
venous plexus
Figure 4.3. Epidural venogram done retrograde from one ascending lumbar vein Venogram reveals details of the
internal vertebral venous plexus, including ascending vertebral veins, emissary veins from vertebral body pediculate
veins at the superior and inferior margins of the intervertebral foramina, the anterior internal vertebral veins, and the
presacral venous plexus. The pedicles of L3. L4. and L5 vertebrae are well-outlined, and the approximate position of
the intervertebral discs at three levels are indicated by clashed lines.
.
venograms reveal many details of the inter- orbit through the optic foramen, ventral and
nal vertebral venous plexus and usually fill lateral to the optic nerve ( N. II ). The posterior
the pediculate veins which outline the supe- communicating artery arises from the dorsal
rior and inferior margins of the intervertebral aspect of the carotid siphon and passes poste-
foramina ( Fig. 4.3). riorly and medially to join the posterior cere-
bral artery ( Fig. 4.5). The anterior choroidal
BLOOD SUPPLY OF THE BRAIN artery usually arises from the internal carotid
artery distal to the posterior communicating
The entire brain is supplied by two pairs artery and passes backward across the optic
of arterial trunks, the internal carotid arteries tract and then laterally to enter the choroidal
and the vertebral arteries. On the left , the fissure in the temporal lobe ( Figs. 4.5 and
common carotid artery arises directly from 4.11 ) (10). Lateral to the optic chiasm, the in -
the aortic arch; the right common carotid is ternal carotid artery divides into its two ter -
one of the two branches which arises from
the bifurcation of the brachiocephalic artery .
—
minal branches the smaller anterior cerebral
artery and the larger middle cerebral artery ,
The common carotid artery bifurcates at the which is regarded as the direct continuation
upper level of the thyroid cartilage forming of the internal carotid artery .
the internal and external carotid arteries. Most of the arterial blood within the inter-
nal carotid artery is distributed by the more
Internal Carotid Artery mobile branches of the anterior and middle
cerebral arteries. The rostral parts of the brain
This artery can be divided into four seg- normally supplied by these two arteries are
ments: cervical, intrapetrosal, intracavernous, the anterior half of the thalamus, the basal
and cerebral (supraclinoid ). The intracav - ganglia , the corpus callosum, most of the in-
ernous and cerebral portions of this artery are ternal capsule, the medial and lateral surfaces
referred to as the "carotid siphon" because of of the frontal and parietal lobes, and the lat-
their characteristic configuration (65). The in- eral surface of the temporal lobe ( Figs. 4.5,
tracavernous segment of the internal carotid 4.7, and 4.8).
artery lies close to the medial wall of the cav -
ernous sinus, courses nearly horizontally, Vertebral Artery
and bears important relationships to cranial
nerves III, IV, VI, and portions ( divisions I The vertebral arteries arises as the first
and II ) of nerve V , which is located along the part of the subclavian artery , traverse the
wall of the sinus ( Fig. 4.24 ). The abducens foramen of the sixth cervical vertebra, and as-
nerve ( N . VI ) lies immediately adjacent to the cend though the transverse foramina of all
internal carotid artery within the cavernous higher cervical vertebrae. The artery pierces
sinus ( Fig. 4.6 ). The cerebral segment begins as the atlanto-occipital membrane and the dura
the artery emerges from the cavernous sinus mater to enter the posterior cranial fossa
and passes medial to the anterior clinoid through the foramen magnum ( Fig. 4.15).
process ( Fig. 4.4 ). This portion of the artery, Thin radicular branches of the vertebral
extending upward and backward , gives rise artery pass through the intervertebral foram-
to all major branches of the internal carotid ina to supply the meninges and portions of
artery. The cervical segment extends from the the cervical spinal cord ( Fig. 4.1 ). The rela-
bifurcation of the common carotid to the tionships of the two vertebral arteries to the
carotid canal in the petrous bone and has no anterior and posterior surfaces of the caudal
branches. The intrapetrosal segment of this ves- brainstem are shown in Figures 1.4, 1.8, 4.1,
sel is surrounded by dense bone. Small and 4.5. The two vertebral arteries course
branches given off from the intrapetrosal and along the anterolateral surface of the medulla
intracavernous segments pass into the tym- and unite at the caudal border of the pons to
panic cavity and the cavernous and inferior form the basilar artery ( Figure 4.16). Cervical
petrosal sinuses, as well as the trigeminal portions of the vertebral artery give rise to
ganglion and the meninges of the middle cra - spinal ( radicular ) and muscular branches.
nial fossa. Intracranial branches of the vertebral and
Major branches of the internal carotid basilar arteries supply the cervical spinal
artery are the ophthalmic, posterior commu - cord (via anterior and posterior spinal arter-
nicating, and anterior choroidal arteries (66) (Figs. ies), the medulla , pons, midbrain , cerebellum ,
4.4 and 4.5). The ophthalmic artery enters the posterior parts of the diencephalon, and parts
Emissary vein
Anterior cranial fossa
Olfoctory bulb
Optic chiasm
Ant. communicating a '
Sphenoparietal sinus
Ant. cerebral a
Middle cerebral a .
Post
communicating a I , h kr Middle cerebral v.
Basilar a. s Oculomotor n.
Middle cranial
Cerebral peduncle fossa
Sup. petrosal
Post, cerebral a:. sinus
Cerebellum
Sup. cerebellar a:'
Middle
J meningeal a.
Inf . cerebral v.
Tentorium
cerebelli
Straight sinus Falx cerebri
Sup. sagittal >-

sinus
O ^ Diaphragma sellae ond infundibulum of hypophysis

4 « Great cerebral vein (of Galen ) and inferior sagittal sinus
Figure 4.4. Cranial cavity after brain was removed to demonstrate relationship of the cerebral arterial circle, adja-
cent neural structures, and reflections of the dura mater
of the occipital and temporal lobes of the communicating artery. The posterior communi -
brain ( Fig. 4.5). A labyrinthine branch of the cating arteries arise front the internal carotid
basilar artery supplies the cochlea and arteries, run caudomedially, and anastomose
vestibular apparatus ( Fig. 4.5). with proximal portions of the posterior cere-
bral arteries ( Fig. 4.11 ). The posterior cerebral
Cerebral Arterial Circle arteries are formed by the bifurcation of the
basilar artery at the rostral border of the pons
The cerebral arterial circle (of Willis) is an ( Figs. 4.5 and 4.7). The posterior cerebral ar -
arterial wreath encircling the optic chiasm, teries give rise to numerous small branches
the tuber cinereum, and the interpeduncular that enter the interpeduncular fossa and hy -
region formed by anastomotic branches of pothalamus, while the main vessels pass lat -
the internal carotid artery and the most ros - erally, rostral to the root fibers of the oculo-
tral branches of the basilar artery ( Figs. 4.4, motor nerve (N. Ill ), and encircle part of the
4.5, and 4.11 ). This arterial circle is formed by midbrain before passing above the tentorium
anterior and posterior communicating arter- cerebelli ( Figs. 4.4 and 4.5). The cerebral arter-
ies, and proximal portions of the anterior, ial circle formed by the anastomoses of these
middle, and posterior cerebral arteries. The vessels is said to equalize blood flow to vari -
anterior cerebral arteries run medially and ros- ous parts of the brain, but normally there is
trally toward the interhemispheric fissure. In little exchange of blood between the right and
front of the optic chiasm, these two arteries left halves of the arterial circle because of the
are joined by a connecting vessel, the anterior equality of blood pressure. Alterations of
.
Ant. cerebral a.
Central retinal a .
Ant . communicating a.
Ophtholamic a .
Middle cerebral a. 'i
Int. carotid a .
Striate oa.
% Posterior
communicating a.
Post cerebral a.
,
Ant. choroid a .
Trochlear nerve
Sup. cerebellar a.
Labyrinthine a.
Pontine ao .
Choroid plexus Anterior

f— Inf. cerebellar
V
in loterol operature a.
of E ventricle >y
Vertebral a.
M Vogus nerve
v Post. inf . cerebellar a .

Ant. spinal a.
Figure 4.5. Formation and branches of the arterial circle on the inferior surface of the brain. The relationships of the
arterial circle to structures on the base of the skull are shown in Figure 4.4
Cavernous sinus
s
Oculomotor nerve
Trochlear nerve
Turcica
Trigeminal nerve
Ophthalmic Div.
Maxillary Div.
Internal ^
carotid
artery Mandibular Div.
y?
' •‘I
c. }; v
Sphenoid
sinus
Abducens
nerve
Figure 4.6. Oblique coronal section through the cavernous sinus viewed from behind showing the relationships of this
venous sinus to the sella turcica, the sphenoid sinus, and the locations of cranial nerves in the wall of the sinus The ab-
ducens nerve lies adjacent to the internal carotid artery.
Pericallosal artery
/
Parietooccipital artery
Callosomarginal artery
Frontopolar
artery
Calcarine
artery Orbital artery
7 \ \ Anterior cerebral artery
\
Posterior cerebral artery
Superior cerebellar art Basilar artery
Anterior inferior Vertebral artery
Posterior inferior
cerebellar arteries
Figure 4.7. Principal arteries on the medial surface of the brain shown together with the arteries of the brainstem and
cerebellum.
Rolandic artery
Anterior parietal artery
Anterior cerebral Posterior parietal artery
artery /
Angular artery
Pre Rolandic
artery
/
Posterior
i j cerebral
artery
I
Middle
cerebral
artery ,J
Orbitofrontai artery
Anterior temporal
^- Superior cerebellar
artery
artery
Posterior temporal /
artery Basilar artery Anterior inferior cerebellar
\
Posterior inferior cerebellar artery
Vertebral artery
Figure 4.8 Principal arteries on the lateral surface of the brain and cerebellum
Figure 4.9 Cerebral angiogram demonstrating the Sylvian triangle There are 5 to 8 branches of the middle cerebral
artery on the surface of the insula. As they course upward, they reach the deepest portion of the sulcus formed by
the junction of the Insula and the frontoparietal operculum. Upon reaching this point, the middle cerebral branches
change direction and proceed downward a short distance to emerge from the lateral sulcus (Sylvian fissure). The
points of reversal can be identified in the angiogram, and a line drawn from the most anterior to the most posterior
point ( P) forms the upper margin of the Sylvian triangle. The inferior margin of the triangle is a line from the most poste-
rior point (the angiographic Sylvian point. P) to the anterior extremity of the middle cerebral artery . The anterior bor-
der is a line drawn from the rostral extremity of the middle cerebral artery to the first turn of the opercular branch. The
triangle contains branches of the middle cerebral artery as they are disposed on the insula.
blood flow in the arterial circle undoubtedly bral aneurysms are at the origin of the ante-
occur following occlusion of one or more of rior communicating artery or the posterior
the arteries contributing to the circle. How - communicating artery ( Fig. 4.17). Other sites
ever, the communicating arteries of the arter - include the bifurcation of the middle cerebral
ial circle often form functionally inadequate artery, the cavernous carotid artery, the inter-
anastomoses, which account for the high inci - nal carotid bifurcation, and various loci on
dence of serious disturbances in blood flow the vertebrobasilar arteries. Rupture of these
following unilateral occlusion or compression aneurysms leads to subarachnoid hemor-
of the internal carotid artery, especially in el- rhages, which often result in serious neuro-
derly individuals (5, 12 ). logical impairment. Treatment is neurosurgi-
The circle of Willis is a common site for cal application of an occlusive clip resulting
saccular cerebral aneurysms. High blood tur - in eclusion of the aneurysm from the parent
bulence and congenital defects in the wall of circulation .
blood vessels are major factors involved in Relationships of the arterial circle and its
the development of aneurysms. The com - branches to the inferior surface of the brain
monest sites of occurrence of saccular cere- and the origins of the respective cranial
nerves are shown in Figures 4.5 and 4.11 . The

in situ surgical relationships of the arterial cir-
cle to the base of the skull , following removal
of the brain , can be appreciated by comparing
Figure 4.4 with the relationships illustrated in
Figure 4.5.
From the arterial circle and the principal
cerebral arteries, two types of branches arise,
central and cortical, which form two distinct
systems.
The central ( ganglionic ) arteries arise from
the circle of Willis and the proximal portions
of the three cerebral arteries, dip perpendicu -
larly into the brain substance, and supply the
diencephalon , basal ganglia, and internal
capsule ( Fig. 4.11 ). For a long time, these pen-
etrating vessels have been referred to as ter-
minal or end arteries. Earlier studies by
Scharrer (57 ) indicate that the vast majority of
arteries in the brains in nonprimates are end
arteries, but in the human brain there are no
end arteries. Precapillary anastomoses have
been observed in humans and nonprimates,
but these anastomoses usually are not suffi -
cient to maintain adequate circulation if a
major vessel is occluded suddenly . Occlusion
Figure 4.10. X -rays of fresh cadaver brains In which
of one of these arteries produces a softening
cerebral vessels have been injected with radiopaque
in the area deprived of an adequate blood material . A. Injections of the anterior, middle, and poste -
supply . The anterior and posterior choroidal rior cerebral arteries B. Injection of the posterior cerebral
.
arteries, which are respectively branches of artery Note the filling of the thalamoperforatlng
the internal carotid and posterior cerebral ar- branches
teries, may be included in this group.
The larger cortical ( circumferential ) branches verely involved after vascular injury (5, 12,
of each cerebral artery enter the pia mater, 46 ). Brain damage to these areas, which are
where they form a superficial plexus of more referred to as watershed zones may occur with
or less freely anastomosing vessels, which in
hypotension; the resulting condition is
some places may be continuous with the termed borderzone infarction . The degree of
plexuses derived from the other main arter- brain damage is variable and depends upon
ies. From these plexuses arise the smaller ter- several factors, including site of injury,
minal arteries that enter the brain substance amount of vascular overlap, confluence, and
at right angles and run for variable distances. the rapidity with which an occlusion will
The shorter ones arborize in the cortex, while develop.
the longer ones supply the more deeply
placed medullary substance of the hemi-
Cortical Branches
sphere. Owing to the anastomoses of the
larger cortical branches, the occlusion of one The cortical branches of the cerebral hemi -
of these vessels is compensated to a variable sphere are derived from the anterior, middle,
extent by the blood supply from neighboring and posterior cerebral arteries.
branches, although such collateral circulation
is often not sufficient to prevent brain dam- ANTERIOR CEREBRAL ARTERY
age. The great majority of vascular occlusions
occur in the cerebral vessels before they enter This artery originates at the bifurcation of
the substance of the brain. Areas of the cere- the internal carotid artery lateral to the optic
bral cortex , internal capsule, or basal ganglia chiasm and nerve ( Fig. 4.5). The anterior cere-
that lie between the territorial distributions of bral artery passes rostromedially, dorsal to
two primary arteries are the sites most se- the optic nerve, and approaches the corre-
sponding artery of the opposite side with some cases it terminates in the sylvian fissure
which it connects via the anterior communi- lateral to the anterior perforated substance or
cating artery ( Figs. 4.5 and 4.11 ). The artery in the inferior frontal lobe. This artery sup-
enters the interhemispheric fissure, passes plies the anteromedial part of the head of the
upward on the medial surface of the hemi- caudate nucleus, adjacent parts of the internal
sphere, curves around the genu of the corpus capsule and putamen, and parts of the septal
callosum, and continues posteriorly on the nuclei (1 ) ( Figs. 4.11, 4.13, and 4.14). The medial
superior surface of the corpus callosum. The striate artery is said to anastomose with the
anterior cerebral artery gives rise to the (a ) lenticulostriate arteries and surface branches
medial striate artery, ( b) orbital branches, (c) of the anterior and middle cerebral arteries
frontopolar artery, (d ) callosomarginal artery, ( 34), and frequently gives rise to several
and (e) pericallosal artery. branches supplying the inferior surface of the
The medial striate artery ( recurrent artery of frontal lobe ( 51, 52).
Heubner ) may arise proximal or distal to the Orbital branches of the anterior cerebral
anterior communicating artery (40, 50, 51 ). In artery , arising from the ascending portion of
the majority of the cases (78% ), the artery this vessel ventral to the genu of the corpus
originates just distal to the anterior communi- callosum , extend forward to supply the or-
cating artery; in 14% of the cases it arises bital and medial surfaces of the frontal lobe
proximal to the anterior communicating ( Figs. 4.5 and 4.7).
artery; and in 8% of cases it arises at the level A frontopolar branch is given off as the ante-
of the anterior communicating artery. The rior cerebral artery curves around the genu of
medial striate artery courses caudally and lat - the corpus callosum ( Fig. 4.7). Branches of
erally, doubles back on its parent vessel, and this artery supply medial parts of the frontal
undergoes significant branching prior to en- lobe and extend laterally on reaching the con-
tering the anterior perforated substance as vexity of the hemisphere.
multiple vessels ( Figs. 2.10, 4.11 , and 18.2). In The callosomarginal artery , a major branch
Anteromediol group
Anterior cerebral art
Middle 0 rebral /ort Ant commumcoting art

/ / -"Medial striate ort
ommunicating \l
art lnt carotid art
' Lateral striate
*
»» group
Anterior choroidal
art
^
Posteromedial
group
oculomotor m
Trochlear neiive n Posterolateral group

'' Posterior cerebral
Superior cerebellar ort
Ponlme rami V
Bosilar art
Figure 4.11. The cerebral arterial circle at the base of the brain, showing the distribution of the ganglionic branches
These vessels form anteromedial, posteromedial , posterolateral, and lateral striate arterial groups. The medial striate
and anterior choroidal arteries also are shown
Figure 4.12. X -rays of fresh cadaver brains in which individual arteries have been injected with radiopaque material
A and B are lateral and frontal views, respectively, of the deep ganglionic branches of the middle cerebral artery
that penetrate the brain in the anterior perforated substance .
Caudate nucleus
Thalamus
Putamen
'
> v
V
Globus pallidus
Medial striate art.

i .. i
-Thalamogeniculate
arteries
Lateral striate arteries \
x
XJ Posterior choroidal art
Ant cerebral artery
Amygdaloid nucleus
Internal carotid -
Posterior communicating artery
artery
Posterior cerebral artery
Anterior choroidal art
Middle cerebral artery
Figure 4.13. Arterial supply of the basal ganglia and thalamus.
of the anterior cerebral artery , arises distal to Anomalies of the anterior cerebral artery
the frontopolar artery and passes caudally in occur in about 25% of brains and include un -
the callosomarginal sulcus, dorsal to the cin- paired arteries and instances where branches
gulate gyrus ( Fig. 4.7). Branches of this artery are given off to the contralateral hemisphere
supply the paracentral lobule and parts of the (4, 51 , 52 ). Occlusion of the trunk of one ante-
cingulate gyrus ( 40 ). rior cerebral artery produces contralateral
The pericallosal artery , regarded as the ter- muscle weaknesses and sensory losses, which
minal branch of the anterior cerebral artery, are greatest in distal lower limbs. The main
courses caudally along the dorsal surface of sensory modalities affected are discrimina -
the corpus callosum and supplies the medial tive sensation, such as stereognosis and two-
surface of the parietal lobe, including the pre- point discrimination , and proprioception .
cuneus ( Fig. 4.7) ( 56). Pain, temperature, and light touch sensation
Corona radiata
Internal capsule
Internal capsule ( retrolenticular part )
( posterior limb)
Middle
cerebral Anterior
arlery choroidal art
Optic radiation
internal carotid
( direct branches )
Internal capsule
( anterior limb )
Internal capsule
Anterior cerebral ( genu )
artery
Putamen
Globus pallidus
Figure 4.14. Blood supply of the internal capsule and basal ganglia The putamen and globus pallidus are shown ro-
tated ventrally away from the internal capsule Regions supplied by branches of the middle and anterior cerebral ar -
teries ate shown in red; portions of the internal capsule and basal ganglia supplied by the anterior choroidal artery
are in yellow . Direct branches of the internal carotid artery supply the genu of the internal capsule
are relatively spared . Very proximal occlu - plex of the cerebral arteries, divides into a
sion of the anterior cerebral artery may com - number of large branches, which course up-
promise blood supply to the internal capsule, ward and backward . As these arteries reach
with additional weakening of the contralat - the uppermost portions of the insula , they
eral arm and face. Obstruction of both ante- loop abruptly downward toward the lateral
rior cerebral arteries is associated with bilat - sulcus ( 22 ). The course of the branches of the
eral paralysis, especially in the lower limbs, middle cerebral artery in the insular region is
and impaired sensation that mimics a spinal of great importance in the interpretation of
cord lesion (5, 12). Additionally, bilateral cerebral angiograms (65). In the insular re-
medial prefrontal damage may result in gion , five to eight branches of the middle
motor and psychomotor abnormalities, in - cerebral artery lie within what is called the
cluding bradykinesia, rigidity, abulia , and a Sylvian triangle ( Fig. 4.9). The Sylvian point
variety of other emotional or intellectual im - (or apex ) is established angiographically by
pairments (8). the most posterior branch of the middle cere-
bral artery to emerge from the lateral sulcus.
MIDDLE CEREBRAL ARTERY The inferior margin of the Sylvian triangle is
formed by the lower branches of the middle
Beyond the origin of the anterior cerebral cerebral artery, while the superior margin is
artery, the middle cerebral artery passes lat- formed by looping branches of this artery
erally over the anterior perforated substance that are reversing their course ( Fig. 4.9 ). Dis-
to enter the lateral cerebral fossa between the placement of branches of the middle cerebral
temporal lobe and the insula ( Figs. 4.5 and artery in the Sylvian triangle by mass lesions
4.8). This artery, the largest and most com - can be detected readily in cerebral angio-
grams, and the direction of displacement pro- region supplied by the middle cerebral artery
vides important information concerning the includes the motor and premotor areas, the
localization of these lesions. somesthetic and auditory projection areas,
Branches of the middle cerebral artery and large regions of the association cortex.
emerge from the lateral sulcus and are dis- Occlusion of the middle cerebral artery near
tributed in a "fanlike" fashion over the lateral the origin of its cortical branches may pro-
convexity of the hemisphere. These cortical duce (a ) a contralateral hemiplegia , most
branches supply lateral parts of the orbital marked in the upper extremity and face, (b) a
gyri, the inferior and middle frontal gyri, contralateral loss of position and discrimina-
most of the precentral and postcentral gyri, tive tactile sense, and (c) severe aphasia,
the superior and inferior parietal lobules, and when the dominant hemisphere is involved
the superior and middle temporal gyri, in- (5, 8, 9, 12).
cluding the temporal pole ( Fig. 4.8). The
largest cortical branches appear to supply the POSTERIOR CEREBRAL ARTERY
temporo-occipital and angular areas ( 22). The
cortical arteries arise from stem arteries and This artery, formed by the bifurcation of
supply individual cortical regions. In general, the basilar artery, passes laterally around the
one or two cortical arteries pass to each corti- crus cerebri ( Figs. 4.5 and 4.7). After receiving
cal region supplied. The cortical branches to anastomoses from the posterior communicat-
the frontal, anterior temporal, and anterior ing arteries, it continues along the lateral as-
parietal regions are smaller than those to the pect of the midbrain, and then passes dorsal
posterior parietal, posterior temporal, and to the tentorium to course on the medial and
temporo-occipital regions, but are more nu - inferior surfaces of temporal and occipital
merous. lobes ( Figs. 4.15 and 4.16). Branches of the
Branches of the middle cerebral artery in- posterior cerebral artery extend onto the lat-
clude (a ) the lenticulostriate arteries, (b) the eral surfaces of the hemisphere to supply
anterior temporal artery, (c) the orbitofrontal parts of the inferior temporal gyrus, variable
artery, (d ) pre-Rolandic and Rolandic portions of the occipital lobe, and parts of the
branches, (e) anterior and posterior parietal superior parietal lobule ( Figs. 4.7, 4.8, 4.15,
branches, and ( f ) a posterior temporal branch, and 4.16). Branches of the posterior cerebral
which extends caudally to supply lateral por- artery also are distributed to the brainstem,
tions of the occipital lobe ( Fig. 4.8). the choroid plexus of the third and lateral
The lenticulostriate arteries, the first ventricles, and to regions of the cerebral cor-
branches to arise from the middle cerebral tex (69).
artery, enter the anterior perforated sub- The posterior cerebral artery divides into
stance ( Figs. 4.11 and 18.2 ). These vessels are two main branches: ( a ) the posterior temporal
considered with the central or ganglionic artery, and (b) the internal occipital arteries.
branches. The next branches to arise from the The posterior temporal ( temporo-occipital )
middle cerebral artery are the anterior tem- artery gives off an anterior temporal branch
poral artery and the orbitofrontal artery ( Fig. ( Fig. 4.16), which supplies the inferior surface
4.8). The anterior temporal artery frequently of the temporal lobe anteriorly, and fre-
anastomoses with temporal branches of the quently anastomoses with branches of the an-
posterior cerebral artery, while the or - terior temporal artery ( Figs. 4.7 and 4.1OB ).
bitofrontal artery may anastomose with the The largest branches of the posterior tempo-
frontopolar branch of the anterior cerebral ral artery reach the lateral surface of the
artery. Ascending branches of the middle hemisphere immediately anterior to the pre-
cerebral artery, given off more distally, in- occipital notch (69). More posterior branches
clude pre- Rolandic branches , a Rolandic branch , of this vessel supply the occipitotemporal
an anterior parietal (or post-Rolandic) branch, and lingual gyri.
and a posterior parietal branch. A posterior tem- The internal occipital artery divides into the
poral branch extends backwards to supply lat- parieto-occipital artery and the calcarine artery ,
eral portions of the occipital lobe. The angu- which supply different regions on the medial
lar branches supplying the angular gyrus aspect of the occipital lobe and portions of the
constitute the terminal part of the middle splenium of the corpus callosum ( Figs. 4.7
cerebral artery. and 4.15). The cortical branches of the poste-
The extensive and functionally important rior cerebral artery supply the medial and in-
Medial posterior — Branches of
choroidal arteries parieto-occipital
artery
Thalamoperforating — Branches of
arteries calcarine artery
Posterior cerebral
artery
Superior cerebellar
Posterior — artery
communicating
artery
Basilar artery
“
Posterior inferior
cerebellar artery
Vertebral artery
Figure 4.15. Lateral projection of a vertebral angiogram demonstrating major branches of the vertebral basilar
system.
Posterior
cerebral artery
Posterior temporal
artery (branches)
Superior
cerebellar artery.
Anterior inferior
cerebellar artery
Basilar
artery Posterior inferior
cerebellar artery
Vertebral artery
Figure 4.16. Vertebral angiogram as seen in the Towne projection using a subtraction technique.
ferior surfaces of the occipital lobe and the in- tion of such gadolium substances outlines
ferior surface of the temporal lobe, except for brain vasculature and intracranial structures
the temporal pole ( Figs. 4.7 and 4.10B ). that have no blood -brain barrier (55).
Branches of these arteries extend onto the lat- Cerebral aneurysms are mostly of congeni-
eral surface of the brain and supply the infe - tal origin and appear to arise frequently from
rior temporal gyrus and variable portions of vessels on the inferior surface of the brain
the lateral occipital region. Some of the ( Fig. 4.17). Although it has been stated that
branches from the medial surface supply a aneurysms arise only at the point of bifurca -
considerable part of the superior parietal lob - tion of an artery, Dandy (14) found that many
ule. In these regions, branches of the poste - aneurysms were not associated with arterial
rior cerebral artery anastomose with mar - branching. Vascular malformations also in-
ginal branches of the anterior and middle volved arteriovenous malformations, an ab-
cerebral arteries ( Fig. 4.8). The calcarine normal nest of blood vessels in which there
branch of the posterior cerebral artery is of are direct anastomoses of arteries and veins
major importance because it supplies the pri - ( Fig. 4.18). Cerebral angiography is important
mary visual cortex ( Figs. 4.7 and 4.15). The in diagnosing occlusive vascular disease in
extensive anastomoses appear to explain why the internal carotid ( both cervical and in-
occlusion of the posterior cerebral artery tracranial portions) and in the vertebral and
rarely produces softening (encephalomalacia ) basilar arteries, as well as in the trunk of the
in the total distribution of this vessel. Occlu- middle cerebral artery ( Figs. 4.9, 4.15, and
sion of the posterior cerebral artery produces 4.16). It is more difficult to ascertain the pres-
a contralateral homonymous hemianopsia ence of vascular occlusions in the distal
( Fig. 16.43), frequently with sparing of macu - branches of the anterior, middle, and poste-
lar vision. Anastomoses between branches of rior cerebral arteries (64) because of direct
the middle and posterior cerebral arteries in end -to-end anastomoses between branches of
the region of the occipital pole probably ac- these vessels on the surface of the brain.
count for the preservation of macular vision. While intracerebral hemorrhage cannot be
Cerebral angiography, a technique based distinguished angiographically from cerebral
on the injection of radiopaque solutions into edema or other avascular space-occupying le-
cerebral vessels, followed by serial x-rays sions, they sometimes can be localized on the
photography at about 1-second intervals (48, basis of occlusion of certain vessels and dis-
49), reveal not only the position and configu- placement of cerebral vessels. Certain highly
ration of the cerebral vessels, but also the vascular brain tumors may produce what is
phases of filling and emptying of vessels by called a "tumor stain" in the cerebral an-
the radiopaque solutions ( Fig. 4.18). This ra - giogram (5, 8, 9, 12).
diographic technique shows the contrast While cerebral angiography provides in-
medium in progressive stages of passage valuable diagnostic information, it is unusual
through the arterial tree and venous return. for the contrast medium to permeate the very
This method is particularly useful in localiz- small terminal arteries ( Fig. 4.10). Injection of
ing cerebral aneurysms and vascular malfor- the internal carotid artery usually permits vi-
mations ( Figs. 4.17 and 4.18). Additionally, it sualization of the main branches of the ante-
often provides information concerning occlu- rior and middle cerebral arteries on the side
sive vascular disease and space-occupying of the injection. A radiographic technique for
intracranial masses. While cerebral angiogra- studying individual cerebral vessels and their
phy provides invaluable diagnostic informa- branches in fresh cadaver brains has been de-
tion, it is usually not possible to visualize the veloped by Kaplan ( 33-35) and has been used
small terminal arteries. The larger cerebral extensively to study cerebral vessels (56 ). The
vessels also can be demonstrated by comput- exquisite detail which can be obtained by this
erized axial tomography (CT) after injection method is demonstrated in Figures 4.10 and
of a contrast medium. Brain hemorrhages 4.12.
usually can be seen clearly in CT scans.
Images of brain vasculature also can be obtain- Central Branches
ed by a procedure called MRI angiography, CENTRAL OR GANGLIONIC ARTERIES
which uses magnetic resonance imaging
technology (see Chapter 2 ). This method em- Central or ganglionic arteries arise from
ploys paramagnetic compounds synthe- proximal portions of the major cerebral and
sized with gadolium. The intravascular injec- communicating arteries and supply the dien-
Figure 4, 17. Aneurysm of the anterior communicating artery in a 40- year -old man, as seen with both angiography
( A) and magnetic resonance imaging (MRI) (B C) A. Lateral view of internal carotid injection on early arterial phase
.
Note the aneurysm (arrow) arising from the anterior communicating artery . The internal carotid (/C) middle (MCA),
and anterior (ACA) cerebral arteries are also clearly visible . B, C. This partially trombosed aneurysm (arrow) can be seen
on MRI scans (B axial view C coronal view) The location of the middle and anterior cerebral arteries, as well as that
of the midbrain (M). cerebellum (Q and lateral ventricles (TV) is also indicated
cephalon , basal ganglia, and internal capsule.

Penetrating ganglionic arteries are arranged
in four groups, designated as anteromedial,
anterolateral, posteromedial, and posterolat-
eral ( Fig. 4.11 ).
The anteromedial arteries arise from the an-
terior cerebral and anterior communicating
arteries, but some twigs come directly from
the terminal portion of the internal carotid
( Fig. 4.11 ). They enter the most medial part of
the anterior perforated substance, and are
distributed to the anterior hypothalamus, in -
cluding the preoptic area , and supraoptic re-
gions.
The posteromedial arteries which enter the
tuber cinereum , mammillary bodies, and in
terpeduncular fossa are derived from the
-
most proximal portion of the posterior cere- /
bral, and from the whole extent of the poste- B
rior communicating arteries ( Fig. 4.11 ). Some
twigs come directly from the internal carot -
id artery just before its bifurcation. A rostral
and caudal group may be distinguished . The
rostral group supplies the hypophysis, in-
fundibulum and tuberal regions of the hypo-
thalamus. A number of vessels, the thalamo-
perforating arteries , penetrate more deeply
and are distributed to the anterior and medial
portions of the thalamus ( Figs. 4.12B, 4.13,
and 4.15). The caudal group supplies the mam-
millary region of the hypothalamus, the sub-
thalamic region, and sends small branches
to the medial nuclei of the thalamus. Oth -
er vessels from the caudal group are distrib-
uted to medial regions of the midbrain tegmen-
tum and crus cerebri. Figure 4.18. Angiograms (A. B) and MRI scan (C) of the
The posterolateral arteries arise from the brain of a 56-year -old man with hemorrhage from an an-
teriovenous malformation in the occipital lobe. A B. Lat -
posterior cerebral arteries, lateral to its anas- eral view of internal carotid ( 1C ) injection In the early (A)
tomosis with the posterior communicating and late (B) arterial phase showing the malformation
artery ( Figs. 4.11 and 4.13). These penetrating ( arrow), which is fed by both the posterior and middle
branches supply the caudal half of the thala - .
cerebral arteries C MRI scan (axial view) showing the
resulting tissue damage ( arrow ) in the occipital lobe.
mus ( i.e., the lateral geniculate body, pulv -
inar, lateral nuclear group, and large parts of
the ventral tier thalamic nuclei ). These anterior cerebral artery ( Figs. 4.5 and 4.11 ).
branches of the posterior cerebral artery are The medial striate artery ( Heubner ), which
referred to as the thalamogeniculate arteries derived from the anterior cerebral artery, be-
( Fig. 4.13). Occlusion of these arteries results longs to this group ( Fig. 4.13). These arteries
in the thalamic syndrome of Dejerine and enter the anterior perforated substance and
Roussy. This syndrome includes variable de- supply portions of the basal ganglia and in -
grees of motor loss, sensory loss, pain , and ternal capsule ( Figs. 4.13 and 4.14). The me-
hyperpathia in the contralateral face, body, or dial striate artery supplies the rostroventral
extremities (15). part of the head of the caudate nucleus and
The anterolateral arteries , commonly re - adjacent portions of the putamen and internal
ferred to as the striate arteries , arise primarily capsule. The lateral striate arteries, derived
from proximal portions of the middle cere- from the middle cerebral artery, supply re-
bral artery and , to a lesser extent, from the maining portions of the striatum ( i .e., caudate
.
nucleus and putamen ), except for extreme The posterior choroidal arteries , arising from
caudal parts of the putamen and the tail of the posterior cerebral artery ( Fig. 4.13), con-
the caudate nucleus ( Fig. 4.12). These arteries sist of one medial posterior and at least two
also nourish the lateral part of the globus pal- lateral choroidal arteries ( 20). The medial pos-
lidus, the anterior limb of the internal cap- terior choroidal artery arises from the proximal
sule, and dorsal portions of the posterior limb part of the posterior cerebral artery, curves
of the internal capsule. While it appears around the midbrain to reach the region of
doubtful that the striate arteries supply parts the pineal body. It gives off branches to the
of the thalamus, vessels, referred to as lentic- tectum, the choroid plexus of the third ventri-
ulo-optic arteries, have been described . The cle, and the superior and medial surfaces of
central perforating branches arising from the the thalamus ( Fig. 4.10B). The lateral posterior
middle cerebral artery are shown radiograph- choroidal arteries arise from the posterior cere-
ically in injected specimens in Figure 4.12. bral artery. They encircle the brainstem, enter
the choroidal fissure, and supply the choroid
CHOROIDAL ARTERIES plexus of the lateral ventricle. Some branches
anastomose with branches of the anterior
The anterior and posterior choroidal arter- choroidal artery (10, 16).
ies may be regarded as distinctive central
branches ( Figs. 4.5, 4.11, 4.13, and 4.14 ). BASAL GANGLIA , INTERNAL CAPSULE ,
The anterior choroidal artery usually arises AND DIENCEPHALON
from the internal carotid artery distal to the
origin of the posterior communicating artery, Striatum
but it also may arise from the middle cerebral
artery (10). This artery, characterized by its The striatum is nourished mainly by the
long subarachnoid course and its relatively lateral striate arteries derived from the mid -
small caliber, passes caudally across the optic dle cerebral artery ( Figs. 4.13 and 4.14). Ros-
tract, and then laterally toward the rostrome- tromedial parts of the head of the caudate nu-
dial surface of the temporal lobe ( Figs. 4.11 cleus are supplied by the medial striate artery
and 4.13). It enters the inferior horn of the lat- ( Heubner ), while the tail of the caudate nu -
eral ventricle through the choroidal fissure. cleus and caudal parts of the putamen receive
The artery enters the choroidal fissure at a branches of the anterior choroidal artery. The
point that is identified radiologically as the lateral segment of the globus pallidus is sup-
choroid point . Structures supplied by this plied by branches of both the lateral striate
artery, in addition to the choroid plexus, in- and anterior choroidal arteries (47). The lat-
clude the hippocampal formation, portions of eral part of the medial pallidal segment re-
both segments of the globus pallidus (i.e., lat- ceives branches from the anterior choroidal
eral parts of the medial pallidal segment and artery, and branches of the posterior commu -
medial parts of the lateral pallidal segment), nicating artery nourish the most medial parts
ventrolateral parts of the posterior limb of the of this pallidal segment.
internal capsule, and the entire retrolenticular
portion of the internal capsule ( Fig. 4.14). Internal Capsule
Small branches of this artery supply parts of Both anterior and posterior limbs of the in-
the amygdaloid nuclear complex, ventral ternal capsule are supplied primarily by the
parts of the tail of the caudate nucleus, ex- lateral striate branches of the middle cerebral
treme posterior parts of the putamen, and artery ( Fig. 4.14). The medial striate artery
ventrolateral parts of the thalamus. The ante- supplies rostromedial parts of the anterior
rior choroidal artery is often considered as a limb of the internal capsule. The genu of the
vessel highly susceptible to thrombosis be- internal capsule receives direct branches from
cause of its long subarachnoid course and its the internal carotid artery ( 2), while ventral
relatively small caliber (36). It appears signifi- parts of the posterior limb and its entire retro-
cant that the globus pallidus and hippocam- lenticular part are supplied by branches of
pal formation, two of the most vulnerable the anterior choroidal artery (56).
structures of the brain, are both supplied by
this artery. Interestingly, surgical occlusion of Thalamus
the proximal portion of the anterior choroidal
artery was used for the treatment of Parkin- The thalamus is nourished mainly by
sonian tremor and rigidity (11). branches of the posterior cerebral artery
( Figs. 4.10B, 4.11, and 4.13). Thalamoperforat - meningeal artery. The two vertebral arteries
ing branches , referred to as the posteromedial unite to form the basilar artery at the caudal
arteries, course dorsally and medially to sup- border of the pons. This large vessel passes
ply chiefly medial and anterior regions of the rostrally in the basilar sulcus and bifurcates
thalamus (17, 56). These arteries, arising from at the upper border of the pons, forming the
the most medial part of the posterior cerebral posterior cerebral arteries ( Figs. 4.1, 4.5, 4.7,
artery and from the terminal part of the basi- 4.15, and 4.16 ).
lar artery, course dorsally into the dien-
cephalon and nourish paraventricular re- Basilar Artery
gions of the hypothalamus and medial
regions of the thalamus (21, 24). Perforating Branches of the basilar artery include (a )
branches of these arteries, visualized in verte- the anterior inferior cerebellar arteries , (b) the
bral angiograms ( Fig. 4.15), may be displaced, labyrinthine arteries , (c) numerous paramedian
deformed , or stretched by space-occupying and circumferential pontine rami , (d ) the supe-
lesions or enlargement of the third ventricle. rior cerebellar arteries , and (e) the posterior cere-
Thalamogeniculate branches , referred to as the bral artery ( Figs. 4.1, 4.5, 4.7, and 4.11 ). The
posterolateral arteries, supply the pulvinar posterior cerebral arteries, representing the
and the lateral nuclei of the thalamus. These terminal branches of the basilar artery, fur -
arteries arise from the posterior cerebral nish branches that supply parts of the mid -
artery as it winds around the crus cerebri, brain, thalamus, and large regions of the tem -
and the choroidal arteries (10, 42). The medial poral and occipital lobes ( Figs. 4.7 and 4.16).
posterior choroidal artery supplies the choroid The labyrinthine arteries do not supply the
plexus of the third ventricle and superior and brainstem, but pass laterally through the
medial portions of the thalamus. The inferior internal auditory meati to the inner ear
thalamic arteries arise from the posterior com- ( Fig. 4.5).
municating artery and the bifurcation of the Vertebral angiography is more difficult to
basilar artery. These arteries course rostrally perform than carotid angiography because
and dorsally and enter inferior portions of the this artery is smaller and contained within a
thalamus (42). The inferior thalamic arteries bony canal. Many of the branches of the ver-
supply regions of the thalamus rostral to the tebral and basilar arteries are small and diffi-
territory of the thalamoperforating arteries. cult to identify angiographically, but the pos-
terior inferior cerebellar, the anterior inferior
Hypothalamus cerebellar, the superior cerebellar, and the
posterior cerebral arteries usually can be
The anterior hypothalamus and preoptic seen. Both posterior cerebral arteries are filled
region receive their blood supply from the by contrast media following injection of one
anteromedian ganglionic arteries. Caudal vertebral artery ( Figs. 4.15 and 4.16).
parts of the hypothalamus and the subthala -
mic region are supplied by branches of the Medulla and Pons
posteromedian group derived from the pos-
terior cerebral and posterior communicating These portions of the brainstem are sup-
arteries ( Fig. 4.11). plied by the anterior and posterior spinal ar-
teries, the posterior inferior cerebellar arter-
ies, and branches of the vertebral and basilar
VERTEBRAL BASILAR SYSTEM arteries. The anterior inferior and superior
With the exception of the most rostral por- cerebellar arteries make smaller contributions
tions of the crus cerebri, the entire blood sup - ( Fig. 4.5). There is great variation in the extent
ply of the medulla, pons, midbrain, and cere - of the areas supplied by individual vessel
and considerable overlap in some regions.
bellum is derived from the vertebral basilar
system. These variations are due in part to the differ -
ent levels of origin of the anterior spinal ar -
Vertebral Artery teries, and to the varying level of fusion of the
two vertebral arteries into the basilar artery .
The intracranial part of each vertebral One or another artery may be entirely miss -
artery gives rise to (a ) a posterior spinal artery , ing, and its place taken by a vessel supplying
( b) an anterior spinal artery , (c) a posterior infe- the adjacent territory. Since the vascular sup-
rior cerebellar artery, and (d ) a posterior ply of this region has considerable clinical im-
portance, the main structures normally sup-

plied by the various arteries are summarized
briefly ( Figs. 4.19 and 4.20 ).
The posterior spinal artery supplies the
gracile and cuneate fasciculi and their nuclei,
and the caudal and dorsal portions of the in-
ferior cerebellar peduncle (62) (Figs. 4.1 and 4.20).
There are numerous anastomoses between
branches of the posterior spinal and the pos-
terior inferior cerebellar arteries (16). When
the posterior spinal artery on one side is
small, or even missing, its territory is sup-
plied by the posterior inferior cerebellar
artery . Branches of the posterior spinal artery
also supply parts of the nucleus of the soli -
tary fasciculus and vagal nuclei, and portions
of the spinal trigeminal nucleus. Small
branches of this artery with a superficial
course may penetrate the taenia to supply the
area postrema .
The anterior spinal artery supplies a para-
median region of the medulla which includes
the pyramids, the medial lemniscus, medial
longitudinal fasciculus, most of the hypoglos-
sal nucleus (except its most cephalic portion ),
caudal parts of the solitary nucleus and dor-
sal motor nucleus of the vagus nerve ( N . X ),
and the medial accessory olive ( Fig. 4.20).
Medullary branches arising from the anterior
spinal artery increase in size and number
from caudal to rostral levels. The larger and
longer branches pass in the medial raphe be-
tween the medial lemnisci ( Fig. 4.20C ), and
their terminal rami reach the floor of the
fourth ventricle. Smaller, shorter branches of
the anterior spinal artery run obliquely
through the medial lemnisci to enter the me-
dial reticular formation and medial parts of
the inferior olivary nuclear complex (16). In
the upper medulla , the distribution of the an-
terior spinal artery is reduced gradually, and
it is replaced by branches of the vertebral and
basilar arteries ( 62 ) ( Fig. 4.20 ).
Occlusion of one anterior spinal artery is
associated with a medullary lesion producing
an inferior alternating hemiplegia characterized
by ipsilateral paralysis of the tongue and a
Figute 4 19. Microangiograms of the blood supply of contralateral hemiplegia . Such lesions some-
the midbrain, pons, and medulla made from 4 mm-thick
Injected specimens. In the midbrain ( A ) the tegmentum
times involve portions of the medial lemnis -
cus which result in contralateral sensory
is supplied mainly by branches of the posterior cerebral
and superior cerebellar arteries, but it also receives con -
deficits.
tributions from the paramedian and both long and short The bulbar branches of the vertebral artery
circumferential arteries The upper pons (B) receives arise as a series of rami that enter the brain-
paramedian and circumferential branches from the stem in relation to rootlets of the glossopha -
basilar artery, as well as branches of the superior cere - ryngeal ( N . IX ), vagus ( N . X ), and accessory
bellar artery distributed to dorsal regions. The vascular
pattern in the upper medulla (C) should be compared nerves ( N . XI ). The most densely vascularized
with the diagram of Figure 4.20 lateral medullary region lies dorsal to the infe-
Superior cerebellar
artery
Long circumferential
branches (Basilar artery)
Anterior inferior
cerebellar artery
Paramedian branches Short circumferential

(Basilar artery) branches (Basilar artery)
Posterior inferior- Posterior spinal artery

cerebellar artery
Anterior spinal artery Vertebral artery
Posterior spinal
artery
Vertebral artery
Anterior spinal artery
c
Figure 4.20. Arterial supply of the medulla and pons. The pons (A) is supplied by paramedian and circumferential
branches of the basilar artery Medullary levels shown are through the posterior column nuclei (C) and the inferior oli-
vary nuclear complex ( B) The pons ( A) is supplied by paramedian and circumferential branches of the basilar
artery
rior olivary complex. This region contains nu - rior olivary nucleus, including the dorsal ac-
merous small arteries and veins on the surface cessory olive. These arteries also supply olivo-
that penetrate deeply into the medulla ( Fig. cerebellar fibers traversing the reticular for-
4.20B ) . The inferior rami arise directly from mation , portions of the dorsal motor nucleus
the vertebral artery, enter the medulla be- of the vagus, and the solitary nucleus and fas-
tween the rootlets of the accessory nerve, and ciculus. At the level of the pyramidal decussa -
supply the region between the inferior olivary tion the most caudal branches are distributed
nuclear complex and the inferior cerebellar to practically the whole lateral region of the
peduncle ( Figs. 4.19C and 4.200. A larger medulla lying between the pyramids and the
and more important group of rami enter the fasciculus cuneatus. Two types of arteries
lateral surface of the medulla in relation to the
glossopharyngeal and vagus nerves. These di-
—
enter the medulla short arteries supply
small branches to the spinal trigeminal,
rect branches of the vertebral artery normally spinothalamic, and spinocerebellar tracts,
supply the pyramids at the lower border of while long arteries supply deeper regions.
the pons, the most cephalic part of the hy- Some of the long arteries reach the floor of the
poglossal nucleus, and large parts of the infe- fourth ventricle ( Fig. 4.190.
The posterior inferior cerebellar artery sup- parts of the pontine tegmentum , including a
plies the lateral medullary region rostral to portion of the medial lemniscus.
that supplied by direct bulbar branches of the Short circumferential arteries supply the ad -
vertebral artery ( Fig. 4.19). This retro-olivary jacent anterolateral part of the pons, and vari -
region contains the spinothalamic tracts, the able parts of overlying tegmentum ( Fig. 4.22 ).
spinal trigeminal nucleus and tract, the Neural structures in this intermediate area of
emerging fibers from nucleus ambiguous, the pons include a variable number of fibers
the dorsal motor nucleus of the vagus nerve, of the corticospinal tract and medial lemnis-
as well as the ventral part of the inferior cere- cus, the pontine nuclei and pontocerebellar
bellar peduncle ( Fig. 4.20). Autonomic fibers fibers, and part of the nuclei and fibers of the
are found in this area of the medulla and trigeminal and facial nerves. Some of the cir-
pons. The lateral medullary syndrome (or Wal - cumferential branches may ascend to supply
lenberg' s syndrome ) , produced by sudden oc- part of the superior cerebral peduncle.
clusions of the posterior inferior cerebellar Long circumferential arteries course laterally
artery or bulbar branches of the vertebral over the anterior surface of the pons and
artery , is associated with lesions in the dorso- anastomose with smaller branches of the an-
lateral part of the medulla . Such lesions are terior inferior cerebellar and superior cerebel-
characterized by (a ) loss of pain and thermal lar arteries ( Figs. 4.19 and 4.20). The long cir-
sense in the face ( ipsilaterally ) and over the cumferential and anterior inferior cerebellar
body ( contralaterally ), ( b) ipsilateral paralysis arteries supply most of the tegmentum in the
of the pharynx and larynx, and (c ) an ipsilat - caudal portion of the pons, whereas the long
eral Horner's syndrome (3, 5, 12, 60 ). Distur- circumferential and superior cerebellar arteries
bances of equilibrium usually are transient . supply a similar area in the more rostral lev-
The ventral portion of the pons receives els of the pons. Important neural structures
arterial blood from three series of branches, within this area of vascular distribution are
all derived from the basilar artery ( Figs. the nuclei of oculomotor to vestibulocochlear
—
4.19 4.21 ). These arterial branches are cranial nerves ( N. Ill to VIII ), the spinal
grouped as (a ) paramedian, (b ) short circum- trigeminal nucleus and tract, the medial lon-
ferential, and (c) long circumferential . gitudinal fasciculus, the medial lemniscus,
Paramedian arteries leave the dorsal surface the spinothalamic and spinocerebellar tracts,
of the parent vessel to supply a medial pon- the superior cerebellar peduncle, and the
tine area that includes the pontine nuclei and reticular formation .
the corticopontine, corticospinal , and corti - Sudden occlusion of paramedian branches
cobulbar tracts. Smaller arterial twigs also of the basilar artery on one side usually pro-
penetrate dorsally to supply ventromedial duces lesions in the basilar part of the pons
Figure 4.21. Microangiogram of a 4-mm midsagittal section of the midbrain, pons, and medulla made from an in-
jected specimen. Paramedian arteries form different angles with the basilar artery at various levels. In the caudal
midbrain and upper pons, they are inclined caudally; in the upper medulla and caudal pons, these vessels are in-
clined rostrally .
Superior sagittal sinus
Emmissary veins
\
Cavernous sinus
7 Inferior sagittol sinus
Frontal vein * Great cerebral vein
l- Rectus sinus
Ophthalmic
veins
3 Transverse sinus
Superior petrosal sinus

£
Inferior petrosal sinus
Pterygoid ,
|
plexus
1 Occipital vein
v Deep cervical vein
Anterior facial vein I ,

R0
\
Internal jugular vein
Figure 4.22. The dural sinuses and their principal connections with extracranial veins Intracranial venous sinuses and
veins are light blue; extracranial veins are dark blue.
that result in a contralateral hemiparesis and In the so-called lock -in syndrome , paralysis
damage to the root fibers of the ipsilateral ab- prevents communication with gesture or
ducens nerve (5, 12, 18, 44). Middle alternating voice. The patient may have full comprehen -
hemiplegia is a classic example of such a lesion of his or her environment , but can only
sion. Obstruction of the short circumferential communicate using vertical eye movements
arteries on one side usually results in ipsilat- or blinking. Basilar artery occlusion is a com -
eral cerebellar and autonomic disturbances mon cause of lock-in syndrome ( 54 ).
and impairment of contralateral sensation.
Occlusion of the long circumferential arteries Midbrain
and other arteries supplying the pontine
tegmentum produces cranial nerve distur- Most of the blood supply of the midbrain
bances, paresis of conjugate eye movements, is derived from branches of the basilar artery,
contralateral hemianesthesia , ipsilateral cere- although branches of the internal carotid may
bellar disturbances, and frequently nystag- also contribute ( Figs. 4.15, 4.19, and 4.21 ). Ar-
mus. Complete or partial thrombosis of the teries supplying this part of the brainstem in-
basilar artery may produce precipitous loss of elude branches of ( a ) the posterior cerebral
muscle tone, dilated or pinpoint pupils that artery, ( b) the superior cerebellar artery, (c)
do not react to light, and bilateral Babinski re- the posterior communicating artery, and ( d )
sponses (31 ). Neurologic disturbances usu - the anterior choroidal artery ( Figs. 4.1, 4.4,
ally are bilateral but may be asymmetric and 4.5, 4.7, and 4.11 ). Branches of these arteries,
exhibit fluctuations. like those supplying the pons, can be
grouped into (a ) paramedian arteries, which pontine levels these vessels course obliquely
nourish structures on both sides of the mid - in a caudal direction ( Fig. 4.21 ).
line, and (b) long and short circumferential
arteries, which wind laterally around the crus Brainstem Venous Drainage
cerebri and supply lateral and dorsal regions
of the midbrain ( Fig. 4.19A ). The venous drainage of the hindbrain has
Paramedian arteries , derived from the pos- been demonstrated by stereomicroangiogra-
terior communicating artery and from proxi- phy (29). The paramedian veins which run
mal portions of the posterior cerebral arteries, near the midline to the ventral surface of the
form an extensive plexus in the interpedun- brainstem are inclined caudally in the upper
cular fossa ( Fig. 4.11 ), enter the brainstem in pons, but are nearly perpendicular to the axis
the posterior perforated substance, and sup- of the brainstem in more caudal regions. At
ply the raphe region, the oculomotor com- the junction of pons and medulla, a conspicu-
plex, the medial longitudinal fasciculus, the ously large vein consistently drains the floor
red nucleus, and medial parts of the substan- of the fourth ventricle. Veins draining ventral
tia nigra and crus cerebri. Vascular lesions in- portions of the pons usually empty into
volving paramedian arterial branches at mid - paired longitudinal venous plexuses several
brain levels frequently produce a superior millimeters lateral to the basilar artery. How-
alternating hemiplegia , characterized by ipsilat- ever, in some instances these veins enter a
eral oculomotor disturbances and a contralat- single unpaired vein situated between the
eral hemiplegia (Weber's syndrome). This basilar artery and the brainstem parenchyma.
syndrome results from lesions involving por- In the lower medulla , posterior veins are
tions of the crus cerebri and fibers of the ocu- larger than the anterior veins and penetrate
lomotor nerve ( N. 111). A less frequent lesion deeper regions. Although the veins of the
in the paramedian tegmental zone destroys hindbrain seldom accompany the arterial
portions of the red nucleus, the superior cere- branches in the same vascular sheath, the in -
bellar peduncle, and intra-axial rootlets of the traparenchymatous venous angioarchitecture
oculomotor nerve ( Benedikt's syndrome). resembles the arterial pattern. Anastomoses
Short circumferential arteries, arising from between intraparenchymatous veins occur
the interpeduncular plexus and proximal mainly at the capillary level. Large veins
portions of the posterior cerebral and supe- draining the choroid plexus of the fourth ven -
rior cerebellar arteries, supply central and lat- tricle, most of the pons, and the upper
eral parts of the crus cerebri, the substantia medulla, empty into the sigmoid sinus, or
nigra , and lateral portions of the midbrain the superior or inferior petrosal sinuses.
tegmentum ( Fig. 4.19). In the rostral mesen- Veins draining caudal parts of the medulla
cephalon, some branches of the anterior empty into the anterior and posterior spinal
choroidal artery are distributed to the in- veins (29).
terpeduncular fossa. Numerous veins of the mesencephalon
Long circumferential arteries arise primarily arise from capillaries and, in general, run
from the posterior cerebral artery . The most near the arteries but not directly with them.
important of these, the quadrigeminal or collic- These veins form an extensive peripheral
ular artery , encircles the brainstem and sup- plexus in the pia and are collected by the
plies the superior and inferior colliculi. The basal veins, which drain into either the great
tectum also is supplied by branches of the cerebral vein (Galen ) or the internal cerebral
medial posterior choroidal artery and the su- veins ( Figs. 4.26 and 4.27).
perior cerebellar artery.
Angiographic studies (30) of the arterial Cerebellum
pattern of the human brainstem clearly
demonstrate the distribution of paramedian Each half of the cerebellum is supplied by
and circumferential arteries in the upper three arteries: (a ) the superior cerebellar, (b)
pons and midbrain ( Figs. 4.19 and 4.22). the anterior inferior cerebellar, and (c) the
Sagittal sections show that paramedian arter- posterior inferior cerebellar (Figs. 4.7 and
ies that enter the brainstem at various levels 4.15).
do so at different angles. At the junction of The posterior inferior cerebellar artery , de-
pons and medulla, these vessels are directed rived from the vertebral artery, courses ros-
forward at an oblique angle, while at rostral trolaterally along the surface of the medulla
where small perforating rami supply the dor- cal branches ( 25). Perforating branches of the
solateral region of the medulla . From this artery penetrate the interpeduncular fossa ,
locus the artery curves upward onto the infe- the crus cerebri, and portions of the superior
rior surface of the cerebellum, where and middle cerebellar peduncles. Precerebel -
branches supply the inferior vermis, espe- lar branches supply the colliculi ( midbrain
cially the uvula and nodulus, the cerebellar tectum) and the superior medullary velum.
tonsil, and the inferolateral surface of the The cortical branches are divided into ver-
cerebellar hemisphere ( Fig. 4.7). Medial mian, hemispheric, and marginal arteries.
branches of this artery supply portions of the These branches supply the superior ( ten -
choroid plexus of the fourth ventricle. torial ) and petrosal surfaces of the cerebel -
The anterior inferior cerebellar artery is usu - lum and , in some instances, the region of the
ally the most caudal large vessel arising from horizontal fissure ( marginal branches). The
the basilar artery ( Fig. 4.5), but it is highly hemispheric arteries give rise to numerous
variable both in its origin and area of dis- branches that extend deeply into the cerebel -
tribution ( 36). This artery most frequently lum . These vessels supply the middle and su -
arises as a single vessel, courses caudally and perior cerebellar peduncles, the deep cerebel -
laterally around the pons toward the cere- lar nuclei, the superior medullary velum,
bellopontine angle, and comes into close rela - and the corpus medullary velum . Smaller
tionship with both the facial and vestibu - branches supply portions of the choroid
locochlear nerves ( N. VIII ) (43). After crossing plexus of the fourth ventricle.
the nerves in the cerebellopontine angle, the Cerebellar veins have a course similar to
artery courses laterally above the flocculus that of the arteries. A superior and an inferior
to reach the inferior surface of the cerebel- median vein drain respective portions of the
lum where it supplies the pyramis, tuber, vermis, paravermal regions, and the deep
flocculus, and portions of the inferior sur- cerebellar nuclei. The superior vein termi -
face of the cerebellar hemisphere. Penetrat - nates in the great cerebral vein (Galen ), while
ing branches supply portions of the den - the inferior vein empties into the rectus and
tate nucleus and the surrounding white mat - transverse sinuses ( Fig. 4.27). Superior and
ter. Smaller branches of this artery contribute inferior lateral veins drain respective portions
to choroid plexus of the fourth ventricle. In of the cerebellar hemispheres and empty into
some cases, the flocculus and portions of the the superior and petrosal sinuses ( Fig. 4.22 ).
tonsil and biventer lobule may be supplied
by an inconstant middle inferior cerebellar ARTERIES OF THE DURA MATER
-
artery. Nerve related branches of the anterior
inferior cerebellar artery frequently supply The cranial dura mater is supplied by a
tumors and arteriovenous malformations number of meningeal arteries derived from
arising in the cerebellopontine angle. An in - several sources. The largest and most impor -
ternal auditory artery arising from this vessel tant is the middle meningeal artery , which sup-
appears quite constant, and occlusion of the plies most of the dura and practically its en -
anterior inferior cerebellar artery frequently tire calvarial portion . It is a branch of the
produces nausea , vomiting, deafness, facial maxillary artery, which enters the cranial cav -
paralysis, and cerebellar disturbances ( 43). ity through the foramen spinosum and then
The superior cerebellar artery arises from the divides into an anterior and a posterior
rostral part of the basilar artery, encircles the branch ( Figs. 1.3 and 4.4 ) . Each branch runs
brainstem near the pontomesencephalic junc - outward and upward and extends toward the
tion , and passes onto the superior surface of superior sagittal sinus, giving off numerous
the cerebellum ( Fig. 4.11 ). This vessel runs branches which run forward and backward .
caudal to the oculomotor ( N . Ill ) and A small accessory meningeal artery , which may
trochlear ( N. IV ) nerves and rostral to the arise from the maxillary artery or the middle
trigeminal ( N. V ) nerve. In its proximal por- meningeal artery, enters the middle fossa
tion , the artery courses medial to the free through the foramen ovale. This vessel sup-
edge of the tentorium cerebelli ( Fig. 4.4), but plies the dura of the middle fossa and the
distally it passes beneath the tentorium, mak- trigeminal ganglion . Meningeal branches
ing it the most rostral of the infratentorial ar- from the intracavernous portion of the inter-
teries ( Fig. 4.7). The superior cerebellar artery nal carotid artery also supply the dura of the
gives off perforating, precerebellar, and corti- middle fossa .
The dura of the anterior and the posterior The inferior sagittal sinus extends caudally
fossae also receives a number of arteries, along the free border of the falx cerebri. On
known respectively as the anterior and poste- reaching the anterior border of the tentorium,
rior meningeal rami or arteries. The anterior it is joined by the great cerebral vein (Galen ),
meningeal rami, usually two in number, are which drains the deep structures of the brain,
branches of the anterior and posterior eth - and the two veins form the straight sinus (or
moidal arteries. The dura of the posterior sinus rectus ) ( Figs. 1.3 and 4.22). The straight
fossa is supplied by a variable number of sinus runs backward and downward along
posterior meningeal arteries and include (a ) the line of attachment of the falx and tento-
one or more meningeal branches from the oc - rium and joins the superior sagittal sinus
cipital artery entering through the jugular near the internal occipital protuberance ( 45) ( Figs.
and hypoglossal foramina, ( b) meningeal 4.4 and 4.23).
branches of the vertebral artery reaching the The two transverse sinuses arise from the
posterior fossa through the foramen mag- confluens sinuses and pass laterally and for-
num , and ( c) several branches of the ascend - ward in a groove in the occipital bone ( Figs.
ing pharyngeal artery entering through the 1.3 and 4.4). At the occipitopetrosal junction ,
foramen lacerum and hypoglossal canal. each sinus curves downward and backward
as the sigmoid sinus. The sigmoid sinus is
drained by the internal jugular vein ( Fig.
CEREBRAL VEINS AND VENOUS SINUSES
4.22 ).
Venous Sinuses of the Dura Mater The confluens of sinuses is formed by the
union of the superior sagittal, straight, and
The cerebral veins of the brain do not run transverse sinuses. A small unpaired occipital
together with the arteries. Emerging as fine sinus from the region to the foramen magnum
branches from the substance of the brain, ascends along the margin of the falx cerebelli
they form a pial plexus from which the larger ( Figs. 1.1 and 4.23) and joins the confluens.
venous channels or cerebral veins arise. The confluens is asymmetric and shows
These veins run in the pia for a variable dis- many individual variations ( Figs. 1.3 and 4.4 ).
tance, pass through the subarachnoid space, In relatively few cases is there an actual
and empty into a system of intercommunicat - union of the four sinuses. Most often , the su -
ing endothelium-lined channels, the dural ve- perior sagittal sinus turns to the right to be-
nous sinuses . The dural venous sinuses are lo- come continuous with the right transverse
cated between the meningeal and periosteal sinus, while the straight sinus bends to the
layers of the dura ( Figs. 1.1-1.4 and 4.4). The left as the left transverse sinus ( Fig. 1.1 ). In
walls of these sinuses, unlike those of other general, the venous blood of the superior
veins, are composed of the tough fibrous tis- cerebral veins and the superior sagittal, right
sue of the dura , and exhibit a greater tautness transverse, and right sigmoid sinuses is
and do not collapse when sectioned . The vari- drained by the right internal jugular vein .
ous venous sinuses converge at the internal Most of the venous blood of the Galenic vein,
occipital protuberance into two transverse si- the straight sinus, left transverse, and left sig-
nuses ( Figs. 1.1 and 1.3), one for each side, moid sinuses usually is drained by the left in-
which enter the sigmoid sinuses, and eventu - ternal jugular vein .
ally the jugular foramina , to form the internal The cavernous sinus is a large irregular
jugular veins. Besides draining the blood space located on each side of the sphenoid
from the brain, the venous sinuses communi- sinus, sella turcica , and pituitary gland that
cate with the superficial veins of the head by extends from the superior orbital fissure to
a number of small vessels that perforate the the petrous portion of the temporal bone ( 26).
skull as emissary veins. It is a network of intercommunicating venous
The superior sagittal sinus extends from the channels enclosing the internal carotid artery
foramen cecum to the internal occipital pro- and the abducens nerve ( N. VI ) ( Fig. 4.24).
tuberance, lying along the superior border of The oculomotor ( N . Ill ), trochlear ( N . IV ), and
the falx cerebri . It progressively increases in the ophthalmic division of the trigeminal
caliber as it proceeds caudally ( Figs. 1.1 and nerve ( N . VI ) lie between dural leaves of the
4.22 ). In its middle portion, it gives off a num - lateral wall of the cavernous sinus. The ab-
ber of lateral diverticula , the venous lacunae , ducens nerve ( N. VI ) lies within the sinus, ad -
into which the arachnoid villi protrude jacent to the intracavernous portion of the
( Fig. 1.11 ). carotid artery. The cavernous sinus of each
Superior petrosal sinus
Basilar venous plexus
NN. IX , X , and XI Rectus
NN. VII and VIII
Atlanto-occipital
ligament ~~~~
Separation of dural laminae
Cruciate ligament
Apical ligament Occipital sinus
Tectorial membrane Transverse sinus
Dura Outer lamina of dura
Atlanto-occipital ligament
Transverse ligament
C1
Dens
Atlantoaxial ligament
Cut edge of dura Cut edge ot dura
C2
Internal vertebral
Basivertebral venous plexus
Figure 4.23. Sagittal view of the base of the skull and upper cervical vertebrae, showing ligaments, the dural venous
sinuses, and the internal vertebral venous plexus at the foramen magnum , Communications of the Internal vertebral
venous plexus with the basilar plexus are indicated.
side is connected with the other by venous rates the cavernous sinuses on the two sides
channels that pass anterior and posterior to and , in addition, separates the pituitary gland
the hypophysis, and by the basilar venous from the nasal cavity. The increasing use of
plexus ( Figs. 4.23 and 4.24 ). The latter venous the transsphenoidal approach to tumors of
plexus extends along the basilar portion of the sellar region has created a need for de-
the occipital bone as far caudally as the fora - tailed anatomy of this region (19). Three
men magnum where it communicates with structures producing prominent bulges in the
the venous plexuses of the vertebral canal lateral wall of the sphenoid sinus are ( a ) the
( Figs. 4.23 and 4.24 ). The venous ring, sur - optic nerves ( N. II ), ( b) the internal carotid ar -
rounding the hypophysis and composed of teries, and (c ) the maxillary branches of the
the two cavernous sinuses and their connect - trigeminal nerve ( N. V2). The bone in the lat -
ing channels, often is designated as the circu - eral wall of the sphenoid sinus, separating it
lar sinus . Each cavernous sinus likewise may from the internal carotid artery and the cav-
be regarded as a confluens of sinuses. Ros- ernous sinus, is thin, and extreme care must
trally it receives the two ophthalmic veins be taken to avoid injury to this region, which
through the superior and inferior orbital fis - offers the potential for neural and arterial
sures and the small sphenoparietal sinus , which damage.
runs along the under surface of the lesser The dural sinuses communicate with the
wing of the sphenoid ( Figs. 4.4 and 4.24 ). Pos- extracranial veins by a number of emissaries
teriorly, it empties into the superior and infe- ( Fig . 4.22 ). Thus, the superior sagittal sinus is
rior petrosal sinuses, through which it is con- connected with the frontal and nasal veins
nected , respectively, with the transverse and the emissaries of the foramen cecum ( Fig.
sinus and the bulb of the internal jugular vein 4.4 ). It also sends a parietal emissary to the su -
( Figs. 4.23 and 4.24 ). perficial temporal vein. The confluens of si-
In the adult, the sphenoid air sinus sepa - nuses usually gives off an occipital emissary to
Infundibulum Anterior intercavernous sinus

Hypophysis / Optic nerve
Carotid ortery Sphenoparietal sinus
I Superficial middle
cerebral vein
Posterior
intercavernous sinus -
Trigeminal nerve
Oculomotor nerve
r^ Ophthalmic division
— Maxillary division
A
Trochlear nerve
Abducens nerve
— Mandibular division
Trigeminal ganglion
Petrosal sinuses Internal auditory
superior - meatus
inferior - Jugular foramen
l?iD
Basilar venous plexus Hypoglossal canal

Figure 4.24. The cavernous sinus, its venous connections, and related structures.
the occipital vein , which is connected also channels, both intracerebral and extracere-
with the transverse sinus by the larger mas- bral.
toid emissary ( Fig. 4.22). Smaller emissaries Thus, large surface areas can be drained
from the sigmoid sinus pass through the through the great cerebral vein ( Galen ). Con-
condyloid and hypoglossal foramina and versely, territories supplied by deep cerebral
communicate with vertebral and deep cervi- veins may be drained , w’hen necessity arises,
cal veins. The cavernous sinus, besides re- by surface vessels. This anastomotic venous
ceiving the ophthalmic veins, is connected arrangement facilitates the drainage of capil-
with the internal jugular vein and with the lary beds by shifting the blood from one area
pterygoid and pharyngeal plexuses by fine to another and readily equalizes regional in-
venous nets that pass through the foramen creases in pressure due to occlusion or other
ovale, spinosum, lacerum, as well as the factors. As a result, the occlusion of even a
carotid canal and jugular foramen . large vein , if not too rapid , will produce only
slight transitory effects. When occlusion or
Cerebral Veins increase in pressure occurs suddenly, there
The cerebral veins consist of superficial
will be marked hyperemia and often exten -
sive hemorrhages, as in birth injuries and , oc-
and deep groups and , like the dural sinuses, casionally, in cases of thrombosis in adults
are devoid of valves. Superficial veins drain- ( 58, 59).
ing the blood from the cortex and subcortical
white matter empty into the superior sagittal SUPERFICIAL CEREBRAL VEINS
or basal sinuses (i.e., cavernous, petrosal, and
transverse) ( Fig. 4.25). The deep cerebral Superficial cerebral veins arise from the
veins, draining the choroid plexus, periven- cortex and subcortical white matter, anasto-
tricular regions, diencephalon, basal ganglia , mose freely in the pia, and form larger veins
and deep white matter, empty into the inter- that empty into the dural sinuses. The larger
nal cerebral and the great cerebral veins ( Figs. veins include the superior and inferior cere-
4.26 and 4.27). These two groups of veins are bral veins and the superficial middle cerebral
interconnected by numerous anastomotic vein.
Superior anastomotic vein

{ Trolard ) \
Superior cerebral veins

Superior
cerebral veins
.
..
V V
/
Inferior anastomotic
vein ( Labbe' )
Superficial middle cerebral vein

Inferior cerebral veins
Figure 4.25. The external cerebral veins on the convexity of the hemisphere
The superior cerebral veins , collecting blood motic branches, the most constant and promi-
from the convex and medial surfaces of the nent of which are the superior anastomotic
cerebral hemisphere drain into the superior (Trolard ) and the inferior anastomotic ( Labbe )
sagittal sinus. These veins, 10 to 15 in num - veins. These anastomotic veins connect the
ber, enter the sinus by coursing obliquely for- superficial middle cerebral vein respectively
ward . Blood flow in these veins, as they enter with the superior sagittal and transverse si-
the sinus, is opposite to that in the sinus. nuses.
Some veins on the medial surface of the On the inferior surface, the small inferior
hemispheres drain into the inferior sagittal cerebral veins, arising from extensive pial
sinus, or its venous lacunae ( Fig. 4.25). Many plexuses, drain in part into the basal sinuses.
of them, especially the larger posterior ones, Those from the tentorial surface of the hemi -
run obliquely forward through the subarach - sphere empty into the transverse and superior
noid space and enter the sinus. petrosal sinuses ( Figs. 4.4 and 4.24). Veins
The inferior cerebral veins drain the basal from the anterior temporal lobe and from the
hemispheric surface and ventral parts of the interpeduncular regions drain partly into the
lateral surface. Inferior cerebral veins on the cavernous and sphenoparietal sinuses, while
basal surface of the hemisphere empty into some veins from the orbital region join the su -
the basal sinuses. In rostral regions, these perior or the inferior sagittal sinus.
veins enter the cavernous and sphenoparietal Large cortical regions on the inferior and
sinuses ( Figs. 4.4, 4.24, and 4.25); caudally, medial surfaces of the brain are drained by a
they empty into the petrosal and transverse number of vessels that empty into the great
sinuses. cerebral vein ( Figs. 4.26 and 4.27). Anasto-
The superficial middle cerebral vein courses motic channels connecting the superficial and
along the lateral sulcus and receives smaller deep veins, include the occipital vein, the
veins on the lateral surface of the hemisphere basal vein ( Rosenthal ), and the posterior cal-
( Fig. 4.25). This large vein empties into the losal vein ( Figs. 4.26 and 4.27). Veins of this
cavernous sinus ( Fig. 4.24). The superficial group are best considered in relation to the
middle cerebral vein also receives anasto- deep cerebral veins.
Corpus callosum Septum pellucidum
Septol vein
_ ^
Caudote nucleus
-Anterior terminal vein
Tholamostriote vein
Tronsverse caudate
veins
Tholamus - Choroidol vein
Epithalomic vein
—
Internal
cerebral vein —— Loteral
ventriculor vein
Choroid plexus
Occipital vein - Corpus

callosum
Bosol vein
Greot cerebral vein (Galen j
Figure 4.26. The internal cerebral veins and their tributaries
Anastomotic veins
Tholamostriote vein
Longitudinal caudate /
vein \
Tronsverse caudate
vein
I
Choroidal vein
\
Inf sagittal
sinus
Rectus sinus
y
/
/
Anterior terminal
vein
Septal vein
Transverse /
sinus Basal vein
Great vein Internal cerebral veins
Figure 4.27. Midsagittal view of the internal cerebral veins showing the relationship of the great vein to the rectus
sinus.
DEEP CEREBRAL VEINS course ( Figs. 4.26 and 4.27). Distally the trans-
verse caudate veins enter the white matter
The deep cerebral veins of major impor- adjacent to the lateral angle of the lateral ven -
tance are ( a ) the internal cerebral veins, (b) tricle; their smaller tributaries in this region
the basal veins ( Rosenthal ), and ( c ) the great form the longitudinal caudate veins ( Fig. 4.27).
cerebral vein (Galen ) ( 27). The latter veins divide at acute angles into a
The internal cerebral veins ( paired ) are lo- number of branches that fan out into the
cated near the midline in the tela choroidea of white matter by coursing with the fibers of
the roof of the third ventricle ( velum inter-
position ) ( Figs. 4.26 and 4.27). They extend
—
the corpus callosum ( Figs. 4.27 4.29). Some
of the shorter branches drain the deep capil -
caudally from the region of the interventricu - lary plexuses of the white matter. Longer
lar foramina over the superior and medial branches of these veins, extending almost to
surface of the thalamus. In the rostral part of the cortex, may be regarded as intracerebral
the quadrigeminal cistern , these paired veins anastomotic channels connecting ventricular
join to form the great cerebral vein (Galen ). and surface veins. Additionally, the trans -
The internal cerebral vein on each side reverse and longitudinal caudate veins give rise
ceives (a ) the thalamostriate vein ( terminal to another group of branches known as the
vein ), ( b) the choroidal vein, (c) the septal superior striate veins ( Figs. 4.29 and 4.30).
vein, ( d ) the epithalamic vein , and ( e) the lat - These veins pass ventrally through and
eral ventricular vein ( Fig. 4.26). around the caudate nucleus, perforate the in-
The thalamostriate vein runs forward in the ternal capsule, and break into a number of
terminal sulcus at the junction of the thala - smaller vessels that drain the dense capillary
mus and caudate nucleus. This vein receives plexus of the lentiform nucleus ( Fig. 4.29 ).
the anterior terminal vein, which drains the This capillary plexus is drained from below
ventricular surface of the head of the caudate by the inferior striate veins , which converge
nucleus. Numerous transverse caudate veins upon the anterior perforated substance and
join the thalamostriate vein throughout its enter the deep middle vein .
Figure 4.28. Angiographic appearance of the deep venous system in one intact cerebral hemisphere. Abbrevia-
.
tions : S, septal vein, l thalamostriate vein. I. Internal cerebral vein; 8, basal vein; C. choroidal vein; G great cerebral
vein (Galen); and P. occipital vein (vein of the posterior horn).

Anastomotic vein
Transverse caudate Longitudinal caudate vein

vein
Superior striate veins
lnt cerebral
vein —
Superficial middle
cerebral vein
Inferior striate veins

Choroid plexus
Deep middle cerebral vein

Figure 4.29. Transverse section through the brain of the rhesus monkey, showing the connections between deep
and superficial veins.
portions of the choroid plexus and adjacent

hippocampal regions. The choroid plexus
also is drained by the choroidal branch of the
basal vein and , to a lesser extent, through the
lateral ventricular vein.
The septal vein drains the septum pellu -
cidum and rostral portions of the corpus cal-
losum. Distally, branches of this vein extend
beneath the head of the caudate nucleus into
the white matter at the base of the frontal
lobe ( Figs. 4.26 and 4.27). The septal vein
joins the internal cerebral vein in the region
of the interventricular foramen.
The epitlialamic vein is a small vessel that
drains the dorsal part of the diencephalon .
This vein enters the internal cerebral vein, or
the great cerebral vein, near their junction .
Blood from ventral portions of the thalamus
and from the hypothalamus is drained by
vessels that pass ventrally into the pial ve-
nous plexus of the interpeduncular fossa.
From this plexus venous blood is conveyed
into the cavernous or sphenoparietal sinuses
or into tributaries of the basal vein.
Figure 4.30. Angloarchitecture of the deep cerebral
venous system as shown in a 1 -cm-thick coronal section.
The lateral ventricular vein courses over the
Anastomoses between deep and superficial veins are superior caudal surface of the thalamus ( Fig.
evident. Abbreviations: 1 terminal vein. 8. basal vein; /, 4.25) and enters the internal cerebral vein as
internal cerebral vein. this vessel joins the great cerebral vein. Occa-
sionally, this vein terminates directly in the
great cerebral vein. Distally the lateral ven-
The choroidal vein runs along the lateral tricular vein extends over the surface of the
border of the choroid plexus and distally ex - thalamus and the tail of the caudate nucleus
tends into the inferior horn of the lateral ven- and enters the medullary substance near the
tricle ( Fig. 4.26 ). This tortuous vessel drains angle of the lateral ventricle. Small branches
of this vein arise from the choroid plexus and

from the white matter of the parahippocam -
pal gyrus.
The basal vein ( Rosenthal ) arises near the
basal veins, the paired occipital veins, and the
posterior callosal vein ( Figs. 4.26 1.28) . This
short vein passes caudally beneath the sple-
nium of the corpus callosum and empties into
—
medial part of the anterior temporal lobe the rectus sinus. The paired occipital veins
( Figs. 4.27 and 4.28 ) . This vein receives (a ) the drain inferior and medial surfaces of the oc-
anterior cerebral vein, ( b) the deep middle cipital lobe and adjacent parietal regions . The
cerebral vein , and (c ) the inferior striate veins. posterior callosal vein drains the splenium of
The anterior cerebral vein accompanies the the corpus callosum and adjacent medial sur-
anterior cerebral artery and drains the orbital faces of the brain .
surface of the frontal lobe, anterior portions Angiographic studies (65) of cerebral veins
of the corpus callosum , and rostral portions made by serial x -rays reveal that the superfi -
of the cingulate gyrus. The deep middle cerebral cial frontal veins fill slightly before the pari -
vein , located in the depths of the lateral sul - etal veins. The deep veins usually are the last
cus, drains insular and adjacent opercular to fill , and they retain sufficient concentra -
cortex. The inferior striate veins drain ventral tions of radiopaque material to be visualized
portions of the basal ganglia , emerge through for a longer time. From the standpoint of di -
the anterior perforated substance, and empty agnostic radiology , the deep cerebral veins
into the deep middle cerebral vein ( Figs . are more important than the superficial veins
—
4.28 4.30 ) . In the region of the anterior perfo-
rated substance, these veins unite with the
which exhibit extremely variable configura -
tions. Visualization of the thalamostriate vein
basal vein which courses caudally around the and some of its major tributaries can provide
crus cerebri to join the great cerebral vein . information concerning the position and size
The basal vein receives additional tributaries of the lateral ventricle.
from the interpeduncular region, the mid - The deep veins are concerned primarily
brain , and the inferior horn of the lateral ven - with the drainage of the ventricular surface,
tricle. The hypothalamus and ventral por- the choroid plexuses, the deep medullary
tions of the thalamus also are drained by the substance, the caudate nucleus, and the dor-
basal veins. sal portions of the lentiform nucleus and thal -
The great cerebral vein (Galen ) receives the amus. All these structures also can be drained
paired basal internal cerebral veins, the by surface vessels through numerous intra -
paired internal cerebral veins, the paired cerebral and extracerebral anastomotic veins.
References Rowland LP, ed . Merrit 's textbtK > k vessels. Berlin Springer - V'erlag,
of neurology. 8th ed . Philadelphia: 1978.
1 Aitken HF. A report on the circula -
tion of the lobar ganglia made to Dr . 9.
Lea & Febiger, 1989:206-214 .
Brust JCM. Cerebral circulation:
.
17. Foix C, Hillem ind |. I .es art&res de
I'axe encephalique jusqu 'au di-
James B . Ayer ( with a postscript by Stroke. In : Kandel HR, Schwartz JH , encephale inclusivement. Rev Neu -
JB Ayer, MD ) Boston Med Surg J lessel TM, eds. Principles of neural -
rol ( Paris ) 1925;44:705 739.
1909;160(Suppl ):18. science. Appendix B. New York: El - 18. Frantzen E, Olivarius BIF. On
2. Alexander L. The vascular supply of sevier, 1991:1041-1049. thrombosis of the basilar artery.
the striopallidum . Proc Assoc Res 10. Carpenter MB, Noback CR , Mivss Acta Psychiatr Neurol Scand
Nerv Ment Dis 1942;21:77-132. ML. The anterior choroidal artery . -
1957;32:431 439.
3. Baker AB. Cerebrovascular disease. Its origins, course, distribution and 19. Fujii K , Chambers SM , Rhoton AL
IX . The medullary bltxvi supply and variations. Arch Neurol Psychiatry |r . Neurovascular relationships of
the lateral medullary syndrome. 1954;71:714-722. —
the sphenoid sinus a microsurgical
Neurology 1961; 11:852 -861 11 . Cooper IS. Surgical occlusion of the study.|Neurosurg 1979;50:31-39.
4 . Baptista AP. Studies on the arteries anterior choroidal artery in Parkin - 20. Calloway JR , Greitz T. The medial
of the brain II The anterior cerebral sonism . Surg Gymxrol Obst and lateral choroid arteries: an
artery: some anatomic features and 1954;99:207-219. anatomic and roentgenographic
their clinical implication . Neurology 12. Coronna ]J . Cerebrovascular dis - study . Acta Radiol (St ( K’kh )
5.
111825 833.
Barnett HJM . Cerebrovascular dis-
eases. Textbook of internal medi -
-
cine. 2d ed . Philadelphia : J . B. Lip
-
1960;53:353 356
21. George AE, Salamon G , Kricheff IN .
eases. In : Wyngaarden |B, Smith
I II, eds. Cecil texbook ot medicine. 13.
pincott , 1991:2161-2168.
Crock IIV , Yoshizawa II . The blood
Pathologic anatomy of the thala
moperforating arteries in lesions of
-
18th ed . Philadelphia : YV . B. Sanders, supply of the vertebral column and the third ventricle: Part II Am J
1988:21-59. spinal cord in man. Berlin : Springer- Roentgenol Radium Ther Nucl Med
6. Batson OV . The function of the ver - Verlag, 1977. 1975;124:231-240.
tebral veins and their role in the 14. Dandy VVE . Intercranial arterial 22. Gibs II , Carver CC , Rhoton AL,
spread of metastases. Ann Surg aneurysms. Ithaca , NY: Comstock Lenkey C, Mitchell RJ . Microsurgi -
1940;112:138-149. Publishing Company, 1947. cal anatomy ol the middle cerebral
7. Bolton B . The bltxxi supply of the 15. Dejerine J , Roussy G. Le syndrome artery . J Neurosurg 1981;54 : 151 -169.
human spinal cord . J Neurol Psychi - thalamique. Rev Neurol ( Paris )
1906;14:521-532.
23. Gillilan LA . The arterial blotx.1 sup-
atry 1939;2:137-148 ply of the human spinal cord . J
8. Brust JCM . Cerebral infarction. In : 16. Duvernoy MM . Human brainstem Comp Neurol 1958;110:75- 103.
.
24 . Ilara K , Fujino Y . The thalamoper - determination of cerebral blood stupor and coma. 3rd ed . Philadel -
forate arterv . Acta Radiol 1966;5: flow in man . theory , pnxedure and phia: Davis, 1966.
I 92-2CX1. normal values. ) Clin Invest 55. Reichle ME . Circulatory and meta -
25. Hardy DG , Peace DA, Rhoton AL.
Microsurgical anatomy of the supe -
-
1948;27:484 192.
40. Lazorthes G, Gousze A , Salamo, G.
bolic correlates of brain function in
normal humans. In: Plum F, ed .
rior cerebellar artery. Neurosurgery Vascularisation et Circulation de Handbook of physiology. Vol. V .
1980;6:10-27. I ' Encephale. Paris: Masson et Cie, I ligher functions of the brain. Part 2;
26. Harris FS, Rhoton AL Jr . Anatomy 1976. Section I : The nervous system.
of the cavernous sinus: a micro - 41 . Lazorthes G, Poulhes J , Bastide Bethesda , MD: American Physiolog-
surgical study. J Neurosurg I 976;45: G, Rolleau J , Chancholle AR . ical Society, 1987:643-674.
169-180. Recherche sur la vascularisation 56. Salamon G, Lazorthes G. Atlas of
27. Hassler O. Deep cerebral venous arterielle de la moelle: application a the arteries of the human brain.
system in man: a microangiographic la pathologic medullaire. Bull Acad Paris: Sandoz, 1971 .
study on this areas of drainage and Natl Med 1957;141 :464-477. 57. Scharrer E. The blood vessels of the
its anastomoses with the superfi - 42. Lazorthes G , Salamon G. The arter- nervous tissue. Q Rev Biol 1944;
cial cerebral veins. Neurology 1966;!6: ies of the thalamus: an anatomical 19:308-318.
505-511 and radiological study . J Neurosurg 58. Schlesinger B. Venous drainage of
28. Hassler O. Blood supply to the 1971;34:23-26. the brain , with special reference
human spinal cord . Arch Neurol 43. Martin RG , Grant JL, Peace D, to galenic system. Brain 1939,62: *
1966;15:302-307. Theiss C, Rhoton AL. Microsurgical 274-291 .

29. Hassler O. Venous anatomy of relationships of the anterior inferior 59. Schwartz P, Fink L. Morphologic
human hindbrain. Arch Neurol cerebellar artery and the facial- und F.ntstehung der geburstrauma-
1967;16:404-409 vestibulocochlear nerve complex. tischen Blutungenim Gehirn und
30. Hassler O. Arterial pattern of Neurosurgery 1980;6:483-507. Schadel des Neugeborenen . Z
human brain stem Normal appear - 44 Masucci EF Bilateral ophthalmople- Kinder heilk 1926;40:427-474.
ance and deformation in expanding -
gia in basilar vertebral artery dis - 60. Stephens RB, Stilwell DL. Arteries
supratentorial conditions. Neurol
-
ogy 1967;17:368 375.
- -
ease. Brain 1965;88:97 106.
45. Mettler FA . Neuroanatomy . St .
and veins of the human brain .
Springfield , IL: Charlt*s C. Thomas,
31 Haugsted H . Occlusion of the basi - Louis: C.V. Mosby Co., 1948. 1969.
lar artery . Diagnosis by vertebral 46. Mettler FA, Cooper IS, Liss II , Car- 61 . Stopford JSB. The arteries of the
angiography during life. Neurology penter MB, Noback CR . Patterns of pons and medulla oblongata. Part I.
1956;6:823-828. vascular failure in the central ner -
32. I lerren RY , Alexander L. Sulcal and vous svstem . | Neuropat hoi Exp ^
) Anat Physiol 1915 0:131 164.
62. Stopford JSB. The arteries of the
intrinsic blood vessels of human Neurol 1954;13:528-539. pons and medulla oblongata . Part II.
spinal cord . Arch Neurol Psychiatry 47. Mettler FA, Liss HR , Stevens GH . J Anat Physiol 1916;51:255-280.
1939;41 :678-687. Blood supply of the primate stri- 63. Suh TH , Alexander L. Vascular sys-
3.3. Kaplan HA. Arteries of the opallidum . J Neuropat hoi Exp Neu- tem of the human spinal cord . Arch
brain . Acta Radiol (Stockh ) 1956,46: rol 1956;15:377-383. Neurol Psychiatry 1939;41:659-677.
.364-370. 48. Moniz E Diagnostic des Tu - meurs 64 . Taveras J . Angiographic observation
34. Kaplan HA . Vascular supply of the Cerebrales et Epreuve de I ' Enceph- in exclusive cerebrovascular dis -
base of the brain In: Fields WS, ed . alographie Arterielle. Paris: Masson ease. Neurology 1961; 11 :86-90.
Pathogenesis and treatment of et Cie, 1931 . 65. Taveras JM , Wood EH . Diagnostic
Parkinsonism. Ch. 6. Springfield , IL: 49 Moniz E. L' Angiographie Cerebrate, neuroradiology. 2d ed . Baltimore:
Charles C. Thomas, 1958:138-155. ses Applications et Resultats en Williams & Wilkins, 1976.
35. Kaplan HA . Collateral circulation of Anatomie, Physiologie et Clinique. 66. Truex RC, Kellner CF.. Detailed atlas
the brain. Neurology 1961;11 :9-15. Paris: Masson et Cie, 19.34 . of the head and neck. New York:
36. Kaplan HA , Ford Dll . The brain 50. Ostrowski AZ, Webster JE, Gurdjian Oxford University Press, 1948.
vascular system . Amsterdam . Else- F.S. The proximal anterior cerebral 67. Turnbull 1 M . Blood supply of the
vier, 1966. artery: an anatomic study. Arch spinal cord . In: Vinken PJ , Bruvn
37. Kennedy C, Des Rosiers Mil , Jehle Neurol 1960;3:661-664 . GW , e*ds. I landbook of clinical neu-
JW , Reivich M , Sharp E, Sokoloff I 51 . Perlmutter D, Rhoton AL . Microsur - rology. Vol . 12. Amsterdam : North-
Mapping of functional neural gical anatomy of the anterior cere- Holland Publishing Company,
pathways by autoradiogaphic sur - bral-anterior communicating- recur - 1972:478-491 .
vey of local metabolic rate with |MC| rent arterv complex. J Neurosurg 68. Turnbull IM Blood supply of the
deoxvglucose. Science 1975;187: 1976,45:259-272. spinal cord : normal and pathologi -
-
850 853.
38. Kennedy C, Des Rosiers IL Saku -
52. Perlmutter D, Rhoton AL. Microsur-
gical anatomy of the distal anterior
cal considerations. Clin Neurosurg
1973;20:56-84.
rada ( 3, et al . Metabolic mapping of cerebral artery. Neuri >surg 69. Zeal AA , Rhoton Al.. Microsurgical
the primary visual system of the 1978;49:204-228 anatomy of the posterior cerebral
monkey by means of the autoradi -
,
ographic j 4C| deoxyglucose tech -
.
53. Plum F, C jedde A, Samson FE. Neu
roanatomical functional mapping
- artery . J Neurosurg 1978;48:534-559.
70. Ziilch K|. Mangeldurchblutung an
nique. Proc Natl Acad Sci ( USA )
1976;73:4230-4234.
- -
by radioactive 2 deoxy d -glucose
method. Neurosci Res Program Bull
der Grenzzone zweier Gefassgebiete
als Ursache bisher ungeklarter
39. Ketv SS, Schmidt CF. The nitrous -
1976;14:457 518 Ruckenmarksschadigungen . Dtsch
oxide method for the quantitative 54 . Plum F, Posner JB. The diagnosis of Z Nervenheilk 1954;172:81-101.
Section II
Neurohistology and
Neurocytology
5
Neurons
NEURONS AS SIGNALING UNITS simple basic units. In terms of information

processing, the complexity of the human
A proper knowledge of the histologic or- brain derives not from the contribution of its
ganization of the nervous tissue is required to individual components, but from the highly
understand how the nervous system works ordered connections that exist between these
and to fully appreciate its uniqueness. The innumerable elements. It is through the spe-
tissue of the central nervous system is made cific wiring of its individual elements, which
up of two classes of cells that may be broadly is established during development and can
categorized as neurons and neuroglia . Neu- be modified by learning, that the human
roglia will be discussed in Chapter 6. Despite brain can generate the most complex forms of
great variability in size and shape, all neu - behavior.
rons share common morphologic features, The fact that each neuron is a structural
which are those of the key elements of a and functional unit is known as the neuron
highly complex communication network. doctrine. It was proposed late in the 19th cen-
Typically neurons have several processes, tury in opposition to the then prevailing view
called dendrites, radiating from a central por- that nerve cells form a syncytium or continu -
tion of the cell, known as the soma or ous reticulum. The neuron doctrine or theory
perikaryon . They also possess a single process, was popularized by Waldeyer ( 197), but had
the axon , which extends for variable distances its foundation in the embryologic investiga-
from the soma and breaks out into a multi- tions of Wilhem His in Germany, the neu -
tude of axon terminals that establish special- ropathologic works of August Forel in
ized junctional contacts, called synapses , upon Switzerland, and , particularly , the extensive
the dendrites and cell bodies of other neu - histologic studies of Ramon y Cajal in Spain
rons. The axon is capable of conveying infor- (175). This theory was perfectly congruent
mation over great distances by propagating with the cell theory formulated by Jacob
in an all -or- none fashion a transient electricalSchleiden and Theodor Schwann in the 1930s,
signal termed the action potential . The axon which holds that cells are the structural units
arises from a specialized region of the cell of all living matter.
body called the axon hillock, where the action The neuron doctrine states that the indi-
potential is initiated once a critical threshold vidual nerve cell ( neuron ) constitutes the ge-
is reached . netic, anatomic, trophic, and functional unit
The neuron is a dynamically polarized cell of the nervous system . All neural pathways,
that serves as the major signaling unit of the circuits, and reflex arcs are composed of indi-
nervous system . It comprises four function- vidual neurons arranged in simple or com -
ally distinct components: (a ) an input or re- plex patterns.
ceptive component ( usually the dendrites A variety of staining techniques have re-
and part of the soma ), ( b) an integrative com - vealed the principal features of the neuron
ponent ( usually the axon hillock ), (c) a con - and the manner in which individual neurons
ductile component ( the axon ), and (d ) an out- are interrelated . The electron microscope and
put or secretory component ( the axon cytochemical techniques provided a new in-
terminals). The human brain is known to con - sight into the fine structure and the functional
”
tain about 10 neurons, each being able to roles of specific organelles that occur within
contact at least 10,000 other neurons (3). De- the neuron . All the recent data acquired with
spite their large number, all the neurons in these techniques support the neuron doc-
the central nervous system share the common trine. However, some of these recent findings
features noted earlier and appear as rather have shown that the interactions between
131
132 Section II Neurohistology and Neurocytology
neurons are much more complex and subtle related to synaptic transmission or neurose-
than previously thought. For instance, some cretory activity ( Fig. 9.8). Mitochondrial con-
neurons are known to communicate through centrations, synaptic vesicles, or secretory
ultra microscopic channels formed by special granules are commonly present in their bulb-
proteins in regions referred to as gap junc- like terminals, which release chemical com-
tions. Therefore, it must be realized that most pounds known as neurotransmitters. The
of the unique properties of the nervous tissue telaxons transmit electrical or chemical sig-
stem from the highly differentiated interac- nals capable of producing generator poten-
tions that exist between billions of distinct tials in the dendritic zones of other neurons
cellular units. and in muscle, or they can induce stimulatory
A generalized concept of neurons based effects in innervated glands. The terms axon,
upon the site of impulse origin, rather than dendrite, and cell body, used in this text, are
the location of the cell body, was proposed by in accordance with the functional concepts
Bodian ( 15). In such a scheme, the term " den- earlier described .
dritic zone" is used to denote the receptor Intercellular and intracellular communica -
membrane of a neuron ( Fig. 5.7), which may tion in the nervous tissue is accomplished
be cytoplasmic extensions (i.e., dendrites), through both electrical and chemical mecha -
portions of the cell soma , or specialized re- nisms ( Fig. 5.1 ). Electrical communication is a
ceptors which act as transducers. The cell property of the neuronal surface membrane,
body (soma ) remains the focal point of em- whereas chemical communication results
bryonic outgrowth of dendrites and axons from a specialization of the secretory nature
and of axonal regeneration. It also maintains of neurons. While in this chapter the detailed
the trophic aspects of neuronal activity. The biophysical or chemical aspects of cellular
position of the soma is irrelevant as far as the communication in the nervous system is not
major electrochemical functions of the neuron considered , some introduction to general
are concerned. Its position is related to the concepts is provided for students who have
outgrowth of processes and to metabolic not yet studied neuronal physiology. In a
maintenance, rather than to the polarized "resting" neuron , the interior of the cell is
conduction of the neuron. 60-70 mV negative with respect to the extra-
This functional concept recognizes the site cellular fluid . This resting membrane potential
of impulse origin as the pivotal position in reflects steady-state ionic concentration gra -
the neuron . This site may not necessarily be a dients resulting from the selective permeabil -
fixed point in a particular neuron . Further- ity properties of the cell membrane. Inside
more, all surfaces bearing synapses (den- the cell there is a high potassium concentra-
drites, cell body, and axon ) are related to tion (about 50 times higher than outside) and
response-generating functions. In these func- a low sodium concentration ( about 10 times
tional terms, the axon may be said to arise lower than outside). Potassium ions move
from any response-generating structure, such freely through the membrane, and the resting
as a dendrite, the cell body, or a sensory re- membrane potential is due largely to the dis-
ceptor. The functional role of the axon is to tribution of potassium ions needed to balance
conduct signals away from the response-gen - the charge of impermeant anions.
erating region . In peripheral sensory neurons, In the resting neuron , the surface mem -
-
the response generating zone is the distal tip brane is effectively impermeable to sodium
of the axon which is usually associated with a ions because of a unidirectional transport
connective tissue capsule or other receptor of mechanism called the sodium pump. When a
epithelial or mesodermal origin. The action neuron becomes active, the permeability of
potential generally occurs at or near the ori- the membrane to sodium and other ions
gin of the axon and conducts the nerve im- changes. This movement of ions, termed con -
pulse away from the "dendritic zone." Axons ductance, is inversely proportional to the re-
are ensheathed by neuroglial or Schwann sistance of the membrane. In axons, the con-
cells. Both axon diameter and sheath differen - ductance change has a duration of
tiation are related to the rate of impulse con- approximately 1 millisecond (msec) and is
duction . The branched and variously differ - called an action potential . In dendrites and
entiated terminals of axons are sometimes soma, the conductance change has a duration
called telaxons or telodendria . They may show varying from a few to more than 100 msec.
membrane and cytoplasmic differentiations These longer duration changes are called
5 Neurons 133
ELECTRICAL
Synaptic
A potentials Action potentials
i.
Rate: < 1 to 120 m / sec
6
Rate: < 0.01 to > 4.6 X 10 m / sec
T
B Protein
synthesis
Axoplasmic transport
CHEMICAL
Figure 5.1. Comparison of major type of infra- and intercellular communications in neurons. The dendrites and soma
of the cell are shown toward the left, the axon and synaptic terminals toward the right A . two regions of the neuron
concerned with intracellular electrical communication are shown One zone (the dendrosomatic domain) sustains
graded, nonpropagated synaptic potentials, and the other (axon and axon terminal domain) sustains all or nonprop-
agated action potentials. B. The rates of chemical (axoplasmic) transport between the soma and synaptic terminals
are shown for comparison with rates of electrical communication by action potentials
synaptic potentials and are graded in ampli- minal, the depolarization of the surface mem-
tude. In contrast to synaptic potentials, action brane as it is invaded by the action potential
potentials are always of the same amplitude leads to an influx of calcium ions, which in
once the threshold has been exceeded . A po- turn causes the release of a chemical called a
tential change which causes the inside of a neurotransmitter. The frequency of action po-
cell to become less negative with respect to tentials usually determines the amount of
the extracellular fluid is termed a depolarizing transmitter that is released . Thus, the fre-
potential . An increased negativity of the inte- quency of action potentials ( digital signal ) is
rior of the cell is termed a hyperpolarizing po- transformed into a graded amount of trans-
tential . Synaptic potentials may be either de- mitter (analog signal ) at the level of axon ter-
polarizing or hyperpolarizing, while action minals. Many of the neurotransmitter sub-
potentials are always depolarizing. Hyperpo- stances are synthesized and stored in the
larization decreases a cell's ability to generate synaptic terminals of the axon . However,
an action potential and is therefore inhibitory , their synthesis depends upon enzymes which
whereas depolarization does exactly the in- are synthesized in the cell body and moved
verse and is excitatory. by a process called axoplasmic transport
Action potentials are usually generated in along the axon to the terminal ( Fig. 5.1 ). In
the soma at the region of the emergence of contrast to the rapid rate of propagation of
the axon and propagated along the axonal action potentials, rates of axoplasmic trans-
membrane to its terminal ( Fig. 5.1 ). The ac - port range from less than 0.01 to more than
tion potential can be regarded as a means of 4.6 X 10 h m /sec. Intercellular communica-
transferring a signal from the soma, along the tion, for the most part, is accomplished
axon, to the synaptic terminals, where the through the release of a neurotransmitter at
process of intercellular communication is ini- the synapse ( Fig. 5.34). The transmitter dif -
tiated (105). The rate of propagation of action fuses across the small extracellular space be-
potentials depends upon the diameter of the tween the membrane of the synaptic terminal
axon and its associated myelin sheath and and the surface membrane of the adjacent
can range from less than 1 to about 120 me- neuron.
ters per second ( m / sec) ( Fig. 5.1 ). At the ter- The membrane of the dendrite and soma
of the postsynaptic cell contains specific mo- with hematoxylin ( e.g., Weigert method ) ( Fig.
lecular binding sites for the transmitter. When 10.17). Primary fixation in potassium dichro-
these binding sites can be shown to be associ- mate, followed by an osmic acid solution, se-
ated with a response in the postsynaptic neu - lectively stains the fatty acids of degenerating
ron, they are called receptors. These receptors myelin black, while the normal myelin re-
may be part of an ion conductance channel, mains a yellow -brown color ( Marchi method )
so that the transmitter-receptor interaction re- ( Fig. 11.4). When the initial fixative contains
sults in an opening or closing of a channel for solvents ( e.g., alcohol, ether, chloroform ),
a specific ion . In some cases, the transmitter- lipids of myelin are removed and only a clear
receptor interaction leads to the activation of space remains ( Fig. 5.3A and B ) . If such sol-
enzymes and a sequence of chemical reac- vents are avoided , the lipids of the normal
tions in the postsynaptic cell . When these re- myelin sheath are readily stained by osmic
actions result , over time, in changes in the acid ( Fig. 5.3C- E ) and Luxol fast blue ( Fig.
number of receptors or transmitter synthetic 5.3F and H ) . Positive results with the Marchi
enzyme molecules in the postsynaptic cell, it technique may be obtained several years after
is said to be a trophic effect ( Fig. 5.33). Several degeneration has occurred and in specimen
of these physiologic and chemical properties stored in paraformaldehyde for long periods.
of neurons are at the basis of some of the Despite its limitation in defining the exact site
most currently used neuroanatomic methods. of termination of fiber bundles, this method
can be successfully applied to trace degener-
NEUROBIOLOGIC TOOLS FOR STUDYING ating fiber tracts in human postmortem mate-
rial .
NEURONAL MORPHOLOGY
The nerv ous tissue has a strong affinity for
Histologic Techniques weak silver solutions ( argyrophilia ). Blocks of
nervous tissue are impregnated with silver
Although unstained fresh nervous tissue, salts for several days, and then placed in suit-
or nervous tissue grown in tissue culture, able reducing solutions. This action results in
may be studied with the phase microscope, the deposit of silver particles within the nerve
the customary method is to use stained cell and its processes. The reduced silver par-
preparations. It is essential that fresh nervous ticles in nonneural tissue are removed by
tissue be fixed in a solution which kills bacte- subsequent solutions, so that the neurons and
ria , inactivates autolytic enzymes, and pro- their processes appear golden brown or black
duces minimal shrinkage, swelling, or dis - against a light yellow background . The
tortion. Appropriate fixatives also make Ramon y Cajal (155) and Ranson (156) tech-
components of the nerve cell receptive to niques both permit bulk staining of tissue
suitable dyes or permeable to colloidal solu - blocks and are still used to elucidate the
tions. The most common fixatives for neural structural features of the central and periph -
tissue are aldehydes and alcohols. These fixa - eral nervous system ( Fig. 5.2C ).
tives often are used in conjunction with a va - Other methods have been developed
riety of chemicals, such as chloral hydrate, which permit the staining of mounted sec-
ammonia , pyridine, glacial acetic acid , and tions. In the Bodian (14) method , the slides
mercuric chloride. In experimental studies in are placed in a silver protein solution ( protar-
animals, excellent fixation of neural tissue is gol ) with metallic copper and incubated at
achieved by perfusion techniques, but obvi- 3°C. Again, the silver is reduced as in the
ously this is not possible in humans. Since bulk method . The silvered sections are then
several hours usually intervene between passed through a solution of gold chloride.
death and autopsy, it is rarely possible to ob- Since gold has a higher atomic number and
tain perfectly fixed human neural tissue. Ap- atomic weight than silver, gold replaces the
propriate fixation renders many components silver particles in the nerv e tissue of the sec-
of the nerve cell, such as chromatin, receptive tion. The sections then are developed in ox-
to suitable dyes ( i.e., cresyl violet ) ( Fig. 5.2E ), alic acid , and the nonneural gold particles
or neurofilaments more permeable to col - are removed . Nerve cells, their nuclei and
loidal silver solutions ( Fig. 5.2A and B ) . processes are all beautifully visualized by this
Formalin fixation followed by a mordant- method ( Fig. 5.2A and B ) .
ing in potassium dichromate preserves the The Golgi technique is based on the phe-
normal lipids of myelin , and enhances the ap- nomenon of silver impregnation of neurons
pearance of the myelin sheaths when stained which was accidentally discovered by the
Figure 5.2. Shape, size, and appearance of nerve cells stained by different techniques. ( x 370 except D which is
xl 25.) A. Unipolar neurons of dorsal root ganglion Three larger cells contain melanin granules (silver protargol tech-
nique) B. Multipolar neurons of reticular formation. An area of cytoplasmic lopofuscin pigment appears between the
nucleus and axon (a) of the large cell (silver protargol technique) C. Multipolar neurons of sympathetic ganglion with
interlacing of dendrite dnd small axons (Ramdn y Cajal silver nitrate technique). D. Purkinje cell of cerebellar cortex
whose dendritic branches are studded with small gemmules. Adjacent blood vessels (fc>v) are identified In this prepa-
ration (Golgi technique). E. Cytoplasmic chromatin and nuclear appearance of normal (above) and Injured ( below)
anterior horn cell of spinal cord. The small eccentric nucleus and depleted chromatin pattern (chromatolysis) resulted
from earlier axonal destruction (Luxol-fast-blue and cresyl violet technique). F. Terminal degeneration in the ventral
nucleus of the thalamus following a localized lesion in the internal segment of the globus pallidus. Degenerated palli-
dothalamic fibers appear as black beaded and dots near the soma and dendrites of thalamic neurons (Wiitanen ' s
silver techniaueT .
Figure 5.3. Size and appearance of nerve fibers stained by different techniques A. Longitudinal section of femoral
nerve stained with silver protargol Axons (a), Schwann cell (nn) and connective tissue (cn) nuclei are Identified The
myelin sheath (ms) Is dissolved and remains as a clear space in such silver preparation ( x 370) B. Cross-section of sci-
atic nerve stained with silver nitrate Axons (a), myelin space (ms), and connective tissue of perineurorium (p) are
Identified Small black dots between larger fibers are axons of nonmyelinated fibers ( arrows ) ( x 130) C. Longitudinal
section of myelinated nerve fiber and node of Ranvier ( N) stained with osmic ocid dnd light green Myelin sheath
(ms) stained black, axon (a) is unstained and connective tissue of endoneurium (e) is green ( x 370) D. Cross-section
of lumbar nerve In caudal equina with osmic acid and light green Endoneurium (e) derived from pia mater is green .
5 Neurons 137
Italian histologist Camillo Golgi in the late less than 50 nm, and the preparation of such
19 th century (69). This technique and its nu - sections calls for special attention to fixation
merous variants are among the oldest and and embedding. The necessity of using ultra-
most widely used methods for studying neu - thin sections renders difficult the three-di -
rons and neuroglia (154 ). The Golgi methods mensional reconstruction of a whole neuron
are based on a pretreatment of the tissue with in electron microscopy. Today, electron mi -
potassium dichromate, followed by exposure croscopic methods are used in combination
to silver nitrate, which produces a black de- with histochemical or immunocytochemical
posit that literally fills the cell bodies and methods to visualize neurotransmitters (60 ),
processes of many neurons. Although only a or with anterograde and retrograde axonal
fraction of the total number of neurons and tracing methods to define the connections of
neuroglia are stained black, these often are the neurons under study ( 182 ).
revealed in great detail against a nearly color-
less background ( Fig. 5.2D ). Tract- Tracing Methods
In addition to neurons and neuroglia, the
blood vessels also may be stained by the The study of connectivity , or the relation
Golgi methods. The methods are empirical of one part of the nervous system with an -
and the results are uncertain, but magnificent other, requires tracing of the long axonal
neuronal and neuroglial details are revealed processes of neurons. This was first done by
in successful preparations ( Figs. 6.2 and 15.6 ). placing lesions in the brain and visualizing
The advantage of the Golgi methods are that the degenerating axons with specific stains
they provide a three-dimensional view of the ( Fig. 5.2F). One method which proved valu -
cellular elements of the nervous tissue and able in the past, the Nauta -Gygax reduced sil-
are invaluable for both qualitative and quan- ver impregnation technique (136, 137), results
titative studies of the nervous system (147, in a selective silver impregnation of degener -
205). They have been extensively used to ating axons. Staining of normal nerve fibers
evaluate the extent and analyze the architec- and endings is suppressed and these have a
ture of the dendritic ramifications. (See Am- golden yellow appearance ( Fig. 10.25). Thick,
brogi (5) and Culling (34) for further details as well as thin, degenerating axons of injured
on these classical neurologic stains.) neurons appear as discontinuous black
Much of our recent knowledge of neuron droplets or beaded segments arranged in
cytology has resulted from the use of the elec - an orderly linear fashion (degeneration "en
tron microscope and the freeze etch appara- - passage"). Arborizing degenerating axons,
tus. The short wave length of a beam of elec- observed in close proximity to nerve cells, rep-
trons from a high voltage source permits a resent "terminal" fiber degeneration. Selec-
greater resolution of biologic structures than tive staining of the terminal end -feet of nerve
that obtained from electromagnetic radiation processes (synaptic knobs, boutons termin -
in the visible spectrum ( the light microscope aux ) upon the dendrite or cell body of an -
has a limit of resolution of about 0.2 gm ). other neuron also is accomplished by the use
Electron density is imparted to the specimen of modified silver methods ( Fig. 5.28). Several
by impregnating it with compounds of metal variants of the original Nauta -Gygax method
of high atomic number, such as osmium, have been developed ( 54, 202 ) and used in
lead , and uranium. The electron microscope numerous studies to localize terminal fibers
methods reveal the detail of the internal or pathways within the central nervous sys-
structure of the neurons and the specializa - tem ( Fig. 5.2F ).
tions that exist at synaptic junctions ( Figs. Instead of being dependent on degenera -
5.13, 5.17, 5.18). However, electron mi - tive changes that occur in neurons following
croscopy requires very thin tissue sections, lesions, the current tract - tracing methods uti -
myelin (ms) is black , while axons (a) are unstained ( x 270) E . Longitudinal section of two myelinated nerve fibers with
osmic acid and light green . Lower fibers with thicker myelin sheath exhibit Schmidt -Lantermann clefts (arrows) ( x 370).
F . Cross-section of intradural dorsal root sensory fibers with combined Holmes ' silver and Luxol blue techniques. Axons
(a) appear dark brown, and myelin sheath (ms) is blue. Note variation In size of myelinated and nonmyelinated axons
( x 270) G. Longitudinal section of nerve fibers ( nf ) terminating as motor end-plates (ep) on extrafusal skeletal muscle
. .
fibers (ml) (gold chloride technique xl 45) . H Cross-section of intradural ventral root motor fibers stained as in F
Larger fibers (a) terminate as motor-end plates on extrafusal muscle fibers, while smaller 7-efferent fibers (arrows) end
on intrafusal muscle fibers of neuromuscular spindle ( x 270) .
lize some of the recently discovered physio- HRP uptake by neurons, so that WG A- HRP is
logic properties of neurons. For instance, the readily taken up by both cell bodies and axon
fact that there exists a constant and active in- terminals at the site of injection. This com-
tracellular movement of molecules along the pound is now' widely used as both antero-
axon (axonal flow ) was extensively exploited grade and retrograde tracer. Certain lectins,
to study neuronal connections. In the case of such as the leucoagglutinin extracted from
the autoradiographic tracing method , radioac- kidney beans ( Pliaseolus vulgaris ), are very ef -
tively labeled amino acids are injected into a ficient anterograde tracers. In optimal condi-
small region of the brain where they are tions, anterograde labeling studies with
taken up by nerve cell bodies, incorporated Phaseolus ru /g<? ns-leucoagglutinin ( PHA-L )
into cellular protein, and transported in an display the terminal arborization of axons
anterograde (orthograde) direction from the with as much detail as those obtained for the
cell body to the axon terminals. Autoradi- dendritic arborization with the Golgi meth-
ographs are prepared by coating the slides ods ( Fig. 5.4) (67, 68). PHA- L is visualized by
with a nuclear emulsion. After several weeks using a highly specific antibody raised
of exposure, the emulsion is developed and against this lectin, and the immunoprecipi -
fixed to reveal tracks of silver grains overly- tate can be observed at both light and elec-
ing labeled axons and terminals (Fig. 5.6). A tron microscopic levels.
major advantage of this technique over silver Biocytin is a compound of biotin and ly-
impregnation methods ( Nauta-Gygax and sine ( molecular weight 372.48) that can be
Fink-Heimer methods) is that fibers of pas- used as either an intracellular marker ( Fig.
sage which do not originate at the site of the 5.5) (103) or an extracellular tracer (101 ).
injection will not take up the tritiated amino When utilized as an extracellular tracer, bio-
acids and thus will not be labeled (32). cytin gives results that are as good as those
In contrast, the horseradish peroxidase ( HRP) obtained with PHA-L. Because of its biotin
method is based on the retrograde transport of moiety, biocytin can readily bind to any
material from axon terminals to the cell body. probes that are conjugated to avidin, so that
When this large glycoprotein enzyme ( molec- its visualization does not require the use of
ular weight of about 40,000) is injected into specific antibodies, as is the case for PHA-L.
the nervous tissue, it is incorporated into Furthermore, since both biocytin and PHA- L
neurons by the process of micropinocytosis are equally sensitive, they can easily be com-
(endocytosis). This is most marked at axon bined (.anterograde double-labeling methods ) so
terminals where the HRP is engulfed primar- that the organization of two different axonal
ily into multivesicular endosomes and trans- projection systems can be investigated simul-
ported back to the cell body where it is ulti- taneously (84, 179). This approach is partic-
mately degraded. By reacting the tissue with ularly useful to establish the degree of con-
an appropriate substrate such as tetramethyl vergence or divergence of two afferent
benzidine, an insoluble polymer is formed projections upon a given neuronal popula -
wherever the enzyme is located ( Fig. 5.4) tion. Both biocytin and PHA- L can be visual-
(109, 111, 126, 127). The same marker can also ized at the electron microscopic level and can
be used in intracellular labeling methods (103). be used in combination with immunocyto-
When HRP is injected into individual neu- chemical methods to reveal neurotransmit-
rons through a micropipette, the whole neu- ters ( Fig. 5.4).
ron, including dendrites and axonal projec- Fluorescence retrograde double-labeling meth-
tions, can be stained in a Golgilike fashion. ods make use of the principle of retrograde
This technique can serve to study the mor- axonal transport of several fluorescent dyes
phology of a neuron whose functional char- (e.g., nuclear yellow, fast blue, fluorogold ).
acteristics have been first investigated by When different dyes are injected into various
electrophysiologic recording techniques. brain loci, neurons whose axons provide col-
In current tract-tracing studies, the en- laterals to these brain regions can be identi-
zyme HRP is no longer used alone, but conju- fied by the double, or even triple, labeling
gated to the lectin wheat germ agglutinin that occurs in their cell bodies (8, 106, 194).
( WGA ). Lectins are naturally occurring pro- Therefore, retrograde double-labeling meth-
teins or glycoproteins that bind to cell mem- ods allow investigation of both the cellular
branes and stimulate micropinocytosis. The origin and degree of axonal collateralization
presence of WGA molecules greatly enhances of central nervous system pathways ( Fig. 5.4 ).
5 Neurons 139
Figure 5.4. Examples of retrograde (A - C) and anterograde (D - F) neuronal labeling obtained with various tract - trac-
ing methods in the squirrel monkey ( Saimm sciureus) A. Three brainstem neurons retrogradely labeled after injections
of wheat germ agglutinin-horseradish peroxidase conjugate (WGA-HRP) into the thalamus. The arrowheads indicate
unlabeled neurons that are visible because the section has been counterstained with neutral red ( > 300) B. Two dou-
ble-labeled neurons occurring in the internal segment of the globus pallidus after injections of fast blue into the ante-
rior portion of the thalamus and nuclear yellow into the upper region of the brainstem. These two retrograde tracers
fluoresce at the same wavelength, but can be differentiated from each other by color and because they occupy
different cellular compartments. Fast blue is sequestered within the cytoplasm and proximal dendrites and yields a
rather weak blue fluorescence, whereas nuclear yellow is confined to the nucleus, which displays a very bright yel-
lowish fluorescence when examined under dark-field illumination ( x 350). C. Immunocytochemical techniques can
be easily combined with retrograde tracing methods as exemplified in this photomicrograph which shows a striatal
neuron displaying immunoreactivity for the neuropeptide Y (NPY) adjacent to another striatal neuron (arrowhead)
that is neuropeptide Y-negative but contains HRP granules following injection of WGA -HRP into the globus pallidus.
This result indicates that striatal NPY-immunoreactive neurons do not project outside the striatum and thus should be
considered as interneurons ( x 350). D. Dark - field photomicrograph showing a dense field of anterogradely labeled
fibers in the anterior portion of the globus pallidus after microiontophoretic injections of the tracer Phaseolus vulgaris-
leucoagglutinin (PHA -L) into the striatum ( x 200). E. Similar striatopallida! PHA L-labeled fibers occur more caudally in
the globus pallidus and closely surround dendrites of pallidal neurons. Note that many of these fibers display charac-
teristic varicosities suggestive of terminal boutons ( x 400). F . Fibers anterogradely labeled with biocytln that was mi-
croiontophoretically delivered into the lateral segment of the globus pallidus. These markedly varicose fibers closely
surround the cell body (asterisk) and proximal dendrite of a neurons of the reticular nucleus of the thalamus. ( x 400).
rescence procedure for the localization of bio-

genic amines), or (c) a complex with a labeled
antibody ( i .e., the immunocytochemical ap-
proach that allows cellular localization of
neurotransmitters and related compounds).
The introduction in the early 1960s of
the paraformaldehyde-induced fluorescence
technique bv Falck and Hillarp (50, 51 ) for the
visualization of biogenic amines, particularly
catecholamines and indolamines, kindled in -
terest in the anatomic localization of other
biochemically definable neurons or chemospe -
cific neuronal systems . Since the early 1980s,
the histochemical techniques have been
largely superseded by the immunocytochem-
ical approach, which allows a more sensitive
and specific visualization of neurotransmit-
ters and related substances. The widespread
use of immunocytochemical techniques has
given a strong impetus to a field of research
that is often referred to as chemical neu -
roanatomy.
The immunocytochemical methods are
based on the immunologic concept of anti -
gen -antibody reaction which requires that the
substance to be localized is antigenic. Small
Figure 5.5. Pyramidal neuron of the hippocampal for - molecules, such as serotonin and dopamine,
mation of the rat . This neuron has been electrophysiolog -
ically characterized by in vivo recording and then intra -
can be rendered antigenic by conjugating
cellularly Injected with biocytin at the end of the them to large immunogenic protein by alde-
electrophysiologic recording period . Note that only part hydes ( Fig. 5.19 ). Incubation of a tis-sue sec-
of the profuse dendritic arborization of this neuron is visi-
ble in ttils plane of section The axon (arrowheads ) of this
-
tion in an antibody containing solution leads
to the development of an immunochemical
particular neuron could be followed as far as 4 mm from
its point of origin. ( x 450). bound between the specific antibody and the
antigen in its original in vivo location. In turn ,
the transmitter-specific antibody ( primary
A major disadvantage of this procedure, antibody ) can be visualized either directly or
however, is that most fluorescent dyes fade indirectly after incubation with a second anti -
rapidly and are not amenable to electron mi - body raised in a different species. The use of
croscopic examination . a proper marker facilitates the visualization
of the immunologically bound antibody and
Histochemistry and antigen. The two markers that are most fre-
Immunocytochemistry quently used are fluorescein isothiocyanate
( F1TC ) and horseradish peroxidase ( HRP),
In addition to the general morphology of the latter allowing visualization of the anti-
neurons, it is important to be able to study gen-antibody labeled complex at the ultra-
the cellular localization of specific chemical structural level . Another method uses anti-
substances. In recent years, a number of his- bodies linked to electron-dense gold particles,
tochemical and immunocytochemical tech- Antibodies that are currently available include
niques have been developed to visualize neu- those that were raised against (a ) neuroac-
rotransmitters and neurosecretory products. tive peptides (e.g., substance P, somatostatin,
In general, these methods are based upon for- enkephalin, neurotensin ), ( b) enzymes involved
mation of (a ) a colored, insoluble precipitate ill the synthesis of neurotransmitters (e.g., tyro-
(e.g., the histochemical method for the visual- sine hydroxylase, dopamine-fi-hydroxylase,
ization of acetylcholinesterase), ( b ) a com- glutamate decarboxylase), (c) neurotransmit -
pound with characteristic fluorescence when ter themselves (e.g., serotonin , dopamine, y -
.
excited by ultraviolet light (e.g., the histofluo- aminobutyric acid or C ABA , glutamate), and
5 Neurons 141
(d ) neurotransmitter receptors (e.g. choliner- V

gic, dopaminergic, and serotoninergic recep- >
tors ) ( 33). %
Furthermore, it is now possible to identify
histochemically neurons in which the gene
for a particular neurotransmitter enzyme or
* ' ** *ik
peptide precursor is active by localizing the
**
* VS
messenger ribonucleic acid ( mRNA ) that en -
codes the molecule. Most methods for detect-
ing mRNA are based on the phenomenon of
nucleic acid hybridization, which implies that
single strands of a nucleic acid polymer will
pair if the sequence of bases is complemen-
tary or homologous. This approach can be
applied to the nervous tissue via a technique
called in situ hybridization . This method uses
radiolabeled copied deoxyribonucleic acid
(cDNA ) encoding the peptide of interest,
which is applied to tissue sections under con-
ditions suitable for hybridizing with endoge-
nous mRNA . If the probes are radiolabeled,
autoradiography reveals the location of neu-
rons that contain the complex formed be-
tween the labeled cDNA and the homologous
mRNA ( Fig . 5.6 ) ( 26, 152). Quantitative meth -
ods (autoradiographic grain counting ) can
••
B
also be used to study the variations in the ex-
pression of a given peptide under specific ex- Figure 5.6. A . Dark -field photomicrograph of autoradi
perimental conditions. These very powerful ographically labeled neurons (clusters of silver grains) in
techniques, which can be combined with ret- the substantia nigra pars compacta of the rat These .
dopaminergic neurons have been visualized with in situ

rograde fluorescent tract-tracing methods hybridization using a molecular probe for tyrosine hy-
( 28), allow a molecular biology approach to
droxylase mRNA ( x 350) . B. Bright -field photomicrograph
the study of the nervous tissue. of a neuron autoradiographically labeled in the substan-
tia nigra pars compacta with a tyrosine hydroxylase ribo-
probe as in A. The cell body ( arrow ) and proximal den-
Receptor Localization drites ( arrowheads) are covered by a high number of
silver grains indicating a wide distribution of this mRNA in
Receptors for various neurotransmitters dopaminergic neurons ( x 550)
can be visualized by autoradiography, im -
munocytochemistry, and in situ hybridiza-
tion methods. Receptor autoradiography in- immunocytochemistry, and 2-deoxyglucose
volves the identification of receptors in autoradiographic studies ( 65).
tissue sections with the use of pharmaco- Recently, the molecular biology approach
logic binding techniques. Frozen sections are was used to isolate and clone several trans-
incubated with specific tritium -labeled lig- mitter receptors, such as the dopaminergic re-
ands and apposed to sheets of x -ray sensi- ceptors (186 ). Since the amino acid sequences
live film in the dark room. The x-ray films of these proteins were deciphered , cDNA or
are exposed for the appropriate amount of cRNA probes and specific antibodies are
time and developed . Densitometric mea - available to study the distribution of these re-
surements are made over regions of the au - ceptors with in situ hybridization and im -
toradiographs, as well as the appropriate co- munocytochemistry.
exposed calibrated standards. The data are
then expressed as binding site density per Metabolic Methods
unit weight of tissue. Results obtained from
receptor autoradiographic studies have com - Since there is a general correlation be-
plemented our knowledge of brain func- tween glucose metabolism and functional ac-
tional anatomy derived from tract - tracing, tivity of neurons, a method has been devel-
RECEPTOR NEURONS MOTOR

Olfactory Auditory Cutaneous NEURON
Dendritic
zone
Axon
origin
Axon
Telaxon
TO
Synaptic endings Nerve endings
in muscle
Figure 5.7. Three sensory neurons and a motor neuron based on the site of impulse origin rather than location of cell
body . Dendritic zone is concerned with the generator potential in a receptor, as well as excitatory and inhibitory
input of synoptic endings (dotted lines on motor neurons) on another nerve cell The axon and its terminals are re-
lated to the conduction and synaptic transmission of the generated nerve impulse The perikaryon of a neuron is the
trophic center primarily concerned with the outgrowth and maintenance of processes, and their metabolic functions
other than membrane activity Note that the cell body may be located either in the dendritic zone or the region of
the axon
oped to study regional variations in energy some early onset genes, such as the proto-
metabolism based upon the autoradiographic oncogene c- fos , which acts as a nuclear tran -
.
analysis of [ l 4C ] 2-deoxyglucose ( 2- DC ) incor- scription factor and is often considered as a
poration (181 ). This chemical compound is an -
"third messenger." This proto oncogene and
analog of glucose which is transported from its protein product Fos can be activated in
blood to neurons where it is taken up as if it certain neuronal systems by various stimuli
was glucose and phosphorylated to 2-de- and under specific experimental conditions.
oxyglucose-6- phosphate ( 2- DG-6P04). In con- For instance, dopaminergic agonists produce
trast to glucose, however, 2- DG-6 P04 is not a rapid and transient increase in Fos protein
metabolized further, and its accumulation in levels in the striatum and cerebral cortex
neurons is related to the rate of glucose uti- (157). Likewise, exposure of rodents to light
-
lization of the cell. The 2 deoxyglucose method or noxious stimuli can induce the expression
has proved useful in studying cellular and of different early onset genes, including c- fos ,
synaptic regions active following specific in the cells of the different brain nuclei specif -
forms of sensory stimulation or during repet - ically concerned with the processing of visual
itive movements. However, in terms of and nociceptive information (55, 162). The
anatomic localization , the 2- DG method has a levels of c - fos in the nuclei of neurons that are
relatively poor degree of resolution . activated by various stimuli can be estimated
Another means of monitoring the neu- by immunocytochemistry with antibodies
ronal activity is to visualize the expression of raised against the Fos protein, or by in situ
5 Neurons 143
Figure 5.8 . Characteristic neurons whose axons (A) and dendrites remain within the central nervous system A. Neu-
ron of inferior olivary nucleus B. Granule cell of cerebellar cortex C. Small cell of reticular formation D Small gelati-
nosa cell of the spinal trigeminal nucleus . E. Ovoid cell of nucleus tractus solitarius . F. Large cell of reticular formation.
G. Spindle- shaped cell of substantia gelatinosa of spinal cord H. Large cell of spinal trigeminal nucleus I. Neuron of
putamen J. Double pyramidal cell in Ammon's horn of hippocampal formation K. Cell from thalamic nucleus L. Cell
from globus pallidus. (Golgi preparations, macaque monkeys )
hybridization with cRNA or cDNA probes Golgi ( 70, 71 ). The second type of interneu -
for c- fos . rons is termed either relay , principal , or projec-
tion neurons and correspond to the long axon
NEURONAL DIVERSITY Golgi type 1 neurons. In most regions of the
central nervous system , the Golgi type II neu -
Functionally, neurons of the central ner- rons greatly outnumber the Golgi type I neu-
vous system can be grouped into three broad rons.
categories: afferent, motor, and interneurons. Neurons belonging to each of these three
Afferent or sensory neurons convey informa- categories display a wide variation in size
tion from the periphery to the central nervous and an infinite variety in the arrangement of
system, whereas motor neurons send com- their processes. However, nerve cells serving
mands to muscles and glands. The remaining a similar function or located in a given region
— —
cells the interneurons are by far the most of the nervous system often resemble each
abundant signaling elements in the central other structurally ( Figs. 5.2, 5.8, and 5.10).
nervous system. Their role is to either process Thus, bipolar neurons are sensory in function
the information locally or to convey the infor- and transmit impulses generated by olfac-
mation from one region of the central ner- tory, visual, vestibular, and auditory receptor
vous system to another (97). The first type of endings ( Fig. 5.10A ). The T-shaped unipolar
interneurons is variably termed local interneu- neurons are characteristic of the spinal ganglia
rons, internuncial neurons , local circuit neurons , and mesencephalic nucleus of the trigeminal
or simply interneurons , and corresponds to nerve ( N . V ) ( Figs. 5.2A and 5.10 B- D ). These
the short axon type II neurons as defined by cells are occasionally referred to as pseudo-
Dendritic branches
with gemmules
3,
Apical
dendrite
\
Axon
Purkinje cell of
cerebellar cortex '• Axon
Pyramidol cell of
cerebral cortex
Figure 5.9. Two principal cell types In cerebellar and cerebral cortex . Dendritic branches provide extensive area for
synaptic terminals of many cortical and subcortical neurons (Golgi preparations, macaque monkeys,)
SENSORY NEURONS
SYMPATHETIC NEURONS
PARASYMPATHETIC NEURONS
Figure 5.10. Representative neurons whose axons (A) are distributed in the peripheral nervous system of humans.
Capsular nuclei are shown around all ganglion cells The central (C) and peripheral (P) processes of the sensory neu-
rons are identified. A. Bipolar neuron of nodose ganglion (newborn) B. Pseudo -unipolar neurons of nodose ganglion
(newborn) C. Unipolar neuron of dorsal root ganglion (newborn). D. Unipolar neuron of trigeminal ganglion (new -
born) E. Multipolar neuron of intermediolateral nucleus of spinal cord F. Neuron of superior cervical ganglion (new -
born). G and H. Stellate ganglion neurons. I. Neuron of dorsal motor nucleus of vagus nerve J. Ciliary ganglion neuron
(newborn) K . Intracardiac ganglion neuron L. Myenteric ganglion neuron M. Nucleus ambiguus neuron N. Neuron
of hypoglossal motor nucleus. O. Anterior hom cell
unipolar because they develop from bipolar the pyramidal cell ( Fig. 5.9 ). The brushlike
neurons, in which the initial portion of the spread of dendrites of the Purkinje cell is sim-
two processes approximate and eventually ilar to that of other central integrating neu -
fuse. Such sensory neurons convey nerve rons ( Fig. 5.8 A and I - K ), yet each has individ -
impulses from a variety of specialized and ual characteristics. The large pyramidal cell
nonspecialized receptors. Multipolar neurons ( Fig. 5.9) also has an extensive dendritic
transmit both sensory and motor nerve im- spread and tiny dendritic spines. However,
pulses, and are characteristic of the brain, its basic structure more closely resembles that
spinal cord , and peripheral autonomic ner- of a motor neuron ( Figs. 5.8F and L, and 5.101
vous system ( Figs. 5.2 B- F, 5.8, and 5.10). The and M -O ). Successful Golgi preparations per-
primary , secondary, and tertiary dendritic mit following the processes of a neuron for
branches of some multipolar neurons may be considerable distances. Studies using this
elaborate and enormously increase its synap- method provide clearer concepts of neuron
tic surface ( Figs. 5.8 and 5.9). A Purkinje cell structure, dendritic ramification, and axonal
of the cerebellar cortex serves as an illustra - distribution (167).
tive example. The somatic and visceral neurons of the
The dendrites of Purkinje cells are wide at central and peripheral nervous systems of
the base, and taper rapidly. The primary, sec- humans can be compared in Figure 5.10. The
ondary , and tertiary branches have a smooth peripheral processes and axons of such neu-
surface, while the more distal dendritic rons form the peripheral, cranial, and spinal
branches are studded with thornlike pro- nerves. Nerve cells of the sensory and auto-
cesses called dendritic spines or feminities ( Fig. nomic ganglia are surrounded by a thin, nu -
5.9). The length of the spiny dendritic cleated capsule.
branches of a single Purkinje cell was esti- Although nerve cells in most regions of the
mated to be 40,700 pm , whereas these den - central nervous system do not undergo mi -
dritic branchlets with their 61,000 spines have totic division after birth, they probably in-
a combined synaptic surface area of 222,000 crease in size as their axons and dendrites
pm 2 ( 57). These estimates of the spiny grow in length . The length of some nerve
branchlets are now believed to be too conser- axons is quite remarkable. Giant pyramidal
vative, and probably should be doubled (58). cells of the cerebral cortex may send axons to
This extremely large receptive field is known the caudal tip of the spinal cord , that is from
to receive approximately 150,000 synaptic the top of the head to the lumbar region of
contacts. the spinal cord ( Fig. 11.13). Axons of motor
Arborizations of neurons in other parts of neurons in the spinal cord may extend the
the central nervous system are less extensive, length of the lower extremity to terminate in
yet they reveal a characteristic pattern of muscle fibers of the toes. A sensory unipolar
branching. For example, nerve cells of the in- neuron situated in the first sacral spinal gan-
ferior olivary nuclear complex in the medulla glion may send a peripheral fiber to one of
( Fig. 5.8A ) have radiating dendrites with the toes, while its central fiber may ascend
curly branches, whereas neurons of the thala- the length of the spinal cord and terminate in
mus ( Fig. 5.8K ) have long radiating dendrites the medulla ( Fig. 11.1 ). The total length of
with numerous branches. The cells of the sub- such a neuron would be from the toe to the
stantia gelatinosa of the spinal cord , best seen nape of the neck. The size of the cell body
in stained longitudinal sections, demonstrate fluctuates within wide limits, from a diame-
only a few large dendrites that issue chiefly ter of 4 pm in the smallest granule cells of the
from one side of the cell ( Fig. 5.8G ) . Smaller cerebellum ( Fig. 5.8B ) and cerebral cortex to
branches of these dendrites form a compact well over 100 pm in the largest motor cells of
zone of fine parallel fibers. the spinal cord . In general, the size of the cell
It is instructive to compare the profuse body is proportional to the length, thickness,
dendritic branches of the central sensory and richness of branchings, and terminal ar-
integrating neurons ( Fig. 5.8A, B, D, E, and borizations of its dendrites and axon .
G - K ) with the robust dendrites of motor neu-
rons ( Figs. 5.8C, F, L, and 5.10 M -O ). This NEURONAL CYTOSKELETON
comparison is even more striking if one con-
trasts the two principal cell types of the cere- The shape of the neuron is generated and
—
bellar and cerebral cortex the Purkinje and maintained largely by a multitude of fibril-
5 Neurons 147
lary proteins that form complex and dynamic to facilitate their visualization. Each molecule
networks extending throughout the neuronal of colchicine binds tightly to one tubulin mol -
cytoplasm . These long polypeptide chains ecule and thus prevents its polymerization.
undergo profound changes during aging in By disturbing the complex dynamics of mi-
certain neurodegenerative disorders, such as crotubules assembly, colchicine blocks the ax -
in Alzheimer's and Parkinson's diseases. onal transport and causes an accumulation in
These major constituents of the neuronal cy- the cell body of neurotransmitters and other
toskeleton differ from one another by their molecules that are normally conveyed to the
thickness and molecular composition . They distal ends of the axon through axonal flow.
can be grouped into three broad categories: Two major classes of microtubule-associ-
microtubules, neurofilaments, and microfila - ated proteins ( MAPs ) have been isolated
ments, together with their associated proteins from the brain: high- molecular- weight proteins
(171 ). ( / / MIA proteins ) , which have molecular
weights of 200,000-300,000 or more, and
Microtubules tau proteins , with molecular weights of
-
40,000-60,000 (3). High molecular-weight
These are the thickest cytoskeletal fibril- MAPs, particularly MAP-2, abound in cell
lary components with an outer diameter of bodies and dendrites, whereas tau proteins
25.28 nm. They consist of a ring of 13 protofil- and MAP-3 tend to be segregated in the axon.
aments with a clear lumen, which has a rod - Thus, certain MAPs can specifically label
like structure in its center (150 ). Each protofil - axons and dendrites, and such molecular
ament is formed by the polymerization of markers are very useful in differentiating ax -
a - and p- tubulin dimers ( molecular weight onal from dendritic profiles in developing
100,000 ), which are encoded by a multigene neurons, both in vitro and in vivo. MAPs regu -
family comprising at least six genes. Micro- late the stability of microtubules and promote
tubules have an inherent polarity because their oriented polymerization or assembly.
their tubulin subunits are arranged in a spe- Tau binds to several tubulin molecules simul -
cific orientation in the polymer. Their two taneously, enhancing their polymerization.
ends differ and grow at different rates. In the Other MAPs also enhance microtubule poly-
axon , microtubules are oriented longitudi- merization , but differ in being composed of
nally with polarity always in the same direc- two domains, one that binds to the micro-
tion , an arrangement that appears important tubules and another that extends outward
for the directional specificity of the two forms and is likely to be involved in cross-linking
of fast axonal transport . All microtubules in microtubules to other cellular components.
axons are oriented with their ( + ) ends ( fast Furthermore, MAP-2 and tau can serve as
growing ends) away from the cell body, substrates for both the cAMP-dependent and
whereas in dendrites comparable numbers the Ca 2 ' / calmodulin-dependent protein ki-
—
are found with the ( + ) ends and the ( ) ends
distally oriented . Recent evidence indicates
nases. Phosphorylation of MAPs decreases
their ability to promote assembly and pro-
that the orientation of microtubule polarity duces depolarization of the microtubules.
may play a crucial role in the differential Such a phenomenon is greatly exacerbated in
routing of organelles in dendrites and axons aging neurons and in neurons involved in de-
(13). For instance, the microtubule polariza - generative processes.
tion could explain why ribosomes and Golgi
elements are present in dendrites, but are ab- Neurofilaments
sent from axons. In the axoplasm of periph-
eral and central nerves, one usually can see These are the most abundant fibrillary
microtubules, as well as strands of canaliculi, components in the axon, being three to ten
vesicles of endoplasmic reticulum , and a few times more numerous than microtubules. The
ribosomes ( Fig. 5.23). neurofilaments are about 10 nm in diameter
Microtubules are highly labile molecules and represent the bones of the cytoskeleton
that are sensitive to specific antimitotic drugs, ( Fig. 5.40) . The neurofilaments observed in
such as colchicine. Colchicine, an alkaloid ex- electron microscopy become aggregated dur-
tracted from the meadow saffron , is used in ing some types of fixation and form the neu -
experimental animals to increase the level of rofibrils , which were observed with the light
certain neuroactive peptides in the cell body microscope for the first time by the German
neurologist Robert Remak in the midst of the tration of monomers and polymers, the latter
19th century ( Fig. 5.16). These neurofibrils are being more stable than free monomers. Tread -
the neuronal elements that retain silver ni - milling is a process of directional polymeriza-
trate used in Golgi stains. They are built with tion that requires the energy of a nucleotide
fibers that twist around each other to produce triphosphate to occur. This process can in-
complex coiled structures of increasing thick- duce the rapid growth or disappearance of
ness (10). Neurofilaments are biochemically microtubules, and thus can play a crucial role
related to the intermediate filaments of other in the growth and extension of neurites dur-
cells, all of which belong to a family of pro- ing development. Dynamic instability is an-
teins termed cytokeratins , which includes vi- other complex energy-dependent process
mentin, glial fibrillary acidic protein, desmin, whereby microtubules can abruptly change
and keratin (3, 172). In contrast to micro- their length. In this case, any microtubule
tubules, neurofilaments are rather stable and that happens to encounter a structure that
remain totally polymerized in the cell. Neu- caps its free ( + ) end will be selectively stabi-
rofilaments are among the most phosphory- lized, while other microtubules will depolar-
lated neuronal proteins, and this phosphory- ize (3, 20, 171). This dynamic instability of mi-
lation has direct implications for neurofilament crotubules is said to provide an organizing
function in normal neurons and disease states principle for neuronal morphogenesis. In
characterized by neurofibrillary pathology. fact, dynamic instability plays a crucial role
For instance, in Alzheimer's disease and in in the constant remodeling of cytoskeleton ar-
other neurodegenerative disorders, these fib- chitecture, which is necessary for axonal
rillary proteins are modified and form the so- growth and guidance, signal transduction,
called neurofibrillary tangles (104). and many other fundamental aspects of neu-
ronal function.
Microfilaments
NERVE CELL BODY
Microfilaments are the thinnest of all fibril-
lary components of the cytoskeleton, with a The nerve cell body or soma consists of a
diameter of 3-5 nm. They are composed of nucleus surrounded by a mass of cytoplasm
two strands of polymerized globular (G ) actin whose surface layer forms a delicate plasma
monomers arranged in a helix. Actins, a membrane. It is the trophic center of the neu -
major constituent of all cells, are encoded by ron, and the function and survival of the axon
a gene family that includes, in addition to the and dendrites, which constitute more than
a -actin of skeletal muscles, at least two other 90% of the total volume of the neuron, are de-
forms ( p and y ). Neural actin is a mixture of p pendent on the integrity of the cell body. This
and y species, which differs from a-actin at was first appreciated by the English physiolo-
only a few amino acid residues. Microfila- gist Augustus Waller who, in 1861, referred
ments are attached to the plasma membrane to the cell body of the neuron as "a centre of
by several associated proteins linked to actin nutritive energy." The soma of the neuron
(spectrin, ankyrin, vinculin, and talin ), al- appears as a fine structure in stained sections
though the major anchoring protein in neu- when viewed with the light microscope ( Figs.
rons as in other cells is fondrin or neural spec- 5.2 and 5.11 ). When observed with the elec-
trin ( 3, 171) tron microscope, the plasma membrane, or
plasmalemma ( Fig. 5.13), has a three-layered
Dynamics of Polymerization appearance similar to that of most tissue cells.
It delimits sharply the cytoplasm of the neu -
It is important to realize that, in contrast to ron ( neuroplasm ) from adjacent processes of
the bones that form the body skeleton, the other nerve cells and from neuroglial and
various elements of the neuronal cytoskele- connective tissue cells and fibers. The compo-
ton vary constantly in size and are in a state sition of the neuronal cell membrane is of
of continuous flux in the neurons. Three particular importance because of its role in
major processes of polymerization are recog- the initiation and propagation of action po-
nized: self -assembly, treadmilling, and dy- tentials. The plasma membrane is formed by
namic instability. Self -assembly is the simplest two layers of phospholipid molecules whose
way all fibrillary proteins polymerize. It de- hydrophobic hydrocarbon chains are all di-
pends on an equilibrium between the concen- rected toward the middle. Numerous protein
5 Neurons 149
. .
Figure 5.11. A. Nucleolar satellite in motor cell of spinal cord. B. Betz cell of motor cortex (female cat cresyl violet
x 1200) .
molecules are embedded in this structure and Nucleus

some of them extend throughout the entire
width of the membrane providing hy- This spherical structure has a diameter
drophilic channels through which inorganic that varies from 3-18 |xm. It is usually cen -
ions may enter and leave the cell. Other pro- trally located and its size is generally propor-
teins have side chains bearing carbohydrate tional to the size of the neuron ( Fig. 5.10 ). Be-
groups that form, on the external surface, the cause mature neurons cannot divide, the
outermost layer of the cell membrane known chromosomes are not arranged in compact
as the glycocalyx or cell coat. Action poten- structures. Instead , small aggregates of de -
tials are propagated through ionic changes oxyribonucleic acid ( DNA ) are scattered in a
that occur along the cell membrane of the somewhat homogeneous nucleoplasm and
neuronal surface. account for the pale appearance of the nu -
The cytoplasm of a neuron in a routinely cleus, even when viewed in the electron mi-
stained section appears basophilic and has a croscope ( Figs. 5.2 and 5.13). Usually, one
large, pale nucleus with a prominent nucleo- deeply staining nucleolus occupies a promi-
lus. After appropriate staining procedures, nent position in the nucleus. The nuclear
one also can demonstrate, within the cyto- membrane seen with the light microscope ap -
plasm of nerve cells, neurofibrils, chro- pears sharp and continuous, while electron
mophilic substance ( Nissl bodies), Golgi ap- micrographs reveal it as a double-layered
paratus, mitochondria , at times a central membrane, periodically interrupted by nu -
body, and various inclusions such as pigment clear pores ( Fig. 5.13) through which nucleic
and lipids ( Fig. 5.12). Neurofibrils are charac- acid materials can migrate. The two leaflets of
teristic of nerve cells, whereas the other cyto- the nuclear membrane are continuous only at
plasmic constituents are observed in other tis- the margin of the nuclear pores; the outer
sue cells. The cytoplasm extends throughout leaflet is continuous with the highly folded
the confines of the cell and all of its processes membranes of the endoplasmic reticulum .
and , in the axon, is often called axoplasm. As The nuclear pores have a diameter of 65 nm
observed by light microscopy, the cytoplasm and are arranged in rows with a center to - -
appears open and somewhat dispersed, center spacing of approximately 150 nm . The
whereas it has a compact and crowded ap- nuclei of Purkinje cells have a nuclear mem -
pearance in electron micrographs ( Fig. 5.13). brane that is wrinkled or puckered on the
Many of the neuronal structures seen by light side facing the origin of the dendritic tree
microscopy require specific stains (e.g., neu- (144). This irregular depression in the nu -
rofibrils, mitochondria , Golgi apparatus, cleus, stuffed with granular or rough endo -
Nissl bodies, and lipids), while most of these plasmic reticulum ( Fig. 5.14), has been called
constituents are visualized simultaneously the nuclear cap region. This region appears to
with the electron microscope. contain more nuclear pores than the smooth
Figure 5.12. Neuronal cell body showing major organelles as seen in electron micrographs ( 1) Nuclear membrane .
.
( 2) pores In nuclear membrane, ( 3) interior of nucleus (4) nucleolus, (5) Golgi apparatus, ( 6 ) smooth endoplasmic
. . . .
reticulum ( 7) granular or rough endoplasmic reticulum, ( 8) mitochondrion (?) microtubules ( 10) neurofilaments ( 11 )
. . . . .
axon hillock ( 1?) Initial segment of axon ( 13) soma (perikaryon) of cell ( 14) dendrites ( 15) pinocytotic vesicles ( 16 )
lipofuscin granule
portions of the nuclear membrane. For a because it contains many repetitive sequences
more detailed description of nuclear ultra - of DNA and RNA that display a more com-
structure, the student is referred to the stud - pact organization than the rest of the chromo-
ies of Palay and Chan-Palay (144 ) and Peters, somes, which remain in a dormant or un-
et al. (150). coiled state for most of the life of the neuron.
It is known to have positive histochemical re-
Nucleolus actions for several enzyme systems associ-
ated with respiration, energy production, and
This basophilic structure contains a large the synthesizing functions of the cell. It is
amount of RNA, as well as a diffuse coating particularly related to the production of nu -
of DNA . It also includes a specific portion of cleic acid and protein in nerve cells. In most
DNA encoding the RNA of future ribosomes electron micrographs, the nucleolus shows no
( rRNA ), which are complex cytoplasmic par- limiting membrane and the structure has a
ticles that serve as templates for protein syn- dense granular appearance. A "nucleolar
thesis. The nucleolus stains more intensely satellite" 1 (cm or less in diameter may be
than the rest of the nucleus with basic dyes found closely apposed to the nucleus in nerve
5 Neurons 151
» /. v * • » .
* '"
jP
t *-
5)
> £?« . ’ / Nuc
• <
* /*
: X
_ .... \- Vt' n
iM
v\ » *
\1V :V * -v. & *
: r «r
Figure 5.13. Part of a neuron in the posterior gray column (cat). The plasma membrane { PM) separates cytoplasmic
structures from glial fibers (Gf) and a synapse (sy) which are Identified in the adjacent neuropil. Part of the pale nu-
cleus (Nuc.) and the nuclear membrane (Nuc. m) appear to the upper left The cytoplasm demonstrates pouches
and vesicles of the Golgi complex (G). mitochondria (M), and an array of individual ribonucleoproteln particles.
Some appear as clumps or rosettes (polysomes), while some ribosomes are attached to the outer surface mem-
branes The parallel stacks of cisternae of the granular or rough endoplasmic reticulum (El7) are characteristic of Nissl
bodies ( X 75.000)
cells from female specimens (sex chromatin ) ( b)deoxyribonucleic acid ( DNA: the sugar
( 7 ) as shown in Figure 5.11 . is a deoxyribose-deoxypentose ) . Cytochemi -
cal methods indicate that nucleoproteins of
Chromophilic Substance the deoxyribose type are found chiefly in the
chromatin , which forms the spireme and
There are two main types of nucleic acid in chromosomes in mitosis and , during the in-
the cell: (a ) ribonucleic acid ( RNA : the sugar termitotic period , is partly represented by
of the nucleotide is a ribose-pentose ), and chromatin bodies known as karyosomes. De-
mm
[ t &-
mi M
k.
mi
..
eft
&
V, B&3 .^ -
2’
sfc
I SllIBrJllssllll*i
•tot
ft
f&PWMJW »: $3>
> .-
^ PiipIPip
u v 'wfc
Ir S' *
2 rfV*JSf
->
.
. î
\v W
WK ^< 5
a
sm: ^ 'îPm
*
,, '
-
A is •
^
w S ' '
*4
« ..., P
fpi* 4
)
' *
-
x .<- •
»v. >
«
\ L< M ?'
*
'
Figure 5.14. Purkinje cell nucleus in the rat The nuclear chromatin is thinly and uniformly distributed throughout the
nucleus, except for two sites indicated by arrows . The dendritic pole (DP) of the nucleus is wrinkled and capped by a
t
small Nissl body (N8) ( x 14,000)
oxyribonucleic acid is also found in the nude- clumps of granules known as Nissl ( tigroid )
olar satellite and in small quantities within bodies , after the German neuropathologist
the mitochondria ( Fig. 5.12 ). Conversely, the Franz Nissl ( Fig. 5.2E ). These staining proce-
true nucleolus is, as a rule, a dense, spherical, dures are often called Nissl stains . The Nissl
optically homogeneous body that is rich in ri- bodies are found in the cell bodies and den -
bonucleic acid . Similar ribonudeoproteins are drites of all large, and many of the smaller,
found in the cytoplasm, and there is good ev- cells, but are absent in the axon and in the
idence for the assumption that the nucleolus axon hillock from which that process arises,
plays an important part in cytoplasmic pro- They are most abundant and sharply defined
tein synthesis. in the larger cells, whose clear vesicular nu -
In preparations stained with basic aniline cleus contains practically no basichromatin
dyes (e.g., cresyl violet, toluidine blue, ( Figs. 5.2 and 5.11 ). The Nissl bodies are
thioneine), the chromophilic substance appears larger in motor than in sensory cells. At-
in the form of deeply staining granules or tempts have been made to distinguish the
5 Neurons 153
Figure 5.15 . Cytoplasm of a dorsal root ganglion cell The cytoplasm contains well-defined Nissl bodies ( NB) sepa -
rated by spaces containing microtubules (m) and neurofilaments (.nf ) Some ribosomes in the Nissl bodies are
arranged in rows attached to the outer surfaces of cisternae of the granular or rough endoplasmic reticulum (er),
while others lie free (r) in the cytoplasmic matrix Free ribosomes appear in rosettes of six or more members
(polysomes) G in the upper left indicates part of the Golgi apparatus ( x 46,000)
many neuron types by the size, shape, distri - sheets or membranes ( Figs. 5.13 and 5.15).
bution, and staining capacity of the chro- Dispersed free ribosomes also can be ob-
mophilic granules. served within the neuron cytoplasm. Free
The electron microscopic study of Palay and membrane bound ribosomes are loci for
and Palade ( 145) identified Nissl bodies as active protein synthesis ( Fig. 5.12 ). Neurons,
masses of granular or rough endoplasmic like most cells, produce proteins which are
reticulum ( RHR ). Clusters of punctate RNA used within the cell for both structural and
granules 10-30 nm in diameter, called ribo- metabolic purposes. A number of brain-spe-
somes, were oriented upon and between the cific proteins have been isolated biochemi-
cisterns, tubules, and vesicles to form a series cally, purified , and their cellular localization
-
of flattened , anastomosing, parallel arranged studied by immunocytochemical techniques
in these varicosities are long and slender, and

are arranged either parallel to the long axis of
the dendrite or form gentle swirls ( Fig. 5.17).
Mitochondria , which are about the size of
a bacterial cell, contain 2-10 copies of a small,
-
double stranded circular DNA molecule that
is exclusively maternally transmitted . Human
mitochondrial DNA ( mtDNA ) has been en-
tirely sequenced . The 16.6 kilobase mtDNA
encodes information for mitochondrial trans-
fer RNAs ( tRNA ) and rRNAs, which differ
from those of the rest of the cell, and form a
small number of mitochondrial proteins. The
rest of the mitochondrial proteins are en -
Figure 5.16. Large motor neurons from infant spinal coded by nuclear genes, synthesized on cyto-
cord showing neurofibrillary structures Portions of den- plasmic ribosomes, and then incorporated
drites and axons of other neurons fill the field (Ramon y into mitochondria . From a clinical point of
Cajal silver method)
view, it is worth noting that major deletions
and mutations of mtDNA may be responsible
(119). Additionally, most neurons synthesize for several human abnormal conditions or
neuroactive peptide or transmitters which are diseases, such as chloramphenicol resistance
secreted at the axon terminal. Following sec- and mitochondrial myopathies and en -
tion of the axon , alterations in the discrete cephalopathies (83).
structure of the Nissl bodies can be demon-
strated when stained by basic dyes and Peroxisomes
viewed with light microscopy ( Fig. 5.2E ).
Nissl bodies in the cytoplasm about the nu - These small organelles (diameter of about
cleus appear dispersed or dissolved , a phe- 0.25-0.5 p.m ) are bounded by a single mem -
nomenon termed chromntoli/ sis (see section on brane and represent a highly concentrated
retrograde degeneration ). source of oxidative enzyme, such as catalase,
which form up to 40% of its total protein con-
Mitochondria tent . Microsomes (also called microbodies) do
Granular or filamentous mitochondria are
not contain DNA or ribosome, and thus re -
semble the endoplasmic reticulum in being
scattered throughout the entire cell body, a self -replicating membrane-bounded orga -
dendrites, and axon ( Figs. 5.13, 5.17, and nelle that exists without a genome of its own .
5.27). These organelles occur even in the They sometimes stand out in electron micro-
smallest ramifications and terminals of the
neuron and are prominent electron micro-
graphs because of the presence of a “crystal -
loid " core composed of urate oxidase. Like
scopic features wherever intense metabolic mitochondria , peroxisomes are a major site of
activity occurs, such as at synapses and at oxygen utilization . They are believed to play
sensory and motor endings (145). These a role in detoxification through peroxidation
widely distributed cytoplasmic organelles are reactions, and in preventing accumulation of
involved in glycolysis, biosynthesis, and cell strong oxidizing agents, such as hydrogen
respiration, but their most important function
is to serve as a source of energy for the cell.
peroxide ( H;0:) which is believed to be in -
volved in the complex metabolic cascade
During cell respiration the enzymatic break- leading to neurodegeneration in certain dis-
down of carbohydrates and amino acids
yields C02, water, and energy. The energy,
eases. It has been hypothesized that peroxi -
somes are a vestige of an ancient organelle
bound in adenosine triphosphate ( ATP), is that carried out all the oxygen metabolism in
utilized in the transport of ions across cell the primitive ancestors of eukaryotic cells ( 3).
membranes and protein synthesis. The mito-
chondria ( Figs. 5.13-5.15, 5.27, and 5.30 ) are Centrosome
recognized easily in most electron micro-
graphs. The growing tips of dendrites often A microcentrum often is demonstrated in
exhibit varicosities or swellings which are neuroblasts. It consists of one or two granules
filled with mitochondria (183). Mitochondria surrounded by a clear cytoplasmic area . In
5 Neurons 155
. «•
Figure 5.17. Dendritic expansion (D£) filled with mitochondria (mif )

and glycogen (g/y) granules . This growing dendritic tip shows a
filopodia-like expansion (arrow) and has two axon terminals ( AT)
synapsing upon its surface. Dendritic profiles of this type are abun-
dant in the dorsal part of the lateral vestibular nucleus of the rat
( X 39.000).
Golgi Apparatus
The Golgi complex, a specialization of the
agranular or smooth endoplasmic reticulum
(SER ), is highly developed in nerve cells ( Fig.
5.12 ). In electron micrographs, the Golgi ap-
paratus appears as stacks of closely packed
agranular membranous cisternae associated
with vacuoles and vesicles. Their close pack-
ing ( Fig. 5.15) and the absence of ribosomes,
either free or attached , distinguish the Golgi
apparatus from the agranular or smooth en-
doplasmic reticulum and the Nissl substance
(150 ) . In glandular epithelial cells, the Golgi
apparatus is involved in the segregation of
secretory proteins into membrane bound
vesicles. In the region of the Golgi apparatus,
sugars are added to protein to form glycopro-
teins. It is possible that different cisternae
within the Golgi complex may perform dif -
ferent functions. The innermost Golgi cister-
nae contain acid phosphatase and the "alveo-
late vesicles" of this region are enriched in
hydrolytic enzymes (150). Thus, the Golgi ap-
paratus may be associated with the produc-
tion of lysosomes, which contain hydrolases
that break down protein, carbohydrates and
Figure 5.18. Different types of terminal boutons A. Two nucleic acids (94 ).
PHA- L-labeled terminal boutons ( asterisks ) forming asym-
metric synapses (arrowheads) with dendrites ( d) of stri -
atal neurons after injection of this anterograde tracer
into the parafascicular thalamic nucleus in the squirrel
Inclusion Bodies
monkey The presence of the anterograde tracer is Indi-
cated by a dense immunoprecipitate in the terminal
In addition to the organelles described ear-
boutons and the asymmetric nature of the synaptic con- lier, some nerve cells demonstrate dense cy-
tacts is revealed by the abundant electron-dense mate- toplasmic bodies and pigment granules. Most
rial lying along the postsynaptic membrane. Note the of the larger adult nerve cells contain a yel-
presence of an unlabeled terminal bouton ( star ) con-
lowish auto-fluorescent pigment known as
taining several small electron-lucent vesicles. This bouton
forms a synapse with the head of a spine (sp) that is in di- lipoclirowe or lipofuscin. The amount found
rect continuity with a dendrite ( d ) contacted by one of within nerve cells increases with age, and ap-
the PHA - L -labeled terminal bouton. B Large PHA -L-la-
beled terminal bouton ( asterisk ) forming a symmetric
pears in the form of granules which are usu -
synapse ( arrowheads ) with the perikarya of a neuron of
ally aggregated in a dense mass in some part
the subthalamic nucleus following injection of the an-
of the cell body ( Fig. 5.2 B ). Occasionally, they
terograde tracer into the globus pallidus of the rat Note may be dispersed throughout the cell. They
the absence of abundant electron-dense material at are insoluble in the usual lipoid solvents and
the postsynaptic membrane level in this case , cy cyto- are blackened by osmic acid . The cells of the
plasm; n: nucleus
newborn do not contain the pigment, which
appears about the 6th year in the spinal gan -
some instances, fine wavy fibrils may radiate glia , a few years later in the spinal cord , and
from the clear area of cytoplasm. The signifi- after the 20th year in the cerebral cortex. Pig-
cance of the centrosome is puzzling, for adult ments increase in number with age, and dur-
neurons are incapable of cell division. How- ing senescence may occupy a large part of the
ever, Murray and Stout (131 ) demonstrated cytoplasm of some neurons ( 189). Both histo-
that adult human sympathetic ganglia could chemical and ultrastructural evidence sug-
survive, migrate, and occasionally divide mi- gest that lipofuscin granules are a form of
totically in tissue culture. As is the case in lysosome ( 49 ). Other histochemical studies
many nonneuronal cells, the centrosome may indicate there are really three types of gran-
-
also act as a microtubule organizing center in ules in the autonomic cells, namely, pig-
nerve cells. mented , nonpigmented , and neurosecretory
5 Neurons 157
( 132 ). Granules of a blackish pigment known toskeletal protein MAP-2, a protein consid -
as melanin or neuromelanin are found in the ered to be a marker for the dendritic cy -
substantia nigra, locus coeruleus, and certain toskeleton, and ( b) the mRNA encoding of
other pigmented cells scattered through the the u subunit of the Ca:* / calmodulin-depen -
brainstem . Neuromelanin is also found in dent protein kinase (CaM kinase II ) (185). It
spinal and sympathetic ganglion cells ( Fig. was also demonstrated conclusively that den -
5.2 A ). Melanin appears at the end of the first drites exhibit local protein synthesis and have
year and increases in amount until puberty, translationaily competent mRNA present in
after which it apparently remains constant the form of polyribosomes. In light of these
through senescence. results, it becomes crucial to know how neu -
rons target these specific mRNAs to cellular
SYNTHESIS OF NEURONAL PROTEINS microdomains at a distance from the nucleus.
Recent studies by Steward and Banker
Like in any other cells of the body, the in- (185) revealed three previously unknown
formation for the synthesis of proteins in neu - processes that can account for the differential
rons is encoded in the DNA of chromosomes distribution of mRNAs within neurons.
within the nucleus. This information can be These are (a ) a sorting mechanism that deter-
processed in two major ways: heredity and mines whether particular mRNAs will be
gene expression . Heredity refers to the process transported into dendrites or will remain in
whereby the genetic information is passed the cell body, ( b) a mechanism for transport -
from parent to daughter cell during cellular ing mRNAs selectively into dendrites and ,
division, whereas gene expression alludes to presumably, into the initial segments of
the multistep procedure through which a se- axons, and (c) a mechanism that docks
lected portion of the genetic information is mRNAs and associated translational machin -
transcribed into RNA and then translated into ery ( ribosomes) at postsynaptic sites (185).
proteins. In contrast to other tissues, cell divi- Much of the structural and functional differ-
sion is not possible in the adult nervous sys- ences that exist between the various neuronal
tem, so that in neurons genetic expression can compartments (dendrites, soma , axon, and
only occur through gene expression . Except axon terminals) heavily rely on these three
for the few proteins encoded by the mito- fundamental intracellular transport mecha-
chondrial genome, virtually all the macro- nisms. The molecular base of these transport
molecules of the neuron are made in the cell mechanisms has not yet been fully worked
body from messenger ribonucleic acids out.
( mRNA ) that are transcribed and spliced into The multitude of proteins in a neuron can
the nucleus. The various types of mRNAs are be grouped into three major categories: (a )
then exported from the nucleus to other re- proteins that are synthesized in the cytosol
gions of the cell body by passing through the and remain there, ( b) proteins that are syn-
pores of the nuclear membrane. The mRNAs thesized in the cytosol but are later incor-
that encode the different proteins form either porated into the nucleus, mitochondria, or
free polyribosomes ( polysomes) that are at - peroxisomes, and (c) proteins that are syn -
tached to the endoplasmic reticulum . The thesized in association with the cell mem-
mRNAs are translated on these polysomes. It brane system . In addition to encoding the pri -
must be mentioned that the brain expresses mary sequence of the proteins, the mRNAs
more of the total genetic information encoded contain information that, when translated
in DNA than does any other organ in the into polypeptide sequences, targets the new
body ( 171 ). This probably accounts for the protein to its final destination . Cytosolic pro-
extreme structural and functional diversity teins are by far the most abundant proteins in
encountered in the brain compared to other the neuron . They comprise the fibrillary ele-
organs. ments that form the cytoskeleton and numer -
The various mRNAs species are differen - ous soluble enzymes that catalyze the various
tially distributed in the neuron . Indeed, re- metabolic reactions of the neuron. The nu -
cent in situ hybridization studies revealed clear, mitochondrial, and peroxisomal pro-
that, although the majority of neuronal teins are targeted to the proper organelles
mRNAs are confined to the cell body, two soon after their synthesis by a mechanism
mRNA species are prominent in dendrites. called posttranslational importation . This
These two mRNAs are (a ) the mRNA encod - mechanism relies on specific receptors
ing the high molecular weight form of the cy- around nuclear pores that bind and translo -
Figure 5.19 . Results that can be obtained with immunocytochemistry alone or in combination with retrograde and
anterograde tract-tracing methods In the squirrel monkey . A . PHA -L injection site in the putamen. Note the presence
near the core of the Injection site (asterisk) of a few striatal neurons ( arrowheads) that have actively taken up the
tracer and display a Golgi-like appearance ( x 200). B. Dopaminergic neurons of the substantia nigra as visualized by
Immunocytochemistry with a highly specific monoclonal antibody raised against dopamine Itself ( x 300). C Sero- .
toninerglc neurons ( brown) of the dorsal raphe nucleus Intermingled with a few neurons retrogradely labeled with
cholera toxin B subunit ( dark blue, arrowheads) injected into the globus pallidus. Both serotonin and cholera toxin
were visualized immunocytochemically and immunoprecipitates were revealed by the chromogen diaminobenzi-
dine (DAB) and nickel-intensified diaminobenzidine ( NIDAB), respectively ( x 300) . D. Striatonigral fibers anterogradely
labeled with PHA -L injected into the caudate nucleus. A small contingent of these fibers ( arrowhead) arborize within
the substantia nigra pars reticulata ( SNr ) along the dorsal surface of the cerebral peduncle ( CP) . The presence of the
dopaminergic neurons of the substantia nigra pars compacta ( SNc ) was also revealed immunocytochemically in the
158
5 Neurons 159
cate these newly synthesized polypeptide SIGNALING MOLECULES

chains (171 ). Membrane proteins, which in -
cludes secretory proteins, are of three types: One of the characteristics of most nerve
membrane-spanning ( or integral ), anchored, cells is that they communicate with each
and associated . The names of these proteins other through the release of specific chemical
reflect the strength of their link with the messengers or signaling molecules at synap-
membrane system of the neuron. The differ - tic level. The concept of chemical transmis -
ent receptors that are found on the surface of sion is derived from the classical experiments
the neuronal membrane are typical mem - performed by Otto Loewi ( 121 ). Loewi
brane-spanning or integral proteins (see the demonstrated chemical transmission by
section on the synapses later ). transferring the ventricular fluid of a stimu -
Proteins are polypeptides or polymers of lated frog heart onto a nonstimulated frog
amino acids, with one end having a free heart, showing that the effects of the nerve
-
amino ( N terminal ) group and the other a stimulus were reproduced by the chemical
carboxyl (C- terminal ) group. Translation of activity of the solution flowing onto the sec-
the polypeptide chain always begins at the N- ond heart (30). In that particular case, the
terminal end . Cytosolic proteins are little neurotransmitter involved was acetylcholine,
modified or processed compared to mem - which was released by the vagus nerve inner-
brane proteins. In proteins destined to be vating the heart . The pharmacologic studies
modified, the modification can occur either of Henri Dale on cholinergic and adrenergic
during or after the polypeptide chain is transmission were also instrumental in the
synthesized . These modifications are respec- formulation of the chemical transmission
tively called colranslational and posltransla- concept (36).
ttonal . An example of important cotransla - To be accepted as neurotransmitters, a pu -
-
tional modifications is N acetylation, the tative chemical messenger must fulfill four
transfer of an acetyl group to the N -terminus criteria: (a ) it must be synthesized in the neu -
of the nascent polypeptide. An example of ron, ( b ) it must be present in the presynaptic
important posttranslational modifications is terminal and released in sufficient amount to
the addition of other functional groups to exert its supposed action on the postsynaptic
specific amino acid residues, such as phospho - neuron or the effector organ , (c ) when ap-
rylation and ubiquitination. Phosphorylation, plied exogenously in sufficient concentration,
which is reversible and involves protein ki - it must mimic exactly the action of the en-
nases, is the most common mechanism for al- dogenously released transmitter, and (d ) a
tering the biochemical function of a protein in specific mechanism for removing the pre-
any cell. Ubiquitination consists of adding sumed neurotransmitter from its site of ac-
ubiquitin , a highly conserved protein with tion must exist ( 30, 172 ). The demonstration
77 amino acid residues, to specific amino that a suspected chemical messenger indeed
acid residues throughout the protein mole- fulfills most of these criteria is extremely dif -
cule. Ubiquitination is believed to be a ficult, particularly for a molecule that is pre-
mechanism for tagging proteins for degra - sumed to act as a neurotransmitter at a spe-
dation by special proteases. It is a very im - cific region in the central nervous system .
portant mechanism for protein turnover Nevertheless, the recent development of new
in neurons. Ubiquitination is said to be and powerful methods to localize and phar -
greatly exacerbated in certain neurodegen - macologically characterize putative chemical
erative disorders, such as Alzheimer's dis- messengers has greatly helped the identifica -
ease. tion of synaptic transmitters. At present ,
same section with an antibody raised against the enzyme tyrosine hydroxylase (TH) PHA-L immunoreactivity was re -
vealed with NiDAB (dark blue precipitate), whereas TH was visualized with DAB (brown precipitate) ( > 200) E . Striato-
nigral fibers anterogradely labeled with PHA -L and displaying varicosities (arrowheads) in close contact with the prox -
imal dendrite of a TH-immunoreactive neuron of SNc . In this case. PHA - L immunoreactivity was revealed with NiDAB,
whereas TH-immunoreactivity was visualized with the new chromogen 3-amino-9-ethy!-carbazole (AEC). which ap-
pears red ( * 500) F Double anterograde labeling experiment involving injections of PHA - L and biocytin in two adja
.
cent areas of the putamen. The two types of anterogradely labeled fibers form terminal fields in the substantia nigra
that can be distinguished from one another by their color: the PHA -L-labeled fibers are dark blue (NIDAB). whereas
the biocytin- labeled fibers (arrowheads) are brown (DAB) ( x 200)
her of cholinergic neurons is surprisingly

small. These chemospecific neurons are
largely confined to various basal forebrain
nuclei, including the nucleus basalis of Meyn-
ert that projects widely to the cerebral cortex.
Acetylcholine is also the neurotransmitter
used by the spinal cord motor neurons whose
axon terminate at the nerve-skeletal muscle
junction, and by all preganglionic neurons of
the autonomic nervous system, as well as by
the postganglionic neurons of the parasym-
pathetic system.
Biogenic amines, also called monoamines,
includes the catecholamines ( dopamine, nor-
epinephrine, and epinephrine), that derive
Figute 5.20. Large motor neuron in the anterior gray
horn of an infant 's spinal cord revealing several den-
from the amino acid tyrosine, and the in-
drites and the origin of the axon. The axon arises from dolamine serotonin (or 5-hydroxy try pta -
the lower side of the cell body, tapers to a thin thread for mine), that derives from the amino acid tryp-
a short distance, and thickens at the point where the tophan . As their names imply, catecholamines
myelin sheath develops. Small neuroglial nuclei are
stained black (modified Weigert s stain) -
possess a catechol nucleus, a 3,4 dihydroxy-
lated benzene ring, and are part of a common
biosynthetic pathway with tyrosine hydroxy-
lase as the rate-limiting enzyme. Serotonin
there is a multitude of presumed neurotrans- belongs to a group of aromatic compounds
mitters, but these various signaling molecules called indoles, which is characterized by a
conveniently can be grouped into two broad five-membered ring containing nitrogen
—
categories small- molecule transmitter sub-
stances and neuroactive peptides (172 ).
joined to a benzene ring. Tryptophane hy-
droxylase is the rate limiting enzyme in the
synthesis of serotonin. Histamine is an imida -
Small signaling molecules zole derived from the amino acid histidine.
Although its biochemistry is remote from that
There are only eight low-molecular-weight of catecholamines and serotonin , it is often
chemical messengers that are actually recog- referred to as a biogenic amine. Biogenic
nized as transmitter substances. These signal- amines have been first visualized with the
ing molecules share many biochemical simi- help of the formaldehyde-induced fluores-
larities since they all are amines, and seven of cence method developed by Falck and
them are amino acids or their derivatives. Hillarp in Sweden ( 50, 51 ). They can now be
They are small , charged molecules that are studied in more detail with immunocyto-
synthesized through relatively short meta - chemical procedures and antibodies that
bolic pathways from precursors that ulti- have been raised against either the neuro-
mately derive from carbohydrate substrates transmitters themselves ( Fig. 5.15) or the dif -
of intermediary metabolism . These transmit - ferent enzymes involved in their synthesis
ters are ( a ) acetylcholine, ( b) the biogenic (91, 138). All three catecholamines and sero-
amines, comprising the catecholamines (do- tonin occur in specific brainstem nuclei,
pamine, norepinephrine, and epinephrine), whereas histamine is concentrated in certain
serotonin , and histamine, and (c) the amino neuronal populations of the hypothalamus
acids y-aminobutyric acid (GABA ), glycine, ( 30). At the periphery, norepinephrine is the
and glutamate. neurotransmitter used by postganglionic
Acetylcholine was one of the first neuro- neurons of the sympathetic nervous system .
transmitters to be identified . Yet, it was only In contrast to acetylcholine and biogenic
after the recent application of immunocyto- amines, which are synthesized only in certain
chemical procedures making use of antibod - neurons, the amino acid transmitters GABA,
—
ies able to recognize its synthesizing en-
zyme choline acetyltransferase (Ch AT) that
a proper knowledge of the anatomic organiza-
tion of brain cholinergic system began to
—
glutamate, and aspartate are intermediates in
general biochemical pathways. For instance,
glycine and glutamate are among the 20 com-
mon amino acids incorporated into proteins
emerge ( 128). In the human brain , the num- in all cells. Furthermore, glutamate is the im -
5 Neurons 161
mediate metabolic precursor of GABA. It is leased at the same axon terminals, as is the
thus surprising to see that the same amino case for acetylcholine and vasoactive intesti-
acid may act as transmitter in certain neurons nal peptide ( 25, 92, 93). In such a case, the
and be mostly involved in intermediary me- small signaling molecule usually acts much
tabolism in others. This dichotomy of func - more rapidly than the neuroactive peptide,
tion calls for a compartmentalization of the which often exerts a slow modulatory effect
two types of amino acids, that is the transmit- on the postsynaptic element . Since specific
ter amino acids must somehow be kept sepa- postsynaptic receptors exist for these two
rate from metabolic amino acids (30, 172). In classes of transmitters, cotransmission allows
the brain , glutamate is the major excitatory for a great diversity in the transfer of infor-
transmitter and GABA the major inhibitory mation (172).
transmitter. Glycine, which is probably de-
rived from serine, acts as an inhibitory trans- Neurosecretion
mitter in the spinal cord interneurons.
Certain neurons in the nervous system of
Neuroactive Peptides both vertebrates and invertebrates act as
neurohormonal transducers. These neurose -
Small -molecule transmitter substances can cretory neurons, which are particularly
be synthesized in all parts of the neurons, in
cluding axon terminals (180 ). In contrast,
- abundant at the level of the hypothalamo hy
pophysial system, transform the action po-
- -
neuroactive peptides derive from the pro- tential and chemical signaling they received
cessing of secretory proteins that are only into hormone secretion (9, 61, 142, 143,
formed in the cell body, so that neuroactive 164-166). Thus, neurosecretory neurons can
peptides must be transported to terminals be said to bridge the gap between the ner -
within vesicles by fast axonal transport. An - vous and endocrine systems. Morphologically,
other major difference between the two these neurons possess all the organelles that
classes of chemical messengers is that neu- are present in other neurons, but also display
roactive peptides are much more numerous some differences. For example, the neurofila -
and diversified than small -molecule trans- ments in the axon and its preterminal region
mitter substances. More than 50 neuroactive appear different from those found in other
peptides have been found to be pharmaco- neurons. The microtubules may be as thick as
-
logically active (Table 5.1 ). Interestingly, sev 30-50 nm in diameter, and the axons also dis-
eral of these peptides are also known to act play multilamellate bodies ( 9 ). Neurosecre-
as hormones outside the brain (e.g., an- tory neurons have unusually electron-dense
giotensin and gastrin ) or as products of material associated with Golgi membranes
neurosecretion (e.g., oxytocin, vasopressin, and a very prominent endoplasmic reticu -
and somatostatin ). Despite their diversity, lum . Secretory proteins are synthesized on
neuroactive peptides can be grouped into polyribosomes attached to the endoplasmic
about 10 large families whose members are reticulum and then move to the Golgi ap-
structurally related and often derived from a paratus where it is conjugated to a carrier
common large precursor protein ( polypro- protein, such as neurophysin in the case of
tein ). These large polyproteins are subse- oxytocin and vasopressin hormones. The hor -
quently processed within vesicles and several mones and the carrier protein are packaged
neuroactive peptides are produced through in dense core vesicles that are transported
specific proteolytic cleavages. Specific func- along the axon by fast axonal transport from
tions, such as modulation of pain (substance the cell body to the axon terminals. Large
P and enkephalin ) and control of emotional masses of secretory material ( Herring bodies )
states (adrenocorticotropin and (i-endorphin ) are observed along the axons of these neu -
have been attributed to certain neuroactive rons. The axon terminals containing neurose-
peptides. This topic is dealt with in subse- cretory vesicles are unique in that they abut a
quent chapters. perivascular space rather than another neu -
Because they are synthesized locally in the ron or effector cell. Their secretory product is
terminals, the small-molecule transmitters released by exocytosis into the perivascular
can be released very rapidly , whereas neu - space from where it can reach its distant tar-
roactive peptides are released more slowly. get sites through the blood (150). A typical
Peptides and small-molecule transmitters can example of such a system is the neurons of
coexist in the same neuron and even be core- the supraoptic and paraventricular hypothal -
Table 5.1 .
PARTIAL LIST OF BRAIN NEUROACTIVE PEPTIDES
HYPOTHALAMIC -RELEASING AMINO FUNCTIONS

HORMONES ACIDS
Thyrotropin - releasing hormone ( 3) Control of thyroid hormone

Gonadotropin - releasing hormone ( 10) Stimulation of gonadotropic cells
Somatostatin ( 14 ) Inhibition of secretion of GH
Corticotropin - releasing hormone (41 ) Inhibits gonadotropic cells
Growth hormone releasing hormone ( 44 ) Stimulation of secretion of GH
Luteinizing hormone releasing hormone ( 8) Regulates release of luteinizing hormone
NEUROHYPOPHYSEAL HORMONE
Vasopressin (9) Influences blood pressure

Oxytocin ( 9) Stimulates reproductive system
PITUITARY PEPTIDES
Adrenocorticotropic hormone ( 39) Stimulates adrenal steroid biosynthesis

P- Endorphin ( 31 ) Analgesia , emotion
a-Melanocyte -stimulating hormone (13) Unknown in mammals
Prolactin ( 199 ) Synthesis of milk proteins
Luteinizing hormone ( 96 ) Maturation of reproductive cells
Growth hormone (191 ) Skeletal and soft tissue growth
HEART- DERIVED PEPTIDE
Atrial natriuretic peptide ( 28 ) Control of salt and water intake
amic nuclei ( Fig. 17.18), which produce the eminence is involved in the elaboration and
nonapeptides vasopressin and oxytocin (6 ) control of various releasing hormones ( e.g.,
(see also Figs. 17.2 and 17.4 ). Vesicles contain- tyrotropin-releasing hormone and somato-
ing these hormones can be visualized at both statin ), which regulate the adenohypophysis.
light and electron microscopic levels in mate - Some of the small clear vesicles containing
rial prepared according to specific histochem
ical stains (e.g., chromhematoxylin- phloxine
- dense granules encountered in the nerve ter-
minals that occur in the median eminence re-
stain ). semble those found in adrenergic nerve ter-
In mammals, there is another important minals. This system is discussed further in
neurosecretory system in the hypothalamus Chapter 17.
represented by the arcuate nucleus and the
median eminence. Nerve fibers originating
AXONS
from the arcuate nucleus course into the me-
dian eminence and terminate in relationship The axon is a slender, usually long process
to the perivascular spaces, as described for which arises from a conical mass of special-
the supraoptico-hypophysial neurosecretory ized protoplasm known as the axon hillock . It
system ( Figs. 17.1 and 17.18). Granule-con - is distinguished from the cell body and den -
taining vesicles in these nerve endings are drites by the complete absence of Nissl bod -
smaller and of at least two types. The median ies, which also are lacking in the axon hillock.
5 Neurons 163
Table 5.1 . — continued

PARTIAL LIST OF BRAIN NEUROACTIVE PEPTIDES ( Continued )
GASTROINTESTINAL PEPTIDES AMINO FUNCTIONS

ACIDS
Vasoactive intestinal peptide ( 28 ) Relaxation of smooth muscle, stimulation

of exocrine and endocrine secretion
Cholecystokinin octapeptide (8 ) Induces satiety
Gastrin ( 34 ) Stimulation of gastric acid secretion
Calcitonin ( 32) Inhibits gastric acid secretion
Calcitonin gene- related peptide ( 37 ) Inhibits gastric acid secretion
Substance P (11 ) Stimulates gastrointestinal motility
Neurotensin (13) Inhibits gastric acid secretion
Methionin -enkephalin ( 5) Analgesia
Leucine-enkephalin (5) Analgesia
Insulin (51 ) Induces hypoglycemia
Glucagon (29 ) Induces hyperglycemia
Bombesin ( 14 ) Stimulation of many gastrointestinal
peptides
Secretin ( 27 ) Stimulates water secretion
Somatostatin ( 28) Nociception and pain signals
Motilin ( 22) Initiates myoelectric discharges
(gastric tract)
Neuropeptide Y ( 36) Inhibits gastric and pancreatic secretion
Polypeptide Y ( 36 ) Inhibits gastric and pancreatic secretion
Pancreatic polypeptide ( 36) Stimulates gastric and pancreatic
secretion
OTHERS
Angiotensin II (8) Influences blood pressure

Bradykinin ( 9) Stimulates contraction of smooth muscle
Carnosine ( 2) Sensory information
Dynorphin A ( 17 ) Analgesia
In smaller neurons, an axon hillock is not eas- (e.g., sensory neurons), or effector endings in
ily identified in light microscopic prepara - muscle and glands ( Figs. 5.3G, 5.7, and 10.23).
tions. The reason suggested by electron mi - In the central nervous system , axons may
croscopy is that in these small cells there is be myelinated or unmyelinated . The former
little difference between the cytoplasm of the possess a sheath of myelin for at least a por -
axon hillock and that of the neuronal cell tion of their course, whereas the latter are
body ( 150). As the axon hillock narrows into completely devoid of such a sheath . The
the initial axonal segment, there is a gradual oligodendrocyte forms and maintains the
diminution in the number of ribosomes, but myelin sheath within the brain and spinal
no abrupt change as suggested by light mi- cord , while the Schwann cell plays the same
croscopic descriptions. Beyond the initial role at the periphery. In the peripheral ner-
segment the axon contains mitochondria, vous system, both myelinated and unmyeli-
neurofilaments, microtubules, agranular en- nated fibers have, in addition, an outer deli-
doplasmic reticulum , vesicles, and multi- cate nucleated membrane, the sheatli of
vesicular bodies. No granular endoplasmic Schwann . The peripheral myelinated fiber is
reticulum or ribosomes are present. Distally, structurally the most differentiated , consist -
each axon breaks up into simple or extensive ing of axon (axis cylinder ), myelin, and
terminal arborizations, the telaxon. The latter sheath of Schwann. The myelin sheath is not
may be synaptic endings on other neurons continuous, but is interrupted at fairly regu -
Axon Axon
Neurofibrillae Neurofibrillae
Constriction of Constriction of
axon at node axon at node
Schwann—p Neurokeratin .
cell cytoplasm network r-
Incisure of -
I
Nucleus of — Schmidt -
Schawnn cell
Lantermann
Neurilemma
Neurilemma —
sheath
sheath
Myelin sheath
Myelin sheath
Node of Ranvier
Node of Ranvier
A B
Figure 5.21. A. and B. Peripheral myelin sheaths based on studies of living nerve fibers. Cross-sections of different
fixed preparations of the myelinated fibers are shown in the central portion of each drawing. The cross membrane is
not shown.
Figure 5.22. Nodal regions from peripheral ( PNS) (above) and central nervous system (C/VS) ( below ). In the PNS the
Schwann cell provides both an inner collar ( Si) and an outer collar (So) of cytoplasm in relation to the compact
myelin The outer collar (So) is extended into the nodal region as a series of loosely interdigitating processes . Terminat -
ing loops of the compact myelin come into close apposition to the axolemma in region near the node, apparently
providing some barrier ( arrow at "a ") for movement of material into or out of the periaxonal space ( asterisks). The
Schwann cell is covered externally by a basement membrane In the CNS the myelin ends similarly in terminal loops
( tO near the node, and there are periodic thickenings of the axolemma where the glial membrane is applied in para-
nodal region These may sen/e os diffusion barriers and thus confine the material in the periaxonal space ( asterisks ) so
that movement In the direction of the arrow at ' o' would be restrained. At many CNS nodes there is considerable ex -
tracellular space ( ECS) Compare with CNS node shown in Figure 5 21
5 Neurons 165
Figure 5.23. Node of Ranvier on nerve of spinal cord (cat). The oligoglial cytoplasm ( CY ) forms loops of myelin (M)
around the axon (Ax) and the node (N). Fusion points (fP) between the myelin and axon membranes are also shown.
Neurotubules ( /) and neurofilaments (NF) are identified in the axoplasm ( X 70.000)
lar intervals. The parts of the fiber free from Myelin

myelin appear as constrictions known as the STRUCTURAL ORGANIZATION
nodes of Ranvier, named after the French
pathologist Louis Antoine Ranvier who first The myelin sheath starts at a short dis -
described them at the end of the 19th century tance from the cell body ( Fig 5.20), the proxi-
( Figs. 5.3C and 5.21 ). In the fresh condition, mal portion of the axon, including the axon
the semifluid axon is homogeneous in ap- hillock, being as a rule unmyelinated . The
pearance and occasionally shows faint lon- sheath is of varying thicknesses and is com -
gitudinal striations. In silver stained prep- posed of a semifluid , doubly refracting sub-
arations, it consists of closely packed, stance known as myelin , which in the fresh
parallel-running neurofibrils embedded in a state has a glistening white appearance. Phys-
scanty amount of homogeneous axoplasm . In ical techniques have provided data concern -
most fixatives, the axon usually shrinks to a ing the orderly arrangement of lipoproteins
thin axial thread . With special methods of fix- that form myelin ( 168, 178). Studies based
ation and tissue embedding, its normal size upon polarized light, x-ray diffraction, and
may be more nearly approximated . electron microscopy have yielded a high de-
Between the axon and myelin sheath there gree of correlation and indicate that the
is a delicate layer or membrane known as the myelin sheath is composed of concentric lay -
axolemma ( Fig. 5.22). Although difficult to ers in which protein and lipid alternate. Lipid
demonstrate histologically, the membrane may molecules are radially oriented in their lay-
be seen in ultraviolet photographs of the living ers, while protein molecules are arranged
nerve fiber, since the axolemma shows a much tangentially. Myelin is composed of a funda -
greater ultraviolet absorption than the axon or mental, radially arranged repeating unit
the myelin sheath. The axolemma is part of the membrane with a spacing of 17-18.5 nm. The
neuron plasma membrane, and possesses a repeating unit membrane is formed of two
similar structure and specialized properties. It subunits, each consisting of a bimolecular
is easily identified in high magnification elec- lipid leaflet sandwiched between monolayers
tron micrographs as a delicate membrane sur- of protein . Each of these subunits corre-
rounding the axon ( Figs. 5.22 and 5.23). sponds to a single layer of plasma membrane
derived from the myelin-forming cell ( Figs. Four stages in the " jelly-roll theory" of
5.24 and 5.27 ). myelin formation are depicted in Figure 5.25.
With the limited magnification of light mi- In the peripheral nervous system, the myelin
croscopy, it was presumed that peripheral sheath represents concentric layers of the
myelinated nerves were enclosed by two sep- Schwann cell, while the oligodendrocyte as-
arate layers, the myelin and Schwann cell sumes the role of myelin formation within
sheaths. The histologic appearances of myeli- the central nervous system ( 20). In the latter
nated nerves in cross-section, when stained case, one oligodendrocyte may form a myelin
by the osmic acid and silver nitrate methods, layer on more than one axon ( Fig. 6.9). Note
are shown in Figure 5.3B and D . Electron mi - that the inner surfaces of the plasma mem-
croscopy studies revealed that myelin was branes come into apposition and fuse to form
formed primarily by a double-layered infold - major dense lines which are approximately 3
ing of the Schwann cell membrane, which be- nm thick . Between each major dense line is a
came wrapped spirally around the axon in less dense intraperiod line formed by the union
concentric layers (66, 158, 159). of the outer surfaces of the plasma mem-
Nuc .
m J
Nuc. M.
Figure 5.24. Small myelinated nerve fibers from rat dorsal root ganglion matured In tissue culture The infolding
plasma membrane ( PM) of the Schwann cell forms an external mesaxon ( EM) continuous with the outermost lamella
of the myelin sheath . An internal mesaxon (Im) surrounds the axon ( Ax ) and is continuous with the most internal
lamella of the myelin sheath. Note the small amount of Schwann cell cytoplasm (Cyf ) between the nuclear ( Nu , M )
and plasma membranes At the left are two unmyelinated axons associated with another Schwann cell ( X 27.000)
5 Neurons 167
branes ( Fig. 5.25). This fusion of membranes,

accompanied by a reduction in cell cyto-
plasm , results in the repeating series of light
and dark lines observed in electron micro-
graphs ( Figs. 5.24 and 5.27). Cytoplasmic
remnants of the Schwann cell infolding may
at times be identified at the axon- myelin junc-
tion ( Fig. 5.27A ). The primary infolding of the
Schwann cell membrane is often present as
an internal mesaxon ( Fig. 5.24). Continuity be-
tween the most superficial lamellae of the
myelin sheath and the Schwann cell plasma
membrane forms the external mesaxon ( Fig.
5.24 ).
These intimate relations of Schwann cell
and myelin are further amplified by the tis-
sue culture observations of several investiga -
tors ( 29, 151, 161 ) who found that myelina -
tion began in isolated segments near the
Schwann cell nucleus and extended along the
fiber to a node of Ranvier. Remyelination of
experimentally injured axons of the cat spinal
cord appears to resemble the mechanism
of myelination observed along peripheral
nerves and in tissue culture (18).
MOLECULAR ORGANIZATION
In the peripheral nervous system,
Schwann cells express a myelin -associated gly-
coprotein ( MAG ) early during myelination .
This protein becomes only a minor compo-
nent of mature (compact ) myelin, but may
play a crucial role in the initiation of the
myelination process. It is primarily found at
the margin of the myelin sheath just adjacent
to the axon . Its cellular location, structural
similarity to other surface recognition mole-
cules, and early expression in development
favor the view that MAG is important for the
initiation of myelination . There are two iso-
Figure 5.25. A- D. Stages in the development of the
forms of MAG with molecular weights of myelin sheath about the axon (A). Cytoplasm of the
68,900 and 64,000 generated from a single Schwann cell is stippled and its nucleus is indicated ( N)
gene through alternative RNA splicing. MAG After the initial phase of ensheathment ( A), oddifional lay-
belong to a superfamily of proteins related ers of cell cytoplasm become wrapped around the
axon (B and C) The cytoplasm Is then reduced In
to immunoglobulins and includes several amount and the double layered plasma membrane
cell-surface proteins, such as the neural comes into apposition (D) The outer membrane unit of
cell adhesion molecule ( NCAM ), whose role the Schwann cell will become the future intraperiod line
is important in cellular recognition (see .
of myelin. The dark line ( major dense line) represents the
Chapter 3). apposition of the inner (cytoplasmic) surfaces of the unit
membrane as shown In D . The Internal mesaxon is also In-
Myelin in both the central and peripheral dicated ( arrow In D)
nervous system is composed of the same
group of proteins originally called myelin basic
protein. Recent gene cloning methods revealed
that this group of profeins, previously consid-
ered as a single entity, consists of at least seven In unmyelinated axons, the propagation of
related proteins with molecular weights rang - the action potential is a continuous process.
ing from 14,100-21,400. These proteins are ap- In peripheral myelinated axons with regu -
parently produced by a single gene through larly spaced nodes of Ranvier, the action po-
alternative RNA splicing. These myelin basic tential appears to " jump" from node to node
proteins are all highly antigenic and , when in- rather than proceed at a uniform velocity
jected into animals, produce a cellular autoim- along the axon membrane between nodes.
mune response called experimental allergic This is called "saltatory" conduction and is
encephalomyelitis. This syndrome is charac- the result of the electrical resistance and ca-
terized by focal inflammation and demyelina - pacitance properties of the myelin sheath .
tion in the central nervous system , and has The basic conductance mechanism of the ac-
been used by some investigators as an animal tion potential conduction along the surface
model for human multiple sclerosis. membrane of myelinated and unmyelinated
axons is the same.
Ranvier Nodes, Schmidt - Lantermann
Clefts, and Schwann Sheaths SCHMIDT -LANTERMANN CLEFTS
NODES OF RANVIER The myelin sheath of each internode is di -
vided at intervals into conical segments by
The myelin sheath is interrupted bv con - the so-called Schmidt - Lantermann clefts. They
strictions at varying intervals on both central consist of oblique, funnel-shaped clefts,
and peripheral axons. These areas, which are which extend to the axon. These are best seen
called nodes of Ranvier , are identified in both in preparations treated with osmic acid , but
the light and electron microscopes as regions are also visible in the living fiber when it is
where the myelin sheath is deficient ( Figs. viewed in polarized light. Several cone-
5.3C and 5.23). At the nodal gap of peripheral shaped indentations may occur in a myelin
nerves, the axolemma is ensheathed by a fine segment between two nodes, while the
basement membrane and small fingerlike myelin sheaths of adjacent axons may be de-
processes of the Schwann cell. As shown in void of such clefts for long distances. Al -
Figure 5.22, there are some characteristic dif - though long regarded as artifacts, the clefts
ferences between the nodes of central and pe- have been observed in electron microscopic
ripheral axons. The internodal distance and studies as shearing defects in the lamellae of
nodal gap are both shorter on central axons. the myelin sheath (19, 159). Such clefts were
Such nodes also lack both interdigitating glial shown to be areas of local separation of the
processes and a basement membrane. Thus, spirally wrapped myelin lamellae which are,
the nodes of Ranvier in the central nervous nevertheless, continuous across the incisure
system have a greater extracellular space in ( Fig. 5.26). The light appearing regions be-
the nodal region. The blunt spiral ends of the tween the lamellae consist of Schwann cell
glial processes appear to fuse with the ax- cytoplasm. In other preparations, the myelin
olemma adjacent to a central node, as shown sheath may exhibit a delicate trabecular retic-
in Figures 5.22 and 5.23. Paranodal termina - ulum , the ncurokeratin network ( 31 ) ( Fig. 5.21 ). The
tions of myelin loops, on each side of the network probably represents a precipitated
node, provide close apposition of plasma protein residue of the mvelin sheath rather
membranes rather than complete obliteration than a true cytoplasmic reticulum. The my -
of the extracellular space about the axon ( Fig. elin sheath ends at or near the point where
5.22). The length of the internodal segment the terminal arborizations are given off . No
varies considerably and is proportional to the -
structure similar to the Schmidt Lantermann
diameter of the fiber, the thinner fibers hav- clefts has been identified in myelin sheaths in
ing the shorter internodes. For example, in the central nervous system .
the peroneal nerve of the rabbit the inter-
nodes on fibers with a diameter of 3-18 pm SHEATH OF SCHWANN
range from 400-1500 pm ( 195), and these fig-
ures probably apply to other mammals and The sheath of Schwann consists of a layer of
humans. Electron microscopy has provided flattened cells that form the myelin of larger
essential information on the fine structure of fibers. It also provides a thin , attenuated cyto-
the node (see references 20, 129, 148, 149, 160, plasmic investment on nonmyelinated fibers
and 190 for additional details). of the cranial and spinal nerves ( Figs. 5.24
5 Neurons 169
and 5.27). Schwann cells, like neurons, are of

ectodermal origin ( neural crest and neural
tube; see Chapter 3). Each Schwann cell has a
flat, oval nucleus surrounded by a thin rim of
cytoplasm which contains a Golgi complex
and mitochondria ( Fig. 5.24 ). The Schwann
cells of both myelinated and nonmyelinated
nerve fibers are surrounded by a typical base-
ment membrane approximately 25 nm in
thickness ( Fig. 5.22 ). This is separated from
the plasma membrane of the Schwann cell by
an interval of 25 nm . Ultrastructural studies
indicate that the Schwann cell plasma mem-
brane, with its surrounding basement mem-
brane, correspond to the so-called neurolemma
sheath that was described earlier on the basis
of light microscopic observations ( 24, 188).
Nathaniel and Pease (135) regard only the
granular basement membrane surrounding
the Schwann cell as equivalent to the neu-
rolemma .
One Schwann cell may have extensive cy-
toplasmic processes as it presides over, and
maintains the integrity of , the segment of
myelin between two nodes of Ranvier. If an
ultrathin section were cut through a small
myelinated nerve fiber to include the nucleus Figure 5.26. Schmidt -Lantermann cleft ( arrows ) . Clear
areas consist of Schwann cell cytoplasm
of a Schwann cell, it would reveal ultrastruc-
tural relations similar to those shown in Fig -
ure 5.24. A longitudinally cut nerve fiber with
a thicker myelin sheath is shown in Figure delicate connective tissue that surrounds in -
5.27A . Electron micrographs of adult un- dividual peripheral nerve fibers. It is com -
myelinated nerves may reveal several axons posed of delicate collagenous fibers, disposed
lying within recesses of one Schwann cell longitudinally for the most part, a homoge-
( Figs. 5.24 and 5.27 B ) . The plasma membrane neous ground substance, and an occasional
of the Schwann cell is closely apposed to the flattened fibroblast. A close contact between
axon except for a small periaxonal space of the endoneurial collagen and the basement
15-20 nm ( 20). However, at some point membrane of Schwann cells is an inevitable
around the circumference of each unmyeli- consequence of the ensheathing of nerve
nated axon, the plasma membrane is reflected fibers in collagen. Actual "collagen pockets"
and extends superficially to form the surrounded by Schwann cells have been ob-
mesaxon ( Fig. 5.27B ). served along nonmyelinated axons. Thin
bundles of collagen usually can be observed
Connective Tissue Sheaths within the typical basement membrane sur-
rounding a Schwann cell ( 63). The en -
In addition to the foregoing structures, pe- doneurium is continuous with the more
ripheral nerve fibers are surrounded by pro- abundant connective tissue of the per-
tective sheaths formed by connective tissue. ineurium, which envelops both small and
These sheaths vary in thickness depending large bundles of fibers within a peripheral
on the number of nerve fibers involved . They nerve trunk.
can be grouped into three different types: en -
doneurium , perineurium, and epineurium. PERINEURIUM
ENDONEURIUM The outermost layers of the perineurium

are composed of dense concentric layers of
The endoneurium (sheath of Henle, or of mostly longitudinally arranged strands of
Key and Retzius), is a reinforcing sheath of collagen. A few fibroblasts and macrophages
Figure 5.27. A . Part of a myelinated nerve fiber in cross section. The Schwann cell cytoplasm and axoplasm (Ax)
both contain mitochondria (M) Note the alternation of dense lamellae with less dense intermediate layers in the
myelin sheath, This sheath is composed of thinned out Schwann cell cytoplasm wrapped concentrically around the
axon (Ax). The innermost layer of the myelin sheath displays a local swelling (S) The plasma membrane (PM) of the
Schwann cell envelops the entire structural complex (mouse sciatic nerve. x 39,000) B. Electron micrograph showing
the relationship of several unmyelinated axons (Ax) to the plasma membrane (Pm) of a Schwann cell. The nuclear
membrane (Nuc M), the nucleus (Nuc), and the nucleolus (n) are identified. Mitochondria (M) and the Golgi com-
plex ( G ) can be seen within the cytoplasm, while fine collagen fibrils (Co) surround the Schwann cell (mouse sciatic
nerve, x 26,000).
5 Neurons 171
are also present among the strands. Perineur- the spinal cord and brain . Here they appear
ial tissue is somewhat unique in that it con - as fine naked axons embedded in glial cell
sists of fibroblasts and smooth lamellae that processes with relationships similar to that of
resemble mesothelium ( 41 ). The deeper con - the Schwann cells on the peripheral unmyeli -
centric layers of flattened cells have promi- nated fibers (18, 122, 123).
nent basement membranes, often with closed Myelinated fibers vary greatly in size. The
contacts. The flattened cells also have a fine fibers have a diameter from 1 4 pm; -
slightly granular cytoplasm with scattered those of medium size from 5-10 pm; and
mitochondria and rough-walled vesicles. the largest from 11-20 pm. Collaterals or
Large molecular dyes, silver nitrate, toxins, branches are given off by most fibers of the
and [ ’' IHabeled proteins have been used to
’ central nervous system . They are usually of
investigate the blood -nerve barrier in animals finer caliber than the parent stem, extend at
(196). The peripheral nerve of the rabbit has right angles, and often arise from the proxi -
an effective nerve barrier, interpreted as due mal unmyelinated part of the axon. In the
to the vascular endothelium rather than the myelinated portion they are given off at the
mesothelial cells that accompany the en - nodes of Ranvier and become myelinated
doneurial connective tissue. themselves. In the peripheral nervous sys-
tem, the fibers of somatic motor neurons,
EPINEURIUM which supply skeletal muscle, branch repeat -
edly at acute angles before reaching the mus-
This dense, collagenous layer forms an ex- cle. Within the muscle, the branching may be
ternal connective tissue ensheathment for all very extensive, and a single nerve fiber may
peripheral nerve trunks. It is continuous cen- furnish motor terminals to many muscle
trally with the dura mater of cranial and fibers. Sensory fibers probably branch in a
spinal nerves. Its fibrous nature reinforces the similar manner since their terminal arboriza -
toughness of peripheral nerve trunks. The tions extend over a considerable area . A sin -
collagen strands are disposed mainly longitu- gle myelinated fiber may supply sensory end -
dinally, and the component fibers have diam- ings to more than 300 hair follicle groups.
eters between 70 and 85 nm. A few elastic Myelinated fibers conduct more rapidly
fibers and fibroblasts with elongated pro- than unmyelinated ones. Speed of conduction
cesses are scattered throughout the epineu - is proportional to the diameter of the fiber
rium . Axial arteries to peripheral nerves are and , especially, to the thickness of the myelin
derived from the large arteries adjacent to sheath . The myelin sheath may be regarded
nerve trunks. Arteries that provide nourish- as insulation, while the extracellular space at
ment to a peripheral nerve penetrate the epi- the nodes of Ranvier and the periaxonal
neurium and give off several branches. The space provide ready avenues for ionic diffu -
smaller arterioles pursue proximal or dis- sion .
tal courses within the perineurium of the nerve When an axon is excited, a finite length of
trunk. Most of the capillaries supplying the the axonal membrane is depolarized . This
peripheral nerve fibers are located in the zone of depolarization is propagated along
endoneurium. the length of the axon and is known as a
nerve impulse or action potential . An im -
Grouping of Nerve Fibers pulse consists of a large negative voltage de-
flection of short duration, the spike potential ,
The unmyelinated peripheral nerve fibers which is usually followed by two longer, but
consist of slender axons enveloped by the much smaller, voltage shifts known as the
thin Schwann cell sheath , its basement mem- negative and positive after - potentials . The speed
brane, and fine strands of collagen ( Figs. 5.24 with which the spike potential travels over
and 5.27B ). The critical point for fiber myeli- the nerve fiber constitutes the conduction ve-
nation of an axon in tissue culture is reported locity of the nerve impulse, and the number of
to be a diameter of 1 gm (19). Axons of successive potentials traversing the fiber per
thicker diameters always are invested with a unit time represents the frequency of the im -
myelin sheath. The peripheral axons of most pulses ( Fig. 5.1 ).
postganglionic sympathetic neurons and As early as 1937, Erlanger and Gasser
many cells of the spinal ganglia are unmyeli- demonstrated that different fibers in a nerve
nated ( 47). Numerous unmyelinated fibers trunk conduct at varying velocities ( 48). As
are also found in the gray and white matter of mentioned earlier, the speed of conduction is
proportional to the diameter of the fiber and The more rapidly conducting type B fibers
of the myelin sheath . Each nerve has a char- transmit afferent impulses from viscera . The
acteristic pattern of velocities corresponding unmyelinated type C fibers comprise the ef -
to an analogous pattern of fiber diameters in ferent postganglionic autonomic fibers and
the nerve trunk. As a result of extensive afferent fibers which are believed to conduct
physiologic investigations supported by his - impulses of poorly localized pain from the
tologic studies, nerve fibers have been viscera and the periphery (Table 5.2).
grouped into three main classes, A, B, and C The classification of axons in peripheral
( Table 5.2 ). The A group includes several sub- nerves on the basis of conduction velocity
divisions, designated A„, Atl, Av and A*. Cri - reveals certain correlations with function .
teria for the classification are fiber diameter, When sensory physiologists studied the orga -
conduction velocity, threshold to electrical nization of dorsal root fibers activated by nat-
stimulation , and patterns of electrical signal- ural stimuli, it was convenient to use a classi-
ing (11, 64, 81, 82, 87, 120, 146, 153). fication that applied specifically to sensory
The type A fibers are myelinated , range in neurons, and they identified axons as belong-
diameter from 1-22 gm and conduct at rates ing to groups I, II, 111, and IV. Each group is
of 5-120 m / sec. The more finely myelinated activated by particular types of sensory stim -
B fibers have a diameter up to 3 gm and a ulation and contains fibers of a particular size
conduction rate of about 3-15 m / sec, al- range. These are shown in Table 5.2 along
though a higher velocity has been observed with the corresponding conduction velocity
in some fibers of this group. The C fibers are classification.
unmyelinated and conduct very slowly,
about 0.6-2 m / sec. There is a certain amount SYNAPSES
of overlap so that a fiber of 2 g.m could be-
long to either the A or B group, but certain The simplest segmental reflex requires at
features of the electrical signaling permit a least two neurons. The action potential, initi -
definite classification. The duration of the ated in a peripheral sensory nerve ending,
spike potential is always much longer in type passes centrally along the axon of a dorsal
B fibers than in type A fibers, and the type B root ganglion cell into the spinal cord . There
fibers lack a negative afterpotential. it activates a motor neuron , whose action po-
Studies on various types of nerves ( muscu - tential travels along the motor fiber and
lar, cutaneous, and autonomic ) indicate a causes a group of muscle fibers to contract
general functional grouping of the three ( Fig. 10.23). Even simple reactions have, as a
classes of fibers. This grouping must not be rule, a central neuron interposed between the
regarded as rigid , since many fibers serving afferent and efferent cells ( Fig. 10.24 ). In the
the same function may have widely different more complicated neural circuits, the number
calibers. The type A fibers comprise several of such interneurons , or internuncial central
subdivisions. The largest and most rapidly neurons, may be very large. All neural path -
conducting fibers ( conduction velocity 70-120 ways therefore consist of chains of neurons
m / sec in humans) transmit motor impulses related to each other so as to make possible
to skeletal muscles, while other type A fibers the continuity of signal transfer over the com-
convey afferent impulses from stretch recep- plete circuit . The point of junction of neurons,
tors in muscle. The rest of the type A fibers, that is the region where the axonal arboriza -
varying considerably in diameter and speed tions of one neuron come in contact with the
of conduction, carry afferent impulses from cell body or dendrites of another, is known as
cutaneous receptors. Fibers of intermediate the synapse. The synapse is not a site of cyto-
size are related to touch and pressure. The plasmic continuity between neurons, but a
finest fibers transmit impulses associated functional interface between two neurons.
with pain , and some of these fibers conduct Axons terminating upon the dendrite of an-
thermal and tactile impulses. other neuron form axodendritic synapses,
Type B fibers are associated mainly with whereas axons terminating upon the cell
visceral innervation and are both efferent and soma or perikaryon form axosoinatic synapses .
afferent . All the preganglionic autonomic Less frequently, axon terminals of one neuron
fibers belong to this group, as well as the may be located directly on other axonic ter-
postganglionic fibers from the ciliary gan - minals, or on the initial segment of the axon
glion, which are partly or wholly myelinated . of another neuron (axoaxonic synapses ) . The
5 Neurons 173
Table 5.2 .
PERIPHERAL NERVE FIBER CLASSIFICATION
FIBER TYPE FUNCTION SIZE ( nm ) CONDUCTION

Velocity ( m / sec)
Aa la Proprioception, stretch, -
12 22 70 - 120
Primary muscle spindle afferents
Motor efferent to muscles
( extrafusal )
Aa lb Contractile force: Golgi tendon 12 - 22 70 - 120

organ afferents
Ap II Mechanoreception: discriminative
touch, pressure, joint rotation
5 - 12 ,3 0 - 70
Secondary muscle spindle
afferents
Ay II Muscle spindle ( intrafusal ) 2-8 15 - 30

efferents
A8 III Mechanoreception: touch 1 -5 5 - 30

Nociception: discriminative pain
B Sympathetic preganglionic axons <3 3 - 15
C IV Nociception: in inflammatory or
visceral pain, thermal sense
-
0.1 1.3 0.6 2.0 -
term "synapse," coined by Sherrington at the with which the dendrites are beset ( Fig. 5.9 ).
turn of this century (176), may be expanded Dendritic spines are, in fact, major sites of
to include the functional contacts between synaptic contacts. One axon may convey im -
two neurons and those between neurons and pulses to many neurons, and, conversely, one
effector cells, such as muscle cells. neuron (e.g., anterior horn cell ) may receive
Synaptic junctions show many structural impulses from many other neurons, some of
variations ( Fig. 5.28) (174 ). Commonly, the which are widely separated in the neuraxis.
axon terminals end in small bulblike expan -
sions ( end feet , boutons terminaux ). In terms of
cytoskeletal elements, each terminal consists infrastructural Characteristics
of a neurofibrillary loop embedded in peritib- '
The first electron microscope studies of the
rillary substance; sometimes there are simply synapses in the 1960s ( 37, 75-77, 124 ) showed
small neurofibrillary rings. A large motor that all synapses in the vertebrate nervous
neuron in the spinal cord may receive as system are composed of three basic elements:
many as 1 ( ),( )()() such endings, most of them the presynaptic axon terminal, the postsynap-
1-2 pm in diameter. Approximately 8000 of tic target site, and the minute synaptic cleft
these synapses are located on dendrites and that separates them . The presynaptic element
2000 on the soma of the motor neuron . In an - of the synaptic complex possesses the neces-
other type of synapse, the delicate axon ter- sary metabolic machinery for the synthesis,
minals do not form end feet but come in stocking, release, and inactivation of the neu -
lengthwise apposition with the dendrites or rotransmitter. This is evidenced by the pres-
cell body, often for considerable distances. ence of mitochondria, neurofilaments, and
The most striking example is the climbing numerous synaptic vesicles. In contrast, the
fibers of the cerebellum ( Figs. 15.4 and 15.5). postsynaptic element is specialized for the re-
In some cases, unmyelinated axons run at ception of the neurotransmitter. Its plasma
right angles to the dendrites and come in con- membrane, which often displays electron -
tact with the spiny -excrescences or gemmules dense specializations, contains complex pro-
Figure 5.28. Synaptic endings on human CNS neurons after silver impregnation and observed by light microscopy
.
Note numerous terminal boutons on the dendrites (d axodendritic synapses) and some on the cell body (axosomatic
synapses) The axon (a) and nucleus (n) are identified In A ( x 650) The smaller neurons shown in B are magnified
x 920.
teins that act as a receptor for the neurotrans- p.nr ), there is little or no basement membrane
mitter. The synaptic cleft that separates the material in the cleft, and the postsynaptic
pre- and postsynaptic elements is usually membrane specializations and dense projec-
20-40 nm in width ( Figs. 5.30 and 5.31 ). tions are not obvious. The last feature gives
Two major types of synapses can be recog- this type of synapse a more symmetric ap-
nized on the basis of morphologic criteria. pearance in comparison to the type I
These are referred to as Gray type 1 and type synapses ( Fig. 5.18). The type II , or symmetric
II , after the investigator who first described synapses , are often associated with the
them ( 75). In type I synapses, the cleft is ap- GABAergic inhibitory synapses. Despite that
proximately 30 nm, the presynaptic zone is the notion of symmetric and asymmetric
1-2 pnv in area , and dense projections, the synapses is used in contemporary studies of
presumed release sites for the vesicles, are the synaptologic organization of the central
prominent . The synaptic vesicles are mostly nervous system, it must realized that these
round , although this varies according to the two forms of synapses may represent the
fixative used for electron microscopy. Amor- two extremes of a morphologic continuum .
phous dense basement membrane material
exists in the synaptic cleft and the postsynap- Electrical Synapses
tic membrane displays a markedly dense re-
gion, which gives to this type of synapse a There was a considerable debate during
typical asymmetric appearance (75-77). These the first half of this century as to whether
type I , or asymmetric synapses , are often asso- neural transmission is electrical, as proposed
ciated with glutamatergic excitatory synapses by the physiologic school led by John Eccles,
( Fig. 5.18). In type II synapses, the cleft is 20 or chemical, as advocated by the pharmaco-
nm wide, the active zone is small ( less than 1 logic school led by Henry Dale ( 36, 45).
5 Neurons 175
Choline
Figure 5.29. Motor nerve terminal and muscle end plate showing the major biochemical and biophysical events in
.
neuromuscular transmission. (ATPase) adenosine triphosphate, (cAMP) cyclic adenosine monophosphate ( CHE)
.
acetylcholinesterase, (Ca) calcium ions, (A/a) sodium ions ( K ) potassium ions, ( 17) transmitter receptor.
Today, we know that both electrical and tem. Their two major properties, speed and
chemical synapses exist in the central ner- synchrony, render this type of synaptic con -
vous system . nection ideal for fast, simple, and stereotyped
The term electrical synapse refers to a form behaviors.
of neuronal signaling that consists of current
flow through gap junction channels that di - Chemical Synapses
rectly connect the cytoplasm of both neurons,
which are separated from one another by The chemical synapse is by far the most
only 3.5 nm. Gap junction channels consist of common form of neuronal signaling in the
paired hemicylinders in the membrane of mammalian central nervous system . Chemi -
each interconnected cell that are permeable to cal transmission is strictly unidirectional and
small molecules and some second messen- slower than electrical transmission. This is
gers. Electrical synapses can be either unidi- because the presynaptic neuron must release
rectional ( rectifying ) or bidirectional ( nonrec - a transmitter, which then diffuses across the
tifying ), and are the most rapid form of synaptic cleft and binds to a receptor in the
synaptic transmission. They allow for rapid postsynaptic cell membrane (37-40, 201 ).
and synchronous firing of interconnected However, chemical transmission has the ad -
cells. Electrical synapses are abundant in in - vantage that a single action potential can in-
vertebrates, but occur only in specific loca - duce the release of thousands of transmitter
tions in the mammalian central nervous sys- molecules, allowing amplification of the
(
JV.
'
I
- 4*.
Figure 5.30. Axodendritic synapse in the human cerebral cortex The saclike enlargement comprising the axon ter -
minal ( AT ) contains a mitochondrion (M) and numerous vesicles (SV) The axon terminal is indented by the dendritic
spine (DS) Profiles of the spine apparatus ( arrow ) are seen above, while to the left the postsynaptic membrane of
the dendritic spines is thickened in three places ( x 38, 500). Compare with synapse shown In Figure 5.28.
synaptic response. Perhaps because of its system , and in some sympathetic nerve end -
multistep process, chemical transmission is ings. In cholinergic autonomic neurons, each
said to be more easily modified than electrical synaptic vesicle contains an estimated 1600
transmission . Its plasticity renders chemical molecules of acetylcholine ( 203). The vesicles
synapses more suitable than electrical syn- also contain 1 molecule of ATP for every 4
apses for complex behaviors, such as learn- molecules of transmitter. Furthermore, sev-
ing, which involves stabilization and reinforce- eral proteins (e.g., caldesmin, synapsins, an-
ment of neuronal circuits (98 ). nexins, and synaptophysin ) associated with
In chemical synapses, neurotransmitters the membranes of synaptic vesicles are be-
are largely sequestered within synaptic vesi- lieved to be involved in the mobilization of
cles in the presynaptic element . In the case of synaptic vesicles from a general pool in the
cholinergic neurons, each electron-lucent axon terminal to the docking sites at the
synaptic vesicle is considered to contain a presynaptic membrane. Some of these pro-
quantum of acetylcholine which is released teins are also involved in the Ca 2 + / depen-
when an action potential arrives at the dent mechanisms underlying the fusion and
synapse ( 38, 99, 201, 208). At the neuromus- the recycling of vesicle membranes.
cular junction, quanta of acetylcholine, re-
leased a few at a time during quiescence, are Vesicle Recycling
associated with miniature end plate poten-
tials ( 52, 100). The most commonly occurring As the nerve impulse invades the terminal,
synaptic vesicles are about 40 nm in diame- there is an influx of calcium ions which leads
ter, are roughly spherical and have clear cen- to the exocytosis of synaptic vesicles and the
ters ( Figs. 5.30 and 5.31 ). Vesicles of this type release of transmitter into the synaptic cleft
are found in axon terminals at neuromuscu - ( 184 ) ( Fig. 5.29). The transmitter molecules dif -
lar junctions, throughout the central nervous fuse across the cleft and bind to receptor mole-
5 Neurons 177
mb
- ‘ .J
Figure 5.31. Axodendritic synapse In monkey cerebellar cortex Synaptic vesicles (SV) are present in the axon termi-
nal ( AT ) and in the axon (A) in the upper right . Other organelles are dendrites (0) with spine apparatus, and mito-
chondria ( M) ( x 48.000)
cules in the postsynaptic membrane. Trans - nally . This recycling process is called transcy-
mitter molecules that are not bound to recep- tosis and involves the retrograde transport of
tors are either inactivated in the synaptic cleft membrane material within endosomes. New
region by degrading enzymes (e.g., acetyl - synaptic vesicles are also formed at even fur -
cholinesterase for acetylcholine and mono- ther distances from the active zone by the en-
amine oxidase for biogenic amines) or re- doplasmic reticulum (88, 89 ). In fact, the total
turned back into the presynaptic ending amount of membrane in vesicles, cisternae,
through a highly specific and very powerful and plasma membrane in the axon terminal
reuptake mechanism . This mechanism in- remains constant , indicating that membrane
volves the use of highly specific protein com- is indeed recycled from the plasmalemma
plexes known as transmitter transporters . into the internal organelles.
When a transmitter is released from vesicles
by exocytosis, the membrane of the dis- Receptors
charged vesicles becomes incorporated into
the surface membrane of the presynaptic ter- It is extremely important to realize that, in
minal . If no process compensates for exocyto- the process of chemical transmission, it is the
sis, the membrane of a synaptic terminal receptor, not the transmitter, that determines
would enlarge as a result of nerve activity, whether the synaptic response is excitatory or
because vesicle membrane would be continu - inhibitory . Indeed , the action of transmitters
ously added to the plasmalemma . This does depends on the properties of the receptors,
not happen , however, because new synaptic not on the chemical nature of the transmitter.
vesicles are continuously generated in the ter- For example, acetylcholine produces synaptic
minals through the process of endocytosis that excitation at the neuromuscular junction by
occurs in the presynaptic membrane. Other acting upon a nicotinic receptor, whereas it
synaptic vesicles are recycled at a certain dis- slows the heart by acting on a muscarinic in -
tance from the site where they were origi- hibitory receptor. The notion of receptor was
introduced in the late 19th century by the channel, without the intervention of second
German biochemist Paul Ehrlich to explain messengers.
the action of various toxins and the specificity Directly-gated transmission is only
of immunologic reactions (46). This concept slightly slower than electrical transmission
was substantiated by the work of the English since it is mediated by receptors that are part
pharmacologist John Langley and two of his of the ion channel molecule. This form of
students, Henri Dale and Eliot Smith, on cu - chemical signaling allows for fast synaptic ac-
rare and nicotine. tions that are in the millisecond range. In con-
Receptors are essentially large membrane- trast, indirectly-gated transmission, which in-
spanning ( integral ) proteins that allow the volves formation of second messengers, is
signaling molecule to exert its effect upon the much slower, lasting seconds and even min-
target cell. More specifically, they consist of utes. This form of chemical signaling serves
complex macromolecules containing several to modulate behavior by altering the ex-
protein subunits that form the recognition el- citability of neurons and the strength of
ement and the ion channel. Channels can be synaptic connections (98).
distinguished from one another by their ion The cortical noradrenergic synapse is good
selectivity and the factors that control their example of indirectly-gated transmission.
opening and closing, or gating. Ion selectivity When norepinephrine binds to the postsyn-
is achieved by physical and chemical interac- aptic metabotropic receptor on the surface of
tions between the ion and various amino acid cortical neurons, the enzyme adenylate cy-
residues that line the wall of the pore. Gating clase is activated. Adenylate cyclase then cat-
involves a conformational change of the alyzes the conversion of adenosine triphos-
channel in response to various external stim- phate ( ATP) to cAMP. In the cytoplasm,
uli, particularly voltage and ligands (177). cAMP may activate one or several protein ki-
There are two major classes of receptor pro- nases, which in turn may regulate phospho-
teins that derive from two distinct gene fami- rylation of either plasma membrane proteins
lies: receptors that gate ion channel directly (56) or acidic nuclear proteins ( Fig. 5.32). A
and receptors that gate ion channel indirectly lesion of the noradrenergic fibers innervating
by initiating a second messenger cascade. the cortex or a pharmacologic blockage of the
Receptors that gate ion channel directly, noradrenergic transmission will lead to an in-
such as the cholinergic receptor at the neuro- creased number and / or sensitivity of adren-
muscular junction, consist of a single macro- ergic receptors in postsynaptic cells (130).
molecule that comprises both the recognition This upregulation of adrenergic receptors ac-
element and the ion channel. When bound to counts for the phenomenon called denervation
a transmitter, such inotropic receptor under- supersensitivity.
goes a conformational change that opens the In addition to the directly- and indirectly-
channel. In the brain, the actions of gluta- gated transmission, transmitters, acting
mate, GABA, and glycine are mediated by re- through second messengers, can phosphory-
ceptors of this type (98). Receptors that gate late transcriptional regulatory proteins, alter-
ion channel indirectly, such as those for nor- ing gene expression. Through their action via
epinephrine and serotonin in the cerebral cor- second-messenger kinases, transmitters can
.
tex, are called metabotropic receptors They in- induce the synthesis of new proteins, a phe-
volve separate recognition elements and ion nomenon that could be involved in the regu-
channels that communicate through guano- lation of receptor molecules themselves, as
sine triphosphate (GTP)-binding proteins (G- well as the induction of rate-limiting en-
proteins ). These G-proteins couple the recep- zymes available for the synthesis of new
tor to effector enzymes that produce transmitters in postsynaptic cells ( Fig. 5.33).
intracellular second messengers, like 3', 5'- In the case of catecholaminergic neurons,
adenosine monophosphate (cAMP) and dia- denervation results in lowered levels of
cylglycerol. The second messengers can act cAMP in the postsynaptic cell. This decrease
on the channel directly, but more commonly in cAMP leads to an increase in the amount of
they activate protein kinases, which induce tyrosine hydroxylase (2). These genomic trans-
conformational changes by phosphorylating mitter effects appear to be part of a mechanism
either the channel protein or a regulatory whereby neurons attempt to adjust their
protein that acts on the channel (113). G-pro- input / output sensitivity to compensate for a
teins can also interact directly with the ion reduced number of afferent axons.
5 Neurons 179
Membrane protein
phosphorylation
[ (ionic channel) >
Adenylate cyclase
Binding site
(receptor ) s
ATP_ I _ CAMP_ Protein
kinases
/ ANP
'olyamines l
I
RNA polymerase I ANP- P
NA|
DNi
Ribosomal RNA
synthesis > Nuclei
^
Protein
Plasma membrane
Figure 5.32. How cyclic AMP may participate in synaptic transmission and also initiate trophic changes. A transmitter
receptor site in the surface membrane is shown in the upper left . When the catecholamine transmitter binds to the re-
.
ceptor adenylate cyclase becomes available to form cyclic adenosine monophosphate (cAMP) . cAMP activates
protein kinases, some of which phosphorylate surface membrane proteins presumed to be associated with ionic
channels. Other protein kinases may migrate to the nucleus initiating a chain of events ultimately resulting in in-
. .
creased protein synthesis. (ATP) adenosine triphosphate ( ANP) acidic nuclear protein ( ANP-P) phosphorylated
.
acidic nuclear proteins, (DNA) deoxyribonucleic acid ( mRNA ) messenger ribonucleic acid,
Nerve growth factor
) ACH o
o Tyrosim
o Tyrosine /
hydroxylase
DOPA
Dopamine
DA ®
cAMP
\
Norepinephrin
or
NE
/J-Adrenergic
receptor
Figure 5.33. Cholinergic ( ACH) ond cotecholominergic (dopamine (DA) or norepinephrine ( NE ] ) synapse upon a nor-
adrenergic cell of the superior cervical ganglion The level of the enzyme tyrosine hydroxylase, the rate limiting en-
zyme in the synthesis of DA and NE. is regulated by the level of cAMP Prolonged periods of Increased cAMP levels re-
sults in reduced amounts of tyrosine hydroxylase.
The enduring synthesis of new proteins by nervous system (96, 98). Many of these effects
transmitter genomic action is important be- are mediated through cAMP and cGMP ( Fig.
cause, among other tilings, it appears to be 5.34 ). The specific effects of cAMP and cGMP
involved in the complex phenomenon are not known , but it is hypothesized that
whereby a given chemospecific afferent can each cyclic nucleotide phosphorylates differ-
regulate the concentration of another trans- ent membrane proteins (78, 79 ).
mitter in a postsynaptic target cell ( Fig. 5.34). In recent years, there has been great inter-
Such a regulation occurs in the superior cer - est in the role of a calcium-binding protein
vical ganglion where the amount of norepi - called calmodulin . The calmodulin / calcium
nephrine synthesized is regulated transynap- complex may regulate some of the enzymes
tically through synaptic receptors in response related to cyclic nucleotide formation or
to the activity of cholinergic afferents. If the degradation ( 27). Calmodulin is a highly con -
activity of the cholinergic presynaptic neu- served protein with a molecular weight of
rons is sufficiently prolonged , the released 17,000. In the presence of calcium, this pro-
acetylcholine will induce relatively long-term tein binds reversibly to many enzymes and
changes on the postsynaptic cell, including an other proteins, thereby regulating their func-
increase in the supply of norepinephrine tion. For additional details on the anatomic
through an increase in tyrosine hydroxylase. and functional organization of the synaptic
These genomic regulatory mechanisms also complex the reader is referred to the studies
occur in catecholaminergic cells of the central of Peters, et al. (150), and Kandel, et al . ( 98).
5 Neurons 181
Figure 5.34. Ways in which synaptic actions might be mediated by a second messenger This model is based upon
observations of the nervous system in invertebrates and vertebrates. Cell A is dopaminergic and controls the level of
3',5' -adenosine monophosphate (cAfylP) in the postsynaptic cell cAMP may ( /) phosphorylate a membrane protein
to alter membrane ionic permeability and/ or ( 2) alter synthesis of a rate limiting enzyme for transmitter synthesis Cell
B is serotoninergic and increases cAMP in the presynaptlc terminal of cell C. resulting in an increased calcium perme-
.
ability and transmitter exocytosis Cell C Is cholinergic and increase 3 ' 6' -guanosine monophosphate (cGMP) in the
postsynaptic cell. Increased cGMP (3) may phosphorylate a different specific membrane protein
AXOPLASMIC TRANSPORT Two early observations led to the concept

of axoplasmic flow. It was found that con -
Axoplasmic transport refers to the move- striction of an axon by a ligature led to a
ment of proteins and other substances along buildup of material on the proximal side (199,
the axon . The movement occurs in both direc- 200 ), and that proteins migrated along axons
tions: anterograde , from cell body toward axon in both the peripheral and central nervous
terminal, and retrograde , from terminal to- system ( 42 ) ( Fig. 5.41 B ) . Isotopically labeled
ward cell body ( Fig. 5.40 ). Axonal transport is amino acids injected near the cell body are
extremely important for the growth and transported into the cell and become incorpo-
maintenance of neurons. Indeed , virtually all rated into newly synthesized proteins. The
of the protein synthesis in neurons occurs in movement of the labeled proteins along the
the cell body, with only minor amounts de- axon can be measured by either scintillation
tected in axons, terminals, and distal den - counting or autoradiographic methods. A
drites. The growth and subsequent mainte- method was also devised which permits di -
nance of long axonal and dendritic processes rect labeling of cellular protein (53). More re-
must require some mechanism for moving cently , direct observation made with video-
newly synthesized structural protein and en- enhanced microscopy ( 4 ) has shown that
zymes throughout the neuron . -
large particles move in a stop-and go (salta -
tory) fashion in both the anterograde and ret- subunits (|J ). More than 20 years ago, cross-
rograde directions in the axon . Anterograde bridges between microtubules and vesicular
transport has been found to occur at two dif - particles that were believed to play a role in
ferent rates, termed fast and slow. Further- the transport of vesicles were observed at the
more, the slow axonal transport has fast and electron microscopic level. Kinesin is most
slower components. likely the protein that formed these bridges.
Kinesin appears to contain a pair of globular
heads that bind to microtubules and a fan-
Anterograde Transport shaped tail that binds the organelles to be
moved . Similarities between kinesin and mus-
The fast anterograde transport predomi - cle myosin has led to the hypothesis that or-
nantly serves to export membrane bound ganelles movement during axoplasmic trans-
vesicles derived from the Golgi apparatus port is produced by the sliding of kinesin
and endoplasmic reticulum, including mem- molecules along microtubular tracts (90).
brane bound neurotransmitters, from the cell
body to the axon and axon terminals ( Fig.
5.40 ) ( 35, 74, 107, 108, 141 ). This component Retrograde Transport
has a mean rate of about 400 mm / day (43,
140 ). The fast anterograde transport depends In addition to anterograde axoplasmic
on oxidative metabolism , is not affected by transport from cell body to distal processes, it
inhibitors of protein synthesis, and is inde- was found that some substances can be taken
pendent of the cell body. It is largely based up by axonal terminals or distal dendrites
on microtubules that provide stationary and transported back to the cell body ( Fig.
tracts on which organelles move in a saltatory 5.40). The retrograde transport proceeds at a
fashion (171, 191 ). Fast transport can be rate that ranges from one-half to two-thirds
blocked by the alkaloids colchicine or vin - that of the fast anterograde axonal transport.
blastine, which bind to tubulin and disrupt Endocytosis (or micropinocytosis), which is
microtubules, while slow transport is much the reverse of exocytosis, seems to be an im -
less impaired . portant mechanism for incorporating within
The slower component of slow axonal the axon terminal vesicles and various types
transport occurs at rates of 0.2-2.5 mm / day of adsorbed and unadsorbed materials that
and principally involves cytosol elements, are transported to the cell body and degraded
that is, soluble enzymes and filamentous pro- within the system of lysosomal organelles
teins that make up microtubules and neuro- (17). Retrograde transport may be studied by
filaments, which is approximately 75% of all placing the glycoprotein horseradish peroxi-
proteins transported in the slower compo- dase ( HRP ) in the vicinity of nerve endings.
nent (Table 5.3) (72). Neurofilaments and mi - The enzyme marker adheres to the mem -
crotubules move in a polymerized form as a brane of the axon terminal which is pinocy-
network with regulatory and cross-linking tosed and transported back to the cell body
proteins tightly associated with them . The for lysosomal degradation (110). The enzyme
faster component of the slow transport can be visualized by histochemical treatment
moves twice as fast as the slower component . using a substrate that is converted into a col-
Its protein composition is rather complex, in - ored insoluble polymer.
volving cytoskeletal proteins such as actin, The retrograde transport system has
myosinlike protein, clathrin, calmodulin, as mainly a scavenger function . However, it can
well as enzymes of the intermediary metabo- also inform the cell body about events that
lism formed on free ribosomes. Clathrin is a occur at the distant end of axonal processes.
protein that has a molecular weight of It also has the capability of taking up and
180,000 and forms a highly ordered polyhe- transporting to the cell body important mole-
dral coat around synaptic vesicles that are cules, such as nerve growth factor ( NGF),
destined to be recycled . This protein plays an which can induce long-lasting metabolic
important role in the recycling of synaptic changes in neurons. Furthermore, some
vesicle membrane. viruses and toxins ( e.g., Herpes simplex , rabies,
The motor molecule for anterograde trans- polio viruses, and tetanus toxin ) can reach the
port is believe to be kinesin , an ATPase that central nervous system by ascending from
consists of two large subunits (a ) each with a peripheral nerve terminals to the cell body by
molecular weight of 125,000, and two small retrograde transport . The retrograde trans-
5 Neurons 183
Table 5.3.
AXOPLASMIC TRANSPORT
TYPE SUBSTANCE TRANSPORTED
I. Anterograde transport
a) Fast component Noncytosolic material ; principally

( 400 mm / day) bound vesicles deriving from Golgi
apparatus and endoplasmic reticu-
lum: neuroactive peptides , bound
small transmitter molecules and
some degradative enzymes .
b) Slow component Cytosolic material : principally

(1 -5 mm / day ) cytoskeletal proteins and various
soluble enzymes including those
necessary for transmitter synthe-
sis.
II . Retrograde transport Aging cytoplasmic organelles ,

( 200 - 300 mm / day ) endocytotic organelles ( including
vesicle membrane to be recycled ),
absorbed and unabsorbed exogenous
material : viruses, toxins and vari -
ous growth promoting and inhibit-
ing factors.
port of some of these viruses or toxins may integrates. Crushing injuries or interruption
rapidly lead to various functional impair- of an axon produces detectable changes in the
ments. cell body ( chromatolysis), as well as in the
The molecular mechanisms of retrograde central and distal stumps of the injured fiber.
transport are not as well understood as those When an axon is sectioned , degenerative
of anterograde transport (170, 171). However, changes of a traumatic character first affect
there is recent evidence suggesting that the the cut edges. In the proximal portion of the
motor molecule in retrograde transport is a fiber, which is attached to the cell body, the
form of dynein, which is also a microtubule- degenerative changes ( retrograde degenera -
associated ATPase ( MAP-1c). Dynein is a tion ) extend only a short, although variable
large protein complex containing two or three distance, depending on the nature of the in -
globular heads with an ATPase activity. It is jury. In a clean section, only one or two
involved in the beating of cilia in various uni- internodes may be involved . In more severe
cellular organisms, as well as in the move - injuries, such as gunshot wounds or in-
ment of chromosomes during cell division (3). flammatory processes, the retrograde degen-
eration may extend as much as 2 or 3 cm.
DEGENERATION OF NERVE FIBERS However, the degeneration is soon succeeded
by reparative processes leading to the forma -
The cell body is the trophic center of the tion of new axonal sprouts from the central
neuron, and any process detached from it dis- stump.
Anterograde Degeneration accumulation of mitochondria in the axo-

plasm at the nodes of Ranvier ( Fig. 5.41 A ).
In the distal portion, the axon and myelin This is followed by a breakdown of the <i \ o -
sheath completely disintegrate, and degener- plasm and mitochondria ( 198). Twelve hours
ation occurs throughout the length of the after injury , the axon is swollen and irregular
fiber, including its terminal arborization. This in shape. Within a few days, it begins to
process is known as secondary or Wallerian de- break into fragments. However, the breaking
generation ( Figs. 5.35 and 5.36). The changes, process may continue for a considerable time
as a rule, appear simultaneously along the
length of the nerve fiber distal to the injury .
in some fibers, and fragments of degenerat
ing axons have been found as late as 3-4
-
Functional failure of the nerve also is abrupt weeks after the injury. The synaptic terminals
down the length of the distal nerve trunk, as are affected similarly, and synaptic transmis-
shown by Novak and Salafsky (139 ) and sion is rapidly lost. Degenerating synaptic
Salafsky and Jasinski (163). These electro- terminals become filled with electron-dense
physiologic studies revealed that muscle re- products of degeneration, including whorls
sponses to distal nerve stimulation ceased of neurofilaments that surround swollen and
54-72 hours after sciatic nerve section, de- disrupted mitochondria. The myelin sheath
pending on whether nerve injury occurred in likewise degenerates. Two or three days after
the thigh or at the level of the knee. Axonal section, constrictions appear that fragment
changes begin almost at once. Electron micro- the myelin into elongated ellipsoid segments,
graphs of the sciatic nerve following crush in- which in turn break into smaller ovoid or
jury demonstrate that the initial change is an spherical droplets or granules ( Figs. 5.35 and
III i
Axon —
9 y
Nucleus of
sheath cell e
Myelin
sheath V
dIvisiorfo ,
^ ^ ^ de9ene aton Note increase in sheath cell protoplasm and
0X00
the nucteus
5 Neurons 185
Figure S.36 . A . Distal stump of a nerve cut 3-5 days previously (osmic acid) B. Distal stump of a nerve partly cut
12- 15 days previously (osmic acid). Normal fibers and two nodes of Ranvier are shown at the bottom. C. Distal stump
of a nerve cut 12- 15 days previously (osmic acid and iron hematoxilin). In addition to the clumps or islands of degen-
erating myelin, several bands of fibers and their nuclei (n) are shown
5.36). The whole process resembles the hours after peripheral nerve injury there is a
breakup of a liquid column under surface loosening of the myelin lamellae (112).
tension and is ascribed to the fact that the Myelin disintegration is evident at 4 days in
fiber is no longer kept in a turgid condition Schwann cells and well -advanced % hours
by neuroplasmic pressure emanating from after crushing dorsal roots of the cauda
the cell body ( 206, 207). equina as shown bv Nathaniel and Pease
The myelin changes, at first purely physi - .
( 134 )
cal, are followed by chemical changes as well. These authors have elucidated the key
The myelin breaks into simpler intermediate roles of the Schwann cell and its basement
substances, which react to the Marchi stain . membrane in both degeneration and regener-
Ultrastructural studies provide information ation . Schwann cells undergo hypertrophy,
about the degenerative process. Nineteen demonstrate unusual numbers of ribosomes,
multiply in number, become mobile, and total quantity of RNA in the perikaryon, and
form elaborate basement membranes. These suggest that the cisternae and ribosomes are
cells are almost exclusively responsible for dispersed and less concentrated . That these
the removal of axon remnants and autodiges- cells imbibe water results in a tremendous
tion of disintegrated myelin. There is no con- increase of their volume. Ultrastructural
nective tissue response in the endoneurium, changes also have been observed in many
and leucocytes do not appear to participate in neuronal organelles (e.g., mitochondria, en-
the phagocytosis of neuronal debris. The only doplasmic reticulum, Golgi apparatus, ribo-
endoneurial response is a slow accumulation, somes, and lysosomes ) following nerve sec-
and slight increase, in the amount of collagen tion or x-ray irradiation of ganglion cells in
adjacent to the basement membranes. Newly tissue culture (94, 102, 125). Histochemical
formed and hypertrophied Schwann cells changes occur in a number of oxidative and
have extensive tapering and overlapping cy- hydrolytic enzymes within chromatolytic and
toplasmic processes, which in light mi - regenerating neurons (133). Such changes re-
croscopy were interpreted as multinucleated flect a reduction , or an increase, in glucose
syncytial cords ( band fibers). metabolism, a breakdown of Golgi bodies or
Nuclear division of the Schwann cells be- increased RNA , and nudeoprotein synthesis.
gins around the 4th day and continues ac- The extent and rapidity of these changes
tively to about the 25th day , mitosis occur- depend on the type of neuron involved , on
ring over the whole length of the fiber. The the nature of the lesion, and , especially, on
increase in the number of nuclei is consider- the location of the injury . A lesion of the axon
able, in some instances as much as 13 times near the cell body produces a greater central
the original population (1 ). During degenera - effect than one more distant. The effect de-
tion , the Schwann cell plasma and basement pends upon the percentage of the neuron de-
membranes become separated from each stroyed . If the lesion is near the cell body, the
other to markedly increase the extent and latter may ultimately die and the proximal
complexity of the extracellular spaces (134 ). portion of the nerve fiber attached to it de-
The reactive Schwann cells form new , elabo- generates. Chromatolysis in the cell body
rately folded and successive basement mem - reaches its maximum 12-14 days following
branes, one inside the other. These Schwann injury to the axon . This retrograde alteration
cells and basement membranes form numer- of Nissl material has been employed exten-
ous extracellular compartments or tubes sur- sively in earlier neuroanatomic research to lo-
rounded by collagen of the endoneurium. Re- cate the cells of origin of axons in central
generating axonal sprouts from regions tracts, or in a peripheral nerve ( Figs. 5.2E and
above the injury later enter these extracellular 5.37).
compartments or "tubes" between the base-
ment membrane and Schwann cell. If no ax- REGENERATION AND PLASTICITY
onal sprouts enter the tube, it shrinks consid -
erably and the walls thicken, due to the Regeneration in the Peripheral Nervous
increase in the collagen content of the en - System
doneurium .
If the neuron survives injury, regeneration
Retrograde Degeneration takes place in the peripheral nervous system .
Recovery in the cell body begins at about the
The neuronal cell body whose axon is in- 3rd week and is characterized by the appear-
jured likewise shows marked degenerative ance of Nissl bodies around the nuclear mem -
changes ( Figs. 5.2 E and 5.37). The cell body brane. The swelling of the perikaryon gradu -
swells and becomes distended , the nucleus is ally subsides, the nucleus returns to its
displaced toward the periphery and the Nissl central position, and the Nissl bodies are re-
bodies undergo dissolution. Nissl body stored to the normal amount and distribu -
breakdown begins in the center of the cell tion . Full recovery may take from 3-6
and spreads outward ( central chromatolysis ) months, the time depending on the mass of
(73). With light microscopy the fixed Nissl axon to be reconstituted . While this is going
material appears to undergo lysis ( Fig. 5.37). on , regenerative processes appear in the
Cytochemical and electron microscopic stud - axons of the central stump. As early as the
ies indicate that there is an increase in the 10th hour, the axon terminals begin to swell .
5 Neurons 187
Figure 5.37. Four examples of central chromatolysis In the monkey . A and B. Neurons in the brainstem reticular for-
mation following section of the reticulospinal tract (cresyl violet. x 600. x 500). C. Retrograde cell change in lateral
vestibular nucleus (cresyl violet. x 500) . D. Retrograde cell change in the superior vagal ganglion (cresyl violet, x 500)
Each axon splits into numerous fine strands persists and becomes remyelinated . This is
or fibers ( Figs. 5.38 and 5.39 ) that traverse the usually the largest one ( Fig. 5.39 ). The elimi-
scar formed at the site of the injury and reach nation of excess fibers may take considerable
the Schwann tubes of the degenerating time, and some of them may still be seen in
stump. Many of these fibers enter a single tubes 3 or 4 months after section. The en -
tube where they are disposed peripherally largement of one fiber and the elimination of
( Fig. 5.38) . Later, some of them move to a the others, occur only if the regenerating
more central position and become completely axons make sensory or motor contact with
surrounded by the plasma membrane of the appropriate receptor or effector endings in
sheath cells ( Fig. 5.39 ). Along or within the the periphery.
bands, the regenerating axons grow distally The thin regenerating axons, at first about
for long distances to their peripheral destina - 0.5-3 (xm in diameter, gradually enlarge; the
tions. Nathaniel and Pease (135) have found increase in diameter advances progressively
that regenerating axonal sprouts reach the ex- down the tube, as if propelled by some cen-
tracellular spaces of the membrane envelope trifugal force from the central stump. When
as early as 4 days after a lesion. Although the fiber reaches the periphery , growth in
many sprouts initially may occupy the spaces length ceases, but the increase in diameter
and gutters of the Schwann tube, only one continues until the original thickness is ap-
Axis - cylinder
with terminal
branching
-
Axis cylinder
with terminal
swelling
Terminal enlargements
Figure 5.38 . Regenerating axons in the central stump of a cat ' s sciatic nerve 2 5 days after section of the nerve
proximated. Myelination may occur as early into a mature fiber whose volume in some in -
as the 2nd or 3rd week in some fibers. It like- stances may be several hundred times the
wise advances in a proximodistal direction, volume of the original filament ( Fig. 5.41 A ).
and the process becomes somewhat slower in The manner in which this new axoplasm is
the more distal regions of the fiber . The formed has been investigated by Weiss and
myelin is at first laid down as a thin continu - Hiscoe ( 200 ) in a series of ingenious experi-
ous sheath which subsequently becomes bro- ments. They fashioned small arterial rings
ken up into short internocial segments, about which, when distended, could be slipped
130-700 |j.m in length . In fully regenerated over the end of a cut nerve and placed in the
nerve fibers, the internodes are shorter and desired position. The subsequent contraction
more numerous, and there is no longer any of these rings produced localized constric-
definite relation between internodal length tions with consequent reduction in the diam -
and diameter because fibers of varying thick- eter of the individual fiber tubes ( Fig. 5.4 IB ) .
ness may possess similar internodal lengths. The reduction in the lumen of the tube does
The time course of the events in degeneration not at first interfere with the advance of the
and regeneration overlap each other. As slender regenerating axon, which passes
noted earlier, regeneration of new axonal through the constricted zone and makes con-
sprouts occurs before the disintegration of tact with the periphery. But when the fiber, as
the axon and myelin sheath is completed in it continues to enlarge, attains the dimensions
the distal segments of injured nerves. In a of the constricted zone, a remarkable differ-
similar fashion , regenerating axonal sprouts ence appears between those parts lying at the
may traverse Schwann tubes which still con- distal and proximal sides of the narrow neck .
tain degeneration debris ( 135). The distal segment ceases to grow and re-
The growth processes observed during remains permanently undersized , while the
generation are remarkable (155). A slender proximal segment not only continues to en -
axonal filament ultimately is transformed large, but near the entrance of the constricted
5 Neurons 189
Figure 5.39. A . Transverse section of peripheral stump of rabbit peripheral nerve severed 150 days previously The
stumps were left unsutured, but union was established by outgrowth . Most of the tubules contain one or more myeli-
nated nerve fibers which are surrounded by protoplasm of the Schwann cells B. Diagram of the progress of regener -
ation within Schwann tubule distal to a good nerve suture at different time Intervals (days). At 25 days there are many
fibers near the edge of the tube, at 50 days one or two fibers are enlarged and surrounded by Schwann cell cyto-
.
plasm at 100 days one large myelinated fiber occupies the center of the tube, while other smaller fibers are periph-
eral. At approximately 400 days excess fibers disappear and a single large fiber attains its normal diameter
zone, enlarges excessively ( 200 ). It was con - A knowledge of the mode of nerve regen -
cluded that the axoplasm exerts pressure in a eration is important as a basis for surgical
distal direction and becomes dammed where treatment . If a nerve is severed , it is desirable
the channel narrows ( Fig. 5.41 ). The dam - to surgically approximate the cut ends
ming increases in intensity with time, and -
promptly If some time has elapsed since the
varies with the amount of constriction and injury, it is necessary to resect surrounding
the size of the fiber . Morphologically, it is ex- scar tissue and the neuroma on the proximal
pressed in several ways, such as ballooning, nerve stump before the nerve can be sutured .
beading, telescoping, and coiling of the fibers. This subject is discussed further in Chap-
On release of the constriction, some of the ter 8.
dammed axoplasm flows into the distal por-
tion, which consequently increases in thick - Regeneration in the Central Nervous
ness ( Fig. 5.41 ). The authors concluded that System
the formation of new axoplasm, that is
growth in volume, occurs only in the cell Fiber degeneration in the central nervous
body, and that this axoplasm maintains a system is similar to that observed in the pe-
constant proximodistal motion that causes ripheral nerves. However, the degeneration
the elongation and enlargement of the regen - proceeds at a slower pace, and the removal of
erating fiber. neural debris by glial cells takes a longer
Nucleus
Golgi Microtubule
apparatus
Endoplasmic
. Lysosome reticulum^
Dendrite
©
I ) i
I x Vesicle
VL ~“
moving
a.
Vesicle ^ '
Plasma
° membrane
O 5 - Vesicle
Microfilament moving
f,1 j retrograde
l
O
Vesicle
• '
Axon ?'
I
-
VJ
o Microtrabecular
network l
1 Synaptic
o
terminal N
A lo B C
Postsynaptic neuron Postsynaptic neuron
Figure 5.40. Some of the major features of anterograde and retrograde axonal transport A . The major components
of anterograde axonal transport are filamentous proteins and vesicles originating from the Golgi apparatus and en-
doplasmic reticulum B Retrograde axonal transport involves movement toward the cell body of smaller vesicles
formed by micropmocytosis (endocytosis) at the synaptic terminal. In the cell body, the vesicles coalesce and be-
come incorporated into lysosomes for degradation. C. Organelles that are thought to be associated with axoplasmic
transport . Microtubules form an essential anatomical substrate for the transport of organelles, which are linked to
these cytoskeleton components by microtubule-associated proteins (MAPs).
time. It is known that the large fibers of the tury ( 22, 23, 59, 173, 204 ). Such studies indi -
corticospinal tract and optic nerve degenerate cate that the central axons of injured nerve
faster than the fibers of small size ( 192, 193). cells make abortive attempts to regenerate
Such studies indicate that fibers of equal size across an experimental gap in the spinal cord .
tend to possess equal resistance to secondary Factors that influence and often hamper cen-
degeneration. The large fibers degenerate tral regeneration are similar to those influenc-
faster , but are resorbed more slowly. Hence ing regeneration in the peripheral nervous
the debris of total degeneration in the central system (e.g., length of gap between severed
nervous system is in evidence for several stumps, hemorrhage, and scar formation ).
months. Central regeneration is further thwarted by
Compared to neurons in the peripheral the absence of sheath cells to guide the regen -
nervous system, neurons in the central ner- erating axonal sprouts. As early as 1940,
vous system have only limited capacity to re- Sugar and Gerard found evidence of func-
generate their axon. Regeneration within the tional regeneration in adult rats whose tho-
central nervous system of mammals has been racic spinal cords had been transected with
studied with both anatomic and physiologic care to prevent injury to the blood supply
techniques since the second half of this cen- (187). No significant return of function has
5 Neurons 191
9 9
/
1
- jM
\ /
m
3
^53332 :o^ - «»> —
. c*
4
V> S .* ':•;/ 1* * >*. •r.v*:

; •
; . . ..
•
'
•*
•
--- ;
.
•• ••
/• .'vAV-.'V-,
..
o •
.. .
:4 V yAVyV.; .
z .:
*• 1
' »: • :•:•V:• ..
•••? V -.
V :
*
'.V‘jv ‘ ‘‘ ' ,- ,
t V
* .
v
Dt
4
B
Figure 5.41. Stages of nerve regeneration (A) and the consequences of nerve constriction (B) Following severance
of a nerve (A - 1 ) a fibrin clot forms a bridge between the cut ends, and for a short distance in both stumps, the myelin
(m) breaks into droplets and the axon breaks into granules (g) During the first few days following nerve section, the
axon forms multiple sprouts (A -2, A- 3) which later enter the distal Schwann cell tube (A - 4) B- l depicts a normal nerve
fiber, and B- 2 and B-3 show the proximal accumulation of cytoplasm which occurs gradually over a period of several
weeks following application of a constricting cuff. After removal of the cuff (B- 4), the swelling of the axon diminishes
as axoplasmic transport is restored in the distal segment of the fibers.
been noted in the higher mammals following nervate their targets in the superior collicu-
complete transection of the spinal cord . It lus. At this level, the newly formed axon
was shown that remyelination of experimen- terminals resemble normal presynaptic ter-
tally injured axons of the spinal cord can take minals and appear to be functional and per-
place in the cat (18). manent (16). These experiments demonstrate
that if regenerating axons in the central ner-
Peripheral and Central Grafting vous system are able to reach their target area
Experiments they are capable of forming functional synap-
tic connections.
Recent experiments by Albert Aguayo and Another approach developed by Anders
his colleagues demonstrated that peripheral Bjdrklund and colleagues consists of trans-
nerve grafts promote the growth of central planting cells from fetal or neonatal animals
axons. For example, these investigators re- into adult brain to alleviate experimentally
placed central nervous tissue of the optic induced behavioral deficits in rats. For exam -
nerve of adult rats with segments of the pe- ple, movement disorders induced by lesions
ripheral sciatic nerve. The cut axons of gan - of the dopaminergic input to the basal gan -
glion neurons in the adult retina , which do glia can be prevented by grafts of fetal mid -
not normally regenerate into the optic nerve, brain dopaminergic neurons into the dener -
were able to regrow into the graft and rein - vated striatum ( Fig. 5.42 ). The mechanisms of
Figure 5.42. A and B. Two examples of fetal dopaminergic nigral cells implanted Into the striatum of adult rats whose
nigrostriatal dopaminergic pathway had been previously lesioned with the neurotoxin 6-hydroxydopamine (6-OHDA)
These fetal dopaminergic cells have produced numerous processes that display TH immunoreactivity and arborize
profusely within the dennervated striatum. The arborization of the implanted dopaminergic neurons is particularly ob-
vious in B where numerous TH-immunoreactive processes can be seen not only within the confines of the graft, which
corresponds to the area containing the cell bodies, but also in the adjacent striatal areas where the density of the
dopaminergic innervation appears similar to that found in normal animals. The motor deficits caused by the 6-OHDA
dopaminergic denervation of the striatum in these two animals were largely alleviated by the grafts ( x 250).
5 Neurons 193
action of such neural grafts are not fully un- pie, neurons that are insensitive to NGF were
derstood . The grafts may release transmitters shown to be dependent on other trophic fac -
that act at distance upon target cells and / or tors, such as brain-derived neurotrophic factor
release some trophic factors that influence ( BDNF), ciliary neurotrophic factor (CNF), and
cells in the damaged brain. The fetal surface fibroblast growth factor ( FGF) ( 169 ). Further-
adhesion molecules of the grafted cells may more, Schwann cells contribute to the regen -
also provide a suitable microenvironment eration of peripheral axons. In addition to
within which damaged host neurons can re- providing an anatomic substrate for the sup-
connect with their targets ( 12, 62, 93, 118). port and guidance of regenerating axons, the
This approach was recently used to treat proliferating Schwann cells secrete several
motor disorders in Parkinsonian patients. Al - extracellular proteins, such as laminin , which
though promising, the results of these prelim- promote axon extension . Laminin, together
inary clinical trials clearly call for further im - with fibronectin , are glycoproteins that occur
provement of the transplantation approach, in large concentrations in the extracellular
as well as more detailed animal experiments matrix in both the central and peripheral ner-
(12 ). The fetal cell transplant approach was vous systems early in neural development.
also used in rats to partially restore cognitive These two proteins persist in the periphery,
function deficits, such as maze learning prob- but are absent in the adult brain and spinal
lems, induced by cortical lesions or by lesions cord . This may explain , at least in part , the
of the corticallv projecting cholinergic neu - marked difference between central and
rons of the septum and basal forebrain peripheral neurons in their capability of re-
( 44, 85). generating their axon . Developing axons,
themselves, contain intracellular proteins as -
Growth Promoting and Inhibiting sociated with active growth . One of these
Factors proteins, GAP-43 , which has a molecular
weight of 43,000, disappears from the axons
Over the years, various chemical com- of most adult central neurons, but is present
pounds were used in an attempt to stimulate in many adult peripheral neurons. Although
the growth of neurons and their processes. the exact function of this protein is not
One of the best characterized molecules that known , it is interesting to note that it is ex-
can promote nerve regeneration is the nerve pressed in some adult brain neurons that
growth factor ( NGF) ( 114-117). NGF plays a have the capacity to sprout axons after
crucial role in the development of the ner- injury , such as the neurons of the hippo-
vous system, as seen in Chapter 3. However, campus.
recent studies revealed that NGF can also act Conversely, recent biochemical and cell bi -
as a potent neurotrophic agent in specific re- ologic studies by Martin Schwab showed the
gions of the adult brain . For example, NGF existence of two membrane proteins localized
has been used successfully to promote regen - exclusively on oligodendrocytes and central
eration of basal forebrain cholinergic neurons myelin and which exert a powerful inhibitory
whose cortically projecting axons had been effect on neurite growth. These two neurite
experimentally lesioned in the rats (85, 86, growth inhibitory proteins ( NI ) have a molecu -
128). These cholinergic neurons possess spe- lar weight of 33,(X)-35,000 ( NI -35 ) and 250,000
cific NGF receptors on their surface. Corti- ( NI -250), respectively, and are normal con -
cally applied NGF is apparently able to pre- stituents of myelin in the central nervous sys-
vent the cell loss of experimentally damaged tem. Specific antibodies raised against these
basal forebrain cholinergic neurons, as well two proteins, and applied to rats with com -
as allow recovery of memory function, which plete transection of the corticospinal tract ,
is altered in these animals. On the basis of greatly helped regeneration of the corti-
these animal experiments, the use of NGF is cospinal axons. Similar results were obtained
presently envisaged as a possible treatment in rats lacking myelin and oligodendrocytes
for Alzheimer's disease, which is character- in the spinal cord (169 ). These results raise
ized by a marked dysfunction of cortically- the interesting possibility that the difference
projecting basal forebrain cholinergic neu- between central and peripheral neurons in re-
rons. generation capability does not result from a
Since the discovery of NGF, several other lack of trophic factor but from the presence
molecules with growth promoting capability of inhibitory factors in the central nervous
were isolated and characterized . For exam- system .
References -
reticulum like cisterns. J Comp tion of brain catecholamines and
-
Neurol 1980;190:519 532. serotonin. Neurosci Res Program
1 . Abercrombie M, Johnson ML . The 18. Bunge MB, Bunge RP, Ris 11. Ultra - Bull 1971;9:197-205.
effect of reinnervation on collagen structural study of remyelination 36. Dale M. Pharmacology of nerve-
formation in degenerating sciatic in an experimental lesion in adult endings. Proc R Soc Med (Lond )
nerves of rabbits. J Neurol Neuro- cat spinal cord. J Biophys Biochem -
1935;28:319 332.
surg Psychiatry 1947;10:89-92 . Cytol 1961;10:67-94. 37. De Robertis E. Synaptic complexes
2. Acheson AL, Zigmond MJ , Strieker 19. Bunge MB, Bunge RP, Peterson ER, and synaptic vesicles as structural
M. Compensatory increase in tyro- Murray MR A light and electron and biochemical units of the cen -
sine hydroxylase activity in rat microscope study of long term or - tral nervous system. In: Rodahl K ,
brain after intraventricular injec- ganized cultures of rat dorsal root Issekuts B Jr, eds Nerve as a tissue.
tions of 6-hydroxvdopamine. Sci - ganglia . J Cell Biol 1967;32:439-466. New York: Harper & Row ,
ence 1980;207:537-540. 20. Bunge MB. The axonal cytoskele - 1966:88-115.
3. Alberts B, Bray D, Lewis J , Raff M , ton: Its role in regenerating and 38. De Robertis E. Ultrastructure and
Roberts M , Watson JD. Molecular maintaining cell form . Trends cytochemistry of the synaptic re-
biology of the cell . 2d ed . New Neurosci 1986;9:477-487. -
gion . Science 1%7;156:907 914.
York: Garland , 1989. 21 . Bunge RP. Glial cells and the cen - 39. De Robertis E, Bennett 1 IS. Submi -
-
4 . Allen RD. New directions and re
-
finements in video enhanced mi -
- tral mvelin sheath. Physiol Rev
1968;48:197-251.
croscopic vesicular component in
the synapse. Fed Proc I 954;13:35.
croscopy applied to problems in 22. Campbell JB, Bassett CAL, Husby 40. De Robertis E , De Iraldi AP .
-
cell motility Prog Clin Biol Res J, Noback CR. Regeneration of De Lores R , Arnaiz G, Salganicoff
1985;196:3-11. adult mammalian spinal cord . Sci - L. Cholinergic and non -cholinergic
5. Ambrogi LP. Manual of histologic ence 1957;!26:929. nerve endings in rat brain . 1.
and special staining technics. 2d 23. Campbell ) B, Bassett CAL, Husby Isolation and subcellular distribu -
ed . Newr York: McGraw Hill, - |, Noback CR . Axonal regeneration tion of acetylcholine and acetyl -
1960:157-174. in the transected adult feline spinal cholinesterase. J Neurochem 1962;
6. Bargmann W . Neurosecretion. Int cord . Surg Forum , Clin Cong Am 9:23-35.
-
Rev Cytol 1966;19:183 201. Coll Surgeons 1958;8:528-532. -
41 . Dennv Brown D. Importance of
7. Barr ML, Bertram LF, Lindsay HA . 24. Causey G. The cell of Schwann. neural fibroblasts in the regenera -
The morphology of the nerve cell Edinburgh: Livingston , 1960. tion of nerve. Arch Neurol Psychi-
nucleus according to sex. Anat Rec
-
1950;107:283 297.
-
25. Chan Palay V , Palay SL. Coexis
tence of neuroactive substances in
- atry 1946;55:171- 215.
42. Droz B, Leblond CP. Axonal mi -
8. Bentivoglio M , Kuypers HGJM , neurons. New' York: John Wiley & gration of proteins in the central
Catsman - Berrevoets CE, Loewe H, Sons, 1984. nervous system and peripheral
Dann O. Two new fluorescent ret - 26. Chesselet M - F, ed . In situ hy- nerves as shown by radioautogra -
rograde neuronal tracers which are bridization histochemistry. Boca phy. J Comp Neurol 1963;
transported over long distances. Raton , FL: CRC Press, 1990 121:325-346.
Neurosci Lett 1980;18:25-30. 27. Cheung, WY . Calmodulin plays a 43. Droz B, Rambourg A , Koenig HL .
9. Bern , HA, and Knowrles, FGW . pivotal role in cellular regulation. The smooth endoplasmic reticu -
Neurosecretion. In: Martini LM, Science 1980;207:19-27. lum : structure and role in the re-
Ganong WF, eds. Neuroen- 28. Chronwall BM , Lerois ME, newal of axonal membrane and
docrinology. Ch. 5. New' York: Schwaber JS, O' Donohue TL. In synaptic vesicles by fast axonal
Academic Press, 1966:139-186. situ hybridization combined with transport. Brain Res 1975;93:1-13.
10. Bershadsky AD, Vasiliev JM Cy - retrograde fluorescent tract trac - 44. Dunnett S. Cholinergic grafts,
toskeleton. New York . Plenum ing. In : Heimer L, Zaborsky L, memorv and ageing . Trends Neu -
Press, 1988.
11 Bishop TW , I leinbecker P, O' Leary
-
eds. Neuroanatomical tract tracing
methods 2. Ch . 10. New York :
-
rosci 1991;14:371 376.
45. Eccles JC. The physiology of
JL . The function of non myelinated Plenum Press, 1989:265-297. synapses, Berlin: Springer- Verlag,
fibers of the dorsal roots. Am J 29. Chu LW . Cytological study of an - 1964 .
Physiol 1933;106:647-669. terior horn cells isolated from 46. Ehrlich P. On immunity w ith spe-
12. Bjorklund A. Neural transplanta - human spinal cord . J Comp Neurol cial reference to cell life. Croonian
—
tion an experimental tool with -
1954;100:381 413. Lecture Proc R Soc ( Lond ) 19(X);
clinical possibilities. Trends Neu - .
30. Cooper JR Bloom RE, Roth RH. 66:424-448 .
rosci 1991 ; 14:319-322. The biochemical basis of neu - 47. Elfvin LG . The ultrastructure of
13. Black MM , Baas PW . The basis of ropharmacology. 6th ed . Newr unmyelinated fibers in the splenic
polarity in neurons. Trends Neu - York: Oxford University Press, nerve of the cat . J Ultrastruct Res
rosci 1989;12:211 -214. 1991. 1958;1:428-454 .
14 . Bodian D. A new method for stain - .
31 . Copenhaver WM Bunge RP, 48 Erlanger |, Gasser HS. Electrical
ing nerve fibers and nerve endings Bunge MB. Bailey's textbook of signs of nervous activity Philadel -
in mounted paraffin sections. Anat histology 16th ed . Baltimore: phia: University of Pennsylvania
Rec 1936;65:89-97. Williams & Wilkins, 1971 . Presa, 1937.
15. Bodian D. The generalized verte
brate neuron . Science 1962;
- 32. Cowan WM, Gottlieb DL, Hen
drickson AE, Price JL, Woolsey TA.
- 49 Essner E, Novikoff AB. I luman he
patocellular pigments and lyso
-
-
137:323-326. The autoradiographic demonstra - somes, J Ultrastruct Res I 960;
16. Bray GM , Vllegas- Perez MP, Vidal- tion of axonal connections in the 3:374-391.
Sanz M , Aguayo AJ . The use of central nervous system. Brain Res 50. Falck B. Observations of the possi-
peripheral nerve grafts to en - 1972;37:21-51. bilities of the cellular localization
hance neuronal survival, promote 33. Cuello AC . Immunohistochem - of monoamines by a fluorescence
growth and permit terminal recon - istrv . IBRO handbook series: Meth - method . Acta Physiol Stand 1962;
nections in the central nervous sys- ods in the neurosciences. Vol . 3. 56(Suppl 197):1 -25.
tem of adult rats. J Exp Biol New York: John Wilev & Sons, 51. Falck B, Hillarp NA , Thieme G,
1987;132:5-19. 1983. Torp A . Fluorescence of catechol
17. Bn tad well RD, Oliver C, Bright - 34. Culling CFA . Handbook of amines and related compound
man MW . Neuronal transport of histopathological techniques. 2d condensed with formaldehyde. J
acid hydrolases and peroxidase ed . London: Butterworths, 1963: Histochem Cytochem 1%2;10:
within the lysosomal system of or - 348-375. 348-354.
ganelles : involvement of agranular 35. Dahlstrom A . Regional distribu - 52. Fait P, Katz B. Spontaneous sub-
5 Neurons 195
threshold activity of motor nerve morphology of neurons, their 83. Harding HA . Neurological disease
endings. | Physiol ( Lond ) 1952; axons and terminals: immunohis- and mitochondrial genes. Trends
117: 109-128. tochemical localization of an axon - Neurosci 1991; 14:132-138.
53. Fink DJ , Gamor H. Axonal trans - ally transported plant lectin , 84. Ha / rati L- N , Parent A . Conver-
port of proteins: a new view using
in vivo covalent labeling. J Cell
—
Phaseolus vulgaris leucoagglu -
tinin ( PIIA - L ) Brain Refi
gence of subthalamic and striatal
efferents at pallidal level in pri-
Biol 1980;85:175-186. -
290:219 238. mates: an anterograde double- la -
54 . Fink RI \ Heimer L. Two methods 68. Gerfen CR, Sawchenko PE, Carlsen beling study with bioevtin and
for selective silver impregnation of J . The PIIA - L anterograde axonal -
PIIA L. Brain Res 1992; 569:
degenerating axons and their tracing method . In : Heimer L, 336-340.
synaptic endings in the central ner - Zaborsky L, eds. Neuroanatomical 85. Hefti F. Nerve growth factor pro-
vous system. Brain Res 1967; -
tract tracing methods 2. Ch . 3. motes survival ot septal choliner -
-
4:369 374. New York: Plenum Press, 1989: gic neurons after timbrial transec-
35. -
Fitzgerald M . C Fos and the chang - 19-47. tions. J Neurosci 1986,6:603-616.
ing face of pain. Trends Neurosci 69. Golgi C. Sulla fine anatomia degli 86. Hefti F, Wainer WJ Nerve growth
1990;13:439-440. organi centrali del sistems nervoso. factor and Alzheimer's disease.
36. Forn J , Greengard P. IXpolari / ing Riv Sper Frenia Med Leg Ann Neurol 1986;20:275 281 .-
agents and cyclic nucleotides regu -
late the phosphorylation of specific
1882 1885;8:165 195, \< , \
-
9:1
17, 161 - 192, 385 402; 11:72-123,
- 87. 1 ieinbecker P, Bishop GH, O' Leary
JL. Functional and histologic stud -
neuronal proteins in rat cerebral 193-220. ies of somatic and autonomic
cortex slices. Proc Natl Acad Sci 70. Golgi C. Untersuchungen liber den nerves of man . Arch Neurol Psy-
-
USA 1978;75:5195 5199. feineren Bau des centralen und pe - chiatry 1936;35: 1233-1255.
57. Fox CA , Barnard JW . A quantita -
tive study of the Purkinje cell, den -
ripherischen Nervensystems . Jena:
Gustav Fischer, 1894 .
88 lleuser |F , Reese TS. Structure of
the synapse. In : Kandel ER , ed .
dritic branchlets and their relation - 71 . Golgi C. Sur la structure des cel - I landbook of physiology , cellular
lules nerveuses. Arch Ital Biol
- .
ship to afferent fibres. J Anat biology of neurons. Vol . 1, Part I .
1957;91:299 313 1898;30:60-71 . Washington, IX American Physi -
58. Fox CA, Hillman DE, Siegesmund 72. Grafstein B Axonal transport: the ological Society, |977;26 l -294 .
KA . Dutta C’R . The primate cere - ultracellular traffic of the neuron . 89. Heuser JE, Reese TS. Structural
bellar cortex: a Golgi and electron In : Kandel ER , ed. I landbook of changes after transmitter release at
microscope study . In : Fox CA, physiology - Section I: The nervous the frog neuromuscular junction . J
Snider RS, eds. The cerebellum , system . Vol. I: Cell biology of neu - Cell Biol 1981 ;88: 564 - 580.
progress in brain research . Vol . rons, Part I . Washington , DC: 90. Hirokawa N , Pfister KK , Yorifuji
25. Amsterdam. Elsevier, 1967: American Physiological Society, II , Wagner MC , Brady ST, Bloom
-
174 225. 1977;691-717. GS. Submolecular domains of
59. Freeman LW. Return of function 73. Grafstein B. Chromatolysis recon - bovine brain kinesin identified by
after complete transection of the sidered : a new view of the reaction electron microscopy and mono-
spinal cord of the rat, cat and dog. of the nerve cell body to axon in - clonal antibody decoration. Cell
-
Am Surg 1952;136:193 205. |ury . In : Seil FJ , ed . Nerve, organ, 1989,56:867-878.
60. Freund T, Somogyi P. Synaptic re - and tissue regeneration : research 91. 11okfelt T, Bjdrklund A . I landbook
-
lationship of Golgi impregnated perspectives. New York : Academic of chemical neuroanatomy. Vol. 3:
neurons as identified by electro- Press, 1983:37-50. Classical transmission and the
physiological or immunocyto - 74. Grafstein B, Miller JA , Ledeen RW, transmitter receptors in the CNS.
chemical techniques. In : Heimer L, I laley J , Specht SC . Axonal trans- Part 2 Amsterdam: Elsevier, 1985.
Zaborsky L, eds. Neuroanatomical port of phospholipid in goldfish 92 Hokfelt T, Fuxe K , Pemow P. Co-
-
tract tracing methods 2. Ch . 8. optic system. Exp Neurol 1975; existence of neuronal messengers:
New York: Plenum Press, 1989; 46:261-281. a new principle in chemical trans -
- .
201 238 75. Gray EG . Electron microscopy ot mission , progress in brain re -
61 . Gabe M. Neurosecretion . ( Craw - presvnaptic organelles in the spinal search . Vol. 68 Amsterdam : Else-
ford R . trans. ) Oxford : Pergamon , cord . J Anat 1963; 97:101 - 106. vier , 1986
1966:427-736. 76. Gray EG, Guillery RW The basis 93. I lokfelt T, Johansson O, Ljungdahl
62. Gage FH, Fisher LJ . Intracerebral for silver staining of synapses of A , Lundberg JM , Schultzberg M
grafting: a tool for the neurobiolo- the mammalian spinal cord: a light Peptidergic neurones . Nature
gist. Neuron 1991 ;6: 1 -12. and electron microscope study . J 1980284:515 521
63. Gamble HJ . Comparative electron - Physiol ( Lond ) 1961;157:581 588 . .
94 Holtzman E Novikoff AB, Villa -
microscopic observations on the 77. Gray EG, Guillery RW . Synaptic verde H. Lysosomes and GERl. in
connective tissues of a peripheral morphology in the normal and de - normal and chromatolytic neurons
nerve and a spinal nerve root in generating nervous system . Int of rat ganglion nodosum . J Cell
the rat . I Anat 1964,98:17-25.
*
Rev Cytol 1966;19:111-182. Biol 1967,33:419-435.
64. Gasser HS, Grundfest II Axon di - 78. Greengard P. Possible role for 95. Jessell TM . Reactions of neurons to
ameters in relation to the spike di - cyclic nucleotides and phosphory - injury . In : Kandel ER, Schwartz JH ,
mensions and the conduction ve - lated membrane proteins in post - Jessell TM , eds. Principles of
locity in mammalian A fibers Am ) synaptic actions of neurotransmit - neural science. Ch . 18. New York:
Physiol 1939;127:393-414 . -
ters. Nature 1976;260:101 108. Elsevier, 1991;258- 269.
65. Gearv WA II , Wooten GF. Receptor 79. Greengard P. Cyclic nucleotides, 96. Kandel E. Cellular insights into be-
autoradiography . In: Heimer I., phosphorylated proteins and neu - havior and learning . In . The Har -
Zaborsky L, eds. Neuroanatomical ronal structure. New York: Raven vey Lectures, series 73. New York :
-
tract tracing methods 2. Ch 12. Press, 1978. Academic Press, 1979:19-92
New York: Plenum Press, 1989; 80. Greengard P. Cyclic nucleotides, 97. Kandel ER. Nerve cells and behav -
66.
-
311 330.
Geren BB. The formation from the
phosphorylated proteins and the
nervous system . Fed Proc 1979,
ior . In: Kandel FR , Schwartz JII ,
Jessell TM , eds. Principles of
Schwann cell surface of the myelin 38:2208-2217. neural science. Ch. 2. New York:
in peripheral nerves of chick em - 81. Grundfest 11. The properties of Elsevier, 1991 is 12
-
bryos. Exp Cell Res 1954;7:558 562. mammalian B fibers. Am | Physiol 98. Kandel ER , Siegelbaum SA,
67. Gerfen CR , Sawchenko PE. An an - 1939;127:252-262. Schwartz JII . Synaptic transmis-
terograde neuroanatomical tracing 82. Grundfest H . Bioelectric potentials. sion . In: Kandel ER, Schwartz JII ,
method that shows the detailed - -
Aimu Rev Physiol 1940,2:213 242. Jessell TM , eds Principles of
neural science. Ch. 9. New York: -

116. Levi Montalcini R , Hamburger V . 131 . Murray MR, Stout AP. Adult
-
Elsevier, 1991:123 134. Selective growth stimulating ef - human sympathetic ganglion cells
99. Katz B. Nerve, Muscle and -
fects of mouse sarcoma on the sen cultivated in vitro. Am J Anat
synapse. New York: McGraw Hill,
1966.
- sory and sympathetic nervous sys-
tem of the chick embryo. J Zool
1947;80: 225-273.
132. Mvtilineou C, Issidorides M ,
100. Katz B The release of neural trans- ( Lond )
1951;116:321-362. Shanklin WM . Histochemical reac-
mitter substances. Springfield IL:. 117. Levi- Montalcini R , Meyer H , Ham- tions of human autonomic ganglia .
Charles C. Thomas, 1969 . burger V . In vitro experiments on J Anat l %3;97:533-542.
101. King Mil , Louis PM , Hunter BE, the effects of mouse sarcomas 180 133. Nandv K. Histochemical study of
Walker DW . Biocytin: a versatile and 37 on the spinal and sympa - chromatolytic neurons. Arch Neu-
anterograde neuroanatomical tract -
tracing alternative. Brain Res 1990;
thetic ganglia of the chick embryo.
-
Can Res 1934;14:49 57.
-
rol 1968;18:425 434.
134. Nathaniel EJH, Pease DC , Degen -
497:361-367. 118. Lind vail O. Prospects of transplan - erative changes in rat dorsal roots
102. Kirkpatrick JB. Chromatolysis in tation in human neurodegenera- during Wallerian degeneration . J
the hypoglossal nucleus of the rat: tive diseases. Trends Neurosci - -
Ultrastruct Res l %3a ,9:511 532.
an electron microscopic analysis, j 1991;14:376-384. 135. Nathaniel EJH, Pease DC . Regener -
-
Comp Neurol 1968;132:189 212. 119. Livett BG. Immunohistochemical ative changes in rat dorsal roots
.
103. Kitai ST Penny GR, Chang HT. In - localization of nervous system spe - following Wallerian degeneration .
tracellular labeling and immuno- cific proteins and peptides. Int Rev J Ultrastruct Res l %3b;9:533-549.
cytochemistry. In: Heimer L,
Zaborsky L, eds. Neuroanatomical
Cytol 1978;7:53-237.
120. Lloyd DPC . Conduction and
.
136. Nauta WJH, C ygax PA . Silver im -
pregnation of degenerating axons
tract - tracing methods 2. Ch. 7. synaptic transmission of reflex rein the central nervous system : a
New York: Plenum Press, 1989; sponse to stretch in spinal cats. J modified technic Stain Technol
173-199. Neurophvsiol 1943;6:317-326. -
1954a ;29:91 93.
104. Kosik KS. Alzheimer plaques and 121. Loewi O. Uber humorale Ubertrag- 137. Nauta WJH , Gygax PA. Silver im -
tangles: advances on both fronts. barkeit der Herznervenwirkung. pregnation of degeneration axon
Trends Neurosci 1991 ; 14:218-219. Pfluegers Arch 1921;189:239-248. terminals in the central nervous
103. Kuffler SW , Nicholls JG . Martin 122. Luse SA . Electron microscopic ob - system . I. Technic; II. Chemical
AR . From neurons to brain . 2d ed. servations of central nervous sys - notes. Stain Technol 1954 b;26:5-11.
Sunderland , MA : Sinauer, 1984 .
106. Kuvpers HGJM , Bentivoglio M,
tem . J Biophvs Biochem Cytol
1936a ;2:531-542.
138. Nieuwenhuys R Chemoarchitec -
ture of the brain. Berlin : Springer -
-
Catsman Berrevoets CE, Bharos 123. Luse SA . Formation of myelin in Yerlag , 1983
AT. Double retrograde neuronal the central nervous system of mice 139. Novak J , Salafsky B. Early electro -
labeling through divergent axon and rats, as studied with the elec- physiological changes after dener -
collaterals, using two fluorescent tron microscope. J Biophvs Bio- vation of slow skeletal muscle. Exp
tracers with the same excitation chem Cytol 1956b;2:777-783. Neurol 1%7;19:388-400.
wavelength which label different 124. McLennan H. Synaptic transmis- 140. Ochs S. Rate of fast axoplasmic
features of the cell. Exp Brain Res sion . Philadelphia : VV . B. Saunders, transport in mammalian nerve
-
1980;40:383 392. -
1963:3 15. fibers. J Physiol ( Lond ) 1972;
107. Lasek RJ . Protein transport in neu - 125. Masurovsky F.B, Bunge MB, Bunge 227:627-645.
rons. Int Rev Neurobiol 1970; RP Cytological studies of organ - 141 Ochs S, Ranish N . Characteristics
13:289-324 . otypic cultures of rat dorsal root of the fast transport system in
108. Lasek RJ . Axonal transport: a dy- ganglia following x-irradiation in mammalian nerve fibers. J Neuro -
namic view of neuronal structures. vitro. I Changes in neurons and biol 1%9;1 :247-261 .
Trends Neurosci 1980;3:87-91. satellite cells. J Cell Biol 1967; 142. Ortmann R . Neurosecretion. In:
109. La Vail Jll , La Vail MM . Retrograde 32:467-4%. Field J , ed . Handbook of physiol-
axonal transport in the central ner - 126. Mesulam M - M . Tetramethylbenzi - .
ogy neurophysiology . Vol . II, Ch.
vous system. Science 1972; 176: dine for horseradish peroxidase 40. Washington, DC: American
1416 1417 neurohistochemistry: a non car - - Physiological Society, I 960;1039-
110. LaVail JH , LaVail MM The retro- -
cinogenic blue reaction product 1065.
grade intraaxonal transport of with superior sensitivity for visual - 143. Palay SL . Neurosecretion. VII . The
horseradish peroxidase in the izing neural afferents and effer- preopticohvpophysial pathway in
chick visual system : a light and ents. J Histochem Cytochem 1978; fishes. J Comp Neurol 1945;
electron microscopic study . J 26:106- 117. 82:129-143.
Comp Neurol 1974;157:303-358. 127. Mesulam M - M , ed .. Tracing neural -
144 . Palay SL, Chan Palay V . Cerebellar
111 . LaVail JH , Winston KR , Tish A A connections with horseradish per- cortex: cytology and organization.
method based on retrograde intra - oxidase*. IBRO handbook series: Berlin : Springer - Verlag, 1974.
axonal transport of protein for methods in the neurosciences. Vol. 145. Palay SL, Palade GE. The fine
identification of cell bodies of ori- 1 . New York: John Wiley & Sons, structure of neurons. J Biophvs
gin of axons terminating within the 1982. Biochem Cytol 1955;1:69-88.
-
CNS. Brain Res 1973;58:470 477. -
128. Mesulam M M, Geula C, Bothwell 146 . Patton HD. Special properties of
112. Lee JCY . Electron microscopy of MA , llersch LB. Human reticular nerve trunks and tracts. In : Ruch
Wallerian degeneration. J Comp formation: cholinergic neurons of TC, ed . Neurophysiology. Ch. 3.
Neurol 1963;120:65 79.- the pedunculopontino and lat - Philadelphia: VV . B . Saunders, 1961:
113 Lefkowitz RJ , Caron MG, Stiles CL. erodorsal tegmental nuclei and -
66 95.
Mechanisms of membrane- recep- Mime cvtochemical comparisons to 147. Percheron , G, Yelnik, J , and
tor regulation . N Engl J Med forebrain cholinergic neurons. J FranCois, C. A Golgi analysis of the
1984;310:1570-1574 . Comp Neurol 1989;281 :611-633. primate globus pallidus. III . Spatial
114 Levi - Montalcini R , Angeletti PV. 129. Metuzals, J . Ultra structure of the -
organization of the striato pallidal
Growth control of the sympathetic nodes of Ranvier and their sur- complex . J Comp Neurol 1984;
system bv a specific protein factor . rounding structures in the central 227:214-227.
Q Rev Biol 1961;36:99-108. nervous system. Z Zellforsch 148 Peters A . The formation and struc-
113 Levi -Montalcini R, Angeletti PV . Mikrosk Anat 1%5;65:719-759. ture ot myelin sheaths in the cen -
Essential role of the nerve growth 130. Minneman KP, Dibner MD, Wolfe tral nervous system. J Biophvs
factor in the survival and mainte-
nance of dissociated sensory and
.
BB Molinoff PB. pi - and (32-adren-
ergic receptors in rat cerebral cor-
-
Biochem Cytol 1960;8:431 446.
149. Peters A. The node of Ranvier in
sympathetic embryonic nerve cells tex are independently regulated . the central nervous system. Q J
in vitro. Dev Biol 1963;7:653-639 . Science 1979;204:866-868 Exp Physiol 196651:229 236
5 Neurons 197
150. Peters A, Palay SL, Webster H deF. and neuroglial cells as seen with neuroglial cells. ) Cell Biol
The fine structure of the nervous the light microscope. In : Windle 1968;36: 151-179.
system : neurons and their support - WF, ed . Biologv of neuroglia . 184 . Standaert FG, Dretchen KL . Cyclic
ing cells. 3rd ed . New York: Ox - .
Springfield 1 L: Charles C. Thomas . nucleotides and neuromuscular
ford University Press, 1941. -
1958 5 23. transmission. Fed Proc 1979;
151. Peterson ER , Murray MR . Myelin
sheath formation in cultures of
168. Schmitt FO Bear RS Palmer KJ . X -
, ,
rav diffraction studios on the struc -
-
38:2183 2192 .
185. Steward O, Banker ( il 1. Getting the
avian spinal ganglia . Am J Anat ture of the nerve mvelin sheath . ) message from the gene to the
1955;96:319-355. Cell Comp Physiol 1941,18:31 42. - synapse: sorting and intracellular
152. Polack JM , McGee OD. In situ hy - -
169. Schwab ME . Myelin associated in - transport of RNA in Neurons .
bridization. Principles and prac- hibitors of neurite growth and re - Trends Neurosci 1992;15:180-186.
tice. Oxford: Oxford University generation in the CNS. Trends 186. Strange PE Interesting times for
Press, 1990. Neuioed I99(fct3rf 52 456 dopamine receptors Trends Neu -
153. Quensel W. Uber die Faserspezi - 170. Schwartz III . Axonal transport: rosci 1991;14:43 45.
fitat in sensiblen Hautnerven. components, mechanisms and 187 Sugar O, Gerard RW. Spinal cord
Ptlugers Arch . Gesamte Physiol
Menschen Tiere 1944;248: 1 -20.
-
specificity Annu Rev Neurosci
1979;2:467-504.
regeneration in the rat . J Neuro-
physiol 1940;3: 1 - 19
154 . Ramon y Cajal , S. Histologie du 171. Schwart / 111. Synthesis and traf - 188. Thomas PK . The connective tissue
Systeme Nerveux de I' Homme ficking of neuronal proteins. In: of peripheral nerve: an electron mi -
et des Vertebres. ( Azoulav L, Kandel ER , Schwartz JH , Jessoll croscope study I Anat 1963;
trans.) Paris: Maloine, 1909, 1911 TM, eds. Principles of neural sci- 97:35-44 .
( Reprinted , Consejo Superior de ence. Ch. 4. New York: Elsevier, 189. Truex RC. Morphological alter -
Investigaciones Cientificas, Insti - 1991:49-65. ations in the Gasserian ganglion
tute Ramon v Cajal , Madrid , 1972 ). 172. Schwartz JIL Chemical messen - cells and their association with
155. Ramon v Cajal, S.. Degeneration gers: small molecules and pep- senescence in man . Am J Pathol
and regeneration of the nervous tides. In : Kandel ER , Schwartz III , 1940;16:255-268
system. ( Mav RM , trans. and ed ., Jessell TM, eds. Principles of -
190 Uzman BG, Nogueira Graf G . Elec -
1959 ). New York: Hafner, 1928. neural science. Ch. 14. New York: tron microscope studies of the for -
156. Ranson SW. The tract of Lissauer Elsevier, 1991:213-224 . mation of nodes of Ranvier in
and the substantia gelatinosa 173. Scott D Jr, Clemente CD. Mecha - mouse sciatic nerves . J Biophys
Rolandi . Am | Anat 1914;16: nism of spinal cord regeneration in Biochem Cytol 1957;3:589-598
-
97 126. the cat. Fed Proc 1952;11:143-144 . 191 Vallee RB, Bloom GS. Mechanisms
157. Robertson HA, Paul ML, Moratalla 174. Shepherd GM . The synaptic orga - of fast and slow axonal transport.
R , Graybiel AM . Expression of the nization of the brain . 3rd ed . New -
Annu Rev Neurosci 1991;14:59 92.
-
immediate early gene c fos in basal York: Oxford University Press, 192 . Van Crevel H , Verhaart WJC. The
ganglia: induction by dopaminer - 1990. rate of secondary degeneration in
gic drugs. Can J Neurol Sci 175. Shepherd GM Foundation of the the central nervous system . I . The
1991;18:380-383. neuron doctrine. New York: Ox - pyramidal tract of the cat . J Anat
158. Robertson JD. Ultrastructure of ford University Press, 1991 . 1 %3a,97:429-449
*
adult vertebrate peripheral myeli - 176. Sherrington C. The integrative ac- 193. Van Crevel H , Verhaart WJC . The
nated nerve fibers in relation to tion of the nervous system . 2d ed . rate of secondary degeneration in
myelinogenesis j Biophys Bio-
, New Haven : Yale University Press, the central nervous system . II . The
-
chemCytol 1955;1:271 278. 1947. optic nerve of the cat . J Anat
159. Robertson JD. The ultrastructure of 177. Siegelbaum SH, Koester J . Ion 1963b;97:451-464
Schmidt -Lantermann clefts and re- channels. In: Kandel ER , Schwartz 194 . Van der Kooy D, Kuypers HGJM,
lated shearing defects of the JH , Jessell TM , eds. Principles of -
Catsman Berrevoets CE. Single
mvelin sheath . J Biophys Biochem neural science. Ch. 5. New York: mammillary cell btniies with diver-
-
Cytol 1958;4:39 46. Elsevier, 1991:66-79. gent axon collaterals. Demonstra -
160. Robertson JD. Preliminary obser - 178. Sjostrand FS. The structure and tion by a simple, fluorescent retro-
vations on the ultrastructure of formation of the myelin sheath . In: grade double labeling technique in
nodes of Ranvier . Z Zellforsch Rose AS, Pearson CM , eds. Mecha - the rat. Brain Res 1978;150: I 89-
Mikrosk Anat 1959;50:553-560. nisms of demyelination . New 196.
161. Ross LL , Bornstein MB, Lehrer G. - -
York: McGraw Hill, 1963:1 43. 195. Vizoso AD, Young JZ. Internode
Electron microscope observations 179. Smith Y, Bolam JP. Convergence of length and fibre diameter in devel -
of rat and mouse cerebellum in tis- synaptic inputs from the striatum oping and regenerating nerves. J
sue culture. J Cell Biol 1962; and the globus pallidus onto iden - -
Anat 1948;82: 110 134.
14:19-30. tified nigrocollicular cells in the 195. Waksman B1 L Experimental study
162. Rusak B, Robertson HA , Wisden rat: a double anterograde labeling of diphtheritic polyneuritis in the
W , Hunt SP. Light pulses that shift study. Neuroscience 1991;44:45-73. rabbit and guinea pig. III . The
rhythms induce gene expression in 180. Snyder SH . Brain peptides as neu - blood nerve barrier in the rabbit . J
the supraoptic nucleus. Science rotransmitters. Science. 1980; 209: Neuropathol & Exp Neurol
1990;248:1237-1240. -
976 983. 1961;20:35-77
163. Salafskv B, Jasinski D. Early elec- 181 . Sokoloff L. Relation between phys- 197. Waldeyer W Ueber einige neuere
trophvsiological changes after de - iological function and energy me- Forschungen im Gebiete der
nervation of fast skeletal muscle tabolism in the central nervous Anatomic des Centrainervensys-
Exp Neurol 1967;19:375-387. system . J Neurochem 1977; 29: tems. Dtsch Med Wochenschr 1891 ;
164 . Scharrer B Recent progress in the 13-26. 17:1213-1218, 1244-1246, 1267-
study of neuroendocrine mecha - 182. Somogvi P, Freund T. Immunocy- 1269, 1287-1289, 1331 -1332, 1352 -
nisms in insects. Arch Anat tochemistrv and synaptic relation - 1356.
Microscop Vlorphol Exp 1965,54: ships of physiologically character- 198 Webster H del Transient , focal ac-
331-342. ized HRP-filled neurons. In : cumulation of axonal mitochon -
165. Scharrer E, Scharrer B. Secretory
cells within the hypothalamus.
Heimer L, Zaborsky L, eds. Neu
roanatomical tract- tracing methods
- dria during the early stages of
Wallcrian degeneration J Cell Biol
Proc Assoc Res Nerv Ment Dis 2. Ch. 9. New York : Plenum Press, 1962;12:361-377.
-
1940;20:170 194 1989:239-264. |W. Weiss P. Neuronal dynamics and
166. Scharrer E, Scharrer B. Neurosecre- 183. Sotelo C, Palay SL. The fine struc- neuroplasmic flow. In: Schmidt
tion . Physiol Rev 1945;25:171-181 ture of the lateral vestibular nu - FD, ed . The neurosciences . Second
167. Scheibei ME, Scheibel AB. Neurons cleus in the rat . I . Neurons and study program New York : Rock -
feller University Press, 1970; ( Macaca mulatta ). Brain Res mate globus pallidus. II Quanti -
840-850. 1969;14:546-548. tative morphology and spatial
200. Weiss P, Miscoe MB. Experiments 203. Wilson WS, Schulz RA, Cooper JR . orientation of dendritic arboriza-
on the mechanism of nerve growth. The isolation of cholinergic synap- tion . ) Comp Neurol 1984;227:
J Exp Tool 1948,107: 315-396. tic vesicles from bovine superior 2(X)-213.
201. Whittaker VP. The application of cervical ganglion and estimations 206. Young JZ. The functional repair of
subcellular fractionation tech- of their acetylcholine content . J nervous tissue. Physiol Rev 1942;
niques to the study of brain func- Neurochem 1973;20:639-667. -
23:318 374.
tion . Prog Biophvs Chem 1965; 204. Windle WF, Chambers WW. Re- 207. Young jZ. Factors influencing the
15:39-96. generation in the spinal cord of the regeneration of nerves. Adv Surg
202. Wiitanen JT. Selective silver im - cat and dog. j Comp Neurol 1950; 1949;1:163-220.
pregnation of degenerating axons 93:241 - 257. 208. Zimmerman H. Vesicle recycling
and axon terminals in the central 205. Yelnik J, Percheron G , Francois and transmitter release. Neuro-
nervous system of the monkey C. A Golgi analysis of the pri - science 1979;4:1773-1804.
6
Neuroglia
CHANGING CONCEPT OF NEUROGLIA portant clue about glial function came from
the description of their behavior in diseases
As seen in Chapter 5, the central nervous or injuries. These cells were found to be ex-
system is made up of only two cell types, tremely sensitive to disturbance, modifying
neurons and neuroglia, the latter being far their shape and location in response to the
more numerous than the former in all regions most minor changes in brain tissue (95). At
of the brain and spinal cord and in all species. the beginning of the 1970s, careful studies by
Neuroglia ( nerve-glue) occur first during on- Pasko Rakic and others (96) revealed the fun -
togeny, but the bulk of glial cells do not arise damental role that neuroglia play during em-
until the majority of neurons have developed , bryonic development in guiding the migra -
that is around the time of birth or in the tion of neurons from the neuroepithelium to
early postnatal period (12). Cell counts made their adult location (see Chapter 3). More re-
in different species suggest that the cent studies confirmed and greatly extended
neuroglia / neurons ratio has steadily in- this view by showing the very active role of
creased during phylogeny (104). Indeed, the glial cells in establishing and maintaining the
numerical preponderance of glia over neu- fundamental patterns of neuronal circuits (33,
rons, already obvious in rodents, markedly 68, 93).
increases in primates and reaches its peak in During the last decade, the application of
humans. Of all living species, the human ap- technical approaches as diverse as tissue cul-
pears to possess the brain that has, both in ture, immunology, patch-clamp electrophysi-
relative and absolute terms, the greatest num- ology, receptor localization, and molecular
ber of glial cells (95, 104). biology have radically changed our view of
It is, therefore, surprising to see that, com- neuroglia . Biochemical and immunologic in-
pared to neurons, relatively little is known of vestigations produced , among other things,
the roles of neuroglia. In fact, until recently, highly specific biochemical markers for
the only functions attributed to neuroglia studying the neuroglia cell lineage. Electro-
were those already postulated by the first physiologic investigations revealed that glial
neuroanatomists that discovered and charac- cells possess different voltage-dependent
terized these elements in the first half of the ions channels that can be activated by specific
19th and the beginning of the 20th century transmitter receptors located on their mem-
( 27, 43, 98, 99 129, 130 ). The neuroglia was left brane (55, 73, 77, 121 ). Some glial cells were
with the rather passive role of supporting also shown to play a crucial role in the main-
and protecting neurons during the perfor- tenance of the homeostasis of the microenvi-
mance of their noble functions, upon which ronment (71, 132) and the immunologic re-
the entire complexity of the human brain was sponse to various infectious or toxic agents
thought to rely. This rather simplistic view of (122). Neuroglia is now known to produce
the brain has lost much of its original signifi- various growth and trophic factors, which
cance and the role and status of neuroglia has makes it a key element in central nervous sys-
been reappraised in the light of new data tem regeneration and plasticity (85). It is also
gathered during the last decade. thought to be directly involved in the basic
The supporting and protecting role of neu- mechanisms underlying certain neurodegen-
roglia was confirmed , particularly through a erative diseases (31, 48, 65).
multitude of very detailed light and electron It is clear that glial cells are now viewed in
microscopic studies of glial cells. These stud- a much more dynamic way than previously.
ies provide a clear picture of the immense di- These central nervous system elements are
versity of this cell population. Another im- now believed to be much more closely associ-
199
ated with neuronal functions. The various •„ .

changes through which the concept of neu - \
roglia went since the discovery of these cells . '
in the middle of the 19th century are certainly

unique in the history of neurobiology. First
thought of as a sort of "glue" or simple con-
nective tissue, then later regarded as support -
ing and protective tissue, neuroglia is now
believed to play a key role in association with
neurons in the overall functioning of the cen-
tral nervous system. It seems that we have
now entered the era of "neurogliobiology"
( 86 ) .
GENERAL FEATURES AND CELL LINEAGE

The discovery of neuroglia is attributed to
the German pathologist Rudolph Virchow, , * .
who first called it Bindesubstanz (connective
X £ V ~
i \ TOfcfcUv
'
tissue) and later Nervenkitt nerve-cement 9

(
( 55, 95, 116, 136 ). Early investigators recog-
) "
»,
yf
•* V' • >*
Idfa f A k
#.]L
«
y
3
nized that neuroglia separated neural ele- VK jrg

ments from blood vessels and regarded neu -
roglia as an interstitial material in which Figure 6.1. Astrocytes showing their radially arranged
characteristic stellate and spindle-shaped processes and " end feet " (Ramon y Cajal gold-subli-
, x
cells were suspended . Although peripheral mcrte method 150)
nerves have a supporting framework formed
by connective tissue, this is lacking in the cen -
tral nervous system . In the brain and spinal separated from each other by extracellular
cord , connective tissue is limited to the mem - fluid contained in a space 10-20 nm in width
branes which surround and envelop them, ( 32, 84).
the meninges, and small extensions of these In contrast to other epithelial tissues, there
membranes which accompany blood vessels is relatively little extracellular space in the
that penetrate neural tissue (see Chapter 1 ). central nervous system . Electron microscopic
At the light microscopic level the structural studies indicate that neurons and neuroglia
features of neuroglia are difficult to demon- are tightly packed in the central nervous sys-
strate except by complex selective staining tern with spaces no greater than 20 nm wide
methods. In ordinary preparations stained between individual cells. However, measure-
with basophilic dyes, usually only the nuclei ments of the extracellular space, based upon
are seen . Sections impregnated by the metal - equilibration with sucrose, suggest that the
lie techniques of Golgi ( 43), Ramon y Cajal small size of the extracellular space in elec-
(97,98, 99 ), and Del Rio Hortega ( 27, 28 ) reveal tron micrographs of conventionally proces-
the different cell types, their processes and sed tissue is an artifact probably due to cellular
their relationships to neurons and blood ves- swelling resulting from asphyxia (67). In
sels ( Figs. 6.1-6.4, and 6.7). In the first half of fact, the real extracellular space in mature
the 20th century, the morphologic character- brain appears to be approximately 15-20%
istics of neuroglia as observed in the light mi- in volume ( 25, 67).
croscope were described by several authors: Information concerning the volume, the
Pen field (87), Del Rio Hortega (30), Glees ( 42 ), nature of the fluid filling the extracellular
Scheibel and Scheibel (109), Windle (135), and space, and the possibilities for controlling
Polak (91 ). Electron microscopic studies indi- both its composition and volume is of great
cate that the interstitial material of the central practical significance in relation to cerebral
nervous system is composed only of neu - edema . Electron microscopic investigations
roglia ( 40, 90). Thus the central nervous sys- suggest that experimental and clinical edema
tern is composed almost entirely of two ele- in the gray matter of the brain may be due to
ments, neurons and neuroglia , which are swelling of glial cells, particularly astrocytes
6 Neuroglia 201
Protoplasmic
astrocytes of Fibrous astrocytes
gray matter of white matter
Figure 6.2 . Distribution and appearance of astrocytes in gray and white matter of human spinal cord. Smaller nerve
cell bodies are often obscured by profuse branches of protoplasmic astrocytes. Blood vessels (b. v.) also are stained In
such preparations and receive vascular end feet from adjacent astrocytes (Golgi stain, x 175).
( 26). In the white matter, where edema is the central nervous system and Schwann cells
more severe, the enlargement is primarily in in the peripheral nervous system ) in the for-
the extracellular region with marked widen - mation of myelin sheath ( 16, 17).
ing of the 20 nm extracellular space (128). It is Classically, two categories of glial cells are
apparent that cerebral edema is not a uniform recognized in the central nervous system,
reaction in neural tissue. macroglia and microglia ( Fig . 6.3). The
In mammals, neuroglial cells outnumber macroglia , comprising astrocytes and oligo-
nerve cells 10:1 and form about half of the dendrocytes, are derived from ectoderm,
total volume of the human brain . Their coun - have only one type of cytoplasmic process,
terparts also are a constant feature of the pe- do not generate action potentials, and have
ripheral nervous system . Similar supportive not been observed to provide or receive
cells are present in all vertebrate nervous sys- synapses. In contrast to macroglia, there is
tems and in some invertebrate nervous tissue still a debate about the origin of microglia .
as well ( 14, 22, 37, 61 ). The wide distribution Microglia are considered by some authors to
of this class of cells throughout the animal be of mesodermal origin and to derive from
kingdom suggests that their functional role monocytes ( macrophage precursor cells) that
must be of great importance. Glial cells of the infiltrate the embryonic brain and spinal cord
mammalian brain are difficult to study be- when these developing structures are pene-
cause of their inaccessibility. For this reason trated by blood vessels ( Fig. 6.3). However, a
information has been sought concerning neu - neuroectodermal origin was proposed re-
roglia in invertebrates and nonmammalian cently by Federoff and his colleagues, based
vertebrates (37, 56, 57, 61 ), as well as in tissue on the appearance of macrophages in culture
culture studies ( 41, 74, 75, 78, 92). Among the derived from a mouse brain before vascular-
most widely accepted functions of neuroglia ization ( 45). Whichever turns out to be true,
is the role of glial cells (oligodendrocytes in microglia have more in common with periph -
Figure 6.3. .
Various types of neuroglia cells . AS- 1 Fibrous astrocyte with one or two processes forming foot plates
.
against a neighboring blood vessel; AS-2 protoplasmic astrocyte with foot plate containing gliosomes (dark gran-
ules) in its body and processes; M/C. microglial cell whose delicate spiny processes embrace the bodies of two neu-
.
rons; OL - I . oligodendrocyte in the white matter (interfascicular form); OL -2 two oligodendrocytes lying against a
nerve cell (perineuronal satellites).
oral macrophages than with other cells in the cells), and the satellite cells of peripheral sen -
nervous system, both in the molecule they sory ganglia, in addition to the macroglia and
express and in their behavior when activa- microglia. Ependymal, neurilemma and satel -
ted ( 2 ). lite cells are all derived from ectoderm;
In the broadest sense, neuroglia, often re- neurilemma and satellite cells are derivatives
ferred to simply as glia , should include the of the neural crest. Unlike neurons, neuroglia
ependyma, the neurilemma cells (Schwann retain the ability to divide throughout life.
6 Neuroglia 203
iJAM*
Figure 6.4. ( A . ) Fibrous and (B.) protoplasmic astrocytes in white matter of adult cerebral cortex Note numerous
gliosomes ( g ) in the processes of the fibrous astrocyte and vascular end foot on blood vessel (b. v ) (Golgi-staln,
x 550).
Proliferation of macroglia occurs particularly whereas oligodendrocytes and type-2 astro-

in response to injury in the nervous system cytes develop from a common , bipotential
( 58, 68, 112, 118). precursor called the 0-2 A progenitor cells. The
No morphologic classification of neuroglia 0-2A progenitor cells differentiate au-
is entirely satisfactory, for there may be many tonomously into oligodendrocytes in culture,
intermediate forms between oligodendro- while their differentiation into type-2 astro-
cytes and astrocytes (21, 42, 62, 63, 93, 100, cytes requires two or more inducing factors
105, 111, 133), and some authors do not con - produced by other cells as well as extracellu-
sider microglia to be true neuroglial cells (90). lar matrix signals. Two of the effective induc-
In fact, considerable evidence for glial hetero - ing factors are the ciliary neurotrophic factor
geneity exists and there are many examples (CNTF) and the platelet-derived growth fac-
of regional variations in the phenotypic ex
pression of glial cells ( 21, 93, 101, 133). The
- tor ( PDGF), which are produced by type-1 as-
trocytes and / or mesenchymal cells ( 41 ). The
development of macroglia has been studied existence of the type-2 astrocyte in the mature
extensively in cell culture of the developing central nervous system is still a matter of con-
rat optic nerve, which has served as a very troversy (41 ). These results suggest that glial
useful model for the study of complex cell-to- cells, like neurons, defy rigid classification
cell interactions that underlie macroglial dif - because of their remarkable phenotypic plas-
ferentiation (41, 94). Such cultures were ticity in response to changes in their environ-
shown to contain three antigenically distinct ment.
types of macroglial cells: oligodendrocytes
and two types of astrocytes ( type-1 and type- ASTROCYTES
21. These three cell types appear to arise from
two separate lineages: type-1 astrocytes de- Astrocytes are the largest, most numerous,
velop from one type of precursor cells, and most elaborate of all the glial elements.
They are recognized by their stellate-shaped lar walls, (c) being coupled with gap junc--
cell body and their many processes which ex- tions, and (d ) most express glial fibrillary
tend into the surrounding neuropil ( Figs. 6.1 acidic protein (GFAP) at one specific time-
and 6.2). Some of the long, branched pro- frame during their development (121).
cesses from each cell form expansions that are
applied to the surface of blood vessels, where Fibrous and Protoplasmic Astrocytes
they form the so-called end feet , a major
component of the blood -brain barrier (see Two main types of astrocytes can be dis-
Chapter 1 ). Processes of astrocytes ex- tinguished in both light and electron mi-
tending to the surface of the central nervous croscopy. The fibrous astrocyte (spider cell ) is
system form similar expansions that consti- characterized by its thin, poorly branched
tute the superficial glial membrane ( glia limi- processes, which radiate from the cell body
tans ) beneath the pia mater. Each neuron has for considerable distances. These glial ele-
a specific relationship with the astrocytic ments are often interposed between neurons
processes in its vicinity, ranging from com- and adjacent blood vessels and have promi-
plete encapsulation to none at all (83, 89). As- nent perivascular end feet (9)( Figs. 6.1, 6.3 and
trocytes form a continuous lining separating 6.4). Fibrous astrocytes are most numerous in
brain from mesenchymal structures capil -—
laries, meninges, and vascular adventitia en-
the white matter ( Fig. 6.2). With appropriate
stains the cell body and processes are seen to
closing the Virchow-Robin ( perivascular ) contain many delicate fibrils. Each intracellu-
spaces. A basal lamina is invariably inter- lar gliofilament is 10 nm in width and of vari-
posed between astrocytes and mesenchyma ous length. Such filaments correspond to the
(see Chapter 1). thicker fibrils observed in muscle and epithe-
The astrocytes are densely packed within lial cells (i.e., myofibrils and tonofibrils ) and
the neuropil of the nervous system ( Fig. 6.2), are part of the group of intermediate fila-
and reduce the extracellular space to a series ments, which form neurofilaments in neurons
of irregular and interlacing small clefts. With (see the section entitled Neuronal Cytoskeleton
the Golgi stain, these glial cells show a deli- in Chapter 5). In the larger processes, they are
cate, but pervasive, framework in which the arranged in straight parallel bundles and can
neural elements appear to be suspended ( Fig. be followed for considerable distances. Such
6.2). In sharp contrast to this somewhat rigid gliofibrils are much less numerous in the pro-
configuration, astrocytes in tissue culture toplasmic astrocytes described later. Another
show flowing veil-like expansions in all di- feature common to both types of astrocytes
rections, and migrate with a slow, gliding are small granular swellings along the pro-
motion ( 39, 40, 74). cesses called gliosomes ( Figs. 6.3 and 6.4).
Astrocytes form a highly heterogeneous They occur in the cell body as well, and in
cell population in the central nervous system electron micrographs they are seen to be
(39, 40, 93). In fact, astrocytes belong to a clumps of mitochondria which contain a
large family of cells displaying various mor- dense matrix material.
phologic and functional phenotypes, as well The protoplasmic astrocytes ( mossy cells) are
as regional specificity. The family comprises most numerous and easy to identify in the
radial glia, the probable precursor of fibrous gray matter ( Fig. 6.2). They have numerous
and protoplasmic astrocytes (131 ), ependy - freely branching processes, perivascular end
mal cells, Bergmann glia in the cerebellum, feet, and often are observed in close proxim-
Muller glia in the retina , tanycytes in the hy- ity to neuronal soma and dendrites. If fibrous
pothalamus, and specialized glial cells that and protoplasmic astrocytes are examined in
are found in the posterior lobe of the hypoph- Golgi preparations ( Fig. 6.4 ), one can find
ysis ( pituicytes) and in the pineal gland sharp distinctive cells in each category . In the
( pinealocytes). It also contains a relatively same sections, one can also observe a host of
large number of cell subpopulations that can intermediate and transitional cells that defy a
be differentiated from one another by their precise morphologic classification. Electron
receptors, ionic channels, and antigenicity microscopic studies suggest that they may
( 21, 93, 133). These cells all share common represent different forms of the same cell (69,
features, including ( a ) interactions with neu - 90). Variations in cell type may in part be a
rons, ( b) close contacts with either the glia reflection of the cytoarchitectural differences
limitans, perivascular walls, or with ventricu- that exist between the gray and white matter
6 Neuroglia 205
of the brain and spinal cord . Electron micro- tive morphologic features. Their camera lu -
scopic features common to both types of as- cida reconstructions clearly show the differ -
trocytes ( Fig. 6.5) are the usual cytoplasmic ence between the very long, threadlike
organelles: dense mitochondria , scanty rough processes of fibrous astrocytes in the white
and smooth endoplasmic reticulum, gliofila - matter compared with the shorter, sinuous
ments, and an abundant watery cytoplasm. processes with clusters or lamellar ap-
The nucleus is finely granular and only mod - pendages of protoplasmic astrocytes in gray
erately dense, and nuclear pores have been matter ( 107 ).
identified , as shown by Palay (82 ) and
Maxwell and Kruger (69 ). Fine structural Specific Biochemical Markers
characteristics that identify the astrocyte
alone were described by the latter authors. The various astrocytes can be distin-
These include a watery cytoplasm that con - guished from one another by different molec-
tains gliofilaments and dense glycogen granular characteristics, including specific endoge-
ules 15-40 nm in diameter. Furthermore, re- nous proteins and cell -surface antigens. For
cent intracellular HRP experiments by Sasaki example an acidic protein, with a molecular
and colleagues have shown that gray matter weight of 24,000, and termed S-100 because of
and white matter astrocytes possess distinc- its solubility in saturated ammonium sulfate,
Figure 6.5. Fibrous astrocyte (As) from normal, adult rat optic nerve The astrocytic cell body contains numerous fila-
.
ments (F) as do the astrocytic processes (AP) which subdivide the myelinated axons ( MA) of the optic nerve into
bundles ( x 12.000)
is found mainly in glial cells in the adult rat system microenvironment. Because of their
( 70). However, one of the most widely used close contacts with neurons, astrocytes are
astrocytic markers is glial fibrillary acidic pro-
ideally located for this purpose. Furthermore,
tein (GFAP), which differs from S-100 in due to the presence of gap junctions, astro-
amino acid sequence and electrophoretic mo- cytes form a functional syncytium so that
bility, and also differs from the fibrillary pro-
changes in the concentration of ions and small
teins tubulin and filarin found in neurons (6) solutes can be rapidly equilibrated (71 ). It is
worth noting that, because of the high synap-
( Fig. 6.20). GFAP is the subunit of the interme-
diate filaments in astrocytes. In immature tic activity, the homeostasis requirements are
skeletal muscle, 10- ntn filaments were first particularly stringent in the gray matter. The
called "intermediate" because their diameter maintenance of adequate extracellular con -
was between that of thin actin and thick centrations of potassium ( K ) and glutamate
*
myosin filaments. The term is now applied to are two examples of the role of astrocytes in
all 10-nm filaments regardless of their lo- the control of the microenvironment.
cation . In all nonmuscle cells, the term inter- Potassium concentration |K 4 ] is much
mediate refers to filaments with a diameter lower in the extracellular than in the intracel -
ranging from that of microfilaments and lular space. The membrane of both astrocytes
microtubules. Intermediate filaments have a and neurons are permeable to potassium and
similar appearance in most cells, but their this, together with the large concentration
protein subunits are regarded as highly spe- gradient, is the reason for their negative
cific and can be used as a taxonomic criterion membrane potential (see Chapter 5). Al-
to differentiate the major cells of the body: ep-
though the amount of potassium release dur-
ithelia ( keratins ), mesenchyma ( vimentin ), ing neuronal signaling is relatively small, it
muscle (desmin ), astroglia (GFAP), and neu - nevertheless produces a significant increase
rons ( neurofilament proteins; see Chapter 4) in extracellular ( K ]. Increase of extracellular
*
( 4 ). Because of the large number of intermedi -

|K ] depolarizes neurons and astrocytes due
4
ate filaments in fibrous astrocytes, compared to the decrease of concentration gradients.

to protoplasmic astrocytes, GFAP is closely To avoid excessive neuronal depolarization
associated with fibrous astrocytes in both nor- (spreading depression ) due to high extracel -
mal and pathologic brain tissue (5), and with lular IK ' |, potassium needs to be buffered in
some way. Dispersal of this ion through the
embryonic radial glial cells ( 60 ). Of high clini-
cal relevance is that increased production of astrocyte syncytium, a phenomenon called
GFAP is one of the most sensitive indicators spatial buffering , is one of the most effective
of central nervous system damage ( Fig. 6.20). mechanisms for extracellular |K ' | regulation.
Another biochemical marker for astrocytes The astrocytes membrane is more permeable
is glutamine synthetase, the enzyme responsi- to potassium than the neuronal membrane.
ble for the formation of glutamine from gluta - Increase in extracellular |K ] results in more
mate, ATP, and ammonia . In the brain, this potassium influx in astrocytes than in neu -
enzyme is exclusively found in astrocytes. It rons. If the increase of extracellular |K ‘ l is
is involved in the regulation of glutamate and local , potassium will be redistributed to dis-
GABA pools in the microenvironment . Astro- tant areas where extracellular [ K + ] is lower
cytes can also be readily identified by the via the astrocyte syncytium. This remarkable
monoclonal antibody A2 B5 ( 35), which recog- mechanism allows for a return of extracellu-
nizes specific gangliosides that are express at lar |K ’ | to normal values without loss of
the cell surface of astrocytes. This monoclonal potassium from the brain . This is important
antibody is extensively used as an astrocytic because the cerebral capillary endothelium is
marker, particularly in tissue culture studies relatively impermeable to potassium (132 ).
( 41 ) . Since astrocytes possess other distinctiveThe regulation of extracellular IK 4 ] is pos-
features, such as specific receptors and ionic sible because of numerous ionic pumps pre-
channels, other biochemical markers or elec- sent within the membrane of astrocytes. In a
trophysiologic properties can be used to iden- first step, potassium ions enter into the astro-
tify the various types of astrocytes. cyte through passive, voltage-independent
channels. However, if the intracellular ( K '|
Homeostasis and Ionic Channels increases significantly, this will activate
potassium and sodium ATPase-dependent
One of the major functions of astrocytes is pumps, as well as various transport systems
to ensure the stability of the central nervous for potassium chloride ( KC1) and sodium
6 Neuroglia 207
chloride ( NaCl ) ( 79 ). The potassium influx tamate by the enzyme glutamate transami-
transforms the astrocyte into a polarized cell nase (GABA -T) and then to glutamine by the
-
whose surface expresses voltage dependent enzyme glutamine synthetase. Glutamine is
potassium, sodium, chloride, and calcium again exported into the extracellular space
ionic channels. Compared to neurons, volt- where it can be taken up by neurons and
age-dependent ionic channels are relatively transform into glutamate and / or GABA
few in astrocytes and this may explain why ( 121 ). Large concentrations of GABA in the
astrocytes do not generate action potentials. microenvironment can induce lethargic
The roles of the voltage-dependent ionic states, whereas lack of this major inhibitory
channels in astrocytes remain to be deter- transmitter can produce convulsions. There-
mined . fore, the role that astrocytes play in the con -
Astrocytes also control the extracellular trol of extracellular concentrations of gluta -
concentrations of glutamate, GABA, and bio- mate and GABA is a perfect example of the
genic amines. It appears that the segregation importance of glial -neuronal interactions in
of glutamate and GABA within glial and neu - the control of homeostasis in the central ner-
ronal compartments is one of the major vous system .
mechanisms involved in the control of these
two amino acids transmitters. Astrocytes pos- Transmitter Receptors
sess the highly specific uptake mechanisms
for these two transmitters, as well as the en - Astrocytes display a high degree of pheno-
tire enzymatic machinery to metabolize them typic plasticity since they are able to respond
( 3, 36, 48 ). Despite some regional differences, to various stimuli by changing their form,
the uptake capacity of glutamate is much functional state, and even their rate of multi -
higher in astrocytes than in neurons, whereas plication. Among these various stimuli are
the reverse is true for GABA . Glutamate is several small-molecule transmitters and neu -
released in large amounts at excitatory roactive peptides, which can bind to astro-
synapses in the central nervous system , cytes via specific cell membrane receptors
where it binds to specific neuronal receptors ( 73, 119). Specific astrocytic receptors exist for
(see Chapter 3). Those molecules that did not a large number of molecules, including epi-
bind to the appropriate receptors or the ones nephrine («- and [J-adrenergic receptors), his-
that are liberated from the receptors after tamine, dopamine, serotonin, substance P,
they exerted their action are actively taken up bradykinin, secretin, adenosine, vasoactive
by astrocytes and metabolized into glutamine intestinal peptide, and calcitonin ( 134 ) . These
by glutamine synthetase, an enzyme that is receptors are, like their neuronal homo-
specific to astrocytes. Since glutamate, like logues, often coupled to second messengers.
other acidic amino acids, is neurotoxic in The physiologic responses to the activa -
large concentration (excitotoxins), a failure in tion of many of these receptors are not yet
the astrocytic glutamate uptake and meta - known. However, it is well-established that
bolic mechanisms is believed to be a factor the activation of [J-adrenergic, vasoactive in-
contributing to neuronal necrosis in status testinal peptide, and serotonin astrocytic re-
epilepticus and anoxia . Furthermore, since ceptors induces glycogenolysis. It must re-
astrocytic glutamine synthetase uses ammo- membered that glycogen particles are one of
nia and ATP to transform glutamate into glu - the distinguishing features of astrocytes, al -
tamine, astrocytes are thought to play an im - lowing their identification especially where
portant role in brain ammonia detoxification . intermediate filaments are few in number
After diffusion into the extracellular space, ( e.g., in the neocortex ) ( 4 ). In addition to nor-
glutamine may be taken up by neurons and adrenaline, several substances released bv
hydrolyzed back to glutamate by glutami- neurons during depolarization, such as
nase, which is mainly a neuronal enzyme. adenosine and potassium, stimulate glyco-
GABA is synthesized from glutamate by genolysis. It is thus possible that one func-
the enzyme glutamate decarboxylase (GAD). tion of the astrocytic is to provide energy to
It is released in large amounts at the level of active neurons (66). In turn, astrocytes have
inhibitory synapses in the central nervous been found to release arachidonic acid deriv-
system (see Chapter 5). After its release in the atives, such as prostaglandins and leu -
synaptic cleft, GABA may be taken up partly cotrienes, as well as other vasorelaxing fac-
by neurons and partly by astrocytes. Within tors with properties similar to nitrous oxide.
astrocytes, GABA is first metabolized to glu - Furthermore, activation of (J-adrenergic, va -
soactive intestinal peptide, and serotonin ing neurons, but these glial cells appear also
astrocytic receptors, coupled to cAMP or involved in the control of neuronal morpho-
phosphoinositides, can produce significant genesis. This is exemplified by the now clas-
changes in the phosphorylation of GFAP. sic experiment of Prochiantz and Mallat (93),
Therefore, through their action on the major which showed that neurons of the substantia
astrocytic cytoskeletal elements, neurotrans- nigra developed dendrites when grown in
mitters can modify the shape of astrocytes culture with astrocytes from this nucleus,
( 59, 64, 121 ). whereas they developed axons in the pres-
Catecholamines released normally at ence of astrocytes from the striatum, which
synaptic junctions, as well as neurotrophic they are supposed to meet in situ only at the
viruses, endogenous toxins, and interferon y end of their axogenesis. Furthermore, it was
released at the level of cerebral lesions, can shown that the shape of substantia nigra
activate specific astrocytic genes and induce dopaminergic neurons, or, especially , the ex-
the expression of the encoded proteins. This tent of their dendritic arborization, depends
is the case of NGF, as well as other factors, in large part from the local astrocyte popula -
such as interleukins and cytokins (121 ). Ac - tion (33). It remains to be seen whether astro-
tive astrocytes can also release interferon ot / (i cytes affect neuronal shape by providing a
and become associated with lymphocyte T to suitable substrate for dendritic growth or by
induce the expression of class II major his- secreting appropriate soluble trophic factors.
tocompatibility antigens. They also secrete Through all these effects on neuronal migra-
factors capable of affecting the survival and tion, axogenesis, and neuronal morphogene-
maturation of microglia , and modulating sis, astrocytes appear to provide much of the
inflammatory and immunologic responses basic pattern for the establishment of the
( 121 ) . major neuronal circuits.
Neuronal Development and Plasticity Blood- Brain Barrier

The role of radial glia for the guidance of The endothelium of brain microvessels
migrating neurons, first suggested by Ramon constitutes a highly specialized , metabolically
y Cajal, was convincingly demonstrated by active barrier responsible for the stable envi-
the work of Pasko Rakic and his collabora - ronment of the central nervous system . The
tors, which showed the close apposition of passage of different substances across the
migrating neuroblasts to radial glia in the blood -brain barrier into cerebral interstitial
cerebral hemispheres and to Bergman radial fluid is regulated by this endothelial layer,
glia in the cerebellar cortex (96, 118). How- which possesses several structural and bio-
ever, note that not all neuronal migrations chemical properties distinct from those of
occur along radial glial fibers. Heynes and noncerebral capillaries. Among other things,
collaborators showed that neuroblasts form - the end feet of astrocytes and their basal lam-
ing the germinal layer of the cerebellum mi- ina are believed to be major components of
grate from the caudolateral margin of the the blood -brain barrier (see Chapter 1 ). En -
fourth ventricle to the surface of the cerebel - dothelial cells of brain capillaries are linked
lum while remaining in close contact with by tight junctions that form a continuous
preexisting axonal bundles ( 49). It appears belts around contiguous endothelial cells
that migrating neuroblasts can use different ( 76). This elaborate junctional network is con-
surfaces as long as they lead to the right di- sidered a major structural component of the
rection . -
blood brain barrier to macromolecules. The
Astrocytes are also involved in various ability of brain endothelial cells to form a bar-
recognition systems that guide axon elonga - rier depends on the environment in which
tion during development. Among these they grow. If a developmental, postnatal in -
recognition systems, astrocytes are simply in crease in the ensheathment of endothelium
those comprising either cell interactions me- by astroglia occurs, there appears to be a re-
diated through cell adhesion molecules lated maturation of the blood -brain barrier.
(CAM ) or interactions with the extracellular Furthermore, the astrocytic processes that en -
matrix mediated by integrins and other ma - velope the brain capillaries appear to alter the
trix glycoproteins (see Chapter 3). The role of capillaries' passive permeability by modulat-
astrocytes in neuronal development is not re- ing the formation of tight junctions between
stricted to the support and guidance of grow - the endothelial cells. A close interaction be-
6 Neuroglia 209
tween endothelium and astroglia was space. If the infarct is deeper into the brain ,
demonstrated by allowing permeable vessels like in the basal ganglia , the resulting cyst is
from nonneuronal tissue to grow into embry - then part of the perivascular space. Thus, as
onic avascular brain fragments in vivo. Upon in normal conditions, astrocytes always form
entering the brain , the permeable vessels be- the boundary between central and noncentral
came impermeable to circulating tracers nervous tissue in pathologic conditions ( 4 ).
( 117). The component of the brain environ - The astrocyte scar resulting from severe brain
ment responsible for this permeability change damage is called anisomorphic gliosis because
appears to be astroglia. Indeed , when dissoci - of the irregular arrangement of the glial fib-
ated astrocytes are grafted to the anterior rils with no preservation of the preexisting
chamber of the eye, the permeable vessels of structure. In cases of more selective brain in -
the iris become impermeable as they pene- juries, such as the loss of a given neuronal
trate the astrocytic domain ( 51 ). This hypoth - population following anoxia or retrograde
esis was confirmed and further extended by degeneration of nerve fibers, the reactive as-
experiments involving the insertion of fetal trocytes retain their normal architecture and
cerebellar tissue into the anterior chamber of the resulting scar is called isomorphic gliosis .
the eye in the rat ( 76). Thus, astrocytes induce Protoplasmic astrocytes undergo charac-
-
the formation of the blood brain barrier in teristic changes in hepatic encephalopathy .
vivo and the organization of the tight junction These consist of swelling and vacuolation of
in vitro, but the nature of the inductive fac - astrocytic nuclei and mitochondria , most
tors ) remains to be discovered ( 76 ). The in - prominent in cerebral cortex and basal gan -
volvement of astrocytes in the formation of glia . As seen earlier, astrocytes play a role in
the blood - brain barrier reveals that these glial ammonia detoxification, but the relation be-
cells actively interact not only with neurons, tween this astrocytic function and the mor-
but with other elements of the central ner- phologic changes seen in protoplasmic astro-
vous system as well . cytes in the hyperammonemia condition that
is characteristic of hepatic encephalopathy is
Pathologic Conditions still uncertain . However, it is worth noting
that cerebral cortex and basal ganglia, where
The most common astrocyte reactions to nuclear swelling is most severe, are among
injury are hypertrophy and the production of the brain regions with the highest concentra -
intermediate filaments, that is, fibrillary tions of glutamine synthetase.
gliosis. Numeric increase of astrocytes due to Astrocytes are also thought to be involved
cell division is also part of the response, but is in some forms of Parkinsonism and Hunting-
probably less important compared to hyper- ton 's disease. The drug 1-methyl-phenyl-
trophy and fibrillogenesis in scar formation 1,2,3,6-tetrahydropyridine ( MI’TP ) is known
( 4 ) . The increase in fibrillogenesis can be eas- to cause clinical symptoms and neuropatho-
ily monitored with GFAP immunocytochem- logic signs that are indistinguishable from
istry since the production of this protein is those occurring in idiopathic Parkinson's dis-
greatly enhanced in case of central nervous ease. Furthermore, it has been established
system damage ( Fig. 6.20 ). that astrocytes convert MPTP into its toxic
Astrocytic reactions vary considerably de- metabolite l -methyl -4-phenylpiridinium ion
pending on the type and extent of injury ( Fig. ( MPP ). The toxic metabolite appears to be
6.6 ). In case of severe brain injury, such as in produced by the enzyme monoamine oxy-
ischemic necrosis ( infarct ) involving blood dase B ( MAOB ) which , in the brain, is pre-
vessel damage at the surface of the brain, pro- dominantly located in astrocytes ( 102 ).
tein - rich fluid pours out from the necrotic Studies of the pathogenesis of Hunting-
brain tissue causing severe white matter ton 's disease have shed new light on the
edema . Reactive astrocytes rapidly surround function of the reactive astrocytes. Hunting-
the infarct with a thick mesh of fibrils, demar- ton's disease is characterized by a massive
cating the necrotic tissue from viable brain neuronal loss in the caudate nucleus and
and probably preventing the spread of putamen (striatum ) resulting in a marked at -
edema . Finally , the glial scar covered by a rophy of both structures. The important neu -
basal lamina forms the new surface of the ronal depletion is accompanied by a marked
brain. The cyst resulting from the absorption astrocytes hypertrophy together with in -
of the necrotic tissue by blood -born mac- crease of filaments and GFAP ( reactive gliosis )
rophages is now part of the subarachnoid in the striatum. Recent findings suggest that
Figure 6.6. Reactive astrocytes in gray matter of adult human spinal cord 4 weeks after a spinal stereotaxic lesion . A .
Anterior horn cell with adjacent oligodendrocytes (o) and swollen astrocytes (arrows) B . A prominent and bizarre as-
trocyte with enlarged vascular end foot Several smaller astrocytes with gliofibrils are indicated by arrows. The cell
body of an oligodendrocyte (o) is identified for comparison of relative sizes. (Holzer stained sections. x 550.)
reactive gliosis may play a role in the patho- marily involved in the production of quino-
genesis of Huntington's disease. Lesions sim- linic acid since they are the main cell popula-
ilar to those observed in 1 luntington 's disease tion that remains intact and even proliferates
can be experimentally produced by intrastri- in these conditions.
atal injection of various exogenous amino Most primary brain tumors are gliomas
acids (excitotoxins) (e.g., kainic and ibotenic and most gliomas derive from astrocytes as
acid ). Quinolinic acid , an endogenous shown by GFAP immunocytochemistry ( 4).
metabolite of tryptophan metabolism , can In various organs of the body, local spread of
produce changes similar to those of exoge- malignant tumors mainly occurs through
nous excitotoxins (7) and this suggests that it lymphatic and interstitial tissue spaces. How-
could play a role in the pathogenesis of Hunt - ever, the brain is different in that lymphatics
ington 's disease. The marked increase of the are missing and interstitial tissue spaces are
anabolic enzyme for quinoline in both experi- sealed . Therefore, metastatic carcinomas are
mental excitotoxic lesions and in Hunting - not able to infiltrate brain tissue and grow as
ton ' s disease, suggests that astrocytes are pri- solid nodes. Astrocytomas are different in
6 Neuroglia 211
that the cells forming the tumor are able to in - Major Types of Oligodendrocytes
filtrate brain tissue because of their organiza-
tion in the form of a functional syncytium. Two principal types of oligodendrocytes
The extent of infiltration depends on the ma - can be identified by their location and rela -
lignancy of the tumor. It is possible that the tionships with other elements of the central
characteristic patterns resulting from astrocy- nervous system . Perinenroml satellite cells are
toma infiltration in the brain are relevant to closely apposed to neuron perikarya or their
the question of glial migration in develop- dendrites in the gray matter . This type is the
ment. most easily identified in adult material ( Figs.
6.3 and 6.7). Interfascicular cells occur in the
white matter and often appear in rows be-
OLIGODENDROCYTES tween the myelinated fibers ( Fig . 6.3). The in -
The term oligodendroglia was introduced
terfascicular oligodendrocytes are numerous
in the white matter of the fetus and newborn .
bv Ramon y Cajal's student Pio Del Rio Hort- However, they rapidly diminish in number
ega ( 29) to describe small neuroglial cells
as myelination progresses. After the myelin
with relatively few processes. The delicate
sheath is formed , only the nucleus remains,
slender processes of oligodendrocytes radiate
so that in adult material their processes rarely
only a short distance from a spherical or are observed ( Fig. 6.7 B ). As mentioned ear-
-
pear shaped cell body ( Figs. 6.3 and 6.7). In
sections stained with basic dyes, the nuclei of
oligodendrocytes are smaller, more regular,
and more chromophilic than astrocytic nu -
clei . These glial cells differ from astrocytes in
that ( a ) their nuclei are smaller, rounder, and
more dense, ( b ) the cell body is smaller and
gives rise to fewer processes, and (c) their cy-
toplasm is more dense, containing chiefly ri-
bosomes, mitochondria, and microtubules.
The dense chromatin of the nucleus has light
patches adjacent to numerous nuclear pores,
while the cytoplasm has a crowded appear-
ance, due to large quantities of free ribosomes
and rough endoplasmic reticulum. Other dis-
tinguishing features of their cytoplasm are
prominent microtubules, dark and light mul
tivesicular bodies, and granular inclusions.
-
The cytoplasm has mitochondria and a Golgi
apparatus, but contains neither fibrils nor
glycogen granules (15, 54, 72 ). The plasma
membrane of the oligodendrocyte makes
close contact with adjacent myeiin sheaths
and the processes of adjacent glial cells ( Fig.
6.8) .
In contrast to astrocytes, oligodendrocytes
are more numerous in the white matter than
in the gray matter. They can also be differen-
tiated from astrocytes by different morpho-
logic, physiologic, and biochemical criteria .
Oligodendrocytes' distinctive features in -
clude (a ) the intracellular enzyme carbonic
anhydrase, ( b ) the cell membrane surface Figure 6.7. Oligodendrocytes in human spinal cord A .
molecule galactocerebroside, which can be Newborn gray matter to demonstrate relative size of a
recognized with specific antibodies, (c) neuron cell body (n). perineuronal (satellite) oligoden-
myelin and the expression of mRNA for drocyte (o), astrocyte (o). and microglial cell (m)
(Ramon y Cajal gold sublimate stain, < 666) B. Posterior
myelin basic proteins, and ( d ) weak electro- white column of adult cord with oligodendrocyte (o)
tonic coupling through gap junctions (101 ). .
(Golgi stain x 550).
Her, all oligodendrocytes appear to derive Ranvier to the next, instead of spreading con -
from the bipotential 0-2A progenitor cells. tinuously along the axon. This is why myeli -
nated axons conduct faster than nonmyeli-
Myelination nated axon of the same size.
In terms of myelination, the efficiency of
One of the major function of oligodendro- oligodendrocytes far exceeds that of the
cytes is to form and maintain myelin sheaths Schwann cells because a single oligodendro-
in the central nervous system ( Fig. 6.8). The cyte can myelinate from 7 to 70 axons, de-
fine structural continuity of the plasma mem - pending on the brain region or the species
brane of oligodendrocytes with the myelin ( 44 ). Oligodendrocytes are not only involved
sheath ( 23)( Fig. 6.9 ), and their active partici- in myelination during development, but also
pation in remyelination , has been reported in play an important role in the maintenance of
detail ( 15, 18, 44, 47), and the mechanisms of myelin in the adult. Oligodendroglia are par-
myelination were discussed in Chapter 5. As ticularly involved in the process called spon -
in the peripheral nervous system, the mvelin taneous remyclination , which refers to the
sheath in the central nervous system allows rapid and spontaneous repair of myelin that
saltatory action potential conduction, since sometimes occurs in the adult brain in re-
nerve impulse jumps from one periodic inter- sponse to acute or chronic demyelination
ruption of the myelin sheath at the node of conditions, such as those found in multiple
Figure 6 8 Myelin-forming oligodendrocyte (oO in o 6-doy postnotol rat Specimen is token in the ventrolateral fu-
niculus of the spinal cord near unmyelinated axons (A) and axons (MA) exhibiting different stages of myelination
Oligodendrocytic processes ( OP) are closely associated with several newly formed myelin sheaths ( xl 6.000)
6 Neuroglia 213
Figure 6.9. Relationship of the oligodendrocyte to the central myelin sheath The trilaminar plasma membrane (pm)
is designated by two lines, separated by a space, except in the mitochondrion, where it is represented by a single
line The inner mesaxon ( im), formed as a glial process, completes the initial turn around the axon (a) and starts a sec -
ond turn, it is retained after myelin formation is complete Some cytoplasm of the glial process is trapped occasionally
(cy) and some is also retained on the fully formed sheath exterior . In transverse sections, this cytoplasm Is confined fo
d loop ( ol ), but along the internode length it forms a ridge (r) continuous with the glial cell body (g) at the level of glial
processes (c). Viewed transversely, the sheath components form a spiral with only the innermost and outermost layers
ending in loops. In the longitudinal plane, every myelin unit terminates in a separate loop near a node (n). Glial cyto-
plasm is retained within these loops
sclerosis. Experiments with different animal -

the acid base equilibrium through several
models of demyelinating diseases have re- mechanisms involving acid extruders and
vealed that spontaneous remyelination is a acid loaders (110). Among the acid extruders
general rule rather than an exception in the that contribute to pH regulation are (a ) Na + -
central nervous system. Since the formation HCO , -
cotransport, (b) Na + dependent
of the myelin sheath is viewed as the last step in ,
Cl / HCO exchange, and (c) NaVH ' ex -
oligodendrocyte maturation (115), the mecha- change across the glial membrane. In con-
nisms whereby mature oligodendrocytes can trast, pH recovery from alkalosis involves at
be mobilized and reengaged in the myelina- least one acid loader, which is Na ‘ -indepen -
tion process appear complex and are still not dent Cl / HCCV exchange (110).
fully understood . They most likely necessi- Like astrocytes, oligodendrocytes precur-
tate the recruitment and activation of the sor cells express a defined set of voltage and-
bipotential 0-2A progenitor cells, which are -
ligand dependent ionic channels, but the ex-
still present in the mature central nervous pression of the channels changes markedly
system. Spontaneous remyelination is a well- during development (52). Voltage gated -
documented phenomenon that may explain channels that occur in oligodendrocyte pre -
the sudden clinical improvements occasion- cursor cells include potassium channels,
ally seen in different demyelinating diseases, sodium channels, and calcium channels.
such as multiple sclerosis and lateral amy- More mature oligodendrocytes also possess
otrophic sclerosis. It must be realized , how- pH-activated channels, as well as GABA and
ever, that spontaneous remyelinization does glutamate receptors, whose expression is
not, in any way, allow for complete recovery greatly reduced in more advanced stages. It
from demyelinating diseases. Use of grafts of was suggested that during their development
oligodendrocyte precursors, or even more certain chemospecific neurons (e.g., GABAer-
mature oligodendrocytes, as a therapeutic gic neurons) may be able to regulate both the
tool to improve symptoms in demyelinating rate of differentiation and the function of glial
diseases is a very active field of research (44). cells by releasing their transmitter at the axon
growth cone level (52). The transmitter
pH Regulation and Ionic Channels would exert its action by binding to specific
astrocytic membrane receptors that are only
The appropriate regulation of pH in the expressed at a certain time during astrocyte
central nervous system is crucial because of development.
the large number of pH-sensitive processes These data reveal that the electrical prop-
that occur in this tissue. In excitable cells like erties of oligodendrocytes change markedly
neurons, changes in intracellular pH modify during development. The transition from the
various ionic conductances, and the electrical bipotential precursor cell, which can still de-
coupling between adjacent cells is blocked by velop into astrocytes and oligodendrocytes,
decreased intracellular pH . In addition to its into an oligodendrocyte, results in a marked
effects on other ionic conductances, H * change in the ion channel pattern. During
might, itself , act as a carrier through H -spe-
*
this transition, voltage-activated Na ' and
cific channels (110). The control of extracellu - several types of K currents disappear,
lar space pH has been studied extensively in whereas a comparatively passive, inwardly
the central nervous system. It has been rectifying K current becomes dominant.
*
shown that this pH decreases during neu - GABA receptor-mediated Cl currents and a
ronal activity, often after an alkaline shift. For pH-activated Na * current are down-regu-
example, peripheral noxious stimuli and dilated at this transition, but still present at all
rect stimulation of the nervous tissue induce developmental stages. These changes in the
a significant decrease of the extracellular pH. receptors and ionic channels repertoire dur-
More dramatic changes in the extracellular ing oligodendrocytes development are at
pH were observed in pathologic conditions. variance with the situation in astrocytes,
The mechanisms involved in pH control in where the various receptors and channels are
the central nervous system are complex and still fully expressed in mature cells.
not fully understood . Data derived from
studies of the invertebrate nervous system indi- MICROGLIA
cate that glial cells enriched with the enzyme
carbonic anhydrase, which correspond with Microglia were first recognized as distinc-
mammalian oligodendrocytes, can control tive glial elements by Del Rio Hortega ( 27, 30)
6 Neuroglia 215
when he introduced his silver carbonate inactive in normal adult brain tissue, inflam -
staining method ( Fig. 6.3). These cells are matory or degenerative processes activate
small in comparison to astrocytes, have elon- these cells which undergo rapid proliferation
gated or triangular nuclei which stain deeply and migrate toward the site of injury. Histio-
with basic dyes, and have wavy, branching cytes from the meninges and blood vessel
processes that give off spinelike projections. walls behave similarly if they reach the cen -
Microglia are found in both white and gray tral nervous tissue. Both types of cells become
matter, but are more abundant in gray matter macrophages and phagocytize debris.
( Figs. 6.10 and 6.11 ) . Approximately 10% of Small numbers of microglia in white mat -
glial cells are classified as microglia in light ter have processes that wind along or follow
microscopic preparations of the cerebral cor- myelinated fibers in a remarkably tortuous
tex ( 2, 13). Although microglial cells appear manner ( 20). A microglial cell has an irregu -
Figure 6.10. Microglial cells in gray and white matter of adult human spinal cord 3 weeks after a spinal stereotaxic
lesion. Note thickened and stubby processes extending toward an adjacent anterior horn cell ( A) and a knobby an-
gular processes of microglial cell extending into the dark zone of degenerating fibers above (B) (Golgi stain, x 555.)
Figure 6.11 . A . Carousel formed by numerous microgliocytes (m) closely surrounding a degenerating anterior horn
cell 4 weeks after injury of its axon Two astrocyte nuclei also are identified (a) Adult human spinal cord (Luxol fast
blue-cresyl violet stain, x 555) B. Three stages { arrows) in the formation of a microglial phagocyte (gitter cell) White
matter of adult human spinal cord. 4 weeks after a stereotaxic lesion (Luxol fast blue-cresyl violet stain, x 655)
lar perikaryon and a few thick processes rived at by a process of elimination (38, 46,
which often appear to take off from each pole 72, 111 ). The cell thought to correspond with
of the cell body. These large antler-like the microglia was small with a dark nucleus,
processes divide after variable distances into dark cytoplasm , and compact organelles.
many smaller branches. Each branch then Microglia have long been considered the
pursues an irregular and tortuous course ei - scavengers of the nervous system . They were
ther to adjacent neurons, or, less often, to a presumed to be pleomorphic cells capable of
blood vessel wall . The nucleus is ovoid or (a ) metamorphosis into a macrophage, ( b ) un -
elongated , which aids in distinguishing the dergoing mitotic division and migrating at
microglia from oligodendrocytes. The cyto- will through the already formed neuropil,
plasm is pervaded by a myriad of minute and (c) autolyzing or phagocytizing neuronal
vacuoles, which often gives the cell, or some and other debris (30, 87).
of its processes, a sievelike appearance ( Fig.
6.10A ). Despite many descriptions of mi- Brain Macrophages
croglia in the light microscopic literature, this
cell is still difficult to identify in electron mi- Our conception of microglia recently
croscopic preparations ( 90). Criteria for iden- changed because of the introduction of vari-
tification of microglial cells initially were ar- ous immunocytochemical techniques with
6 Neuroglia 217
lectin binding and monoclonal antibodies cytoplasmic appearance and ingested mate-
recognizing complement receptors and other rial is called a gitter cell ( Fig. 6.11 B ) . As the cy-
surface antigens common to both microglial toplasm of the macrophages became packed
cells and macrophages outside the central with ingested material, the nucleus was often
nervous system (88). Microglia are currently pushed to the cell periphery. Such phagocy-
referred to as resident brain macrophages. Evi- tosed particles included myelin and lipoid
dence for the existence of resident mac- droplets. Gitter cells abounded in the lesion
rophages in the central nervous system with area for the first week, then decreased in
properties indistinguishable from those of number until 90 days at which time only an
peripheral macrophages, was obtained by occasional phagocyte was seen ( Fig. 6.11 ). A
Streit and Kreutzberg (120 ). Their experiment similar mobilization is observed in the
involved a mechanic and / or toxic lesion of human nervous system after neuron injury
the facial nerve, which induced retrograde ( Fig. 6.11 A ) . Three stages in the formation of
neuronal damage without any increase in a gitter cell are indicated by arrows in Figure
the permeability of the blood -brain barrier, 6.11 B . These large vacuolated macrophages
thus excluding invasion by blood -borne may assume a gigantic size and a bloated ap-
macrophages. In cases where facial motor pearance. When suitable fat stains are used ,
neurons did degenerate because of the retro- the vacuolated gitter cells display an unusual
grade transport of the toxin along their axon, number of fat droplets of varying size. These
resident microglia were capable of phagocy- lipid droplets are formed by cholesterol es-
tosis ( neuronophagia ) and behavior like ters which persist for long periods of time in
blood -born macrophages in viral polio- the tissue.
myelitis. In cases where facial motor neurons Macrophages rapidly remove degenerated
did not degenerate despite lesion of their myelin in peripheral nerves, whereas this
axon, resident microglia surrounding the process is very slow in the central nervous
neuronal perikarva underwent mitosis and system . This difference is surprising because
hypertrophy, but did not phagocytize the resident microglia and peripheral macro-
neurons (120). phages are believed to have similar proper-
Macrophage-like cells in the brain can be ties. Since central and peripheral myelin
subdivided into three types: (a ) those found have different biochemical compositions, it is
in the parenchyma ( the microglia proper); ( b ) possible that some constituents of central
those found in the choroid plexus and cir- myelin act as repellents for resident macro-
cumventricular organs, where there is no phages. Indeed , the occurrence of cen-
blood -brain barrier; and (c) the perivascular tral myelin proteins that inhibit axonal
cells. Unlike the second and third type, which growth was reported by Schwab and his
are always in an activated state, parenchymal collaborators (19 ). Another possibility,
microglia have resting and activated forms suggested by Bignami ( 4 ), is that the hyal -
( 2). uronate- protein complex forming the extra -
Great numbers of discretely arranged mi- cellular matrix of the white matter prevents
croglial cells have been observed in the re- phagocytosis either by "masking" degener-
gions of injury and edema in other experi - ated myelin, or by interfering with microglial
mental conditions (106 ). Such cellular migration from their predominantly perivas-
mobilizations occur as early as 24 hours after cular location .
cold injury ( 50°C ) and persist for days.
Schultz and Pease ( 112) observed a similar ac- Neuronal Shaping
cumulation of microglial elements in the
acute phase, 24 hours after stab wounds of Resident microglia are particularly abun -
the cerebral cortex. The microglia underwent dant during certain phases of neuronal devel -
a remarkable transformation within this pe- opment, particularly those involving "regres-
riod . They exhibited a rounded appearance as sive" events such as neuronal cell death and
the cytoplasmic volume increased and be- axon collateral elimination, in which they
came less dense so that the nuclei became play a very active role ( 68). During these re-
more prominent . In about 1 week, these gressive events, the phagocytic activity of res-
changes culminated in the formation of typi- ident macrophages is not limited to the elimi -
cal macrophages with pale cytoplasm and no nation of neuronal debris. These glial cells
definite processes. An enlarged macrophage actively participate in the shaping of neu -
in the central nervous system with a foamy ronal circuits as exemplified by their selective
involvement in collateral elimination. This in several pathologic processes in specific

phenomenon is very specific in that it must ways. They are the only cell type in the brain
not affect the viability of the rest of the neu- known to be infected by the HIV virus, and
ron. Electron microscopic studies reveal that thus might be crucial to the development of
resident macrophages are able to transiently the acquired immunodeficiency syndrome
sequester specific portions of the axonal arbor ( AlDS)-dementia complex. The extent of neu -
within their cytoplasmic extensions (50). rodegeneration in AIDS-dementia seems to
Phagocytic activity of glial cells can also help correlate well with microglial density (2). In
to shape neurons and neuronal circuits in the Alzheimer's disease, microglia are being im-
mature central nervous system, as shown by plicated in the transformation of soluble amy-
the study undertaken by Raisman and his loid precursor protein (|3A4) into insoluble
collaborators (95) of synaptic plasticity after fibrils and the inflammatory processes within
denervation. These authors observed that the senile plaques. In demyelinating conditions
process of presynaptic terminal replacement such as multiple sclerosis, microglia act both
involves the essential intermediate stage of as antigen- presenting cells and , to some ex-
engulfment by a glial process. This glial tent, to degrade myelin debris.
process must act in a very concerted way, be- Microglia can be imaged in vivo by posi-
cause after phagocytosis of a degenerating tron emitting tomography ( PET ) scanning.
terminal, the glial process must be able to rec- Activated microglia express the peripheral
ognize and give way to the ingrowth of a benzodiazepine receptor, for which there is
newly forming axon terminal, as well as dis- a ligand suitable for PET scanning. This is
criminate among different types of neuronal being used in humans to study microglial ac-
inputs competing for the same target (95). tivation after stroke. Works on multiple scle-
The occurrence of transmitter receptors on rosis in humans show high activation in the
glial cells may explain how such specificity thalamus and correlation of the receptor
may be obtained. binding with hot spots detected with mag-
Phagocytosis is not the only way whereby netic resonance imaging ( MRI ) using gadolin-
resident macrophages can shape neuronal ium (see Chapter 2).
morphology. Indeed , evidence for a facilita-
tory action of resident microglia on neuronal EPENDYMA
growth and survival in the central nervous
system have been documented . For example, The ependyma lines the central canal of
brain macrophages can produce interleukins the spinal cord and the ventricles of the brain.
(1 and 6) which, in turn, can modulate the in- In the embryo, the ependymal processes tra -
tracerebral concentration of nerve growth fac- verse the entire thickness of the neural tube
tor ( NGF) (68). Interleukin-1 can be detected to become attached to the pia mater and su -
biochemically in various brain regions where perficial glial membrane (glia limitans) by
transient expression of brain macrophages terminal expansions. Most of the processes
has occurred . When injected into the cerebral retract, so that at birth these processes reach
ventricles, interleukin -1 induces a marked in- only the pia where the neural wall is thin, as
crease of the expression of the mRNA that en- in the basal plate region ( Fig. 6.12). In fetal
codes NGF within the hippocampus, as well life, the ependyma consists of several layers
as in the cerebral cortex. Furthermore, in vitro of nuclei, and one can see the large pale nu-
studies revealed that interleukins-1 and -6 clei of the germinal cells, as well as mitotic
stimulate NGF production by astrocytes, and cells ( Fig. 6.13A ). Cilia are observed in only
that brain macrophages can, themselves, pro- the embryologic stages of humans, but persist
duce NGF following lipopolysaccharide stim- in some adult animals, such as the rabbit and
ulation (68). Taken together, these results dog ( Figs. 6.13C, 6.14, and 6.16).
clearly indicate that microglia (as well as as- Ependymal cells also have numerous mi-
triglia ) play a very active role in shaping de- crovilli on their ventricular surface ( Fig. 6.16).
veloping neurons and in the constant remod - The surface morphology of ependymal cells
eling of brain neuronal architecture. varies over white and gray matter. In scan -
ning electron microscope studies of rabbit
Pathologic Conditions ependymal cells, those covering myelinated
structures, such as the corpus callosum, have
Apart from contributing to inflammation fewer microvilli and cilia than ependymal
and necrosis, microglia seem to be implicated cells covering neuropil (81). Additional dif -
6 Neuroglia 219
'‘ •t c
Fibrous A M'J.Vv
astrocyte
. i/c
ep
- j
I cc
Protoplasmic j
astrocytes tom
m . a
^7
6
HI
yimM
Fibrous
-
astrocyte YXVV%K« icVfV"
Figure 6.12. Ependyma and neuroglia lining the central canal of the spinal cord of an infant 8 days old (Golgi im-
.
pregnation) . a, Terminal foot plate of ependymal cell: b, terminal foot plate of fibrous astrocyte: cc central canal:
e.p . ependymal cell
Figure 6.13. Ependyma of human and rabbit brains

A . Ependymal cells (E) and subependymal glial mem-
brane ( SE) in a human fetus of 80 mm crown-rump (C-
/?) length Mitotic figures (asterisks) and pale germinal
cell nuclei ( arrow ) are indicated (Luxol fast blue-cresyl
violet stain) B. Ependymal cell lining adult human third
ventricle (Luxol fast blue-cresyl violet stain) C. Ciliated
ependymal cells lining adult rabbit fourth ventricle (Bo-
dian stain).
NEUROGLIAL
•.# •
Figure 6 14 . Ependymal cells with long basal processes (P) lining tne aqueduct of the dog The apical surface may
exhibit short microvilli (Mv) and cilia (Q. or may be relatively smooth Rows of desmosomal-like plaques (arrows) join
adjacent cells apically Most of the mitochondria (M) in the cells are scattered randomly, but they are also aligned In
rows close to the junctions The Golgi complex (G) is usually in a supranuclear position The nucleus (N) may be ovoid
or indented and sometimes a nucleolus is seen Fine filaments (f). similar to those found in the subependymal astro-
cytic processes (As), are present in the ependymal processes ( x 7.800)
6 Neuroglia 221
Figure 6.15. Features of ependymal cells A. The apical cytoplasm of three contiguous ependymal cells (a b. and .
c). The luminal surfaces of cells are joined by the zonula occludens (zo) which is directly continuous with a zonula ad-
haerens (zo) ( X 21.000) B. A zonula occludens forms a dovetail type junction between the base of two ependymal
cells. The interval between the two dense, parallel membranes can be compared with the usual intercellular space
at the right ( x 49.000)
Figure 6.16. Scanning electron micrographs of the ependyma in the rabbit in various locations. A. Over the caudate
nucleus showing clusters of surface cilia ( x 200). B. Over the caudate nucleus showing microvilli (mv) between clliary
c lusters ( x 2000). C. Over periventricular white matter where cilia are more widely separated and nonciliated cells (o)
are outlined by aggregates of microvilli (x200). D. Over periventricular white matter where cilia arise in clusters and
microvilli (mv) aggregate at cell boundaries ( x 2000).
6 Neuroglia 223
ferences are seen in the arrangement of inter- reflection are observable in gross brain speci-
cellular clefts and junctional specializations mens after the choroid plexus is removed ,
of ependymal cells in the two regions. These The macroscopic torn edge of the ependyma
morphologic differences may account for the is referred to as the tenia choroidea ( Fig. 2.25).
selective changes observed in ependymal Electron micrographs ( Fig. 6.14 ) reveal
cells over periventricular white matter in ex- that the ependymal cell cytoplasm contains
perimentally induced hydrocephalus (80). small slender mitochondria, vesicles of er-
In the human adult, the single layer of gastoplasm, a smooth endoplasmic reticu -
ependymal cells is cuboidal, while their re- lum, a Golgi complex, and compact bundles
traded processes are entwined in the packed of intermediate filaments (82, 126). Histo-
astrocytic processes of the subependymal ( Fig. chemically, the ependymal epithelium ex-
6.13) or internal limiting glial membrane. There hibits high oxidative activity as reflected by
are few places in the nervous system where its enzyme content, which comprises acid
typical astrocytes and their processes are as and alkaline diphosphatase and adenosine
concentrated as in this subependymal limit- triphosphatase. Both structural and chemical
ing membrane. During development, the pia- reactions reflect the secretory and absorptive
arachnoid pushes a layer of ependymal cells functions attributed to the ependymal cells
ahead of it, and invaginates into each of the and choroid epithelium (1).
primitive brain ventricles to form the tufted Specialized ependymal cells called tany-
choroid plexuses ( Figs. 3.11 and 3.15). The cytes (elongated cells) are found in the base of
points of attachment, composed of pia mater the third ventricle. Tanycyte processes extend
and the cuboid ependymal cells, form the tela for some distance into the neuropil where
clioroidea of the third , fourth, and lateral ven- they are juxtaposed to blood vessels and neu-
tricles ( Fig. 6.17). These points of junction or rons. Indirect evidence suggests that these
Post. inf . cerebellar artery
Choroid
plexus
Ependyma 4. '
&
EZ! ventricle
Dilated
vascular
Medulla channels
.
'A B.
Figure 6.17. Human choroid plexus at (A) low magnification to show topography and relations of the plexus in the
fourth ventricle, and at (B) higher magnification to demonstrate the epithelium and vascularity of two choroid villi
cells selectively transport molecules from the accompany the different stages of choroid
cerebrospinal fluid (CSF) to diencephalic neu - plexus development . Four stages have been
rons concerned with the regulation of go- described (113). For our purpose, it suffices to
nadotropic hormone release from the anterior note that each primordium enlarges, becomes
lobe of the pituitary gland (8, 53). lobulated , and each lobule later demonstrates
The surface layer of ependymal cells and frondlike expansions ( Fig. 6.17). In still later
subjacent astrocytes ( i.e., subependymal glial stages, many villi develop on the surface. The
-
membrane) constitute a brain cerebrospinal entire lobulated , vascularized mass remains
fluid interface ( Fig. 1.14 ). The lateral cell sur- attached by a broad stalk at the point of the
faces of ependymal cells are comparatively original invagination . The covering cells are
simple without elaborate folds or interdigita - at first pseudostratified tall epithelial cells,
tions. Near the apices of contiguous cells, the 50-60 pm in thickness, with a brush border
apposed surface membranes contribute to the on the luminal surface. At 11 weeks, the
formation of complex intercellular junctions, choroid plexus fills 759; of the lateral ventri -
which in light microscopy are called terminal cle, and the covering, tall, columnar cells
bars. Electron microscopic studies of the have an abundance of cytoplasmic glycogen
ependyma in the rat brain indicate that the ( Fig. 6.18). At this stage the mesenchyme of
lateral portions of the plasmalemma of con - the underlying connective stroma becomes
tiguous cells are fused at discrete sites to extremely loose and accumulates a large
form five-layered junctions, referred to as amount of mucin. In the interval between 15
zonulae occludens , which obliterate the inter- and 17 weeks of gestation, the entire plexus
cellular space ( 11 ). These fusions occur at gradually decreases in size and the primary
some distance below the free surface ( Fig. villi are better developed. The epithelium
6.15). Another type of intercellular junction, changes from low columnar to cuboidal and
the zonula adliacrens , occurs near the apices of
contiguous cells. Segments of the plas-
malemma comprising this junction are char-
acterized by their increased density, and the
interspace of the junction contains filamen-
tous material . This structural arrangement
forms the brain-cerebrospinal fluid interface.
Neither the ependymal surfaces of the cere-
bral ventricles nor the pial-glial membrane on
the surface of the brain impede the exchange
of substances between the CSF and the brain
(103). Thus the brain -CSF interface does not
constitute a subbarrier ( Fig. 1.14 ).
CHOROID EPITHELIUM
The choroid plexuses, whose major role is
to secrete the cerebrospinal fluid (CSF), are
formed as a result of the invagination of the
ependymal roof plate into the ventricular
cavities by the blood vessels of the pia mater
( see Chapter 3). In human embryos, the pri -
mordia of all the choroid plexuses develop
during the second month of gestation . A mes-
enchymal invagination into the thin roof area
of the fourth ventricle first appears at 6
weeks. The primordia of the telencephalic
choroid plexuses becomes visible in the 7th Figure 6.18 Choroid epithelium in humans A . Tall
week, followed in the 8th week by an invagi - columnar choroid cells in a humdn fetus of 100 mm
crown-rump length (Holmes' silver with hematoxylin
nation into the roof of the third ventricle. It is
counterstain) B Cuboidal choroid cells of an adult human
not surprising that extensive structural alter - brain. A subiacent blood vessel (b. v ) is identified (Luxol
ations in shape and microscopic appearances fast blue-cresyl violet stain) ( > 655)
6 Neuroglia 225
measures 15 x 15 gm. The loose underlying nism whereby surface solutes can be taken
mesenchyme decreases in amount, while dis- into the cell.
tinct connective tissue fibers ( mostly colla - An occasional cilium may occur on the
gen ) make their appearance in the stroma . Be- apical surface of adult choroid cells. Each cell
tween 29 w'eeks and full term the large is bounded by a dense continuous cell mem
cuboidal cells are replaced by smaller ones brane. On the ventricular surface, each cell is
-
-
which are 10 x 10 gm . The cytoplasm loses its thrown into elaborate, finger like extensions
glycogen, while meningocytes, foamy cells, 80-90 nm in diameter, which contain cyto-
and fat-laden macrophages are scattered plasmic cores. These elements appear to cor
through the stroma . Once removed , the respond to the striated or brush border ob-
-
glycogen never reappears as a normal conserved in light microscopic studies or to the
stituent of the adult choroid epithelium . Such microvilli seen with the electron microscope.
disappearance of glycogen after birth, or at Microvilli in this instance are a structural de-
the beginning of aerobic oxidation , suggests vice to increase the cell surface and enhance
that the developing nervous tissue uses en - its secretory and possibly absorptive func
ergy released by the anaerobic metabolism of tions ( Fig. 6.19 ).
-
glycogen . Electron microscopic studies on the de
Epithelial indentations lining the interlob- veloping choroid plexus of the rabbit by
-
ular clefts may become buried in the stroma Tennyson and Pappas suggest such a dual se-
during early development and form the col- cretary -absorptive role (123-125, 127 ). Their
loid cysts observed in the adult human brain ultrastructural observations also confirm
(113) . They appear red due to the blood in the and greatly extend the embryologic data of
stromal vessels, and the fine, leaflike projec- light microscopy. As shown in one electron
tions endow the choroid plexus with a micrograph ( Fig. 6.19), the adult choroidal
shaggy surface appearance. Hardened bodies cell contains numerous mitochondria, a
composed of concentric rings of calcium car- Golgi complex , cisternal and tubular ele-
bonate, calcium, and magnesium phosphate ments of the endoplasmic reticulum , numer -
also occur in the adult choroid plexus ( psam - ous small vesicles, dense bodies with a het
moma bodies ). They are generally spherical erogeneous content, and occasional cilia .
-
and originate around a group of degenerated These investigators also called attention to
cells (108). Psammomatous bodies are usually the pores present in the capillaries of the
of small diameter (0.01-0.15 gm ) and appear newborn and adult choroid plexus. They
to increase in number with age. Studies of found no evidence that thorium dioxide,
morphologic and histochemical alterations when injected intravenously, traversed these
of the choroid plexus with age, indicate that pores to enter the connective tissue stroma.
the height of the cuboidal epithelium gradu - However, other investigators showed that
ally decreases, proliferated cells eventually protein tracers ( Evans blue-albumin and
desquamate, and cytoplasmic vacuoles in- HRP) injected intravascularly pass through
crease in number ( 114 ). It seems likely that the choroid capillary pores and stain the
lipids in the cytoplasm of desquamated connective tissue stroma , but do not pass be
choroidal epithelial cells may be one source yond the tight junctions which surround
-
of lipids in the cerebrospinal fluid . apical regions of the epithelial cells of the
The histologic appearance of the adult choroid plexus ( 11), 103).
choroid epithelial cells after routine staining Histochemical demonstration of phos
is shown in Figures 6.17 and 6.18B They are phatase activity in choroid cells, particularly
-
low cuboidal cells with round and basally lo- the intracellular location of adenosine tri
cated nuclei . The bases of the cells are moder- phosphatase and acid phosphatase, should
-
ately smooth, while the lateral boundaries be noted . These hydrolytic enzymes play key
interdigitate with adjacent cells and dem- roles in metabolically active cells; adenosine
onstrate terminal bars. Tight junctions sur- triphosphatase participates in the ionic trans
rounding and connecting apical regions of port at membrane surfaces, and in oxidative
-
epithelial cells of the choroid plexus consti- phosphorylation within mitochondria . Acid
-
tute the blood CSF barrier ( Figs. 1.16 and phosphatase is an important constituent of
6.19; see Chapter 1 for further details ). Small the lysosomes (dense bodies of electron mi -
inpocketings can be seen on surfaces of the crographs) which appear to play an impor-
-
cell ( pittocytosis ) and are regarded as a mecha tant part in transcellular transport and diges-
'
• " vr .-.
.
.*X i j
Figure 6.19. Adult rabbit choroid plexus of the fourth ventricle A. The cuboidal epithelial cells have a large nucleus
( N) An occasional cilium (Q and polypoid microvilli (Mv) line the ventricular surface. Apically, a tight junction seals
adjacent cells ( arrow ), near their base, elaborate infoldings ( I) of the cell surfaces occur A paranuclear Golgi com-
plex (G), numerous mitochondria ( M). heterogeneous dense bodies ( B). and vesicles are present in the cytoplasm. A
basement membrane ( double arrows) separates the choroidal epithelial cells from the connective tissue which con-
.
tains collagen ( Q processes of fibroblasts, and other interstitial cells and blood vessels (bv). The thin wall of this
choroidal capillary is typical ( x 8.000) B. The thin capillary wall is interrupted by "pores. " which exhibit a diaphragm
( arrows ) between the lumen (bv) and the interstitial space A basement membrane (bm) coats the surface of the
capillary . Fibroblast ( F ) ( X 66.000)
6 Neuroglia 227
Figure 6.20. A and B Dark - field photomicrographs showing astrocytic processes displaying immunoreactivity for the
glial acidic fibrillary protein (GFAP) In the vicinity of a lesion site in the spinal cord of the rat . These GFAP - positive fibers
invade the injection site which harbors an artificial collagen-chondroitin sulfate biomatrix implanted 6 months earlier
to favor axonal regeneration. In B. several GFAP-positive fibers are clustered together to form a fascicle that directly
penetrates the biomatrix (asterisks) The small round and brightly fluorescent profiles in the lower part of A most proba -
bly represent macrophages. The GFAP-positive fibers were visualized with the immunofluorescence method using flu-
orescein isothiocyanate (FITC) as a marker
tion , as well as phagocytosis, necrosis, and dyes). However, such substances injected
autolysis ( 1 ). Additional information con- into the ventricles can pass through the
cerning structure and function of the choroid ependyma and subependymal glia to enter
plexus is available in reviews ( 24 , 34 ) . the extracellular space of the brain which is
The tight junctions surrounding and con- guarded by astrocytes ( Fig . 1.14; see Chapter
necting apical regions of the cuboidal epithe- 1 ) . Thus, all the neuroglial elements must be
lial cells of the choroid plexus ( Fig. 6.19 ) act considered not only as an impressive struc-
as an effective barrier which prevents large tural skeleton , but also as dynamic units that
molecular substances from entering the CSF regulate the chemical milieu of nerve cells
proteins, inulin , and fluorescent
(e . g . , serum and probably their metabolism .
References ods of cell enumeration in the 25. Davson H, Bradbury M . The extra -
white rat. In : De Robertis EDP, cellular space of the brain . In: De
1. Adams C WM . Disorders of neu - -
Carreas R , eds . Biology of the neu Robertis EDP, Carreas R , eds. Biol -
rons and neuroglia . In: Adams roglia , progress in brain research. ogy of the neuroglia , progress in
CWM, ed . Neurohistochemistry. Vol . 4 . Amsterdam : Elsevier, 1964 : brain research . Vol. 15. Amster-
Ch. 10. Amsterdam Elsevier, 136-149. dam: Elsevier, 1965:124-134.
-
1965:403 436.
2. Altman |. Microglia emerge from
13. Brownson Rll . Perineuronal satel-
lite cells in the motor cortex of
26. De Robertis EDP. Some new elec-
tron microscopical contributions to
the fog. Trends Neurosci 1994 ; aging brains. J Neuropathol Exp the biology of neuroglia . In : De
17:47-49. Neurol 1956;15:190-195. Robertis EDP, Carreas R , eds. Biol -
3. Bardakdjian |, Tardv M , Pimoule 14 Bullock Til , Horridge GA . Struc- ogy of the neuroglia, progress in
C, Gonnard P. GABA metabolism ture and function in the nervous brain research . Vol . 15. Amster -
in cultured glial cells. Neurochem
Res 1979;4:519-529.
systems of invertebrates. Vols. 1
and 2. San Francisco: W . ll Free-
-
dam : Elsevier, 1%5:1 11
27. Del Rio Hortega P. El "tercer ele-
4. Bignami A . ('dial cells in the central man , 1965. mento" de los centres nerviosus.
nervous system . In: Magistretti PJ , 15. Bunge RP. Glial cells and central Bui Soc Espan Bio 1919;9:69-120.
ed . Discussions in the neuro - myelin sheath. Phvsiol Rev 1968;
48:197-251 .
28 . Del Rio Hortega P. F.I tercer ele-
mento de los centres nerviosus.
science. Vol. 8. Amsterdam: Else-
-
vier, 1991:11 45. 16 . Bunge RP, Bunge MB, EldridgeCF.
Linkage between axonal ensheath -
Histogenesis v evolution normal :
5. Bignami A , Dahl D. Astrocyte-spe- exoda y distribution regional de
cific protein and neuroglial differ- ment and basal lamina production microglia. Mem R Soc Espan Hist
entiation: an immunofluorescence by Schwann cells. Ann Rev Neu - -
Nat 1921a; l 1:213 268.
study with antibodies to the glial rosci 1986;9:305-328. 29. Del Rio Hortega P. Estudios sobre
fibrillary acidic protein. I Comp 17. Bunge RP, Bunge MB, Kleitman N . la neuroglia. La glia de escasas ra -
Neurol 1974;153:27-38. Role of peripheral extracellular diaciones ( oligodendroglia ). Bol R
6. Bignami A , Eng LF, Dahl D, Uyeda matrix in Schwann cell function Soc Espan Hist Nat 192 lb;21:63-92.
CT. Localization of the glial fibril - and in neurite regeneration . Dev 30. Del Rio Hortega P. Microglia . In:
lary acidic protein in astrocytes by -
Neurosci 1989;11:348 360. Penfield WG, ed . Cytology and cel -
immunofluorescence. Brain Res .
18 Bunge MB, Bunge RP Ris 11. Ultra - lular pathology of the nervous sys -
structural study of remyelination tem . Vol ii Now York: Paul D
*
1972 3:429 435
7. Bjbrklund A , Olson L, Dahl D, in an experimental lesion in adult I loeber, 1932:483-534.
Schwarcz R . Short - and long - term cat spinal cord . J Biophys Biochem 31 . Delacourte A . General and chro -
consequences of intracranial injec - Cytol 1961;10:67-94. matic glial reaction in Alzheimer
19. Cadelli DS, Schwab ME . Myelin - -
brains. Neurol 1990;40:33 37.
tions of the excitotoxin quinolinic
acid, as evidenced by GFAP im
munohistochemistry of astrocytes.
- associated inhibitors of neurites
outgrowth and their role in CNS
-
32. IX mpsey EW, Luse S. Fine struc-
ture of the neuropil in relation to
Brain Res 1986;371:267-277. regeneration . In : Abbott N|, ed . neuroglia cells. In: Windle WF, ed .
.
8 Bleier R . The relations of ependyma -
Glial neuronal interaction . Ann NY Biology of neuroglia. Springfield ,
to neurons and capillaries in the - -
Acad Sc i 1991,633:234 240. II. Charles C. Thomas, 1958:
hypothalamus: a Golgi -Cox study. 20. Cammermeyer j. Histiocytes, jux - 99-108.
-
I C omp Neurol 1971;!42:439 162. ta vascular mitotic cells and mi - 33. Denis- Donini S, Glowinski ) ,
9. Bodian D. Neurons, circuits and croglia cells during retrograde Prochiantz A. Glial heterogeneity
neuroglia . In: Quarton GC, Mel - changes in the facial nucleus of may define the three-dimensional
nechuk T, Schmitt FO, eds. The rabbits of varying age. Ergeb Anat shape of mouse mesencephalic
neuroscience. A study program. - -
Entwickl Gesch 1965;38:195 229. dopaminergic neurons. Nature
1984;307:641-643.
New York: Rockefeller University 21 . Cholewinski AJ , Hanley MR ,
.
Press 1967:6- 24 .
10 Brightman MW , Reese* TS, Feder
.
Wilkin GP. A phosphoinositide
linked peptide response in astro
-- 34 Dohrmann GJ . The choroid plexus :
a historical review. Brain Res
N. Assessment with the electron cytes: evidence for regional hetero - 1970;18:197-218.
.
microscope of the permeability to geneity. Neurochem Res 1988; 35. Eisenbarth CS, Walsh FS, Niren -
peroxidase of cerebral endothe- »
13:389 4. berg M. Monoclonal antibody to a
lium and epithelium in mice and 22. Coggeshal! RE, Fawcet DW . The plasma membrane antigen of neu -
sharks. In : Crone C, Lassen NA, fine structure of the central ner- rons. Proc Natl Acad Sci ( USA )
eds. Capillary permeability. New vous system of the leech, Hirudo 1979;76:4913-4917.
York: Academic Press, 1970: medicinalis. | Neurophvsiol 1964; 36. Erecinska M , Troeger MB, Wilson
468-476. 27:229-289. DF, Silver 1A. The role of glial
11 . Brightman MW , Palav SL. The fine 23. Copenhaver WM , Bunge RP, cells in regulation of neurotrans-
structure of ependyma in the brain Bunge MB. Bailey's textbook of niitter aminoarids in the external envi -
ot
19:415 439.
-
tin rat I c VII Biol 1963«
-
histology. 16th ed. Baltimore:
Williams & Wilkins, 1971.
ronment . Brain Res 1986; 369;
203 214
12. Bri /ee KR , Vogt ) , Kharetchko X . 24 . Cserr HF. Physiology of the 37. Evans PD, Reale V, Merzon RM ,
Postnatal changes in glial / neurons choroid plexus. Phvsiol Rev 1971; Villegas ) . Mechanisms of axon -
index with a comparison of meth - 51:273-311. Schwann cell signaling in the squid
6 Neuroglia 229
-—
nerve fiber. In : Abbott NJ , ed. neuronal interaction. Ann NY J . Reactive astrocytes a review.
-
Glial neuronal interaction. Ann
NY Acad Sei Vol 1991;633:434-447. 53.
Acad Sci 1991;633:64-77.
Knigge K , Joseph SA , Sladek JR Jr,
Cytobiol 1990;61:133 160.
68. Mallat M , Chamak B, Thery C. Les
38. Farquhar MG , Hartmann |F. Neu - Hoffman G, Scott DE . Structure macrophages cerebraux : Role dans
roglial structure and relationships and function of the endocrine hy - les remaniements morphologiques
as revealed by electron micros- pothalamus. In : Morgane PJ, et la degenerescence des neurones.
copy J Neuropathol Exp Neurol Panksepp J , eds . Physiology of the Medeeine / Sciences 1991;7:768-774 .
1957;16:18-39. hypothalamus. New York: Marcel 69. Maxwell DS, Kruger L. The fine
39. Federoff S. From neuroepithelium Dekker, 1980. structure of astrocytes in the cere -
to mature astrocytes. In : Althaus 54. Kruger L, Maxwell DS. Electron bral cortex and their response to
HH, Seifert VV, eds. Glial-neuronal microscopy of oligodendrocytes in focal injury produced by heavy
communication in development normal rat cerebrum . Am J Anat ionizing particles J Cell Biol
and regeneration. Berlin: Springer- -
1966;118:411 436. 1965;25:141-157.
Verlag, 1987:4-25.
40. Federoff S, Vemadakis A , eds. As-
55. Kuffler SW, Nicholls JG, Martin 70. -
Moore BW . Bra in specific proteins.
AR . From neuron to brain: a cellu - In : Schneider DJ , ed . Proteins of
—
trocytes. Vol. I III. New York: Aca - lar approach to the function of the the nervous system . New York :
demic Press, 1986. nervous system . 2d ed . Sunder- Raven Press, 1973| 12.
41 . Fulton BP. Burne JF, Raff MG. Glial land , MA: Sinauer, 1984. 71 . Mugnaini F.. Gell junctions of as-
cells in the rat optic nerve. In : Ab- 56. Kuffler SW , Nicholls JG, Orkand trocytes, ependyma , and related
bott NJ , ed. Glial - neuronal interac- RK. Physiological properties of cells in the mammalian cerebral
tion . Ann NY Acad Sci 1991; glial cells in the central nervous nervous system , with emphasis on
633:27-34 system of amphibia . J Neurophvs - the hypothesis of a generalized
42. Glees P. Neuroglia , morphology iol 1966;29:768-787. functional syncytium of support -
and function . Springfield , 1 L: 57. Kuffler SW , Potter DD. Glia in the ing cells. In: Federoff S, Vernadakis
Charles G . Thomas, 1955. leech central nervous system : A , eds. Astrocytic. Vol . 1. New
43. Golgi G . Sulla tine anatomia degli physiological properties and neu - York: Academic Press, 1986:
organi centrali del sistema ner - ron-glia relationships. J Neuro- 329-371.
voso. Riv Sper Freniat Med Leg physiol 1964;27: 290-320. 72. .
Mugnaini E Walberg F. Ultrastruc -
.
1882- 1885;8: 165-195 361-391 , 9; 58. Laywell ED, Steindler DA . Bound - -
193-220. —
1 - 17, 161 - 192, 385 402; 11 :72 123,
44. Gumpel M , Tmirback A , Baron -

aries and wounds, glial and gluco
conjugates In : Abbott NJ , ed.
-
Glial neuronal interaction . Ann
-
73
ture of neuroglia Hrgeb Anat En
twickl -Gesch 1964 ; 37:194-236.
Murphy S, Pearce B. Functional re
ceptors for neurotransmitters on
-
Van Evercooren A Li reparation *
-
NY Acad Sci 1991,633:122 141. astroglial cells Neuroscience 1987;
myelinique dans le systeme 59 Le Prince G, Gopin MG, Hardin 11, 22:381-394.
nerveux central des mammiferes. Belin MF, Bouilloux JP, Tardy M. 74 Murray MR Response of oligpden -
Medeeine/Sciences 1991;7:782- Neuron -glia interactions: effect of droevtes to serotonin. In : Windle
789. serotonin on the astroglial expres- WF, ed . Biology of neuroglia .
45. Hao C, Richardson A , Federoff S. sion of GFAP and its encoding Springfield, II Chariest rhomas,
Macrophage- like cells originate message. Exp Brain Res 1990; 1958:176-180 .
from neuroepithelium in culture: 51:295-290. 75. Murray MR . Nervous tissue in
characterization and properties of 60. Levitt P, Rakic P. Immunoperoxi - vitro. In : Wilmer I N , ed . Cells and
-
the macrophage like cells Int J dase localization of glial fibrillary tissues in culture Vol . 2 . Methixls,
Dev Neurosci 1990;9:1-14 . acidic protein in radial glial cells biology and physiology. New
46. Herndon RM. The tine structure ot and astrocytes of the developing York: Academic Press, 1965;
the cerebellum. II . The stellate neu - rhesus monkey brain. J Gomp 373-455.
rons, granule cells and glia . I Gell Neurol 1980;193:815-840. 76. Nagy I ., Martinez K . Astrocytic in -
-
Biol 1964;23:277 293. 61 l .ieberman FM . Role of glutamate duction of endothelial tight junc -
47. Herndon RM , Price DL, Weiner in axon -Schwann cell signaling in tions. In: N .J . Abbott , ed . Glial -
LP. Regeneration of oligoden - the squid . In : Abbott NJ , ed. Glial - neuronal interaction . Ann NY
droglia during recovery from de- neuronal interaction . Ann NY -
Acad Sci 1991;633: 395 404.
mvelinatmg disease. Science 1977; Acad Sci 1991,633:448-457 . 77. Newman F.A . Regulation of potas-
195:693-694. 62. Fuse SA . Electron microscopic ob- sium levels by glial cells in the
48. Hertz L. Is Alzheimer's disease an servations of central nervous sys- retina . Trends Neurosci 1985,
anterograde degeneration, origi- tem. J Biophys Biochem Gytol
'
7:156-199.
nating in the brainstem , and dis- 1956;2:531-432. 78. Noble M , Ataliotis P, Barnett SC, et
rupting metabolic and functional 63. Luse SA. Ultrastructure of reactive al . Development , regeneration , and
interactions between neurons and .
and neoplastic astrocytes Lab In - neoplasia of glial cells in the cen -
glial cells? Brain Res 1989; 514: -
vest 1958;7:401 417. tral nervous system. In : Abbott NJ ,
-
335 353. 64. McCarthy KD, Salm H , Lera LS. ed . Glial-neuronal interaction . Ann
49. Heynes RO, Patel R , Miller Rll . Astroglial receptors and their regu - NY Acad Sci 1991;633:34-47.
Migration ot neuroblasts along lation of intermediate filament pro- 79. Orkand , RK . Glial electrophysiol -
preexisting axonal tracts during tein phosphorylation . In: Kimel - ogv and transport , In : Abbott NJ ,
prenatal cerebellar development . | berg HK , ed . Glia cells, receptors. -
ed . Glial neuronal interaction . Ann
Neurosci 1986;6:867-876. New York: Raven Press, 1988:1 - NY Acad Sci 1991;633:245 247. -
50. Innocenti GM , Clark S, Koppel H 22. 80. Page RB, Roscnstein |M , Dovev
Transitory macrophages in the 65 McCeer PL, Itagaki S, McGeer EG. -
BJ, Leure DuPree AE. Ependy -
white matter of the developing vi - Expression of the histocompatibil - mal changes in experimental
sual cortex . II . Development and ity glycoprotein 11 LA - DR in neuro- hydrocephalus. Anat Ree 1979a , 194:
relations with axonal pathways. logical disease. Acta Neuropathol 83-104 .
Dev Brain Res 1983;11:55-66. -
1988;78:550 557. 81 . Page RB, Rosenstein JM , Leure-
51 . Janzer RG , Raff MG. Astrocytes in - 66. Magistretti PJ , Hof PR , Martin J - l . DuPree AE. The morphology of ex -
duce blood - brain barrier proper - Adenosine stimulates glycogenolv - trachoroidal ependyma overlying
ties in endothelial cells. Nature sis in mouse cerebral cortex : a pos - gray and white matter in the rabbit
1987;325:253-257. sible coupling mechanism between lateral ventricle Anat Rec 1979b;
52. Kettenmann H , Btankenfeld GV, neuronal activity and energy 194:67-82.
Trotter |. Physiological properties metabolism . J Neurosci 19K6;6: 82 . Palav SL. An electron microscopi -
of oligodendrocytes during devel - -
2558 2562. cal study of neuroglia. In: Windle
opment . In : Abbott NJ , ed . Glial - 67. Malhotra SK , Shnitka TK , F.lbrmk WF, ed . Biology of neuroglia .
Springfield, IL: Charles C. Thomas, imates. Trab Lab Invest Biol Univ 115. Skoff RP, Knapp PE. Lineage and
1958:24-38. Madrid M 5; 11.2 N- 237 differentiation of oligodendrocytes
83. Palay SL. The role of neuroglia in 99. Ramon y Cajal S. El proceder del in the brain. In: Abbott NJ, ed.
the organization of the central ner- oro- sublimado para la coloracion Glial-neuronal interaction. Ann
vous system. In: Kodahl K , Is- de la neuroglia . Trab Lab Invest NY Acad Sci 1991;633:48-55.
sekutz B Jr, eds. Nerve as a tissue. Biol Univ Madrid 1916;14 :155- 162. 116. Somjen GG. Nervenkitt: notes on
New York: Harper & Row, 1966: 1(X ). Ramon-Moliner E. A tungstate the history of the concept of neu-
VH). modification of the Golgi-Cox roglia. Glia 1988;1 :2-9.
84 . Palay SL, Palade GE. The fine method. Stain Technol 1958;33: 117. Stew'art PA , Wiley MJ . Developing
structure of neurons. J Biophys 19- 29. nervous tissue induces formation
BiochemCytol 1955;1:69-88. 101. Ransom BR . Vertebrate glial classi- of blood-brain barrier characteris-
85. Patel AJ, Hunt A . Regulation of fication, lineage, and heterogene- tics in invading endothelial cells.
production bv primary cultures of ity . In; Abbott NJ, ed. Glial-neu- Dev Biol 1981;84:183-192.
rat forebrain astrocytes of a trophic ronal interaction. Ann NY Acad Sci 118. Stitt TN, Gasser UE. flatten ME.
factor important for the develop- 1991;633:19-26. Molecular mechanisms of glial-
ment of cholinergic neurons. Neu- 102. Ransom BR , Kunis DM, Irwin I, guided neuronal migration . In: Ab-
rosci Lett 1989;99: 223- 228. Langston JW . Astrocytes convert bott NJ, ed . Glial-neuronal interac-
86 . Peschanski M Le temps venu de la the Parkinsonism inducing neuro- tion. Ann NY Acad Sci 1991;633:
"neurogliobiologie. " toxin, MITT, to its active metabo- 113- 121 .
Medecine / Science 1991;7:766-767. lite, MPP + . Neurosci Lett 1987; 119. Stone EA , Ariano MA . Are glial
87. Penfield W . Neuroglia , normal and 75:323-328. cells targets of central noradrener -
pathological . In W .G. Penfield, ed. 103. Rapoport SI. Blood - brain barrier in gic system ? A review' of the evi-
Cytology and cellular pathology of physiology and medicine. New dence. Brain Res Rev 1989;14 :
the nervous system. Vol. II . New' York: Raven Press, 1976. 297- 309.
York: Paul B Hoeber 1932123 104 . Reichenbach A . Glia / neurons 120. Streit WJ, Kreutzberg GW . The re-
479. index: review and hypothesis to sponse of endi>genous glial cells to
88. Perry VII , Gordon S. Macrophages account for different values in vari- motor neuron degeneration in-
and microglia in the nervous sys- ous mammals. Glia 1989;2:71-77. duced bv toxic ricin. J Comp Neu-
tem. Trends Neurosci 1988;ll : 105. Robertson DM, Vogel FS. Concen- rol 1988;268:248- 263.
273-277. tric lamination of glial processes in 121 . Tardy M. Astrocytes et homeostasie .
89. Peters A , Palay SL. An electron oligodendrogliomas. J Cell Bio Mederine / Sciences 19^1 ,7:799-
microscope study of the distribu- 1962;15:313-334. 804 .
tion and patterns of astroglial 106 . Rubinstein LJ, Klat / o 1, Miquel J 122. Tedeschi B, Barret JN , Keane RW .
processes in the central nervous Histochemical observations on ox - Astrocytes produce interferon that
.
• \ stem I Anat
>
1965299 119
90. Peters A , Palay SL, Webster H deF.
idative enzyme activity of glial
cells in a local brain injury . J Neu-
enhances the expression of H- 2
antigens on a subpopulation of
The fine structure of the nervous ropathol Exp Neurol 1%2;21: brain cells. J Cell Biol 1986;
system: neurons and their support- 116 136. 102:2248-2252.
ing cells. 3rd ed . New' York: Ox - 107. Sasaki II, Sato F, Mannen H. Mor - 123. Tennyson VM. The differences in
ford University Press, 1991 . phological analysis of single astro- fine structure of the myelen-
91 Polak M . Morphological and func- cytes of the adult cat central ner - cephalic and telencephalic choroid
tional characteristics of the central vous system visualized by HRP plexuses in the fetuses of man and
and peripheral neuroglia ( light mi- microinjection. Brain Res 1989;501: rabbit , and a comparison with the
croscopic observations). In: De 339 mature stage . In : Walker AE,
Robertis F.DP. Carreas R, eds Biol - 108. Schaltenbrand G. Plexus und Arana- Iniguez R , eds. Cere-
ogy of the neuroglia, progress in Meningen. Saccus vasculosus. In: brospinal fluid in health and dis-
brain research. Vol. 15. Amster- von Mollendorff W , ed . Handbuch ease. Acta Neurol Lat Am 1971;
dam: Elsevier, 1965:12- 34. der mikroskopische Anatomie des 17:( Suppl 1 ): 11-52.
92. Pomerat CM. Functional concepts Menschen. Vol. 4, part 2. Berlin: 124. Tennyson VM. Pappas GD. Elec -
based on tissue culture studies of Springer- Verlag, 1955:94-98. tron microscope studies of the de-
neuroglia cells. In: Windle WF, 109 Scheibel ME, Scheibel AB. Neurons veloping telencephalic choroid
ed. Biology of neuroglia . Spring- and neuroglial cells as seen writh plexus in normal and hydro-
field, IL : Charles C. Thomas, 1958: the light microscope. In: Windle cephalic rabbits. In: Fields W ,
162- 175. WF, ed . Biology of neuroglia . Desmond M, eds. Disorders of the
93. Prochiant / A , Mallat M . Astrocytes Springfield, IL: Charles C. Thomas, developing nervous system . Ch.
diversity . Ann NY Acad Sci 1958:5-23. 12 . Springfield, IL: Charles C.
1988;540:52-63. 110. Schlue W - R , Dorner R , Rempe L, Thomas, 1% 1 :267-318.
94 Raff MC. Glial cell diversification Riehl B. Glial H + transport and 125. Tennyson VM, Pappas GD. Fine
in the rat optic nerve. Science control of pH . In: Abbott NJ, ed . structure of the developing telen-
1989;243:1450-1455. Glial-neuronal interaction. Ann cephalic and myelencephalic
95. Raisman G. Glia, neurons, and NY Acad Sci 1991;633:287-305. choroid plexus of the rabbit . J
plasticity . In: Abbott NJ, ed . Glial- 111. Schultz RL, Maynard EA , Pease Comp Neurol 1964;123:379-412.
neuronal interaction. Ann NY DC. Electron microscopy of neu- 126. Tennyson VM , Pappas GD. Some
\ I .KISI 1991;633:209-213 rons and neuroglia of cerebral cor- aspects of the fine structure of the
96. Rakic P. Guidance of neurons mi- tex and corpus callosum. Am J ependyma. In: Minckler J, ed .
grating to the fetal monkev neocor- Anat 1957;100:369-407. Pathology of the nervous system.
lex . Brain Res 1971;33:471-176. 112. Schultz RL, Pease DC. Cicatrix for- Vol. 1. New York: McGraw -Hill,
97. Ramon y Cajal S. Histologie du mation in the rat cerebral cortex as 1968a;518-531.
Syst me Neveux de l' Homme et revealed by electron microscopy. 127. Tennyson VM, Pappas GD. The
^
des Vertebres. ( Azoulay L, trans.) Am J Pathol 1959;35:1017- 1041 fine structure of the choroid
Paris: Maloine, 1909, 1911 . 113. Shuangshoti S, Netsky MC» . Histo- plexus: Adult and developmental
( Reprinted , Consejo Superior de genesis of choroid plexus in man. stages. In: Lajtha A , Ford DlI, eds.
Investigaciones Cientificas, Insti- Am J Anat 1966;118:283-316. Brain barrier systems, progress in
tuto Ramon y Cajal, Madrid , 1972. ) 114 Shuangshoti S, Netsky MG. brain research. Vol. 29. Amster-
98. Ramon v Cajal S. Sobre un nuevo Human choroid plexus: morpho- dam: Elsevier, 1968b;63-86.
proccder de impregnacion de la line and histochemical alterations 128. Terry RD. Electron microscopy of
neuroglia y sus resultados in los with age. Am J Anat 1970;128: the central nervous system. In:
centros nerviosos del hombre v an- 73-%. Bailey OT, Smith DE, eds. The
6 Neuroglia 231
central nervous system . Baltimore: rect tracing of their transformation tivation and its biochemical conse-
Williams & Wilkins, 1968:335-346. from radial glia to astrocytes. J quences in astrocytes. In: Abbott
129. Virchow R . liber das granulierte Comp Neurol 1989;289:74-88. -
NJ , ed . Glia I neuronal interaction .
Ansehen der Wandungen der Ger- 132. Walz W . Role of glial cells in the Ann NY Acad Sci 1991;633:
himventrikel. Allg Zeitschchr Psv- regulation of the brain ion neu - 475-489.
chiatr 1846;3:242-250. roenvironment . Prog Neurobiol 135. Windle WF, ed Biology of neu -
130. Virchow R . Cellular pathology. 1989;33:309-333. roglia . Springfield , II .: Charles C.
(Translated from the 2 nd German 133. Wilkin GP, Marriott DR , Cholewin- Thomas, 1958.
edition by F. Chance.) London: ski A ) Astrocytes heterogeneity . 136. Young JZ. The concept of neu -
Churchill , 1860. -
Trends Neurosci 1990;13:43 46. roglia . In : Abbott NJ , ed . Glial - neu -
131. Voigt T. Development of glial cells 134 . Wilkin GP, Marriott DR, ronal interaction Ann NY Acad Sci
in the cerebral wall of ferrets: di- Cholewinski AJ , et al. Receptor ac- 1991 ;633:1-18.
Section III
Peripheral Nervous System
7
Receptors and Effectors
SENSORY RECEPTORS body, such as the hand or face (23). Certain

forms of sensation arising in abdominal and
All information we have concerning the thoracic viscera are poorly localized , difficult
world about us is conveyed to the brain by an for the patient to describe, and sometimes re-
elaborate sensory system. This input, initi- ferred to false locations. A peripheral receptive
ated from the external world , reaches the cen- field is the area within which a stimulus of ap-
tral nervous system via first order sensory propriate quality and strength will cause an
nerve fibers. Sensory receptors and sensory afferent neuron to discharge. The receptive
endings act as transducers, which change field may represent an area of skin in which a
physical and chemical stimuli in our environ- mechanical stimulus will excite cutaneous re-
ment into coded nerve impulses the brain can ceptors, the angle of joint rotation necessary
decode. A sensory unit consists of a single pe- to excite sensory units, or an area of the vi-
ripheral neuron, located in a spinal or cranial sual field in which a light stimulus will evoke
nerve ganglion, its peripheral and central discharges in retinal ganglion cells. Within a
ramifications, and , in certain instances, the peripheral receptive field the threshold for
nonneural transducer cells with which the adequate stimulation varies in that it is usu -
distal end of the peripheral nerve fiber may ally lowest in the central region where the
be associated. Information conveyed cen- density of receptor elements is highest. Pe-
trally by sensory units provides an ongoing, ripheral branches of one sensory unit often
constantly changing global picture of the ex- overlap those of adjacent sensory units, and
ternal environment and the stimuli which it peripheral receptive fields on the body sur-
presents. From this massive barrage of sen- face vary greatly in size. Cutaneous receptive
sory impulses generated in many different fields on the digits of the hand are small in
types of receptors and nerve endings, the cen- comparison to those on proximal portions of
tral nervous system derives precise informa- the limbs and on the trunk, but the central
tion concerning the quality, the intensity, the representation of these densely innervated
locus, and the spatial and temporal patterns areas in the cerebral cortex is massive.
of stimuli. Muller's "doctrine of specific energies," in-
Stimuli in our environment elicit sensory terpreted in modem physiologic terms, states
experiences that, within certain limits, can be that different sets of nerve fibers, when acti-
recognized , described and classified. Each vated, elicit different sensations by virtue of
more or less unique sensory experience is re- their unique central connections (61-63). A
ferred to as a sensory modality . Sensations of particular sensory nerve fiber provokes an
color compose a single modality, as do those identical sensation regardless of how it is ex-
of tones. General somatic sensibility consists cited, that is, by a natural adequate stimulus
of several sensory modalities that differ in or by an artificial stimulus. Within a receptive
quality and can be distinguished readily as surface, such as the skin, different sets of
touch-pressure, pain, warmth, cold , and nerve endings and receptors are distributed
sense of position or movement of limbs at in a mosaic fashion. Why a particular set of
joints. Certain substances can be readily dif - nerve fibers that terminates in an area com -
ferentiated by the way they taste, and the ca- mon to other receptive elements responds se-
pacity of humans and animals to distinguish lectively to a stimulus of a particular quality
and discriminate a great diversity of odors is is unknown. The modalities and qualities of
well-known. The spatial position of a tactile sensation seem to depend upon the temporal
stimulus can be located with considerable ac- and spatial patterns of activation, the speci-
curacy, especially on certain surfaces of the ficity of the sensory endings, and the central
235
236 Section III Peripheral Nervous System
connections ( 24 ). The four elemental qualities rapidly adapting . Other receptors respond to a
of cutaneous sensibility are not distributed continuing stimulus with a high frequency
uniformly over an area of skin. Within a cuta- discharge for its full duration; these receptors
neous area there is a local differential sensi- are called slowly adapting .
tivity to touch , warmth, cold , and pain (8). The transduction of mechanical, chemical,
Each spot receives terminal branches from or electromagnetic energy into a train of nerve
several afferent nerve fibers and a single impulses is accomplished by receptors that de-
nerve fiber may innervate several sensory velop in three distinct ways in the embryo (92)
spots. Regardless of how a particular spot is ( Fig. 7.1 ). Some transducing elements, such as
excited , only one elementary sensory experi - olfactory receptor cells in the nasal cavity, hair
ence is evoked , if the excitation is local. Varia - cells in the inner ear, and taste receptors, differ-
tions of the elementary sensory experience entiate within localized thickenings of the
can be produced by temporal and quantita - cephalic surface ectoderm. Photoreceptors of
tive variations of the stimulus. The wide vari- the eye develop from the neural tube, and
ety of complex sensory experiences are other sensory receptors arise from neural crest
thought to be generated in the central ner- tissue. Many of the latter types of receptor cells
vous system from the combinations of activi- may be in contact with a specialized ectoder-
ties evoked in afferent nerve fibers, each of mal or mesodermal structure such as a layered
which, when acting alone, is associated with capsule or a muscle fiber. The categorization of
a sensory quality of some purity (61-63). receptors on the basis of their embryology is
The manner in which receptors behave in important for comparative purposes, but a
response to a continuing stimulus varies. functional classification is most useful for the
Some receptors discharge only at the onset of study of sensory mechanisms in mammals.
a steady stimulus; these receptors are called Sensory receptors may be regarded as
Nervous system
Surface ectoderm
;
Origin of sensory
elements
Origin of neural
conductor
- <©
Olfaction (I) _ «>
< •
Placode Placode
- «rI
Vision (II)
•
Ganglionic cell
<© - —- Neural
tube
Neural
tube
u »vi;i
|
Audition ( VIII) O
2 ~
and
equilibrium _ 2.
<J)*“
— --- - ~
Placode Placode
Sensory
- <S» differentiation
Taste — •<S>> £ cQ of certain Neural crest
( VII. IX , X ) - <£>>
- <Sfy 2 —* —
(•) „
ectodermal
cells of the
(cranial ganglia)
tongue
Spinal nerve
Pain v - £ <©
*
> »
**
Free nerve ending
(neural crest ) Neural crest
<3* £ ( spinal ganglia)
Mesenchymal
Touch >-
® £ ***** + -* * * cells
Figure 7.1. Classification of sensory receptor cells according to embryonic origin. All sensory cells are derived from
surface ectoderm, except those associated with vision and touch. Sensory elements in the visual system are derived
from the central nervous system (neural tube), but their nature, concentration, and specialization are similar to placo-
dal cells. Touch receptors below the surface ectoderm are derived from mesenchymal cells.
miniature transducers capable of responding older individuals. Different regions and tis-
readily to appropriate forms of energy (ade- sues of the body have marked differences in
quate stimulus). An appropriate external stim- the type and number of receptors. Detailed
ulus applied to a receptor gives rise to a graded reviews of cutaneous innervation have been
electrical response, known as a "receptor po- published (32, 33, 73, 87).
tential." The term "generator potential" is used
to define the electrical potential that triggers RECEPTOR ’ S DIVERSITY
the "all or none" response in the initial seg-
ment of the sensory nerve fiber. If the receptor No single classification of receptors has
potential is generated in the first sensory neu- evolved which adequately correlates the
ron, then it is also the generator potential (24, principles of structural organization, distrib-
33). Such physiologic events are demonstrated ution, and function. The three simple cate-
Biochemical and
-
best in the Pacinian corpuscle (45 48).
electrophysiologic
gories suggested by Miller and collaborators
( 58, 59) are the least elaborate and restrictive.
studies of sensory receptors revealed that the They suggested that the entire body is served
transduction of different types of stimulus by a basic triad of sensory nerve endings
energies into neural activity is based on vari- which are either "free," "expanded -tip," or
ous specific mechanisms, involving mem- "encapsulated ." Such designations are ap-
brane channels and second -messenger sys- plicable to the endings in glabrous skin and
tems. Mechanoelectric transduction is the subpapillary dermis. These terms also
produced by direct mechanical interaction apply to the endings observed in fascia, ten-
between the stimulus and membrane chan- dons, ligaments, periosteum, and synovial
nels. Few channels are open in the unstimu- membranes (75) ( Figs. 7.2 and 7.4 ). However,
lated condition, whereas mechanical stimula- difficulty is encountered with such categories
tion deforms the membrane and cause in hairy skin and muscle spindle receptors
channels to open. Influx of Na * and K 4
where free nerve and expanded -tip endings
causes the receptor terminal to depolarize lo- are also encapsulated .
cally producing the receptor potential. Sherrington (86) classified all receptors
Chemoelectric transduction is similar, except into three main groups: exteroceptors , proprio-
that a receptor-ligand interaction produces ceptors , and interoceptors ( Fig. 10.23). Extero-
channel opening. A second messenger medi- ceptors on the external body surface receive
ates channel opening in olfactory receptors stimuli from the outside which may, or may
and certain gustatory receptors. Photoelectric not, result in somatic movements. They in-
transduction involves the absorption of light clude touch, pressure, pain, temperature,
by photoreceptors. A photon-photopigment smell, sight, and hearing. Some of these are
interaction on intracellular membrane pro- contact receptors; others, such as smell, sight,
duces a three-dimensional change in the hearing, and aspects of thermal sense, are ac-
photopigment. The resulting change in tivated by distant stimuli and are known as
membrane permeability also involves a teloreceptors.
second - messenger system. For further details The proprioreceptors, which receive stim-
on the physiology, biochemistry, and molecu-
lar biology of sensory receptor the reader is
referred to the excellent reviews by Shepherd
(85), Martin ( 50), and Martin and Jessell ( 51 ).
Receptor endings have numerous mito-
chondria, microvesicles, neurofilaments, and
even acetylcholinesterase in the case of nerve
endings related to hairs. Other receptors are
associated with supportive cells that demon-
strate a variety of enzyme activities. Free
nerve endings appear to be the receptors in
fetal life, whereas encapsulated endings ap-
pear after birth (16). Throughout life recep-
tors show a continuous cycle of breakdown,
renewal, and reorganization (12). This obser-
vation accounts for the variable appearance -
Figure 7.2. Sensory nerve terminations in corneal ep
of Pacinian and Meissner's corpuscles in ithelium .
uli from the deeper portions of the body wall, cles, and deep afferents probably end in
-
especially from the joints, joint capsules, liga Pacinian corpuscles.
ments, and fascia , give rise to position sense In an analysis of clinical problems related to
and the sense of movement (i.e., kinesthesis). sensation, Head (35, 36) proposed that there
They are primarily concerned with the regu- are two different kinds of sensation subserved
lation of movement in response to exterocep- by dual sensory mechanisms at the periphery.
tive stimuli. These receptors provide sensory This dual innervation was postulated to con-
information which is utilized in the cerebral sist of a protopathic system and an epicritic sys-
cortex to generate a conscious awareness of tem. Protopathic sensation was considered to
bodily muscle activity and joint movements be mediated by a primitive system subserving
( kinesthetic sense ). Most of the receptors re - pain and extreme temperature differences
lated to the knee and temporomandibular which yield ungraded , diffuse impressions of
joints are diffuse unencapsulated nerve ter- a marked affective character. Epicritic sensa-
minals (30, 41 ). Other specialized receptors tion was thought to be mediated by a phyloge-
(spindles) in skeletal muscle and tendon are netically more advanced system sensitive to
activated by muscle contraction and stretch. smaller temperature changes and concerned
Their encoded signals regulate muscular ac - with the discriminative aspects of tactile sensa-
tivities, either at spinal cord levels (e.g., my- tion (i.e., precise localization and gradation of
otatic, flexor, and extensor reflexes), or they stimulus intensity). The concept of a duality of
reflexively regulate muscle tone and coordi - cutaneous sensations has been severely criti-
nation of muscle activities (i.e., synergy) via cized (93), but it has been useful in studying
projections to specific parts of the cerebellum. pain in humans. It is likely that the two cate-
Nerve endings in skin, joints, fascia , muscle, gories of pain reflect central rather than pe-
and tendons all transmit afferent nerve im - ripheral mechanisms. It also seems likely that
pulses from the soma or body wall. Hence ex - the protopathic system may be anatomically
teroceptors, proprioceptors, and stretch re - related to free nerve endings of small diameter
ceptors in muscles and tendons, are grouped axons (81). Affective sensations are related pri-
together as somatic receptors. marily to reactions indirectly involving bodily
The interoceptors ( visceroceptors) are the welfare, and neuronal activities in the limbic
visceral sense organs that receive and trans - cortex may play an important role in this form
mit poorly localized sensory impulses related of sensation. Discriminative sensibility forms
to digestion, excretion, circulation, and respi- the basis for cognitive and complex associative
ration, which are primarily under the control reactions which involve the cerebral cortex;
of the autonomic nervous system. They give this form of sensation is regarded as gnostic or
rise to sensations of visceral pain and con - cortical . In a general way, pain, thermal, vis-
tribute to forms of visceral sensibility such as ceral sensibility, and certain aspects of touch
hunger, thirst, and sexual feelings, and to the are predominantly affective, while tactile
-
general feelings of well being or malaise. sense, kinesthesis, and teloceptive sensibilities
Smell, although not interoceptive, has close are predominantly discriminative.
visceral affiliations and may be considered Physiologically, receptors can be classified
partly visceral. in terms of the form of energy to which they
Sensibility may also be divided into super - respond at the lowest stimulus intensity.
ficial and deep. The former obviously coin - Mechanoreceptors , responding to mechanical
cides with exteroceptive sense and the latter forces, include those that subserve touch-
comprises both interoceptive and propriocep- pressure in the skin, position sense, and
tive sense, including deep pressure. A special kinesthesis ( joints and joint capsules), as well
form of sensation is the ability to recognize as stretch receptors in muscle, visceral pres-
the vibrations of a tuning fork applied to sure receptors, and hair cells in the cochlea.
bone or skin. This is known as vibratory sense, Thermoreceptors , responding separately and
a form of mechanoreceptive sensibility de - differentially to warmth and cold , are distrib-
pendent for its unique qualities upon the uted in spotlike fashion in the skin and vary
temporal pattern of the neural inputs. The greatly in their density in different parts of
perception of vibratory sense appears depen - the body. Photoreceptors subserving vision re-
dent upon two sets of primary afferents, one spond to light, and chemoreceptors initiate im-
innervating the skin and one innervating pulses concerned with taste and olfaction.
deep tissue (64). Cutaneous afferents proba - Pain receptors are collectively referred to
bly convey impulses from Meissner's corpus - as nociceptors since pain can be produced by
different forms of energy ( mechanical, chemi- or corpuscles, which are enclosed in a capsule
cal, or thermal). Pain, frequently a frightening of modified supporting cells.
sensory experience, is associated with nox-
ious stimuli that injure tissue. Because almost Free Nerve Endings
all descriptions of pain come from studies in
humans, many distinctive forms are recog- Free nerve endings are the most widely
nized. Descriptions of particular kinds of distributed receptors in the body . They are
pain guide the astute physician in his search most numerous in the skin, but also are
to determine the nature and extent of the un- found in the mucous and serous membranes,
derlying pathologic process. Two aspects of muscle, deep fascia , and the connective tissue
pain are recognized : (a ) the distinct sensation, of many visceral organs. The skin is supplied
and ( b) the psychologic reaction to pain by many cutaneous nerve trunks composed
which depends upon many variables. Certain of myelinated and unmyelinated fibers. Some
stimuli which commonly produce pain evoke of the large myelinated fibers are destined for
other kinds of sensory experience at weaker the encapsulated organs, but the majority are
intensities. Melzack and Wall (54 ) proposed of a relatively small caliber. The fibers of
that pain perception is modulated by both these small nerve trunks separate as they ap-
sensory feedback mechanisms and the influ- proach the epidermis, lose their myelin
ences of the central nervous system. sheath, undergo branching, and form exten-
From a morphologic point of view, two sive unmyelinated plexuses in the deeper
main types of receptors are found : (a ) the free portion of the dermis and immediately be-
and diffuse endings , which are always unen- neath the epidermis ( Fig. 7.3). From this
capsulated, and ( b) the encapsulated endings subepithelial plexus, delicate fibers penetrate
— Hair shaft
Epidermis
Cutaneous nerve-
Nerve endings
on hair follicle
I Sebaceous
glands
Arrector
pili muscle
Nerve
r
it
Papilla ' Subcutaneous
fat cells
.
Figure 7.3. Nerves and nerve endings in skin and hair follicle.
the epithelium , divide repeatedly, and form from fine myelinated fibers, while the subepi-
terminal arborizations composed of delicate dermal arborizations and plexiform nets are
terminal fibrils, which wind vertically in the main terminals of unmyelinated nerve
through the epidermis and end in small fibers (96 ). Such terminal unmyelinated fibers
knoblike thickenings, upon the surface of the are never naked , but are always invested by
epithelial cells d ig''. 7.2 and 7.3). In the Schwann cells (13). Diffuse nerve endings in
cornea , which has no horny layer, these in- the form of nerve nets, or arborizations of
traepithelial endings may reach the surface, varying complexity, are distributed widely in
but in the skin they do not extend beyond the visceral organs. They have been described in
germinative layer. Intraepithelial endings the serous membranes, heart, bronchial tree,
also are found in mucous membranes lined alimentary canal, and blood vessels (11 ,25,89 )
by stratified epithelium , such as the esopha - ( Fig. 7.4 ). Such endings also are found in the
gus and bladder. Similar endings may be choroid plexuses of the brain and in skeletal
seen in simple columnar epithelium as well. muscle. For the most part , they are terminals
Other nerve fibers form unmyelinated ar - of unmyelinated fibers. Complicated arboriza -
borizations or terminal nets in the connective tions were found in the smooth muscle of the
tissue of the dermis. There is some evidence bronchi by Larsell and Dow ( 43) ( Fig. 7.4 ).
that the intraepithelial endings are derived These visceral receptors are endings of
C7
1
V-
\
Figure 7.4. Afferent nerve endings in various visceral structures A . On a large pancreatic blood vessel. B. In endo-
cardium of dog; C. In bronchial musculature of child, and D. In longitudinal muscle coat of stomach of cat
medium-sized or large myelinated fibers and

may initiate proprioceptive bronchial re-
flexes.
An important type of diffuse cutaneous re-
ceptor is represented by the peritrichal end
ings of the hair follicles, which are activated
-
by the movements of hairs ( Fig. 7.3). They
vary considerably in complexity and are best
developed in the vibrissae of certain mam-
mals. In the simpler forms, several myeli -
nated fibers approach the hair follicle just
below its sebaceous gland , lose their myelin
sheath, and divide into several branches
which encircle the outer root sheath ( Fig. 7.3).
From these branches numerous fine fibers
run for a short distance upward and down-
ward in the outer root sheath and terminate
in flattened or bulbous endings. The smallest
hair follicles have at least two stem nerve
fibers which form an outer circular plexus
and an inner palisading one formed by the
corpuscle
longitudinally directed fibers. Larger follicles
are supplied by 6 to 10 fibers, while the Figure 7.5. Papillary ridge in glabrous skin showing
largest receive between 20 and 30. In the rab- Meissner 's corpuscle in a dermal papilla and Merkel' s
bit, each myelinated fiber sends branches to 4 discs (M) on the deep edges of the sweat ridges A free
nerve ending ( F) is shown in adjacent papilla. Arrow indi-
to 120 hairs, and an average of 4 different cates direction of most effective epidermal stimulation
dorsal root fibers supply each hair ( 94 ). Only to elicit touch and tactile two point discrimination
free epidermal and dermal endings, and the
fibers associated with hair follicles, are found cles. In glabrous skin, such as the volar sur-
in truly hairy skin . face of the finger, the epidermis and dermal
Besides the intraepithelial endings, which papillae contain a profuse array of free nerve
end among or upon ordinary epithelial cells, endings, Merkel 's discs, and the encapsulated
the deeper portion of the germinative layer Meissner's corpuscle ( Fig. 7.5). The subpapil -
contains somewhat more specialized endings lary dermis under such skin contains a wide
known as the tactile discs of Merkel ( 55) ( Fig. variety of endings including the end bulbs of
7.5). Each consists of a concave neurofibril- Ruffini, Krause, and Pacinian corpuscles.
lary disc or meniscus closely applied to a sin- The tendency toward modification of ep-
gle epithelial cell of modified structure. A sin - ithelial cells receiving sensory nerve endings
gle epidermal nerve fiber may, by repeated is found in various neuroepithelial cells which
branching, give rise to a number of such have special forms and show staining affini -
discs. These simple endings lie along the ties similar to nerve cells. The specific cells of
deeper sweat ridges between dermal papillae the taste buds ( Fig. 7.6 ), olfactory mucosa ,
( Fig. 7.5). They are numerous at birth but and hair cells in the sensory epithelia of the
gradually diminish with age. With the elec- cochlear and vestibular apparatus, are exam -
tron microscope, the Merkel cell of humans ples of such neuroepithelial cells . These sup-
and opossums can be distinguished from epi- portive cells, as well as those forming the
dermal cells (65, 66 ). The Merkel cell has a lamellae of encapsulated endings, have sur-
lobulated nucleus and a massive accumula - rounding basement membranes. It remains to
tion of secretory granules ( glycoprotein ) in be determined whether they are modified ep-
the cytoplasm that is apposed to the neurite. ithelial or transformed Schwann cells.
Cauna (12 ) believes them to be touch recep-
tors which respond to the lever movement Diffuse Endings
that results from deformation of the surface
epidermis. In areas of transition to glabrous The deep somatic structures of the human
skin, there is a gradual increase in the num- bodv have unencapsulated sensory endings
ber of Merkel 's discs and Meissner's corpus- that are more profuse than those observed in
scribed an encapsulated fusiform end organ

in the skin and adipose tissue. Although long
considered as a corpuscle, its morphology is
vague and most investigators have failed to
verify its abundant distribution in humans. It
may well represent a variation of the diffuse,
expanded -tip, unencapsulated endings de -
scribed by Miller, et al ( 59 ). Encoded mes-
sages from these diffuse unencapsulated re-
ceptors appear to be an important component
of impulses carried by the axons of the poste -
rior white columns. Proprioceptive nerve im -
pulses from these deep receptors play an
important role centrally in that they make
us aware of the numerous localized body
changes that occur during locomotion, stand -
Figure 7.6. Taste bud from circumvallate papilla of ing or sitting.
. .
tongue, a Taste pore: b nerve fiber entering taste bud When recordings are made from single
and ending upon neuroepithetiol cells. On either side primary afferent neurons innervating the
are some free intraepithelial endings.
general body surface, cutaneous receptors
sensitive to mechanical stimuli can be classi -
fied into 11 groups. The characteristics used
visceral structures ( Fig. 7.4). Elaborate nerve for classification include: (a ) conduction ve -
endings have been disclosed by Ralston and locity, ( b) distance the central axon ascends in
collaborators ( 74 ) in the tendons, ligaments, the spinal cord , and (c) pattern of action pc-
joint capsules, deep fascia, and periosteum of tentials generated by defined stimuli (38)
man ( Fig. 7.7). Ruffini (83) originally de- (Table 7.1 ).
Figure 7.7. Unencapsulated nerve endings in deep somatic tissues of humans A. Patellar ligament B. Capsule of knee
joint C. Periosteum of femur
Encapsulated Endings
Encapsulated endings include the tactile
corpuscles of Meissner , the end bulbs , the Pacin -
-
ian corpuscles , the Golgi Mazzoni corpuscles, the
neuromuscular spindles , and the neurotendinous
organs of Golgi.
CORPUSCLES OF MEISSNER
The tactile corpuscles of Meissner are elon-
gated ovoid bodies, 90-120 p.m in length,
found in the dermal papillae, close to the epi -
dermis ( Figs. 7.5 and 7.8). Each corpuscle is
surrounded by a thin, nucleated connective
tissue sheath, while the interior consists of
many flattened epithelioid cells whose nuclei
are placed transversely to the long axis of the
corpuscle. From one to four myelinated nerve
fibers supply each corpuscle. As each fiber en-
ters, its connective tissue sheath becomes con-
tinuous with the fibrous capsule. The myelin Figure 7.8. Meissner ' s corpuscle in a dermal papilla of
sheath disappears and the naked axon winds human finger tip
spirally among the epithelioid cells, giving off
numerous branches which likewise spiral,
show numerous varicosities, and end in flat- which vary greatly in dimension. The sim-
tened neurofibrillary expansions. Besides the plest and smallest ones are found in the con-
myelinated fibers, the corpuscles also may re- junctiva (68); the largest in the connective tis-
ceive one or more fine unmyelinated fibers. sue of the external genitalia, where they are
Meissner corpuscles occur mainly in the hair- known as genital corpuscles . In its simplest
less portion of the skin and are most numer- form ( 26)( Fig. 7.9A ), the end bulb consists of a
ous on the volar surface of the fingers, toes, nucleated capsule enclosing a soft gelatinous
hands, and feet. They are found in lesser core in which nuclei may often be seen. One
numbers in the lips, eyelids, tip of the tongue, or more myelinated fibers lose their myelin
and volar surface of the forearm (60). Meiss- on entering the capsule, and give off numer-
ner's corpuscles are formed in excess of adult ous lateral branches which form a compli-
requirements, and those that survive possess cated terminal arborization. Some end bulbs
a capacity for continuous growth and reorga- may be compound . End bulbs of various
nization (12, 59). In young persons, nearly forms have a wide distribution , being found
every dermal papilla contains a small Meiss- in the conjunctiva, mouth, tongue, epiglottis,
ner corpuscle, 25 p.m in length. In older indi- nasal cavity, peritoneum ( and other serous
viduals, only a few papillae contain corpus- membranes), lower end of rectum , and exter-
cles which are larger and of more irregular nal genitalia, especially the glans penis and
arrangement. These endings always are asso- clitoris. They also are found in tendons, liga-
ciated with the papillary ridge which plays an ments, synovial membranes, and in the con-
essential role in their stimulation. Their rela- nective tissue of nerve trunks.
tionship is designed so that the nerve endings
are stimulated effectively through one surface PACINIAN CORPUSCLES
elevation of the epidermis, which is in line
with the long axis of the corpuscle ( Fig. 7.5). The Pacinian ( Vater- Pacini ) corpuscles are
This arrangement makes the Meissner corpus- the largest and most widely distributed of the
cle particularly suitable for tactile two- point encapsulated receptors ( Fig. 7.10 ). They are
discrimination (12). laminated, elliptical structures of whitish
color, and each is supplied by a large myeli -
END BULBS nated fiber. They differ from the other encap -
sulated organs mainly in the greater develop-
End bulbs resemble the tactile corpuscles in ment of their perineural capsule. This capsule
structure and are spherical or ovoid bodies is formed by a large number of concentric
ro
Table 7.1. Properties of Cutaneous Axons Responding to Mechanical Stimulation of the Skin°
$
n
MEAN
LEVEL AT WHICH
MOST FIBERS
TV' PE OF RAMP
RESPONSE: PROBABLE OR
=
±
0
PERIPHERAL LEAVE THE MEAN SLOPE POSSIBLE
-
MECHA NO RECEPTOR CONDUCTION FASCICULUS OF TUNING PLATEAU ON vs. OFF RECEPTOR
TYPE VELOCITY ( m / sec ) GRACILIS CURVES RESPONSE SENSITIVITY6 STRUCTURE U
a
2
Tj
C <2 Does not follow < 20 sec V / D; little or no off , Free nerve ending?* IT
above 2 Hz but has an after CO
discharge Q.
z
T>
AS 20 Lower lumbar - 0.4d Little or none V; on = off Free nerve endings <
in skin or around O
hair follicles?*
C
GO
CO
<
.
C: hair 30 1 / 2 upper lumbar,
1 / 2 nucleus gracilis
-
0.2 Little V / D; on > off ID
3
Gl hair 63 Nucleus gracilis - 0.4 None V; on off lanceolate,
pallisade or circular
endings of follicle*
G , Hair 75 Nucleus gracilis -1 None V / A; on = off
F, field 30 1 / 2 upper lumbar, 0.15 < 20 sec V / D; little or no off

I / 2 nucleus gracilis
FI field 55 112 upper lumbar, -0.25 None V ; on > off Sparsely laminated
1 / 2 nucleus gracilis corpuscles (such as
Meissner's corpus-
cles, Krause end
bulbs, Golgi -
Maz /oni organs)?'
F, field 65 Nucleus gracilis - 0.6 None V ; no off
Ruffini 55 Nucleus gracilis 0 Persists D; no off Ruffini endings

Haarschiebe 65 Upper lumbar 0 Persists D / V; no off Merkel cells
Pacinian corpuscle 65 Nucleus gracilis -2 None A; on = off Pacinian corpuscles
° A classification scheme for mechanoreceptors that is based upon the morphology of receptors in the skin of cats and their physiologic
properties. The scheme derived from primary afferent neurons which ascend in the dorsal column of the spinal cord . The free ending of
A5 (delta ) axons are exquisitely sensitive to slight movement of the skin and act as velocity detectors. On hairy skin , two types of hair fol-
licles are distinguished . Fine "down" hairs emerge in groups from a follicle and the larger "guard " hairs emerge singly. Receptors associ-
ated with guard hair follicle are designed tvpe G . Receptors responding to stimulation of the skin between hairs or movement of clumps of
hairs are field receptors ( type F). F receptors are also found in glabrous skin . "Haarschiebe" is the term given to small, fairly evenly
,
spaced protuberances on the surface of the skin . Field ( F) and guard (G ) receptors are subdivided according to their phasic. ( F, , G ), tonic
( F:, Gi ), or intermediate ( FI ,GI ) response patterns.
b
A = acceleration response; D = displacement response; V = velocity response; FI = intermediate field receptors; Gl = intermediate guard
hair receptors.
c
Receptor identification uncertain and based on supposition .
d
Estimated .
9
, .
It is not known to what extent G endings differ in structure from G;, if at all. Both G , and G can innervate the same hair.
' Receptor identification based on reasonable likelihood .
TO
CD
T
T3
7
Q.
—
:
Figure 7.9. A . End bulb of Krause from conjunctiva B . Compound corpuscle of Golgi-Mazzoni from the subcuta-
neous tissue of the finger tip.
lamellae. Each lamella of the outer bulb con- nerve fiber to the capsule, but ramify only in
sists of a single continuous layer of flattened the outer bulb. At birth the Schwann cell and
cells, and is supported by fine collagen fibrils myelin sheaths are lost as the large nerve
of the interlamellar spaces. The interlamellar fiber enters the inner bulb. However, the cap-
spaces contain a network of fine fibers, blood sule continues to grow and enlarge, so that in
vessels, and some free cells in a semifluid the human adult both the Schwann cell and
substance. Blood vessels accompany the myelin elements can at times be identified
within the inner bulb (14, 15). No fine nerves
enter the inner bulb with the large fiber.
Cauna and Mannan found that the average
length of the corpuscle at birth ranges from
500-700 gm. The size increases gradually
Connective tissue throughout life to become 3-4 mm in the
lamellae adult . In persons over 70 years of age, the cor-
puscles are less numerous, show regressive
changes, and are smaller and more irregular.
Inner bulb The entire length of the unmyelinated fiber
within the corpuscle is sensitive to deforma-
tion, and can initiate “all or none" responses,
as shown by Ozeki and Sato (69, 70). These
investigators removed the surrounding cap-
Axis-cylinder sule and found the mechanoreceptor function
was still intact. They concluded that the
short-lasting receptor potential, obtained
from intact corpuscles, must be attributed to
properties of the lamellae. In addition to pres-
Nerve fiber sure, the Pacinian corpuscle deep in the limbs
may be sensitive to vibratory stimuli. The
corpuscles are found in subcutaneous tissue,
especially of the hand and foot, in the peri-
Figure 7.10. Human Pacinian corpuscle toneum, pleura, mesenteries, penis, clitoris,
urethra, nipple, mammary glands, and pan -

creas, and in the walls of many viscera . They 1 Intramuscular
are especially numerous in the periosteum,
i nerve trunk
ligaments, and joint capsules, and they also I i

occur in muscular septa and occasionally in
the muscle itself . HI
CORPUSCLES OF GOLGI- MAZZONI
Mu I
The lamellated corpuscles of Golgi-Mazzoni, | Gommo
found in the subcutaneous tissue of the fin - » efferent
fibers
gers and on the surface of tendons, are re-
lated to the Pacinian corpuscles ( Fig. 7.9 B ) .
Primary Primary
They are ovoid bodies with lamellated cap- annulospiral afferent
sules of varying thickness and a central core endings fiber
of granular protoplasm in which the single
myelinated fiber forms a rich arborization
with varicosities and terminal expansions. Nucleor bag'
I Secondary
afferent
fiber
Stretch Receptors Secondory x

-efferent
Gamma
fiber
flower spray
Among the most highly specialized encap- endings
sulated end organs are the stretch receptors, • rf - Ml of or end plates
represented by the neuromuscular spindles

and neurotendinous organs.
L -Extrafusal
NEUROMUSCULAR SPINDLES I muscle
fiber
The neuromuscular spindles ( muscle spin -
dles) are fusiform in shape and widely scat -
tered in the fleshy bellies of skeletal muscles.
ijjl
Aponeurosis
/
Each spindle consists of 2 to 10 slender stri -
ated muscle fibers, enclosed within a thin Figure 7.11. Nuclear bag intrafusal muscle fiber within a
connective tissue capsule, and attached at neuromuscular spindle. The intrinsic sensory and motor
both ends to the epimysium or ordinary stri- nerve endings on the spindle fiber are identified, and the
polar and equatorial regions are indicated on the left .
ated muscle ( Fig. 7.11 ). These slender muscle Normally there are 2- 10 small and large intrafusal fibers
fibers are known as intrafusal fibers and are within each neuromuscular spindle.
small compared with the extrafusal fibers that
produce contractile tension within a muscle.
In nonmammalian species, muscle spindles the spindle primary endings to changes of
are innervated by collateral branches of axons muscle length. Static y-axons reduce spindle
which supply extrafusal striated muscle afferent sensitivity to changes of muscle
fibers. In mammals, muscle spindles are length, but increase spindle afferent firing at
largely supplied by an independent group of a constant length .
motor axons, called fusimotor or 7-axons. It is Intrafusal muscle fibers are of two distinct
now recognized that mammals have a signifi- sizes. One is of smaller diameter (10-12 pm ),
cant number of muscle spindles innervated is shorter in length ( 3-4 mm ), and has a single
by collaterals of axons also innervating the chain of central nuclei. The second , or larger,
extrafusal muscle fibers. These axons, which spindle fibers are about 25 pm in diameter,
show the innervation pattern previously as - are 7-8 mm in length , and in the equatorial
sociated exclusively with nonmammalian region are enlarged to accommodate an area
species, are called, beta ( (3)-axons to distin- of numerous small nuclei ("nuclear bag" of
guish them from exclusively skeletomotor Barker ) (3). The small intrafusal fibers are
alpha (a Faxons and exclusively fusimotor known as "nuclear chain fibers," and the
gamma (yFaxons (1, 6, 42). Fusimotor axons larger ones are designated "nuclear bag
—
are of two types dynamic and static. The
dynamic y-axons increase the sensitivity of
fibers" (5, 9, 10 ). The ends of the nuclear
chain fibers are attached to the polar parts of
the longer nuclear bag fibers . There are usu- 7.12. Two or more myelinated afferent fibers
ally two of the longer fibers and five of the enter each spindle. A thick primary afferent
smaller fibers in each spindle, but these num- fiber forms a spiral , branching and reticulated
bers are variable. A nuclear bag fiber with its ending within the nuclear bag area ( primary ,
capsule and associated sensory and motor annulospiral , or nuclear bag ending ) . Silver-
nerve endings is shown in Figures 7.11 and stained primary and secondary sensory end-
0.1 mm
Figure 7.12. Human intercostal neuromuscular spindle. A. Longitudinal squashed preparation showing sensory and
motor neural elements related to the intrafusal muscle fibers ( IF ). Compare diameters of sensory fibers ( la) related to
.
primary (P. annulospiral) ending, sensory fiber ( II) of secondary ( S flower -spray) ending, and y -efferent (Ge) fiber An
-
adjacent extrafusal muscle fiber ( EF ) and artery ( A ) are identified B. Cross-section of muscle spindle demonstrating its
multilayered capsule and the diameters of the nuclear bag ( IFb) and nuclear chain ( IFc ) intrafusal fibers. y-Efferent
axons (Ge) and extrafusal ( EF) muscle fibers are identified (modified De Castro silver stain).
ings on intrafusal muscle fibers are shown in axon ( Figs. 7.11 ). The neuromuscular spindle
Figure 7.13. The primary receptor has a low is arranged parallel to the extrafusal or con -
threshold to stretching of the muscle or its tractile fibers of the muscle. Tension on the
tendon, and also discharges a volley of im - spindle is relaxed and afferent volleys from
pulses when the intrafusal fiber contracts as a the annulospiral endings cease during active
result of stimulation by a 7-efferent motor muscle contraction ( i.e., the spindle is un -
Figure 7.13. Human intercostal neuromuscular spindles with two types of sensory endings. A . Primary (P, annulospiral)
ending on each intrafusal muscle fiber has a thick axon with many side branches and terminal enlargements. The
.
slender coil ( arrow ) is not seen on all primary endings Adjacent efferent axons (Ge) are identified B. secondary ( S.
.
flower -spray) endings found on both bag and chain intrafusal muscle fibers ( IFb) Architecture is similar to that of pri-
mary ending except for the slender, delicate nature of the branches. The axon related to this secondary ending is
identified ( II) (modified De Castro silver stain).
loaded , and its receptors are silent ). The pri- nuclear bag area . These are called secondary,
mary afferent fibers ( la in Fig. 7.12A ) are 8-12 flower-spray, or myotube endings ( Figs. 7.11
gm in diameter, have fast conduction veloci - and 7.13B ). Secondary endings are the princi-
ties, and their central processes within the pal sensory terminals associated with nuclear
spinal cord participate in the monosynaptic chain fibers (5, 9, 10). Both the primary and
stretch ( myotatic) reflex that regulates muscle secondary endings are terminals of sensory
tone ( Figs. 10.29 and 10.30). fibers, for they degenerate after section of ap-
The myelinated secondary afferent fibers propriate dorsal roots.
( Fig. 7.13B ), with diameters of 6-9 gm also Small fusimotor fibers (7-efferents), 3-7
enter the spindle to form small rings, coils, gm in diameter, enter each spindle and ter-
and spraylike varicosities on both sides of the minate. Two kinds of 7-fiber endings upon
Figure 7.14. Human intercostal neuromuscular spindle. A. -Efferent axons near sensory area that demonstrate trail
^
( Te) and coiled (Ce) endings . In other sections, these axons and endings are found on bag (/Fb) and chain (ifc) intra-
fusal muscle fibers. B. y-Efferent (Ge) motor endplates (Me) found toward capsular pole of spindle. Pairs of endplates
occur frequently Here two endplates are seen on one bag fiber (modified De Castro silver stain).
the intrafusal muscle fibers have been de - (Ia ) from the annulospiral ending is stimu -
scribed . Some end as diffuse, multiterminal lated , there is a central delay of 2 msec before
"trail fibers," while others terminate in minia- the efferent fiber response is recorded . Hence,
ture "endplates" ( Fig. 7.14). Barker (4) main - the annulospiral collaterals use central inter-
tains that both nuclear bag and nuclear chain -
nuncial neurons to influence y-efferent neu -
muscle fibers usually receive each type of y rons, and such connections are polysynaptic
motor endings. Boyd (9 ) pretends that nu- (52).
clear bag intrafusal fibers usually receive
"plate endings," and nuclear chain muscle
NEUROTENDINOUS ORGANS
fibers usually receive "trail endings."
The contraction of intrafusal muscle fibers Neurotendinous organs (Golgi tendon or-
--
by y efferent nerves induces discharges in the gans) are encapsulated spindle-shaped recep-
afferent nerves from the spindle. The fusimo- tors found at the junction of muscle and ten-
tor fibers thus reset the spindle mechanism, don, and occasionally in muscular septa and
thereby regulating the sensitivity of the re- sheaths. They have been demonstrated in
ceptor. Contraction of the spindle fibers con - practically all muscles. The capsule of the
tributes nothing per se to the contractile ten- Golgi tendon organs is approximately 8-10
sion of the muscle (72). Additionally, the times longer than it is wide, and consists of
neuromuscular spindles receive a variable several concentric lamellae that form cyto-
number of fine unmyelinated fibers which plasmic sheets closely applied to each other
appear to be vasomotor to the small vessels (57). Cells of one lamella extensively overlap
within the spindle. Other fine nerve fibers adjacent cells in the same concentric lamella.
ramify in the capsule and probably mediate The outer lamina appears as typical squa-
pain impulses. mous epithelium without fenestrations, and
The recorded dimensions of human mus- the extensive overlap of neighboring cell
cle spindles vary enormously, the extremes processes suggests that intracapsular fluids
for length being 0.05 and 13 mm. The usual are not easily exchanged with extracapsular
-
length is 2 4 mm. Spindles have been found fluids. The cells which form the capsule of
in practically all muscles but they are most the neurotendinous organs resemble those of
numerous in the muscles of the extremities. the perineural epithelial sheath surrounding
They are especially abundant in the small nerve trunks, and the capsule is regarded as a
muscles of the hand and foot. Fewer muscle direct continuation of the perineural sheath.
spindles are present in the extraocular mus- The capsule of the Golgi tendon organ ex-
cles ( 20, 21, 34, 56). Cells in part of the trigem- hibits four morphologically distinct levels
inal ganglion convey afferent impulses from (84). At the proximal opening, several loosely
muscle spindles in the extraocular muscles organized cellular lamellae surround enter-
(49). ing muscle fibers. At a slight distance below
information conveyed centrally from the the capsule opening is the proximal collar,
neuromuscular spindles play a major role in where collagen bundles of the muscle fibers
the reflex regulation of muscle tonus. As - are tightly enveloped by capsule cells so as to
cending impulses from these receptors are provide an effective seal between intracapsu -
conveyed via nuclei in the spinal cord and lar and extracapsular fluids ( Fig. 7.15). Dis-
medulla mainly to the cerebellum, and are tally there also is a capsular collar from which
secondarily concerned with conscious sen- collagen bundles leave their capsular invest-
sory experience. Responses of primary and ments in a staggered fashion to join the cen-
secondary endings to mechanical stimuli dif - tral tendon. The receptor body, occupying
fer in that the primary ending is more sensi- nearly 80% of the length of the Golgi tendon
tive to the dynamic component of the stimu - organ, lies between the proximal and distal
lus. Thus, primary endings measure both collars. The capsule wall of the receptor body
velocity of stretching and length, while sec - is uninterrupted except for an opening near
ondary endings measure mainly length. Col - the midpoint through which the primary af -
laterals from these sensory fibers have mono- ferent fiber ( lb) enters the lumen of the cap-
synaptic junctions with a-motor neurons sule. The lumen of the receptor body is di-
( Figs. 10.23 and 10.30). More than one inter- vided by thin cytoplasmic processes into
nuncial neuron is interposed between these longitudinally oriented compartments which
-
collaterals and the y efferent neurons as in cross section have a honeycombed appear-
shown in Figure 10.23. If the primary fiber ance. Cells and their processes which parti-
Muscle fibers
tion, or passive muscle stretch , will tighten
the braided strands of collagen in the neuro-
Proximal collar lb afferent tendinous organ , reduce the size of the septal
of receptor
capsule r nerve fiber
spaces, and pinch nerves laced between them
(84 ).
The afferent nerve fibers from tendon
organ receptors are large fibers of about 12
gm diameter. The neurotendinous organs are
relatively insensitive to passive stretch be-
cause they lie in series with the contractile
muscle that absorbs most of the stretch and
prevents elongation of the tendon. Muscle
contraction causes the tendon organs to dis-
Distal collai of
receptor capsule charge proportional to the tension developed .
— Collagen fibers
lotning tendon
Contractions which shorten the muscle with-
out developing much tension produce only
weak excitation of the tendon organ. If the
contraction shortens the muscle, lengthens
Figure 7.15. Golgi tendon organ Muscle fibers con- the tendon , and develops tension, the tendon
verge as they enter the proximal opening of receptor organs fire vigorously ( Fig. 10.29 ) (37). If the
capsule, below which is a slight constriction known as
the proximal collar lb afferent fiber emerges from the
stimulus is appropriate
rr \ . , the tendon organ is
„ °
an extremely sensitive receptor . Contractions
central region of the receptor capsule in a connective
tissue sleeve Near the distal collar of the capsule colia- produced by stimulation of an isolated motor
gen bundles emerge, and at staggered levels join the unit can easily cause individual tendon or-
fibrils of the central tendon gans |yjng jn serjes with it to discharge ( 39).
Afferent nerve fibers from the muscle
spindle ( primary ) and the Golgi tendon or-
tion the lumen are termed septal cells. These gans are ]arge and conduct impulses centrally
cells resemble fibroblasts and probably origi- at rapid rates. To distinguish between these
nate from lamellae of the capsule wall . In the two subgroups, the annulospiral afferent
greater part of the receptor body, compart - nerves are designated as la, while the tendon
ments contain a mixed assortment of collagen organ afferents are referred to as lb nerve
fibrils from muscle fibers ( Fig. 7.16). A large fibers. While stretch receptors in muscle fur-
number of collagen fibers appear to terminate nish some information which enters the con-
within the capsule lumen in an undetermined scious sphere signaling the position of a limb
manner . or joint, these receptors function mainly in
The primary afferent fiber ( lb ) enters the the automatic control of muscle tone.
capsule lumen in the equatorial region of the Besides the neuromuscular and neuro-
receptor body and divides into major ascend - tendinous organs, muscle and tendon have a
ing and descending branches. Unmyelinated
collaterals from the major branches project
variety of other sensory structures free
nerve endings, end bulbs, and Pacinian cor
— -
radially through openings between septal puscles. The latter are especially numerous in
cells to penetrate peripherally located com- tendons.
partments containing longitudinal collagen
bundles derived from muscle fibers. Preter- SENSORY RECEPTORS AND SENSORY
minal nerve fibers branch extensively and
MODALITIES
spiral around discrete collagen bundles. At-
tempted serial reconstructions of the Golgi Overall View
tendon organ indicate that collagen bundles
spiral about one another like the strands of a It is generally maintained , although not
rope and often split to entrap smaller nerve proven, that each type of receptor is activated
fibers and terminals ( Fig. 7.16). Evidence sug- by only one kind of physical or chemical
gests that the mechanical component of the change and is associated with only one kind
transducer process must involve physical dis- of sensory modality. The problem of relating
tortion of the axonal membranes during an the various receptors to specific sensory
increase in tensile forces along the collagen modalities has been exceedingly difficult and
strands. It has been suggested that contrac- many important details remain unknown
Figure 7.16. Three-dimensional reconstruction of relationships between axonal branches (Ax) and longitudinally ori-
ented collagen bundles (Cfc>) in a septal cell compartment of a Golgi tendon organ. The spiraling axon threads its
way through the collagen bundles. Most collagen bundles do not run a straight parallel course through the lumen of
the Golgi tendon organ, but twist like the strands of a braided rope. Increasing tensile forces on the collagen strands
cause them to straighten and twist which results in pinching of the axonal branches trapped between them.
(87). It seems probable that painful stimuli are probably end bulbs of various kinds. Pos-
are received by the diffuse, cutaneous end ar - sibly, some are diffuse endings. It is known
borizations. Not only would their universal that the margin of the cornea is sensitive only
presence and unspecialized terminals indi - to cold and pain, and is provided only with
cate this, but also their sole presence in places diffuse endings and end bulbs of Krause.
where stimuli give rise only to pain (e.g., the Hence the latter and similar subcutaneous
tympanic membrane of the ear and the pulp end bulbs are believed to be receptors for
of the teeth ). Touch is represented by the end - cold . In the same way, the diffuse unencapsu -
ings in hair follicles, Meissner's corpuscles, lated nerve endings are believed to be related
and probably by tactile discs and some other to warmth .
intraepithelial endings. The peritrichal end - The different parts of the body surface vary
ings, stimulated by movements of the hair, considerably as to their capacity for affective
give rise to a delicate and discriminative sen - and discriminative sensibility. The skin of the
sibility with a marked affective tone. Shaving hand and fingers is particularly sensitive, and
greatly reduces sensibility to touch . On the provides a variety of exteroceptive impulses
hairless part of the body, tactile stimuli are that are integrated in the cerebral cortex. In
received primarily by the corpuscles of other regions, such as the back, abdomen, and
Meissner, which are probably the chief sense especially the genitalia, affective sensibility
organs of discriminative touch . The receptors predominates, to the partial exclusion of dis-
for temperature are not well-known, but they criminative aspects of sensation .
The Pacinian corpuscles, found in both Referred Pain

deep subcutaneous and visceral structures,
appear physiologically to be pressure trans- One peculiarity of visceral pain is that
ducers, but there is no evidence that they sub- painful visceral stimuli are often "felt" in the
serve steady pressure, or that pressure sensi- corresponding somatic segment, or segments,
tivity is particularly acute in regions where of the body wall, a phenomenon known as
Pacinian corpuscles are found . The rapidly "referred pain." Centrally, the receptive nu -
adapting nature of the Pacinian corpuscle clei for somatic and visceral pain impulses
suggests that it may be particularly sensitive are associated closely within the dorsal gray
to vibration . This receptor may play a role in column of the spinal cord . Referred pain is
the threshold detection of tactile stimuli, de- most likely due to central mechanisms within
spite its deep position , because it has a lower the spinal cord, although the precise neurons
threshold for short mechanical stimuli than involved have not been ascertained . A com -
more superficial intracutaneous receptors mon explanation is that the constant bom -
( 44 ). bardment of pain impulses, from a diseased
The proprioceptive senses of position and viscus, lowers the threshold of stimulation of
movement are initiated by the constant or adjacent central (somatic) relay neurons. Nor-
varying tension states of the skeletal muscles, mally these relay neurons are concerned with
and their tendons, and by the movements of somatic sensations and not with transmission
the joints. The changes in tension and pres- of visceral pain . As a result, normal incoming
sure are received by the Pacinian and unen - somatic sensory impulses that terminate in
capsulated corpuscles found in the joint cap- this "sensitized " neuron pool are relayed to
sules, ligaments, and periosteum ( Fig. 7.7). higher centers, where they are misinterpreted
Such afferent inputs are transmitted to corti- as painful stimuli coming from body sur-
cal levels where they are utilized in the for - faces.
mulation of kinesthetic sense (conscious pro- Sinclair and collaborators have suggested
prioception or kinesthesis). Proprioceptive that the production of referred pain may be
impulses from neuromuscular spindles are due to the branching of the sensory fibers
used for regulation of the spinal myotatic re- which conduct pain impulses (88). One limb
flex, or project via cerebellar pathways to reg - of a branched axon goes to the visceral site
ulate muscle tonus and synergy ( i.e., such where the disturbance originates, while oth-
sensory inputs are for subcortical reflex con - ers go to the peripheral area to which the
trol of skeletal muscle). The subcortical regu- pain is referred .
lation of muscle tone and posture provides a Pain referred to the skin from a viscus
background of muscle tone upon which dis- tends to be "felt" in a relatively small circum-
crete cortical ( voluntary ) activity , such as scribed area , usually, but not always, within
locomotion and fine finger movements, is the dermatome of the same spinal segment
based . that supplies the viscus. This pain rarely oc-
There is much that is still obscure about cupies the whole, or even the major part , of
visceral sensibility. It is known that the vis- the corresponding dermatome. In the refer -
cera are insensitive to many mechanical and ence zone, there may be changes in the qual -
chemical stimuli , yet they may be the source ity of sensation in response to stimuli and al -
of intense pain, as well as contribute to the terations of threshold (87). Pain is the only
sensations of hunger, thirst, etc. Visceral pain sensory modality commonly referred to in
is due mainly to either distension or spasm of this manner. Thus, referred pain has a der-
the muscle coats. Diffuse intramuscular nerve matomal distribution corresponding to the
endings appear to be the receptors for these spinal nerves. Some classical examples of a
stimuli ( Fig. 7.4 ). The blood vessels also may diseased viscus that causes pain to be re-
give rise to painful sensation , which is like- ferred to the overlying body wall and cor -
wise due to spasms in their muscular walls responding dermatomes are: diaphragm
and to the resulting stimulation of similar dif - referred to dermatome C4; heart referred
fuse endings. The totality of stimuli, con - to dermatomes C8-T8; bladder referred to
stantly received by these diffuse visceral dermatomes T1-T10; stomach referred to der-
receptors during normal and abnormal func- matomes T6-T9; intestine referred to der-
tion , probably gives rise to the general affec- matomes T7-T10; testes, prostate, and uterus
tive sensibility of internal well- being or of referred to dermatomes T10-T12; kidneys re-
malaise. ferred to dermatomes Tll-Ll ; and rectum re-
ferred to dermatomes S2-S4 ( Figs. 8.1, 8.11, and branch even more extensively as they
and 8.12 ). spread out within the fleshy belly of the mus-
cle. In this manner, a single motor nerve fiber
EFFECTORS provides endplates to a variable number of
the large extrafusal muscle fibers ( Fig. 5.3G ).
The endings of the peripheral fibers in the Each terminal nerve branch loses its myelin
effector organs of the body fall into two sheath as it approaches the sarcolemma of a
groups: somatic efferent and visceral efferent . muscle fiber, while the Schwann cell sheath
The somatic efferent terminations represent
the motor terminals of myelinated axons
continues to invest even the smallest termi -
nals. Electron microscopy has confirmed and
whose cell bodies are located in the anterior elucidated many of the structural features of
gray horn of the spinal cord . These fibers go the motor endplate ( 22, 76-7*1, 97). The axo-
directly to the skeletal muscles. The visceral plasm of the small nerve branches contains
endings are terminals of unmyelinated fibers numerous mitochondria , vesicles, round and
which arise from cells of the various auto- oval profiles, small granular elements, and
nomic ganglia . These fibers supply the heart tubular-appearing components of the endo-
(cardiomotor ), visceral muscle ( visceromo- plasmic reticulum . Such nerve terminals do
tor ), blood vessels ( vasomotor ), hair ( pilomo- not lie within the sarcoplasm of the muscle
tor ), salivary and digestive glands (secretory ), fiber, as believed previously, but occupy
and sweat glands (sudomotor). troughs which are hollowed out by infold -
During development, cholinergic axons ings of the sarcolemma ( Fig. 7.17). The floor
form a specialized synapse, the myoneural or of the trough is usually corrugated by numer -
neuromuscular junction , with skeletal muscle
fibers which already contain acetylcholine re-
ous secondary invaginations of the sar -
coplasm ( junctional folds). The entire de-
ceptors distributed over the whole of the pressed area is called a "synaptic gutter."
muscle membrane. As the neuromuscular Within the gutter, the axon membrane and
junction is formed , acetylcholine receptors sarcolemma remain as discrete structures
cluster in the muscle membrane at the site of separated by a gap, or synaptic cleft . The
axon contact and gradually disappear from whole ending is covered over by Schwann
the extrajunctional membrane ( 7). In the case cell cytoplasm . The membranes of the
of sympathetic motor neurons, differentiation Schwann cell, axon, and sarcolemma are all
to become either cholinergic or noradrenergic separated from each other by a thin layer of
is made relatively late in development and moderately electron dense material ( basal
depends both on the local environment of the lamina ) which also extends out into the extra-
neurons and their activity (71 ). cellular space around the entire ending.
The synaptic vesicles within the axon ter -
Somatic Effectors minals of the endplate are presumed to repre-
sent the storage sites of acetylcholine ( Fig.
The somatic efferent fibers terminate upon 7.17). With the arrival of a nerve impulse, nu -
the skeletal muscle fibers in small, flattened , merous quanta of acetylcholine are released
oval expansions, the motor endplates , or neuro- through the presynaptic membrane into the
muscular junction ( Figs. 5.3G and 7.14). synaptic gutter. The liberated acetylcholine
Motor endplates are located in narrow zones binds to postsynaptic receptor sites, and al -
in a given muscle. Each endplate always lies ters the permeability of the postsynaptic (sar -
in the midportion of the fiber it supplies. colemmal ) membrane of the muscle fiber.
Larger muscle fibers have larger endplates, Acetylcholine receptors and acetylcholines-
and in the rabbit and monkey the diameters terase were localized to the sarcolemma
of endplates differ in "red " and "white" mus- at the apical portions of the junctional
cle fibers ( 18). For example, in red extrafusal folds ( 29 ) ( Fig. 7.17). Depolarization and a
fibers the endplates are significantly larger. muscle action potential result from this series
These muscle fibers are known to be slow re- of events.
acting and capable of sustained contraction. When a foreign motor nerve is implanted
According to Coers (17), the mean diameter into an adult rat soleus muscle and the nerve
of adult human limb motor endplates is 32.2 normally providing innervation severed ,
pm. In humans, most of the endplates have a changes in four molecular components of the
length of 40-60 pm. The myelinated fibers, in newly formed neuromuscular junctions can
their course to the muscle, repeatedly divide, be followed . Within 2 days, acetylcholine re-
Schwann cell cytoplasm
Axon terminal
Mitochondria
Basal lamina
Sarcolemma
Synaptic gutter
Junction folds
Figure 7.17. Motor ending on a skeletal muscle fiber as seen in transverse section by electron microscopy The mito-
chondria are presumed to play an active role in the synthesis of acetylcholine, whereas the numerous smaller vesicles
shown here represent a stored state of acetylcholine Small clusters of dark granules are also found in the axon termi-
.
nal Note the separation of axon Schwann cell, and muscle membranes by the basal lamina
Figure 7.18 . Motor nerve terminations in the smooth muscle bands of a bronchus (rabbit): fft terminal fibrils
ceptors appear in clusters in the new endplate lier and accumulate with a time course paral-
region. The clusters continue to grow in size leling that for acetylcholinesterase. The matu-
and receptor number over the next 30 days. ration of the synaptic basal lamina appears to
About 2 weeks following reinnervation, an occur only after acetylcholine receptors form
endplate-specific form of the enzyme acetyl - clusters (95). A large number of microscopic
cholinesterase is present. Specific antigens of histochemical techniques have been used to
the synaptic basal lamina appear slightly ear- localize the enzymes of the motor endplate in
humans and numerous animals. These have

been reviewed extensively by McLennan ( 53)
and Zacks ( 97), and more recently by Cooper,
et al. (19 ), and by Kandel and Siegelbaum ( 40 ). /
If an inadequate amount of acetylcholine is Motor neuron

(cholinergic)
produced (or if it is destroyed too rapidly by
acetylcholinesterase), muscle contraction is al -
tered and the involved muscles are prone to
early fatigue ( Fig. 7.19). If the enzyme acetyl -
cholinesterase is inactivated by anticholin -
esterase drugs (e.g., by neostigmine), the en -
dogenous acetylcholine is preserved at the
endplate for longer periods.
The excitation of a striated muscle fiber by
a motor neuron can be blocked in several
Tetrodotoxin (TTX )
ways by naturally occurring toxins. These *
1 (Na’conductance block )
toxins are useful tools for analyzing mecha-
nisms of nerve conduction and transmitter re-
lease ( Fig. 7.19). Tetrodotoxin blocks Na
channels in the axon membrane, thereby pre-
venting the generation of action potentials. Botulinum toxin
Botulinum toxin blocks the release of acetyl - ( Acetylcholine release block )
choline from synaptic vesicles. tx- Bungaro- a-BungarotoxIn

toxin , derived from the venom of a snake, ( Acetylcholine receptor
binding block )
binds irreversibly to the acetylcholine recep-
tor, blocking access of the transmitter. These
three toxins block neuromuscular transmis -
sion through different mechanisms.
The number of muscle fibers innervated
by a single motor neuron varies greatly de-
— liber
pending on the function of the particular

muscles. In muscles that control fine move- Figure 7.19. Examples of sites of action of some animal
and bacterial neurotoxins Tetrodotoxin ( ffX). obtained
ments, such as those of the ocular muscles from the ovaries of the puffer fish, prevents the influx of
and the small muscles of the hand, motor Na ions, thereby blocking the propagation of the ac -
units comprise only 3 to 6 muscle fibers. In tion potential along the axon. Botulinum toxin, of bacter -
ial origin, blocks the release of acetylcholine from the
contrast, there are about 2000 muscle fibers in
synaptic terminal. The venom of the Formosan krait. «-
each motor unit of the gastrocnemius, the bungarotoxin. binds almost irreversibly to acetylcholine
muscle that flexes the foot in the movement receptors at the muscle end-plate, thereby preventing
of walking (82 ). Namba and collaborators acetylcholine ( ACh ) from initiating an action potential in
have described two kinds of motor endings the muscle fiber .
in the extraocular muscles of humans. The su -
perior rectus muscles had both en plaque and
en grappe endings. The levator palpebrae had motor neuron that emerges from the ventral
only en plaque terminals with a mean diame- spinal root and runs in the peripheral nerve,
ter of 27 (cm . As many as 12 en grappe endings (c ) the neuromuscular junction, and (d ) the
were found on superior rectus fibers 10-20 muscle fibers innervated by that motor neu -
(cm thick . En grappe endings had a mean di - ron (82). A muscle with many motor units for
ameter of only 9.6 (cm ( 67). a given number of muscle fibers is capable of
In 1925, Edward Liddell and Charles Sher - more precise movements than a muscle with a
rington introduced the term motor unit to des - few motor units for the same number of mus-
ignate the basic unit of motor function, that is cle fibers. It also follows that only a few motor
a motor neuron and the group of muscle units are required to maintain reflex muscle
fibers it innervates. The motor unit comprises tone during periods of rest or sleep. However,
four functional components: ( a ) the cell body many or all motor units may be called into op-
of the motor neurons located in the ventral eration when demands are made upon the
horn of the spinal cord , ( b) the axon of the muscle for maximal contraction .
Myasthenia Gravis with the help of the highly specific choliner-

gic receptor ligand a-bungarotoxin. The in-
Most diseases of the motor unit cause jection of purified cholinergic receptor into
weakness and wasting of skeletal muscles. rabbits to produce specific antibodies was
The distinguishing features of these diseases accompanied by the onset of myasthenia -like
depend upon which of the four components symptoms in the injected animals, and these
of the motor unit is primarily affected . Patho- symptoms could be alleviated by the use of
logic changes affecting markedly central acetylcholinesterase inhibitors. These find -
nerve cell bodies or peripheral nerves and ings led to the production of useful animal
only slightly muscle fibers, are characteristics models of this human disease, which greatly
of neurogenic diseases, or neuropathies (e.g., helped unravel the molecular basis of the au -
central motor neuron diseases or peripheral neu - toimmune reaction involved in myasthenia .
ropathies ). In contrast , advanced degeneration The autoimmune reaction depends on 3
of muscle fibers with little change in motor molecules: ( a ) the antigen , the immunogenic
neurons or their axons are characteristics of peptide of the cholinergic receptor, or a pep-
myopathic diseases, or myopathies (e.g., tide that mimics the receptor, ( b ) an antigen-
muscular dystrophies ). Myasthenia gravis specific T ( thymus ) cell receptor, and ( c) class
( severe muscle weakness), which was first II molecules of the major histocompatibility
described by the famous English anatomist complex ( MUC ) expressed on the antigen
Thomas Willis in 1672, involves mainly cra - presenting cells. In myasthenia, the T cells be-
nial muscles ( eyelids, eye muscles, and come reactive against cholinergic receptor for
oropharyngeal muscles) as well as limb mus- a reason that is still not known. One possibil-
cles ( 2 ). It is a very peculiar myopathy since, ity is an infection in which a viral protein in -
unlike any other diseases of muscle or nerve, cludes a peptide homologous to one in the
the severity of weakness varies markedly in cholinergic receptor, a form of molecular
time and there are no clinical signs similar to mimicry (82). For whatever reason, antibod -
those that characterize disorders of the motor ies directed against nicotinic acetylcholine re-
unit , such as loss of tendon reflex or atrophy ceptors occur in the serum of patients with
of muscle. This disease is particularly inter- myasthenia and can serve as a reliable
esting in that it affects specifically the trans- marker for the disease.
mission of information between the two The symptoms of myasthenia can be al -
major components of the motor unit, the leviated to a certain extent with anti-
nerve and muscle. More specifically, it is an cholinesterase drug therapy or thymectomy.
autoimmune disorder which alters the However, the recent discovery of the im -
cholinergic transmission at the neuromuscu - munologic basis of this disease leads to even
lar junction . Detailed physiologic and im- more promising approaches. For example,
munologic studies of this human disease the use of either antibodies against the anti-
helped understanding of the basic mecha - cholinergic receptor antibodies ( anti-idiotype
nisms involved in the synaptic transmission . antibodies) or peptide competitors for cholin-
The first evidence that myasthenia is a dis- ergic receptors that might block T-cell reac-
order of the neuromuscular transmission tion , are therapeutic tools that are currently
came from the demonstration that acetyl - being tested in animal models of myasthenia
cholinesterase inhibitors, such as physostig- (82 ).
rnine and neostigmine, which amplify the ac- The history of the work on myasthenia
tion of acetylcholine at the neuromuscular gravis is particularly instructive, as it shows
junction, reverse the symptoms of myasthe- the crucial role that interactions between
nia gravis. Indications that it may be an au - clinical and basic research play in the un-
toimmune disease came from observations derstanding of human disorders. It must be
that about 15% of adult patients with myas- realized that the therapeutic effect of thymec-
thenia had a benign tumor of the thymus and tomy was discovered by clinicians long be-
removal of such thymosas results in a reduc- fore the immunologic role of thymus was
tion of the symptoms. However, the major known. In turn , basic scientists have deci-
breakthrough came after the identification of phered the major immunologic and molecu -
antibodies to the nicotinic acetylcholine re- lar mechanisms involved in the pathogenesis
ceptors of the neuromuscular junction ( 27, of myasthenia gravis, providing new thera -
82 ). The cholinergic receptors at the neuro- peutic approaches for the treatment of this
muscular junction were isolated and purified disease.
Visceral Effectors has several widely separated single axon con -

tacts (80). Axon terminals have either a pre-
The unmyelinated autonomic fibers which dominance of granular or agranular vesicles
supply visceral muscle either end in simple and numerous mitochondria .
arborizations, or first form extensive intra - A plethora of fine nerve fibers and plexuses
muscular plexuses from which the terminals have been demonstrated about blood ves-
arise. The terminal fibrils wind between the sels and in a variety of tissues by the parafor-
smooth muscle cells and end in small neu - maldehyde-induced fluorescence technique
rofibrillary thickenings, or delicate loops on developed by Hillarp, Falck , and collabora -
the surface of the muscle fibers ( Fig . 7.18 ) . tors for the visualization of monoamines ( 28 ) .
Similar terminals arise from delicate plexuses This technique, as well as the more recent im-
which surround the tubules or acini of munocytochemical procedures (see Chapter
glands, pass between the cells and terminate 5 ) , reveals an exquisite array of adrenergic
upon the plasma membrane of the glandular nerve fibers and their terminals and has been
cells . Terminal endings occupy small troughs used to study the course and relations of
in the plasma membranes of both cardiac and adrenergic nerve fibers to the smooth muscle
smooth muscle fibers, sometimes for long dis- within several organs . The meticulous studies
tances. However, no endplates, or specialized of Thaemert (90, 91 ) are equally informative.
endings, have been observed on visceral He has made three-dimensional montages
muscle by either light or electron microscopy . from serial section electron micrographs to
Groups of tiny axons surrounded by demonstrate the intricate nerve muscle fiber
Schwann cell cytoplasm do come into inti - relationships in both smooth and cardiac mus-
mate contact with single smooth muscle cells cle. The gut contains a population of intrinsic
of the small intestine ( multiaxonal junctions) . neurons termed the "enteric nervous system ."
In the large intestine, single axons diverge Some of these cells are serotoninergic in-
from nerve bundles and come to lie, free of terneurons which probably act upon other
the Schwann sheath, in shallow grooves in cholinergic and purinergic intrinsic neurons
the muscle cell . It is likely that one muscle cell that control smooth muscle (31 ).
References veloping in vivo. J Phvsiol ( Lond ) cles ( Corpuscula lamellosa ) and its
8.
-
1977;267:195 213.
Blix M . Experimented Beitr.ige zur
functional significance I Anal 1958;
92:1 -20.
1 . Adal MN , Barker D. Intramuscular
branching of fusimotor fibres . J Ldsung dcr Frage liber die specifis- 15 . Cauna N , Mannan ( . Development
Physiol ( Lond ) 1965; 177:288-299 . che Energie der Hautnerven . Z Biol and postnatal changes of digital
2. Adams RD, Bradley WG . Myasthe-
nia gravis and episodic muscular
weakness . In : Isselbacher KJ , Adams
9. . ^
( Munchen ) 1884 0:141 156 .
-
Boyd I A The nuclear-bag fibre and

nuclear-chain fibre systems in the
Pacinian corpuscles (Corpuscula
lamellosa ) in the human hand J
Anat 1959.93: 271 - 286
.
.
RD, Braunwald E, Petersdorf RG , muscle spindles of the cat . In : 16 . Cauna Mannan ( . Organization
Wilson JD, eds. Harrison's princi - Barker D, ed . Symposium on muscle and development ot the preterminal
ples of internal medicine. 9th ed . receptors. Hong Kong: Hong Kong nerve pattern in the palmar digital
Section 14 : Disease of striated mus- University Press, 1962a:185-190. tissues of man . J Comp Neurol
cle. New York : McGraw - Hill , 1980: 10. Boyd I A . The structure and innerva - 1961 ; 117:309- 328 .
2064- 2068. tion of the nuclear-bag fibre system 17. CoersC . Les variations structurelles
3. Barker D . The innervation of the and the nuclear-chain fibre system normales et pathologiques de la
muscle- spindle. QJ Microscop Sci in mammalian muscle spindles. Phil junction neuromusculaire . Acta
1948;89: 143- 186 . Trans R Six Lond ( Biol ) 1962b; Neurol ( Belg ) 1955;55:741 -866.
4. Barker D The innervation of mam -
. 245:81 -136. 18. CoersC, Woolf AL . The innervation
malian skeletal muscle. In : de Reuck 11 . Carpenter FW . Nerve endings of of muscle: a biopsy study. Oxford :
AVS, Knight J , eds. Myotatic, kines- sensory type in the muscular coat of Blackwell Scientific Publications,
thetic and vestibular mechanisms . the stomach and small intestine I . I
Boston : Little, Browrn and Companv , Comp Neurol 1918;29:553-560 . 19 . Cooper JR , Bloom RE. Roth RH . The
1967:.V 15. 12. Cauna N . The effects of aging on the biochemical basis of neuropharma -
5. Barker D, Cope M . The innervation receptor organs of the human der- cology . 6th ed . New York : Oxford
of individual intrafusal muscle fi - mis . In : Montagna W , ed . Advances University Press, 1991 .
bres In : Barker D, ed . Symposium
. in biology of skin Vol . 6. Aging.
. 20. Cooper S, Daniel PM . Muscle spin -
on muscle receptors. Hong Kong: New York : Pergamon Press , 1965: dle's in human extrinsic eye muscles
Hong Kong University Press,
1962: 263-269 .
63 69.
13. Cauna N . Fine structure of the re-
Brain 194
^72:1-24.
21 . Cooper S, Daniel PM , Whitteridge D
6. Bessou P, Emonet - Denand F, La - ceptor organ and its probable func - Muscle spindles and other sensory
Porte Y . Occurrence of intrafusal tional significance . In: DeReuck endings in the extrinsii eye muscles:
muscle fibre innervation by branches AVS, Knight J , eds . Touch , heat and the physiology and anatomy of
of slow A motor fibres in the cat . Na - pain. Ciba Foundation Symposium . these receptors and their connec-
ture 1963; 198: 594-595. Boston : Little , Brown and Company , tions with the brainstem. Brain
7. Bevan S, Steinbach |H . The distribu - 1966: 117-127. 1955;78:564 - 583.
tion of a-bungarotoxin binding sites 14 . Cauna N , Mannan C» . The structure 22. Couteaux R . Morphological and cy -
on mammalian skeletal muscle de- of human digital Pacinian corpus- tochemical observations on the
postsynaptic membrane at motor -

rectly gated transmission at the The pattern of cutaneous innerva -
end plate* and ganglionic synapses.
Exp Cell Res 1 MSS;3: 2M4-322
-
nerve muscle synapse. In: Kandel
.
EC, Schwartz JH Jessell TM eds. .
tion of the human hand . Am J Anat
1958;102:183-218.
-
23. Danan Smith I. Touch in primates. Principles of neural science. Chap. 59 Miller MR , Ralston HJ , Kasahara M .
Annu Rev Psychol 1982;33:155-194. 10. New York: Elsevier, 1991: The pattern of cutaneous innerva -
24 Davis H. Some principles of sensory 135-152. tion of the human hand , foot, and
receptor action . Physiol Rev 1961 ; 41 . Keller JH , Moffett BC Jr. Nerve end - breast In: Montagna W', ed . Ad -
41:391-416. ings in the temporomandibular joint vances in biology of skin. Vol. I: Cu-
23. De Castro F. Contribution la con - of the Rhesus macaque. Anat Rec taneous innervation. New York .
naissance de I'innervation du pan - 1968;160:587-594. Pergamon Press, 1960: 1-47
creas. Y a t -il des conducteurs 42. UiPorte Y, F.monet 43enand F, Janu 60. Montagna W Morphology of cuta -
sptViliques pour les ilots de -
L. The skeleto fusimotor or inner - neous sensory receptors. I Invest
l .angerhatis, pour les acini glandu - vation of mammalian muscle spin - Dermatol 1977;69:4-7.
laires et pour les vaisseaux . Trav dles. Trends Neurosci 1981;4:97-99. 61 . Mountcastle VB. Sensory receptors
l ab Rech Biol Univ Madrid 1923; 43. Larsell O, Dow RS. Innervation i > f and neural encoding: Introduction
21:423-457. the human lung. Am | Anat 1933; to sensory processes. In : Mountcas -
2b. Dogiel AS. Die Nervenendkor - 52:414-438. tle VB, ed . Medical physiology . Vol .
perchen ( Endkolben. W. Krause ) in 44 l indblom U , Lund L. The discharge 1 . St. Louis: C.V . Mosbv , 1974:
der Cornea und Conjunctiva Bulbi -
from vibration sensitive receptors in -
285-306, 348 381.
des Menschen. Arch Mikri >sk Anal the monkey foot . Exp Neurol 1966; 62. Mountcastle VB. Sensory receptors
FntwickKiesch 1891;37:602-6 l 9. 15:401-417. and neural encoding: Intrinluction
27. Drachman DB, ed . Myasthenia 45. l.oewenstein WR . The generation of to sensory pnxvss. In: Mountcastle
gravis Biology and treatment. Ann electric activity in a nerve ending. VB, ed . Medical physiology. 14 th
-
NY Vi 1987;505:1 914. Ann NY Acad Sci 1959;81: 367-387. ed . Vol. 1. St . Louis: C.V . Mosbv ,
28. Falck B. Uillarp NA . Thieme C . 46. Loewenstein WR . Biological trans - -
1980:327 347.
Torp A . Fluorescence of cate - -
ducers. Sci Am 1960;203:99 108. 6.3. Mountcastle VB . Central nervous
cholamines and related compounds 47. Loewenstein WR . Mechano-electric mechanisms in mechanoreceptive
condensed with formaldehyde. J transduction in the Pacinian corpus - -
sensibility . In: Darian Smith I , ed .
llistochem Cytochem 1962:10: 348 cle: initiation of sensory impulses in Handbook ot physiology Section I :
354. mechanoreceptors. In: Loewenstein The nervous system . Vol . 3: Sensory
29. lertuck IK . Salpeter MM . Quantita - WR . ed . Principles of receptor phys- processes, part 2. Bothesda , MD:
tion ol junctional and extrajunc - iology . Ch . 9. Berlin: Springer- Ver- American Physiological Society .
tional acetylcholine receptors by lag, 1971:269-290. 1984:789-878.
electron microscope autoradiogra - 48. Loewenstein WR , Altamirano-Or - 64 . Mountcastle VB, Talbot WH , Dar -
phy after 1 ’I y - bungarotoxin bind - rego R . The refractory stale of the ian -Smith I , Kornhuber HIL The
ing at mouse neuromuscular junc - generator and propagated poten - neural base for the dense vibration .
tions.|Cell Biol 1976;69:144-158. tials in a Pacinian corpuscle.|Gen Science 1967;155:597-600.
30. Gardner F The distribution and ter - Physiol 1958;41 :805-824 65. Munger BL. The intraepidermal in -
mination ol nerve fibers in the knee 49. Manni F , Bortolami R, Desole C. Eye nervation of the snout skin of the
joint ol the cat I Comp Neurol muscle proprioception in the semi - opossum: a light and electron mi -
1944;80:11-32. lunar ganglion. Exp Neurol 1966; croscope study , with observations
31 Gershon MD, Dreyfus CF. Seroton - 16:226 236. - of the nature ot Merkel's Tastzellen.
ergic neurons in the mammalian 50. Martin JH. Coding and processing ) Cell Biol 1965;26:79-97.
gut In : Brooks FP, Evers PW , eds. of sensory information. In : Kandel 66. Munger Bl Discussion o! fine struc -
Nerves and the gut . Thorofare, N|: EC, Schwartz JH , lessell TM , eds. ture of the receptor organs and its
Charles B Slack . 1977:197-206. Principles of neural science. Chap. probable functional significance. In :
32. Granit R . Receptors and sensory 23. New York: Elsevier, 1991 . De Reuck AVS, Knight J , eds
perception Yale New Haven . CT: 329-340. Touch , heat , and pain . Ciba Founda-
University Press, 1955. 51. Martin JH, Jessell TM . Modality tion Symposium . Boston: Little,
33. Cray , JAB. Initiation of impulses at
receptors. In: Field J , ed . Handbook
coding in the somatic sensory sys-
tem . In : Kandel FC, Schwartz III . 67. Namba T, Nakamura T, Grob D.
-
Brown and Company , 1966:129 130.
.
of physiology. Section I Vol . I . Ch . .
lessell TM eds . Principles of neural Motor nerve endings in human ex -
4 Washington , DC: American Phys- science. Chap. 24. New York: Else- traocular muscle. Neurology 1968;
-
iological Vniety, 1959:123 145. .
vier 1991:341-352. 18:403-407.
54 . Greene |, Jampel R . Muscle spindles 52. Matthews PBC . Muscle spindles 68. Oppenheimer DR , Palmer F , Wedell
in the extraocular muscles of the and their motor control . Physiol Rev G . Nerve endings in the conjunctiva.
Macaque I Comp Neurol 1966; 126: 1964 ;44:219-288. J Anat I 958;92:321 352.
547- 550. 5.3. McLennan H. Synaptic transmis- 69. Ozeki M , Sato M Initiation of im -
35. I lead 11. The afferent nervous sys - sion . Philadelphia : W.8. Saunders. pulses at the non myelinated termi -
tem from a new aspect. Brain 1905; I%33 * 15. nal in Pacinian corpuscles. J Physiol
28:99-116 .
54 . Melzack R Wall I’D. Pain mecha - ( Lond ) 1964;170:167- 185.
36 Head H. Studies in neurology Ox - nisms: A new theory. Science 1965; 70. O/ eki M , Sato M Changes in the
ford : Oxford University Press, 1920. 150:971-979. membrane potential and the mem -
37. Henneman E. Peripheral mecha - 55. Merkel F. Tast /.ellen und Tastkor - brane conductance associated with a
nisms involved in the control of perchen beiden I lausthieren und sustained compression of the non -
muscle. In V . B. Mountcastle, ed . beim Menschen . Arch Mikrosk Anat myelinated nerve terminal in Pacin -
Medical physiology . Ch . 73 St. Fntwick Mech 1975;11:636-652. ian corpuscles. ) Physiol ( Lond )
l.ouis: C.V . Mosbv Company, 1968: 56. Merrillees N, Sunderland S, Hay- 1965;180:186-208
1697-1716. how W . Neuromuscular spindles in 71 . Patterson PH . Environmental deter -
.
38 Horch KW , Tuckett RP Burgess PR . the extraocular muscles in man . mination of autonomic neurotrans-
A key to the classification of cuta - Anat Rec 1950;108:23-30. mitter functions. Annu Rev Neu -
neous mechanoreceptors. | Invest 57. Merrillees NCR. Some observations rosci 1978;1:1-17.
Dermatol 1977;69:75-82. on the fine structure of a Golgi ten - 72. Patton HD. Reflex regulation of
39. Ilouk |, Henneman F. Responses of don organ of a rat . In. Barker D, ed. movement and posture In : Ruch
tendon organs to active contractions Symposium on muscle receptors. TC , ed . Neurophysiology. Ch . 6.
of the soleus muscle of the cat . | Hong Kong: Hong Kong University Philadelphia : W B. Saunders, 1961 :
Neurophvsiol 1967;30:466 481 . Press, 1962: 19M 206
40. Kandel ER , Siegelbaum SA . Di - 58. Miller MR , Ralston III , Kasahara M .
-167 198.
73. Quilliam TA . Unit design and array
patterns in receptor organs. In: De 81 Rose IF, Mountcastle VB. Touch and venendigungen im Her/ en bei Am-
Reuck A VS, Knight J, eds. Touch, kinosthesis. In: Fields J, eel. Hand- phibien und Saugetieren. Anal An/
heat and pain. Ciba Foundation .
book of physiology. Section I Vol. I: 1895;10:737-749
Symposium. Boston: Tittle, Brown Neurophysiology. Ch. 17. Washing- 90. Thaemert |C. Ultrastructural inter *
& Company, 1966:86- 112. ton. IX American Physiological So- relationships ot nerve processes and
74 . .
Ralston HJ III, Miller MR Kasahara ciety, 1959:387-429. smooth muscle cells in three dimen -
M. Nerve endings in human fasciae, 82. Rowland TP. Diseases of chemical sions. I Cell Biol l%6a;28:37-4<
tendons, ligaments, periosteum, and transmission at the nerve-muscle *
91. Thaemert JC. Ultrastructure of car -
joint synovial membrane. Anal Rec synapse: myasthenia gravis. In: diac muscle and nerve contiguities I
1960;136:137-148. Kandel EC, Schwartz 111, Jessell TM . Cell Biol 1966b;29:152 162
75. Ramon y Cajal S. I listologie du Sys - eds. Principles of neural science. 92. Tuchmann- Duplessis II, Auronx VI ,
teme Nerveux de THomme et des Chap. 16. New York: Elsevier, 1991: Haegel P Illustrated human embry -
Vertebres . ( A / oulav T, trans. ) Paris 235-243. ology. Vol . 3: Nervous system and
Maloine, 1909, 1911. ( Reprinted, 83. Ruffini A. Sur un nouvel organe endocrine glands ( translated from
Consejo Superior de lnvestigaciones
.
nerveux terminal et sur la presence French ) New York: Springer - Verlag,
'
Cientificas, Instituto Ramon v Cajal,

Madrid, 1972.)
-
des corpuscules Colgi Mazzoni
dans le conjonctif sous-cutane de la
1974.
93. Walshe FMR. The anatomy and
76. Reger JF. Electron microscopy of the pulpe des doigts de Thomme. Arch physiology of cutaneous sensibility :
motor endplate in rat intercostal Ital Biol 1894;21:249-265. a critical review Brain 1942;65 :
77.
muscle. Anat Rec 1955;122:1-10.
Reger JR . The ultrastructure ol nor -
84. Schoultz TW, Swell JE. The fine
structure of the Golgi tendon organ .
48- 114
94 Weddell .
( , Taylor HA , Williams
mal and denervated neuromuscular
synapses in mouse gastrocnemius
.
muscle Exp Cell ' Res 1957;12:
.
J Neumcytol 1972;1:1-26.
85. Shepherd CM. Neurobiologv 2d ed.
Oxford: Oxford University Press,
CM. Studies on the innervation of
skin. Ill The patterned arrangement
of the spinal sensory nerves to the
661-665. 1988. rabbit ear. J Anal 1955;89:317-342.
78. Robertson JD. The ultrastructure of 86. Sherrington CS. The integrative ac - 95. Weinberg C, Sanes JR, Hall Z. For -
a reptilian myoneural junction. I tion of the nervous system. New mation of neuromuscular junctions
Biophys Biochem Cytol 1956;2: York: Charles Scribner's Sons, 1906. in adult rats: accumulation of
381-394 . (Reprinted, New Haven, CT: Yale acetylcholine receptors, acetyl-
79. Robertson JD. Electron microscopy University Press, 1947.) cholinesterase*, and components of
of the motor end-plate and the neu- 87. Sinclair DC. Cutaneous sensation the synaptic basal lamina Dev Biol
romuscular spindle. Am J Phvs Med New York: Oxford University Press, 1981;84:255-266
1960;39:1-43. 1967:35-80. 96. Woollard HI I Observations on the
80 Rogers PC, Bumstix’k G. Multiax - 88. Sinclair DC, Wedded G, Feindel terminations of cutaneous nerves.
onal autonomic junctions in smooth WIT Referred pain and associated Brain I935;58:352 367
muscle of the toad (Bufo Marinus ). I phenomena. Brain 1948;71:184-211 97. Zacks SI. The motor end plate.
Comp Neurol 1966;126:625-652. 89. Smirnow A . Uber die sensiblen Nor Philadelphia: W H Saunders, 1964
8
Spinal Nerves and Peripheral
Innervation
PERIPHERAL NERVOUS SYSTEM sory-afferent root and a ventral motor-effer-
ent root. The two roots traverse the dural sac,
The peripheral nervous system comprises penetrate the dura , and reach the interverte-
the cerebrospinal and autonomic groups of bral foramen, where the dorsal root swells
nerves, as well as their associated ganglia, to- into the spinal ganglion that contains the cell
gether with the cellular and connective tissue
elements which ensheathe them . All these
-
bodies of origin of the sensory afferent fibers
( Figs. 5.2 A and 8.1 ). Distal to the ganglion,
structures lie peripheral to the pial envelope the dorsal and ventral roots unite and emerge
which covers the central nervous system and from the intervertebral foramen as a mixed
through which the central and peripheral spinal nerve or common nerve trunk , containing
nervous fibers are continuous at many points. both sensory-afferent and motor-efferent
The peripheral nervous system is composed fibers. There are usually 31 pairs of segmen-
of somatic and autonomic divisions. The so - tally arranged spinal nerves, which receive
matic division includes sensory neurons of and distribute fibers to various parts of the
the dorsal root and cranial ganglia that inner- body. In most individuals these nerves are
vate the skin, muscles, and joints, and pro- grouped as: cervical, 8; thoracic, 12; lumbar,
vide sensory information about the environ- 5; sacral, 5; and coccygeal, 1. The abbrevia -
ment outside the body. The axons of somatic tions C, T, L, S, and Co, followed by the ap-
motor neurons innervate skeletal muscles propriate number, are commonly used to
and are currently considered part of the so- identify the individual nerves. The first cervi-
matic division , although their cell bodies lie cal nerve ( the suboccipital nerve) emerges
within the central nervous system. The auto- from the vertebral canal between the atlas
nomic division of the peripheral nervous sys - (Cl ) and the occipital bone ( Fig. 1.4 ). The
tem can be viewed as the sensorimotor sys- eighth cervical nerve emerges from the inter-
tem for the viscera , the smooth muscles, and vertebral foramen between C7 and T1 . All
the exocrine glands. It has three spatially seg- more caudal spinal nerves emerge from the
regated components: the sympathetic system, intervertebral foramina caudal to the verte-
the parasympathetic system , and the enteric brae of the corresponding number ( Fig. 10.3).
nervous system (13). The sympathetic and
parasympathetic systems act in concert to
maintain homeostasis. The enteric nervous DORSAL ROOTS
system exerts a local action to control the ac- The dorsal roots contain most fibers that
tivity of smooth muscles at the level of the convey somatic and visceral sensory informa-
gastrointestinal tract. The organization and tion to the central nervous system ( Fig. 10.23).
function of these three components of the au - These fibers are the central processes of the
tonomic nervous system are described in de- dorsal ganglion cells. As a rule, the dorsal roots
tail in Chapter 9. The present chapter princi- are thicker than the ventral ones and their size
pally focuses on the organization of the varies with that of their respective ganglia. The
somatic division of the peripheral nervous first cervical and the first coccygeal nerves rep-
system . resent exceptions in that the dorsal root fibers
Spinal Nerve
are absent in many individuals. About 1 mil -
lion dorsal root fibers have been found on each
GENERAL ORGANIZATION side in the human adult. Considering the fact
that about two-thirds of the afferent fibers may
Each spinal nerve arises from a region of be unmyelinated, a more realistic number of
the spinal cord by two roots, a dorsal sen - dorsal root fibers should be 2-2.5 million (35).
262
The size of the myelinated and unmyeli- pm ) of large anterior horn cells (general so -
nated nerve fibers that form each dorsal root matic efferent, GSE ) of the spinal cord ( Figs.
varies from 0.5-20 pm . The larger myelinated 8.6 B and 10.19 ). They conduct rapidly and
fibers (10-20 pm ) convey sensory impulses to have functional properties similar to the large
the spinal cord from elaborate receptors lo- sensory A fibers of the dorsal root . Each large
cated in the dermis, subcutaneous connective A alpha (a ) fiber in the ventral root enters a
tissue, muscles, tendons, joint capsules, liga - peripheral nerve and supplies motor im-
ments, periosteum, and deep fasciae (see pulses to a variable number of extrnfusal skele -
Chapter 7). Large afferent fibers conduct tal muscle fibers ( Fig. 5.3G ). Smaller myeli-
rapidly (5-120 m / sec) and , by virtue of their nated fibers, 3-6 pm in diameter, form a
several physiologic properties, are classified second component of the ventral root
as the A fiber component of peripheral nerves. (gamma ( y ) efferent fibers). These finer axons
Smaller myelinated nerve fibers in dorsal arise from smaller multipolar neurons scat-
roots (0.5-10 pm ) convey sensory informa - tered among the larger cells of the anterior
tion to the cord from less specialized recep- gray horn ( Figs. 10.19 and 10.23). Such small
tors, and from free nerve endings in the skin, motor axons of ventral roots and motor
viscera, muscles, and connective tissues of nerves are designated as "y-efferents," and
the body. Small , unmyelinated , slow-con - they innervate the intrafusal skeletal muscle
ducting sensory fibers of the dorsal roots are fibers of the neuromuscular spindle ( Figs. 7.11
classified physiologically as C fibers. The di - and 10.23). A third fiber component is found
ameter spectra of the fibers within a dorsal only in the ventral roots of spinal nerves T1
root are shown in Figure 8.6. to L 2 and S2 to S4. These myelinated fibers
range from 3-10 pm in diameter and are the
VENTRAL ROOTS preganglionic axons of visceral motor neu -
rons (general visceral efferent, GVE ) located
The major portion of the ventral root of a in the intermediolateral cell column of the
spinal nerve is composed of myelinated spinal cord . Preganglionic visceral efferent
axons with a diameter that ranges from 3-13 fibers from spinal levels T1 to L2 leave the
pm . The vast majority are the axons (9-13 ventral root to enter the ganglia of the sympa -
Dorsal primary Spinal Dorsal root Spinal cord

ramus ganglion
Spinal nerve
>* ^ /
Ventral primary
ramus
Gray White Ventral root
ramus ramus
- - - 7'
' tr '
Lateral — Paravertebral Prevertebral

cutaneous sympathetic sympathetic
branch ganglion ganglion
Anterior cutaneous
branch
Muscular
branch
.
Figure 8.1 Typical thoracic spinal nerve and its branches
thetic trunk through a white communicating

ramus ( Figs. 8.1, 9.1, 9.2, and 10.23). Similar
preganglionic visceral efferent fibers ( para -
sympathetic) are found in the ventral roots of
sacral nerves (S2, S3, and S4). The pregan-
glionic visceral components of the ventral
spinal roots conduct more slowly ( 3-15
m / sec). They are concerned with visceral re-
flexes and are designated as B fibers .
In recent years, it became evident that
there are a large number of sensory fibers in
certain ventral roots ( 47). Electron micro-
scopic studies have revealed a surprisingly
large number of unmyelinated fibers in the
ventral roots of several mammals including
humans (9). Approximately 28% of the axons
in the ventral root in humans are unmyeli-
nated . Additionally, there are a small number
of myelinated sensory fibers in the ventral
root ( 48). Evidence that these fibers were af -
ferent originally was based upon the observa -
tion that following ventral root section, some
fibers distal to the cut survived , while proxi-
mal root fibers degenerated (10). Retrograde
transport techniques provided more conclu -
sive evidence in that horseradish peroxidase
( HRP) injected into the spinal cord after dor-
sal root section ( proximal to the ganglion ) re- Figure 8.2. Photomicrographs of normal cells in lumbar
sulted in labeling of spinal ganglion neurons spinal ganglion (A) and the superior glossopharyngeal
( 28). Additionally, physiologic recording ganglion (B) of macaque monkeys Note variations in
ganglion cell size and small dark nuclei of the capsule
from fine filaments of the ventral roots pro-
vided information that support the existence
.
cells (cresyl violet stain x 500).
of unmyelinated sensory fibers ( 7, 11 ). An im -

portant question, not entirely resolved , is on the dorsal roots ( Figs. 1.4, 1.5, 8.1, and 9.1 )
whether these unmyelinated sensory ventral and are commonly referred to as dorsal root
root fibers enter the spinal cord directly, or ganglia . The dorsal root ganglia are usually
whether they curve back and enter the spinal located in the intervertebral foramina , imme-
cord via the dorsal root. At least some of diately lateral to the sites where the nerve
these fibers enter the spinal cord directly roots perforate the dura mater . However, the
through the ventral root. As yet, no special Cl and C2 ganglia lie on the vertebral arches
sensory mechanism has been demonstrated of the atlas and axis, those of the sacral
for the ventral root afferents (47 ). Since their nerves are inside the vertebral canal, and that
large numbers were only recently demon- of the coccygeal nerve is usually within the
strated , their precise function is not yet estab- dura mater. The Cl ganglia are missing in
lished . These observations suggest that com - some individuals.
plete deafferentation cannot be accomplished Each spinal ganglion is surrounded by a
by dorsal root section ( rhizotomy ) alone. connective tissue capsule that is continuous
with the epineurium of the spinal nerves.
Spinal Ganglia Cells of the spinal ganglia have a peripheral
location beneath the capsule, and bundles of
The spinal and autonomic ganglia are part nerve fibers entering and leaving the ganglia
of the peripheral nervous system . Almost all form a central core. In the trigeminal gan-
-
of the sensory afferent fibers, both somatic
and visceral, have their cell bodies in the
glion, the cells and fibers are more loosely
arranged . In dorsal root ganglia , the in -
spinal ganglia . These aggregations of unipo- terneural spaces contain large and small
lar nerve cells form spindle-shaped swellings axons, satellite cells, Schwann cells, and
blood vessels. Studies of the topographic or-

ganization of cells in dorsal root ganglia of
the cat indicate that cells in medial and cau -
dal regions project processes into the most
Capsule o ;
caudal rootlets, while cells in rostral parts of
Glomerulus
the ganglia project fibers into rostral rootlets
( 4 ). Cells in the trigeminal ganglion also have
a topographic arrangement in that cells con -
tributing fibers to the ophthalmic division are - Myelin
sheath
located anteromedially and those distributing
fibers to the mandibular division are situated
posterolaterally ( 24 ).
The spinal ganglia are derived from the
embryonic neural crest (see Chapter 3) and
are populated by typical unipolar neurons
whose cell body is ovoid or spherical and
B
often has indentations on its surface ( Fig. A
5.1 A ). The cell diameters range from 20 to Figure 8.3. Two cells from vagus ganglion of cat A .
over 100 pm. Sensory ganglion cells grown in Large clear cell. B. Small " obscure " cell with deeply
tissue culture and studied by electron mi - staining cytoplasm (Ehrlich' s methylene blue)
croscopy have all the cytoplasmic organelles
possessed by other neurons (3, 31, 43). How -
ever, these sensory neurons have less promi- the processes of surrounding satellite cells.
nent Nissl bodies and scattered cytoplasmic Such ultrastructural extensions of the peri -
chromatin, and each cell has a variable num - karyon explain the surface spines and ex-
ber of satellite cells. The unipolar ganglion crescences observed in Golgi , silver, and
cells give rise to a single process (sometimes methylene blue preparations. These typical,
termed dendroaxonal process) which bifur- and often bizarre, sensory neurons com-
cates at a T- junction into a peripheral and a monly are observed in ganglia from older in-
central branch . In the case of myelinated dividuals ( Fig. 8.4 ). The numerous processes
fibers, such a junction occurs at a node of may divide repeatedly or terminate as elabo-
Ranvier. The proximal portion of this process rate end bulbs within the capsule. Sensory
often follows a highly convoluted course and neurons with such supernumerary processes
is referred to as the glomerular segment or have been mistaken by some as multipolar
initial glomerulus. The peripheral process ter- ( motor ) neurons. However, no one has yet re-
minates in a sensory ending. Although this ported vesicle-containing axon terminals or
process is functionally an elongated dendrite, morphologic evidence of synaptic contacts
it possesses all the morphologic and physio- within the spinal or trigeminal ganglia . A
logic characteristics of a peripheral axon . Re- more detailed study of the sensory ganglia
cently, it was suggested that a single ganglion and neuronal variations that accompany
cell may give rise to more than one peripheral aging can be found in the literature (14, 33,
and central branch. Although not yet firmly 39, 44-46 ). Furthermore, attempts have been
established (8, 34 ), the possible branching of made recently to better characterize the mor-
peripheral axons is clinically highly relevant phologic and neurochemical phenotypes of
since it bears on the problem of referred the two major populations of ganglion cells
pain (8). with the help of physiologic, anatomic,
On the basis of their staining properties and immunocytochemical techniques ( 12, 26,
two types of ganglion cells were described in 27, 30).
the light microscope. The larger cells are Satellite cells , variously termed capsular
lighter, while smaller cells often appear dark nuclei, capsular cells, or amphicytes, are also
( obscure cells ) ( Fig. 8.3) ( 32 ). Bunge, et al . ( 3), derived from the embryonic neural crest and ,
observed light and dark cells in tissue culture in the adult, form a concentric layer which
and believed this appearance depended on closely invests the perikaryon and its un -
the amount of cytoplasmic neurofilaments. myelinated axonic coils ( 49 ). The round or
Angular and indented surface margins of the elongated nuclei of the satellite cells are more
perikaryon represent interdigitations with dense than the adjacent perikaryon, and are
Figure 8.4. Photomicrographs of atypical sensory neurons of adult human trigeminal ganglion A. Fenestrated cell
with three looped processes on surface of perikaryon Satellite and capsular nuclei are identified (c) B. Pericellular
plexus of nerve fibers surrounding a unipolar ganglion cell. C. Frayed cell (of Ramon y Cajal) with multiple short
processes most of which terminate in the surrounding capsule The preparations were counterstained with hema-
toxylin to demonstrate capsular nuclei (c). D . Erethized or irritated cell (of DeCastro). Note thick, palm-leaf expansions
or supernumerary processes that issue from perikaryon and axon Types shown in A C, and D are often observed in
.
sensory ganglia of older individuals (Ramon y Cajal silver stain, all photographs xd>50).
identified easily with the light microscope birth, and may play a role in the metabolism
( Figs. 5.2A , 8.2, and 8.4). They show ultra - of the ganglion cells.
structural features that distinguish them from Studies of cell changes in sensory ganglia ,
Schwann cells. Satellite cells display plasma spinal and cranial, in the monkey indicate
membrane redundancy in the form of folds that (a ) the section of the nerve proximal to
on the surface that faces the neuron. Such the ganglia produces no cellular changes but
folds and processes may form several layers causes centrally projecting fibers to degener-
and interdigitate with the surface evagina- ate, and (b ) the section of sensory nerves dis-
tions of the perikaryon . The outer surface of tal to the ganglia produces profuse chroma-
the satellite cell is invested with a basal lam- tolytic changes in the cells of all sizes and
ina which is continuous with that investing types within the ganglia ( Fig. 8.5), but no cen-
the myelin at the first internode (31 ). The cap- tral degeneration (5). Severance of nerve
sule of satellite cells separates the perikarya fibers distal to sensory ganglia appears to
from adjacent ganglionic capillaries, and eliminate peripheral neurotrophic influences
must be involved in fluid transport mecha- necessary for the growth and maintenance of
nisms. They can increase in number after the ganglion cell. The integrity of this influ -
glionic fibers which rejoin the dorsal and ven -

tral rami to be distributed to the body wall.
The white rami also contain afferent fibers
from the viscera whose cell bodies are situ -
ated in the spinal ganglia ( Fig. 10.23). The
meningeal ramus is a small nerve trunk which
usually arises as several twigs from both the
common trunk and the ramus communicans
( Fig. 8.1 ). It reenters the intervertebral fora -
men to supply the meninges, blood vessels
and vertebral column .
The dorsal and ventral rami divide into
superficial (cutaneous ) and deep ( muscular )
peripheral nerves. These nerve trunks branch
repeatedly and become progressively smaller
as they extend peripherally. Ultimately, these
branches break up into individual nerve
fibers which terminate in receptors or effec-
tors. The cutaneous nerves are composed
mainly of sensory fibers of various size, but
they also contain efferent vasomotor, pilomo-
tor and secretory fibers for the blood vessels,
hair and glands of the skin . In muscle nerves
there also is a mixture of sensory and motor
fibers. Both somatic a and y efferent fibers go
to the skeletal muscle fibers, while numerous
large ( A ) and small afferent fibers pass cen-
Figure 8.5. Photomicrographs of chromatolytic cells in trally from receptors in the neuromuscular
lumbar spinal ganglion (A) and the superior vagal gan-
glion (B) of macaque monkeys after section of the nerve
spindles and tendon organs. Small pain affer-
fibers distal to the ganglia. Although lesions of this type ents anti postganglionic vasomotor ( C ) fibers
produce classic retrograde cell changes, they do not in- to the blood vessels also are found in the
duce degeneration in the centrally projecting fibers nerves that enter each muscle. In each periph -
.
(cresyl violet stain x 500). eral nerve there are fibers of various cate-
gories: myelinated and unmyelinated , large
ence is sufficient to .sustain sensory ganglion and small, visceral and somatic, sensory and
cells after their central processes have been motor ( Fig. 8.6).
sectioned . With the exception of the thoracic nerves,
which retain their segmental distribution, the
Mixed Nerve cervical and lumbosacral ventral rami branch
and anastomose to form the cervical, brachial,
After union of the dorsal and ventral roots, and lumbosacral plexuses ( Figs. 8.14, 8.15,
the common nerve trunk divides into four 8.19, and 8.20 ). In these plexuses a regroup-
—
branches or rami dorsal ramus, ventral
ramus, meningeal ramus, and ramus commu - ing of fibers occurs, so that each of the pe-
ripheral nerves which arises from the plexus
nicans ( Figs. 3.9 and 8.1). The dorsal rami (or contains contributions from two, three, or
posterior primary rami ) supply the deep even four ventral rami . The peripheral nerves
muscles and skin of the back. The larger ven-
tral rami innervate the ventrolateral portion of
are therefore "mixed " in a double sense
they consist not only of afferent and efferent
—
the body wall and all the extremities, as well fibers, but also of fibers which come from
as all the superficial muscles of the back. The several spinal cord segments.
ramus communicans connects the common
spinal trunk with the sympathetic ganglia Connective Tissue Sheaths
and consists of white and gray portions ( Fig.
9.2). The former contains the myelinated pre- Morphologically, each peripheral nerve
ganglionic fibers passing from the spinal cord consists of parallel-running nerve fibers in -
to the sympathetic ganglion, while the gray vested by a thick sheath of rather loose con -
rami contain the unmyelinated postgan- nective tissue, the epineurium ( Fig . 8.7). From
*
;
Figure 8 6. Photomicrographs of nerve fibers of dorsal and ventral roofs A. Cross-section of L4 dorsal root within the
dura mater . Arrows indicate groups of unmyelinated C fibers. B. Cross-section ot L4 ventral root within the dura mater .
-
Arrows indicate axons of smaller y -efferent neurons to spindle muscle fibers. Larger a axons supply groups of skeletal
.
muscle fibers (Holmes ' silver - Luxol fast blue stain, photograph x 275)
this sheath septa extend into the interior and SEGMENTAL INNERVATION
divide the fibers into bundles or fascicles of
varying size, each of which is surrounded by The external segmentation of the spinal
a fairly distinct perifascicular sheath or per - cord produced by the spinal nerves corre-
ineurium . These fascicles do not run like iso- sponds to the general metamerism of the
lated cables but repeatedly divide and join body . Each pair of spinal nerves innervates
adjacent fascicles in an interchange of fibers symmetrically arranged paired somites
( Fig. 8.7). As a result, the fascicular arrange- ( metamere ) . The embryonic somites formed
ment at different levels varies greatly in por- from paraxial mesoderm differentiate into (a )
tions of the same nerve. a myotome , which give rise to muscle, ( b) a
From the perineurium delicate strands in - sclerotome , concerned with the development
vade the bundle as intrafascicular connective of the axial skeleton , and ( c ) a dermatome. Ef -
tissue or endoneurium . This tissue separates ferent fibers in the ventral roots innervate so-
the fibers into smaller and smaller bundles matic musculature ( myotonies) and some
and ultimately invests each fiber as a delicate ventral roots contain preganglionic auto-
tubular membrane. In the epineurial and per- nomic fibers which pass to autonomic ganglia
ineurial connective tissue, blood vessels and which in turn give rise to postganglionic
endothelial lined spaces communicate with fibers that innervate blood vessels, smooth
lymph channels within smaller fascicles. muscle, and glandular epithelium . The dorsal
On emerging from the spinal cord , the roots contain most afferent fibers, somatic
dorsal and ventral roots receive an invest - and visceral ( Fig. 9.28). The cutaneous area
ment of connective tissue as they pass supplied by the sensory fibers from a single
through the pia. This tissue is reinforced by dorsal root and its ganglion is called a der -
additional connective tissue as the roots pass matome ( Figs. 8.8, 8.9, and 8.11-8.13).
through the arachnoid and dura , the latter be- In the adult, the correspondence between
coming continuous with the epineurium of neural and body metameres is recognized
the spinal nerve ( root sleeve ) ( Fig. 10.2). readily in the trunk region , where each spinal
Perineural Perineurium
septum . .
A
mi
/: .R
A
Ppineurium
* «
v
/ »
| '
Kte m$$m
v $r
,
.
( >j .
l1
v
:
—
- •
p L isltf tj/
’ '
»
SS*-' - %
Artery
Figure 8.7. Drawing of a cross-section of sciatic nerve of macaque monkeys
Figure 8.8 . Diagram of various stages in the development of the limb bud for the upper extremity Dermatomes C5 .
. .
C6 and C 7 occupy the preaxial part of the limb bud, while dermatomes C8, Tl and 12 are postaxial. The axial line Is
indicated by a red dashed line.
nerve supplies the musculature and cuta- the upper extremity ( Figs. 8.8, 8.9, 8.11, and
neous area of its own segment . In this region, 8.12 ). For similar reasons, the dermatomes of
the dermatomes follow one another consecu- L2 and S3 are adjacent posteriorly ( Figs. 8.9
tively, each forming a band encircling the and 8.12). The intervening segments migrated
body from the midposterior to the midante- peripherally to form the more distal der -
rior line ( Figs. 8.11 and 8.12 ). In the extremi- matomes of the lower extremity. This migra -
ties, the dermatomes have a more complex tion of metanieres in the formation of limbs
arrangement. During development, the and the rotation of the lower extremity ap-
metameres migrate distally into the limb pears to explain the more complex arrange-
buds and arrange themselves parallel to the ment of dermatomes in the extremities ( Fig.
long axis of the future limb ( Fig. 8.8). In each 8.8). In each extremity, an axial line is formed
extremity, consecutive segments which have along which are placed a number of consecu-
migrated peripherally are arranged about an tive segments which have wandered out
axial line ( Figs. 8.8 and 8.9 ). As a consequence from the axial portions.
of limb development, the C4 dermatome As early as 1893, Sir Charles Scott Sher-
comes to lie adjacent to the T2 dermatome, rington , the English physiologist, demon -
and the dermatomes of C5 through Tl lie in strated experimentally the cutaneous areas
Figure 8.9. Position of the posterior (red dashed lines ) and anterior (red line) axial lines. In the upper extremity, the
axial lines extend down the middle of the corresponding surfaces of the limb. In the lower extremity, the posterior
axial line (red dashed line) courses down the more lateral part of the leg to the region of the ankle The anterior axial
line (.red) begins in the pubic region and winds around the inner aspect of the thigh to reach the posterior surface of
the thigh The pattern of dermatomes is shown with respect to the axial lines.
supplied by the various dorsal roots in the below. He found that each dermatome over-
monkey ( 37). Because section of a single root lapped the sensory cutaneous areas of adja-
did not produce a detectable anesthesia any- cent roots, being coinnervated by the one
where, he selected a specific root for study above and the one below ( Fig. 8.10). Hence, at
and cut two or three adjacent roots above and least three contiguous dorsal roots had to be
sectioned to produce a region of complete
anesthesia. Findings similar to those of Sher-
Spinal cord Spinal Cutaneous
segments ganglia field rington were obtained by the French physiol-
I •' > • • t I ogist Dusser de Barenne (15) who irritated
1
single spinal roots or ganglia with strychnine
I and noted the resulting hypersensitive areas.
Dermatomes in humans were first out-
1 lined by mapping the areas of cutaneous
eruption and hyperalgesia occurring in asso-
3 1
ciation with herpes zoster (shingles), a virus
A which often affects a single ganglion ( 23). Fo-
erster (17, 18) furnished a remarkably com-
—
plete map of human dermatomes based upon
• • / •/•'’ i •*/•
* i
/
• surgical section of various dorsal roots for the
alleviation of spastic conditions, and cases of
i
I root injury due to tumors or other causes. His
mm dermatomal maps correspond closely to
m
Z 1 \ those of Head ( 23), and show the same over-
i
lap described by Sherrington (37) in mon-
3 keys. Most dermatomes are supplied by
B \ \ \ \ « t\ t ,
fibers of three, occasionally four, dorsal roots.
Figure 8.10. Overlap of cutaneous fields of segmental
The distribution of the three principal divi-
innervation A. Three intercostal nerves are shown B. The sions of the trigeminal nerve and the cervical
analogous arrangement is shown for a peripheral nerve spinal nerves innervating cutaneous regions
In an extremity . The cutaneous distribution of fibers from of the head and neck are shown in Figure
the spinal ganglion associated with segment 2 of the 8.13. The only spinal root whose section pro-
spinal cord is shown in red in both A and B Because of
the extensive overlap, the section of one spinal dorsal duces an area of complete anesthesia is C2.
root produces virtually no loss In cutaneous sensibility. Neither C3 nor branches of the trigeminal
nerve supply cutaneous regions in the back of tomes. In spinal dermatomes, the overlap is
the head . There also is virtually no overlap in greater for tactile sense than for pain and
the areas supplied by the three divisions of thermal sense. The distribution of the human
the trigeminal nerve, in sharp contrast to the dermatomes is shown in Figures 8.11 and
overlap demonstrated for spinal derma - 8.12.
Ophthalmic n.
Mandibular n.
Great Auricular n.
C2
C3 Transverse Colli n.
C4 Supraclavicular nn.
C5 Intercostal nn
1- Ant . cutaneous rami
2- Lat. cutaneous rami
Axillary n.
C6 Med. Brachial Cutaneous
T6 and Intercostobrachial nn.
T8 Med. Antebrachial
C7 Cutaneous n.
T 12
—— TIP
Lat. Antebrachial
C8 Cutaneous n.
T1 — 112 Radial n.
u%
L1
Median n.
\\s Ulnar n.
L2 Iliohypogastric n.
Ilioinguinal n.
Genitofemoral n.
Obturator n.
Lat. Femoral Cutaneous n.
Ant. Femoral Cutaneous n.
L3 w Saphenous n.
L4
L5 Lat. Sural Cutaneous n.
Superficial Peroneal n.
S1
Sural n.
la Deep Peroneal n.
Medial Plantar n.
.
Figure 8.11 Anterior view of dermatomes ( left) and cutaneous areas supplied by individual peripheral nerves ( right )
Greater occipital n.
C2 Lesser occipital n.
Great auricular n.
C3
Transverse colli n.
C4 Cutaneous branches of
dorsal rami of spinal nn.
C5
Supraclavicular n.
C6 Lat . cutaneous branches
of intercostal nn.
C7 Axillary n.
C8 o Post brachial cutaneous n.
,
Med. brachial cutaneous

and intercostobrachial nn.
Post antebrachial
,
cutaneous n.
Lat. antebrachial
cutaneous n.
Med. antebrachial
cutaneous n.
Ulnar n.
Radial n.
Median n.
Iliohypogastric n.
Clunial nn .
Obturator n.
Ant. femoral cutaneous n.
Lat. femoral cutaneous n.
Post, femoral cutaneous n.
L4 Lat. sural cutaneous n.
L5 Sural n.
Saphenous n.
S1 Calcaneal nn.
Saphenous n.
I?
L5 is Plantar branches of tibial n.
Figure 8.12. Posterior view of dermatomes ( left) and cutaneous areas supplied by Individual peripheral nerves
( right )
In individuals with sensory loss of the seg- Wrist trillion reflexes ( flexion of fingers on
mental type, it is important to determine the percussion of wrist tendons ), C8 to Tl .
level of the lesion . Diagrams such as those Movements of trunk , Tl to T12.
shown in Figures 8.11 and 8.12 are useful for Abdominal superficial reflexes (ipsilateral
reference, but certain features of the der- contraction of subjacent abdominal mus-
matomal maps are worth remembering: (a ) cles on stroking the skin of the upper, mid -
the nipple is located in the region of T4 or T5 dle, and lower abdomen ); upper (epigas-
dermatome, ( b ) the umbiculus lies in the T9 tric ), Tf > and T7; middle T8 and T9; lower,
or T10 dermatome, and (c ) the inguinal re- T10 and T12.
gion corresponds to LI dermatome. The Movements of lower extremity , LI toS2.
anogenital region is supplied by the S3 to S5 Cremasteric superficial reflex (elevation of
sacral nerve roots. scrotum on stroking skin on the inner as-
The segmental innervation of the skeletal pect of the thigh ), T 12 to L 2 .
musculature (myotonies) has been worked Genital center for ejaculation , LI and L2
out in humans and animals by (a ) selective (smooth muscle); S3 and S4 ( skeletal mus-
stimulation of the ventral roots; ( b) study of cles).
the pathologic changes which occur in the an - Vesical center for retention of urine , T 12 to L 2.
terior horn cells when a ventral root or motor Patellar tendon reflex or knee jerk ( extension
nerve is cut ( Figs. 5.2 E, 10.19, and 10.23); or of leg on percussion of patellar ligament ),
(c) study of secondary degeneration of pe- L 2 to L4.
ripheral nerve fibers to muscle after central Gluteal superficial reflex ( contraction of
and peripheral lesions. As in the derma - glutei on stroking skin over glutei ), L4 to
tomes, the majority of the muscles, especially SI.
those of the extremities, are innervated by Plantar superficial reflex ( flexion of toes on
two or three, and occasionally four, ventral stroking sole of foot ), L5 to S2.
roots. Hence injury to a single ventral root Achilles tendon reflex or ankle jerk ( plantar
may only weaken a muscle or have no appar - flexion of foot on percussion of Achilles
ent effect. Only the very short muscles of the tendon ), L5 to S2.
trunk and spinal column and a few others, Genital center of erection , S2 to S4.
such as the abductor pollicis, are formed from Vesical center for evacuation of bladder , S3 to
single myotomes and retain a monosegmen
tal innervation. The peripheral projection of
- S5.
Bulbocaveruosus reflex (contraction of bulbo-
fibers from individual spinal cord segments cavernosus muscle on pinching penis), S3
to a specific muscle thus provides a clue to to S4 .
the myotonic origin of skeletal muscle. The Anal reflex (contraction of external rectal
segmental motor supply to the major trunk sphincter on stroking perianal region ), S4,
and extremity muscles is shown graphically S5, and coccygeal.
in Figures 8.16-8.18. Because this information
is essential to a full appreciation of muscle PERIPHERAL INNERVATION
physiology, these figures are included for ref -
erence. Dorsal and Ventral Rami
Following is a list of some of the important
reflex and visceral and motor activities with Although each spinal nerve supplies its
the locations in the spinal cord of the anterior
own body segment, there is considerable in -
horn cells that carry them out . termixing and anastomosing of adjacent
nerve trunks before they reach their periph -
Movements of the head ( bv muscles of neck ), eral termination. The primary dorsal rami re -
Cl to C4. main relatively distinct, but interconnections
Movements of diaphragm ( phrenic center ), are common in the cervical and sacral regions
C3 to C5. ( 29 ). The ventral rami form more elaborate
Movements of upper extremity , C5 to Tl . connections. Except for the thoracic nerves,
Biceps tendon reflex ( flexion of forearm on which largely retain their segmental distribu -
percussion of biceps tendon ), C5 and C6. tion, the cervical and lumbosacral rami inner-
Triceps tendon reflex (extension of forearm vating the extremities anastomose and
on percussion of triceps tendon ), C6 to C8. branch to form extensive plexuses in which a
Radial periosteal reflex ( flexion of forearm on radical regrouping of fibers occurs. Each of
percussion of distal radius), C7 and C8. the peripheral nerves arising from these
plexuses contains fibers contributed by two, ( Fig. 8.10 ) .Each ramus usually divides into a
three, four, or five ventral rami . As a result medial and a lateral branch, both of which
the cutaneous areas supplied by the periph - may contain sensory and motor fibers, al-
eral nerves do not correspond with the cuta- though the lateral branches of the cervical
neous areas supplied by the individual dorsal rami are purely motor. Deviations are found
roots ( dermatomes ). The peripheral and der- in the upper two cervical nerves ( Fig. 8.13)
matomal distributions of sensory nerve fibers and in the lumbosacral rami . The first or suh-
are contrasted in the anterior and posterior occipital nerve is purely motor and terminates
bociy views in Figures 8.11 and 8.12. Simi- in the short posterior muscles of the head
larly , several ventral roots may contribute ( rectus capitis and obliquus capitis). The
fibers to a single muscle, and , conversely , main branch of the second cervical ramus,
several muscles may receive fibers from a sin- known as the greater occipital nerve, ascends
gle ventral root . A knowledge of the cuta - to the region of the superior nuchal line,
neous and muscular distribution of the pe- where it becomes subcutaneous, and supplies
ripheral nerves is of importance to the the scalp on the back of the head to the ver-
neurologist in determining the level of pe- tex, occasionally extending as far as the coro-
ripheral nerve injuries; hence, the more im - nal suture ( Figs. 8.12 and 8.13). This nerve is
portant morphologic features are presented joined by a filament from the third cervical
briefly . A more complete account is found in ramus. The lateral branches of the upper
textbooks of anatomy and clinical neurology. three lumbar and upper three sacral rami
send cutaneous twigs which supply the
DORSAL RAMI upper part of the gluteal area , extending lat-
erally to the region of the great trochanter.
The dorsal rami of the spinal nerves inner- These branches are known as the superior
vate the intrinsic dorsal muscles of the back ( lumbar ) and medial (sacral ) clunial nerves
and neck, and the overlying skin from vertex ( Fig. 8.12).
to coccyx ( Figs. 8.11 and 8.12 ). In the middle
of the back , the cutaneous area roughly corre- VENTRAL RAMI
sponds to that of the underlying muscles, but
in the upper and lower portions of the trunk The ventral rami of the spinal nerves sup-
it widens laterally to reach the acromial re- ply the ventrolateral muscles and the skin of
gion above and the region of the greater the trunk, as well as the extremities ( Figs. 8.1
trochanter below . With certain exceptions the and 8.9). With the exception of most thoracic
dorsal rami have a typical segmental distrib- nerves, the ventral rami of adjacent nerves
ution , the field of each overlapping with that unite and anastomose to form the cervical,
of the adjacent segments above and below brachial and lumbosacral plexuses.
Figure 8.13. Diagram of cutaneous fields

of the head and neck . The distribution of
the three peripheral divisions of the trigem-
.
inal nerve are shown in red (I ophthalmic
. .
division: II maxillary division: III mandibular
*
division). Abbreviations indicate the fol- Greater occipital narva
lowing nerves within the trigeminal divi- ( C2 I
.
sions: At auriculotemporal, 8, buccal; IO . lesser occipital nerve
.
Infraorbital; IT unfratrochlear; L lacrimal;
.
M, mental; NC nasociliary (external
( C2. C3)
.
branch); SO supraorbital; ST supra- .
.
trochlear; ZF zygomaticofacial; ZT, zygo-
- Great (auricular nerve
maticotemporal. There is no dermatomal C2. C3)
M
overlap between the three divisions of the
trigeminal nerve Branches of cervical
spinal nerves innervate cutaneous regions
Anterior cutaneous
over the back of the head and In the
neck.
nerve of the neck
.
IC2 C 3) \\C 5
>
Supraclavicular nerves
(C3 C4).
Cervical Plexus sory nerve, with sensory fibers that join it

through a branch of C2. The trapezius re-
The cervical plexus is formed from the ceives major motor contributions from the
ventral rami of the four upper cervical spinal accessory nerve, and additional motor
nerves. It furnishes cutaneous nerves for the fibers from C2, C3 and C4. Brendler ( 2 ) has
ventrolateral portions of the neck and shoul- demonstrated that Cl may contribute motor
der and for the lateral portions of the back of fibers to the trapezius, while the spinal acces-
the head . The muscular branches supply the sory nerve sends most of the motor fibers to
deep cervical muscles of the spinal column, the middle and lower portions of the muscle.
the infrahyoid muscles, and the diaphragm . These motor and sensory fibers form one or
They also contribute to the innervation of the more bundles, and may be intermixed with
trapezius ( nerves Cl to C4 ) and sternocleido- the supraclavicular nerves.
mastoid , which are chiefly supplied by the Paralysis as a result of injury of the short
accessory nerve ( N. XI ). segmental nerves is rare and usually associ-
The lesser occipital nerve (C2 and C3) is dis- ated with involvement of the spinal cord .
tributed to the upper pole of the pinna and to However, the trapezius and sternocleidomas-
the lateral area on the back of the head , over- toid frequently are involved as a result of
lapping only slightly the field of the greater penetrating stab and bullet wounds of the
occipital nerve ( Figs. 8.12 and 8.13). The great posterior triangle of the neck which injure the
auricular nerve (C2 and C3) supplies the spinal accessory nerve. These muscles are su -
larger, lower portion of the pinna and the perficial and palpable so that their respective
skin over the angle of the mandible. The muscle actions are of diagnostic value. The
transverse colli (C2 and C3) innervates the sternocleidomastoid and trapezius may be in -
ventral and lateral parts of the neck from chin volved along with axial and limb muscles in
to sternum (supra- and infrahyoid region ). diseases of the basal ganglia . One particularly
The supraclavicular nerves (C3 and C4 ), which troublesome disorder is the condition known
have a variable number of branches, are dis- as torticollis. Due to spasm , the contracted
tributed to the shoulder, the most lateral re- sternocleidomastoid muscle stands out as a
gions of the neck and the upper part of the large cord , and the head usually is involun-
breast, where their terminal branches overlap tarily rotated toward the opposite side . This
those of the second intercostal nerve ( Figs. awkward position may be maintained for
8.11-8.13). long periods. Spasmodic torticollis may be
The major muscular nerve of the cervical associated with neuroses. In the latter cases, it
plexus, the phrenic nerve, supplies the di- is often difficult to distinguish between a
aphragm and is derived mainly from C4, but functional disorder and organic disease.
receives smaller contributions from C3 or C5, Emotional stress usually aggravates these in -
or from both ( Fig. 8.15). It frequently receives voluntary muscle movements.
an anastomotic branch from the subclavian
nerve of the brachial plexus, which enters the Brachial Plexus
phrenic at a variable height. Hence in high le-
sions of the phrenic nerve, paralysis of the di- The nerves supplying the upper extremity
aphragm may not be complete. The deep cer - and forming the brachial plexus are derived
vical muscles are innervated by direct as a rule from the ventral rami of the four
segmental branches from the ventral rami, as lower cervical and the first thoracic nerves,
indicated in Figure 8.16. with a small contribution from the fourth cer-
The hyoid muscles, except those supplied vical nerve ( Figs. 8.14 and 8.15). However,
by the cranial nerves, are innervated by twigs considerable variations are not uncommon. If
from Cl to C3. These twigs unite into a com- the contribution from the fourth cervical
mon trunk known as the ansa cervicalis . The nerve is strong and that of the first thoracic
geniohyoid and thyrohyoid are supplied en- negligible, the plexus is referred to as the pre -
tirely from Cl . The sternohyoid, sternothy- fixed type. It is called post fixed when the
roid , and omohyoid are innervated from C2 fourth cervical does not participate at all but
and C3 by motor twigs from the ansa cervi - the first thoracic makes a significant contribu -
calis. The cervical plexus also aids in the in
nervation of the sternocleidomastoid and
- tion and the second thoracic sends a branch.
Between these extremes there are many inter-
trapezius. The sternocleidomastoid is sup- mediate conditions, depending on the degree
plied mainly by the spinal root of the acces- of participation of the fourth cervical, on the
VENTRAL
TRUNKS DIVISIONS CORDS MAIN BRANCHES
RAMI
Figure 8.14. Formation of the brachial plexus indicating ventral rami trunks, divisions, cords, dnd main branches. The
, ,
posterior divisions and the posterior cord are shaded
one hand, and the second thoracic, on the their branches before these unite to form the
other. These variations are dependent on em - secondary cords. Thus the dorsal scapular
bryologic factors. The limb buds of both arms nerve supplying the rhomboid muscles arises
and legs may vary in longitudinal extent and from the dorsal surface of C5, and the long
especially in their relative position to the neu - thoracic nerve to the serratus anterior muscle
raxis. The more cephalic the position of the arises from the dorsal surface of C5, C6, and
limbs, the more cephalic will be the nerves C7. From the superior trunk the suprascapular
contributing to the plexus, and vice versa. nerve (C4, C5, and C6 ) for the supraspinatus
The ventral rami supplying the plexus and infraspinatus muscles emerges dorsally,
give rise to three primary trunks ; C5 and C6 and the small nerve to the subclavius muscle
unite to form the superior ( upper ) trunk ; C8 (C5 and C6) arises ventrally - The roots of the
and Tl form the inferior ( lower ) trunk ; and C7 medial and lateral pectoral nerves (C5 to Tl ),
is continued as the middle trunk ( Fig. 8.14). which innervate the pectoralis major and
Each trunk splits into a posterior and an ante- minor muscles, arise in part from the ventral
rior division . The posterior divisions of all surface of the superior and medial trunks,
three trunks fuse to form the posterior cord , and in part from the medial cord ( Fig. 8.15).
situated behind the axillary artery. The ante- The three large peripheral nerves of the
rior divisions of the superior and middle forearm ( radial, median and ulnar ) are
trunk form the lateral cord , while the anterior formed in the following manner. The poste-
division of the inferior trunk is continued as rior cord , which receives contributions from
the medial cord ( Fig. 8.14). all the plexus nerves, gives off the thoracodor -
Many of the nerves supplying the shoul- sal (C6 to C8) and the subscapular nerves (C5
der muscles are given off directly from the to C8), the former supplying the latissimus
ventral rami, or from the primary trunks and dorsi muscle, and latter innervating the teres
C3
Superior trunk
C4
Middle trunk
C5
Dorsal scapular n.
C6
Suprascapular n.
C7
Fasciculi (cords) :
C8 — Medial
— Lateral
— Posterior
T1 Axillary n.
—
Inferior trunk
Phrenic n.
N. to subclavius
Long thoracic n.
Medial pectoral n.
Lateral pectoral n.
Subscapular nn -
Thoracodorsal n -
Radial n.
Med. brach. cutaneous n.
Med. antebrach. Musculocutaneous n.
cutaneous n.
Ulnar n. Median n.
Figure 8.15. Brachial plexus. The posterior divisions, posterior cords, and peripheral nerves formed from the posterior
divisions are shaded. Cords and peripheral nerves formed from the anterior divisions of the ventral primary rami are in
white.
major and subscapularis muscles ( Fig. 8.15). primitive musculature, many simple muscles
Then the posterior cord splits into its two ter- fuse to form larger and more complex ones
minal branches, the larger radial nerve and innervated by two or more spinal nerves
the smaller axillary nerve. The lateral and me- ( Figs. 8.17 and 8.18). Such fusion usually oc-
dial cords each split into two branches, thus curs within either the posterior or the ante-
forming four nerves ( Fig. 8.14). The two mid - rior musculature, and the muscles are inner-
dle branches, one from the lateral cord and vated , respectively, by posterior or anterior
one from the medial cord , unite to form the divisions of the nerves. At the cephalic
median nerve. The outer branch, derived from ( preaxial ) and the caudal ( postaxial ) borders
the lateral cord , becomes the musculocuta - of the limb, some muscles may be derived
neous nerve. The large innermost branch , de- from both the posterior and the anterior mus-
rived from the medial cord , gives off the culature. These muscles are supplied by
purely sensory medial brachial cutaneous and nerve fibers from both posterior and anterior
medial antebrachial cutaneous nerves, and its divisions. A well - known example is the
continuation becomes the ulnar nerve ( Fig. brachialis muscle, which receives branches
8.15). from the radial and musculocutaneous
A brief reference to embryology aids in ex- nerves. Thus, the primitive plexus shows a
plaining the formation of the plexus. During division into posterior and anterior plates.
early development the primitive muscle mass The posterior plate innervates the posterior
of the limb is split into posterior and anterior or extensor half of the arm and the posterior
layers, which are separated by the anlage of shoulder muscles; the anterior plate supplies
the humerus. The primary ventral nerve rami the volar or flexor half of the arm and the an -
invading the limb split into posterior and an - terior muscles of the shoulder. The nerves
terior branches to supply corresponding arising from the posterior plate are the dorsal
muscles and the overlying skin. Within the scapular, long thoracic, suprascapular, sub-
ro
SEGMENTAL INNERVATION OF THE TRUNK MUSCLES X
f
o_
CERVICAL SEGMENTS THORACIC SEGMENTS LUMBAR SACRAL COC.
SEGMENTS SEGMENTS
1 2 3 4 5 6 7 8 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 1 2 3 4 5
Deep long muscles of the back
a
o
Short Levator , sphinc-
deep Splenius muscles Serrat. post , Serrat. post. ter ani, perineal ,
neck sup. inf. and coocyg. m 's. Q.
muscles Z
:
Trapezius Latissim .
dorsi O
5
Levat. scap. (S )
CO
:
Rhom
boids
- r
Longus capitis Longus colli Rectus abdominis
Scalenes Ext. oblique, abdom.
Pectorali8 major Transverse abdom.
Pectorabs minor Int . oblique, abdom .
Sub. Quadratus lumborum

clavius
Serrat. ant.
Diaphragm Intercostal muscles
Figure 8.14. Segments of spinal cord that contribute somatic motor nerve fibers to individual trunk muscles
SEGMENTAL INNERVATION OF MUSCLES OF THE UPPER LIMB
CERVICAL SEGMENTS THORACIC

SEGMENTS
4 5 6 7 8
Supraspinatus
Teres minor
SHOULDER Deltoid
Infraspinatus
Subscapular
Teres major
Biceps brachii
Brachialis
ARM Coracobrachialis
Triceps brachii
Anconeus
Brachioradialis
Supinator
Extensor carpi radialis
Pronator teres
Elexor carpi radialis
Flexor pollicis longus
Abductor pollicis longus
Extensor pol icis brev .
FOREARM Extensor pollicis longus
Extensor digitorum communis
Extensor indicis proprius
Extensor carpi ulnaris
Extensor digiti minimi
Flexor digitorum sublimis
Flexor digitorum profondus
Pronator quadratus
Flexor carpi ulnaris
Palmaris longus
Abductor pollicis brevis
Flexor pollicis brevis
Opponens pollicis
Flexor digiti minimi
Opponens digiti minimi
HAND
Abductor pollicis
Palmaris brevis
Abductor digiti minimi
Lumbricals
Interossei
Figure 8.17. Segments of spinal cord that contribute somatic motor nerve fibers to the individual muscles of the
shoulder and upper extremity .
SEGMENTAL INNERVATION OF MUSCLES OF THE LOWER LIMB
THORACIC LUMBAR SEGMENTS SACRAL SEGMENTS

SEGMENTS:
12 1 1 2 3 4 5 1 2 | 3
Iliopsoas
Tensor fasc. lat .
Gluteus medius
Gluteus minimus
Quadratus femoris
HIP Gemellus inferior
Gemellus superior
Gluteus maximus
Obturat . int .
Piriformis
Sartorius
Pectineus
Adduct longus
Quadriceps femoris
Gracilis
Adductor brevis
THIGH
Ôbturator ext.
Adduct magn .
,
Adduct minim .
,
Articularis gen .
Semitendinosus
Semimembranosus
Biceps femoris
Tibialis ant .
Extensor halluc. long .
Popliteus
Plantaris
Extensor digit longus ,
LEG Soleus
Gastrocnemius
Peroneus longus
Peroneus brevis
Tibialis posterior
Flexor digit longus ,
Flexor hallucis longus

Extensor halluc. brev . I
Extensor digit brevis ,
Flex digit brev .

, ,
Abduct hall. ,
Flexor hall brevis ,
FOOT Lumbricals
Adduct hall. ,
\bduct . digit min . ,
Flexor digiti min .

Jpponens digit m ,
Quadrat plant . ,
Interossei
Figure 8.18. Segments of spinal cord that contribute somatic motor nerve fibers to individual muscles of the hip and
lower extremity
scapular, thoracodorsal, axillary, and radial with wrist drop being the most striking fea -
nerves ( black in Fig. 8.15). Those from the an- ture. The sensory loss is most marked on the
terior plate include the subclavius, pectoral, dorsum of the hand and thumb in the terri -
musculocutaneous, median, and ulnar , as tory supplied by the superficial radial nerve.
well as the purely sensory medial brachial Anesthesia in the arm is negligible, but usu-
and medial antebrachial cutaneous nerves. ally is present in a narrow strip on the dorsal
A summary of the peripheral distribution surface of the forearm from the elbow to the
of the principal nerves of the upper extremity wrist . The limited sensory loss is due to over-
follows. The cutaneous areas innervated by lap by adjacent cutaneous nerves. The most
each nerve are shown in Figures 8.11 and vulnerable parts of the radial nerve lie adja -
8.12. In their peripheral courses, some of the cent to the middle third of the humerus and
nerves of both the upper and lower extremity over the lateral epicondvle. The radial nerve
are particularly prone to trauma, or entrap- is frequently injured in fractures of the
ment by fibrous tissue related to either mus- humerus and those involving the elbow . The
cles, tendons, ligaments, or fascia (25). Sen- nerve also may be compressed against the
sory and motor symptoms that accompany humerus during sleep, especially when the
such neuropathies depend on whether the patient is anesthetized or intoxicated .
nerves are primarily motor or sensory.
MUSCULOCUTANEOUS NERVE
AXILLARY NERVE
This nerve (C5 to C7) sends muscular
This nerve (C5 and C6) innervates the del- branches to the coracobrachialis, biceps, and
toid and teres minor muscles and sends the brachialis muscles, and continues as the lat -
lateral brachial cutaneous nerve to the skin of eral antebrachial cutaneous nerve to supply the
the upper outer surface of the arm, mainly in radial half of the forearm , on both posterior
the deltoid region. After complete section of and volar surfaces ( Figs. 8.11 and 8.12 ). In
the axillary nerve, the deltoid muscle is para - complete lesions of the nerve, flexion and
lyzed and abduction without external rota - supination of the forearm are weakened . The
tion is practically impossible. In time, deltoid lateral portion of the brachialis muscle may
atrophy leads to loss of the round contour be spared since it receives, as a rule, a branch
normally present at the shoulder. The sen - from the radial nerve, and forearm flexion
sory loss is less extensive, owing to the over - can still be produced by the brachioradialis
lap of neighboring cutaneous nerves. muscle. The sensory loss is variable in extent.
It is poorly defined posteriorly , due to over-
RADIAL NERVE lap with the posterior antebrachial cutaneous
nerve (a branch of the radial nerve). On the
This nerve (C5 to C8) supplies motor volar side, sensory loss is more extensive and
branches to the triceps muscle and all of the approximates the territory supplied by the
extensor muscles of the elbow, hands, and lateral antebrachial cutaneous nerve ( Fig.
fingers, and to the brachioradialis, supinator 8.11 ).
and abductor pollici longus. Additionally, it
usually sends a twig to the brachialis muscle. MEDIAN NERVE
Its cutaneous branches, distributed to the
posterior surface of the extremity, are the pos- This nerve ( C6 to Tl , and sometimes C5)
terior brachial cutaneous nerve to the arm, the supplies all the muscles on the volar surface
posterior antebrachial cutaneous nerve to the of the forearm except the flexor carpi ulnaris
forearm , and the superficial radial nerve which and the ulnar head of the flexor digitorum
innervates the radial half of the dorsum of the profundus. In the hand , its branches inner-
hand and fingers as far as the distal interpha - vate the outer lumbricals ( I and II ) and the
langeal joints ( Fig. 8.12 ). The segmental inner- muscles of the thenar eminence, except for
vation of the muscles supplied by the radial the adductor pollicis brevis. The sensory in -
nerve is indicated in Figure 8.17. nervation is limited to the hand . It comprises
Injuries of the radial nerve give variable the volar surface of the thumb, index, and
symptoms which depend upon the location middle fingers, the radial half of the fourth
of the lesion. Complete section of the nerve finger, and corresponding portions of the
above all its branches produces inability to palm ( Fig. 8.11 ). Posteriorly, the nerve sup-
extend the elbow, wrist, fingers, and thumb, plies the distal phalanx of the index and mid -
die fingers and the radial half of the fourth juries here, as well as lesions of the nerve
finger. An inconstant palmar branch is distrib- anywhere along its course, may be accompa -
uted to the radial half of the volar surface of nied by secondary autonomic system overac-
the wrist, but usually this area is completely tivity. Following incomplete regeneration of
overlapped by the lateral antebrachial branch the nerve, an intense, persistent "burning
of the musculocutaneous nerve. The flexor pain" may be found over one or more points
and pronator muscles supplied by the motor in the distal course of the nerve ( causalgia ).
branches of the median nerve have a segmen- The median nerve is commonly involved in
tal innervation, as indicated in Figure 8.17. causalgia.
Injury to the nerve along its course in the
arm affects all its branches. Complete inter - ULNAR NERVE
ruption causes severe impairment of prona -
tion of the forearm and weakens flexion at This nerve (C8 and Tl ) supplies the flexor
the wrist . The wasting of the thenar eminence carpi ulnaris and the ulnar head of the flexor
and the abnormal position of the thumb give digitorum profundus in the forearm . In the
the hand a characteristic appearance after hand, it innervates the adductor pollicis, the
median nerve injury ( simian hand ). Nor- deep head of the flexor pollicis brevis, the in -
mally, the thumb is partially rotated and its terossei, the two inner lumbricals, and the
metacarpal bone is in a more volar plane than muscles of the hypothenar eminence. It gives
the other metacarpals. In injury of the median off three cutaneous branches. The palmar cuta -
nerve, this rotation is lost, and the flexion of neous branch supplies the ulnar half of the
the terminal phalanx is completely lost, as are volar surface of the wrist, an area extensively
abduction and opposition. Makeshift move- overlapped by the medial antebrachial cuta -
ments of opposition, without abduction and neous nerve ( Fig. 8.11 ). The posterior branch
rotation, can still be affected by the abductor innervates the ulnar half of the dorsum of the
pollicis and the deep head of the flexor brevis hand , all of the little finger, and the proximal
muscle ( pseudo-opposition ). The motor de- phalanx of the ulnar half of the ring finger.
fects are brought out readily in attempts to The superficial volar branch supplies the volar
make a fist . The fourth and fifth fingers flex, surface of the fifth digit, and the ulnar half of
but the thumb and index finger, and to a vari- the fourth finger, and the corresponding
able degree the middle finger, remain par- ulnar portion of the palm ( hypothenar re-
tially extended . gion ) ( Figs. 8.11 and 8.12). The segmental in -
Sensory loss following a lesion of the me- nervation of muscles supplied by the ulnar
dian nerve is somewhat variable. Usually it is nerve is indicated in Figure 8.17.
less extensive than the area supplied by the As in the case of the median nerve, injury
nerve ( Figs. 8.11 and 8.12), and it is most con- to the ulnar nerve in the arm affects its whole
stant on the volar surface of the index and distribution. Flexion of the wrist is weakened ,
middle finger . Loss of appreciation of light as are flexion of the fourth and fifth fingers
touch generally is more constant and exten- and adduction of the thumb. There is marked
sive than appreciation of pinprick, and ex - wasting of the hypothenar and interossei
tends from the radial border of the thumb to muscles. The paralysis of these small muscles
the base of the thenar eminence and across is particularly disturbing, for it makes execu -
the palm to include the palmar aspects of the tion of the finger movements required for
ring finger on the radial side. On the dorsum writing, sewing, and other skilled activities
of the hand it includes the radial side of the exceedingly difficult. The interossei flex the
terminal two-thirds of the ring finger and the basal phalanges and extend the middle and
middle and index fingers as far proximal as distal ones. Hence paralysis of the interossei
the middle of the proximal phalanges. Deep results in (a ) overextension of the basal pha-
sensibility usually is lost in the terminal phalanges by the extensor digitorum communis
langes of the index and middle fingers. The muscle, and ( b) flexion of the middle and dis -
median nerve is prone to injury in deep cuts tal phalanges by the flexor digitorum sub-
at the wrist and to entrapment as it passes be- limis muscle ( claw hand ). Sensory distur-
neath the transverse carpal ligament with the bances are variable and depend upon the
flexor tendons, a condition referred to as the level of nerve injury. Total anesthesia as a
carpal tunnel syndrome. Nerve compression rule is limited to the little finger and the hy -
may follow fractures (carpal and distal radial pothenar region . The ulnar nerve is prone to
bones) or occur without external stress. In- trauma as it crosses the medial epicondyle of
the humerus, and to entrapment as it passes ( Fig. 8.17).

The palmaris longus and the long
from the wrist to the hand . digital flexors usually are involved , with the
chief disabilities being in finger and wrist
MEDIAL ANTEBRACHIAL CUTANEOUS NERVE movements. The sensory loss is along the me-
dial aspects of the arm, forearm, and hand . If
This nerve (C8 and T1 ) supplies the medial preganglionic sympathetic fibers of the first
half of the forearm, on both posterior and thoracic root are included in the injury, there
volar surfaces ( Figs. 8.11 and 8.12). The extent is drooping of the eyelid, diminution in the
of the sensory deficits caused by injury to this size of the pupil, and narrowing of the palpe-
nerve varies in individual cases. On the volar bral fissure ( Horner' s syndrome ) (see Fig.
side it often reaches to the middle of the arm . 11.30).
On the posterior surface the sensory deficit is Injuries of the cords of the brachial plexus
somewhat smaller than the area of supply produce symptoms similar to those of periph-
shown in Figure 8.12. eral nerves, except that they are multiple and
often incomplete. A lesion of the posterior
MEDIAL BRACHIAL CUTANEOUS NERVE cord involves the radial and axillary nerves
and often the thoracodorsal and subscapular
This nerve (Tl ) usually is associated with nerves (Fig. 8.15). Interruption of the lateral
the intercostobrachial nerve derived from the cord affects the musculocutaneous and the
second, and often from the third , thoracic (in - lateral portion of the median nerve. Injury to
tercostal ) nerve. These two nerves supply the the medial cord involves the ulnar and the
axillary region and the inner surface of the medial portion of the median nerve, as well
arm, the area being considerably larger on the as the medial brachial and antebrachial cuta -
volar surface than on the posterior surface neous nerves.
( Figs. 8.11 and 8.12). The area is overlapped
extensively by adjacent cutaneous nerves. In- Lumbosacral Plexus
jury to one of the nerves produces negligible
symptoms. In injuries of both, the region of The plexus innervating the lower extrem-
anesthesia is limited to the axillary region ity is, as a rule, formed by the primary ven-
and medial surface of the upper arm . tral rami of LI to S2 and the larger portion of
S3. Frequently, there is a small contributing
Injuries of the Brachial Plexus branch from T12 ( Figs. 8.19 and 8.20). As in
the case of the brachial plexus, anatomic vari-
The motor and sensory deficits of the ations occur. The plexus is prefixed when it is
brachial plexus lesions vary considerably, de- supplied by T12 to S2, and poslfixed when it is
pending on the extent of the injury and its lo- formed from roots L2 to S4. There are also
cation . In injury of the trunks, the symptoms many intermediate forms, but the maximum
are segmental in character, and two main shift in either direction rarely exceeds the ex-
syndromes may be recognized . One syn- tent of a single spinal nerve. These conditions
drome affects the upper (superior ) trunk and are determined by the individual variations
the other the lower ( inferior ) trunk. The in the position of the limb buds during devel-
upper trunk syndrome ( Duchenne- Erb syn - opment. According to Foerster (16), prefixed
drome ) involves the muscles supplied by lumbosacral plexuses are rare. The lum-
C5 and C6, namely the deltoid , biceps, bosacral plexus, excluding the pudendal and
brachialis, brachioradialis, supinator, teres coccygeal portions, which are not distributed
major, teres minor, supraspinatus, and infra- to the leg, is conveniently subdivided into an
spinatus. In this syndrome there is difficulty upper lumbar and a lower sacral plexus.
in elevation and external rotation of the arm, The lumbar plexus , formed by LI , L2, L3,
accompanied by a severe loss of flexion and and the larger part of L4, usually receives a
supination of the forearm. Owing to the over- communicating branch from T12 ( Fig. 8.19).
lap of adjacent roots, the sensory deficit is as The larger sacral plexus is supplied by the
a rule limited to the deltoid region and lateral smaller portion of L4 ( furcal nerve), which
aspect of the arm. joins L5 to form the large lumbosacral trunk,
The lower (inferior ) trunk syndrome and by SI , S2, and the greater portion of S3
( Klumpke or Duchenne- Aran syndrome ) is rela- ( Fig. 8.20 ). Except for the uppermost portion
tively rare and affects primarily the small supplied mainly by LI , where the conditions
muscles of the hand innervated by C8 and Tl are somewhat obscure, both plexuses show
T 12
L1
Iliohypogastric n.
L2
Ilioinguinal n .
Genitofemoral n.
L3
Lat femoral
cutaneous n.
L4
Nn to Iliopsoas
L5
Femoral n.
Obturator n.
Lumbosacral trunk
Figure 8.19 . Lumbar plexus Peripheral nerves formed by anterior divisions of ventral primary rami are white nerves
formed by posterior divisions of ventral primary rami are gray
L4
L5
Sup. gluteal n.
S1
Inf . gluteal n.
S2
N to piriformis
S3 Sciatic n.
S4
Pudendal n Common
peronal n.
Post femoral cutaneous n .
N. to quadratus femoris
and inferior gemellus
N. to obturator internus
and superior gemellus Tibial n.
Figure 8.20. Lumbosacral plexus Peripheral nerves formed by anterior divisions of ventral primary rami are white;
nerves formed by posterior divisions of ventral primary rami are gray
an organization into posterior and anterior brane as it passes through the obturator
divisions, and the arrangement is simpler canal.
than in the brachial plexus. The undivided
lumbosacral primary rami do not form inter- FEMORAL NERVE
lacing trunks but split directly into posterior
and anterior divisions related , respectively, to The femoral nerve ( L2 to L4 ) sends motor
the primitive posterior and anterior muscula- branches to the extensors of the leg, the ilio-
ture of the leg. The peripheral nerves to the psoas, the sartorius, and also the pectineus.
extremity are formed by the union of a vari- Occasionally, a branch may go to the adduc-
able number of either posterior or anterior di- tor longus. The cutaneous branches are the
visions ( Figs. 8.19 and 8.20). In the lumbar anterior femoral cutaneous nerves for the thigh
plexus, the anterior divisions give rise to the and the saphenous nerve for the leg and foot
iliohypogastric (anterior branch ), ilioinguinal , ( Figs. 8.11 and 8.12). The former supply the
genitofemoral , and obturator nerves. The poste- anterior and anteromedial surface of the
rior divisions give rise to the iliohypogastric thigh, comprising a relatively large au -
eral femoral cutaneous nerves.
-
( posterior branch ), iliopsoas , femoral , and lat tonomous sensory field . The saphenous nerve
sends an infrapatellar branch to the skin in
In the sacral plexus , the anterior divisions front of the kneecap and then is distributed to
furnish the tibia! nerve and the nerves to the the medial side of the leg, and the lowermost
hamstring, quadratus femoris, obturator in- branches are distributed from the medial
terims, and gemelli muscles. The posterior di- margin of the foot to the proximal phalanx of
visions form the common peroneal and the su - the great toe. The segmental innervation of
perior and inferior gluteal nerves. The posterior the quadriceps femoris, iliopsoas, sartorius,
femoral cutaneous nerve, which supplies the and pectineus muscles is shown in Figure
back of the thigh , receives fibers from both 8.18.
posterior and anterior divisions. As in the Injury of the femoral nerve causes inability
case of the arm , muscles derived from both to extend the leg. If the lesion is high enough
the posterior and the anterior primitive mus- to involve the iliopsoas, flexion of the thigh at
culature are innervated by both posterior and the hip is severely impaired. Sensory distur -
anterior divisions. Thus the biceps femoris re- bances are manifested throughout the field of
ceives branches from the tibial , as well as per- supply , and there are relatively large areas of
oneal portions of the sciatic nerve. Following total anesthesia . If the thigh nerves alone are
is a summary of the peripheral distribution of involved , the anesthesia is most extensive on
the principal nerves of the lower extremity. the anterior surface of the thigh above the
The cutaneous areas supplied by these nerves knee. In isolated lesions of the saphenous
are shown in Figures 8.11 and 8.12. nerve, the anesthetic field extends on the
inner surface of the leg from below the knee
OBTURATOR NERVE to the medial margin of the foot . The femoral
nerve may become involved secondary to an
The obturator nerve ( L2 to L4) supplies the abscess in the psoas muscle. The terminal
adductor muscles of the thigh and the gracilis sensory branch of the femoral (saphenous
muscle. It sends an inconstant branch to the nerv e) is subject to entrapment as it leaves the
pectineus muscle, which more often is inner- subsartorial canal .
vated by the femoral nerve. Its cutaneous
branch is distributed to the inner surface of LATERAL FEMORAL CUTANEOUS NERVE
the thigh ( Figs. 8.11 and 8.12 ), the area being
extensively overlapped by adjacent cuta - The lateral femoral cutaneous nerve ( L 2
neous nerves. The segmental innervation of and L3) supplies the lateral half of the thigh,
the muscles supplied by the obturator nerve from the lateral buttock region to the knee
is indicated in Figure 8.18. In injury of this -
( Figs. 8.11 and 8.12 ) . In spite of overlap by ad
nerve, adduction of the thigh is weakened se- jacent cutaneous nerves, injury of this nerve
verely, but not lost, since the adductor mag- produces a considerable area of anesthesia on
nus muscle also receives some fibers from the the lateral aspect of the thigh. The cutaneous
sciatic nerve. The sensory defects usually in- areas supplied by the iliohypogastric ( LI ), il -
volve only a small triangular area of the ioinguinal ( LI ), and genitofemoral ( LI and L2 )
anatomic field . The obturator nerve is vulner- nerves are shown in Figures 8.11 and 8.12.
able to entrapment by the obturator mem - The iliohypogastric and ilioinguinal nerves
also send motor fibers to the internal oblique stretching of the sciatic nerve. Stretching of
and transverse abdominal muscles. Sensory the sciatic nerve in the presence of meningi-
loss due to injury to one of these nerves is rel- tis, intervertebral disc disease, peripheral
atively small or may be absent, but such le- neuritis, or nerve trauma, produces pain in
sions may cause neuralgia . the distribution of the nerve. The patient usu -
ally attempts to relieve the pain by automati-
SCIATIC NERVE cally flexing the leg at the knee ( Kernig' s sign ).
This nerve is accompanied by the popliteal
The sciatic ( ischiadic) nerve ( L4 to S3), the artery and vein , as well as a large number of
largest nerve in the body, is the chief continu - postganglionic sympathetic fibers. Injuries of
ation of all the roots of the sacral plexus. It is this nerve, like the median nerve described
composed of two parts, the tibial nerve and earlier, are particularly prone to be followed
the common peroneal nerve, enclosed for a by causalgia .
variable distance within a common sheath
( Fig. 8.20 ). Emerging from the greater sciatic
TIBIAL NERVE
foramen, or while still within it, the nerve
sends branches to the main external rotators The tibial nerve ( L4 to S3) supplies the
of the thigh , namely, the obturator interims, posterior calf muscles concerned with (a )
the gemelli and the quadratus femoris ( L4 to plantar flexion and inversion of the foot, and
SI ). Lesions of these nerves are compara- ( b ) plantar flexion of the toes. It also supplies
tively rare, and only external rotation is the intrinsic muscles of the sole, which aid in
weakened , since other external rotators are maintaining the arch of the foot. One cuta -
available. In the region of the thigh , branches neous branch given off in the thigh , the sural
are given off to the flexors of the knee ( ham- nerve, is distributed to the posterior and me-
string muscles) and to the adductor magnus, dial surface of the calf , where it is overlapped
the latter being innervated also by the obtura- extensively by branches of the saphenous and
tor nerve. These branches, all derived from lateral sural ( peroneal ) nerves. Terminal
the tibial portion of the sciatic nerve, often branches of the sural nerve ( lateral calcaneal )
spring from a common trunk, which either supply the outer margin of the heel and a tri-
runs independently or is loosely incorporated angular area on the outer surface of the foot
in the medial side of the sciatic nerve. An ad - which extends to the lower portion of the
ditional branch from the common peroneal Achilles tendon ( Fig. 8.12). Other cutaneous
nerve supplies the short head of the biceps branches of the tibial nerve ( medial calcaneal
femoris muscle. In injuries of the hamstring and plantar ) supply the back and medial mar-
nerves flexion of the knee is impaired se- gin of the heel, the plantar surface of the foot
verely , but weak flexion still may be pro- and toes, and the dorsal phalanges ( Figs. 8.11
duced by the action of the gracilis and sarto- and 8.12 ). The terminal branches of the tibial
rius muscle. The sciatic nerve splits into its nerve are the medial and lateral plantar nerves.
two terminal nerves at varying levels in the The segmental innervation of the calf and
thigh . The muscular branches of the common plantar muscles supplied by the tibial nerve
trunk provide motor and sensory fibers to the is indicated in Figure 8.18.
quadratus femoris, the obturator internus, the Complete interruption of the tibial nerve
gemelli , the semitendinosus, the semimem- above all its branches abolishes plantar flex-
branosus, and the biceps femoris. ion of the foot and toes and severely impairs
Normal peripheral nerve can be damaged inversion of the foot. Atrophy of the plantar
by excessive stretch, as may occur in the roots muscles increases the concavity of the plantar
and cords of the brachial plexus following arch ( pes cavus). Sensory disturbances are
undue angulation of the head and shoulder, negligible in the calf region, in which only a
or arm traction , during delivery. Reaction to narrow strip may show reduced sensitivity.
stretch in an injured or irritated nerve with a Total anesthesia is found on the sole of the
long course, such as the sciatic, often pro- foot, the plantar surface of the toes, the heel,
duces pain, and paresthesias. One of the best and often in a triangular area on the outer
known nerve stretching mechanisms is the surface of the foot. This nerve is vulnerable to
straight leg- raising test ( sign of Lasegue ). In a fractures and dislocations of the medial
person lying supine with the legs extended , malleolus, calcaneus, and astragalus bones. It
elevation of one extended (straightened ) leg also can be compressed as it passes through
by flexion of the thigh at the hip causes the osseofibrous canal with three tendons,
deep to the flexor retinaculum or deltoid liga - GLUTEAL NERVES

ment ( tarsal tunnel syndrome ).
The superior gluteal nerve ( L4 to SI ) sup-
plies the gluteus medius, gluteus minimus,
COMMON PERONEAL NERVE and tensor fasciae latae muscles, which
The common peroneal nerve ( L 4 to S2 ) abduct the hip and rotate it internally. These
supplies the lateral and anterior muscles of movements are impaired by injury to the
the leg and the dorsal muscles of the foot, nerve. The inferior gluteal nerve ( L5 to S2) is
effecting dorsal flexion and eversion of the distributed to the gluteus maximus, the
foot and dorsal flexion of the toes. The chief strongest extensor of the hip. Injury causes
cutaneous nerves are the lateral sural euta- wasting of the buttock . There is difficulty in
neous and the superficial peroneal nerve ( Fig. rising from a sitting position , walking uphill,
8.11 ) . The former, given off in the thigh , is or climbing stairs, where powerful contrac-
distributed to the outer side of the leg from tion of the muscle is required for raising the
the knee region to nearly the outer margin body.
of the sole, where it invades the territories
of the superficial peroneal and sural nerves. POSTERIOR FEMORAL CUTANEOUS NERVE
The superficial peroneal nerve supplies the
dorsum of the foot and toes to the distal The posterior femoral cutaneous nerve (SI
phalanges and a portion of the anterior sur - to S3) gives off several branches < inferior clu-
face of the leg. A small cutaneous branch of nial ) which supply lower portions of the but -
the deep peroneal nerve is distributed to the tocks. These nerves overlap branches of the
cleft between the adjacent surfaces of the lumbar and sacral dorsal rami ( superior and
great and second toe ( Fig. 8.11 ) . The com - medial clunial nerves) ( Fig . 8.12 ). Another
mon peroneal nerve divides into its superfi- small branch < perineal ) goes to the lower in-
cial and deep branches as it passes to the nermost part of the buttock, the dorsal sur-
lateral side of the neck of the fibula under face of the scrotum ( or labia majora ) and
cover of the peroneus longus muscle. The reaches the inner surface of the thigh . The
segmental innervation of the peronei, tib- main nerve supplies the posterior aspect of
ialis anterior, and extensor muscles on the the thigh, often extending below the knee
dorsum of the foot is indicated in Figure and widely overlapping the territories of ad -
8.18. jacent nerves. Injuries produce a relatively
Complete section of the peroneal nerve broad strip of anesthesia on the posterior
causes paralysis of dorsal flexion and ever- surface of the thigh from the buttocks to the
sion of the foot and paralysis of dorsal flexion knee.
(extension ) of the toes. The most striking fea -
ture is inability to elevate the foot and toes FUNCTIONAL CONSIDERATIONS
( foot drop). If the condition is prolonged,
Spinal Roots and Nerves
shortening of the Achilles tendon will pro-
duce a permanent plantar hyperflexion and Knowledge of the origin, si /e, course, and
the foot will assume an equinovarus defor- relations of the spinal nerves to their respec-
mity. Sensory defects will be found on the tive vertebrae ( Figs. 10.1 and 10.3) is clinically
dorsum of the foot, the outer part of the leg, highly relevant. Meninges, intervertebral
and between the great and second toe. The discs, size of the intervertebral foramina , and
extent of the sensory loss is much smaller vertebral mobility often can be correlated
than the anatomic field , since cutaneous areas anatomically with a variety of spinal nerve
on both , foot and leg, are overlapped exten - root syndromes. For example, a ruptured or
sively by the adjacent cutaneous nerves. The herniated intervertebral disc may lead to
common peroneal nerve is subject to injury compression of spinal nerve roots as they ap-
both by compression and fracture at the neck proach the intervertebral foramen , or the
of the fibula . A terminal branch of the deep foramina may be narrowed due to os-
peroneal nerve is frequently injured as it teoarthritis. Effects of stress and strain on the
crosses the dorsum of the foot. The terminal erect spine appear first at the weakest points.
sensory fibers of the superficial peroneal Here motion occurs and the mechanical im -
nerve may become entrapped as they pierce pacts of postural strain and trauma usually
the deep fascia at the distal and lateral part of are recorded ( i.e., cervical and lumbar re-
the leg. gions ). Dorsal roots, except for Cl , are nearly
three times larger than ventral roots. How - ventral root fibers usually produces the same
ever, the spinal roots vary in size in different motor deficits as those resulting from de-
regions. The largest nerve roots are those that struction of anterior horn cells ( discussed
participate in the formation of the nerve later ). However, at certain levels ( i.e., thora -
plexuses that supply the limbs. The sixth cer - columbar and sacral ), section of ventral root
vical is the largest of the cervical nerves and fibers produces additional autonomic deficits
from this point upward the roots diminish in which may not accompany lesions of the an-
size. Root size in relation to bony foramina terior horn cells. Section of a single ventral
have some interesting correlations with at- root, for example C5, would produce weak -
tendant liability to mechanical irritation or ness in the supraspinatus, infraspinatus sub-
compression. Cervical roots occupy only scapularis, biceps brachii, and brachioradi-
one-fourth of their respective intervertebral alis, but not complete paralysis of any of
foramen. In contrast, from the first lumbar these muscles. This pattern of distribution is
nerve downward, the size of the nerve roots unique to the C5 ventral root and different
increase in relation to the size of the foramen . from that of any single peripheral nerve.
The first to third lumbar nerves never com - Lesions of mixed spinal nerves produce
pletely fill the foramina, and the fourth root motor and sensory deficits that correspond to
rarely does, whereas the fifth lumbar nerve those of combined dorsal and ventral root le-
root frequently fills the intervertebral fora - sions. While the motor deficits correspond al-
men. This suggests a possible explanation for most exactly to those seen with pure lesions
the high incidence of compression of the of the ventral root, sensory deficits follow a
fibers of the fifth lumbar nerve root. dermatomal distribution and tend to be less
Nerve compression by disease or injury extensive because of the overlapping innerva -
can result in a variety of root symptoms, usu - tion characteristic of dermatomes ( Fig. 8.10 ).
ally associated with pain of short duration If only one mixed spinal nerve were injured ,
( radicular or root pain ). Pain often dominates for example C5, the motor weakness ( paresis)
the clinical picture, but the patient may also would be the same as described earlier, but
complain of numbness, tingling, and prickly no sensory loss would be detectable. Involve-
sensations ( paresthesia* ) localized to the der- ment of several contiguous mixed spinal
matome supplied by the affected dorsal roots. nerves would produce marked weakness or
If the ventral roots are involved , muscle paralysis in the muscles innervated by those
spasm , weakness, and vasomotor distur- spinal segments and detectable sensory loss
bances may accompany the pain. A knowl- in at least one dermatome, usually the one in -
edge of the radicular (segmental) distribution nervated by the intermediate nerves.
of the spinal nerves is helpful in evaluating These findings are in sharp contrast to the
root lesions which may lie in and around the motor and sensory deficits associated with
vertebra of a given region . peripheral nerve lesions. With a peripheral
Injury to the spinal nerves or their periph - nerve lesion , the muscle paralysis and the
eral branches causes disturbances of both sensory loss correspond to the peripheral dis-
sensation and movement. Section of a dorsal tribution of the particular nerve.
root rarely produces a loss of sensation ( anes-
thesia ) , although it may impair reflexes ( hy- Lower Motor Neuron
poreflexia ) initiated by appropriate stimuli in
the areas supplied by that root. Owing to the The behavioral expression of central ner-
overlapping distribution of fibers of adjacent vous system activities involved a conver-
roots, anesthesia will not be detectable unless gence of various central neuronal systems
several contiguous roots are injured or cut onto projection neurons, whose axons reach
( Fig. 8.10). The hyporeflexia involves superfi - peripheral effector organs belonging to either
cial and deep reflexes and it is associated the somatic or visceral components of the pe-
with a diminution of tone ( hypotonia ) in the ripheral nervous system . For example, the
affected muscles. large a motor neurons of the anterior horn of
It is clinically important to clearly distin- the spinal cord give rise to axons which
guish the deficits which occur as a conse- emerge via the ventral root and innervate
quence of lesions in spinal segments from striated muscles. The n motor neurons and
those that occur in spinal roots, mixed spinal their axons constitute anatomic and physio-
nerves, and peripheral nerves. A lesion in logic units, referred to as the final common
pathway or the lower motor neurons (38). The cle no longer responds to stimulation of its
concept of the lower motor neuron is not lim- motor nerve. However, the muscle still re-
ited to the spinal cord , even though it is fre- sponds to direct stimulation with slow wave-
quently used in that context . Cells of the like contractions, but it is the positive pole or
motor cranial nerve nuclei (nerves III to VII, anode which induces the strongest response
IX to XI , and XII ), which innervate the mus- on closing the circuit. If preganglionic vis-
cles of the head and neck, also must be classi - ceral fibers are involved by a lesion , as in the
fied as lower motor neurons. Lesions selec- case of the thoracic and upper lumbar roots,
tively involving the cell bodies of lower there are sudomotor, vasomotor, and at -
motor neuron in the spinal cord, or their rophic disturbances expressed by dryness
axons in the ventral root or in a peripheral and smoothness of the skin .
nerve, produce complete or partial loss of In certain diseases of the lower motor neu -
motor function ( paralysis or paresis ) , complete ron, the muscles exhibit small, localized
or partial loss of muscle tone ( atonia or hypoto- spontaneous contractions known as fascicula-
-
nia ) , loss of reflex activity (areflexia or hypore tions. These muscle twitches, visible under
flexia ) , and muscle atrophy. All of these the skin , represent the discharge of squads of
changes are confined to the affected muscles muscle fibers innervated by nerve fibers aris-
(6 ). Atrophy as a consequence of a lower ing from lower motor neurons, Fasciculations
motor neuron lesion develops gradually and occur asynchronously in different parts of
in time is obvious on inspection . various muscles and are thought to be trig-
Since the anterior horn cells that inner- gered by motor unit discharges that occur
vate a single muscle extend longitudinally within the cell body of the degenerating
through several spinal segments, and since motor neuron . Fasciculations commonly are
several such cell columns exist at each spinal seen in amyotrophic lateral sclerosis ( Fig. 11.28),
level , a lesion confined to one spinal segment occasionally in acute inflammatory lesions of
will cause weakness, but not complete paral- peripheral nerves ( i.e., polyneuritis ) , and gen -
ysis, in all muscles innervated by this seg- erally do not occur when the anterior horn
ment. Complete paralysis will occur only cells are rapidly destroyed ( i .e., acute po-
when the lesion involves the column of cells liomyelitis). The term fibrillations , frequently
in several spinal segments that innervate a misused as the equivalent of the term fascicu -
particular muscle, or the ventral root fibers lations, refers to small (10-20 pV ) potentials
that arise from these cells. Because most ap- of 1-2 msec duration that occur irregularly
pendicular muscles are innervated by fibers and asynchronously in electromyograms of
arising from parts of three spinal segments denervated muscle. These spontaneous dis-
( Figs. 8.16-8.18), complete paralysis of a mus- charges cannot be observed under the skin
cle implies a central lesion involving anterior and produce no detectable shortening of
horn cells in several spinal segments, or a le- muscles. These potentials represent the spon-
sion involving ventral root fibers from sev- taneous activation of individual muscle
eral spinal segments ( Figs. 10.19 and 10.23). fibers.
Since neighboring cell columns are likely to
be affected at each level, such lesions usually Regeneration of Injured Peripheral
produce paralysis in muscle groups rather Nerves
than individual muscles.
The denervated muscle also shows certain Our knowledge of the processes of degen -
changes in its reaction to electrical stimula- eration and regeneration has been greatly in -
tion. Healthy muscle responds to stimulation creased in recent years by investigations on
by both the faradic (interrupted ) and galvanic mammalian nerves under various experi-
(continuous) current . In faradic stimulation, mental conditions. Valuable information was
the response lasts as long as the stimulus is obtained by clinical and surgical studies of
applied . In galvanic stimulation , the response the peripheral nerve injuries during World
occurs only on closing or opening the circuit. War II ( 21 , 22 ) . Seddon (36) distinguished
Normally it is the application of the negative three types of nerve injury: ( a ) complete
pole or cathode which produces the strongest anatomic division ; ( b ) crush or compression
contraction on closing the current. In the injuries in which the continuity of the nerve
complete reaction of degeneration , which ap- fibers is broken but the sheaths and support -
pears 10-14 days after nerve injury, the mus- ing tissue remain intact; and ( c ) temporary
impairment or nerve block . Nerve section section or injury. Many of these fibers are
nearly always demands surgical intervention "functional" processes of dorsal root gan -
to reestablish continuity. The recovery is glion cells, and these tangled ends can trans-
more or less successful, but never complete, mit nerve impulses into the spinal cord . Such
since many of the regenerating fibers fail to neuromas explain why a patient may have lo-
reach their respective end organs. After nerve calized phantom pain and / or paresthesias in a
crush there also is complete degeneration of previously amputated hand or foot.
the severed nerve fibers. Both nerve section The behavior of the Schwann cells after
and nerve crush are followed by loss of sen- anatomic severance is especially significant .
sation and movement, wasting of muscles, About the 4th day, they become elongated
and degenerative reaction. However, the and migrate out of the stumps into the scar,
damaged nerve fibers and their sheaths are in coming mainly from the peripheral stump
close anatomic contiguity after nerve crush, but, to a lesser extent, also from the central
and subsequent regeneration usually leads to one. These cells arrange themselves end - to -
a nearly complete recovery. In mild compres- end , and form strands which traverse the
sion or block , there are varying degrees of fibrous tissue of the scar and establish conti -
paralysis, but electrical excitability remains nuity between the intact axons and the de-
normal . Because the nerve fibers are not sev- generating tubes of the peripheral stump.
ered , there is no peripheral degeneration . Re- In some animals, under suitable conditions,
covery is more rapid . It begins in a few weeks gaps of 2 cm have been naturally bridged in
and usually is completed within 2 or 3 this manner. In humans, gaps of several mil -
months. These three types of nerve injury limeters may be similarly bridged . Under
may appear as separate entities or in various most circumstances, however, the mass of
combinations. Since the clinical symptoms scar tissue is too extensive to be handled by
after nerve section and crush are the same the sheath cells themselves and surgical inter-
until regeneration is completed , surgical ex- vention is required . Scar tissue must be re-
ploration usually is indicated to determine moved from both ends of the severed nerve,
the nature of the injury (40 ). and these ends must be approximated and
In a simple crush, although the continuity maintained by epineural sutures. The central
of the axons is interrupted , the endoneurium axonal tips swell and produce a number of
and other supporting tissues remain essen - fine branches which enter the injured area by
tially intact. As a result, regenerating nerve the 3rd day. At first they appear free in the
fibers from the central stump can grow dis- connective tissue. Soon they apply them-
tally, traverse the minimal scar tissue be- selves to the surface of the sheath cell strands
tween the severed axonal ends, and enter ap- and are led to the peripheral stump, where
propriate Schwann cell tubes of the distal many of the branches enter the old Schwann
stump. After complete anatomic severance, cell tubes ( Figs. 5.38 and 5.39). However, the
the conditions are quite different at the site of number of fibers entering the distal tubes is
injury. The cut ends are separated by a gap of always smaller after section of the nerve than
variable extent which becomes filled with after crush . Moreover, many nerve fibers
connective tissue and sheath cells, so that a enter tubes which are structurally unsuitable
scar of union is formed between the stumps. for full functional maturation . Once the fibers
Hemorrhage and the vascular mesenchyme have entered the distal tubes, the processes of
contribute cells to the scar tissue. These cellu - growth and maturation are the same as after
lar elements in the lesion area seriously im- crush . These are described in Chapter 5.
pede the growth of fine sprouts of regenerat- The rate of nerve regeneration has been
ing axons from the proximal stump of the studied by a number of investigators. After
nerve. An enlarged heterogeneous mass at primary suture of the peroneal nerve in the
the cut end of a previously injured nerve is rabbit, it takes about 7 days for the growing
known as a traumatic neuroma (amputation or axon tips of the central stump to traverse the
pseudoneuroma ). It consists of Schwann scar of the gap and reach the peripheral
cells, connective tissue cells and fibers, stump (19, 20, 42). After crush the "scar"
macrophages, and an abundance of tangled delay was about 5 days. Then the fastest ax-
aberrant nerve fibers. Such a skein of "lost" onal tips grew at the rate of 3.5 mm a day
nerve fibers in scar tissue can be a most seri- after suture, and 4.4 mm after a crush . Most
ous complication following peripheral nerve of the axons grow distally at 3 mm a day after
the peroneal nerve is crushed , and 2 mm a reestablishing appropriate peripheral connec-

day after nerve section and suture. When the tions are reduced . Myelinization is delayed
fine regenerated axons attain the periphery and increase in diameter of the nerve fiber is
they increase in diameter and most of them restricted by the thickened endoneurium,
ultimately become remyelinated . If a suffi - which forms a large portion of the tube.
cient number of such fibers reach and suc- Of special importance is the progressive
cessfully reestablish contact with appropriate atrophy of the muscles and end organs. In
sensory and motor end organs, there will be early stages, where the motor end plates re-
an eventual return of function. The total la- main intact and connected with the Schwann
tent period in the rabbit between nerve re- cell tubes, new fibers can enter directly and
generation and functional recovery was 20 restore the original pattern. In later stages,
days following nerve crush and 36 days after these channels become occluded and the end
nerve suture. organs may completely disintegrate. The re-
In the longer nerves of humans, the generating fibers often fail to enter the old
process is slower, although a rate of 4.4 mm sensory and motor endings or their previous
a day for growing axons was found after a locations. These fibers wander along the mus-
crush of one of the digital nerves (1 ). The cle fibers, ultimately forming new motor end
rate of functional regeneration falls off with plates of a more primitive character, whose
the distance traversed , since increases in di - distribution is irregular and different from
ameter and myelinization occur more slowly the original pattern of innervation. All stud -
in the distal portions of the fiber . A justifi - ies favor early nerve suture, perhaps 3 or 4
able assumption for axonal growth in hu - weeks after injury. At this time sheath cell ac-
mans under ideal conditions is about 3 tivity is at its height and the somewhat thick-
mm / day. The average latent period until ened perineurium permits easier surgical ap-
functional maturity after distal nerve in - position of the injured nerve stumps ( 50).
juries is 20 days after crush and 50 days after Delays of 6 months or more before suture
suture. may seriously interfere with the reparative
Regeneration can occur when two stumps processes but failure is not necessarily en-
are sutured after being left apart for a consid - countered in all cases. Good recovery is pos-
erable period of time. However, it is gener- sible after long-delayed suture if enough
ally agreed that functional recoveries after axons reach appropriate Schwann cell tubes
long-delayed sutures usually are unsatisfac - and the muscles are maintained in good con-
tory. The difficulties occasioned by long dition by appropriate therapy . Sunderland
delay are due to a number of factors which ( 41 ) has reported good restoration of function
interfere with the regenerative processes, and in human hand and finger muscles which
these effects become progressively more seri - had been denervated for 12 months.
ous. Some of the factors are briefly men- Recent experimental studies have under-
tioned . After a long delay, the distal stump lined the importance of various growth fac-
atrophies and the outgrowth of sheath cells is tors and other molecules in the nerve regen-
reduced or ceases. Hence good apposition of eration processes. Several procedures,
the cut nerve ends is difficult , and many including the use of peripheral nerve grafts to
axons fail to reach the degenerated atrophic promote axonal growth , have also been de-
Schwann cell tubes of the distal stump. The veloped . These novel approaches to the prob-
tubes themselves are greatly shrunken and lem of nerve regeneration are reviewed in
receive fewer fibers, so that the chances for Chapter 5.
References ganized cultures of rat dorsal root motor neurons. In Downey ) A , Dar -
ganglia . J Cell Biol 1967;32:439- ling RC , eds. Physiological basis
1. Bowden REM , Gutmann E . Dener - 466. of rehabilitation medicine. Ch. I .
-
vation and re innervation of the 4 . Burton H, McFarlane )). The organi - Philadelphia: W . B Saunders, 1971:
human voluntary muscle. Brain zation of the seventh lumbar spinal 3-27.
-
1944;67:273 313. ganglion in the cat . J Comp Neurol 7. Clifton GL, Coggeshall RE, Vance
Wl I , Willis WD Receptive fields of
2. Brendler S) The human cervical 1973;149: 215- 232 .
myotomes: functional anatomy 5. Carmel PW, Stein BM . Cell changes unmyelinated ventral root afferent
studies at operation . J Neurosurg in sensory ganglia following proxi - fibres in the cat I Physiol ( Lond )
1968;28:105-111. mal and distal nerve section in the 1976;256:573-600.
3. Bunge MB, Bunge RP, Peterson ER , monkey . J Comp Neurol 1969; 8. Coggeshall RE . Nonclassical fea -
Murray MR . A light and electron 135:145-166. tures of dorsal root ganglion cell or-
-
microscope study of long term or- 6. Carpenter MB. Upper and lower ganization . In: Yaksh L, ed. Spinal
afferent processing. New York: 24 . Kerr FW1., Fysak WR . Soma totopic human nervous system. Ch. 4 . New
Plenum , 1986:83-%. organization of trigeminal -ganglion York: Academic Press, 1990:77-92.
9. Coggeshall RF, Applebaum Ml., .
neurons Arch Neurol 1964;11: 36. Seddon HJ . Three types of nerve in -
Frazen M , Stubbs TB III , Sykes MT. 593-602. jury . Brain 1943;66:237-288.
Unmyelinated axons in human ven - 25. Kopell HI’, Thompson WAF. Pe - 37. Sherrington CS. Experiments in ex -
tral rtx > ts, a possible explanation for ripheral entrapment neuropathies. amination of the peripheral distrib-
the failure of dorsal rhizotomy to re- Baltimore: Williams & Wilkins* ution of the fibers of the posterior
lieve pain. Brain 1975;98:157-166 . 1963. roots of some spinal nerves Phil
10. Coggeshall RF , Coulter JD, Willis 26. Fawson SN, I larper El, Harper AA, Trans R Soc Fond ( Biol ) 1893;
WO. Unmyelinated axons in the Garson JA, Coakham HB, Randle BJ . 184:641-763.
ventral roots of the cat lumtx >sacral Monoclonal antibody 2C5: a marker 38 Sherrington CS. The integrative ac-
enlargement . | Comp Neurol for a subpopulation of small neu - tion of the nervous system . New
1974;153:39-58. rons in rat dorsal root ganglia . Neu- York: Charles Scribner's Sons, 1906.
11 . Coggeshall RF , Ito II . Sensory fibers
in ventral roots L7 and SI in the cat . . -
roscience 1965;16:365 374 .
27. Fawson SN Wadell PJ , McCarthy
( Reprinted , Yale University Press,
New Haven , 1947 )
-
J Physiol ( Fond ) 1977;267:215 235. PW . A comparison of the electro- 39. Sosa |M , DeZorrilla NB. Spinal gan -
12 Dixld J , jessell TM . Factoseries car - physiological and immunocyto - glion cvtological responses to axon
bohydrates specify subsets of dorsal chemical properties of rat dorsal and to dendrite sectioning. Acta
riH > t ganglion neurons projecting to ganglion neurons with A and C Anat ( Basel ) 1966;65:236-255.
the superficial dorsal horn of rat fibers. In: Schmidt RF, Schaible HG, 40. Stookey B, Scarff J . Injuries of pe-
spinal cord. ) Neurosci 1985; -
Vahle Hinz C, eds. Fine afferent ripheral nerves. In: National Re-
5:3274-3278. nerve fibers and pain . Weinheim search Council Committee on
13. Dodd I , Role FW . The autonomic and New York: VCH Publisher, Surgery. Neurosurgery and thoracic
nervous system. In: Kandel ER , 1987:193-203. surgery . Philadelphia : W . B Saun -
Schwartz ) l I , Jessell TM , eds. Princi - 28. Maynard CW, Fconard RB, Coulter ders, 1943:81 - 184.
ples of neural science. Ch. 18. New JD, Coggeshall RE. Central connec - 41 . Sunderland S. Capacity of reinner -
York: Elsevier, 1991:258-269. tions of ventral root afferents as vated muscles to function efficiently
14 . Dogiel AS. Der Bau der Spinalgan - demonstrated by the HRP methixJ . J after prolonged denervation. Arch
glien des Menschen und der Comp Neurol 1977;172:601-608. Neurol Psychiatry 1950;64 : 755-771 .
Saugetiere. Jena . Gustav Fisher, 29. Pearson AA, Sauter RW , Buckely 42. Sunderland S. Factors influencing
1908 TW . Further observations on the cu - the course of regeneration and the
15. Dusser de Barenne JG . Experimental taneous branches of the dorsal pri- quality of the recovery alter nerve
researches on sensory localization in mary rami of the spinal nerves. Am suture. Brain 1952;75:19-54.
.
the cerebral cortex of the monkey.
Pm K Six Lond (Biol) 1924;%
272-291 .
I Anat 1966;118:891 -904.
30. Philippe E, Garosi M , Droz B. Influ -
ence of peripheral and central tar -
43. Tennyson VM . Electron microscopic
study of the developing neuroblast
of the dorsal rtxit ganglion of the
16. Foerster O. Die Feitungsbahnen des gets on subpopulations of sensory rabbit embrvo. J Comp Neurol
Schmerzgefiihies und die chirurgis- neurons expressing calbindin im - 1965;124:267-318.
che Behandlung der Schmerz - munoreactivity in the dorsal root 44 . Truex RC . Morphological alterations
zustande. Berlin : Urban and ganglion of the chick embryo. Neu - in the Gasserian ganglion cells and
Schwarz.enberg, 1927. • roscience 1988;26:225-232. their association with senescence in
17. Foerster O. The dermatomes in man . 31. Pineda A , Maxwell DS, Kruger F. -
man. Am J Pathol 1940;16:255 268.
Brain 1933;56:1-39. The fine structure of neurons and 45. Truex RC . Degenerate versus multi -
18. Foerster O. Sensible cortical Felder. satellite cells in the trigeminal gan - polar neurons in sensorv ganglia.
In : Bumke O, Fixers ter O, eds. I land -
buch der Neurologic. Vol 6. Berlin:
-
Julius Springer, 1936:358 448.
19. Gutmann E, Guttmann F, Medawar
—
glion of cat and monkey. Am J Anat
l %7;121 :461 488.
32. Ramon y Cajal S. Histologic du
Systeme Nerveux de 1'Horn me et
Am J Pathol 1941;17:211-218.
46. Warrington WB, Griffith F. On the
cells of the spinal ganglia and on the
relationship of their histological
PB, Young JZ. Rate of regeneration des Vertebres. ( Translated by F. structure to axonal distribution.
Brain 1904 7 297 326 .
of nerve j Fxp Btol 1942;19:14-44 .
-
20. Gutmann F., Young J 7.. The re inner -
Azoulav ), Paris: Maloine, 1909,
1911. ( Reprinted , Consejo Superior ^
47. Willis WD, Coggeshall RE . Sensory
vation of muscle after various peri - de Investigaciones Cientificas, Insti - mechanisms of the spinal cord . New
-
ods of atrophv J Anat 1944;
78:15-43.
tuto Ramon y Cajal, Madrid , 1972.)
33. Ranson SW. The structure of the
York: Plenum Press, 1978.
48. Windle WF. Neurons of the sensorv
21 Haymaker W . Bing's local diagnosis spinal ganglia and of the spinal type in the ventral roots of man and
in neurological diseases. St . Fouis: nerves. J Comp Neurol, 1912;22: other mammals . Arch Neurol Psy -
C.V . Mosbv . 1956:52; 105-112. 159-175. -
chiatry 1931;26:791 800.
22. I laymaker W , Woodhall B . Periph - 34 . Sehmalbruch IF The number of 49. Wvburn GM . The capsule ol spinal
eral nerve injuries: principles of di - neurons in dorsal root ganglia F4 - F6 ganglion cells. J Anat 1958;92:
agnosis. Philadelphia: W . B Saun -
ders, 1945.
ot the rat Anat Ret I987;219
315-322.
-
528 533.
50. Young JZ. Factors influencing the
23. Head IF Studies in Neurology Fon- , 35. Schoenen J , Grant G. Spinal cord: regeneration of nerves. Adv Surg
don: Oxford University Press, 1920. connections. In : Paxinos G, ed . The -
1949;1:165 220.
9
Autonomic Nervous System
TRIPARTITE INTEGRATED SYSTEM which arc viewed as closely interrelated sys -

tems working in a highly concerted fashion .
The portions of the central and peripheral -
Visceral sensory afferent signals are initi -
nervous system that are concerned primarily ated mainly by internal changes that activate
with the regulation and control of visceral visceroceptors. Visceral reactions processed
functions are termed collectively the visceral , by the central nervous system are usually
vegetative , or autonomic nervous system ( Fig. vague, poorly localized and predominantly
9.1 ) . The vegetative nervous system is said to of an affective character. Tactile sensibility is
have been first recognized in 1807 by the Ger- practically absent , and temperature sense is
man anatomist Johann Christian Reil (113). appreciated only in certain places, such as the
Nearly 90 years later, John Newport Langley, esophagus, the stomach, the colon, and the
the English physiologist, introduced the term rectum. On the other hand , distension or
"autonomic nervous system" to include the
spasms of the muscular walls of hollow vis-
cranial and spinal components of the vegeta - cera or blood vessels may produce severe dis -
tive nervous system . While doing so he com - tress or acute pain . As defined by Langley
mented: (70), the autonomic system was purely a vis -
ceral motor system consisting of "visceral ef -
"the word 'autonomic' does suggest a much
ferent cells and fibers that pass to tissues
greater degree of independence of the central ner-
vous system than in fact exists, except perhaps in
other than the skeletal muscle." This rigid de-
that part which is in the walls of the alimentary finition , which is still used in some recent
canal. But it is, I think , more important that new textbooks (39), limits the term autonomic to a
words should be used for new ideas than that the two neuron visceral efferent system and ex-
word should be accurately descriptive" (69). cluded visceral afferent fibers. Yet , sensory
fibers accompany most visceral motor fibers
In 1921, Langley proposed a subdivision of and form the afferent links of most visceral
the autonomic nervous system that is still reflex arcs . Recent clinical studies underline
widely used today. In this partitioning, neu - the importance of visceral afferent mecha -
rons of the autonomic system are classified in nisms in functional disorders of various vis-
three groups ( a tripartite integrated system ) cera (81 ). Visceral afferent fibers have their
according to the origin of the preganglionic cells of origin in the spinal and specific cra -
input : (a ) sympathetic neurons, with pregan - nial nerve ganglia ( Figs. 9.2 and 10.23). They,
glionic input from nerve cell bodies located in like the higher brain centers, play a constant
the thoracolumbar region of the spinal cord ; and dynamic role in the regulation of auto-
( b ) parasympathetic neurons, with pregan - nomic activities.
glionic input from neurons located either in During the years that have followed the
the brainstem (cranial parasympathetic out - pioneering studies of Walter I less ( 60), the
flow ) or in the sacral region of the spinal cord foregoing limited concept has been liberal -
( sacral parasympathetic outflow ); and ( c) en - ized to make the term "autonomic" more
teric neurons, with little or no preganglionic synonymous with "visceral," and to include
input from the central nervous system ( 53). In both peripheral and central neural structures.
the present account , the terms sympathetic It behooves all concerned with visceral func-
and parasympathetic are not restricted to tion to remember that central neurons and
postganglionic neurons. They are applied to visceral afferent neurons are vital and inte-
both the pre- and postganglionic elements of gral parts of the autonomic system, regard -
the thoracolumbar and craniosacral subdivi - less of arbitrary definitions. In similar fash -
sions of the autonomic nervous system, ion , no attempt should be made to sharply
293
SYMPATHETIC Projections of Projections of PARASYMPATHETIC 8
NERVOUS SYSTEM sympathetic parasympathetic NERVOUS SYSTEM
nervous system nervous system
O
MIDBRAIN O
3
Ciliary Oculomotor (III) T3

Eye ganglion nerve PONS 0)
=2.
>
PONS
D
Lacnmal and Submandibular MEDULLA 3
MEDULLA Supenor cervical r
D
ganglion salivary glands. I and otic ganglic
C1 Q>
C2
C3
Facial ( VII) nerve , z
CD
Glossopharyngeal
c4
a
( IX ) nerve
Cervical— C5
Cervical
O
C
C6 Middle
cervical
\ co
C7 co
ganglion <
C8 CO
T1 Stellate ganglion CD
T2 Q- Vagus ( X ) i
T3 nerve
T4 Greater splanchnic Liver
T5
T6
o- nerve
V Celiac ganglion /
Stomach
& Pancreas Thoracic
Thoracic - T7 o X
T8
T9
O-
o- Large —
intestine
T 10 o
T 11 a S
T 12 o
o-
Lesser
splanchnic £
Adrenal
Small intestine
L1 V nerv£ medulla
L2 o-
Lumbar L3 o- Lumbar
L4 tectum
Superior
L5 mesenteric Splanchnic
S1 ganglion o: nerve
O
Sacral
S2
S3 Inferior
Bladder Z o — Sacral
mesenteric o
S4 ganglion
S5
Paravertebral
o: —
1
chain Reproductive
ganglia organs
Figure 9.1. General arrangement of the autonomic system The sympathetic components are shown in red. while the
parasym-
sep-
pathetic components are in blue For clearness the sympathetic fibers to the blood vessels, hair, and sweat glands are shown
arately in Figure 8.2
Visceral afferent
fiber .
Spinal <t
Vf -
ganglion Hair ll >' ikin
o
\ Sebaceous
\\ \ VX glands
Peripheral V
Lateral > > Arrecfor pili
horn nerve < muscle
Postganglionic
Preganglionic ‘• ft fibers
fibers
Postganglionic White ramus

fiber
Gray ramus Blood vessel
Paravertebral
ganglion
t
Prevertebral Sympathetic trunk
ganglion
Digestive tube
Figure 9.2. Neural reflex arcs of the sympathetic system
delineate the nervous system into somatic nerve cells known as the autonomic ganglia .
and visceral portions. This is a convenient The cells of these peripheral ganglia are in
physiologic subdivision, but the two are synaptic relation with fibers from the spinal
merely different parts of a single integrated cord or brainstem, and they send out axons
neural mechanism . The higher brain centers which terminate in the visceral effectors:
regulate both somatic and visceral functions, smooth muscle, heart muscle, and glandular
and throughout the neuraxis there is inter- epithelium . There are fundamental differ-
mingling and association of visceral and so- ences in the innervation of striated and
matic neurons. Moreover, visceral reflexes smooth muscle. In striated muscle, each mus-
may be initiated by impulses passing through cle fiber is innervated by a single axon, but a
somatic afferent fibers from any receptor, single motor neuron may send axons to many
and , conversely, visceral changes may give muscle fibers. Furthermore, the efferent path-
rise to somatic activities. Through some way to striated skeletal muscle is mottosynap-
mechanism, as yet unexplained , stimulation tic; the central motor neuron, whose cell body
of peripheral visceral efferent neurons also resides in the ventral horn of the spinal cord ,
can alter the activity of somatic sensory re- projects directly to the striated muscle. The
ceptors. Also of interest are the results of a re- nerve-muscle junction in striated fibers has a
cent immunohistochemical study of the em - characteristic morphology and is called the
bryonic development of the enzyme choline motor end plate or the neuromuscular junc -
acetyltransferase (ChAT ) in thoracic spinal tion.
motor neurons of the rat, which suggests that In smooth muscle, the efferent axon has
both somatic and autonomic neurons at this numerous swellings or varicosities which
level are derived from a common cellular constitute sites of transmitter storage and re-
group (93). lease. There may be no specialized structure
Interposed in the efferent peripheral path- on the postjunctional membrane of the
way between the central nervous system and smooth muscle fiber, and not all muscle cells
the visceral structures are aggregations of are innervated . Smooth muscle cells are often
electrotonically coupled through gap junc- racic communicating rami in the cat show
tions, so it is not necessary for each muscle that about 10% of the axons in the white rami
fiber to be directly contacted by the axon ( 25, are sensory. About half of the sensory axons
125 ). Peripheral autonomic neurons usually are unmyelinated . In the gray rami, less than
discharge at low frequencies, and may pro- 1% of the axons are sensory ( 28, 29 ) . While
duce their maximal effect at rates of 4-10 Hz the number of afferent axons in the sympa-
(55). The visceral motor system also differs thetic rami is small , they will need to be con-
from the somatic voluntary motor system in sidered in functional studies relating to vis-
that its efferent pathway to the target is disyn - ceral sensation.
optic ; a synapse in the peripheral autonomic The autonomic ganglia , which have a wide
ganglion is always interposed between the ef - distribution in the visceral periphery, may be
ferent neuron in the central nervous system classified in three groups: (a ) paravertebral , (b)
and the target organ in the periphery. An- prevertebral ( collateral ), and (c) terminal . Par-
other important difference concerns the avertebral ganglia are arranged in a segmen -
mechanisms by which motor output is inhib- tal fashion along the anterolateral surface of
ited . Since all somatic motor neurons are exci- the vertebral column and are connected with
tatory , inhibition can only be obtained by act- each other by longitudinal fibers to form the
ing directly onto the motor neuron . Thus, two ganglionated cords called sympathetic
relaxation of the striated muscle is achieved trunks ( Fig. 9.1). The prevertebral ganglia are
not bv inhibiting the muscle directly but by irregular aggregations of cells found in the
inhibiting the motor neurons in the spinal mesenteric neural plexuses surrounding the
cord that excite the striated muscle. In con- abdominal aorta and its larger visceral
trast , smooth muscle typically receive in- branches. The terminal ganglia are parasym -
hibitory , as well as excitatory, inputs from pathetic and are located within, or close to,
different autonomic postganglionic neurons. the structures they innervate. These ganglia
This organization allows the autonomic ner- show extreme variations in size and compact-
vous system to respond to environmental ness. Some are organized into distinct,
changes in a highly ordered fashion. anatomically encapsulated structures, as in
the case of the sympathetic trunks and the au -
PRE - AND POSTGANGLIONIC NEURONS tonomic ganglia of the head. Others form ex-
tensive plexuses of nerve cells and fibers, as
The transmission of impulses from the in the intramural intestinal plexuses. Small
central nervous system to the viscera is disyn- ganglionic masses ( microganglia ) or scattered
aptic; it always involves two different neu - cell groups are found within , or near, the
rons ( Figs. 9.1 and 9.3). The first neuron , the walls of visceral structures (e.g., heart,
preganglionic neuron , is situated in the brain - bronchi, pancreas, and urinary bladder ).
stem or spinal cord and sends a thinly myeli- The outflow of preganglionic fibers from
nated fiber to an autonomic ganglion where it the central nervous system, which establishes
synapses with one or more postganglionic synaptic connections with peripheral auto-
cells. Preganglionic fibers of the cranial and nomic ganglia, arises from three well -defined
spinal nerves are approximately 3 p. m in di- regions. The cranial outflow originates from
ameter, have slow conduction velocities ( 3-15 visceral cell groups ( nuclei ) of the brainstem
m / sec ), and are designated as the B fibers of associated with the oculomotor ( N. Ill ), facial
peripheral nerves (91 ). The usually unmyeli- ( N . VII ), glossopharyngeal ( N . IX ), and vagus
nated axons of postganglionic neurons (auto- ( N. X ) nerves, and emerges from the brainstem
nomic ganglion cells) then pass to visceral ef - in association with these cranial nerves ( blue
fectors ( Fig. 10.23). Postganglionic autonomic in Fig. 9.1 ). These preganglionic fibers are
axons have smaller diameters (0.3-1.3 gm ), parasympathetic and terminate either in cra-
possess slower conduction velocities (0.7-2.3 nial autonomic ganglia ( ciliary, pterygopala-
m / sec), and are usually classified as C fibers tine, submandibular, or otic), or in terminal
in peripheral nerves (Tat>le 5.2 ). Therefore, ganglia within the walls of thoracic or abdomi-
even the simplest visceral reflex arc will in- nal viscera (e.g., heart, lungs, esophagus, and
volve at least three neurons: (a ) visceral affer- stomach ). The thoracolumbar outflow arises
ent , ( b ) preganglionic visceral efferent, and from cells of the intermediolateral cell column
(c) postganglionic visceral efferent ( Figs. 9.2 in all thoracic and the upper two or three lum-
and 10.23). Quantitative studies of midtho- bar spinal cord segments. The peripheral ax-
SYMPATHETIC PARASYMPATHETIC
Structure Preganglionic Cell Postganglionic Cell Preganglionic Cell Postganglionic Cell

Bodies in CNS Nuclei Bodies in Peripheral Bodies in CNS Nuclei Bodies in Peripheral
supplied Ganglia Ganglia
Iris of eye intermediolateral sup. cervical ganglion Edinger-Westphal ciliary ganglion

nuc. in cord segments and scattered along nuc. of midbrain
C8 T2 ( 3) carotid plexus
Lacrimal gland intermediolateral sup. and middle cervi- sup. salivatory nuc. pterygopalatine gan -
nuc. in cord segments cal symp. ganglia in pons glion
-
T1 2
Submandibular and intermediolateral sup. and middle cervi- sup. salivatory nuc. submandibular gan -
nuc. in cord segments cal symp. ganglia in pons glion
sublingual glands T1 - 3 ( 4 )
Parotid gland intermediolateral sup. and middle cervi - inf. salivatory nuc. in otic ganglion
nuc. in cord segments cal symp. ganglia medulla
-
T1 3 ( 4 )
Sweat glands of intermediolateral 3cervical sympathetic

nuc. in cord segments ganglia
head and neck T1 - 3
Lungs and intermediolateral inf. cervical and tho- dorsal motor nuc. N. ganglia of pulmonary
nuc. in cord segments racic (T1 - 5) symp. X plexi
bronchi T1 - 5 ganglia
Heart intermediolateral 3 cervical and thoracic dorsal motor nuc. N . intra -cardiac ganglia
nuc. in cord segments
T1 - 5 ( 6, 7)
-
(T1 6 ) symp. ganglia X of atria
Esophagus intermediolateral
nuc. in cord segments 4 -6 ganglia
-
thoracic Bymp. T( 1 3) dorsal motor nuc. N.
X
myenteric and sub
mucous plexi
-
T1 - 6
Stomach , small in - intermediolateral

nuc. in cord segments
celiac and sup .
mesenteric ganglia
dorsal motor nuc. N.
X
myenteric and sub-
mucous plexi
testine ; ascending
and transverse colon -
T5 11
Descending colon intermediolateral lumbar and inf. autonomic nuc. of ganglia of hemor -
nuc. in cord segments mesenteric symp. gan - intermediate gray in rhoidal myenteric and
and rectum T12 - L3 glia cord segments S2 - 4 submucous plexi
Sex organs intermediolateral lumbar, sacral and inf. autonomic nuc. of Ganglia along bran -
nuc. in cord segments mesenteric symp gan - intermediate gray in ches of aorta and int.
T10 - L2 glia cord segments S2 4 - iliac artenes
( e.g. ovarian , uterine )
intermediolateral lumbar and inf. autonomic nuc. of ganglia along visceral

Urinary bladder nuc. in cord segments mesenteric symp. gan - intermediate gray in branches of int. iliac
T12 - L2 glia cord segments S2 - 4 artery
Sweat glands and intermediolateral lumbar and sacral

blood vessels of nuc. in cord segments symp. ganglia
lower extremity LI - 2
Figure 9.3. Location of preganglionic and postganglionic autonomic neurons in relation to important visceral struc -
tures
onal processes of these cells form the pregan- nate upon cells in the paravertebral ganglia or
glionic sympathetic fibers which emerge from pass through the trunk to synapse in preverte-
the spinal cord via the ventral roots of the tho- bral ganglia ( Fig . 9.2) . Although the thora -
racic and upper lumbar spinal nerves ( red in columbar outflow arises from a cell column in
Fig . 9.1 ) . Peripherally, these fibers leave the a restricted region of the spinal cord (T1 to 13),
mixed spinal nerve and contribute to the it represents the total sympathetic output for
white rami communicantes , or communicating the entire body. This is possible because some
branches, which appear white because they preganglionic sympathetic fibers ascend and
are composed of myelinated fibers. The fibers descend in the sympathetic trunk for consider-
then enter the sympathetic trunk and termi- able distances before terminating upon post-
ganglionic neurons. The sacral outflow arises Experimental studies with powerful tract-
from preganglionic visceral neurons in the in- tracing techniques have revealed new infor-
termediate gray matter of the second, third, mation regarding the organization of the
and fourth sacral segments of the spinal cord. autonomic nervous system in different
These preganglionic parasympathetic fibers species. For example, studies with retrograde
emerge from sacral spinal segments via their tracers such as wheat germ agglutinin conju-
corresponding ventral roots and pass to termi- gated to HRP (WGA- HRP), cholera toxin sub-
nal ganglia within the walls of pelvic viscera unit B, or fluorogold , revealed with great de-
( blue in Fig. 9.1). tail the cellular origin of the sympathetic
Although preganglionic neurons are lo- innervation of various structures, including
cated in three distinct regions of the central the adrenal medulla and the aorticorenal gan-
nervous system, they are regrouped in two glion (65), the elbow and knee joints (131), the
main divisions: (a ) the sympathetic or thora- cornea (80), the spleen (105), and the lumbar
columbar system and (b) the parasympathetic or visceral nerves (7). Other studies have used
craniosacral system ( Figs. 9.1 and 9.2). In spite WGA- HRP as an anterograde tracer to label
of the restricted central origins of pregan- entirely the terminal plexus of sympathetic
glionic sympathetic and parasympathetic nerve fibers innervating the cerebral arterial
fibers, most viscera receive a double auto- system (58). This investigation has detected
nomic innervation. Notable exceptions are differences in the distribution pattern of the
the glands of the skin and peripheral blood nerve plexus. These differences appear clini-
vessels, which receive only a sympathetic in- cally relevant as they may account for the
nervation. Peripherally fibers of the two divi- variations in the strength and quality of the
sions of the autonomic nervous system often sympathetic-induced vasoconstriction at var-
are intermingled , but they retain their func- ious points along the cerebral arterial system
tional independence, which usually is antag- (58). Furthermore, the use of two different
onistic but closely integrated . The thora- retrograde tracers (double retrograde label-
columbar outflow provides sympathetic ing techniques; see Chapter 5), have revealed
innervation for all visceral structures of the that the sympathetic preganglionic neurons
body via synaptic articulations with postgan- are organized according to a highly ordered
glionic sympathetic neurons in peripheral au- pattern (65, 123). For example, despite their
tonomic ganglia. The cranial portion of the similar segmental distribution (T2 to L2 ), the
parasympathetic system supplies specific vis- preganglionic sympathetic neurons project-
ceral structures in the head via postgan- ing to the adrenal gland and the adjoining
glionic parasympathetic fibers from auto- aorticorenal ganglion belong to separate pop-
nomic ganglia, and thoracic and abdominal ulations (65). On the other hand , intracellular
viscera via the vagus nerve, and postgan- injections of HRP have provided detailed
glionic fibers from terminal ganglia. Pelvic views of the preganglionic sympathetic neu-
viscera are innervated by the parasympa- rons, particularly its dendritic tree (47).
thetic sacral outflow and postganglionic One of the most promising tools for the
fibers from terminal ganglia . anatomic study of the autonomic nervous
The investigation of the origin of auto- system, and perhaps of the central nervous
nomic preganglionic axons using horseradish system as well, is the pseudorabies virus,
peroxidase ( HRP) retrograde tracing methods which can be used as a retrograde transneu-
is leading to some revision of the classical ronal cell body marker (104, 119, 120). Results
view. For example, there is evidence that from recent studies designed to identify cen-
some sympathetic fibers to the small intestine tral nervous system cell groups regulating
arise in the cervical sympathetic ganglia and the sympathetic outflow to the adrenal gland
reach the gut by traveling in the vagus nerve in the rat exemplify the usefulness of this
(75). Where it was once thought that distinct marker (119, 120). When injected directly into
portions of the gut were innervated by vagal the adrenal medulla, the pseudorabies virus
and sacral parasympathetic fibers, it now ap- induces retrograde viral infections of the ipsi-
pears that there is overlap in the descending lateral sympathetic neurons (T4 to T13) and
colon and rectum (108). There is some species causes retrograde transneuronal cell body in-
difference in autonomic innervation of the fections in several areas of the brain, includ -
heart, the cornea and other peripheral struc- ing the caudal raphe nuclei, various portions
tures (30, 51, 80). of the medulla, and the paraventricular nu-
clous of the hypothalamus. In the spinal cord , This ganglion frequently fuses with the first
the segmental distribution of virally infected thoracic ganglion to form the stellate ganglion
neurons is the same as the retrograde cell la - ( Fig. 9.1 ). The stellate ganglion may extend
beling that can be observed following fluoro - up to 2.8 cm. In the thoracic, lumbar, and
gold injection in the adrenal medulla, except sacral regions, the ganglia are segmentally
that there is almost a 300% increase in the arranged . There are 11 or 12 thoracic, 3 or 4
number of labeled cells (120). Furthermore, lumbar, and 4 or 5 sacral ganglia . In the sacral
this retrograde labeling method can be easily portion, the two trunks gradually approach
combined with standard immunohistochemi - each other and fuse at the coccyx in the un -
cal procedures so that neurotransmitter(s) paired coccygeal ganglion. Sometimes, the
used by central neurons regulating the sym - stellate and all the thoracic ganglia down to
pathoadrenal outflow can be identified . In - the fourth segment are fused . The thoracic
deed , the combination of these two ap- and lumbar sympathetic ganglia are rela -
proaches has revealed that neurons in the tively small, each containing about 50,000-
medullary raphe nuclei that project to the 100,000 nerve cell bodies.
sympathetic preganglionic neurons innervat - The prevertebral ganglia are irregular gan -
ing the adrenal medulla display immunore- glionic masses lying in complex plexuses as-
activity for either serotonin, substance P, thy - sociated with the abdominal aorta and its
-
rotropin - releasing hormone, met enkephalin, major arterial branches. The largest preverte -
or somatostatin ( 120 ). Virally infected neu - bral ganglia are the paired celiac ganglia em -
rons lying in other portions of the medulla, or bedded within the celiac plexus, which sur-
in the hypothalamus, were found to be either rounds the proximal segment of the celiac
adrenergic or noradrenergic, while others artery and the root of the superior mesenteric
displayed immunoreactivity for neuropep- artery. The celiac ganglion has two major
tide Y, substance P, and somatostatin. Future poles, each about 20-25 mm by 10-15 mm,
studies with such powerful techniques and about 3-5 mm thick . Together, they con -
should greatly increase our knowledge of the tain approximately 1 ,800,000 cell bodies .
anatomic and functional organization of the Other prevertebral ganglia are the aorticore-
autonomic nervous system . nal, the phrenic and the superior and inferior
mesenteric. These ganglia are closely inter -
connected by numerous nerve fibers ( Fig. 9.1 )
SYMPATHETIC SYSTEM and are described in relation to the celiac and
Topographic Organization subsidiary plexuses.
The sympathetic ganglia receive pregan -
The sympathetic trunks are two ganglion - glionic fibers from the lateral horn of the
ated cords symmetrically placed along the spinal cord through the ventral roots of all
anterolateral aspects of the vertebral column the thoracic and the upper two lumbar nerves
that extend from the base of the skull to the (95, 114, 115 ). These fibers leave the ventral
coccyx. The cervical portion contains three roots, pass through the white rami communi-
ganglia formed by the fusion of the original cantes, and enter the sympathetic trunk to
eight segmental ganglia . The superior cervical reach either the paravertebral or prevertebral
ganglion , the largest of the paravertebral gan - ganglia . The fibers that terminate in the par -
glia, is situated near the second and third cer- avertebral sympathetic ganglia either end in
vical vertebrae. It is about 2.5-3.0 cm long the first one entered , or pass up or down in
and contains more than 1 million neurons the sympathetic trunk giving off collaterals,
(92). The small middle cervical ganglion is pre- and finally terminate in ganglia above or
sent only in about 60% of the individuals. It is below the level of their entrance ( Fig. 9.1 ).
about 0.7-0.8 cm long and lies near the sixth The preganglionic fibers from the upper five
cervical vertebra , just superior to the inferior thoracic segments pass mainly upward , those
thyroid artery. In some cases, the middle cer- from the middle thoracic segments ( T7 to
vical ganglion fuses to the inferior pole of the T10) pass up or down, while those of the low -
superior cervical ganglion to form a com- est thoracic and lumbar segments pass only
bined mediosuperior cervical ganglion up to downward . The preganglionic fibers that ter -
4.5 cm long (53). The inferior cervical ganglion minate in the prevertebral ganglia do not
lies at the lower border of the seventh cervi - synapse in the paravertebral ganglia, but
cal vertebra , behind the subclavian artery. merely pass through them and emerge as the
splanchnic nerves ( Figs. 9.1 and 9.2). While from the middle and inferior cervical ganglia ,
the sympathetic pathway from the spinal Additionally, the middle and inferior cervical
cord to the viscera always involves two neu - ganglia give off , respectively, the middle and
rons, there are never more than two. Thus, inferior cardiac nerves, which take part in the
synapses between pre- and postganglionic formation of the cardiac plexus ( Fig. 9.1 ).
neurons occur either in the paravertebral or
prevertebral ganglia, but not in both . Spinal Ganglia and Related Nerves
While the white rami communicantes are
limited to the thoracic and upper lumbar The thoracic, lumbar, and sacral ganglia
nerves, each spinal nerve receives a gray furnish gray rami to the remaining spinal
minus communicans from the sympathetic nerves. Delicate branches from the upper
trunk ( Fig. 9.2). The gray ramus consists of four or five thoracic ganglia go to the cardiac
unmyelinated postganglionic fibers which in- plexuses as the thoracic cardiac nerves. Other
nervate the blood vessels, arrector pili mus- fibers from the inferior cervical ganglion
cles, and glands of the body wall. The cervi- reach the pulmonary plexuses to innervate
cal sympathetic ganglia receive ascending the bronchial musculature and blood vessels
preganglionic fibers from the white rami of of the lungs ( Fig. 9.3). Shorter mediastinal
the upper thoracic nerves, most of which go branches from both the thoracic and lumbar
to the superior cervical ganglion. ganglia form plexuses around the thoracic
and abdominal aorta . In addition to these,
Cervical Ganglia and Related Fibers there are two, sometimes three, important
branches known as the splanchnic nerves
The superior cervical ganglion gives rise to which arise from the thoracic portion of the
postganglionic fibers distributed as gray rami sympathetic trunk, pierce the diaphragm,
to (a ) the lower four cranial nerves, ( b) the and terminate in the prevertebral ganglia of
upper three or four cervical nerves, (c) the the mesenteric plexuses ( Fig. 9.1). Although
pharynx, (d ) the external and internal carotid the splanchnic nerves appear to be branches
arteries, and (e ) the superior cervical cardiac of thoracic ganglia, they represent axons of
nerve. Postganglionic sympathetic fibers preganglionic neurons which merely pass
passing to the external and internal carotid through paravertebral ganglia and the sym-
arteries form plexuses about these vessels pathetic trunk en route to the celiac and
and their branches (83). From these vascular mesenteric ganglia . Thus, the splanchnic
plexuses the postganglionic fibers pass nerves correspond to white rami communi -
through cranial autonomic ganglia to join cantes. The greater splanchnic nerve arises by
branches of the cranial nerves. Such sympa- roots from the fifth to the ninth thoracic gan -
thetic postganglionic fibers supply the dilator glia and goes to the celiac plexus. The lesser
muscle of the iris, the smooth muscle portion splanchnic nerve usually arises by two roots
of the levator palpebrae, the orbital muscle of from the tenth and eleventh ganglia , and ei-
Miiller, the blood vessels, sweat glands, hair ther unites with the greater splanchnic, or
of the head and face, and the lacrimal and continues as an independent nerve to that
salivary glands ( Fig. 9.3). The superior cervi- portion of the celiac plexus which surrounds
cal cardiac nerve passes to the cardiac plexus. the roots of the renal arteries and terminates
The middle cervical ganglion , when present, in the aorticorenal ganglion (83). The smallest
supplies gray rami to cervical nerves C5 and splanchnic nerve, when present , arises from
C6, and sometimes also to C4 and C7, and the last thoracic ganglion and goes to the
contribute to the esophageal, tracheal, and renal plexus. Often this nerve is represented
aortic plexuses. When this ganglion is absent by a branch from the lesser splanchnic nerve.
the cervical spinal nerves C5 and C6 receive The celiac plexus , the largest of all auto-
gray rami from the sympathetic trunk. nomic plexuses, surrounds the celiac and su -
The inferior comical ganglion furnishes gray perior mesenteric arteries. This asymmetric
rami to spinal nerves C7, C8, and T1 ( Fig. paired plexus extends cranially to the di -
9.3). Thus a single ganglion may supply two aphragm, caudally to the renal arteries and
or more of the lower cervical nerves, and a laterally to the suprarenal bodies. It becomes
single nerve may be supplied by two ganglia , continuous below with the abdominal aortic
Potts (96) has found that the lower four cervi- plexuses. From the main plexus, paired and
cal nerves may each receive three gray rami unpaired subsidiary plexuses are given off
derived from the sympathetic trunk, and which accompany the branches of the celiac
and superior mesenteric arteries as well as Cranial Region

other branches of the abdominal aorta . The
paired plexuses include the phrenic, supra- Central neurons whose axons form
renal, and spermatic (or ovarian ) plexuses. parasympathetic preganglionic fibers of cra -
The gastric, hepatic, splenic, and superior nial nerves VII, IX, and X in the rodent brain
mesenteric plexuses are unpaired . Within the have been analyzed using retrograde tracing
celiac plexus are found two relatively large methods (31 ). The preganglionic cell bodies
ganglionic masses, the celiac ganglia , lying on form a column extending from the level just
either side of the celiac artery and connected below the obex to the level of the seventh cra -
with each other by delicate fiber strands. Oc- nial nerve in the pons. The column is rather
casionally, the two may be so close as to form compact and is located medial to the nucleus
a single unpaired ganglion encircling the of the solitary tract and dorsolateral to the hy-
artery. Other ganglionic masses found in the poglossal nucleus. At more rostral levels, the
plexus include the paired aorticorenal gan - cell column is located progressively more lat -
glia and the superior mesenteric ganglion lying erally until the level of the facial nucleus. One
near the roots of their respective arteries. All group of cells sending axons in the greater
these ganglia receive preganglionic fibers superficial petrosal nerve ( lacrimal neurons)
from the splanchnic nerves. is located lateral to the facial nucleus while
Caudally the celiac plexus becomes contin - neurons sending axons to the chorda tympani
uous with the abdominal aortic plexuses nerve or the otic ganglion are distributed
lying on either side of the aorta . From these more widely through the lateral tegmentum
plexuses nerve strands pass to the root of the at the pontomedullary junction ( 31 ).
inferior mesenteric artery and form the infe- In the cranial region four ganglia are re-
rior mesenteric plexus, which surrounds that lated topographically to the branches of the
artery and its branches. Within this plexus, trigeminal nerve ( Fig. 9.1 ). The ciliary ganglion
-
and lying close to the root of the artery, is an lying against the lateral surface of the optic
other prevertebral ganglionic mass, the infe - nerve receives preganglionic fibers from the
rior mesenteric ganglion ( Figs. 9.1 and 9.11 ). visceral nuclei of the oculomotor complex ( N.
Further caudally, the abdominal aortic Ill ) and sends postganglionic fibers ( short cil -
plexuses are continued into the unpaired hy- iary nerves) to the sphincter of the iris and
pogastric or pelvic plexus , which also receives the smooth muscle of the ciliary body. The
strands from the inferior mesenteric plexus. pterygopalatine ganglion , in the pterygopala -
On entering the pelvis the plexus breaks up tine fossa, and the submandibular ganglion ,
into a number of subsidiary plexuses adjacent lying over the submandibular gland , receive
to the rectum , bladder, and accessory genital fibers from the superior salivatory nucleus
organs ( Figs. 9.9 and 9.11 ). The preganglionic via the intermediate portion of the facial
fibers supplying the pelvic organs come from nerve ( N. VII ) ( Figs. 9.1 and 13.23). The pre-
the white rami of the two upper lumbar ganglionic fibers pass by way of the major
nerves and from the lowest thoracic nerve. petrosal nerve to the pterygopalatine gan -
They pass through the corresponding ganglia glion , and by way of the chorda tympani
of the sympathetic trunk , and terminate in nerve to the submandibular ganglion . The
the inferior mesenteric ganglion ( Fig. 9.1 ). latter usually is broken into submandibular
The cells of this ganglion then send their and sublingual portions. The pterygopalatine
postganglionic axons by way of the inferior ganglion sends postganglionic fibers to the
mesenteric and hypogastric plexuses to the lacrimal glands and to the blood vessels and
pelvic viscera ( Fig. 9.11 ). glands of the mucous membranes of the nose
and palate. Postganglionic fibers from the
PARASYMPATHETIC SYSTEM submandibular ganglion go to the sub-
mandibular and sublingual salivary glands
The preganglionic fibers of the cranio - and also to the mucous membranes of the
sacral division form synaptic relations with floor of the mouth . The otic ganglion is situ -
postganglionic neurons in cranial autonomic, ated medial to the mandibular nerve as it
or terminal, ganglia . Thus, most parasympa- leaves the oval foramen . It receives pregan-
thetic preganglionic fibers are longer than the glionic fibers from the inferior salivatory nu -
sympathetic preganglionic fibers, which ter- cleus of the glossopharyngeal nerve ( N . IX )
minate in the more proximal paravertebral by way of the minor petrosal nerve and sends
and prevertebral ganglia . postganglionic fibers to the parotid gland
( Fig. 9.1 ). All of these cranial autonomic gan- recording variations in the tension of the gut
glia receive sympathetic fibers from the supe- wall and the chemical environment, as well
rior cervical ganglion, passing by way of the as interneurons and motor neurons that con-
internal and external carotid plexuses. These trol the muscles of the gut wall, together with
fibers do not synapse with the ganglionic the vasculature and the secretory activity of
cells, but merely pass through the cranial the mucosa (48). Although the activity of the
parasympathetic ganglia to furnish sympa- enteric neurons can be modified by inputs
thetic innervation to blood vessels, smooth from the central nervous system, much of the
muscle and glands. control of the gastrointestinal function can be
The largest source of preganglionic achieved by the enteric system independent
parasympathetic fibers is the dorsal motor of central influences. The complex intrinsic
nucleus of the vagus nerve ( N . X ), which sup- neuronal circuits of the enteric system regu -
plies practically all the thoracic and abdomi- late gastrointestinal motility, mucosal secre-
nal viscera except those in the pelvic region tion and absorption , and local blood flow,
( Figs. 9.1, 9.3, and 12.21 ). In the thorax, these largely as a result of activating intrinsic re-
preganglionic fibers enter the pulmonary, flexes (53). As such , the enteric system plays a
cardiac, and esophageal plexuses to be dis- crucial role in the maintenance of homeosta-
tributed to the terminal ( intrinsic) ganglia of sis. It is important to realize that enteric neu -
the heart and bronchial musculature. Short rons outnumber by far all the rest of the auto-
postganglionic fibers then go to the heart and nomic neurons. There are probably over 100
bronchial muscle. In the abdomen, the para- million neurons in the enteric system of hu -
sympathetic fibers of the vagus nerve go to mans (49, 52, 66). Furthermore, the anatomic
the stomach, and pass through the celiac and and functional complexity of the enteric ner-
its subsidiary plexuses, to end in the terminal vous system is second only to the central ner-
ganglia of the intestine, liver, pancreas, and vous system (53). Most enteric neurons are
probably the kidneys. In the gastrointestinal multipolar. Some have relatively short den-
tract, these terminal ganglia form the exten- drites with irregular shapes and a prominent
sive ganglionated plexuses of Auerbach axon ( type I neurons of Dogiel), whereas oth-
( myenteric) and of Meissner (submucosal ), ers have several long processes which cannot
which are part of the enteric system (dis- be identified easily as axons or dendrites
cussed later ). The alimentary innervation of ( type II neurons of Dogiel ) (53). Numerous
the vagus extends as far as the descending putative neurotransmitters have been local-
colon ( Figs. 9.1 and 9.3). ized in the different classes of enteric neu-
rons. These transmitters, which include
Sacral Region acetylcholine, a vast array of neuroactive
peptides, and probably serotonin and y -
The sacral preganglionic parasympathetic aminobutyric acid (GABA ), are colocalized in
fibers exit from the spinal cord via the sec - combinations that are specific for particular
ond , third , and fourth sacral nerves which populations of neurons with well-defined
form the pelvic nerve ( N. erigentes) and go to shapes, projections, and functions (39, 49, 53).
the terminal ganglia of the pelvic plexuses, as Interestingly, the enteric nervous system
well as to the myenteric and submucosal shares some neuroactive peptides with the
plexuses of the descending colon and rectum central nervous system. Such "brain-gut"
( Fig. 9.1 ). Postganglionic fibers from terminal peptides include cholecystokinin, vasoactive
ganglia supply the urinary bladder, descend- intestinal peptide, substance P, neurotensin,
ing colon, rectum, and accessory reproduc - and somatostatin (see Chapter 5).
tive organs. These sacral parasympathetic The neurons of the enteric system are
fibers innervate viscera not supplied by the arranged in interconnected plexuses that ex-
vagus nerve ( N . X ) ( Figs. 9.3 and 9.11). tend over much of the gastrointestinal tract
and also invest the pancreas and the gall
ENTERIC SYSTEM bladder. The plexuses, which comprise gan-
glia and interconnecting nerve fibers, are sit-
The enteric system is a highly complex uated between the various layers of muscle
neuronal network extending over the full ex- and endothelium. The two major intrinsic
tent of the gastrointestinal tract. It is com- plexuses are the myenteric (or Auerbach's)
posed of local sensory neurons capable of and the submucous (or Meissner's) plexuses.
The myenteric plexus lies between the exter - VISCERAL AFFERENT FIBERS
nal longitudinal and circular smooth muscle
layers while the submucosal plexus lies There are numerous receptors in the vis-
within the connective tissue of the submu - cera whose afferent fibers, myelinated or un-
cosa between the circular muscle and the mu - myelinated, travel centrally by way of the
cosa ( Fig. 9.4 ). Although the myenteric plexus autonomic nerves, both sympathetic and
extends virtually the full length of the gas- parasympathetic. The largest myelinated fi -
trointestinal tract, the submucosal ganglia are bers come principally from Pacinian corpus-
rare or absent in the esophagus and stomach . cles, while the smaller myelinated and the
The enteric system is regulated to some ex - unmyelinated ones come from the more nu -
tent by parasympathetic and sympathetic in - merous diffuse visceral receptors ( Fig. 7.4 ).
puts. Parasympathetic preganglionic neurons Sensory fibers from the thoracic, abdominal,
project directly to enteric ganglia of the stom - and pelvic viscera traverse sympathetic and
ach , colon , and rectum through the vagus splanchnic nerves to reach the sympathetic
and the pelvic splanchnic nerves. The sympa - trunk. They pass uninterrupted through the
thetic input comes principally from the post - trunk and white communicating rami to their
ganglionic fibers of the prevertebral sympa
thetic ganglia and , to a lesser extent , the
- perikarya of origin in the dorsal root ganglia
( Figs. 9.2, 9.11, and 10.23) . The parasympa -
cervical paravertebral chain . These ganglia thetic nerves likewise contain many visceral
project to plexuses embedded in the wall of afferent fibers. The visceral afferent fibers of
the stomach, the small intestine, and the the vagus nerve, whose cell bodies are in the
colon. This extrinsic innervation of the gut by inferior ( nodose) ganglion, and are distrib-
the parasympathetic and sympathetic compo- uted peripherally to the heart, lungs, and
nents of the autonomous nervous system pro- other viscera . Similar fibers from the bladder,
vides a second level of control of motility and rectum, and accessory genital organs pass by
secretion , but also can override intrinsic en- way of the pelvic nerves and enter the spinal
teric activity in cases of emergency or stress. cord through the second , third , and fourth
Mesentery
Submucous
plexus
Mucosal — Deep muscular

plexus plexus
Figure 9.4 . Cross-section through the intestinal wall showing the location of the mucosal, submucosal, and myen-
teric plexuses, which form the essential portion of the enteric nervous system The nerve fibers are black and the
blood vessels are white. The insert provides a more detailed view of this highly complex neuronal network .
304 Section ill Peripheral Nervous System
sacral dorsal roots ( Fig. 9.11 ). Their cell bod - ferent neurons does not enter the cord
ies are located in corresponding sacral spinal through the dorsal root . Instead, the axon
ganglia . Visceral sensory fibers from the blad - takes a recurrent course and enters the ven-
der also enter the spinal cord through the tral root, finally terminating in the gray mat-
lower thoracic and lumbar spinal nerves ( Fig. ter of the spinal cord (see Chapter 8). About
9.11 ). The sacral visceral afferent fibers, one-third of the ventral root afferent fibers
which convey impulses from stretch recep - carry information from somatic structures,
tors in the wall of the urinary bladder, play a while the remaining two- thirds are visceral
dominant role both in reflex control and the sensory afferents with receptive fields in the
mediation of vesical pain impulses. These af - lower bowel and pelvis ( 26, 27, 135).
ferents accompany the sacral parasympa -
thetic outflow and convey the sensory im - STRUCTURE OF AUTONOMIC GANGLIA
pulses that signal bladder distension. The
sensation of a distended bladder is abolished The autonomic ganglia are aggregations of
by anesthetic block of the pelvic nerves, re- multipolar neurons of varying size and
section of these nerves, or the cutting of dor- shape, each surrounded by a loosely orga-
sal roots S2, S3, and S4. Visceral afferents nized connective tissue capsule. Trabeculae
from the bladder and adjacent viscera which extending from the capsule form an internal
ascend to the lumbar and lower thoracic dor- framework which contains numerous, often
sal root ganglia appear to play a minor role in pigmented , perikarya, between which are ir-
the regulation of the bladder. Resection of the regular plexuses of myelinated and unmyeli-
presacral nerve and hypogastric plexus in hu- nated fibers ( Fig. 9.5). Besides these ganglia ,
mans produces little or no alteration of vesi- isolated autonomic cells or nonencapsulated
cal function. aggregations of such cells are found widely
The afferent visceral fibers are important distributed throughout the viscera .
in the initiation of various visceral and vis - The diameter of autonomic cells ranges
cerosomatic reflexes mediated through the from 20-60 gm, and the number and length
spinal cord and brainstem. Many of these re- of their branching dendrites is exceeding
actions remain at a subconscious level, but af - variable. The morphology of the dendritic
ferent impulses also give rise to visceral pain tree of autonomic ganglia neurons has been
or distress, nausea , hunger, and other poorly studied in detail in recent studies making use
localized visceral sensations. It is the constant of intracellular HRP injections ( 47). There
stream of afferent visceral impulses that is re - may be as few as 3 or 4 on some perikarya,
sponsible for the general feeling of internal and as many as 20 on others. In the thoracic
well-being or of malaise. segments of the rat, the average total den-
Visceral pain from most abdominal and dritic length for preganglionic sympathetic
pelvic organs is carried chiefly by the sympa- neurons is 2343 gm (47). In humans, the
thetic nerves. Vagal sensory fibers are con- number of dendrites and their degree of
cerned with specific visceromotor, vasomo- branching increase with age. The cell bodies
tor, and secretory reflexes, most of which do have a clear ovoid, and often eccentric, nu -
not reach consciousness. It should be recalled cleus, delicate neurofibrils, and fine chro-
that pain carried by visceral afferent fibers mophilic bodies. Binucleated or even multi -
from diseased or inflamed organs may be "re- nucleated cells are not uncommon . Most of
ferred " to skin areas supplied by somatic af - the cells are surrounded by cellular capsules
ferent fibers of the same segment (see Chap- that share some similarities with those sur-
ter 8). The sense of taste is mediated by rounding spinal ganglion cells ( Figs. 5.10 and
afferent fibers of the vagus, glossopharyn- 8.2 ). Electron microscopic studies of auto-
geal, and facial nerves, while impulses giving nomic ganglion cells reveal large pigmented
rise to the sensation of hunger probably are granules, numerous small dense bodies, and
carried by the vagus. the usual perikaryonal components. Neu -
Up to 30% of the axons in lower lumbar ronal processes are readily identified as they
and upper sacral ventral roots in some spinal emerge from cells or, when viewed without
cord segments are unmyelinated afferent this continuity, by the striking number of
fibers . The cell bodies of these axons are lo- synaptic and presynaptic junctions with
cated in the dorsal root ganglion. Unlike most which they are studded (59, 94). Synapses di-
sensory fibers, the central process of these af - rectly on the nerve cell bodies are rare.
Figure 9.5. Adult human sympathetic neurons. Interdigitating dendrites often form a complex pericellular plexus.
Perikarya frequently show eccentric nuclei, melanin granules (m), and lipofuscin granules ( L ) . The nuclei of the cap-
.
sule cells are not stained (Ramdn y Cajal silver stain x 490) .
Processes filled with Nissl substance, mito- from the proximal portion of a large dendrite
chondria, large inclusion bodies, and pig- and do not emit collaterals within the ganglia .
ment particles usually are considered to be Preganglionic fibers end in synaptic rela -
dendrites. Neuronal processes containing tion with dendrites of many postganglionic
only neurofilaments and some smooth vesi - cells (99) ( Fig. 9.6 B ). They branch repeatedly
cles are regarded as axons, but the distinction within the ganglion and form pericellular ar -
between dendrites and axons on the basis of borizations. Some of the terminals contain
the presence or absence of Nissl substance is neurofibrillary rings or loops. More common
not easy to make. Furthermore there are no are the axodendritic synapses where the pre-
reliable morphologic criteria for distinguish - ganglionic fibers end in diffuse arborizations
ing between cells and fibers belonging to the about the intracapsular and extracapsular
sympathetic and parasympathetic systems. dendrites. These ganglia are not simple relays
Some of the cells have short dendrites transmitting impulses between preganglionic
which ramify within the capsules. These are and postganglionic neurons ( 62). Small cells
numerous in the autonomic ganglia of hu - interpreted as internuncial neurons have
mans ( Fig. 9.5). Others have long, slender been described (133). Depending upon the
dendrites which pierce the capsule and run species examined , these interneurons contain
for varying distances in the intercellular dopamine or norepinephrine. When visual-
plexuses. Still other cells possess both short -
ized with the paraformaldehyde or glyoxylic
and long processes. The long dendrites may acid -induced fluorescence techniques (see
branch considerably and bear varicose termi- Chapter 5), the cell fluoresces brightly. Con -
nations that form "dendritic nests" enclosing sequently these intemeurons are known as
other ganglion cells within a single capsule. small, intensely fluorescent, or SIF, cells ( 134 ).
Commonly, the long branching dendrites The capsule cells of the autonomic ganglia
from several nearby cells intermingle to form are known to contain a variety of enzymes ( 1,
complex "dendritic glomeruli" (98) ( Fig. 124 ). They are considered as homologous to
9.6A ). Such cells probably receive common the oligodendrocytes by Schwyn ( 111 ), to
terminal arborizations of preganglionic fibers. satellite and Schwann cells of dorsal root gan -
The shorter dendrites usually end as fine ta- glia by Barton and Causey (9), or as connec -
pering processes, but often terminate with tive tissue fibroblasts and interstitial cells.
bulbous expansions (53). Axons usually arise These supportive cells show a marked hyper -
Preganglionic
Capsule
oy. fibers
; Axon I
Glomerulus
;( 0 ): Postganglionic
fibers
A B
Figure 9.6. A. Glomerulus formed by dendrites of two sympathetic ganglion cells B. Relationship between pregan-
glionic fibers and sympathetic ganglion cells. One preganglionic fiber may come into synaptic relationships with sev-
eral sympathetic postganglionic cells
plasia following stimulation of the pregan- tion, which we can no longer regard as corre-
glionic fibers for periods of 105-180 minutes sponding to their anatomical origin , 1 suggested
( 111 ). Thus, like neuroglia in the central ner- the term 'cholinergic' to describe those which
vous system (see Chapter 7), these cells are transmit their action by release of acetylcholine,
likely to play a role that is much more com- and 'adrenergic' for those which employ a sub-
stance resembling adrenaline" (36).
plex than that of simple supportive tissue.
Nerve impulses conveyed by cholinergic
CHEMICAL ANATOMY fibers produce rapid , localized responses of
short duration in postjunctional effectors.
Cholinergic Transmission Acetylcholine ( ACh ) is the transmitter at vari-
The investigations of Dale ( 35), Loewi ( 72, ous peripheral junctions, including the neu -
73), Cannon ( 19 ), and many others demon- romuscular junction, but does not always
strated that autonomic effects are mediated have the same physiologic effect on the post -
by transmitter molecules that are liberated at synaptic membrane. This is due to the exis-
preganglionic and postganglionic nerve ter- tence of two different postjunctional receptor
minals. The principal transmitter molecule in molecules to which ACh can bind to initiate a
the autonomic nervous system is acetyl - postsynaptic response. The action of ACh on
choline ( ACh ). This small-molecule transmit- one type of receptor is mimicked by the drug
ter acts in conjunction with one or more nicotine and on the other by the drug mus-
neuroactive peptides. It is present in all carine; hence, the two receptor types are
preganglionic autonomic fibers, all postgan- called nicotinic and muscarinic ( see Chapter
5). Atropine blocks all muscarinic responses
glionic parasympathetic fibers, and in post - to ACh and related cholinomimetic drugs.
ganglionic sympathetic nerve fibers innervat-
ing sweat glands. Norepinephrine ( NE ) is the Nicotinic receptors in autonomic ganglia and
principal small-molecule transmitter in post - skeletal muscle are not identical in that
ganglionic sympathetic neurons, except those tetraethylammonium and hexamethonium
destined to the sweat glands. Dale was the selectively block ganglionic transmission , and
first investigator to propose a functional clas - -
d tubocurarine blocks transmission at both
sification of neurons based on their chemo- the somatic motor end plates and at auto-
specificity: nomic ganglia , although its action at the
motor end plate predominates. These differ -
"Feeling the need of terms to describe nerve- fi- ences could be related to the fact that, unlike
bres, or their impulses, in terms of a chemical func- the ACh receptors of skeletal muscle, neu -
ronal ACh receptors contain only two types newly synthesized enzyme is then trans-
of subunits, termed alpha (« ) and beta ( (}). ported throughout neuronal processes. This
Expression of different combinations of the feature allowed the development of a phar-
several neuronal a -subunits with any of the macohistochemical procedure that improves
different p-subunits are likely to result in the visualization of AChE-containing neu -
ACh receptor-channels with distinct conduc- rons, particularly in those regions of the brain
tance, kinetics, and pharmacology.
Stimulation of presynaptic fibers destined
-
where intense AChE positive neuropil tends
to obscure the neuronal somata and proximal
to an autonomic ganglia induces the release processes (16, 90 ).
of ACh and evokes a fast excitatory synaptic A monoclonal antibody was raised against
potential ( EPSP) that is mediated by nicotinic neural AChE (13). When injected systemi-
receptors. This fast EPSP is often large cally in rats, this antibody causes a perma -
enough to generate an action potential in the nent destruction of presynaptic fibers in
postganglionic neuron . In addition to the fast sympathetic ganglia and adrenal medulla .
nicotinic excitation, all sympathetic, and This results in a syndrome consisting of pto-
some parasympathetic ganglia exhibit slow sis, hypotension , and bradycardia . In sympa-
synaptic potentials that can modulate the fir- thetic ganglia , AChE activity disappears
ing of the principal neurons. There is a slow from the neuropil but not from nerve cell
EPSP and a slow IPSP ( inhibitory postsynap- bodies. Ultrastructurally defined synapses
tic potential ) mediated by ACh , and a slow and ChAT activity are also lost at the gan-
EPSP mediated by peptides. The slow ACh - glionic level . Electrical stimulation of presy-
mediated EPSP is produced by muscarinic re- naptic fibers to the superior cervical ganglion
ceptors opening NA and Ca 2 channels
'
ceases to evoke end organ responses. On the
while closing the K * channel. The slow ACh- other hand , direct ganglionic stimulation re-
mediated IPSP is produced by activation of mains effective, and the postsynaptic adren-
muscarinic receptors that open K + channels. ergic system appears intact . Motor perfor-
This inhibition does not suppress action po- mance and ChAT content of skeletal muscle
tentials elicited by fast nicotinic EPSPs but in- are preserved , as is parasympathetic ( vagal )
hibits repetitive firing initiated by the slow function (13). This new animal model of se-
peptidergic EPSP (39 ). lective cholinergic autoimmunity is a novel
At cholinergic junctions a specialized en- and potent tool for autonomic physiology,
zyme, acetylcholinesterase ( AChE ), which read- and may be relevant to the pathogenesis of
ily hydrolyzes free acetylcholine to choline various human disorders involving the auto-
and acetate, is found in both the synaptic ter- nomic nervous system .
minal and in the postsynaptic cell . Thus,
AChE serves to terminate the transmitter ac- Adrenergic Transmission
tion of ACh at postsynaptic sites and at effec-
tor junctions. Drugs which inhibit or inacti- The majority of postganglionic sympa -
vate AChE cause ACh to accumulate at thetic nerves release noradrenaline ( nor-
cholinergic sites and produce effects equiva - epinephrine, NE ) and are classified as
lent to continuous stimulation of cholinergic noradrenergic, although the older term,
fibers. Physostigmine ( eserine) and neostig- adrenergic, is still widely used ( 20, 21, 32, 77,
mine are "reversible" anticholinesterase 88, 126, 127). The widespread distribution of
drugs useful in treating myasthenia gravis, sympathetic nerves and the demonstration of
glaucoma , and atony of smooth muscle. monoaminergic neurons in the central ner-
Anticholinesterase compounds of the "irre- vous system suggest that monoaminergic
versible" type, such as those of the organ- mechanisms are important. The paraformal -
-
ophosphate group (e.g., di isopropyl fluoro-
phosphate, DFP) form the basis for "nerve
dehyde-induced fluorescence histochemical
method ( 44, 45), and , more recently, the
gases," which are among the most potent immunohistochemical procedures, allow
synthetic toxic agents known (68). Recov- anatomic localization of monoamines and in -
ery of neuronal AChE activity after intoxi- vestigations of problems related to the syn-
cation with DFP or similar drugs occurs thesis, storage, release, and metabolism of the
primarily, if not exclusively, by synthesis of amines in neurons and their terminals ( Figs.
new enzyme molecules. Such de novo synthe- 5.19, 9.7, 13.35, and 14.20 ). Pioneering obser -
sis takes place first in the cell body, and the vations with the histofluorescence method
have indicated that in postganglionic sympa- formed in the cell body, transported periph-
thetic nerves, NE is present not only in erally in the axon, and stored in terminal
synaptic terminals, but in the entire sympa - varicosities (32-34, 88).
thetic neuron ( 43, 88, 126, 127). The noradren - It is important to realize that NE axonal
ergic fibers are markedly varicose and each varicosities in the autonomic nervous system
varicosity appears to be enriched with NE. do not display the usual synaptic junctional
Axonal varicosities form a ground plexus in features typical of central nervous system
close contact with effector cells, and , accord - synapses (see Chapter 5). This phenomenon
ing to Hillarp (61 ), the transmitter is released suggests that NE released from axonal vari -
along the entire length of the terminals cosities may diffuse over a rather large terri-
( Fig. 9.7 ). tory and can influence vast neuronal popula-
Evidence indicates that the norepineph- tions. Interestingly, noradrenergic fibers in
rine content of the terminals can be depleted certain brain areas also appear to lack junc-
by electrical stimulation (79, 88). Thus, there tional specializations (10, 112). It is presumed
is little doubt that the varicosities are special- that such central noradrenergic fibers exert a
ized structures involved in the storage and rather diffuse influence over large neuronal
release of the transmitter . Histochemical assemblies in a manner similar to that found
studies have shown that the transmitter is in the autonomic nervous system.
stored in special granules within the adrener- In the adrenal medulla the release of ACh
gic neurons and electron microscopic obser- by preganglionic sympathetic fibers and its
vations indicate that the small "dense-cored " combination with receptors on chromaffin
vesicles ( Figs. 9.7 and 9.8) are the storage cells is followed by the liberation of epineph -
granules (128, 136, 139 ). In addition to NE, rine into the extracellular fluid which ulti -
these storage vesicles contain dopamine- (i- mately enters the circulation. Osmophilic
hydroxylase, ATP, and a characteristic-bind - granules have been isolated from the adrenal
ing protein termed chromogranin (32 ). These medulla which contain high concentrations of
storage granules have several functions: (a ) catecholamines and collectively represent a
they bind and store NE, thereby retarding its major storage site of epinephrine.
diffusion out of the neuron and protecting it The adrenergic neuron also contains
from degradation by monoamine oxidase, (b) mechanisms for the inactivation of the trans-
they serve as a depot of NE that may be re- mitter substance, but these are not as rapid
leased following appropriate stimuli, and (c) and efficient as those involved in the break-
they oxidize dopamine to NE ( 32 ). All parts down of ACh. Monoamine oxidase ( MAO ) is
of the sympathetic noradrenergic neuron con- an intraneuronal enzyme involved in regulat -
tain norepinephrine, but the terminals con- ing the amine level within the neuron ( 22).
tain the highest concentrations (126). Trans- The adrenergic transmitter released at synap-
mitter granules in adrenergic neurons are tic junctions is inactivated by several mecha-
nisms: (a ) diffusion, ( b) the enzyme catechol-
- -
o methyl transferase (COMT), which occurs
extraneuronally, and (c) binding to extraneu-
ronal sites not involved in nerve conduction .
The inactivating mechanism of greatest phys-
iological importance is the powerful trans -
mitter reuptake mechanism present at adren-
ergic terminals. This uptake occurs at the
neuronal cell membrane by an active mecha-
nism involving specific transporter enzymes.
It is of historic interest to note that NE was
the first monoamine for which a presynaptic
transporter system was implicated in neuro-
transmission (4), and that 20 years later the
human NE transporter was the first
monoamine transporter to be cloned (89 ).
Figure 9.7. Normal rat iris. Strands of the adrenergic
ground plexus over the dilator muscle are demonstrated
Monoamine transporters play a crucial role in
by formaldehyde-induced fluorescent technique. Sev- the regulation of monoaminergic transmis-
eral axons are markedly varicose ( x 250) sion . Additionally, monoamine transporters
4* X *i £ J
/
•
HI
Figure 9.8. A . A noradrenergic axon from the enteric nervous system of a mouse The tissue has been fixed with
NaMn04 to specifically reveal this axonal subtype. Note that the axon is varicose. Two varicosities appear in the field.
Varicosities are thought to be points where neurotransmitter is released They are distinguished by their swollen ap-
pearance and content of 50 nm synaptic vesicles that, after permanganate fixation, contain characteristic dense
cores Note that the varicosities seem to lack synaptic membrane specializations and that no preferential distribution
of synaptic vesicles or an active zone can be discerned. The varicosities also contain accumulations of mitochondria.
The narrow intervaricose segment between the two varicosities contains few organelles, and no synaptic vesicles or
mitochondria. At the lower right , the noradrenergic terminal appears to end on the basal lamina that surrounds this
portion of the enteric nervous system and that separates it from the smooth muscle of the gut ( x 28,600) B ( inset ) A
,
section through a noradrenergic varicosity is shown . The tissue was fixed with NaMnO. 1 hour following injection of a
mouse with the neurotoxin, 6-hydroxydopamme Noradrenergic axons actively take up and concentrate norepi-
nephrine 6-Hydroxydopamine is specifically taken up and concentrated by these axons because its chemical struc -
ture resembles that of norepinephrine sufficiently well for it to be subject of the norepinephrine transport mechanism.
The 50 nm dense cored vesicles permit the varicosity to be identified as noradrenergic . The accumulation of dense
material in the cytosol of the varicosity is an early degenerative change due to uptake of 6-hydroxydopamine Note
that the varicosity is apposed to the basal lamina. This is typical of autonomic postganglionic axon terminals and
makes it necessary for the transmitter to act across a wide synaptic gap
appear to be major action sites of drugs such can we suppose that the discovery and identifica-
as cocaine and antidepressants. Thus, the -
tion of a chemical transmitter of axon reflex va-
study of these molecules furthers our knowl- sodilatation would furnish a hint as to the nature
edge of the complex mechanisms involved in of the transmission process at a central synapse?
neurotransmission , and helps elucidate the -
The possibility has at least some value as a stimu
lus to further experiment" (36).
molecular basis of addictive and mental dis-
orders. This generalization was formulated as a
Smooth muscle can be either excited or in- principle in 1957 by Sir John Eccles who was
hibited by norepinephrine or epinephrine, studying the spinal motor neuron, which was
depending upon the site of action and the then known to form a cholinergic synapse at
concentration of the transmitter. Norepineph- the neuromuscular junction. Eccles correctly
rine excites smooth muscle, isoproterenol in- predicted , on the basis of Dale's works on au-
hibits smooth muscle, and epinephrine can tonomic cholinergic and adrenergic neurons,
both excite and inhibit . Ahlquist (2) postu - that the synapse formed by the recurrent col-
lated two types of adrenergic receptors: «-re- lateral of the same spinal motor neuron onto
ceptors associated with excitatory responses the Renshaw cell of the spinal cord would
and (3-receptors associated with inhibition. also be cholinergic. Since most of the neurons
There are two major exceptions to this: (a ) examined at that time were found to use only
stimulation of (3- receptors in cardiac muscle one transmitter, Dale's principle was inter-
produces excitatory effects and ( b ) stimula - preted to mean that neurons use only one
tion of either u - or (3- receptors in the gastroin- transmitter molecule. However, developing
testinal tract produces inhibitory responses neurons have been shown to synthesize and
that are additive. Synthetic compounds release more than one transmitter. Further-
which structurally resemble naturally occur- more, numerous mature neurons, including
ring catecholamines can combine with a - or those of the autonomic nervous system , were
(3- receptors and produce sympathomimetic found to contain more than one putative
effects. The term adrenergic blocking agent is chemical messenger. Such a coexistence of
used for compounds that interfere with bind - several transmitters almost always involved a
ing of the transmitter to postsynaptic recep- low-molecular-weight transmitter and a neu -
tors. Pharmacologic studies with blocking roactive peptide. In autonomic ganglia , for
agents have allowed further differentiation of example, noradrenergic neurons often con-
,
adrenergic receptor into a ,-, a,-, (3 -, and (32- tain neuropeptide Y while cholinergic neu -
subtypes (82, 86 ). Genes for these subtypes of rons are frequently enriched with vasoactive
adrenergic receptors were cloned , showing intestinal peptide. Thus, Dale's principle
that these receptors are members of a larger might better be reformulated to state that: A
family of hormone receptors whose activity is neuron makes use of the same combination of
mediated through G- proteins ( 32). chemical messengers at all of its synapses ( 110 ).
A wide variety of neuroactive peptides
Dale’ s Principle occur in autonomic neurons and are thought
to be coreleased with ACh and NE. In
Early studies of the autonomic nervous addition to neuropeptide Y and vasoactive
system, followed by many years of attempts intestinal peptide, one can note bombesin,
to characterize neurons on the basis of their cholecystokinin , dynorphin, enkephalin , gas-
neurotransmitter content, led to this impor- trin -releasing hormone, luteinizing hormone-
tant generalization: A neuron makes use of the releasing hormone, neurotensin, somato-
same transmitter molecule at all of its synapses. statin, substance P, calcitonin gene-related
This concept was first suggested by Sir Henry peptide, and peptide histidine isoleucine (53,
Dale: 67). These peptides appear to be distributed
with either ACh or NE in a highly ordered
" It is to be noted , further, that in the cases for
fashion in the different regions of the auto-
which direct evidence is already available, the phe- nomic nervous system. For example, about
nomena of regeneration appear to indicate that the
nature of the chemical function, whether choliner-
75% of the neurons in lumbar sympathetic
gic or adrenergic, is characteristic for each particu - ganglia are noradrenergic. Approximately
lar neurone, and unchangeable. When we are deal- half of these neurons also contain neuropep-
ing with two different endings of the same sensory tide Y (76), while a small proportion of them
neurone, the one peripheral and concerned with also contain somatostatin ( 64 ). The remaining
vasodilatation and the other at a central synapse, 25% are devoid of NE and represent the
cholinergic elements of the ganglia. Some of type, as assessed by measurements of ChAT

these NE-negative neurons contain the activity and histochemical visualization of
vasoactive intestinal peptide as well as the AChE, but continued to express intense cate-
calcitonin gene-related peptide (6, 118). In cholamine fluorescence. Additionally, im-
addition to neuroactive peptides, various munoreactivity for vasoactive intestinal pep-
small -molecule transmitters other than ACh tide, normally expressed by the sympathetic
and NE are believed to play an active role in neurons that innervate the sweat glands but
the function of the autonomic nervous sys- not by those innervating the parotid , was ob-
tem. Particularly convincing evidence exists served in only a small percentage of the
for the involvement of serotonin, dopamine, parotid-associated fibers (109 ). These findings
GABA, and glutamate (52, 53, 71, 132). suggest that cellular interactions between
One of the major functions of neuroactive neurons and their targets play an important
peptides in autonomic ganglia is to alter neu - role in the differentiation of chemical messen -
ronal excitability and thereby modulate the ger phenotype in vivo.
effectiveness of cholinergic and noradrener- The terms "adrenergic" and "cholinergic"
gic synaptic transmissions. In contrast to the do not correspond completely with "sympa -
fast nicotinic- mediated effect of ACh, the ac- thetic" and "parasympathetic," respectively.
tion of peptides on ganglionic neurons is For instance, the postganglionic fibers to the
slow, lasting up to several minutes. This sweat glands (sudomotor fibers), although
delay is probably due to the fact that these anatomically part of the sympathetic system ,
peptides bind to receptors that are coupled to are cholinergic. Moreover they react to cer-
guanine nucleotide-binding regulatory pro- tain drugs, such as pilocarpine and atropine,
teins (G- proteins) (see Chapter 5). The results in the same way as parasympathetic fibers. It
of several recent pharmacologic studies are in should be recalled that the upper and lower
keeping with the idea that peptides in auto- extremities have no parasympathetic nerve
nomic ganglia act more like neuromodulators fibers. In these regions, the sympathetic post -
than transmitters. For example, the neu -
ropeptides vasoactive intestinal polypeptide,
ganglionic fibers are of two distinct types
most are adrenergic, but those to the sweat
—
neuropeptide Y, and peptide histidine iso- glands are cholinergic (130) ( Figs. 9.9 and
leucine modulate the release of tritiated NE 9.10). There are other instances of mixed au -
from the sympathetic nerves in the choroid tonomic nerves. For example, the splanchnic
plexus of the rat (87). nerves contain both adrenergic and choliner-
In the excerpt quoted earlier, Dale alludes gic fibers. The latter are destined for the
to the phenomenon of regeneration as indi- adrenal medulla, where acetylcholine is the
cating that the nature of the chemical func- transmitter substance. Overactivity of both
tion is characteristic for each particular neu - adrenergic and cholinergic fibers is indicative
ron, and is also unchangeable. Although of either autonomic imbalance, irritating le-
basically true, particularly for mature neu- sions, or abnormal regeneration along the
rons, this assertion must be modulated to ac- course of the fibers. These may be expressed
count for recent experimental evidence of a as excessive or abnormal sweating and sali-
remarkable degree of neuronal plasticity in vation, alterations in gastrointestinal motility,
both the central and peripheral nervous sys- or increased peripheral vasoconstriction as in
tems. Of particular interest in the present hypertension. Appropriate drugs can either
context are the results of an experiment deal- enhance or inhibit impulses at the sympa -
ing with the development of the innervation thetic and parasympathetic ganglionic
of the sweat gland and the parotid gland in synapses, or block the membrane receptor
the rat (109). In this experiment, the sweat sites upon which the neurotransmitter sub-
gland , a target of the cholinergic sympathetic stances produce their effects (e.g., muscle,
neurons, was replaced with the parotid heart, glands, blood vessels).
gland , a target of noradrenergic sympathetic
neurons, in neonatal rats. This transplanta- DENERVATION SENSITIZATION
tion paradigm allowed sympathetic neurons
that would normally innervate the sweat If the superior cervical ganglion ( Fig. 9.1 )
glands and develop a cholinergic phenotype is isolated by section of all incoming pregan-
to innervate the parotid gland instead . The glionic fibers, the postganglionic perikarya
neurons innervating the transplanted parotid do not degenerate. The isolated postgan -
gland did not develop a cholinergic pheno - glionic perikarya may decrease slightly in di -
FUNCTION SYMPATHETIC PARASYMPATHETIC
Iris dilates the pupil ( mydriasis ) Constricts the pupil ( miosis )
Lacrimal gland little or no effect on secretion stimulates secretion
Salivary glands secretion reduced in amount and vis- secretion increased in amount and
cid watery
Sweat glands of stimulates secretion ( cholinergic fibers I little or no effect on secretion

head , neck , trunk, nerve fibers
and extremities
Bronchi dilates lumen constricts lumen
Heart accelerates rate, augments ventricu - decreases heart rate

lar contraction
GI motility and inhibits stimulates

secretion
GI sphincters constricts relaxes
Sex organs contraction of ductus deferens, semi- vasodilatation and erection

nal vesicle, prostatic and uterine mus-
culature; vasoconstriction
Urinary bladder little or no effect on bladder -

contracts bladder wall, promotes emp
tying
Adrenal medulla stimulates secretion ( cholinergic nerve little or no effect

fibers )
Blood vessels of constricts no effect

trunk and extre-
mities
Figure 9.9. Sympathetic and parasympathetic actions upon visceral structures
ameter and show alterations of Nissl sub- suits in increased sensitivity of the isolated
stance, endoplasmic reticulum, and mito- neurons and the tissues they supply to circu -
chondria , but they survive. In such a condi- lating adrenaline. At least a part of the dener-
tion , the perikarva do not demonstrate vation hypersensitivity is due to an increase
transneuronal degeneration (9, 56). However, in the number of adrenergic receptor sites on
following section of postganglionic axons of the postsynaptic cell membrane and / or to an
the cervical and ciliary ganglia , the perikarya increase in the degree of affinity of the recep-
show central chromatolysis and changes in tors for the transmitter molecule. This phe-
their electrophysiologic properties (9, 63, nomenon is often referred to by pharma -
129). cologists as "up-regulation." The receptor
Although postganglionic perikarya and molecules are proteins and their synthesis is
their processes can survive to a section of under genetic control, which in turn is influ -
their preganglionic fibers, such a section re- enced by diminished transmitter availability
Sacral
• Preganglionic fiber Postganglionic fiber Degenerated fiber
Figure 9.10. Anatomic course of preganglionic and postganglionic sympathetic vasoconstrictor fibers projecting to
the upper and lower extremities A . After cervicothoracic ganglionectomy (inferior cervical ganglion. 11 and T2 .
white) all of the postganglionic fibers to the hand degenerate B. Resection of sympathetic ganglia L2 and L3 (white)
interrupts only descending preganglionic fibers to lower lumbar and sacral sympathetic ganglia . Postganglionic fibers
In the sciatic nerve to the foot region do not degenerate.
over a period of several weeks (see Chapter in Hie isolated structure or structures. The effect
5). This form of trophic / genomic interaction being maximal in the part direct! }/ denervated .
between pre- and postsynaptic neurons has Such denervation accounts for the increased
been observed in many regions of the central sensitization of the superior cervical ganglion
and peripheral nervous system . It was ob- cells to acetylcholine which occurs after sev-
served that complete section of the postgan - erance of its preganglionic fibers.
glionic fibers to an organ or region resulted in The paralysis after denervation of smooth
far greater sensitization to adrenaline than muscle is very different from that seen in
that which followed complete preganglionic skeletal muscle where there is a persisting
nerve section. Hampel (57) observed the flaccid paralysis. Restoration of smooth mus-
qualitative responses of the nictitating mem - cle tone is due in part to the sensitization of
brane of the cat to adrenaline on successive the neuroeffector mechanism to circulating
days after denervation. He found that the re - epinephrine. The anatomic arrangement of
sponse reached a maximum about 8 days the preganglionic and postganglionic sympa -
after preganglionic denervation. Postgan - thetic vasoconstrictor fibers to the hand and
glionic denervation resulted in sensitization foot serves as an excellent example to illus-
responses that were twice as great as those trate this point ( Fig. 9.10 ). In Reynaud 's dis-
that followed preganglionic section. Similar ease, the small arteries and arterioles of the
responses are observed in most other tissues upper extremities, usually the hands, un-
supplied by the adrenergic fibers. Increased dergo episodic vasoconstriction in response
sensitivity has been observed as well in struc- to cold . As a result , the extremity demon -
tures supplied by the cholinergic fibers ( e.g., strates pallor and reactive hyperemia ( i.e., an
lacrimal, sweat, and salivary glands). The lat- increased amount of blood in a part or con -
ter become sensitive to ACh, which is equally gestion ). In chronic cases, trophic changes de-
true of denervated skeletal muscle. This pe- velop with atrophy of the skin and subcuta -
culiar phenomenon often is referred to as neous tissues. Long-standing cases may
Cannon 's ( 19 ) law of denervation: When in a develop skin ulceration or even ischemic gan -
series of efferent neurons a unit is destroyed , an grene. Removal of the inferior cervical, first
increased irritability to chemical agents develops and second thoracic sympathetic ganglia ,
eliminates the vasoconstriction but destroys continuum and phylogenetically older deriv-
both the preganglionic as well as the postgan- atives of the forebrain .
glionic fibers to the forearm and hand ( Fig. Most brain regions involved in the control
10 A ). The smooth muscle of the arteries and of the autonomic nervous system outflow
arterioles will, in time, regain some vascular exert their influence by way of the hypothala -
tone since the smooth muscle is also highly mus, which may be considered as the head
sensitized by removal of the postganglionic ganglion of the autonomic nervous system .
cells and fibers. Better results usually are ob- The hypothalamus regulates the autonomic
tained in the foot following removal of the nervous system in two ways. First, it projects
second and third lumbar sympathetic ganglia to the brainstem and spinal cord nuclei that
( Fig. 9.10 B ) . Here the partial sympathectomy act on preganglionic autonomic neurons to
interrupts the preganglionic outflow but control temperature, heart rate, blood pres-
leaves intact the postganglionic cells and sure, and respiration . The nucleus of the soli-
fibers in the lower lumbar and sacral ganglia, tary tract is one of the brainstem nuclei that
which reach the foot through the sciatic nerve are actively involved in the regulation of car-
and its branches. Thus the vessels of the leg diovascular and respiratory functions. Sec-
and foot regions are less sensitized to neuro- ond , the hypothalamus acts on the endocrine
humoral catecholamines. system to release hormones that influence au -
tonomic function.
CENTRAL AUTONOMIC PATHWAYS Investigations using silver impregnation
methods for degenerating axons indicated no
Visceral structures innervated by the auto- direct descending connections from the hy -
nomic nervous system normally maintain a pothalamus that extended beyond the mes-
constant internal environment within the or - encephalic tegmentum (54, 97, 137). Later
ganism ( homeostasis ). Preganglionic neurons studies with newer tract-tracing and immu -
in the central nervous system ( Figs. 9.1 and nohistochemical methods, showed that hypo-
9.3) are maintained in a continuous, but thalamic neurons project directly to medul -
quantitatively variable state of activity by a lary autonomic nuclei and the spinal cord
multitude of segmental and suprasegmental (11, 106, 107, 121 ) ( Figs. 11.23, 12.24, and
mechanisms. Regulation from higher levels is 17.17). Mesencephalic structures receive an
accomplished by multiple neuronal path- input from the hypothalamus via (a ) a de-
ways. This regulation appears to be medi- scending component of the medial forebrain
ated , in part, by a series of synaptic relays be- bundle, ( b ) the mammillary bodies ( mamil -
tween several interposed neurons located at lotegmental tract ), and (c ) descending projec-
successively lower levels of the brainstem tions in the periventricular gray ( Fig. 17.16 ).
and forming a somewhat diffuse multisynap- Hypothalamic impulses conveyed to the mes-
tic descending system. encephalon are transmitted to more caudal
The hypothalamus commonly is regarded parts of the neuraxis via numerous synaptic
as the principal locus of central autonomic relays within the brainstem reticular forma -
integration. Simply stated , the most volu- tion , as well as the smaller number of direct
minous afferent connections of the hypo- projections (84 ). It is presumed that reticular
thalamus originate from the hippocampal neurons convey impulses to visceral motor
formation, the amygdaloid nuclear complex, nuclei in the brainstem and spinal cord .
and the olfactory cortex, and indirectly from In the midbrain and upper pons, these de-
cortical regions that are part of the limbic sys- scending tracts are located dorsally and me-
tem (85, 97, 106 ). Many of these structures are dially near the central gray matter and floor
involved in a neural circuitry that begins in of the fourth ventricle (12, 24, 117, 137). In
the septal region and extends in a parame- most mammals that have been studied, in -
dian zone through the preoptic region and cluding humans, the fibers descending into
hypothalamus into the rostral mesen- the upper midbrain stream through the pre-
cephalon ( Fig. 17.14 ). In this view, the hypo- rubral field and region above the red nucleus.
thalamus is the central part of a continuum Stereotaxic surgery for dyskinesia in this area
that has been termed the "septo- hypothal- of the human brain has resulted in wide-
amo- mesencephalic continuum" (85). There spread autonomic deficits ( 23). These deficits
are a great number of reciprocal connections include ptosis (drooping) of the eyelid , miosis
between structures within this subcortical (constriction ) of the pupil, and a loss of
sweating ( hemianhydrosis) on the same side cord transection the autonomic reflexes are at
( ipsilateral ) of the body as the lesion . In hu - first depressed (spinal shock ), temperature
mans, these descending fibers are uncrossed regulation and sweating are absent , and
below the level of the red nucleus. These blood pressure falls profoundly. Weeks later,
fibers are located more laterally in the pon- after spinal shock has waned, segmental re-
tine tegmentum and reticular formation of flexes caudal to the lesion reappear. Somatic
the medulla . Through this descending fiber segmental reflexes in time become exagger-
system, the hypothalamus and other su- ated , but visceral reflexes usually are slug-
prasegmental structures contribute to the reg- gish .
ulation of a variety of visceral reflex activities
( e.g., blood pressure, body temperature, FUNCTIONAL CONSIDERATIONS
sweating, secretion, eye, vesicle, rectal, and
sexual reflexes). Lesions of these descending Antagonistic Effects of Sympathetic and
central tracts can result in a complete loss, or Parasympathetic Systems
altered control, of visceral activities at lower Gaskell (50 ) pointed out that when a vis -
segmental levels. For example, lesions in the ceral structure is innervated by both sympa -
lateral reticular formation of the medulla in- thetic and parasympathetic fibers, the effects
terrupt the fibers regulating sympathetic con - of the two are as a rule antagonistic. The sym -
trol of the smooth muscle of the eye and may pathetic neurons dilate the pupil , accelerate
result in a Horner's syndrome. the heart , inhibit intestinal movements, and
Familial dysautonomia or Riley- Day syn - contract the vesical and rectal sphincters. The
drome is an unusual clinical entity that affects parasympathetic neurons constrict the pupil,
children of Jewish extraction (101 , 102 ). It can slow' the heart, further peristaltic movement,
serve as an excellent example of the dissemi- and relax the vesical and rectal sphincters
nated and abnormal functional activities of ( Fig. 9.9). The apparently haphazard effects
central descending autonomic fibers. This on smooth and cardiac muscle produced by
syndrome is characterized by deficiency of each autonomic division in different organs
lacrimation, transient and extreme elevation (contraction in one, inhibition in another ) are
in blood pressure induced by mild anxiety, more readily explained when the overall ac-
excessive sweating and drooling of saliva, tivities of the two systems are taken into con-
and the occurrence of sharply demarcated , bi- sideration . The parasympathetic deals pri -
lateral and symmetric erythematous blotches marily with anabolic activities concerned
on the skin . A central , possibly congenital, di- with the restoration and conservation of bod -
encephalic dysfunction has been postulated ily energy and the resting of vital organs. In
to account for these symptoms. Subsequent the words of Cannon:
studies revealed other disturbances, includ -
"A glance at these various functions of the cra -
ing postural hypotension , feeding difficulties
from birth onward, a relative indifference to nial division reveals at once that they serve for
pain, erratic control of body temperature, bodily conservation; by narrowing the pupil they
shield the retina from excessive light ; by slowing
emotional lability, loss of corneal reflexes, the heart rate they give the cardiac muscle longer
corneal anesthesia, loss of deep tendon re- periods for rest and invigoration; and by providing
flexes, abnormal pupillary response to metha- for the flow of saliva and gastric juice, and by sup-
choline, and an abnormal intradermal re- plying the necessary muscular tone for the contrac-
sponse to histamine. Hvpotonus, poor motor tion of the alimentary canal , they prove fundamen-
coordination , and developmental retarda- tally essential to the processes of proper digestion
tion may accompany the mentioned symp- and absorption, by which energy-yielding material
toms. The precise pathologic causes remain is taken into the body and stored . To the cranial di -
unknown, but lesions have been found in the vision belongs the great service of building up re-
thalamus, reticular formation of pons and serves and fortifying the body against times of
medulla , spinal cord , sympathetic ganglia, need and stress" (18) .
and the myenteric plexus (102). The sacral division supplements the cra -
Bilateral lesions of the lateral white funi- nial by ridding the body of intestinal and uri-
culi may result in altered sweating in regions nary wastes.
supplied by the cord segments below the On the other hand , stimulation of the sym -
level of such lesions. Control of the bladder pathetic component equips the body for the
and rectum also may be lost. After spinal intense muscular action required in offense
and defense. It is a mechanism that quickly ratio is only 1:2 (138). Parasympathetic action
mobilizes the existing reserves of the body is more discrete and is limited to the portion
during emergencies or emotional crises. The of the target that is stimulated . The liberation
pupils dilate, respiration is deepened , and the and rapid hydrolysis of acetylcholine by the
rate and force of the cardiac contractions are parasympathetic postganglionic fibers is
increased. The blood vessels of the viscera compatible with such localized autonomic re-
and the skin are constricted , the blood pres- sponses. Thus, stimulation of the glossopha-
sure is raised and an ample blood supply is ryngeal nerve ( N . IX ) increases parotid gland
made available to the skeletal muscles, lungs, secretion, while stimulation of the oculomo -
heart, and brain. The peaceful activities are tor nerve constricts the pupil, in each case
slowed or stopped , blood is drained from the without the appearance of other parasympa -
huge intestinal reservoir, peristalsis and ali- thetic effects. These data indicate that the
mentary secretion are inhibited , and the uri- sympathetic system is much more divergent
nary and rectal outlets are blocked by con - than the parasympathetic system.
traction of their sphincters.
The two systems are reciprocal and their Autonomic Innervation of the Eye and
dual activities are integrated into coordinated Salivary Glands
responses ensuring the maintenance of an ad -
equate internal environment to meet the de- The functions of the two subdivisions of
mands of any given situation. The parasym - the autonomic system are most easily under -
pathetic activities are initiated primarily by stood by contrasting the individual structures
internal changes in the viscera themselves. innervated and noting the reciprocal actions
The sympathetic system is in considerable of their dual nerve supply ( Fig. 9.9 ). The au -
part activated by exteroceptive impulses that tonomic fibers to the eye provide an excellent
pass over somatic afferent fibers and are initi- example of this dual innervation. The sympa -
ated by favorable or unfavorable changes in thetic division stimulates the smooth muscle
the external environment. fibers of the dilator muscle of the iris, the
The preganglionic fibers of the sympa- tarsal muscle and the orbital muscle (of
thetic system arise from a continuous cell col- Muller ). The tarsal muscle extends from the
umn in the spinal cord , and a single fiber may levator palpebrae muscle to the tarsal plate of
form synaptic relations with many cells in the upper lid and aids in full elevation of the
different paravertebral or prevertebral gan - upper eyelid . The orbital muscle, at least in
glia ( Fig. 9.6 B ). Both types of ganglia are nonprimate species, keeps the ocular bulb
placed at considerable distances from the or- forward in the bony orbit. Lesions in either
gans innervated , and from them postgan - the central or peripheral sympathetic path -
-
glionic fibers are distributed to extensive vis ways to the eye produce a triad of symptoms
ceral areas ( Figs. 9.1 and 9.11). Such a known as Horner' s syndrome. As a result of
mechanism permits a wide radiation of im- sympathetic injury, the parasympathetic in -
pulses. The NE released at most sympathetic nervation is unopposed , and results in con -
terminals further enhances the widespread striction of the ipsilateral pupil (miosis),
and prolonged effects of sympathetic stimu - dropping of the upper eyelid ( pseudoptosis),
lation. Thus, stimulation of a thoracic ventral and an apparent sinking in of the eyeball
root, or white ramus, causes piloerection and (enophthalmos) ( 46). Vasodilation and dry-
vasoconstriction in five, six, or even more ness of the skin of the face also may be evi -
segmental skin areas. dent. Sympathetic fibers destined for the eye
In the parasympathetic system the pregan- follow the internal carotid artery, while those
glionic neurons are represented by more iso- to sweat glands on the face course along the
lated cell groups whose fibers pass out in sep- branches of the external carotid artery. This
arate nerves and go directly to the terminal dichotomy of postganglionic fibers from the
ganglia within or near the organs. Each pre- cervical ganglia explains the altered patterns
ganglionic parasympathetic fiber enters into of autonomic function that can occur after in -
synaptic relations with fewer postganglionic juries of the face, deep neck, or within the
neurons than is the case in the sympathetic skull. There may be loss of sweating on the
division. Thus, in the superior cervical gan- face with preservation of sympathetic inner-
glion of the cat, the ratio of preganglionic vation to the eye or vice versa . Lesions of the
fibers to postganglionic neurons is about 1:15 cervical sympathetic trunk, inferior cervical
or more, while in the ciliary ganglion the ganglion, or ventral roots of the upper tho -
Autonomic fibeis
no
Sympathetic trunk
11
12
LI
2
3
Inferior mesenteric plexus 4
Hf 5
h SI
2
Hypogastric plexus <V;,' 3
4
5
Pelvic nerve Pelvic nerve

(parasympathetic!
to muscles of the
bladder wall
Sympathetic fibers
to blood vessels and
muscle of bladder wall
Figure 9.11. Sensory and autonomic innervation of the urinary bladder Preganglionic parasympathetic visceral
motor ( purple) fibers from S2, S3, and S4 pass to terminal ganglia which give rise to postganglionic fibers that induce
contractions of the detrusor muscle Afferent impulses from stretch receptors (black) in the bladder wall enter upper
lumbar and lower thoracic spinal segments via the hypogastric plexus, and S2, S3, and S4 spinal segments via the
pelvic nerve. Descending sympathetic fibers (red) synapse in the inferior mesenteric plexus and travel in the hypogas-
tric nerves and plexus. Somatic motor fibers from S2, S3, and S4 spinal segments (not shown) innervate the external
vesicle sphincter Relaxation of the external sphincter and contraction of the detrusor muscle are essential for micturi-
tion.
racic nerves interrupt the fibers before they glands. Sympathetic fibers provide for vaso -
divide to follow separate courses. constriction of blood vessels, contraction of
Parasympathetic fibers to the eye stimulate the myoepithelial cells of the ducts, and se-
the sphincter muscle of the iris and bring cretory fibers to the demilune gland cells (5).
about constriction of the pupil . These axons Stimulation of the human sympathetic trunk
also stimulate the ciliary muscle. Contraction in the neck, or the injection of adrenaline into
of the circular fibers of the ciliary muscle the salivary duct, evokes a flow of saliva from
causes relaxation of the ciliary zonule and the submandibular, but not from the parotid
thereby decreases the tension of the lens cap- gland . The secretory response to sympathetic
sule. As a result of such parasympathetic ac - stimulation is of short duration when com -
tivity, the pupil is constricted and the convex- pared to the long-acting response that follows
ity of the lens is increased for near vision parasympathetic stimulation (42 ). Parasym -
(accommodation ). pathetic fibers in cranial nerves VII and IX
Innervation of the salivary glands was provide for vasodilation of the blood vessels
long believed due solely to secretory fibers in and secretory fibers to the alveolar and acinar
the cranial parasympathetic nerves ( Fig. 9.9). cells of the parotid , submandibular sublin -
Many differences have been found between gual, and retrolingual glands. The vagus
the several glands of the different species nerve ( N. X ) contains secretory fibers to the
studied , but both parts of the autonomic sys- glands of the trachea and upper digestive tract.
tem send secretory fibers to the salivary For additional details on the innervation of the
salivary glands the reader is referred to the with vasomotor control and the mechanism
classic reviews by Babkin (5), Lundberg (74), of ejaculation. However, recent anatomic and
Burgen and Emmelin (15), and Emmelin ( 41 ). pharmacologic studies led to the idea that the
sympathetic outflow to the bladder counter-
Autonomic Innervation of the act, and even control, the activity of the
Urinary Bladder parasympathetic system ( 39). In humans, the
sympathetic innervation of the bladder arises
The innervation of the urinary bladder from the thoracic and lumbar segments (T12
and the control of micturition represent a to L2 ) of the spinal cord. Preganglionic fibers
complex and specific autonomic function of reach the inferior mesenteric ganglion or
great practical importance ( Fig. 9.11 ). The plexus and from there postganglionic fibers
smooth muscle of the urinary bladder ex- travel in the hypogastric nerve to the pelvic
hibits two types of activity: (a ) intermittent ganglion, the bladder wall, and the internal
contractions which occur as the organ adapts urethral sphincter muscle. It should be noted ,
its capacity to an increasing volume, and ( b) however, that the internal sphincter is proba-
sustained contractions associated with relax- bly not a distinct anatomic entity. It is more
ation of the external sphincter which occur likely formed by a continuation of the longi -
during micturition . These activities are con- tudinal detrusor fibers around the bladder
trolled by the interplay not only of sympa- outlet . This sympathetic outflow can be stim-
thetic and parasympathetic neurons but also ulated by the activity of sensory afferents re-
of somatic motor neurons. All three systems sponding to tension in the bladder wall
are activated by reflexes that are regulated at (stretch receptors). These sensory afferents
both spinal and supraspinal levels (39). How - travel through the pelvic nerve or, if the blad -
ever, the various neuronal events involved in der is greatly distended , by way of the hy -
the control of micturition are not fully under - pogastric nerves and plexus to arborize at the
stood and the subject is still a matter of some level of spinal segments T10 to T12. Stimula-
controversy . tion of the sympathetic outflow results in an
Most investigators agree that the excita - a -adrenergic inhibition of parasympathetic
lory input to the bladder wall that causes activity in the pelvic ganglion, relaxation of
contraction and promotes emptying is the muscles of the bladder wall ( mediated by
parasympathetic. Cholinergic axons originat - -
p adrenergic receptors), and excitation of the
ing in the intermediolateral region of the internal sphincter muscle (14, 39). Thus, dur-
spinal cord (S2 to S4 ) leave the sacral nerves, ing the bladder filling, the sympathetic sys-
and , as the pelvic nerve , course to the lateral tern promotes bladder wall relaxation di-
wall of the bladder where the fibers terminate rectly, and also indirectly through inhibition
in the pelvic ganglion plexus, whose neurons of the parasympathetic activity (37), and
are dispersed near to and within the bladder causes closure of the internal urethral sphinc-
wall . Short postganglionic parasympathetic ter.
fibers to the bladder musculature induce con- The somatic motor neurons that partici -
traction of the detrusor smooth muscle by re- pate in the control of bladder function are lo-
leasing ACh , which acts on muscarinic recep- cated in the ventral horn at the sacral spinal
tors ( 116) ( Fig. 9.11 ). The parasympathetic segments 2, 3, and 4. Their axons become in -
neurons are quiescent during initial bladder corporated in the pudendal ( pudic) nerve,
filling, but bladder distension initiates im- and, via a branch of that nerve, the perineal
pulses in visceral afferents that course in the nerve, innervate the external urethral sphinc-
pelvic nerve to the sacral spinal cord and acti - ter and cause contraction . These motor neu -
vate parasympathetic preganglionic neurons. rons are stimulated by the activity in visceral
While there is a general consensus about afferents to low levels of bladder distension ,
the role of the parasympathetic system in At high levels of distension, supraspinal neu -
micturition, the involvement of the sympa - rons that inhibit both the sympathetic and the
thetic system is much debated . The major somatic motor neurons are activated so that
problem stems from the fact that the sympa - the sympathetic inhibition of the parasympa -
thetic innervation of the bladder appears to thetic activity is released and both sphincters
be largely restricted to the muscle fibers of relax, allowing bladder contraction and uri -
the vesical trigone, including the orifices of nation (39).
the ureters and the urethra. The trigone mus- It should be noted that the desire to uri-
cles are believed to be concerned principally nate is dependent upon intravesical pressure
rather than fluid-volume content . The vesical functional status of the autonomic nervous
capacity and frequency of urination vary system. Vital body processes such as circula -
with age and are influenced by reflex, psy- tion , secretion, digestion , and excretion, are
chic, and local irritative factors. In children essentially autonomic reflex responses. The
8-10 years of age, the initial desire to void oc- autonomic nervous system also participates
curs with an intravesical pressure of 9-11 cm in many somatic-visceral and visceral -so-
of water (bladder volume 80-100 ml of urine ). matic reflexes which involve either cranial or
In adults with a fluid capacity of 140-180 ml, spinal nerves (e.g., respiration, pupillary,
an intravesical pressure of 15-16 cm of water lacrimal, palatal, pharyngeal, sneeze, cough ,
induces the desire to void (17). swallowing, vomiting, carotid sinus, vasomo-
Sensory information about the status of tor, sudomotor, pilomotor, vesicle, genital,
the bladder reaches conscious level through and emotional reflexes ). Some of these re-
long and poorly defined multisynaptic path - flexes are presented as individual nerves are
ways. It was suggested that these pathways discussed . Metabolic or mechanical irritations
lie in the dorsal half of the lateral funiculus of autonomic nerve fibers in the periphery
(8, 78, 103). Facilitating and inhibiting su - may cause exaggerations of some of the sym-
prasegmental influences upon spinal mecha - pathetic and parasympathetic functions in-
nisms concerned with micturition suggest cluded in Figure 9.9. Partial or complete le-
that regions in the pontine and midbrain sions of autonomic fibers may occur in either
tegmentum are involved ( 122). Additionally, the central or the peripheral nervous system
the cerebral cortex appears to exert some con- ( Fig. 11.28). An appreciation of the nuclei,
trol over bladder function . Clinical studies in - fiber pathways, and resulting reflex deficits
dicate that portions of the superior frontal from injuries are useful as a diagnostic aid in
gyrus on the medial surface of the hemi- exploring the diffuse distribution of the auto-
sphere may be specially concerned with con - nomic system. In the periphery, the postgan -
trol of micturition and defecation ( 3). Lesions glionic sympathetic fibers that rejoin spinal
in this region , involving one or both frontal nerves ( Fig. 9.2 ) have a distribution which
lobes, may cause urgency, frequency of mic- compares closely to that of the sensory der-
turition, or incontinence. Such lesions are also matomes (38, 100). Hence changes in cuta -
associated with lack of awareness of all vesi- neous sudomotor and vasomotor reflexes,
cal events, including the sensation of the de- changes in skin temperature, and increased
sire to micturate and the sensation that mic- skin resistance to passage of a minute electric
turition is imminent. Disturbances of bladder current indicate the involvement of sympa-
function associated with spinal cord injury thetic nerve fibers. A knowledge of der-
are described in Chapter 11. matomal and peripheral nerve distributions
( Figs. 8.11, 8.12, and 8.16-8.18), correlated
Clinical Notes with the segmental nuclear origins of auto-
nomic neurons ( Figs. 9.1 and 9.3), often can
A familiarity with the information in Fig- provide additional evidence to substantiate
ure 9.9 proves useful in evaluating the overall both the location and level of a nerve injury.
References torv mechanism of the digestive vical ganglion . ) Anat 1958;92:

glands. 2d ed . Ch . 27. New York: -
399 407.
1 . Adams CWM. Disorders of neu - P.B. Iloeber, 1950:733-766. 10. Beaudet A , Descarries L. The
rons and neuroglia. In : Adams 6. Baldwin C. Sasek CA , Zigmond monoaminergic innervation of rat
C WM , ed . Neurohistochemistry. RE. Evidence that some pregan - cerebral cortex; synaptic and non -
Ch. 10. Amsterdam : Elsevier, glionic sympathetic neurons in the synaptic axon terminals. Neuro-
1965:403-436. (See also Chs. 1-8: rat contain vasoactive intestinal science 1978;3:851-860.
1-332.) peptide- or peptide histidine 11 Bjorklund A, Skagerberg G. Evi -
2. AhU|uist RP. A study of the
adrenotropic receptors. Am I Phys -
isoleucine amide-leke immunore
activities. Neuroscience 1991 ;40:
- dence for a major spinal cord pro-
jection from the diencephalic A 11
iol 1948;153:586-600. 175-184. dopamine cell group in the rat
3. Andrew J , Nathan PW. Lesions of
the anterior frontal lobes and dis-
7. Baron R , Janig, W. Afferent and
sympathetic neurons projecting
-
using transmitter specific fluores
cent retrograde tracing Brain Res
-
turbances of micturition and defe- into lumbar visceral nerves of the -
1979;177:170 175.
cation . Brain 1964;87:233-262. male rat . J Comp Neurol 1991; 12. Bradley WE, Conway CJ . Bladder
4 Axelrod ). Noradrenaline: fate and -
314:429 436. representation in the pontine - mes -
control of its bii >svnthesis. Science 8. Barrington FJF. The relation of the encephalic reticular formation. Exp
1971 ;173:598-606. hind brain to micturition . Brain Neurol 1966;16:237-249.
5. Babkin BP Significance of the dou-
ble innervation of the salivary
-
1921;44:23 53.
9. Barton AA , Causey G. Electron mi -
13. Brimijoin S, Lennon VA . Selective
destruction of preganglionic sym -
glands. In : Babkin BP, ed . Secre - croscopic study of the superior cer - pathetic nerves by antibodies to
acetylcholinesterase. J Neurol mafic vagus of the rat . J Auto Nerv report . Optom Vis Sci 1992;69:
Transm 1991;34:139-145. 481 -485.
.
14 . Brindley CS. Autonomic control of
the pelvic organs . In : Bannister R ,
Syst 1979;1:203-211 .
31 . Contreras RJ , Gomez MM , Nor -
gren R . Central origins of cranial
47. Forehand CJ . Morphology of sym
pathetic preganglionic neurons in
-
ed . Autonomic failure. 2d ed . Lon - nerve parasympathetic neurons in the neonatal rat spinal cord : an in -
don and New York : Oxford Uni - the rat . ) Comp Neurol 1980; tracellular horseradish peroxidase
versity Press, 1988:223-237. 190:373-394 . study. I Comp Neurol 1990;
15. Burgen ASV , Emmelin NG . Inner -
vation of the glandular elements.
32. Cooper |R , Bloom FE, Roth RH
The biochemical basis of neuropsy -
-
298:334 342.
48. Furness JB, Costa M . Types of
In Burgen ASV, Emmelin NG, eds. chopharmacology . 6th ed . New nerves in the enteric nervous sys-
Physiology of the salivary glands. York: Oxford University Press, tem. Neuroscience 1980;5:1 -20.
Ch. 3. Baltimore: Williams & 1991 . 49. Furness JB, Costa M. The enteric
Wilkins, 1961:38-71. 33. Dahlstrom A . Observation on the nervous system. Edinburg: Living -
16. Butcher II , Talbot K , Bile / ikjian L. accumulation of noradrenaline in stone, 1987.
Acetylcholinesterase neurons in the proximal and distal parts of pe- 50. Gaskell WH. The involuntary ner -
-
dopamine containing regions of ripheral adrenergic nerves after vous system . London: Longmans
the brain . J Neural Transm compression. J Anal 1965;99: & Green , 1916.
1975;38:137-153. 677-689. 51 . Geis GS, Wurster RD. Horseradish
17. Campbell ME. Neuromuscular 34. Dahlstrom A, Carlsson A. Making peroxidase localization of cardiac
uropathy In: Campbell MF, ed . visible the invisible. In : Parnham vagal preganglionic somata . Brain
Principle's of urology. Ch. 9. M|, Bruinvels |, eds. Pharmacology Res 1980;182:19-31 .
Philadelphia: W . B Saunders, 1957: methods, receptors and chemo- 52. Gershon VII ). The enteric nervous
337-378. therapy Vol 3. Amsterdam: Else- system. Annu Rev Neurosci 1981 ;
18. Cannon WB. Bodily changes in -
vier, 1986,97-125. 4:227-272.
pain, hunger, fear and rage. An ac - 35. Dale Hll The action of certain es- 53. Gibbins I Peripheral autonomic
count of recent researches into the ters and ethers of choline, and their nervous system In : Paxinos G, ed .
function of emotional excitement . relation to muscarine. J Pharmacol The human nervous system . Ch . 5.
New York: Appleton, 1929. ExpTher 1914;6:147- 190 New York: Academic Press, 1990:
19. Cannon WB. A law of denervation. 36. Dale H . Pharmacology and nerve 93-123.
-
Am | Med Sci 1939;98:737 750. endings. Proc R Soc Med 1935; 54 . Guillery RW . Degeneration in the
20. Cannon WB, Rosenblueth A . Stud - 28:319-332. hvpothalamic connexions of the al -
ies on activity in endocrine organs: 37. IX* Groat WC, Steers WD. Neural bino rat. ) Anal 1957;91:91-115.
sympathin E and svmpathin I . Am control of the urinary bladder and 55. I laefely VV , I lurhmann A, Thoenen
-
) Physiol 1933;104:557 574. sexual organs. In : Bannister R , ed . II Relations between the rate of
21 Cannon WB, Rosenblueth A . Auto- Autonomic failure 2d ed . London stimulation and the quantity of
nomic -
neuro effector systems.
New York : Macmillan , 1937
and New York: Oxford University
-
Press, 1988;196 222.
noradrenaline liberated from the
sympathetic nerve endings in the
22. Carlsson A . Drugs which block the 38. IX’Jong RN . The neurological ex - isolated perfused spleen of the cat .
-
storage of 5 hydroxytryptamine amination . 4 th ed . New York: J Physiol ( Lond ) 1965;181 :48-58.
and related amines. In : Eichler O, I iarper & Row , 1979. 56. Ilamlv n 1 11 The effect of pregan -
Farah A, eds. I landbuch der exper - 39. Dodd |, Role l .W . The autonomic glionic section on the neurons of
imentellen Pharmakologie. Vol . nervous system . In : Kandel FR , the superior cervical ganglion in
19. Heidelberg: Springer, 1965: Schwartz JH, Jessell TM , eds. Prin - rabbits. J Anal 1954;88: 184-191 .
5» 592 ciples of neural science. Ch . 49. 57. Hampel CW . The effect of dener-
23. Carmel PW . Sympathetic deficits New York : Elsevier, 1991 :761- vation on the sensitivity to adrena -
following thalamotomv - Arch 775. line of the smix > th muscle in the
-
Neurol I %8;18:378 387, 40. Feck’s JC. The physiology of nerve nictitating membrane of the cat .
24 Cheatham ML, Matzke HA . De - cells. Baltimore: Johns Hopkins Am ) Physiol 1935;61 :611-621 .
scending hypothalamic medullary Press, 1957. 58. Handa Y, Caner II, Hayashi M ,
pathways in the cat . ) Comp Neu - 41 . Emmelin N . Nervous control of Tamamaki N , Nojyo Y. The distri -
rol 1966;127:369-380 . salivary glands. In : Code CF, ed . bution of the sympathetic nerve
25. Cobb ) LS, Bennett T. A study of Handbook of physiology . Vol . II : fibers to the cerebral arterial sys-
plexuses in visceral smooth mus- Secretion . Sec. 6. Ch . 37. Washing - tem in rat as revealed by antero-
cle. ) Cell Biol I 969;4 I :287 297. ton , EXT : American Physiological grade labeling with WGA - HRP.
26. Coggeshall RE, Applebaum ML,
Frazen M , Stubbs TB 111 , Sykes MT
Society, 1967:595-632.
42. Emmelin N , Stromblad BCR . A 59. Hervonen A , Pelto- Huikko M,
-
Fxp Brain Res 1990;82:493 498.
Unmyelinated axons in human method of stimulating and inhibit - Helen P, Halho H . Electron micro-
ventral roots, a possible explana - ing salivary secretion in man. Acta scopic localization of enkephalin -
tion for the failure of dorsal rhi- Physiol Scand 1954;31(Suppl 114 ): like immunoreactivity in axon ter -
zotomy to relieve pain. Brain 12 13. minals of human sympathetic
1975;98: 157- 166 43. Falck B. Observations on the possi - ganglia . Histochemistry I 980;70:
27. Coggeshall RE, Coulter ) D, Willis
WD. Unmyelinated axons in the
bilities of the cellular localization
of monoamines by a fluorescence
-.
16
60. Hess WR. Die Funktionelle Organ -
ventral riH > ts of the cat lumbosacral method . Acta Physiol Scand isation des Vegetativen Nervensvs-
enlargement . J Comp Neurol 1962;56<Suppl 197): 1 -25. tems. Basel: Schwabe, 1948.
1974;153:39-58. 44 . Falck B. I lillarp NA , Thieme G , 61. I lillarp N - A . The construction and
28. Coggeshall RF , Galbraith SL. Cate- Torp A. Fluorescence of cate - functional organization of the au -
gories of axons in mammalian cholamines and related com - tonomic innervation apparatus.
rami commonicantes, part II . ) pounds condensed with formalde- Acta Physiol Scand l 959;46(Suppl
Comp Neurol 1978;181:349-360. hyde. | Histochem Cyti >chem 1962; -
157):1 38.
29. Coggeshall RE , Hancock MB, Ap- 10:348-354 . -
62. I lillarp N A . Peripheral autonomic
plebaum ML. Categories of axons
in mammalian rami communi -
45. Falck B, Torp A . A new evidence
for localization of noradrenaline in
mechanisms , In : Field ) , ed Hand
book of physiology . Vol. II . Sec. I :
-
cantes. ) Comp Neurol 1976; adrenergic nerve terminals. Med Ch. 38 . Washington, DC: American
-
167:105 124. Exp ( Basel ) I 2;6: l 69-172. Physiological Society, 1960:979 -
30. Coil |D, Norgren R . Cells of origin . ^
46. Fields CR Barker EM 2d . Review 1006.
of motor axons in the subdiaphrag - of Homer's syndrome and a case 63. I lunt CC, Riker WK . Properties of
frog sympathetic neurons in nor- minals produced by nerve im- acetvltransferase in thoracic spinal
mal ganglia and after axon section. pulses after the inhibition of nora - motor neurons: somatic and auto-
I Neurophysiol, 1966;29:1096- 1 114. drenaline synthesis of reabsorp- nomic neurons may be derived
64 larvi K , Pelto-Huikko M, Helen l\ tion l ifeSd 1964 :1397 1402 from a common cellular group J .
Hervonen A. Somatostatin-like im - ^
80 Marfurt CF, Kingsley RE, Echt - Comp Neurol 1991;307:77-86.
munoreactivity in human sympa - enkamp SF. Sensory and sympa- 94. Pick J . The autonomic nervous svs
thetic ganglia . Cell Tissue Re's thetic innervation of the mam- tern. Philadelphia: J .B. I.ippincott,
1987;249:1-5. malian cornea. A retrograde 1970.
.
65. Jensen I Pilowsky I’M, Llewellyn- tracing study. Invest Ophthalmol 95. Pick I, Sheehan D Sympathetic
Smith IJ, Minson IB, Chalmers JP. 1989£0:461 472 . rami in man J Anat 1946;80:12-20.
Sympathetic preganglionic neu - 81 Mayer EA, Raybould HE. Role of 96. Potts TK . The main peripheral con -
rons projecting to the adrenal visceral afferent mechanisms in nections of the human sympathetic
medulla in the rabbit . Brain Res functional bowel disorders. Gas- nervous system | Anat 1924
1992;586:125-129. troenterology 199();99: 1688- 1704. 59:129- 135.
66 . Johnson LR, ed.. Physiology of the 82 Minneman KP, Pittman RN, Moli- 97. Raisman G. Neural connexions of
gastrointestinal tract. 2d ed. New noff PB. Ji-adrenergic receptor sub- hypothalamus. Br Med Bull 1966;
York: Raven Press, 1987. types: properties, distribution and 22:197-201.
67. Karc / mar AG, Koketsu K, Nishi S, regulation. Ann Rev Neurosci 98. Ramon v Cajal S. I listologie du
eds. Autonomic and enteric gan - 1981;4:419-461. Systeme Nerveux de I' Homme et
glia: transmission and its pharma - 83. Mitchell GAG. Anatomy of the au - des Vertebres. ( Azoulay I , Trans.)
cology' . New York: Plenum Press,
1986.
tonomic nervous system. Edin-
burgh: Livingstone, 1953.
Paris: Maloine. 1909.
( Reprinted, Consejo Superior de
1911
68. Koelle GG . Anticholinesterase 84. Nauta WJH. Hippocampal projec - Investigaciones Cientificas, Insti -
agents. In: Goodman LS, Gilman tions and related neural pathways tuto Ramon y Cajal, Madrid, 1972. )
A, eds. The pharmacological basis to the midbrain in the cat. Brain 99. Ranson SW, Billingsley PR. The su -
of therapeutics. Ch. 22. New York: 1958;81:319-340. perior cervical ganglion and the
Macmillan, 1970: 442 -465. 85. Nauta WJH. The central viscero- cervical portion of the sympathetic
69. Langley JN. On the union of cra - motor system: a general survey. In: trunk. J Comp Neurol I9|8;29
nial autonomic ( visceral) fibres Hockman CH, ed. Limbic system 313-358 .
with the nerve cells of the superior mechanisms and autonomic func - 100. Richter CP, Woodruff BG. Lumbar
cervical ganglion. I Physiol ( Lond ) .
tion. Ch. 2. Springfield IL : Charles sympathetic dermatomes in man
1898:23:240 C. Thomas, 1972:21-33. determined by the electrical skin
70. Langley JN. The autonomic ner - 86. Nickerson M. Drugs inhibiting resistance method I Neurophysiol
vous system. Vol. I Cambridge: adrenergic nerves and structures 1945;8:323-338.
Hefler & Sons, 1921. innervated by them. In: Goddman 101 . Riley CM. Familial autonomic dys -
71. Llewellyn-Smith IJ, Phend KD, LS, Gilman A, eds. The pharmaco- function. |AMA 1952,149: 1532
Minson JB, Pilowsky PM, logical basis of therapeutics. Ch. 1535.
Chalmers JP. Glutamate- immuno- 26. New York: Macmillan, 1970; 102. Riley CM, Moore RH. Familial
reactive synapses on retrogradelv - 549-584. dysautonomia differentiated from
labelled sympathetic pregan - 87. Nilsson C, Kannisto P, Lindvall- related disorders. Pediatrics 1966,
glionic neurons in the rat thoracic Axelsson M,Owman C, Rosengren 37:435-446.
spinal cord. Brain Res 1992;581: E. The neuropeptides vasocative 103 . Root WS. Physiology of micturi -
67-80. intestinal polypeptide, peptide his- tion: a specific autonomic function.
72. Loewi O. Uber humorale Lber - tidine isoleucine and neuropeptide In: Mountcastle VB, ed . Medical
tragharkeit der Herznerven- Y modulate pll| noradrenaline re- physiology. 12th ed. Ch . 79: St .
wirkung. Arch Gesamte Pvsiol lease from sympathetic nerves in .
Louis; CV . Mosby 1969:1831-
Menschen Tiere 1921,189:239-242. the choroid plexus. Eur J Pharma - 1838.
73. Loewi O. Chemical transmission of col 1990;181:247-252. 104. Rotto- Percelay DM, Wheeler JG,
nerve impulses. Sci Prog 1945; 88 . Norberg KA . Transmitter histo- Osorio FA, Platt KB, Loewy AD.
4:98-119. chemistry of the sympathetic Transneuronal labeling ot spinal
74. Lundberg A . Electrophysiology of adrenergic nervous system. Brain interneurons and sympathetic pre-
the salivary glands. Physiol Rev Res 1967;5:125-170. ganglionic neurons after pseudo-
1958;38:21-40. 89. Pacholczyk T, Blakeley RD, Amara rabies virus infections in the rat
75 .
.
Lundberg JM, Dahlstrdm A, Lars-
son I, Petersson C, Ahlman H,
Kewenter J. Efferent innervation of
SG. Expression cloning of a co-
-
caine- and antidepressant sensitive
human noradrenaline transporter .
medial gastrocnemius muscle.
Brain Res 1992;574:291-306.
105. Saito II. Innervation of the guinea
the small intestine by adrenergic Nature 1991;350:350-354. pig spleen studied by electron mi -
neurons from the cervical svmpa - 90. Parent A , Poirier LJ, Boucher R , croscopy . Am J Anat 1940;189
thetic and stellate ganglia, studied Butcher LL. Morphological charac- 213- 235.
by retrograde transport of peroxi- teristics of acetylcholinesterase- 106. Saper CB. Hypothalamus. In : I’axi-
dase. Acta Physiol Scand 1978; containing neurons in the CNS of nos G, ed. The human nervous sys-
104 33 42 DFP- treated monkeys. Part 2. Di - tem. Ch. 15. New York: Academic
76. Lundberg .
JM Terenius L, Hdkfelt encephalic and medial telen- Press, 1990:389-413.
T, et al. Neuropeptide Y ( NPY )-like cephalic structures. I Neurol Sci 107. Sapor CB, Loewy AD, Swanson
immunoreactivity in peripheral 1977;32:9-28. LW, Cowan WM. Direct hypothal-
noradrenergic neurons and effects 91. Patton HD. Retlex regulation of amo-autonomic connections. Brain
of NPY on sympathetic function. movement and posture. In: Ruch Res 1976;117:305-312.
Acta Physiol Scand I982;1l6: TC, ed. Neurophysiology. Ch. 6. 108. Satomi H, Yamamoto T, Iso II.
477-480.
77. McLennan IJ. Synaptic transmis-
sion. Philadelphia: VV.B. Saunders,
Philadelphia: \ \ B
1961:167-198.
Saunders,
92. Pearson J, Pytel B. Quantitative

Takatama H. Origins ol the
pa rasympa t hot ic .
preg inglionit
fibers to the cat intestine, as
1963. sudies of sympathetic ganglia and demonstrated by the horseradish
78 McMichael J Spinal tracts subserv - spinal cord intermedio-lateral gray peroxidase method . Brain Res
ing micturition in a case of Erb' s columns in familial dysautonomia. 1978;151:571- 578.
spinal paralysis. Brain I 945;68:162. J Neurol Sci 1978;39:47- 59. 109. Schotzinger RJ, Landis SC. Acqui -
79. Malmfbrs T. Release and depletion 93 Phelps PF., Ruber RP, Vaughn JE. sition of cholinergic and peptider -
of the transmitter in adrenergic ter - Embryonic development of choline gic properties by sympathetic in -
nervation of rat sweat glands re- 120. Strack AM, Sawyer WB, Platt KB, 131. Wiberg M, Widenfalck B An
quires interaction with normal tar - Loewy AD. CNS cell groups regu- anatomical study of the origin of
get . Neuron 1990;5:91- 100. lating the sympathetic outflow to sympathetic and sensory innerva -
110. Schwartz III Chemical messen- adrenal gland as revealed by tion of the elbow and knee joint in
gers: small molecules and pep- transneuronal cell body labeling the monkey . Neurosci Lett 1991;
tides. In: Kandel ER , Schwartz JH, with pseudorabies virus. Brain Res 127:183- 188.
Jessell TM, eds. Principles of 1989;491:274 - 296. 132. Wiley JW , Lu YX , Owyang C.
neural science. Ch. 14 . New York: 121 . Swanson LW , McKellar S. The dis- Evidence for a glutamatergic
Elsevier, 1991:213- 224 . tribution of oxytocin-and neuro- neural pathway in the myenteric
111. Schwyn RC. An autoradiographic physin-stained fibers in the spinal plexus. Am ) Physiol 1991;261:
study of satellite cells in autonomic cord of the rat and monkey. J 693-700.
ganglia . Am | Anat 19f»7; 121: Comp Neurol 1979;188:87 106.
- 133. Williams TH . Electron microscopic
727-740 . 122. Tang IK.', Ruch TC. Localization of evidence for an autonomic in-
112. Seguela P, Watkins KC, Geffard M , brain stem and diencephalic areas terneuron. Nature 1%7;214:309-
Descarries L. Noradrenaline axon
terminals in adult rat neocortex: an
controlling the micturition reflex . J
Comp Neurol 1956;106:213-26.
310 .
134. Williams TH, Black AC, Chiba T,
immunocytological analysis is ser- 123. Tollefson L, Bulloch K . Dual-label Jew JY. Species differences in
ial thin sections. Neuroscience retrograde transport: CNS innerva- mammalian SIF cells. In: Costa E,
1990;35:249-264. tion of the mouse thymus distinct Gessa GL, eds. Advances in bio-
113. Sheehan D. Discovery of the auto- from other mediatinum viscera. J chemical psvchopharmacologv .
nomic nervous system. Arch Neu- Neurosci Res 1990;25:20- 28. Vol. 16. New York: Raven Press,
rol Psychiatry 1936;35: 1081- 1115. 124 Truex RC. The sympathetic gan - 1977:505-511 .
114 Sheehan D. Spinal autonomic out- glions of hypertensive patients. 135. Willis W . Visceral pain. In: Brtniks
flows in man and monkey . | Comp AM A Arch Pathol 1951;51: 186- 191 . FP, Evers PW , eds. Nerves and the
Neurol 1941;75:341- 370 . 125. Uehara Y , Burnstock G. Demon- gut. Thorofare, NJ: C.B. Slack,
115. Sheehan I ). The autonomic ner - stration of gap junctions between 1977:350- 364.
vous system. Annu Rev Physiol smooth muscle cells. J Cell Biol 136. Winkler H. Occurrence and mech-
PMl 1970;44:215- 217. anism of exocytosis in adrenal
116. Sjogren C, Andersson K -E, Husted 126. Von Euler US. Noradrenaline. medulla and sympathetic nerve.
S, Mattiasson A , Moller - Madsen B Springfield, IL: Charles C. Thomas, In: Trendeienberg U, Weiner N,
Atropine resistance of transmu- 1956. eds. Handbook of experimental
rally stimulated isolated human 127. Von Euler US. Neurotransmission pharmacology . Vol. 90. Part II.
bladder muscle. J Urol 1982; in the adrenergic nervous system. Berlin: Springer Verlag, 1988:
128: 1368- 1371. The I larvey Lectures, Ser . 55. New 43- 118.
117. Smith OA Jr, Clarke NP. Central York: Academic Press, 1961:43-65. 137. Wolf G, Sutin J. Fiber degeneration
autonomic pathways: a study in 128. Von Euler US. Catecholamines in after lateral hypothalamic lesions
functional neumanatomv. J Comp nerve and organ granules. In. Von in the rat . J Comp Neurol
Neurol 1964; 122:399-406. Euler US, ed . Mechanism of release 1966;127:137- 156 .
118. Sternini C, Anderson K . Calcitonin of biogenic amines. New York: 138. Wolf GA Jr. The ratio of pregan-
gene-related peptide-con t aining Pergamon, 1966:211- 222. glionic neurons to postganglionic
neurons supplying the rat diges- 129. Warwick R . The ocular parasym- neurons in the visceral nervous
tive system: differential distribu - pathetic nerve supply and its mes- system . J Comp Neurol 1941;
tion and expression pattern . So- encephalic sources. J Anat 1954; 75:235-243.
matosen Mot Res 1992;9:45-59. 88:71-93. 139. Wolfe DE, Potter LT, Richardson
119. Strack AM, Loewy AD. Pseudora - 130. White JC. Okelberry AM, KC, Axelrod J . Localizing tritiated
bies virus: a highly specific Whitelavv GP. Vasomotor tonus of norepinephrine in sympathetic
transneuronal cell kxly marker in the denervatcd artery. Arch Neu- axons by electron microscopic au-
the sympathetic nervous system . I rol and Psychiatry I 936;36:1251 - toradiography . Science 1%2;138:
Neurosci 1990;10:2139- 2147. 1276. 440-442 .
Section IV
Spinal Cord
10
Spinal Cord: Regional Anatomy
and Internal Structure
TOPOGRAPHIC ORGANIZATION nerves do not change, but there is a lengthen -
ing of root filaments between the interverte-
The spinal cord is the least modified por- bral foramina and the spinal cord . This is
tion of the embryonic neural tube and the most marked for the lumbar and sacral spinal
only part of the adult nervous system in roots. These roots descend for a considerable
which the primitive segmental arrangement distance within the dural sac before reaching
clearly is preserved. It is a long, cylindrical their respective intervertebral foramina . The
structure, invested by meninges, which lies in large number of lumbosacral roots surround -
the vertebral canal . It extends from the fora - ing the filum terminale is known as the cauda
men magnum ( Fig. 1.4 ), where it is continu - equina ( Fig. 10.1 ). Spinal nerves emerge from
ous with the medulla , to the lower border of the vertebral canal via the intervertebral
the first lumbar vertebra ( Fig. 1.6 ). The spinal foramina . The first cervical nerve emerges be-
cord has two enlargements, cervical and lum - tween the atlas and the occiput ( Fig. 1.4 ). The
bar or lumbosacral, each associated with eighth cervical root emerges from the inter-
nerve roots which innervate, respectively, the vertebral foramen between C7 and Tl ; all
upper and lower extremities ( Fig. 10.1). The more caudal spinal nerves emerge from the
spinal cord has a conical termination, the intervertebral foramina beneath the vertebrae
conus medullaris ( Figs. 1.6 and 10.1 ). A con - of their same number ( Fig. 10.3). Dorsal root
densation of pia mater, extending caudally fibers usually are absent in the first cervical
from the conus medullaris, forms the filum and the coccygeal roots, and there are no cor-
terminale. The latter structure joins the dural responding dermatomes for these segments.
tube at levels of the second sacral vertebra, The length of the spinal cord from its junc-
becomes invested by dura, and continues as tion with the medulla to the tip of the conus
the coccygeal ligament to the posterior sur- medullaris is about 45 cm in the male and 43
face of the coccyx ( Fig. 1.6). cm in the female. In contrast, the length of the
While the spinal cord is a continuous un- vertebral column is about 70 cm. The weight
segmented structure, the 31 pairs of spinal of the spinal cord is about 35 g. In the
nerves associated with localized regions pro- mid thoracic region, the transverse and sagit-
duce an external segmentation ( Fig. 10.1 ). On tal diameters of the spinal cord are about 10
the basis of this external segmentation, the mm and 8 mm, respectively; in the cervical
spinal cord is considered to consist of 31 seg- enlargement (sixth cervical ), 13-14 mm and 9
ments, each of which receives and furnishes mm; in the lumbar enlargement ( third lum-
paired dorsal and ventral root filaments ( Fig. bar ), about 12 mm and 8.5 mm (see Fig. 10.5).
10.2 ). The spinal cord is divided into the fol - When freed from its meninges, the surface
lowing segments: 8 cervical, 12 thoracic, 5 of the cord shows a number of longitudinal
lumbar, 5 sacral, and 1 coccygeal. Up to the furrows ( Figs. 10.1, 10.2, 10.6, and 10.7). On
3rd month of fetal life the spinal cord occu- the anterior surface, an anterior median fissure,
pies the entire length of the vertebral canal, penetrating the cord for a depth of some 3
but after that time the differential rate of mm, contains an epipial fold with sulcal
growth of the vertebral column exceeds that branches of the anterior spinal artery and
of the spinal cord . At birth , the conus vein ( Fig. 4.2). On the posterior surface is
medullaris is located near the L3 vertebra; in the shallow posterior median sulcus . This sul -
the adult it is between the LI and L2 verte- cus is continuous with a delicate glial par-
brae, and the spinal cord occupies only the tition , the posterior median septum , which
upper two-thirds of the vertebral canal ( Fig. extends into the cord and reaches the deep-
10.3). The sites of emergence of the spinal lying gray matter. Lateral to the midline
325
326 Section IV Spinal Cord
Dorsal root of Ventral root of

spinal nerve spinal nerve
C2 C1
Post median
,
sulcus Post inter-

,
mediate sulcus
Cervical
enlargement
Dorsal root
Posterolateral
sulcus
Dorsal root
Lumbar
enlargement
Conus
medullaris Dorsal root
Dorsal root
Filum terminale Coccygeal nerve
Figure 10.1 Posterior view of the spinal cord showing attached dorsal root filaments and spinal ganglia letters and
,
numbers Indicate corresponding spinal nerves ,
posteriorly are two less distinct sulci associ- filaments emerge at less regular intervals and
ated with spinal roots. The posterolateral sul - are less numerous than dorsal roots, the an -
a/s is a shallow furrow into which filaments terolateral sulcus may be more difficult to
of the dorsal roots enter the spinal cord ( Fig. distinguish. In cervical and upper thoracic
10.6 ). The anterolateral sulcus marks the site of spinal segments, the posterior intermediate sul -
emergence of ventral root fibers. Since ventral cits indents the spinal cord between the poste-
10 Spinal Cord: Regional Anatomy and Internal Structure 327
Posterior median septum

Posterior intermediate septum
Posterior funiculus Posterior gray horn
zone Lateral funiculus

Dorsal root entry
Anterior funiculus
Anterior gray horn
Root filaments
Dorsal root
Dorsal
ganglion
Ventral-
Pia mater
Arachnoid
Mixed spinal
nerve
Dura mater
Root sleeve
Anterior median /
/
fissure
Figure 10.2 Spinal cord, nerve roots, and meninges The blood supply and venous drainage of the spinal cord are
shown in Figures 4.1 and 4 2
rior median and posterolateral sulci ( Figs.

10.2 and 10.6). This sulcus is associated with a
.
gives rise to fibers tli it form the lumbar plexus
( LI to L4 ) and the sacral plexus ( L4 to S2 ) .
glial partition, the posterior intermediate sep- Spinal segments vary in cross-sectional diam-
tum , that extends internally toward the spinal eters and in length . Thoracic spinal segments
gray matter ( Figs. 10.2 and 10.6). The anterior have the longest length while sacral segments
median fissure and posterior median septum have the shortest length . The tapered termi-
divide the cord into incompletely separated nal portion of the spinal cord , the conus
halves connected by a narrow mid line com - medullaris provides cutaneous innervation to
missure, composed of gray and white matter. the saddle area, motor innervation for the
Although the spinal cord is a symmetric sphincters, and parasympathetic innervation
structure, it is not uniform in diameter. It for the bladder ( Fig. 9.11 ). The filum terminate
contains two enlargements, cervical and lum - extending caudally from the conus med -
bosacral, associated with the largest nerve ullaris lies in the lumbar cistern surrounded
roots which innervate the extremities. The by lumbosacral nerve roots forming the cauda
ceri ical enlargement , consisting of the four
’ equina ( Figs. 1.6 and 10.1 ).
lowest cervical segments and the first tho- In transverse section the spinal cord con -
racic segment, gives rise to the nerve roots sists of ( a ) a butterfly-shaped central gray
that form the brachial plexus ( Figs. 10.1 and matter composed of collections of cell bodies
10.3) and provide innervation for the upper and their processes, and ( b ) a surrounding
extremity ( Figs. 8.14 and 8.15). The lumbar or mantle of white matter composed of bundles
lumbosacral enlargement ( Figs. 10.1 and 10.3) of myelinated fibers, most of which are either
root entry zone. An anterior ( ventral ) gray col-

umn or horn extends anteriorly but does not
reach the surface. Thoracic spinal segments
are characterized by a small, pointed lateral
horn near the base of the anterior horn ( Fig.
10.7). Gray anterior and posterior commissure,
connecting the gray matter of the two sides,
encompasses the central canal ( Fig. 10.4). Sur-
rounding the central canal is a light granular
area composed mainly of neuroglia, known
as the central gelatinous substance (substan-
tia gliosa ). Anterior to the gray commissure is
a bundle of transverse fibers, the anterior ( ven-
tral ) white commissure , composed of crossing
fibers arising from nerve cells in the gray
matter ( Figs. 10.4 and 10.7).
Ascending and descending fibers occupy-
ing particular regions of the white matter of
the spinal cord are organized into more or
less distinct bundles ( Figs. 10.6 and 10.13).
Fiber bundles having the same, or similar,
origin, course and termination are known as
tracts or fasciculi. The white matter of the
spinal cord is divided into three paired funi-
culi: posterior, lateral, and anterior. The poste-
rior funiculus lies between the dorsal horn and
the posterior median septum ( Fig. 10.2). In
upper thoracic and cervical regions, a small
posterior intermediate septum divides each pos-
terior funiculus into two white columns. The
lateral funiculus lies between the dorsal root
entry zone and the site where ventral root
fibers emerge from the spinal cord . The ante-
rior funiculus lies between the anterior me-
dian fissure and the emerging ventral root fil-
aments. The posterior funiculus is the largest
and is composed almost exclusively of long
ascending and short descending fibers that
arise from cells in the spinal ganglia.
The cervical enlargement , consisting of the
four lowest cervical segments and the first
thoracic segment, gives rise to nerve roots
Figure 10.3 . Position of the spinal cord segments with which form the brachial plexus ( Figs. 8.14 and
reference to the bodies and spinous processes of the
vertebrae.
8.15). The lumbar ( or lumbosacral ) enlargement
( Figs. 8.19 and 8.20) gives rise to fibers that
form the lumbar plexus ( LI to L4) and the
sacral plexus ( L4 to S2).
ascending or descending ( Figs. 10.2 and 10.7). Although the spinal cord constitutes only
The symmetric butterfly-shaped gray consists 2% of the central nervous system by weight,
of cell columns, some of which extend the its functions are tremendously important
length of the spinal cord , and vary in con- since it (a ) receives afferent inputs via the
figuration at different levels ( Figs. 10.5 and dorsal roots from somatic and visceral recep-
10.6) . tors in most parts of the body, ( b) gives rise to
Each half of the spinal cord has a posterior ascending pathways which transmit impulses
( dorsal ) gray column or horn which extends to higher levels of the neuraxis, (c) gives rise
posterolaterally almost to the surface near the to fibers emerging in the ventral roots that in-
Cervicol cord - 80 mm Socrol cord - newborn Cervical cord - odull

embryo
Figure 10.4 Ependymal cells and central canal of embryonic and adult human spinal cord. The sulcus llmitans (s/ in
A) becomes lost in the adult Processes of the ependymal cells entering the posterior median septum (ps) can be
seen and the fibers of the anterior white commissure are identified (ac) A Holmes silver stain. x 263 B . Luxol fast blue-
cresyl violet, x 112 C. Holmes silver-cresyl violet. x ! 08
nervate somatic and visceral effectors, (d ) vessels and their contents. The larger vessels
conveys descending pathways from higher are accompanied by prolongations of pial
levels of the nervous system, and (e) partici- connective tissue. The gray matter contains
pates in a variety of somatic and autonomic the nerve cells, dendrites, portions of myeli -
reflexes. Meninges surrounding the spinal nated and unmyelinated nerve fibers, and
cord and nerve roots are described in Chapter glial cells. These fibers are axons of nerve
1 and the blood supply of the spinal cord is cells located in the gray matter which pass
discussed in Chapter 4. into the white matter, or portions of the axons
in the white matter which enter the gray mat -
INTERNAL STRUCTURE ter to terminate there. The preponderance of
neurons, neuroglia , and capillaries imparts a
The microscopic appearance of the adult -
firm consistency to the butterfly or H shaped -
spinal cord is vastly altered from the three- gray matter ( Fig. 10.7). This density is en -
layered embryonic neural tube ( Fig. 3.5). The hanced further by a multitude of fine glial
incoming and outgoing processes of ganglion processes, fibrils, synaptic terminals, and
cells and intrinsic neurons produce marked dendrites, which invests neurons in an in -
changes in the embryonic marginal and man- tricate meshwork, or neuropil . In sections
tle layers. The embryonic layers become lon- stained with either hematoxylin and eosin or
gitudinal columns of gray and white matter cresyl violet, the gray matter has a highly cel -
in the adult spinal cord , each having micro- lular appearance, while the fibrous elements
scopic landmarks and subdivisions ( Figs. 10.2 of the neuropil are unstained . In such sec-
and 10.6). Individual segments of the spinal tions only the neuronal perikarva , glial , and
cord show variations at different levels, for endothelial nuclei are apparent. The enor-
there is great variation in the size and num- mous dendritic plexus of the neurons and
ber of fibers in the individual spinal nerves their synaptic endings remain unstained ( Fig.
( Fig. 10.1 ) . 5.28). Lorente de No ( 74 ) estimated that the
soma of the perikaryon forms only 69; of the
Gray and White Matter surface of a neuron . Hence the neuropil of the
gray matter, which is not visible in Nissl-
The gray and white matter ( or substance) stained sections, is where most dendritic
are composed of neural elements supported plexuses are located . The central canal, sur-
by an interstitial neuroglial framework. The rounded by ependymal cells, is located in the
mesodermal structures comprise the blood crossbar of the 11-shaped gray matter ( Figs.
SPINAL CORD below the central canal form the posterior

and anterior gray commissures. The anterior
Segment
commissure is much more massive than the
posterior commissure, which is composed
only of a small group of myelinated fibers.
The white matter contains few neurons or
dendrites, but is composed of ascending and
descending myelinated and unmyelinated
nerve fibers. The longitudinally arranged
fiber bundles and their supportive neuroglial
cells surround the gray matter as the poste-
rior, lateral, and anterior white funiculi . Nu -
merous myelinated axons can be observed
entering or leaving the white funiculi as dark
fibers in sections stained by the Weigert
method ( Figs. 10.7 and 10.10 ). The structure
and distribution of the glial cells are pre-
sented in Chapter 6. The processes of astro-
cytes form a superficial glial membrane which is
adherent to the deep surface of the pia mater.
Segmental Variations
The different segments of the spinal cord
vary ( a ) in size and shape, ( b ) in the relative
amounts of gray and white matter, and ( c) in
the disposition and configuration of the gray
matter ( Fig. 10.5). Cervical spinal segments
contain the largest number of fibers in the
white matter because (a ) descending fiber
systems have not yet contributed fibers to
lower segmental levels and ( b ) ascending
fiber systems at each successively rostral seg-
ment reach their maximum . The gray cell
columns are maximal in the cervical and lum -
bar enlargements which are associated with
the larger nerves that innervate the extremi -
ties. Lumbosacral segments contain large
amounts of gray matter, relative to both the
size of the cord segments and the amount of
white matter ( Figs. 10.16 and 10.17).
Figure 10.5 Selected spinal cord segments at different
levels showing the variations in size, shape, and topogra-
phy of gray and white matter . CERVICAL SEGMENTS
These segments are characterized by their
relatively large size, relatively large amounts
10.4 and 10.7). A sharply delineated central of white matter, and oval shape ( Figs. 10.5,
canal is seen only in fetal and newborn spinal
cords. In the adult , the ependymal lining
—
10.8 10.10). The transverse diameter exceeds
the anteroposterior diameter at nearly all lev-
often is discontinuous and the lumen may els. On each side, the posterior funiculus is
contain debris, round cells, macrophages, divided by a prominent posterior intermedi-
and neuroglial processes ( Fig. 10.4C ). Sur- ate septum into a fasciculus gracilis ( medial )
rounding the central canal are clumps of fi - and a fasciculus cuneatus (lateral ). In the lower
brous astrocytes rarely seen in other parts of cervical segments (C5 and below ) related to
the gray matter ( Figs. 6.2 and 6.12 ). The two the brachial plexus, the posterior ( dorsal )
slender bands of gray matter above and horns are enlarged , and well-developed ante-
A
Posterior median Sulcus
Posterior intermediate
Posterior lateral sulcus Central gray columns
Sulcus
- Septem
Posterior gray column
Funicular white matter
Anterior gray column / / Anterior lateral

sulcus
Anterior median fissure
Anterior median fissure
Spinal ganglia — f
Dorsal root filaments
Ventral root filaments
Figure 10.6 A . infernal arrangement of gray and white matter of the spinal cord B External and internal topogra -
phy of cervical spinal cord
Posterior median sulcus Posterior median septum

Posterior funiculus
Substantio gelatmosa
Dorsolateral fasciculus
Zono spongiosa
Post groy horn
Reticular process
Intermediate gray
Lateral horn
Lateral funiculus
Anterior gray horn
Anterior funiculus
Nuc dorsalis
(Clorke' s column )
Anterior white commissure
Central canal
Figure 10.7 Section through a lower thoracic segment of adult human spinal cord to demonstrate subdivisions of
the gray and white matter Photograph of Weigert ' s myelin stain on left and schematic drawing on right Area sur -
rounding the gray matter, and limited peripherally by the dotted line, is composed of shorter ascending and de-
scending fibers of the fasciculus proprius system
Fosc . gracilis
Fasc . interfascicularis
Fasc . cuneatus
A i Dorsal root fibers
As Substantia gelatinosa
Lot. corticospinal tr.
A Post spinocerebellar tr
,
i
v v
L,. Rubrospinal tr .
t
h Reticulospinal tr.
Ant spinocerebellor tr.
1 r~ *A Lot. spinothalamic tr.
w — Spinotectal tr .
\ J '
Spino - olivary tr .
Ant . spinothalamic tr.
Vestibulospinal tr.
Ant. corticospinal tr .
Figure 10.8 Photomicrograph ( left) and drawing (right) of a section through upper portion of first cervical segment
of adult human spinal cord Some of the important fiber tracts are identified (Weigert s myelin stain)
Figure 10.9 Transverse section through the second cervical segment of the adult human spinal cord Note the nar -
rowness of the anterior and posterior gray horns and the abundant white matter Cell groups are identified in Figure
10 11 (Welgert 's myelin stain)
Figure 10.10 Transverse section through the fourth cervical segment of the adult human spinal cord demonstrating
entering dorsal root fibers At this level the substantia gelatinosa is larger and a well-developed lateral process of the
anterior gray horn is seen Cell groups in the spinal gray are identified in Figure 10.11 (Weigert ' s myelin stain)
Post, median septum Fasc gracilis

Post intermediate septum \ Fosc interfascicularis
Oorsal root Fosc cuneatus
Zone of Lissauer Nuc. posteromarginalis

Post, spinocerebellor tract
Nuc . proprius dorsalis
Lot corticospinol tract

Nuc reticularis
Nuc . dorsalis
Rubrospinal tract
ft
- Ant . spinocerebellar tr
- Lot. spinotholomic tr.
Nuc . motorii lateralis
-Spinotectal tract
Spino - olivary tr.
Ventral root
Vestibulospinal tract
Ant corticospinal tr. tract
Ant. spinothalamic
Medial longitudinal fasc. Nuc motorii medialis
Figure 10.11 Section through eighth cervical segment of adult human spinal cord The important cell groups and
fiber tracts are identified 1 , Nucleus comucommissuralis posterior. 2. nucleus cornucommissuralis anterior (Weigert ' s
myelin stain)
rior ( ventral ) horns extend into the lateral fu- ( below about T6). In general, the anterior ( ven-
niculi ( Figs. 10.11 and 10.12 A ). Near the neck tral ) and posterior (dorsal ) horns are small and
of the posterior horn is a serrated cellular somewhat tapered . The first thoracic segment
area known as the reticular process ( reticular is an exception in that it forms the lowest seg-
nucleus); this process is present in all cervical ment of the cervical enlargement and con-
segments. In upper cervical segments (Cl tributes to the brachial plexus. A prominent,
and C2), the dorsal horn is enlarged , but the but small, lateral horn is present at all thoracic
anterior ( ventral ) horn is relatively small levels and contains the intermediolateral cell
( Figs. 10.8-10.10). The transverse diameter of column which gives rise to preganglionic sym-
the most rostral cervical spinal segment is pathetic fibers ( Figs. 10.12 B and 10.13). At the
about 12 mm, while it is 13 14 mm at C8. — base of the medial aspect of the posterior horn
is a rounded collection of large cells, the dorsal
THORACIC SEGMENTS nucleus of Clarke (Figs. 10.7, 10.12B, 10.13, and
10.15). While this nucleus is present in all tho-
These segments show variations at differ- racic segments it is particularly well -devel-
ent levels ( Figs. 10.5, 10.7, 10.13, and 10.15). oped at T10 through T12. The large cells of this
Both the fasciculi gracilis and cuneatus are nucleus have a characteristic appearance in
present in upper thoracic segments (T1 to T6 ), that their large vesicular nuclei often are ec-
while only the fasciculus gracilis is seen in the centric, and chromophilic material is distrib-
posterior funiculus at more caudal levels uted peripherally in the perikaryon .
Substantia Posterior
gelatinosa gray horn
Dorsal nucleus
Posterior of Clarke
Intermedio- Intermedio -
gray horn
medial lateral
nucleus nucleus
Intermediate
zone - Intermediate
x I VII '
gray horn
Anterior Central
canal VIII
- gray Anterior
Central horn IR gray
canal Intermediomedial
nucleus IX horn
A (C 6 ) B O 10)
’
ii Postero-
Substantia Substantia- II marginal
Intermediomedial IV gelatinosa
gelatinosa in nucleus
nucleus
v
Intermediate Proper sensory -, IV Sacral
VI zone nucleus autonomic
V
V
nucleus
Central X
canal VII
VII Central
> IX
VIII IX canal
VIII
IX Intermediomedial
IX-
nucleus
IX
IX Commissural nucleus
C (L 5 ) D (S 4 )
Figure 10.12 Structural lamination of human spinal cord segments at C6 (A). T10 (B). L5 (C). and S4 (D) Additionally ,
the laminae of Rexed. several distinct nuclei, and structures are identified, including the central canal The drawings
are derived from analyses of thick human spinal cord sections stained with thionin.
Fasc . gracilis
Nuc . dorsalis (of Clorke )
Nuc , proprius dorsalis
Substantia gelatinoso
Nuc . posteromarginalis
Lot . corticospinal troct
Nuc . reticularis
Rubrospinal tract
Nuc intermediolateralis
Lat. spinotholamic tract
Nuc . motorius lateralis
Ant. spinotholomic troct

/
Med long. fasc. Nuc . motorius medialis
Vestibulospinal troct
Figure 10.13 Photomicrograph ( left ) and drawing ( right ) of a section through the fifth thoracic segment of adult
.
human spinal cord important cell groups and fiber tracts are identified, I . Nucleus cornucommissuralis posterior; 2
,
nucleus cornucommissuralis anterior (Weigert ' s myelin stain).
Upper thoracic spinal nerves, except for ments L3 through L5 innervate large muscle
Tl , supply motor innervation only to axial groups in the lower extremities. Upper lum-
musculature ( i.e., the back and intercostals). bar levels ( LI and L2 ) resemble lower tho-
Lower thoracic nerves supply the same mus- racic spinal segments ( Figs. 10.7 and 10.15) in
cles and the abdominal musculature. Thus, that they contain the dorsal nucleus of Clarke
the anterior horns of lower thoracic spinal and the intermediolateral cell column . The
segments are a little larger. The small diame- dorsal nucleus of Clarke is especially well -de-
ter of the thoracic segments is due primarily veloped at LI and L 2. The transition between
to the marked reduction of gray matter ( Fig. T12 and LI is subtle, and these levels are dif -
10.13). ficult to identify precisely.
LUMBAR SEGMENTS SACRAL SEGMENTS

These segments are nearly circular in These segments are characterized by their
transverse section, have massive anterior small size, relatively large amounts of gray
( ventral ) and posterior ( dorsal ) horns, and matter, relatively small amounts of white
contain relatively and absolutely less white matter, and a short, thick gray commissure
matter than cervical segments ( Figs. 10.5, ( Figs. 10.5, 10.12 D , and 10.17). The anterior
10.12C, and 10.16). The fasciculi gracilis ( ventral ) and posterior ( dorsal ) horns are
which compose the posterior funiculus are large and thick, but the anterior horn is not
not as broad as at higher levels, especially bayed out laterally as in lumbar spinal seg-
near the gray commissure, and have a highly ments. In caudal sequence, sacral segments
characteristic configuration ( Fig. 10.16). The conspicuously diminish in overall diameter
well -developed anterior ( ventral ) horns have but retain relatively large proportions of gray
a blunt process that extends into the lateral matter. The substantia gelatinosa is particu -
funiculi. Motor cells in this process in seg- larly well -developed in sacral segments, and
Figure 10.14 Cutaneous input into the posterior gray horn Roman numbers /. II. Ill and IV represent laminae of
Rexed. SP is the spinal ganglion, and ZL ( shaded area) is the zone of Lissauer . Primary nociceptive afferents (reef)
enter lateral parts of the root entry zone, traverse the zone of Lissauer. and synapse upon distal dendrites of larger
cells in the posteromarginal nucleus (lamina I). Gelatinosa neurons in lamina II provide axons, or axon collaterals, that
synapse on the soma of cells in lamina I, and longer axons that ascend/or descend in the zone of Lissauer to ulti-
mately return to lamina II at other levels Nonnociceptive primary afferents ( blue) enter as part of the medial division
of root fibers by either passing medial to or through the superficial gray laminae. These larger caliber fibers enter lam-
ina II from its ventral aspect and arborize near gelatinosa neurons and in relation to dendrites of large cells of the
.
proper sensory nucleus in lamina IV Large cells in lamina IV ( blue) give rise to projection fibers ( PF ) some of which
cross in the anterior white commissure and project to the thalamus.
Post medion sulcus

Nuc cornucommissurolis posterior
Nuc dorsalis (of Clorke)
Substantia gelotinoso
Nuc. posteromarginolis
Nuc . proprius cornu

dorsalis
Nuc . reticularis
Nuc . intermediolateralis
Nuc . intermediomedialis
/ Nuc . motorius lateralis
7 Nuc . motorius medialis
Nuc . cornucommissurolis anterior

Anterior medion fissure
Figure 10.15 Photomicrograph ( left ) and drawing ( right ) of a section through the twelfth thoracic segment of the
adult human spinal cord Important cell groups are identified on the right (Weigert ' s myelin stain).
Fasc gracilis
Dorsal Nuc cornucommissurolis posterior
root fibers
Substantia gelotmosa
Nuc . posteromorginalis
Zone of Lissauer
corticospinal tr.
Nuc . proprius cornu dorsolis
Nuc reticularis
Nuc dorsalis ( of Clarke )
Ant . spinocerebellar tr.
Lot. spinotholomic tr.
Fasc . proprius
spinothalamic tr.
ventral
root fibers Vestibulospinal tr .
Nuc motorii medialis
Figure 10.16 Photomicrograph ( left ) and drawing ( right ) of a section through the fourth lumbar segment of adult
human spinal cord. The important cell groups and fiber tracts are identified (Weigert ' s myelin stain).
Septomarginal fasc
Fosc gracilis
. Dorsal root
posteromorginalis
Substantia gelotinosa
proprius cornu dorsalis
corticospinal tr
Nuc . mtermediomedialis
Lat spinotholomic tr .
Nuc motorius medialis
spinothalamic tr
Vestibulospinal tr
Figure 10.17 Photomicrograph ( left ) and drawing ( right ) of a section through the third sacral segment of adult
.
human spinal cord The important cell groups and fiber tracts are Identified I Nucleus comucommissuralis posterior.
2. nucleus comucommissuralis anterior (Weigert ' s myelin stain).
processes, and appearance) and the topo-

graphic location of cells within the spinal
gray matter, but this scheme has been rather
crude. While some believe that the terminol -
ogy should be based upon synaptology (ac-
cording to synaptic connections of neurons ),
this suggestion appears overly complex. The
most satisfactory terminology is based upon
the cytoarchitectural lamination of the spinal
gray matter as observed in thick sections
(80-100 |im ) of the spinal cord stained with
cresyl violet . In a series of papers, Rexed
( 118-120) described an architectural organi-
zation of neurons in the cat spinal cord that
has proven to be valuable in research and has
gradually become the accepted standard . His
several zones have been corroborated and
used by many investigators to describe termi-
nal arborizations of fibers within the spinal
gray matter. It is generally accepted that a
similar lamination or zoning of the gray mat -
ter exists in all mammals. A preliminary re-
port by Truex and Taylor (150 ) mentioned
that the cytoarchitectural laminae described
by Rexed in the cat are also present in hu -
mans. This has been confirmed by a detailed
study of the cytoarchitecture, dendroarchitec
ture, and myeloarchitecture of the spinal cord
-
in the newborn and adult human (131 ). This
lamination of cell populations within the
spinal gray matter has become the most pre-
cise and most widely used method for de-
Figure 10.18 Transverse sections through (A) the fifth scribing cell groups within the mammalian
sacral and (B) first coccygeal spinal segments of the spinal cord .
adult human spinal cord Note the abundance of spinal Studies of the cytoarchitectonic organization
gray in the anterior and posterior horns, the thickness of of the spinal gray matter recognize 10 distinct
the gray commissures, the size of the gray surrounding
the central canal, and the configuration of fasciculus
cellular laminae in most regions, which are
gracilis (Welgert s myelin stain) represented by Roman numerals ( Rexed's
laminae I to X ) ( Fig. 10.12 ). Lamina X refers to
the gray matter surrounding the central
this accounts for the thickened posterior gray canal. It is present in all segments and ap-
column d ig''. 10.17 and 1 o . 1 sA ). Coccygeal pears fairly uniform throughout the spinal
segments resemble lower sacral spinal seg- cord .
ments but are reduced in size ( Fig. 10.18B ). Drawings taken from thick frozen sections
The posterior gray horn and especially the of the human spinal cord from different seg-
substantia gelatinosa are greatly increased in mental levels are shown in Figure 9.12A - D.
size, while the anterior gray horn becomes The sections were stained with a combined
smaller. Weigert - Nissl method to demonstrate neu -
rons and delineate the boundaries of Rexed 's
Cytoarchitectural Lamination laminae . There are differences in laminar con-
figuration at various segmental levels of the
A variety of eponyms and inconsistent ter- spinal cord . The laminae constitute regions
minologies have long been used to describe with characteristic properties, but their
the nuclear groups in the spinal gray matter . boundaries are zones of transition, where
Terminology has been based largely upon changes may occur either gradually or
cytologic features (i.e., cell size, shape, abruptly . Only the principal features of indi-
victual lamina are included in this brief pre- jections from cutaneous nociceptors but have
sentation. Some of the laminae correspond to no direct input from cutaneous receptors re-
recognized cell columns and nuclei , while sponding to innocuous stimuli (68). Ion-
others are regional admixtures of cells. tophoretically injected HRP into single neu -
rons of lamina I has revealed the dendritic
LAMINA I arborizations, spines, and terminal varicosi -
ties of these neurons (69 ). No correlation
This lamina is, in the words of Rexed (118), could be made between cell size, configura -
"a thin veil of gray substance" that caps the tion, or dendritic arborizations and distinct
surface of the posterior horn and bends physiologic characteristics of those neurons.
around its margins. It does not have a uni - Other evidence indicates that axons of fibers
form thickness, being thicker at the level of in the dorsolateral fasciculus of Lissauer end
the Lissauer tract and on the lateral border of upon neurons in lamina 1 ( 58). A large pro-
the posterior horn . The lamina has a spongy portion of axons in the dorsolateral fasciculus
appearance and is penetrated by small and arise from cells of the substantia gelatinosa
large fiber bundles ( Figs. 10.12C and 10.16 ). (lamina II ). An electron microscopic study
The neuronal density is low and most cells has shown that axons of neurons in lamina II
are found in its dorsolateral part . It contains end axosomatically upon cells in lamina I ,
small and medium -sized cells with scant cy - while primary afferent fibers terminate axo-
toplasm and scattered , fairly large, spindle- dendritically (89 ). Almost all evidence sug-
shaped cells oriented parallel to the convex gests that neurons of lamina I respond specif -
surface of the posterior horn ( Figs. 10.14, ically to nociceptive and thermal stimuli ( Fig.
10.16, and 10.17). The cytoplasm of the large 10.14 ). The suggestion that cells of lamina I
cells ( the marginal cells of Waldeyer ) is rich contribute some fibers to the spinothalamic
in granular endoplasmic reticulum and other tract is based upon (a ) retrograde cell changes
organelles (107, 108). The majority of den - following spinothalamic tractotomies for re-
drites are oriented tangentially to the edge of lief of pain in humans ( 64 ), and ( b) an -
the posterior horn. However, besides their tidromic stimulation and retrograde labeling
disc-like dendritic domain being restricted to with HRP indicating that cells of lamina 1
the tangential plane (127), most cells also pos- project axons to the thalamus ( 63, 148, 161,
sess ventrally oriented dendrites, which im - 162).
pinge deeply into lamina II and can even In humans, spinothalamic cells in lamina I
reach laminae III and IV (129, 131 ). The den - represents only a small percentage of the total
drites of lamina I neurons are poorly cell population (130). Input to this lamina is
branched and moderately covered with ses- chiefly from peripheral nociceptors through
sile or pedicled spines, which appear more A & and C fibers (13, 76 ). These afferents form
numerous on the ventral dendrites. The com - a dense tangentially oriented terminal plexus
plex array of nonmyelinated axons, small which covers almost entirely the disc-like
dendrites, and synaptic knobs that lies within dendritic domains of lamina I neurons. There
this lamina corresponds to the posteroinarginal is evidence that lamina I also contains poly-
nucleus . In light microscopic preparations, it modal neurons, that is cells responding to
is best identified in sections through the lum- noxious as well as to innocuous stimuli con-
bar enlargement ( Figs. 10.16 and 10.17). veyed by Afi fibers ( 159, 160 ). The latter are
Studies in the rat, cat, and monkey, in distributed mainly in the deeper laminae of
which horseradish peroxidase ( HRP) has the posterior horn ( 76). There is also the pos-
been used to trace anterograde projections of sibility that Afi fibers might contact lamina I
dorsal root fibers into the spinal cord , indi - neurons on their ventral dendrites, which are
cate that thin fibers of the lateral division end particularly obvious in humans. These ven-
principally in lamina I and the outer part of tral dendrites lie within the rich plexus of
lamina II (67). The high density of terminals lamina II , where part of the control exerted
in lamina I ( marginal zone) and in the outer by the substantia gelatinosa on nociceptor-
part of lamina II indicate that these parts of driven projection neurons may be localized
the spinal gray matter receive a major affer- (131 ).
ent input ( Fig . 10.14 ). Physiologic observa- Other evidence indicates that some cells,
tions further demonstrate that lamina I and or dichotomizing axons of cells, in lamina I
the outer zone of lamina II receive direct pro- give rise to descending propriospinal projec -
tions extending for 8 or more spinal segments ture of the substantia gelatinosa is the pres-
(9 ).These descending fibers may influence ence of numerous small unmyelinated axons
motor neurons involved in withdrawal regrouped in bundles running parallel to the
flexes, or be part of an indirect input to other long axis of the spinal cord , or perpendicular
ascending systems. to that axis. Large myelinated axons repre-
senting primarily dorsal root fibers, pass
LAMINA II through lamina II into deeper regions of the
spinal gray matter . Myelinated fibers, fre-
This lamina which forms a well-delimited quently in bundles, are especially common in
band around the apex of the posterior horn is the medial half of lamina II .
readily identified in both myelin sheath and Afferent fibers to lamina II are derived
cell stains ( Figs. 10.8, 10.11, 10.15-10.17). This -
from collaterals in (a ) the dorsolateral fascicu
fairly broad band is covered dorsally and lus, ( b ) the posterior funiculus, and (c) parts
dorsolaterally by lamina I , but its medial bor- of the lateral funiculus adjacent to the poste-
der is the posterior funiculus. Lamina II is rior horn ( 143). Collateral fibers from these
composed of tightly packed small cells, corre- sources enter the substantia gelatinosa in a
sponds to the substantia gelatinosa of Rolando, radial fashion and form flame-shaped termi -
and is the oldest cytoarchitectonic region de- nal arborizations which establish synaptic
limited in the spinal cord (118). Although contact with large numbers of neurons ( Fig.
found at all spinal levels, it is massive in the 10.14). Fibers entering from the posterior fu -
cord enlargements. In the cat lamina II con - niculus traverse medial parts of laminae 1 and
sists of a dorsal or outer zone and a ventral or II , penetrate parts of laminae IV and V, and
inner zone . In the outer zone, about one-quar- recurve dorsally and laterally to enter lamina
ter of the thickness of the whole lamina , cells II from its ventral surface. Terminal arboriza -
are slightly smaller and more tightly packed tions within lamina II have a columnar
than in the inner zone. In humans, the separa - arrangement with little overlap. Synaptic
tion between the outer and the inner zone is profiles with round synaptic vesicles were
much less clear (131 ). found to be the dominant type in lamina I
Neurons in lamina II are round or elon- and the outer zone of lamina II (109, 110, 117 ).
gated with their long axis oriented radially to Anterograde transport of HRP via spinal
the surface of the lamina ( Fig. 10.14 ). The dorsal roots reveal that the outer zone of lam -
spindle-shaped cell bodies are hardly larger ina II receives terminations from the very
than the nucleus and give rise to rich den- finest afferent fibers, while the inner zone of
dritic trees from one or both poles of the this lamina receives endings from some of the
soma (143). Based on dendritic geometry and finest fibers, as well as from small myelinated
axonal course, neurons in human lamina II fibers ( 32, 67). Physiologic observations on
were classified into four types: (a ) islets cells, morphologically identified cells in laminae I
present in the central part of the lamina , ( b ) and II suggest that thinly myelinated primary
filamentous cells, located either in the outer afferents from nociceptors end mainly in lam -
or inner portion of the lamina, (c) curly cells, ina 1, while unmyelinated afferents from no-
generally located in the outer substantia ciceptors, thermoreceptors, and mechanore-
gelatinosa , and (d ) stellate cells, preferentially ceptors terminate predominantly in lamina II
found in the inner portion of the lamina ( 131 ). (69 ). Soma location could not always be cor-
Although the dendritic architecture of these related with afferent input, but cell bodies of
neurons varies from simple (e.g., stellate nociceptive and thermoreceptive neurons
cells ) to highly complex (e.g., curly cells ), the tended to be in lamina I, or the outer zone of
main axes of the dendritic arborizations in lamina 11, while innocuous mechanoreceptive
most cases are radial ( i.e., perpendicular to neurons tended to be in the inner zone of
the curved lamina ). At the ultrastructural lamina II ( Fig. 10.14 ).
level, cells of lamina II show a striking The majority of neurons in lamina II send
paucity of granular endoplasmic reticulum axons into the dorsolateral fasciculus, or into
which is correlated with the absence of dis- the adjacent lateral fasciculus proprius, al-
crete Nissl bodies in light microscopy (106, though some cells give rise to fine axonal
111 ). Thus, the cytoplasm of cells in lamina II plexuses retained within this lamina ( 25, 143).
is unusually pale in comparison with other Cells in medial parts of lamina II give rise to
spinal neurons. The most characteristic fea - commissural fibers that can be followed into
the contralateral substantia gelatinosa. Axons nosa over a considerable rostrocaudal dis-
originating from cells of lamina II have al- tance. Axons of these neurons emerge from
ways been traced back into this same lamina the proximal part of one ventral dendrite, bi -
at different levels. None of these axons have furcate a number of times, and the collaterals
been followed into other structures which form a dense plexus in laminae III and IV . Al -
might forward impulses to known sensory though the length of these axons is great they
pathways. Thus, lamina II has been regarded appear to ramify entirely within the gray
as a "closed system," although it can influ - matter and have been regarded primarily as
ence larger neurons in deeper laminae whose interneurons transmitting impulses from in -
dendrites are embedded in lamina II ( Fig. coming afferent fibers to the cells of origin of
10.14 ). Because neurons in lamina II appear sensory tracts. Most of the primary afferent
organized to exert their main synaptic influ - fibers to cells in lamina III are intermediate to
ences upon the larger cells in laminae III and thick fibers that follow a recurving course to
IV, whose dendrites lie within lamina II , it enter the ventral aspect of the lamina II ( 67,
has been postulated that the substantia gelati- 109, 110). Ultrastructural studies indicate di-
nosa may function as a controlling system verse synaptic populations in the posterior
modulating synaptic transmission from pri- horn derived from difference sources. The
mary sensory neurons to secondary sensory round synaptic profiles, dominant in laminae
systems (59, 60, 69, 83, 143, 156 ). I and II, decline in numbers in lamina III ,
where flattened synaptic vesicles predomi-
LAMINA III nate (109, 117 ). Thus, most cells in lamina 111
appear anatomically organized to function as
This lamina forms a band across the poste- interneurons. Although a few' of the larger
rior horn parallel with laminae I and II , ex - neurons in this lamina may contribute to as-
cept that the lateral bend is not so sharp ( Figs. cending sensory pathways, most of the long
10.12 A - D ). The neurons of this lamina are not ascending sensory fibers originate from cells
so closely packed as in lamina II, but are simi- of laminae I , IV, and V (1, 148, 149, 161 ).
larly round or spindle-shaped. Cells show
more variations in size and, in general, are LAMINA IV
larger than those in lamina II . Most of the
cells are oriented transversely to the lamina This lamina is the thickest of the first four
and vertically to its surface ( Fig. 10.14 ). Occa - laminae of the posterior horn . It extends
sionally, an exceptional large cell may be straight across the gray column ( Fig. 10.12C,
seen, but such cells properly belong to lamina D ). The borders of this lamina are sometimes
IV . The border between lamina II and III is diffuse and its cells, w' hich vary greatly in
well-defined due to the presence of large size, give it a less compact appearance than
numbers of medium -sized and small axons in lamina III . Most cells of this lamina are
lamina III w' hich form a meshwork of fibers round , triangular, or multipolar with a diam -
running longitudinally ( 109, 110 ). Neurons of eter ranging from 25-40 pun . Some very large
lamina III have a large light -staining nucleus, cells ( 50-75 pan ) also occurs. The cytoplasm
relative scant cytoplasm, and small amounts of these cells is more abundant than in the
of Nissl substance (106, 118). cells of lamina III and the plentiful Nissl sub-
Golgi-stained reconstructions of neurons stance in the large cells appears as fine evenly
in lamina III reveal that they belong to two distributed granules (118 ). The dendrites of
neuronal types ( 131 ). The majority of impreg- cells in lamina IV radiate upward into the
nated neurons possess an asymmetric den - substantia gelatinosa in a candelabra fashion
dritic in that the dorsal branches are more de- parallel to the primary afferent fibers ( 111 ,
veloped . These branches ascend vertically -
143). These dendrites have well developed
from the soma (30-50 jxm in diameter ) and spines and it seems likely that a large part of
penetrate deeply into the overlying lamina II, the dendritic surface is covered with synaptic
reaching up to 400 p.m in length ( 78). The contacts of larger primary afferent fibers ( Fig.
ventral dendrites are few' and short. The sec- 10.14 ). Primary afferents terminating on the
ond neuronal type is characterized by a radial somata of these neurons are rare ( 57, 60 ).
dendritic tree and a smaller perikarya ( 20 jxm Neurons of lamina IV respond to low' inten -
or less). In both cases, the dorsally directed sity stimuli, such as light touch, and their dis-
dendrites radiate into the substantia gelati - charge frequency parallels the stimulus inten -
sity (103). Because of these properties they lamina IV, contribute fibers that enter the
have been referred to as "wide dynamic spinothalamic tracts on the opposite side of
range neurons." Cells in laminae Ill and IV the spinal cord (1, 148, 149).
correspond to the proper sensory nucleus ( nu -
cleus proprius cornu dorsalis) of the older LAMINA VI
terminology ( Figs. 10.13 and 10.15-10.17).
In Golgi preparations, and in degeneration This lamina is a broad layer at the base of
studies, there is no evidence that the axons of the posterior horn and extends across its
cells in lamina IV give rise to axons that cross width. It is present only in the cord enlarge-
in the anterior white commissure and enter ments ( Figs. 10.1 and 10.5). There is no lam-
the anterolateral funiculus (143). Neverthe- ina VI between T4 and L2 ( Figs. 10.12 B , D )
less studies using antidromic stimulation and where lamina V forms the dorsal boundary of
the retrograde transport of HRP indicate that lamina VII. Like lamina V, it is divided into
axons of some of these cells cross at spinal medial and lateral regions ( Figs. 10.12A , C ),
levels and ascend to thalamic levels (1, 148, although such a division is less obvious in
149 ). These cells and others in laminae 1 and humans (131). The smaller, more compact,
V thus contribute fibers to the spinothalamic medial region contains numerous dark-stain-
tracts ( Figs. 10.14 and 11.6). -
ing medium and small sized cells. The larger
lateral region contains triangular or stellate
LAMINA V neurons. Many dorsal root group I muscle af -
ferents terminate in the medial zone of layer
This lamina is a broad zone extending VI while descending pathways are known to
across the neck of the posterior horn, which is project to cells in the lateral zone. Physiologic
divided into medial and lateral subdivisions, studies indicate functional differences be-
except in the thoracic region ( Fig. 10.12 B ). In tween laminae in the posterior horn (155).
humans, this mediolateral subdivision is not Cutaneous afferents are distributed more
as obvious as in cats, so that lamina V and dorsally than those concerned with proprio-
lamina VI , which are cytologically similar, ceptive sense or kinesthesis, but , with few ex -
are sometimes considered as a single entity ceptions, no lamina can be related to particu -
( i .e., lamina V - VI ) ( 131 ). Many fiber bundles lar sensory modalities ( 32). There is some
pass through the lateral zone of lamina V, evidence that a group of cells in lamina VI in
giving it a reticulated appearance. The lateral the cervical enlargement, designated as the
part of lamina V gives rise to a reticular centrobasal nucleus gives rise to an uncrossed
process ( i.e., reticular nucleus), prominent at tract projecting to the cerebellum (80, 98).
cervical levels ( Figs. 10.9-10.11 ). The dorsal These cells are considered as the origin of the
and ventral boundaries of this lamina are dif - rostral spinocerebellar tract. The centrobasal
fuse. Neurons of lamina V are highly variable nucleus is a major terminus of dorsal root
in size and shape, and commonly are triangu - fibers (134 ).
lar or multipolar, although spindle-shaped
neurons are seen. Cells have large clear nu - LAMINA VII
clei, relatively large amounts of cytoplasm
and fine Nissl granules; coarse Nissl granules This lamina occupies a large heteroge -
occur only in the largest cells. Dendrites of neous region anterior to laminae V and VI,
some neurons in lamina V extend dorsally in extending across the spinal gray matter on
lamina II in the same manner as the majority each side. This region, also known as the zona
of cells in lamina IV (143). The ventral den- intermedia (intermediate gray matter ), has
drites may extend as far down as lamina VII . boundaries which vary at different spinal lev-
The dendritic domain of lamina V neurons els ( Fig. 10.7). In the cervical and lumbosacral
has a preferential verticotransverse orienta - enlargements lamina VII extends laterally
tion . Dorsal root fibers synapse upon den- and ventrally into the anterior ( ventral ) horn
drites of cells in lamina V in the substantia and contains cell groups of lamina IX embed -
gelatinosa , and descending suprasegmental ded in it. In the thoracic region lamina VII oc-
fiber systems (e.g., corticospinal and rubro- cupies the zona intermedia and the base of
spinal fibers) appear to establish synaptic the anterior horn. Lamina VIII , which forms
contacts upon cells and their processes within its ventral border, is arched dorsally ( Figs.
lamina V . Neurons in lamina V, like those in 10.7 and 10.12 B ). Lamina VII gives a fairly
homogeneous appearance with evenly dis- occupy the ventromedial part of the anterior
-
tributed light staining nerve cells, a large gray horn, but in the cord enlargements
number of which are local interneurons ( in - greatly increased numbers of motor neurons
ternuncial ). The dendritic tree of these neu - form larger groups. Anterior horn cells of this
rons extends mainly along the mediolateral lamina are large multipolar neurons (30-70
plane. In particular, regions with well -de- pm in diameter ) regarded as the prototype of
fined cell columns are readily recognized . motor neurons. These cells have large central
These well-defined cell columns are the dor- vesicular nuclei, coarse NissI bodies, multiple
sal nucleus of Clarke, the intermediolateral dendrites, and large axons which contribute
nucleus, and the intermediomedial nucleus. to the ventral root . Somatic efferent neurons
Lamina VII and adjacent parts of laminae are largest in size and number in the cervical
V and VI also give rise to crossed fibers that and lumbar enlargements where the cell
ascend in the anterior spinocerebellar tract groups spread both laterally and dorsally
(80, 93). Many of these cells receive nonsy - ( Figs. 10.11 and 10.16 ) . The total number of
naptic excitation and disynaptic inhibition motor neurons in segments LI to S5 is about
from ipsilateral group lb muscle afferents. 52,000-62,000, with segment L5 frequently
containing the largest number of cells
(around 10,01X1) and segment SI showing the
LAMINA VIII
highest density of motor neurons per section .
This lamina includes a zone at the base of The number of motor neurons decreases with
the anterior horn , but its size and shape dif - age. It has been estimated that after 60 years
fers at various spinal levels. In the spinal en - of age, about 200 lamina IX neurons are lost
largements, this lamina occupies only the me- per decade ( 131 ).
dial part of the anterior horn ( Figs. 10.12 A, C, There has been numerous qualitative and
D ) . At other levels it extends across the base quantitative studies of the dendritic arboriza -
of the anterior horn under lamina VII ( Fig. tion of spinal motor neurons performed with
10.12 B ). Cells of this lamina vary greatly in either the Golgi method or the intracellular
size but are mostly triangular and stellate - HRP injection procedures ( 10, 56, 87, 127, 128,
shaped . The cells have relatively large 130, 152). These studies have led to various
amounts of cytoplasm and contain large Nissl classifications and groupings of motor neu -
granules. The larger multipolar neurons dif - rons on the basis of the morphologic organi-
fer from motor neurons only by the finer ap- zation of their dendritic tree. One interesting
pearance of their Nissl bodies. The dendritic characteristic of the dendrites of motor neu -
tree of lamina VIII neurons is predominantly rons is their tendency to gather into bundles.
vertically oriented. These dorsal dendrites are The exact function of these dendritic bundles
directed toward the anterior gray commis- is not known , but it has been suggested that
sure without crossing the midline, or toward they play a role in certain aspects of the exe-
lamina VII. Ventral dendrites run toward the cution of motor programs (127).
ventromedial tip of the posterior horn (131 ). At the levels of the cervical and lumbar en-
Axons of some medially located neurons are largements, the lateral groups of motor neu -
considered to cross the midline in the ante- rons are always sharply delimited . Within
rior white commissure. This lamina consti - each nuclear group both large and small
tutes an entity of importance since specific perikarya are rich in Nissl bodies. The
descending fiber systems terminate upon smaller medial nuclear masses often are less
cells in this region . Descending spinal tracts sharply defined and share a diffuse border
terminating, in part, within lamina VIII in- with lamina VIII ( Figs. 10.12 B , C ).
clude the vestibulospinal, the medial longitu - The large somatic motor cells of the ante-
dinal fasciculus, the pontine reticulospinal, rior ( ventral ) horn which innervate striate
and the tectospinal ( Figs. 10.8 and 11.25). muscle are referred to as alpha ( a ) motor neu -
rons. Scattered among these large motor cells
LAMINA IX are a number of smaller gamma ( 7 ) neurons
which give rise to efferent fibers. These
This lamina consists of several distinct emerge via the ventral root and supply the
groups of somatic motor neurons ( Figs. 10.8, contractile elements of the muscle spindle
10.11, 10.12, 10.15-10.17) . In thoracic regions ( i.e., intrafusal muscle fibers ). 7- Efferent
of the cord , several islands of motor neurons fibers play an essential role in the mainte-
nance of muscle tone and bring the muscle motor neurons ( 26, 27, 114-116, 128, 163, 164 ).
spindle under spinal and supraspinal con- These interneurons make synaptic connec -
trols ( Fig. 10.30). Studies of the retrograde tions with several populations of motor neu -
transport of HRP from muscle to spinal neu - rons, including the motor neurons that send
rons in the anterior horn indicate qualitative collaterals to the same interneurons. Ren -
differences between a and y motor neurons shaw cells are part of a negative feedback
(142). The y motor neurons, most of which loop, which regulates the firing rate of the
are less than 37 jim in average somal diame- motor neurons via a phenomenon termed re -
ter, exhibited the heaviest and largest intracy - current inhibition (100). If the firing rate of the
toplasmic granules. Cells in the a motor neu - motor neuron increases, recurrent inhibition
ron range ( i.e., somal diameters greater than of the motor neuron increases, limiting the
37|xm ) showed less intensely stained , smaller changes in firing rate. Decreases in motor
HRP granules. While it is suggested that y neuron firing rate lead to less inhibition and
neurons may take up and transport more increase the net excitability of the motor neu-
HRP per unit cell volume than a motor neu - ron . Recurrent inhibition stabilizes the motor
rons, this difference may be due to a variety neuron firing rate by counteracting large
of qualitative features that distinguish these transient changes (37). Renshaw cells also
cells. make inhibitory connections with the la in -
In addition to the a and y motor neurons, hibitory interneurons that act on antagonistic
the anterior ( ventral ) gray horn contains a motor neurons. Thus, when they fire they do
large population of local interneurons which not only inhibit certain motor neurons, they
have been studied with both anatomic and also disinhibit antagonistic motor neurons.
electrophysiologic techniques. One group of Renshaw cells receive significant synaptic
these interneurons is the Renshaw cells , dis - input from descending pathways, which can
covered by Birdsey Renshaw in the early change the excitability of these cells and ad -
1940s. Renshaw cells have attracted much at- just the sensitivity of motor neurons to other
tention because they are known to receive re- descending inputs or to afferent peripheral
current collaterals of a motor neurons and inputs. Recurrent collaterals of a motor neu -
exert inhibitory influences upon adjacent rons and their relationship with Renshaw
Substantia
gelatinosa
Trunk
Shoulder v . _
s
y
Arm X
Forearm
O 1 °° 0 6A '
' " "I

Hand
,2 ° °8V°<ô 4}. oo°5° A.
“ t
OtfT °> A Oo ft
Somatic efferent Gamma efferent

fibers fibers
Figure 10.19 Motor nuclei in anterior gray horn of a lower cervical segment of spinal cord On the left is shown the
general location of anterior horn cells that send motor axons to specific muscle groups of the upper extremity Motor
. .
nuclei indicated on the right are: I . posteromedial. 2. anteromedial. 3. anterior 4 central: 5. anterolateral. 6 postero-
lateral; 7. retroposterolateral Smaller anterior horn cells send axons (y-efferents) to supply small muscle fibers of neu-
romuscular spindle (Fig 10 30) Note the collaterals from somatic efferent axons that return to gray matter and
synapse on small medially placed Renshaw cells. Smaller cells appearing as the dotted zone in the intermediate gray
indicate the area of the Intemunclal neuron pool.
cells are schematically diagrammed in Figure tribute axons to the ventral roots of respective
10.19. spinal nerves and are organized into named
Recently, two types of physiologically nuclear groups, which may vary from seg-
identified Renshaw cells were visualized ment to segment ( Figs. 10.11 , 10.13, 10.16, and
after intracellular HRP labeling ( 33). In addi- 10.17). Large multipolar neurons have 3 to 20
tion to the common multipolar neurons, a dendrites with ramifications which extend
distinctive group of fusiform interneurons oc- into laminae VII and VIII . Some longitudi -
curs in the anterior horn . These neurons may nally oriented dendrites may enter adjacent
represent a subset of Renshaw cells having spinal segments (128, 140). Axons of a motor
separate function and / or synaptic transmit- neurons arise primarily from the axon
ter. Furthermore, light and electron micro- hillock, are quite thin in the initial unmyeli-
scopic studies involving the intracellular nated segment ( i.e., 3.5 g.m ), exhibit a vari-
staining of both Renshaw cells and a motor able course in the gray matter, and increase in
neurons in the cat (34) revealed that, in con- diameter as they enter the white matter (18).
trast to the synapses made by la inhibitory in- A large number of these axons give off multi-
terneurons, Renshaw cell synapses on motor ple collaterals in the gray matter which be-
neurons are located on dendrites and not on come myelinated and ramify among a motor
the cell body . This finding raises the possibil - neurons ( Fig. 10.20) upon which some termi -
ity that the recurrent inhibitory pathway se- nals make direct synaptic contact (18, 19 ).
lectively inhibits particular dendritic inputs. Each cell has a large central vesicular nucleus
and coarse Nissl bodies in the cytoplasm
( Figs. 5.2E and 5.11 A ) . These somatic efferent
Somatic Efferent Neurons
neurons are largest in the lumbar and cervical
Motor nuclei in the anterior horn have enlargements and smaller in the thoracic seg-
been subdivided and named on the basis of ments of the spinal cord ( Fig. 10.12 B ) . Scat-
their location in the gray matter ( Fig. 10.19 ). tered among the large anterior horn ( a motor
As shown in Figure 10.19, there is a topo- neurons) cells are y neurons whose axons are
graphic distribution of perikarya whose destined for the muscle spindles ( Fig. 10.30 ).
axons supply the different muscle groups of Several ways of regrouping the large
the extremity. The somatic efferent neurons motor neurons of the anterior horn have been
are referred to as a motor neurons. They con - proposed (131 ). However, these subdivisions
bI
--
Figure 10.20 Transverse reconstructions ot the trajectories of axons of motor neurons injected intracellularly with
horseradish peroxidase (HRP). One a motor neuron (red) demonstrates recurrent collaterals that establish direct
synaptic contacts with other « motor neurons. Axon collaterals of a motor neurons are not restricted to the ventrome-
dial region of the anterior horn referred to as the Renshaw cell area.
are somewhat arbitrary and only the most ob- Multipolar neurons found along the lateral
vious medial and lateral groups, each with and medial borders of the anterior gray horn
their several subdivisions, are retained here. in the thoracic, lumbar, and sacral segments
of the spinal cord are known as spinal border
MEDIAL NUCLEAR GROUP cells (16). These border cells form the nucleus
pericomualis anterior , considered to contribute
This cell group or column is divisible into fibers to the anterior spinocerebellar tracts.
a posteromedial and anteromedial group. Similar neurons have been identified in the
The latter extends throughout the whole cord posterior and intermediate regions of the an-
and is most prominent in Cl , C2, C4, Tl , T2, terior gray horn of the monkey (138).
L3, L4, S2, and S3. The nucleus of the hy- Data based upon retrograde cell changes
poglossal nerve in the medulla appears to be following sectioning and crushing of periph -
a rostral continuation of this column. The eral nerves in various combinations indicate
posteromedial group is smaller and most dis- that motor neurons supplying flexor limb
tinct in the cervical and lumbar enlargements muscles are aligned longitudinally in dorso-
( Fig. 10.19 ). It may be missing in the sacral lateral regions of the lateral cell column,
portions of the cord . The medial motor cell while extensor motor neurons lie ventral to
column innervates the short and long mus- flexor motor neurons (141 ). A schematic rep -
cles attached to the axial skeleton.
LATERAL NUCLEAR GROUP

This motor cell group innervates the rest C3
of the body musculature. In the thoracic seg-
ments, it is small and undivided and inner -
vates the intercostal and other anterolateral
trunk muscles ( Fig. 10.13). In the cerv ical and
lumbar enlargements, it is increased and a
number of subgroups may be distinguished .
The group is especially prominent in those
segments which participate in the innerva -
tion of the most distal portions of the extremi-
ties. Here may be distinguished anterolateral,
posterolateral, anterior, central, and retropos-
terolateral groups ( Figs. 10.16 and 10.19 ). The
exact innervation of individual muscles in the
extremities by each of these groups has not
been completely worked out, but, in general,
the more distal muscles are supplied by the
more lateral cell groups. Passing from the
most medial part of the anterior horn to its
lateral periphery, a motor neurons succes-
sively innervate muscles of the trunk, shoul -
der and pelvic girdle, upper leg and arm , and
lower leg and arm ( Fig. 10.19). The retropos-
terolateral group supplies the muscles of the
hand and foot. Experimental denervation
studies in animals have produced variable re-
sults. Sectioning of specific peripheral motor
nerves of the cat produced central chromatol-
ysis in discrete anterior horn cells. Cell
columns that supplied nerve fibers to the dor-
sal divisions of the ventral primary ramus
were located anterolaterally. Cell groups
Figure 10.21 Cell groups in the anterior gray horn in
placed posteromedially contributed fibers to .
cervical segments C3, C4 and C5. Phrenic nerve motor
the ventral division of the ventral primary neurons ( PN ) lie ventrally between medial and lateral so-
ramus (123). matic cell columns,
reservation of a motor neurons innervating horn , which is characteristic of thoracic lev -

the muscles of the upper extremity is de- els. The nucleus begins in the lower portion
picted in Figure 10.19. Neurons in the most of C8 and extends caudally through L 2 or L3.
ventral portion of the anterior horn between Neurons of this nucleus are considerably
the medial and lateral cell columns in cervical smaller than somatic motor neurons and their
segments C3, C4, and C5 give rise to axons cell bodies are either spindle-shaped or ovoid
which form the phrenic nerve ( Fig. 10.21 ) with vesicular nuclei and fine Nissl granules
( 141 ). Dendrites of these neurons display a ( Figs. 10.12 B, 10.13, and 10.15). Axons of neu -
striking longitudinal orientation . rons in the intermediolateral nucleus leave
Neurons embedded in a tract of unmyeli - the cord in the ventral roots of spinal nerves
nated fibers in the most ventral part of the T1 and L3 (8, 99 ) to reach the ganglionated
sacral spinal cord form the nucleus of Onuf . sympathetic chain or, in more peripheral gan -
The axons emerging from this nucleus con - glia , along the aorta via the white rami com -
tribute to the pudendal nerve ( roots S2 to S4 ), municantes ( Figs. 9.1 and 10.23). Each pre-
and supply muscles in the pelvic floor, in - ganglionic axon has synaptic endings upon
cluding the striated muscle sphincters that the dendrites and cell bodies of many post -
contribute to urinary and fecal incontinence. ganglionic neurons in outlying sympathetic
The Onuf nucleus also contributes fibers to ganglia .
the ischiocavernous and bulbospongiosus
muscles, and contains more neurons in men SACRAL AUTONOMIC NUCLEI
than in women .
Scattered small neurons are found along
Visceral Efferent Neurons the lateral surface at the base of the anterior
gray horn in sacral segments S2, S3, and S4
Axons of these neurons pass by way of the ( Fig. 10.17). Such cells bear a striking resem -
ventral roots and white rami communicantes blance to those found in the intermediolateral
to the various sympathetic ganglia. They are nucleus and occupy a corresponding position
small ovoid or spindle-shaped cells with thin, in the lateral part of lamina VII (133), even
short dendrites, vesicular nuclei, and fine though no lateral horn is present ( Fig. 10.17).
chromophilic bodies ( Figs. 5.10E and 10.12 B ). Axons of these scattered cells leave the cord
They range in size from 12 to 45 pm, and may in the corresponding ventral roots as pregan-
be divided into two groups. glionic (sacral ) parasympathetic fibers that
form the pelvic nerves. These fibers, in turn ,
INTERMEDIOLATERAL NUCLEUS have multiple synapses with many postgan-
glionic cells located in or near the wall of the
This nucleus ( Figs. 10.12 B and 10.13) is lo- pelvic viscera ( Fig. 9.1 ).
cated in Rexerd 's lamina VII and consists of
several adjacent cell columns. The most lat- Posterior Horn
eral apical cell group constitutes the lateral
The posterior ( dorsal ) horn is composed of
Collaterals
neurons that belong to laminae I to VI and
of dorsal whose cytologic features were examined ear-
Dorsolateral fasciculus root fibers lier. These neurons and their processes are
confined entirely to the central nervous sys-
Dorsal root tem. They receive collaterals or direct termi-
nations of dorsal root fibers. In turn, they
Substantia send their axons either directly to anterior
gelatinosa . horn cells of the same segments or to the
white matter, where, by bifurcating, they be-
Corticospinal tract come ascending and descending longitudinal
(nonmyelinated)
fibers, forming intersegmental tracts of vary-
ing length ( Fig. 10.24 ). The cells vary in size,
form, and internal structure. Some are orga -
nized into definite cell groups that are easily
Figure 10.22 Transverse section of the lumbar spinal distinguished in transverse sections, others
cord In an infant showing entrance of dorsal root fibers are scattered irregularly in the gray matter.
and collaterals (Weigerts myelin stain) Among the most clearly defined cell groups
A GENERAL SOMATIC AFFERENT

Proprioctpfiv r #c* ptof from :
* I
Skeletol mutclo f MEDIAL BUNDLE - Composed of thickly
Tendon ^Lp? myelinated nerve
Joint copeule ¥
Exteroceptive receptor* for |
LATERAL BUNDLE-Compottd of thinly
myelinated ond non -
^ 8 /
Touch
myelinated nerve
PrtMUfO o fiber t
2
Heot Spinol
Cold nerve
Poln
B GENERAL SOMATIC EFFERENT 5 9 3' /

3
Effector * ot
Motor end plott « of gommo
efferent axone on email
introfutoi fiber* of mo*cle *pindle
Motor endplote* of olpho efferent 1
ff V 4 4'
o*on* on lorge extrofutol mutcle /
fiber* ^
NEURAL ELEMENTS OF MOST REFLEX ARCS
C. GENERAL VISCERAL AFFERENT
l. Receptor ending of »en*ory neuron
Vitceroceotive receptor * for
dittentron ond *po«m of
tmooth mutcle
I
4
\
Sympathetic
2 Afferent ( tentory ) neuron
3 Intemunciol ( Intercalated ) neuron
4 Efferent ( motor ) neuron axon*
0 GENERAL VISCERAL EFFERENT ganglion 3 Effector ending of motor neuron
Effectors os tlmple nerve tndlngiktr jf ' i
Glandular epithelium r' ®

Smooth muscle
Cordioc muscle
Figure 10.23 Functional components of a thoracic spinal nerve, and the arrangement of dorsal root fibers as they
enter the spinal cord. Skeletal muscle afferent and efferent fibers are indicated in red . Visceral afferent and efferent
fibers are shown in blue. An afferent fiber from a Pacinian corpuscle ( black ) and a thin pain fiber ( black ) also are
shown Numbers correspond to neural elements that form reflex arcs
of the posterior horn are (a ) the posteromar- present at all spinal levels and is best devel -
ginal nucleus, ( b) the substantia gelatinosa, oped in the enlargements and in the first two
and (c) proper sensory nucleus. cervical spinal segments ( Figs. 10.8, 10.11,
10.14, and 10.16). It corresponds to Rexed 's
POSTEROMARGINAL NUCLEUS lamina II . Variations in size and configuration
of the substantia gelatinosa are related to the
This nucleus is situated in lamina 1 and size of the respective dorsal roots and the
forms a thin layer of cells covering the tip of spinal level . The nucleus is composed of
the posterior (dorsal ) horn ( Figs. 10.12 B, tightly packed , spindle-shaped cells oriented
10.13, 10.14, and 10.17). It is composed of radially that give rise to rich dendritic
large, tangentially arranged stellate or spin- arborizations. Small unmyelinated axons
dle-shaped cells reaching a diameter of over course longitudinally in the substantia gelati-
50 jim . Cells of the posteromarginal nucleus nosa and bundles of myelinated dorsal root
receive axons of primary afferent fibers con- fibers pass through this lamina to deeper re-
veying impulses related to nociceptive and gions of the spinal gray matter. Afferent
thermal stimuli and axons from cells in the fibers project to the substantia gelatinosa in a
substantia gelatinosa ( Fig. 10.14 ) (68, 89). radial fashion from the dorsolateral fascicu -
Axons of cells in this nucleus contribute lus, the posterior funiculus and parts of the
fibers to the contralateral spinothalamic tract lateral funiculus. The organization of these
( 159, 160, 162 ) and give rise to descending fibers, as well as other details about the mor-
propriospinal projections that may influence phology of the substantia gelatinosa, were
motor neurons (9). Cells of this nucleus are discussed earlier with the anatomic charac-
found throughout the cord , and are most nu - teristics of lamina II.
merous in the lumbosacral segments.
PROPER SENSORY NUCLEUS
SUBSTANTIA GELATINOSA
This nucleus occupies the head and neck
This structure, forming the outer cap-like of the posterior horn and corresponds to
portion of the head of the posterior horn , is Rexed 's laminae 111 and IV as seen in Figures
/ s Ascending secondary sensory pathways

k --mr
xr - (axons of neuron II - e g spinocerebellar tracts)
Ascending sensory pathways
( central process of dorsol — II
II Descending motor pathwoys ( axons of
root ganglion cell - neuron I- II ' ’ suprasegmentol neurons- e g corticospinal tract )
II
eg posterior white column ) II
* II Anterior horn cell (lower motor neuron)
Collateral branches
Receptors
-"
J
'II
11
1
II 741 J.. ,
Three neuron or disynaptic reflex
II ( e 9 extension and crossed
^ ? extension reflexes)
3
Pacinian corpuscle
II
Muscle spindle i
Tendon organ
AL
- Two neuron or monosynaptic
reflex ( e g stretch reflex )
$88
Meissner 's corpuscle
Free nerve endings

Gonglion cells
( neuron I )
«7
<
«
Several neuron or multisynaptic
reflex ( closed , reverberoting ,
feed back neural mechanism )
Descending sensory pathways

(central process of dorsol Internunciol ( intercalated ) neurons
root ganglion cell - neuron I-
eg septomarginal and inter -
fascicular fasciculi )
Figure 10.24 Major branches and collaterals of dorsal root ganglion cells within three spinal cord segments On the
left are various receptors that generate impulses in response to different kinds of stimuli . Impulses from muscle spindles
initiate the myotatic or stretch reflex involving two neurons (monosynaptic reflex). Impulses from the tendon orgon ini-
tiate disynaptic reflex circuits involving inhibitory mechanisms. Other reflex circuits may Involve many neurons (multisy-
naptic). Also indicated dre ascending and descending branches of dorsal root fibers in the posterior white column
and collateral pathways that project fibers to the cerebellum (see Chapter 11).
10.11 and 10.13-10.16. Cells of this nucleus Intermediate Gray Zone

are of mixed types. Round or spindle shaped -
cells which predominate dorsally are ori - Neurons of the intermediate gray zone be-
ented vertically, while in deeper parts of the long to Rexed's lamina VII. As those of the
nucleus, round , triangular, and polygonal dorsal horn, neurons of the intermediate gray
cells with abundant Nissl substance are con- zone and their processes are confined to the
spicuous. Dendrites of cells in the proper sen - central nervous system and receive collaterals
sory nucleus radiate into the substantia or direct terminations of dorsal root fibers.
gelatinosa where they make synaptic contact They form several distinct nuclear masses, in -
with primary afferent fibers ( Fig. 10.14). cluding ( a ) the dorsal nucleus of Clark, ( b ) the
Axons of larger cells in this nucleus cross in intermediomedial nucleus, (c ) the central cer-
the anterior white commissure and contribute vical nucleus, (d ) the intermediolateral nu -
fibers to the spinothalamic tracts ( Fig. 10.16 ) cleus, and (e ) the sacral autonomic nuclei.
( 1 , 148) . Cells composing this poorly defined The latter two groups of nuclei were dis-
cell column are found at all spinal levels but cussed earlier in the section on visceral effer-
are most numerous in lumbosacral segments. ent neurons.
Lateral to the nucleus proprius the reticular
process of the posterior horn protrudes fin - DORSAL NUCLEUS OF CLARKE
ger-like extensions into the lateral funiculus
( Figs. 10.9 and 10.11 ). Cells of this process are This nucleus forms a prominent round or
part of lamina V and are called the reticular oval cell column in the medial part of lamina
nucleus . The reticular process is most evident Vll that extends throughout thoracic and
in cervical spinal segments. upper lumbar segments ( Figs. 10.7, 10.12B,
laterals of dorsal root afferents establish secure

synapses upon cells of this nucleus at their lev-
els of entrance and at adjoining levels which
exhibit extensive overlap (38). The large cells
of the dorsal nucleus give rise to the uncrossed
fibers of the posterior spinocerebellar tract.
INTERMEDIOMEDIAL NUCLEUS
This nucleus, unlike other cell columns in
lamina VII , extends virtually the entire length
. -
of the spinal cord (Figs 10.12A D and 10.15).
.
EFf y VOT
It is not as sharply outlined as the intermedi-
olateral nucleus occupying the lateral horn.
This nucleus consists of a group of small - and
-
medium sized cells, 10-24 pm in size, with a
triangular shape that lie in the most medial
part of lamina VII , lateral to the central canal .
The nucleus consistently receives a small
Figure 10.25 Degenerated dorsal root fibers in the rhe-
sus monkey projecting directly to the dorsal nucleus of
number of fibers from the dorsal root at all
Clarke at L2 Lumbar dorsal roots were sectioned proxi- levels (12, 134 ). It has been suggested that the
.
mal to the dorsal root ganglia (Nauta-Gygax stain x 80) intermediomedial nucleus may receive vis-
ceral afferent fibers and serve as an interme-
10.13, and 10.15). It begins to be well-defined
diary relay in transmission of impulses to vis -
ceral motor neurons (97).
in C8 and extends through the thoracic and
upper lumbar segments, being most promi- CENTRAL CERVICAL NUCLEUS
nent in T10, T12, and LI ( Figs. 10.12 B and
10.15). Below 12) it becomes indistinguishable, This nucleus is located in the upper four
although occasional cells may be found. Col - cervical spinal segments and forms an inter-
Lateral cervical
\ nucleus
Central cervical
nucleus
Lateral cervical
\ nucleus
Central cervical
nucleus
C- 2
Figure 10.26 First two cervical spinal segments in a dog showing the locations of the central cervical nucleus.
rupted cell column consisting of a series of resenting the central processes of smaller
discrete cell groups ( Fig. 10.26 ). Cells are ganglion cells related to free nerve endings
fairly large, polygonal in shape, and resemble tactile, thermal, and other somatic and vis-
motor neurons. This group of cells lies lateral ceral receptors.
to the intermediomedial nucleus ( 20, 119). Upon entering the spinal cord , central
Cells of the central cervical nucleus receive processes of each spinal ganglion cell divide
direct projections from dorsal root ganglion into ascending and descending branches
cells (97, 134 ) and give rise to a crossed spin- (112 ), which in turn give rise to numerous
ocerebellar tract ( 20, 79). collaterals ( Fig. 10.24 ). Most of the collateral
Two less distinct cell columns extending branches are given off in the segment of
the length of the cord are the nuclei cornucom- entry, where they either relay impulses to
missurales posterior and anterior ( Fig. 10.17). second order neurons, or participate in in -
The former, in section, is a thin strip of cells trasegmental reflexes ( Fig. 10.24). Primary as-
occupying the medial margin of the posterior cending and descending branches extending
horn and extending along the border of the into adjacent spinal cord segments, together
posterior gray commissure. It lies over the with their collaterals, constitute the anatomic
column of Clarke when the latter is present. basis of intersegmental reflexes, and the relay
The anterior nucleus is a similar cell group of impulses to secondary sensory pathways
along the medial surface of the anterior horn ( Figs. 10.23 and 10.24 ). The longer ascending
and anterior gray commissure. These nuclei primary branches of the medial bundle enter
-
consist of small and medium-sized spindle - the ipsilateral posterior funiculus, and many
shaped cells whose axons probably form in- of these ascend without synapse as far as the
tersegmental tracts in the posterior and ante- medulla. Fine, thinly myelinated and un-
rior white funiculi, respectively. myelinated fibers of the lateral bundle of the
dorsal root, conveying impulses related to
PRIMARY AFFERENT FIBERS pain, thermal, and light tactile sense, enter
the medial part of the zone of Lissauer ( fascicu-
Topographic Organization lus dorsolateralis ) and terminate directly in
portions of laminae I and II (67, 68) ( Figs.
Central processes of cells in the spinal gan- 10.7, 10.14, and 10.16). Physiologic data cou -
glia enter the dorsolateral aspect of the spinal pled with detailed anatomic studies indicate
cord in small fascicles over a considerable that lamina 1 and the outer zone of lamina 11
distance ( Fig. 10.2). The dorsal roots break up receive direct projections from cutaneous no-
into a number of filaments, or rootlets, which ciceptors, but have no direct input from cuta -
enter the spinal cord in a linear manner. Pe- neous receptors responding to innocuous
ripheral processes of spinal ganglion cells stimuli (68). Primary afferent fibers terminat-
convey impulses centrally from various so- ing in the inner zone of lamina II are a
matic and visceral receptors. As central mixture of fine and small myelinated fibers
processes of spinal ganglion cells approach related physiologically to innocuous mech -
the dorsal root entry zone, small fine fibers anoreceptive neurons ( 69).
become segregated in lateral portions of the
rootlets and enter lateral parts of the poste- Zone of Lissauer
rior horn and the dorsolateral fasciculus di-
rectly ( 32, 58, 60, 67, 111-113, 127, 131, 137). This zone is composed of (a ) fine myeli -
Larger fibers, shifting medially in the rootlets, nated and unmyelinated dorsal root fibers,
enter the posterior (dorsal ) columns directly which enter medial parts of the bundle, and
or traverse medial parts of the posterior horn ( b) a large number of endogenous pro-
in passage to deeper laminae of the spinal priospinal fibers, which interconnect different
gray matter ( Figs. 10.22 and 10.23). Thick levels of the substantia gelatinosa ( 25, 32, 113,
myelinated fibers of the mediaI bundle are de- 127, 131, 143). According to Chung and
scribed as representing the central processes Coggeshall ( 15), 80% of the axons in the dor -
of spinal ganglion cells conveying impulses solateral fasciculus are unmyelinated in the
from large encapsulated somatic receptors, cat and approximately 50% of the axons rep-
such as neuromuscular spindles, neurotendi- resent primary afferent fibers derived from
nous organs, Pacinian corpuscles, and Meiss- the entering dorsal roots. In Golgi prepara -
ner's corpuscles ( Fig. 10.23). The smaller, less tions, axons of cells in laminae I, II , and 111
conspicuous lateral bundle , composed of have been followed into lateral parts of the
thinly myelinated fibers, is described as rep- zone of Lissauer and most of these fibers
have been traced back to lamina II at other sal root fibers become concentrated especially
levels. Because few , if any, of the axons of in the central part of lamina VI , and from this
cells in the substantia gelatinosa appear to region fibers pass in numerous small bundles
relay impulses into known sensory pathways into lamina IX where they arborize about the
and the dendrites of larger sensory neurons soma and dendrites of large motor neurons.
in laminae Ill and IV extend radially into Dorsal root fibers also give off collaterals
lamina II, this structure is regarded as a mod - which pass into lamina VIII . Since collaterals
ulator of synaptic transmission from primary of dorsal root fibers passing to laminae VIII
to secondary sensory neurons (59, 60, 83, and IX traverse broad regions of lamina VII ,
143). it is likely that many fibers, or collaterals, end
Most of the primary afferent fibers enter- upon interneurons in this lamina , as well as
ing laminae III and IV are intermediate to on dendrites of motor nuclei which extend
thick fibers that pass through or around lam - beyond the limits of Rexed's lamina IX. Dor-
ina II and , after a recurving course in the gray sal root fibers from group la afferent fibers
matter, approach cells in the proper sensory projecting to lamina IX are involved in the
nucleus from a ventral direction ( Fig. 10.14 ). monosynaptic myotatic reflex ( Figs. 10.29 and
Primary afferent fibers largely terminate on 10.30). Group lb and group II afferent fibers
dendrites of these neurons. Most of the neu - also generate synaptic potentials in central
rons of lamina IV appear to respond to low parts of laminae V, VI , and VII ( 140 ).
intensity stimuli such as light touch (103). The central course of major branches and
Cells in laminae 1, IV , and V have been identi - collaterals of dorsal root ganglion cells within
fied as giving rise to fibers that form the three spinal segments are diagrammed
crossed spinothalamic tracts (1, 32, 148, 149). schematically in Figure 10.24. This simplified
diagram summarizes information concerning
Other Sites of Termination sensory pathways and certain spinal reflexes.
One of the principal sites of termination of CHEMOARCHITECTURE

large myelinated dorsal root fibers is the dor-
sal nucleus of Clarke ( Fig. 10.25 ). Clarke's nu - During the last decade, immunohisto
cleus receives fibers from all ipsilateral spinal chemistrv, receptor autoradiography, and re-
-
roots except the upper cervical roots ( 38, 134 ). fined biochemical methods have been applied
Studies of dorsal root afferents to Clarke's the study of the spinal cord in experimental
nucleus ( 38, 71 ) indicate (a ) the greatest num - animals and , less extensively, in humans.
ber of fibers come from dorsal roots of the These studies have significantly increased
hindlimb, ( b ) there is considerable overlap of our knowledge of the anatomic and func-
different dorsal root fibers distributed to the tional organization of the spinal cord . Inter-
nucleus, and (c ) fibers enter the nucleus via esting information regarding transmitter al -
both ascending and descending collateral terations in various spinal cord diseases also
branches of the dorsal root. Synapses of dor- has been gathered. The following is a brief
sal root afferents upon the cells of Clarke's survey of the major small-molecule transmit -
nucleus appear unique in that terminal fibers ters and neuroactive peptides that are
have long parallel contact with the dendrites thought to play a role in the function of the
of Clarke's neurons, and unusually large ter- spinal cord . Before proceeding, however, a
minal boutons are partially buried in depres- word of caution . Much of the data that is re-
sions on the cell surface (144 ). These "giant viewed here derive from experimental stud -
synapses" between dorsal root fibers and ies in animals. Because of considerable
cells of the dorsal nucleus are said to be species differences in the distribution of
larger than any other spinal cord synapses. transmitters, care should be taken in extrapo-
Anatomic observations are in agreement with lating the results of animal experiments to
physiologic studies ( 72 ) which show that se- humans. Thus, when available, results de-
lective stimulation of group 1 afferent fibers rived from human materials are emphasized
establish secure synaptic relationships with in the present account .
the cells of Clarke's nucleus.
Collateral branches of dorsal root fibers Acetylcholine
also are distributed to parts of the anterior
horn ( Figs. 10.23 and 10.30). According to Acetylcholine ( ACh ) is one of the key
Sprague ( 139 ) and Sprague and Ha (140), dor- transmitters at spinal cord levels. However,
because of the lack of straightforward meth- afferents (132 ). Furthermore, the high density
ods for visualizing ACh , much of our knowl - of Ml receptors in human lamina II , contrast -
edge about the localization of spinal choliner- ing with the mixed population of Ml and M 2
gic neurons relies on indirect methods, such receptor subtypes in the anterior horn, sug-
as the histochemical procedures for ACh gests that Ml and M 2 may be differentially
hydrolyzing enzyme, acetylcholinesterase involved in sensory and motor function in
( AChE ), or the immunohistochemical method the human spinal cord ( 153).
for ACh synthesizing enzyme, choline acetvl-
transferase (ChAT ). While ChAT is believed Monoamines
to occur only in neurons that synthesize ACh,
AChE is known to be present in both neurons The monoaminergic innervation of the
that uses ACh as a neurotransmitter (cholin- spinal cord in animals is well-known and has
ergic neurons) and in neurons that receive a been reviewed elsewhere ( 51, 70, 147 ). This
cholinergic input (cholinoceptive neurons). innervation was studied first with histofluo-
Hence, ChAT is considered a more reliable rescence methods ( 21 ), and subsequently
marker than AChE for cholinergic neurons with immunohistochemical techniques using
( 3). Cholinergic neurons in the central ner- antibodies against synthesizing enzyme or
vous system also can be demonstrated by in against the transmitters themselves. It is com -
± itu hybridization of choline acetyltransferase monly admitted that the noradrenergic fibers
mRNA (92 ). The principal cholinergic neu- arborizing in the anterior horn derive from
rons in the spinal cord are the large « motor the locus coeruleus and subcoeruleus,
neurons ( Fig. 10.27C, D ), which use ACh as a whereas those terminating in the posterior
transmitter at the neuromuscular junction pe- horn originate from neurons located in the
ripherally and at the synapse of its recurrent lateral portion of the pontomedullary
collaterals with Renshaw cells centrally. At tegmentum , that is, groups A 5 and A 7, ac-
both sites the ACh effect is mediated through cording to the nomenclature of Dahlstrdm
nicotinic receptors. The other major collection and Fuxe ( 21 ). However, some conspicuous
of spinal cholinergic neurons is in the interspecies variations of this scheme have been
mediolateral cell column at thoracolumbar noted in rodents ( 47, 136). It must also be
levels ( Fig. 10.27B ). These are the pregan - mentioned that in the cat about 70% of the
glionic sympathetic neurons that project to noradrenergic coeruleospinal neurons exhibit
noradrenergic neurons in the paravertebral enkephalin immunoreactivity (165), whereas
or prevertebral ganglia . approximately 20% display neuropeptide Y
In addition to nicotinic receptors, mus- immunoreactivity ( 31 ).
carinic cholinergic receptors also occur in the The noradrenergic fibers terminate prefer-
spinal cords. They are particularly abundant entially in the deeper layers of the posterior
in laminae II and IX (126, 153). As is the case horn , in the intermediolateral column , in the
in the rat, muscarinic receptors in the human motor neuron region , and in lamina X around
spinal cord are predominantly of the Ml type the central canal. At the ultrastructural level ,
in lamina II , but significant densities of both they make conventional synapses with den -
Ml and M 2 receptor subtvpes are found over drites in the motor neuron region and in the
the columns of motor neurons in the anterior intermediolateral column, and contact poste-
horn ( 153). These results indicate that, in ad- rior horn neurons probably via nonjunctional
dition to using ACh as a neurotransmitter, synapses ( 105). This finding suggests that no-
motor neurons receive a prominent choliner- radrenergic fibers may exert a direct influ -
gic input whose effect is mediated through ence on somatic and autonomic motor neu -
muscarinic receptors. The marked reduction rons via conventional synapses, whereas they
in AChE and ChAT activities and the de- may diffusely modulate the activity of poste-
crease in the number of muscarinic receptors rior horn neurons through nonconventional
in the anterior horn following degeneration synapses.
of spinal motor neurons encountered in amy- A direct dopaminergic input to the spinal
otrophic lateral sclerosis are consistent with cord arising mainly from the diencephalic
the concept that motor neurons use ACh as a group All was described in rodents ( 70 ).
neurotransmitter and also receive a choliner- This diencephalospinal dopaminergic system
gic innervation. The latter is most likely pro- arborizes principally in the intermediolateral
vided bv recurrent collaterals of motor neu - column and less abundantly in the superficial
rons and / or supraspinal and propriospinal laminae of the posterior horn , including the
2
S
I
n
o
r
<
s -
5r
a
n
o
2 50 prn
Figure 10.27 Immunocytochemical staining of spinal neurons in a macaque monkey A. Neurons in deep portions of lamina II at Cl im-
munoreactive to leucine enkephalin B. Visceral neurons in the intermediolateral cell column at thoracic level immunoreactive to choline
acetyltransferase (ChAT) C and D. Spinal motor neurons in the anterior horn immunoreactive to ChAT,
reticular nucleus, and in lamina X. Also serotonin-containing nerve cell bodies have
worth noting is the demonstration of a sub- been visualized in lamina X of the monkey
population of catecholaminergic, probably spinal cord ( 65), but similar neurons have not
dopaminergic, neurons in the dorsal root been identified in human material ( 132).
ganglion in the rat ( 104 ). This finding indi- The prominent serotoninergic pericellular
cates that, although the catecholaminergic in- innervation of primary motor neurons sug-
nervation of the spinal cord arises in large gests that serotonin plays an important role
part from suprasegmental regions, part of the in the control of motor functions. Indeed , sys-
dopaminergic input may come from primary
peripheral afferents.
-
temic injections of 5 hydroxytryptophan, the
immediate precursor of serotonin, facilitates
There is also evidence in rodents and non - spinal reflexes and locomotor activity. On the
human primates for a brainstem cate- other hand, the dense serotoninergic innerva -
cholaminergic afferent to the spinal cord that tion of the superficial laminae of the posterior
uses epinephrine ( adrenaline) as a neuro- horn favors the idea of a direct involvement
transmitter (11 ). This adrenergic projection of serotonin and its accompanying peptides
arises from medullary neurons of the C1 in the processing of sensory information, par-
group, according to the nomenclature of ticularly nociception ( 6). Furthermore, the
Hdkfelt ( 45), and terminates preferentially in serotoninergic bulbospinal system is thought
the intermediolateral cell column, the superfi- to play a role in the control of various aspects
cial laminae of the posterior horn, the inter- of autonomic function, including the regula -
mediate gray matter, and lamina X. This tion of blood pressure (17).
adrenergic input may directly influence the
cholinergic autonomic motor neurons and
may also contribute to the modulation of no- Amino Acids
ciceptive processing at spinal cord level (11, GLUTAMATE AND ASPARTATE
45). These effects are most probably mediated
by a -adrenergic receptors, which are particu - These two amino acids are the major exci-
larly abundant in lamina II and in the inter- tatory transmitters in the central nervous sys-
mediolateral cell column in both rodents and tem and experimental studies in animals re-
humans (151). The density of (3-adrenergic reveal that they play a crucial role in the
ceptors is weak in the spinal cord . functional organization of the spinal cord .
The serotoninergic innervation of the The presence of glutamate has been detected
spinal cord arises chiefly from nuclei raphe in neurons of the dorsal root ganglion as well
pallidus, magnus, and obscurus ( groups B1 to as in their afferent fibers terminating in the
B3, according to Dahlstrom and Fuxe) ( 21 ), superficial laminae of the posterior horn ( 7).
whose neurons are scattered from caudal In these dorsal root neurons, substance P is
medulla to middle pons (91, 147). Most fibers coexpressed with glutamate ( 22 ). At the ultra -
descend in the lateral funiculi and terminate structural level, the central boutons of the pri -
chiefly in laminae 1 and II, in the intermedio- mary afferent fibers in the substantia gelati-
lateral cell column, and in the primary motor nosa , as well as the giant terminals formed by
neuron region. The serotoninergic fibers form the la muscle spindle afferents in the Clarke's
a dense pericellular network around the so- column, were found to be enriched with glu -
mata and proximal dendrites of somatic and tamate (81, 82 ). A detailed ultrastructural
autonomic motor neurons. These pericellular analysis in the rat revealed that glutamate
plexuses are more prominent in primates and aspartate immunoreactivity in laminae I
than in rodents ( 91 ). Neurons of the sero- to III are displayed by distinct sets of neu -
toninergic bulbospinal system display vary- ronal profiles (86). Glutamate-containing pro-
ing combinations of neuroactive peptides ( 40, files are about 10 times more numerous than
41 ). In rodents, somatostatin is the peptide the aspartate-immunoreactive profiles, and
that coexists most frequently with serotonin, these two types of profiles are distinct from
followed by substance P, enkephalins, and those displaying GABA immunoreactivity .
thyrotropin -releasing hormone ( 14 ). More- These results suggest that both glutamate and
over, many raphe neurons that project to the aspartate are neurotransmitters used by sepa -
spinal cord are immunoreactive for two or rate, non-GABAergic neuronal populations.
more peptides. In addition to these The same study also revealed that glutamate
supraspinal serotoninergic projections, local is often coexpressed with either substance P
or calcitonin gene-related peptide in terminal monkeys ( 2). Immunohistochemical studies

boutons. In such a case, the immunoreactivity in the rat with antibodies raised against
for glutamate is found in small clear vesicles, GABA itself or its synthesizing enzyme glu -
whereas that for the peptide occurs in larger tamic acid decarboxylase (GAD) have re-
dense-cored vesicles (86 ). vealed the presence of GABAergic cell bodies
In humans, the three major types of gluta- in all regions of the spinal cord except lamina
mate receptors ( i.e., NMDA, quisqualate, and IX ( 4, 145). This widespread distribution sug-
kainate receptors) abound in lamina 11 (52), a gests that GABAergic neurons in the spinal
finding consistent with electrophysiologic cord may exert diverse functions. As a rule,
and pharmacologic data indicating that glut - GABAergic neurons are smaller in dorsal
amate is a transmitter of primary afferent laminae of the spinal gray matter than in ven -
terminals in the spinal cord . Recently, the tral laminae. In some neurons in the superfi-
metabolism of excitatory amino acids, cial laminae of the superior gray horn in the
particularly that of glutamate, was shown to rat, GABA was found to be coexpressed with
be altered in patients suffering of amy- the peptides methionine enkephalin or neu -
otrophic lateral sclerosis (124). This finding rotensin (102, 146 ). In addition to the large
raises the possibility that such an alteration in number of intrinsic GABAergic neurons, evi-
glutamate metabolism may play a role in dence for a spinal GABAergic input of
motor neuron loss. suprasegmental origin was recently reported
in the rat ( 46 ). This projection arises from the
GLYCINE ventromedial region of the lower brainstem
tegmentum and synapses directly on the pri -
This amino acid is believed to be the major mary dendrites of motor neurons. It is likely
inhibitory transmitter in the spinal cord. to exert a powerful inhibitory effect on spinal
Light and electron microscopic analysis com- motor neurons capable of counteracting the
bined with electrophysiologic recording has facilitation produced by the bulbospinal sero-
provided convincing evidence that Renshaw toninergic projection that arises from the
cells are glycinergic ( 35). As seen , these cells same brainstem area.
project principally on u motor neurons, but In the human spinal cord , autoradi-
also on la interneurons and other Renshaw ographic binding studies have revealed that
cells. la interneurons, which inhibit antago- both GABAA and GABAt, receptors are highly
nistic motor neurons when activated by la af - concentrated in lamina II ( 132, 154). Both
ferent coming against muscles, might also use GABAA and GABAH receptors are scarce in
glycine as a transmitter. Glycinergic inhibi- the human inferior horn , but they exist in ap-
tion at the spinal cord level , however, may preciable amounts in lamina X. Benzodi -
not be entirely derived from local interneu - azepine receptors, which are linked to the
rons. Indeed, recent neuroanatomic evidence GABAA receptor-chloride ionophore, are very
in the rat suggest the existence of a glyciner- dense in lamina II, particularly in its inner
gic projection that arises in the ventromedial zone ( 132, 154 ). This highly specific distribu -
portion of the lower brainstem ( at levels of tion , together with physiologic evidence from
the inferior olive and caudal facial nucleus) animal experiments, suggests that benzodi-
and terminates directly on motor neurons azepines act by enhancing GABA- mediated
( 48). In the human spinal cord , glycine is de- presynaptic inhibition on primary dorsal root
tected biochemically at appreciable levels in afferent terminals ( 39, 132 ).
the anterior horn (132 ).
Neuroactive Peptides
r AMINOBUTYRIC ACID
SUBSTANCE P
y - Aminobutyric acid (GABA ) is an in -
hibitory transmitter that has been implicated In humans, all spinal laminae contain sub-
in presynaptic inhibition in the spinal cord . stance P-immunoreactive fibers (132 ). How -
Indeed , the GABAergic nature of the presy- ever, these fibers are particularly abundant
naptic inhibition that occurs between intrinsic and densely packed in lamina I and in the
GABAergic neurons in laminae I and 11 and inner portion of lamina II . In the inferior
the incoming afferents of the A5 type has -
horn , some substance P positive terminals are
been demonstrated convincingly in cats and in close association with motor neurons. Cell
bodies immunoreactive for substance P occur OPIOID PEPTIDES

in lamina 111. Their dendrites are mostly con -
fined to the sagittal plane, suggesting that The spinal cord is one of the major sites of
they correspond to the "radial" cell type de - action of opioid peptides. In humans, numer-
scribed in Golgi material (132). ous leucine enkephalin - and methionine
-
Substance P immunoreactive cell bodies -
enkephalin immunoreactive fibers and axon
and axonal profiles have also been visualized terminals occur in most laminae of the spinal
in different regions of the spinal cord of vari- cord . However, enkephalin fibers are hetero-
ous animal species ( Fig. 10.28) and the cellu - geneously distributed at this level . Their den -
lar localization of this peptide has been stud - sity is highest in lamina II , particularly in its
ied in detail in the rat ( 42, 43). Substance outer zone, and lowest in laminae IV, VII,
P-positive fibers and terminals are particu - and VIII ( Fig. 10.27A ) ( 132 ). Lamina X and the
larly abundant in the posterior horn where intermediolateral cell column also receive a
they are thought to play an important role in dense enkephalinergic innervation. A sub-
transmission and / or modulation of noxious stantial number of enkephalin fibers is found
information (55). In this regard , it is interest - in lamina IX , where some of them closely sur-
ing to note that there is a marked decrease in round the soma and proximal dendrites of
substance P immunoreactivity in lamina II in motor neurons. Some enkephalin cell bodies
postmortem tissue from patients suffering occur in laminae I and II . The positive cells in
from familial dysautonomia ( Riley- Day syn - lamina II are bipolar, dorsoventrally oriented ,
drome) and who had a profound analgesia and appear to correspond to stellate cells that
(94). can be seen in Golgi material.
-
Some substance P immunoreactive cell The high concentration of enkephalin im-
bodies and axon terminals in laminae l - III in munoreactivity in laminae 1 and II closely
the rat also contain methionine enkephalin matches the distribution of opiate receptors
(122), suggesting that these neurons may re - in the human spinal cord . Opiate receptor
lease one or the other peptide depending on were found to be located mainly within lami-
physiologic conditions. In addition to its role nae I, II and III of the posterior ( dorsal ) horn
in nociception , substance P could also be in- and in Lissauer's tract, with the highest den-
volved in the modulation of both somatic and sity of receptors in the inner zone of lamina II
autonomic motor neurons. ( 28, 132 ). These receptors appear to be princi -
Figure 10.28 Monkey spinal cord revealing the localization of substance P in lamina I and parts of lamina II. Tissue
has been treated by immunocytochemical techniques with antibodies specific for substance P, which is present only
in laminae of the dorsal horn that receive peripheral pain fibers . The morphlne-like peptide enkephalin, also present in
lamina I, may regulate the input of painful stimuli by modulating (l.e.. inhibiting) the release of substance P .
pally of the kappa ( K ) type ( 28). The pattern and IX (132). The exact role of cholecys-
of distribution of both enkephalin and opiate tokinin in the spinal cord remains to be estab-
receptors in humans is strikingly similar to lished . However, the fact that cholecystokinin
that described in various animal species ( 66 ). fibers are particularly abundant in lamina
Numerous fibers displaying dynorphin VIII may be taken as an indication that this
immunoreactivity occur in the rat spinal peptide modulates the activity of neurons
-
cord . Dynorphin immunoreactive fibers and that are specific to this region, including in -
terminals abound principally in the lumbar terneurons, propriospinal neurons, and long-
anterior horn and appear to arise largely projection neurons involved in the control of
from intrinsic neurons. Some dynorphin pos - - axial musculature.
itive fibers were found to closely surround
the cell bodies and proximal dendrites of a CALCITONIN GENE-RELATED PEPTIDE
subpopulation of motor neurons that inner - In humans, fibers demonstrating the calci -
vate flexor muscles ( 61 ). Electrical stimulation
of primary afferent fibers of the C type, but tonin gene-related peptide are confined to
not of the A type, causes a decrease in dynor- laminae I to IV of the posterior horn, lamina
phin immunoreactivity in the anterior horn . X, the intermediolateral column , and the
This finding underlines the fact that dynor - sacral parasympathetic nuclei. Fibers contain -
-
phin neurons are well positioned to modu - ing the calcitonin gene- related peptide are
late nociceptive inputs as well as to act as in - particularly abundant in laminae I and II,
terneurons in somatic motor reflexes. The whereas they are scarce in the entire inferior
decrease in dynorphin immunoreactivity ob- horn . This peptide is the only one identified
served after stimulation of the C fibers or so far in motor neurons ( 36). Only weak im -
after intense nociceptive stimuli may be the munoreactivity can be found in motor neu -
trigger for the upregulation of dynorphin ex- rons of the human spinal cord. Receptor
pression that occurs in animal models of binding sites for this peptide are particularly
chronic pain states ( 61 ). numerous in laminae II and X, and in the in -
Physiologic and pharmacologic studies in termediolateral column ( 132).
animals have revealed that the effects of en -
dogenous opioids ( i.e., enkephalins, but also NEUROPEPTIDE Y AND SOMATOSTATIN
-
(1-endorphin , dynorphin , and a neoendor-
-
Neuropeptide Y immunoreactive fibers
phin ), the most powerful agents in alleviating
pain , are largely mediated by opiate receptors are found in all laminae of the human spinal
in laminae I and II of the spinal cord (95). Part cord (132 ). Dot -like immunoreactivity charac-
of the enkephalin action in nociception ap- terizes the superficial posterior horn , whereas
pears to be mediated by its inhibitory action on long and varicose fibers occur in other lami -
the release of substance P (53). In this regard , nae. Lamina 1, the outer zone of lamina II ,
it is interesting to note that experimental and the intermediolateral column receive the
nerve injuries and inflammation in animals densest innervation . It is also worth recalling
induce an upregulation of the opioid gene ex- that some of the brainstem noradrenergic de-
pression ( 24 ). This is consistent with the in - scending fibers also express neuropeptide Y.
crease of enkephalin immunoreactivity that In humans, somatostatin-immunoreactive
occurs in laminae I and II in patients after fibers are confined to the three superficial
limb amputation (132 ). laminae of the posterior horn, the motor neu -
ron cell column , lamina X, and the sacral au -
CHOLECYSTOKININ tonomic nuclei. As is the case with many
other peptides, the greatest number of so-
Cholecystokinin fibers are present in all matostatin - positive fibers is found in lamina
laminae of the spinal cord in humans. Their II, chiefly in its inner zone, where they form a
distribution is comparable to that of sub- dense longitudinal reticulum (132 ). A large
stance P, except for a heavier innervation of number of somatostatin -positive cell bodies
laminae VII and VIII . The innervation is are found in lamina II in humans. The organi -
densest in lamina 1, the lateral part of laminae zation of their dendritic tree suggests that
V and VI , in lamina VIII , and in the interme- they belong to the islet cell type identified in
diolateral cell column. It is weakest in the Golgi material. Animal studies have also re-
outer zone of lamina I , and in laminae III, IV , vealed the presence of numerous somato-
-
statin positive nerve cell bodies, axons and and / or in peripheral neurons that provide
terminal boutons in the superficial laminae of input to the spinal cord .
the superior horn. Ultrastructural evidence
suggests that there may be two morphologi- FUNCTIONAL CONSIDERATIONS
cally distinct somatostatin systems in the sub-
stantia gelatinosa in the rat ( 121 ). Pain Mechanisms
THYROTROPIN RELEASING HORMONE. Pain is one of the most common com -

OXYTOCIN, AND VASOPRESSIN plaints in medicine. Yet, because it is so de-
pendent on personal experience and because
Thyrotropin releasing hormone im- it is influenced by emotion and the environ -
munoreactivity is confined to laminae II, VII , ment, pain is a very difficult clinical problem.
IX, and X , as well as the intermediolateral col - Its nature is unresolved and is the subject of
umn in humans. Some of the immunoreactive great controversy. Pain has been described as
fibers are closely apposed to the perikarya or a sensory experience evoked by stimuli that
primary dendrites of lamina VII neurons, injure or threaten to destroy tissue, which is
suggesting that this peptide may modify the defined introspectively by every human (88 ).
excitability of somatic and autonomic motor More specifically, pain can be defined as the
neurons by acting at the level of the pool of perception of an aversive or unpleasant sensa -
interneurons in lamina VII . Experiments in tion that originates from a specific region of
rats reveal that a significant proportion of the body. It should not be confused with noci-
the bulbospinal neurons that contain thy- ception , which refers to the neural mecha -
rotropin - releasing hormone make direct nisms involved in signaling and modulating
synaptic contact with the autonomic motor noxious stimuli (54 ).
neurons in the intermediolateral column Pain in humans is mediated by different
(101 ) . In humans, receptor binding sites for classes of nociceptive afferent fibers. Thermal
this peptide are abundant in lamina II, but or mechanical nociceptors convey impulses
much less so in lamina IX ( 77). through the small-diameter, thinly myeli-
Oxytocin-immunoreactive fibers are scarce nated A8 fibers that conduct at about 5-30
in human spinal cord and are confined to m / s, whereas polymodal receptors respond -
laminae 1, III , IV , and IX . The immunoreactiv- ing to mechanical, chemical and thermal
ity in lamina IX is chiefly concentrated in the stimuli use the small diameter, unmyelinated
dorsolateral portion of the motor neuron cell C fibers that conduct slowly at 0.5-2.0 m / s.
column. Scattered vasopressin-immunoreac- These two types of nociceptive fibers termi -
tive are restricted to laminae II , III , IV, and nate primarily in lamina I ( marginal zone)
the medial portion of laminae V and VI (132 ). and lamina 11 (substantia gelatinosa ) of the
Oxytocin receptor binding sites in human posterior horn . Both A8 and C fibers use
cervical spinal cord and lower brainstem amino acids and neuroactive peptides as
were found to L>e particularly numerous in transmitters. Ultrastructural studies of noci -
the substantia gelatinosa of the caudal spinal ceptive terminals in the superficial posterior
trigeminal nucleus and in the dorsal portion horn suggest that the excitatory amino acid
of the superior horn ( 75). and the peptide are stored in small electron -
These three different peptides are likely to translucent and dense-cored vesicles, respec-
originate in large part from suprasegmental tively. Glutamate and substance P represent
centers. Indeed , examination of lumbar en - the most common combination of small - mol -
largements in patients with spinal cord tran- ecule transmitters and neuroactive peptides
section at upper cervical or upper thoracic encountered in primary afferent fibers ( 125 ).
levels (C7-T2 ) has revealed that the im- The release of glutamate and the release of
munoreactivity for both oxytocin and vaso- substance P evoke, respectively, fast and slow
pressin was absent, whereas that for thy- excitatory postsynaptic potentials ( Hl’SPs ) in
rotropin - releasing hormone was reduced nociceptive neurons of the posterior horn .
( 131 ). In contrast, the immunoreactivity for After complex, local processing in the poste-
somatostatin, substance I’, cholecystokinin, rior horn , nociceptive signals are conveyed to
and enkephalins was virtually unchanged . higher brain centers through projection neu -
Thus, the latter peptides appear to be present rons whose axons segregate into several as-
in neurons that are intrinsic to the spinal cord cending fiber systems (see Chapter 11 ).
Activation of neurons in the superficial may relieve pain in patients with peripheral
laminae of the posterior horn by noxious nerve disease (73, 90, 138).
stimuli was elegantly demonstrated by the It is also important to realize that pain can
use of the proto-oncogen c-/os, which can be be controlled by central mechanisms. Indeed ,
used as a reliable marker of neuronal activity there is ample evidence that various brain
(85). Both noxious stimuli and joint stimula - centers and their descending projections to
tion have been shown to induce the expres- the spinal cord modulate the excitability of
sion of c- fos in neurons primarily located in neurons that transmit signals initiated by
lamina 1, the outer portion of lamina II , the noxious stimuli ( 3, 6). For example, electrical
lateral neck of the posterior horn, and in lam - stimulation of certain brain regions, such as
inae VII , VIII , and X . Injection of retrograde the periventricular gray matter, in experi-
tracers in thalamic and brainstem regions mental animals results in profound anesthe-
concerned with the processing of nociceptive sia . In humans, stimulating electrodes placed
-
signals, combined with c fos immunohisto- for therapeutic reasons in the periventricular
chemistry , revealed that a significant propor- gray region, the ventrobasal nuclei of the
tion of the posterior horn neurons that are ac- thalamus, or the internal capsule, can signifi -
tivated by noxious stimuli project to the cantly reduce the severity of pain ( 34 ). Con-
thalamus and brainstem (85). versely , the occurrence of spontaneous le-
Early neurophysiologic studies revealed sions at various levels along central
that stimulation of low-threshold myelinated nociceptive pathways may produce chronic
primary afferent fibers decreases the re- intractable pain . Such is the case with lesions
sponse of posterior horn to unmyelinated no- in the ventrobasal nuclei of the thalamus,
ciceptors, whereas blockade of conduction in which may result in pain condition called the
myelinated fibers enhances the response of thalamic syndrome ( 23). All these findings
posterior horn neurons. Thus, the firing of point to the existence of descending path-
nociceptive posterior ( dorsal ) horn neurons ways that may modulate the activity of noci-
appears dependent on the balance of activity ceptor neurons in the spinal cord . Among
between the unmyelinated nociceptors and such important descending pathways are the
the myelinated afferents not directly involved serotoninergic and the noradrenergic bul -
in pain transmissions ( 54 ). This idea was in- bospinal systems described earlier.
troduced by Patrick Wall and Ronald The most important advance in the under -
Melzack as the gate control theory of pain (83). standing of pain mechanisms has been the
According to this theory, the neurons in- identification of opiate receptor binding sites
volved in modifying the output of posterior which are concentrated upon synaptic mem -
horn neurons form a simple basic circuit that branes (96). Because these binding sites medi -
comprises ( a ) low-threshold A« / A 3 myeli- ate all pharmacologic effects of opiate alka -
nated and unmyelinated C fibers, ( b ) the pos- loids, which are universally regarded as the
terior horn neurons that relay the incoming most powerful agents in alleviating pain , opi-
signals to the brain, and (c) an inhibitory in - ate receptors must play a dominant role in
terneuron that presynaptically inhibits the the control of nociception. While most re-
projection neuron . As seen earlier, the projec- gions of the central nervous system have
tion neuron can be directly activated by both some opiate receptors, their density varies
the low-threshold myelinated and the un- greatly; only the white matter and the cere-
myelinated fibers. However, the postulated bellum appear totally devoid of opiate recep-
difference between these two types of inputs tors (62). In the spinal gray matter, opiate re-
is that the myelinated fibers also activated the ceptors are primarily concentrated in laminae
inhibitory interneuron, whereas the unmyeli- I and II , which were identified as containing
nated fibers inhibit the interneuron. Thus, neurons responding to nociceptive stimuli
when low-threshold myelinated fibers are ac- ( 44, 66, 68, 69 ).
tivated , the activity of the projection neuron The central nervous system contains en -
(and ultimately the perception of pain ) is re- dogenous opioids, the enkephalins ( methio-
duced (84, 156, 157). Clinical application of nine and leucine ), whose distribution in the
the gate control concept demonstrated that spinal cord parallels that of opiate receptors
transcutaneous stimulation of large caliber ( 49, 135). Other endogenous opioids that can
peripheral nerves raises the threshold of cen- induce analgesia have been identified, in -
tral neurons by increasing inhibition which cluding 3-endorphin, dynorphin and a -
neoendorphin ( 29). Although enkephalin and either indirectly by activating K conduc-

(J -endorphin exhibit similar opiate receptor tances or directly bv decreasing Ca 2 * conduc-
binding activity, p-endorphin is more potent, tance ( 53, 54 ).
has a longer period of action, and produces It must be remembered , however, that opi-
behavioral disturbances as well as analgesia ate receptors are widely distributed through -
(50). Thus, the opiate receptors and endoge- out the central nervous system , suggesting
nous opioids, such as enkephalin and p-en- that endogenous opioid systems may act at
dorphin, compose an intrinsic "pain suppres- various supraspinal levels and may also have
sion system" that modulates sensory functions other than pain modulation .
processes at multiple levels of the neuraxis
(95). The opiate receptors concentrated in
Spinal Reflexes
laminae I and II probably represent the first
level at which these suppressor mechanism The five essential elements required for
act to modulate pain . Pharmacologic studies most spinal reflexes are (a ) peripheral recep-
indicate that opiates and opioid peptides reg- tors, ( b ) sensorv neurons, (c ) local interneu -
ulate nociceptive transmission in part by rons, ( d ) motor neurons, and ( e ) terminal ef -
presynapticaily inhibiting the release of glu - fectors. The nn/ otatic or stretch reflex is a
tamate, substance P, and other transmitters monosynaptic reflex dependent upon two
from the sensory neurons. Transmitter re- -
neurons. Stretch sensitive proprioceptive
lease is suppressed by activation of opiate re- endings located in muscle ( muscle spindle)
ceptors on the sensory neurons, which de- and tendon (Golgi tendon organ ) are the re-
creases Ca: entry into the sensory terminal . ceptors stimulated by a sudden brisk stretch
THAFUSAL
lUSCLE
11 P-J MUSCLE
I I SINGLE
1
I STIMULATED
SILENCED
GOLGI TENOON ORGAN
MUSCLE STRETCHED MUSCll CONTRACTED
I |l
B
Hilt
A '
»1
C A2
.
X. GOLGI
mini i t i isM Mttr
i
Figure 10.29 Anatomic and functional relationships of the muscle spindle and the Golgi tendon organ to extrafusal
.
muscle fibers. The muscle spindles are arranged ’parallel " with the extrafusal muscle fibers, so that stretching the mus-
cle causes the spindles to discharge Contraction of the muscle tends to ’unload’ or ’silence' the muscle spindles
The Golgi tendon organs are arranged in 'series’ with respect of the extrafusal muscle fibers Thus, the Golgi tendon
organs can be discharged by either a stretch of the tendon or a contraction of the muscle The threshold of the Golgi
tendon organ is relatively higher than that of the muscle spindle The lower diagram summarizes the functional char
acteristlcs of the muscle spindle and Golgi tendon in relation to changes in muscle length At A, the muscle is shown
at its resting length , and the slow spontaneous discharge of the tendon organ and muscle spindle is indicated At 8,
the muscle is stretched and both receptors discharge, though the adaptation of the muscle spindle is more rapid At
A / the muscle resumes its original length and tension and there is a temporary reduction in the frequency of sponta -
,
neous firing of the muscle spindle At C. where the muscle is contracted and shortened, the muscle spindle is si -
lenced. but the rate of discharge of the tendon organ is increased At A2 the muscle is stretched out to its resting
length, and the muscle spindles are therefore discharged , while the tendon organs are silenced by the drop in ten-
sion
of muscle. The muscle spindle , consisting of fire the annulospiral or primary afferent fiber
bundles of specialized slender muscle fibers (group la ) of this receptor. The "/-efferent
( intrafusal fibers ) surrounded by a connective fibers from the smaller anterior horn cells ter-
tissue capsule, is attached to the endomysium minating in the polar (contractile) portions of
of extrafusal muscle fibers ( Fig. 7.11 ). Stretch- the muscle spindle ( intrafusal muscle fibers)
ing of the noncontractile nuclear bag region bring this receptor under the control of spinal
(equatorial region ) of the muscle spindle con- and supraspinal influences.
stitutes the mechanical stimulus required to Golgi tendon organs are found in tendons
Dorsal root
ganglion
L2
Muscle spindle Golgi tendon

organ
L3
Motor end
plates
L4 *<
Descending - X Afferent spindle

fiber systems fiber
Muscle
! o
spindle
Motor end
plates
y efferent fiber —^
a fiber
Golgi tendon organ

V
Figure 10.30 Patellar tendon reflex Motor and sensory fibers of the femoral nerve associated with spindl segments
.
L2 L3, and L4 mediate this myotatic reflex The principal receptors are the muscle spindles, which respond to a brisk
stretching of the muscle effected usually by tapping the patellar tendon Afferent fibers from muscle spindles dre
shown entering only the L3 spinal segment, while afferent fibers from the Golgi tendon organ are shown entering only
. .
the L2 spinal segment . In this monosynaptic reflex, afferent fibers entering spinal segments 12. L3 and L4 and efferent
fibers issuing from the anterior horn cells of these levels complete the reflex arc Motor fibers shown leaving the L4
spinal segment and passing to the hamstring muscles demonstrate the pathway by which inhibitory influences are ex-
erted upon an antagonistic muscle group during the reflex The small diagram below illustrates the y loop. y-Efferent
fibers pass to the polar portions of the muscle spindle. Contractions of the intrafusal fibers in the polar parts of the spin-
dle stretch the nuclear bag region and thus cause an afferent impulse to be conducted centrally . The afferent fibers
from the spindle synapse upon an a motor neuron, whose peripheral processes pass to extrafusal muscle fibers, thus
completing the loop Both a and y motor neurons can be influenced by descending fiber systems from supraspinal
levels. These are indicated separately
close to their muscular attachments ( Figs. femoral nerve is composed of sensory and
7.15 and 7.16). As first pointed out in early motor fibers from spinal nerves L2, L3, and
studies bv Fulton and Pi-Suner ( 30 ), the mus- L 4 . Thus, the synapses between these sensory
cle spindle is arranged in "parallel" with ex- and motor fibers must be within spinal cord
trafusal fibers, so that stretching of a muscle segments L2, 1.3, and 1.4. The myotatic reflex
causes the spindle to discharge, while con- is clinically useful in determining the levels
traction of the extrafusal fibers tends to "un - of motor integrity of the nervous system, and
load " the spindle. The Golgi tendon organ is also may reveal evidence of release of higher
in "series" with extrafusal muscle fibers and control.
thus can be caused to discharge by either a Afferent fibers from Golgi tendon organs
stretch or a contraction of the muscle ( Fig. (group lb ) have disynaptic inhibitory influ -
10.29). Current physiologic belief, based ences upon a motor neurons ( Fig. 10.30). Al -
largely upon indirect evidence, indicates that though Golgi tendon organs have a higher
the low threshold muscle spindles are the threshold than the muscle spindles, afferent
prime receptors involved in the stretch reflex. discharge of lb fibers can exert inhibitory in -
However, y-efferent fibers to the muscle spin - fluences upon a motor neurons which reduce
dle can exert potent influences upon the ac- muscle tone. Unlike the muscle spindle, the
tivity of this receptor. The myotatic reflex can Golgi tendon organ does not receive efferent
be elicited in almost any muscle by sharply fibers from the central nervous system . As
tapping either the muscle or its tendon in shown in Figure 10.24, other spinal reflexes
such a way as to produce a brief sudden have one or more internuncial neurons inter-
stretch of the muscle. Thus, striking the ten - posed between sensory and motor neurons,
don of the quadriceps femoris muscle pro- and some of these may form complex circuits.
vokes a forceful contraction of the stretched An anterior horn cell ( lower motor neuron )
muscle and a quick extension of the leg at the thus may be facilitated, or inhibited , by the
knee ( Fig. 10.29). In this example, both the sum total of all the impulses that play upon it
sensory and motor nerve fibers leave and through literally thousands of synaptic termi-
enter the quadriceps muscle as constituents nals. Such synaptic endings may be terminals
of the femoral nerve. It will be recalled that of incoming sensory fibers, interneurons, or
parts of two, three, or more myotonies are in- several of the descending motor pathways
corporated in each muscle, and that two, arising from higher levels of the neuraxis.
three, or more spinal nerves and cord seg- This is the basic organization of the spinal
ments provide sensory and motor fibers. The cord segment and its attached spinal nerves.
References 6. Basbaum A I , Ralston DD, Ralston and its possible role in modulation
III Bulbospinal projections in the of spinothalamic cells. Brain Res
-
1 . Albe Fessard D, l .evante A , (.am - primate: a light and electron mi - -
1991;543:77 90.
our Y . Origin of spinothalamic croscopic study of a pain modulat - 12. Carpenter MB, Stein BM , Shriver
tract in monkeys. Brain Res ing system . J Comp Neurol IF . Central projections of spinal
1974;65:503-509. 1986:250:311-323. dorsal roots in the monkey . II .
2. Alvarez FJ , Kavookjian AM , Light 7. Battaglia G, Kustioni A. Coexis - Lower thoracic, lumbosacral and
AR . Synaptic interactions between tence of glutamate and substance I’ coccygeal dorsal roots. Am | Anal
CABA -immunoreactive profiles
and the terminals of functionally
in dorsal root ganglion neurons of
the rat and monkey. ) Comp Neu - 1.3.
-
1968;123:75 118*
Cervero F, Iggo A . The substantia
defined myelinated nociceptors in rol 1988;277:302-312. gelatinosa of the spinal cord . A
the monkey and cat spinal cord . J
Neurosci 1992:12:2901 2917.
8. Bok ST. Das Kiickenmark . In : von .
critical review Brain !980;1Q3:
Molendorff W, ed . Handbuch der 711-772.
3. Barber RP, Phelps PF , Houser CR , mikroskopischen Anatomie des 14 Chiba T , Masuko S. Coexistence of
Crawford CD, Salvaterra PM , Menschen. Berlin: Julius Springer, varying combinations of neuropep -
Vaughn JF. The morphology and
distribution of neurons containing 9.
1928:478-578.
Burton H , Loewy AD. Descending
-
tides with 5 hydroxytrvptamine in
neurons of the raphe pallidus el ob-
choline acetvltransferase in the projections from the marginal cell scurus projecting to the spinal cord .
adult rat spinal cord: an immuno - layer and other regions of the mon- Neurosci Res 1989;7:13-23.
cvtochemical study. | Comp Neu - key spinal cord. Brain Res 15. Chung K , Coggeshall RE. Primary
-
rol 1984;229:329 346.
4 . Barber RP. Vaughn IF, Roberts E. 10.
-
1976;116:485 491.
Cameron WD, Averill DB, Berger
afferenl axons in the tract ol I is
sauer in the cat . J Comp Neurol
The cytoarchitecture of GABAergic AJ . Morphology of cat phrenic mo - 1979:186:451 164
neurons in rat spinal cord . Brain
Res 1982;238:305-328.
toneurons as revealed by intracel - 16. Cooper S, Sherrington CS. Gower's
lular injection of horseradish per - tract and spinal border cells. Brain
.
5. Basbaum AR Fields HL. Endoge - oxidase. J Comp Neurol 1983; 1940;63:123-143.
nous pain control systems: brain - 219:70 SO 17. Cootc III . Bulbospinal serotonergic
stem spinal pathways and endor- 11 . .
Carlton SM , Honda CN Willcock - pathways in the control of blood
phin circuitry. Annu Rev Neurosci son VVS, et al . Descending adrener- pressure. J Cardiovasc Pharmacol
-
1984;7:309 338. gic input to the primate spinal cord -
1990;15(Suppl 71:35 41.
. -
18. Cullheim S Kellerth J O. Morpho-
logical study of the axons and re-
spinal cord . Ch. 3. New York: M .
Dekker, 1984:79-136.
46. Molstege JC. Ultrastructural evi
dence for GABAergic brain stem
-
current axon collaterals of cat sci- 33. Fyffe RFVV . Evidence for separate projections to spinal motoneurons
atic u motoneurons after intra - morphological classes of Renshaw in the rat . | NeUTOfid 1991;
cellular staining with horseradish cells in the cat's spinal cord . Brain -
11:159 167.
peroxidase | Comp Neurol 1978; Res 1990;536:301-304. 47. Holstege JC, Bongers CM . A
178:537-558. 34 . Fyffe RFVV . Spatial distribution of glycinergic projection from the
19. Cullheim S, Keller th J -O, Con rad i recurrent inhibitor)’ synapses on ventromedial lower brainstem to
S. Evidence for direct synaptic in - spinal motoneurons in the cat. J spinal motoneurons. An ultrastruc-
terconnections between cat spinal Neurophysiol 1991;b5: l 1.34-1149. tural double labeling study in rat
-
gamma motoneurons via the re- 35 Fyffe RFVV Glycine-like irn - Brain Res 1991;566:308-315.
current axon collaterals: A mor - munoreactivity in synaptic bou- 48. Holstege JC, Bongers CM. Ultra -
phological study using intra - tons of identified inhibitory in- structural aspects of the coeruleo-
cellular injection of horseradish terneurons in the mammalian spinal projection. Prog Brain Res
peroxidase brain Res 1977;132:
, spinal cord . Brain Res 1991; 1991;88:143-156.
1-10. 547:173-179. 49. Hughes J . Isolation of an endoge-
20. Cummings JF, Petras JM. The ori -
gin of spinocerebellar pathways. I .
.
3b. Gibson SJ Polak JM , Bloom SR , et nous compound from fhe brain
al. Calcitonin gene-related peptide with pharmacological properties
The nucleus cervicalis centralis of (CGRP)-immunoreactivity in the similar to morphine. Brain Res
the cranial cervical spinal core. ) spinal cord of man and of eight -
1975;88:295 308.
Comp Neurol 1977;173:655-692 . spec ia I Neurosci 1984 ; 4 : 50. Hughes J . Intrinsic factors and the
21 Dahlstrblm A , Luxe K . Evidence 3101- 3111 . opiate receptor system. Neurosci
for the existence of monoamine - 37. Gordon G . Spinal mechanisms of Res Program Bull 1978;16:141 -147.
containing neurons in the central motor coordination . In : Kandcl FR , 51 Hunt SP. Cytochemistry of the
nervous system. I Demonstration Schwartz III . Jesscll TM , eds. Prin - spinal cord . In : Emson l*C, ed .
of monoamines in the cell bodies of ciples of neural science. Ch. 38. Chemical neuroanatomy . New
brainstem neurons. Acta Physiol New York: Elsevier, 1991:581-595. York: Raven Press, 198.3:53-84 .
Stand l %4;62(Suppl 232 ): l -55 i 38. Grant G, Rexed B Dorsal spinal 52. Jansen KL, Faull RLW, Dragunow
22. IVBiasi S, Kustioni A . Glutamate root afferents to Clarke's column . M , Waldvogel II . Autoradi -
and substance 1’ coexist in primary Brain 1958;81:567-576. ographic localisation of NMDA .
afferent terminals in the superficial 39. Haefely W , Pole P, Pieri L, quisqualate and kainic acid recep -
laminae til spinal cord. Proc Natl Schaflnor R. Laurent JP. Biological tors in human spinal cord . Neu -
Acad Sci USA 1988;85:7820-7824 .
. basis of the therapeutic effects of -
rosci Lett 1990;108:53 57.
.
23. Dejerine J Roussy C . Le syndrome benzodiazepines. In: Costa F, ed . 53. Jessell TM, Iversen Ll.. Opiate
thalamique. Rev Neurol 1906, The benzodiazepine: from molecu - analgesics inhibit substance P re -
14:321-532. lar biology to clinical practice. lease from rat trigeminal nucleus.
24 . Draisci G , Kajander KC , Dubner R , New York: Raven Press, 1983: Nature 1977;268:549-551 .
Bennett G|, ladarola MJ . Up- regu - 21 -66. 54. Jessell TM , Kelly DD. Pain and
lafion of opioid gene expression in 40 I ibkfelt T, l uxe K , Pernow B, eds. analgesia . In: Kandel ER , Schwartz
spinal cord evoked by experimen -
tal nerve injuries and inflamma -
Coexistence of neuronal messen
—
gers a new principle in chemical
- JH , Jessell TM , eds. Principles of
neural science. Ch . 27. New York
-
tion . Brain Res 1991;560:186 192. transmission. Advances in brain Elsevier , 1991:385- 399
25. Earle KM . The tract of lissauer research. Vol . 68. New York: Else - 55. Kellstein DF, Price DD, Hayes RL,
and its possible relation to the pain vier, 1986. Mayer DJ . Evidence that substance
pathway . I Comp Neurol |952;9b
93-111.
41 . Iloktelt T, Johansson O, Ljungdahl
A . l.undberg JM , Schultzberg M .
- -
P selectively modulates C fiber
evoked discharges of dorsal horn
2b. Earles JC, Eccles RM , Iggo A , Peptidergic neurones. Nature nociceptive neurons. Brain Res
l . undberg A . Flectrophvsiological 1980;284:513-521. -
1990;526:291 298.
investigations on Renshaw cells. | 42. I Ibkfelt T, Kellerth JO, Nilsson G . 5b. Kernell D, Zwaagstra B. Dendrites
-
Physiol ( Lond ) 1961;159:4b1 178
27. Eccles JC , Fatt P, Koketsu K . Distri -
Pernow B. Substance P: localiza
tion in the central nervous system
- of cat 's spinal motoneurones: rela -
tionship between stem diameter
bution of recurrent inhibition and in some primary sensory neu - and predicted input conductance.|
among motoneurons. J Physiol
( Lond ) 1954 ; 12b:524-5b2.
rons Science 1975;19ft8W W0,
-
-
43. Hokfelt T, Kellerth J O, Nilsson G,
Physiol (Lond ) 1989;413:255-269.
57. Kerr FWL . The organization of pri -
28. Faull RI M . Villiger JVV. Opiate re- Pernow B. Experimental immuno- mary afferents in the subnucleus
ceptors in the human spinal cord: a histochemical studies on the local - caudalis of the trigeminal: a light
detailed anatomical study compar - ization and distribution of sub - and electron microscopic study of
ing the autoradiographic localiza - stance P in cat primary sensory degeneration. Brain Res 1970;
tion of ll l - diprenorphine binding neurons. Brain Res 1975;100: -
23:147 165.
sites with the laminar pattern of 235-252. 58. Kerr FWL. Neuroanatomical sub -
substance P, myelin and Nissl .
44 Hokfelt TA, Ljungdahl A Terenius strates of nociception in the spinal
staining. Neuroscience 1987;20: L, Fide R , Nilsson G. Immunohis - cord . Pain 1975;1:323- 356.
395-407 tochemical analysis of peptide 59. Kerr FWL. Pain: a central in -
29. Fields ML . Pain . New York: Mc - pathways possibly related to pain hibitory balance theory Mayo Clin
Graw - Hill. 1987. and analgesia: enkephalin and sub - Proc 1975;50:685-690 .
.30. Fulton |F, Pi -Suner J . A note con - stance P. Proc Natl Acad Sci USA 60. Kerr FWL. Segmental circuitry of
cerning the probable function of 1977;74:3081 3085. - the spinal cord and nociception .
various afferent end -organs in .
43 Hokfelt T Martensson R . Bjork - Neurosci Res Program Bull 1978;
skeletal muscle. Am J Physiol lund A , Klcinau S, Goldstein M . 16:51-65.
!927;83:554-5b2. Distributional maps of tyrosine - 61 . Klein CM , Sorkin LS, Chung K ,
31. Fung SJ , Zhuo II , Man /oni D, -
hydroxylase immunoreactive neu - Coggeshall RF. Unmyelinated pri -
Reddy VK , Barnes CD. Coeruleo- rons in the rat brain. In : Bjorklund mary afferent fiber stimulation de-
spinal cells containing neuropep- A , I lokfelt T, eds. I landbook of plete dvnorphin A ( 1-8) im -
tide Y in the cat. Peptides 199|;12: chemical neuroanatomy. Vol . 2. munoreactivity in rat ventral horn.
Ml Classical transmitters in the CNS, Brain Res 1991 ;566:70-76.
32. Fyffe RFVV Afferent fibers. In : Part I . Ch b. Amsterdam : Elsevier, .
62 Kuhar MJ Pert CB, Snyder SH . Re-
Davidoff RA , ed . Handbook of the 1984:277- 379. gional distribution of opiate recep-
tor bindings in monkev and 77. Manaker S, Winokur A, Rhodes ture of the brain. Berlin: Springer -
human. Nature 1973;245:447-450. CM . Rainbow TC. Autoradi - Verlag, 1985.
63. Kuma/awa TE, Perl HR, Burgess ographic localization of thy - .
92 Oh ID, Woolf NJ, Roghani A, Ed -
.
I’K VVhitehorn D. Ascending pro- rotropin-releasing hormone (TRH) wards RlI, Butcher LL. Cholinergic
jections from marginal / one ( lam - receptors in human spinal cord . neurons in the rat central nervous
ina I) neurons of the spinal dorsal Neurology 1985;35:328-332. system demonstrated by in situ hy-
horn. I Comp Neurol 1975; 78. Mannen 11, Sugiura Y. Reconstruc - bridization of choline acetyltrans-
162: 1-12. tion of neurons of dorsal horn ferase mRNA . Neuroscience 1992;
64. kuru M. Sensory paths in the proper using Colgi-stained sec - 47:807-822.
spinal cord and brainstem of man. tions. J Comp Neurol 1976; 93. Oscarsson O. Functional organiza -
Tokyo: Sogenska, 1949:675-713. 168:303-312. tion of spinocerebellar paths. In:
65. Li Motte CC, ) ohns DR, de 79. Matsushita M, Ikeda M. The cen- Iggo A, ed. Handbook of sen -
I anerolle NC. Immunohistochemi - tral cervical nucleus as cell origin sory physiology. Vol. 2. Berlin:
cal evidence of indoleamine neu - of a spinocerebellar tract arising Springer - Verlag, 1973:339-380.
rons in monkey spinal cord. J from the cervical cord: a study in 94. Pearson J, Brandeis L, Cuello AC.
Comp Neurol 1982;206:359-370. the cat using horseradish peroxi- Depletion of substance P-contain-
. .
66. La Motte CC Pert CB Snyder SH. dase. Brain Res 1975;100:412 417 - . ing axons in substantia gelatin-
Opiate receptor binding in primate 80. Matsushita M, Ikeda M Projec -. osa of patients with diminished
spinal cord: distribution and tions from the lateral reticular nu- pain sensitivity . Nature I982;295
changes after dorsal root section. cleus to the cerebellar cortex and i» l 63«
Brain Res 1976;112: 407-412. nuclei in the cat. Exp Brain Res 95. Pert CB. Opiate receptors and pain
.
67. Light AR Perl HR. Reexamination 1976;24:403-422. pathways. Neurosci Res Program
of the dorsal root projection to the 81 Maxwell DJ, Christie WM, Ot - Bull 1978;16:133-141
spinal dorsal horn including obser - tersen OP, Storm - Mathisen |. Ter - 96 Pert CB, Snvder SH. Opiate recep-
vations on the differential termina - minals of group la primary affer - tor demonstration in nervous tis-
tion of coarse and fine fibers. ] ent fibers in Clarke's column are sue. Science 1973;179:1011-1014.
Comp Neurol 1979;186: 117- 132. enriched with L - glutaniate-like 97. Petras JM, Cummings JF. Auto-
68. Light AR , Perl HR. Spinal termina - immunoreactivity . Brain Res nomic neurons in the spinal cord
tions of functionally identified pri - 1990;510:346-350 . of the Rhesus monkey: a correla -
mary afferent neurons with slowly 82. Maxwell DJ, Christie WM, Short tion of the findings of cytoarchitec-
conducting myelinated fibers. J AD, Storm-Mathisen J, Ottersen tonics and sympathectomy with
Comp Neurol 1979;186:133- 150. .
OP Central boutons of glomeruli fiber degeneration following dor -
.
69. Light AR Trevino DL, Perl ER. in the spinal cord of the cat are sal rhizotomy. J Comp Neurol
Morphological features of func- enriched with L- glutamate-like 1972;146: 189-218.
tionally defined neurons in the immunoreactivitv. Neuroscience 98. Petras JM, Cummings JF. The ori-
marginal / one and substantia fc36:83 104. gin of spinocerebellar pathways. II.
gelatinosa of the spinal dorsal .
83. Melzack R, Wall PD Pain mecha - The nucleus centrobasalis of the
horn. J Comp Neurol 1979; nisms: a new theory. Science cervical enlargement and the nu -
186:151-172. 1965;150:971-979. cleus dorsalis of the thoracolumbar
70. Lindvail O, Bjorklund A. 84 Melzack R, Wall PD. The challenge spinal cord. J Comp Neurol
Dopamine- and norepinephrine- of pain. New York: Basic Books, 1977;173:693-716.
containing neuron systems: their 1983. 99. Poliak S. Die Strukureigentum -
anatomy in the rat brain. In: 85. Menetrey D, Gannon A, Levine JD, lichkeiten des Riickenmarkes bei
Emson (XT, ed. Chemical neu- Basbaum Al. Expression of c-fos den Chiroptern . Zugleich ein
roanatomv New York: Raven protein in interneurons and projec- Beit rag zu der Frage liber die
Press, 1983;229-256.
71. Liu CN. Afferent nerves to
Clarke's and the lateral cuneate
tion neurons of the rat spinal cord
in response to noxious somatic, ar -
ticular, and visceral stimulation. |
cus. Z Anal Entwickl -Cesch
1924;74:509- 576.
.
spinalen Zentren des Sympatheti -
nuclei in the cat. Arch Neurol Psy - Comp Neurol 1989;285:177-195 . 100. Pompeiano O. Recurrent inhibi -
chiatry 1956;75:67-77. 86. Merighi A, Polak |M, Theodosis tion. In: Davidoff RA, ed. Hand -
72. Lloyd DPC, McIntyre AK . Dorsal .
DT Ultra struct uraI visualization of book of the spinal cord. Ch. 11 .
column conduction of group I glutamate and aspartate im- New York: M. Dekker, 1984:
muscle afferent impulses and their munoreactivities in the rat dorsal 461 - 557.
relay through Clarke's column. J horn, with special reference to the 101. I’oulat P, Marlier L, Rajaofetra N,
Neurophvsiol 1950;13:39-54. co-localization of glutamate, sub- I’rivat A. 5-Hydroxytryptamine,
.
73. Long DM Hagfors N. Electrical stance P and calcitonin-gene re- substance P and thyrotropin-re-
stimulation in the nervous system: lated peptide. Neuroscience 1991; leasing hormone synapses in the
the current status of electrical stim - 40:67-80. intermediolateral cell column of
ulation of the nervous system for 87. Moschovakis AK, Burke RE, Evffe the rat thoracic spinal cord. Neu -
the relief of pain. Pain 1975; RE. The size and dendritic struc- rosci Lett 1992;136:19 22 .
1:109-124. ture of HRP-labeled gamma mo- 102. Powell JJ, Todd AJ. Light and elec -
74 l.orente de No R. Symposium dis - toneurons in the cat spinal cord. J tron microscope study of GABA -
cussion. In : Malcolm JL, Cray JAB, Comp Neurol 1991;311:531-545 . immunoreactive neurones in lam -
eds. The spinal cord. Ciba Founda- 88. Mountcastle VB. Sensory receptors ina III of rat spinal cord. I C omp
tion Symposium. Boston; Little, and neural encoding: Introduction Neurol 1992;315:125-136.
Brown & Company, 1953:40-41. to sensory processes. In: Mountcas- 103. Price DD, Mayer DJ. Physiological
75. I.oup F, Tribollet H, Dubois - .
tle VB, ed Medical physiology. laminar organization of dorsal
Dauphin M, Pizzolato C», Dreifuss Vol. I. St . Louis: C. V . Mosby, horn of M. Mnlnltu . Brain Res
||. Localization of oxytocin binding 1974:285-306, 348-381. 1974;79:321-325.
sites in the human brainstem and 89. Narot /ky RA, Kerr EWL. Marginal 104. Price |, Mudge AW A subpopula -
.
upper spinal cord: an autoradi - neurons of the spinal cord. Brain tion of rat dorsal ganglion neurons
ographic study. Brain Res 1989; Res 1978;139: 1 -20. is catecholaniinergic . Nature 1983,
500:223-230. .
90 Nathan PVV, Wall I’D. Treatment of 301:241-243.
76 I inn B, I lunt SP. Afferent C - fibers: post - herpetic neuralgia by pro- 105. Rajaofetra N, Ridel JL, I’oulat P, et
physiological and biochemical cor - longed electric stimulation. Br Med al. Immunocytochemical mapping
relations . Trends Neurosci 1984; J 1974;3:645 -647. of noradrenergic projections to the
7:186-188. 91. Nieuwenhuvs R . Chemoarchitec - rat spinal cord with an antiserum
against noradrenaline. J Neurocy- cord . 1 Chem Neuroanat 1990; Daw lev rat . Brain Res 1992;579:
tol 1992;21 :481 -494 . 3:141-153, 67-73.
106. Ralston H| 111. The organization of
the substantia gelatinosa Rolandi
- -
122. Ribeiro da Silva A , Pioro EP,
Cuello AC,. Substance P and -
137. Snyder RL. The organization of
dorsal root entry zone in cats and
in the cat lumbosacral spinal cord . enkephalin - like immunoreactivi - monkeys. J Comp Neurol 1977;
Z Zellforsch Mikrosk Anat 1965; ties are colocalized in certain neu - -
174:47 69.
67:1 -23. rons of the substantia gelatinosa of 138. Sprague JM . Motor and pro -
107. Ralston 111 III . The tine structure of the rat spinal cord : an ultrastruc - priospinal cells in the thoracic and
neurons in the dorsal horn of the -
tural double labeling study. J Neu - iumbar ventral horn of the Rhesus
cat spinal cord . 1 Comp Neurol
1968;132:275-302.
-
rosci 1991;11:1068 1080.
123. Romanes GJ . The motor cell
monkey. J Comp Neurol 1951;
95:103-124.
108. Ralston III III . Dorsal root projec- columns of the lumbosacral spinal 139. Sprague |M . The distribution of
tions to the dorsal horn neurons in cord of the cat. J Comp Neurol dorsal root fibers on motor cells in
the cat spinal cord . J Comp Neurol - -
1951,94:313 363. the lumbosacral spinal cord of the
1968, 132:303-330. 124. Rothstein JD, Tsai G, Kund RW, et cat , and the site of excitatory and
109. Ralston IIJ 111. The fine structure of al . Abnormal excitatory amino acid inhibitory terminals in monosy -
laminae I , II , and III of the metabolism in amyotrophic lateral naptic pathways. Proe K Soc Lond
macaque spinal cord . J Comp Neu - sclerosis. Ann Neurol 1990; ( Biol ) 1958;149:534-556.
rol 1979;184:619-642. 28:18-25. 140. Sprague ) M , Ha H. The terminal
110. Ralston IIJ III , Ralston DD. The 125. Ruda MA , Bennett GJ , Dubner R . fields of dorsal root fibers in the
distribution of dorsal root axons in Neurochemistry and neural cir - lumbosacral spinal cord of the cat ,
laminae I , II and III of the macaque cuitry in the dorsal horn. Prog and the dendritic organization of
spinal cord: a quantitative electron Brain Res 1986;66:219-268. the motor nuclei . In : Eccles JC,
microscope study. J Comp Neurol -
126. Scatton B, Dubois A, Javoy Agid F, Schade JP, eds. Progress in brain
1979; 184:643-684 .
111 . Ramon y Cajal S. Ilistologie du
Camus A. Autoradiographic local
ization of muscarinic cholinergic
- research. Vol. 2. Organization of
the spinal cord . Amsterdam: Else-
Systeme Nerveux de I ' Homme et receptors at various segmental lev - vier, 19h4:12()-152.
des Vertebres. ( Azoulay L, Trans. ) els of the human spinal cord . Neu - 141 . Sterling P, Kuypers HCJM
Paris: Maloine, 1909, 1911. rosci Lett 1984;49:239-245. Anatomical organization of the
( Reprinted , Consejo Superior de 127. Scheibel AB. Organization of the brachial spinal cord of the cat. 11.
Investigaciones Cientificas, Insti- spinal cord . In : Davidoff RA, ed . The motoneuron plexus. Brain Res
tuto Ramon y Cajal, Madrid , 1972. ) Handbook of the spinal cord . Ch. 1967;4:16-32.
112. Ranson SW . The course within the 2. New York: M . Dekker, 1984: 142 . Strick PL, Burke RE, Kanda K. Kim
spinal cord of the nonmyelinated 47-77. CC, Walmsley B. Differences be-
fibers ol the dorsal roots: a study of 128. Scheibel ME, Scheibel AB. Spinal tween alpha and gamma motoneu -
Lissauer's tract in the cat. I Comp motoneurons, interneurons and rons labeled with horseradish per -
Neurol 1913;23:259-281. Renshaw cells. Arch Ital Biol oxidase bv retrograde transport.
113. Ranson SW . The tract of Lissauer 1966;104:328-353. Brain Res 1976;113:582-588.
and the substantia gelatinosa 129. Schoenen J . The dendritic organi - 143. Szentagothai J . Neuronal and
Rolandi. Am J Anat 1914; zation of the human spinal cord : synaptic arrangement in the sub-
16:97-126. the dorsal horn. Neuroscience stantia gelatinosa Rolandi. ) Comp
114 . Renshaw B Activity in the sim - 1982;7:2057-2087. Neurol 1964;122:219-239.
plest spinal reflex pathways. I 130. Schoenen J . Dendritic organization 144. Szentagothai J , Albert A . The
Neurophysiol 1940;3:370-387. of the human spinal cord: the mo - synaptologv of Clarke's column .
115. Renshaw B. Influence of discharge toneurons. I Comp Neurol Acta Morphol Acad Sci Hung
of motoneurons upon excitation of 1982;211:226-247. 1955;5:43-51 .
neighboring motoneurons. J Neu - 131. Schoenen J , Eaull RLM. Spinal 145. Todd A ) , McKenzie J . GABA im --
rophvsiol 1941 ;4:167- 183. cord : cytoarchitectural, dendroar - munoreactive neurons in the dor -
116. Renshaw B. Central effects of cen - chitectural , and mveloarchitectural sal horn of the rat spinal cord .
tripetal impulses in axons of spinal organization. In : Paxinos G, ed . -
Neuroscience 1989;321:799 806.
ventral roots. J Neurophysiol The human nervous system . Ch . 2. 146. Todd I IJ , Spike RC , Russel G,
1946;9:191-204. New York: Academic Press, johnston IIM . Immunhistochemi -
117. Rethelyi M . Types of synaptic con - 1990: 19-53. -
cal evidence that Met enkephalin
nections in the core of the spinal 132. Sclu »encn J , Faull RLM . Spinal and GABA coexist in some neu -
gray matter. In: Davidoff RA , ed . cord : chcmoarchitectural organiza - rons in rat dorsal horn . Brain Res
I landbook of the spinal cord . Ch . tion . In : Paxinos G, ed. The human 1992;584:149-156.
5. New York: M . Dekker, 1984: nervous system . Ch . 3. New York: -
147. Tbrk I , Homung J P. Raphe nuclei
179-198. Academic Press, 1990:55-75. and the serotoninergic system. In:
118 Rexed B . The cytoarchitectonic or - 133. Schnitzlein I IN , Hoffman Hl l , Paxinos G , ed . The human nervous
ganization of the spinal cord in the Hamlett DM , Howell EM . A study system. Ch. 30. New York: Aca-
cat. J Comp Neurol I 952;96: of the sacral parasympathetic nu - -
demic Press, 1990:1001 1022.
415-495. cleus. J Comp Neurol 1963; 148. Trevino DL, Carstens E. Confirma -
119. Rexed B. A cytoarchitectonic atlas 120:477-493. tion of the location of spinothala -
of the spinal cord in the cat. J 134 . Shriver JE , Stein BM , Carpenter mic neurons in the cat and monkey
Comp Neurol 1954;100:297-379. MB. Central projections of spinal by the retrograde transport of
120. Rexed B. Some aspects of the cy * dorsal roots in the monkey. I . Cer - horseradish peroxidase. Brain Res
toarchitectonics and synaptologv vical and upper thoracic dorsal 1975;98:177-182.
of the spinal cord . In : Eccles JC , roots. AmJ Anat 1968;123:27-74. 149. Trevino DL, Coulter JD, Willis
Schade II’, eds. Progress in brain 135. Simantov R , Kuham JJ , Pasternak WD. Location of cells of origin of
research . Vol. II . Organization of GW, Snyder SH . The regional dis- spinothalamic tract in lumbar en -
the spinal cord. Amsterdam : Else- -
tribution of a morphine like factor largement of the monkey . J Neuro -
vier, 1964:58-92. enkephalin in monkey brain. Brain
'
physiol 1973;36:750-761 .
121 . Ribeiro-da -Silva A , Cuello AC . Ul- Res 1976;106:189-197. 150. Truex RC , Taylor M . Gray matter
trastructura ) evidence for the oc- 136. Sluka KA , Westlund KN . Spinal lamination of the human spinal
currence of two distinct somato - projections of the locus cocruleus cord . Anat Rec 1968:160:502.
statin -containing systems in the and the nucleus subcoeruleus in 151 . Unnerstall |R , Kcpajtic TA, Kuhar
substantia gelatinosa of rat spinal the I larlan and the Sasco Sprague- -
M|. Distribution of alpha 2 agonist
binding sites in the rat and human 155. Wall PD. The laminar organization DR Jr. Spinothalamic tract neurons
central nervous systems: analysis of dorsal horn and effects of de- in the substantia gelatinosa. Sci-
of some functional, anatomic corre- scending impulses. J Physiol ence 1978;202:986-988.
lates of the pharmacologic effects -423.
(Lond ) 1967;188:403 162 Willis WD, Trevino DL, Coulter
of clonidine and related adrenergic 136 Wall PD. The gate control theory ot JD, Maunz. RA Responses of pri-
agents. Brain Res Rev 1984;7: pain mechanisms: A re-examina - mate spinothalamic tract neurons
69 10!. -
tion and re statement. Brain 1978; to natural stimulation ol hindlimh.
. .
152. Vanner SJ Rose PK Dendritic dis- 101: 1 - 18. J Neurophysiol 1974;37:358-372.
tribution of motoneurons innervat - 157. Wall PD, Melzack R, eds. Textbook 16.3. Willis WD, WillisJC. Location ot
ing the three heads of the trape/ius of pain. 2d ed. Edinburgh: Renshaw cells. Science I964;204 :
muscle in the cat. J Comp Neurol Churchill Livingstone, 1989. 1214- 1215.
1984;226:96- 110. 158. Wall I’D, Sweet WH. Temporary 164 Willis WD, Willis JC Properties of
153. Villiger JW, Faull RLM. Muscarinic abolition of pain in man. Science interneurons in the ventral spinal
cholinergic receptors in the human 1%7;155:108-109. cord. Arch Ital Biol 1966; 104:
spinal cord, differential localiza- 159. Willis WD. Nociceptive pathways: 354-386.
tion of 'H - pirenzepine and H - anatomy and physiology of noci- .
165 Zhuo II Fung SJ, Reddy VK,
quinuclidinvlbenzilate binding ceptive ascending pathways. Phi - Barnes CD. Immunohistochcmical
sites. Brain Res 1985;345:196-199 los Trans R Soc (Biol ) 1985; evidence for coexistence ol methio-
134. Waldvogel HJ, Faull RLM, Jansen 308:253-268. nine-enkephalin and tyrosine hy -
KL, et al. GABA, GABA receptors 160 Willis WD,Coggeshall RE. Sensory droxylase in neurons of the locus
and benzodiazepine receptors in mechanisms of the spinal cord 2d coeruleus complex projecting to
the human spinal cord. Neuro
science 1990;39:361 385.
- ed. New York: Plenum, 1991.
161 Willis WD, Leonard RB, Kenshalo
the spinal cord in the cat. J C hem
Neuroant 1992;5:1 -10.
11
Spinal Cord: Fiber Tracts
The motor and sensory information that helium receives sensory inputs from all types
flows along the spinal cord is conveyed of receptors but is not concerned with con -
through several, more or less distinct bundles scious sensory perception. Impulses pro-
lying within specific sectors of the white mat - jected to the cerebellum play an important
ter . Fiber bundles having the same origin, role in the regulation of muscle tone and the
course, and termination are known as tracts coordination of motor function .
or fasciculi. Information from the outside
world and internal milieu reach supraseg
mental levels of the neuraxis by coursing
- Posterior White Columns
along various ascending spinal tracts, A large proportion of heavily myelinated
whereas motor and modulatory commands fibers of the dorsal root curve medially
from higher brain centers reach their targets around the posterior horn and enter the pos-
in the spinal cord by running along specific terior or dorsal funiculus. These fibers, aris-
descending tracts. Additionally, local pro- ing from cells of spinal ganglia at all levels,
cessing of information in the spinal cord is bifurcate into long ascending and short de-
ensured by the presence of internuncial neu - scending branches. Ascending fibers from
rons and several fasciculi of varying lengths caudal segmental levels shift medially and
that serve as a link between different spinal dorsally as they ascend in the posterior fu -
segments. Since the white matter of the spinal niculus. Branches of fibers from cervical dor-
cord is divided into three funiculi (see Chap - sal roots ascend lateral to those of thoracic
roots. This pattern of ascending fibers results
ter 10 ), all ascending and descending tracts
lie in one or more funiculi . A funiculus may in an overlapping laminar arrangement in
contain several different tracts conducting which longer sacral fibers are most medial
impulses in different directions. Certain and posterior, shorter cervical fibers are most
spinal tracts are partially intermingled or lateral, and thoracic fibers occupy intermedi-
overlap fibers in other tracts. In general, long ate positions ( Figs. 11.1 and 11.2). The num-
tracts tend to be located peripherally in the ber of ascending fibers derived from a partic -
white matter, while shorter tracts are found ular dorsal root bears a relationship to the
near the gray matter. size of the root, with dorsal roots of the cervi -
cal and lumbar ( or lumbosacral ) enlarge-
ASCENDING SPINAL TRACTS ments contributing the largest number of
fibers.
Dorsal ( posterior ) root afferent fibers en- The posterior funiculus on each side is di-
tering the spinal cord convey impulses from vided by a posterior intermediate septum in
all general types of somatic and visceral re- the upper thoracic and cervical regions. This
ceptors. The signals transmitted rostrallv in septum, which becomes discernible at about
the spinal cord are segregated so that im - T6 ( Fig. 10.5), separates the fasciculus gracilis
pulses concerned with pain, thermal sense, medially from the fasciculus cuneatus laterally
touch , and kinesthesis (sense of movement ( Figs. 10.11 and 11.1 ). The fasciculus gracilis
and joint position ) from various body seg - or gracile fascicle, present at all spinal levels,
ments ascend together in more or less specific contains the long ascending branches of
tracts, sometimes widely separated from each fibers from sacral, lumbar, and the lower six
other. Ascending tracts not only convey thoracic dorsal roots. The fasciculus cuneatus
impulses concerned with specific sensory or cuneate fascicle first appears at about T6
modalities that reach consciousness, but they and contains long ascending branches of the
also transmit impulses from stretch receptors upper six thoracic and all cervical dorsal
and tactile receptors that project directly , or roots. Fibers in the fasciculus gracilis and
via relay nuclei, to the cerebellum . The cere- cuneatus ascend ipsilaterally and terminate
368
Sensory Cerebral cortex

cortex Leg Arm Hand (postcentral gyrus)
Corpus callosum-
. 0 1IT-'
Thalamus ,
Putamen i iir Vent posterolateral
,
Globus pallidus— nucleus ( VPL)
»
iin
MIDBRAIN
••I I I
III
Medial lemniscus
PONS
Trigeminal nerve
MEDULLA
7. -'
* Medial lemniscus
Nucleus gracilis Nucleus cuneatus
V> *
Internal arcuate fibers Spinal trigeminal nucleus

(neuron II) •I l l
I?
Decussation ot medial
Neuron I •i lemniscus
(dorsal root ganglion cell; Fasciculus gracilis
O
- in
in
Il 4
Fasciculus cuneatus
C8
Pacinian
n
corpuscle
O <
T4
Unencapsulated
joint receptor
( .
Fasciculus gracilis
O
L3
Golgi-Mazzoni
corpuscle & o
S4
Meissner's |3
I
corpuscle
.
Figure 11.1 Formation and course of the posterior white columns in the spinal cord and the medial lemniscus In the
brainstem The posterior white columns are formed from uncrossed ascending branches of spinal ganglion cells. Fibers
.
forming the medial lemniscus arise from cells of the nuclei gracilis and cuneatus cross in the lower medulla, and as-
cend to the thalamus. Impulses mediated by this pathway largely concern discriminating tactile sense (touch and
pressure) and kinesthetic sense (position and movement). Different receptors shown at various spinal levels on the left
generate impulses conveyed centrally by this system. Spinal ganglia and afferent fibers entering the spinal cord at dif -
ferent levels (red, sacral; blue, lumbar, green, thoracic; black cervical) are color coded Letters and numbers indi-
cate segmental levels of the spinal cord
Fosciculus Fasciculus Fasciculus

gracilis gracilis gracilis
19
&
Lat
'spinothalamic
spinothalamic
tract HIGH THORACIC tract
LOW THORACIC MIDDLE THORACIC
Post
, spinocerebellor
/ tract \ A
S' ii ii
& ^ \ jig
Lat Ant
spinothalamic^ spinocerebellar Lat
troct tract spinothalamic
CERVICAL ENLARGEMENT SECOND CERVICAL tract
Figure 11.2. Transverse sections of human spinal cord accidentally crushed some time previously in the lumbosacral
region. In this case, the antemortem neurologic signs and symptoms involved the lower extremities and the pelvis. In
the posterior white columns, the progressive diminution of the degenerated area is due to passage into the gray mat -
ter of short and medium length ascending branches of lumbosacral dorsal root fibers The progressive Increase in nor-
mal fibers adjacent to the posterior horn is due to the addition of ascending branches of dorsal root fibers entering
above the level of the injury (Weigert’s myelin stain).
upon the posterior column medullary relay erally in either the fasciculus gracilis or fasci-
nuclei , namely, the nuclei gracilis ami cuneatus culus cuneatus, depending on the level of
( Fig. 11.1 ). Dorsal root fibers projecting to the ganglion, constitute the first-order neuron
nuclei gracilis and cuneatus terminate soma- ( neuron I ). Fibers of the first order terminate
totopically ( 44, 203). The degree of overlap in upon second -order neurons ( neuron II ) in the
the nucleus cuneatus is moderate, but that in posterior column nuclei (i.e., nuclei gracilis
the nucleus gracilis is more extensive.
The nuclei gracilis and cuneatus, collec-
and cuneatus) of the caudal medulla . The sec -
ond -order fibers originating in the posterior
tively termed the posterior or dorsal column nuclei decussate in the caudal medulla , form
nuclei, give rise to second -order fibers, which the medial lemniscus, ascend , and terminate
sweep ventromedially , as internal arcuate -
upon third order neurons ( neuron III ) in the
fibers , decussate, and form a single compact contralateral thalamus. As part of the thala-
bundle, the medial lemniscus . The medial lem- mocortical projection system , the third -order
niscus ascends through the contralateral half
of the brainstem and its fibers terminate in
fibers terminate somatotopically in the post -
central gyrus (somesthetic area ) of the cere-
the ventral posterolateral nucleus, pars cau - bral hemisphere ( Fig. 11.1 ).
dalis ( VPLC), of the thalamus. These thalamic Ascending fibers in the posterior white
relay neurons emit third -order fibers, which columns and medial lemniscus convey im-
ascend through the posterior limb of the in- pulses concerned primarily with touch- pres-
ternal capsule to terminate in the appropriate sure and kinesthesis. These fibers constitute
sensory areas of the cerebral cortex ( Fig. 11.1 ).
Thus, the posterior column system is a trisyn-
part of a large highly specific sensory path -
way in which single elements are responsive
aptic pathway whereby sensory information to one or the other of these forms of physio-
from the outside world can reach the cerebral logic stimuli but not to both (191 ). Fibers of
cortex . In this highly ordered neuronal chain, this system are highly specific with respect to
the central processes of spinal ganglion cells
that enter the spinal cord and ascend ipsilat-
place and endowed with an exquisite capac -
ity for temporal and spatial discrimination .
These fibers convey tactile impulses for pre- posterior columns (37). These cells, located
cise localization and for two- point discrimi - largely in ventral regions of the posterior col-
nation. Ascending impulses from receptors umn nuclei, appear to project to all spinal lev-
on joint surfaces and in joint capsules, which els but the terminal fields established for the
are excited by movement , convey informa - cervical spinal segments are specific for
tion concerning the position of different parts Rexed 's laminae IV and V, and possibly lam-
of the body. Rapid successive stimuli per- ina I of the posterior horn . These descending
ceived on bone or skin by Pacinian corpuscles pathways are regarded as part of a feedback
result in a sense of vibration . "Vibratory mechanism which may regulate the flow of
sense" is not a specific sensory modality but a sensory information to higher levels of the
temporal modulation of tactile sense (39 ). Im - neuraxis. The posterior column system also
pulses concerned with this form of tempo- contains a significant number of long ascend -
rally modulated tactile sense are considered ing unmyelinated primary afferent fibers
to ascend in both the posterior and lateral fu - (166). This finding suggests that fibers within
niculi. the posterior columns may participate in the
The dorsal column fibers system harbors transmission of noxious stimuli. Other recent
several types of fibers other than the sensory findings in the rat reveal that some neurons
axons described earlier. For example, the pos- in the dorsal column nuclei project to the
terior columns contain group la muscle spin- thalamus indirectly via a relay in the pretectal
dle afferents and group lb Golgi tendon area of the midbrain ( 238). This is consistent
organ afferents. Most of the lower limb group with physiologic data suggesting a role for
I afferents ascending in the fasciculus gracilis the pretectal area in sensorimotor integration.
project to the dorsal nucleus of Clark at L2 Lesions involving the posterior columns
levels and above and do not reach the nu
cleus gracilis ( 203). Muscle spindle afferents
- diminish or abolish discriminating tactile and
kinesthetic sense. Mere contact and pressure
( la ) and Golgi tendons afferents ( lb ) from the appear normal, but tactile localization is
upper extremity enter the spinal cord rostral poor, and two-point discrimination and vi-
to the dorsal nucleus of Clarke. These affer- bratory sense are lost or diminished . There is
ents ascend in the fasciculus cuneatus and loss of appreciation of differences in weight
terminate somatotopically upon portions of and inability to identify objects placed in the
the accessary cuneate nucleus . Cells of the ac- hand by feeling them. These symptoms are
cessory cuneate nucleus resemble those of most acute in the fingers and hand . Position
Clarke nucleus and, like that nucleus, project and movement sense is severely affected , es-
fibers to the cerebellum ( Figs. 11.9 and 12.8). pecially in the distal parts of the extremities.
The descending branches of the dorsal Small passive movements are not recognized
root fibers in the posterior columns project as movements, but as touch or pressure. Even
for variable distances. These fibers terminate in long excursions the direction and extent of
upon parts of the dorsal nucleus of Clarke the movement may not be perceived . Loss of
and cells in medial parts of Rexed's lamina position sense greatly impairs the perfor-
VI . Bundles of descending fibers in cervical mance of voluntary motor function. This sen-
and upper thoracic spinal segments are sory loss causes movements to be clumsy, un -
known as the fasciculus interfascicularis certain and poorly coordinated ( posterior
(comma tract of Schultze) and in the lumbar column ataxia ).
region as the septomarginal fasciculus (oval The use of various tract- tracing methods
area of Flechsig ) ( Figs. 10.11 and 11.25). In the has shed new light on the organization of the
sacral region, the fibers of the septomarginal spinal tracts in experimental animals ( 198). In
fasciculus occupy a small triangular area near comparison , our knowledge of spinal path -
the posteromedian periphery ( triangle of ways in humans is much more limited be-
Phillippe-Gombault) ( Fig . 10.17). Besides the cause these experimental methods cannot be
descending root fibers, the above named fas- applied to the study of human material. What
cicles also contain descending fibers from is known about the arrangement of spinal
cells of the posterior gray horn. tracts in humans is largely based on the ex -
Anterograde and retrograde tract-tracing amination of postmortem material from pa -
studies in animals indicate that cells in the tients with lesions at different levels of the
nuclei gracilis and cuneatus give rise to de- spinal cord . For example, since a fiber sev-
scending axons which pass in the ipsilateral ered from its cell of origin degenerates, injury
Fasciculus Fasciculus
cuneatus gracilis
Posterior
spinocerebellar u. Dorsal
root
tract
X Wl
>
i \
: .
&
Anterior
spinocerebellar Lateral
• B spinothalamic
tract
tract
Figure 11.3. Section through the second cervical segment of a human spinal cord which had been accidentally
crushed previously in the lower cervical region. The antemortem posterior column symptoms were far more extensive
in this patient than in the one illustrated in Figure 11.2. Ascending branches of dorsal root fibers In the fasciculi gracilis
and cuneatus are degenerated and demyelinated bilaterally, except for fibers in lateral parts of the fasciculi cunea-
tus which entered above the level of the lesion (about C6). This lesion also produced degeneration in most of the
fibers of the spinocerebellar and spinothalamic tracts (Weigert ' s myelin stain).
Fasciculus Fasciculus
cuneatus gracilis
Posterior
spinocerebellar
fract
Anterior
spinocerebellar
tract
Anterior Lateral
spinothalamic spinothalamic
tract tract
Figure 11.4. Section through the second cervical segment of a human spinal cord which had been crushed several
weeks previously in the upper lumbar region. The ascending degeneration appears as black granules in fibers of the
fasciculi gracilis, the anterior and posterior spinocerebellar tracts, and in the lateral and anterior spinothalamic tracts
(Marchi stain)
to the fibers of the posterior white columns, Spinothalamic Tracts

or to dorsal root fibers proximal to the spinal
ganglia, will cause degeneration in the poste- The Akers dia * lorm die spinothalamic
rior white columns in specific locations de- ^ '^
racts d cr * roni dlose n
' posterior white
columns in that they arise from cells within
pending on the level of the lesion . Further- , ,
more, the large myelinated fibers of the the sPinal « raY matter and cross w th n the
posterior columns are frequently involved in sP n‘d cord before ascending to the thalamus,
'
The ccds * or S n ol dle spinothalamic tracts
toxin-induced neuronal degeneration, as well ° ''
as in demyelinating or metabolic diseases.
Sections of human spinal cord can [x ,
îave keen identified ( a ) physiologically by
antidromic stimulation of the specific sensory
processed according to various histologic relay nuclei of the thalamus and ( b ) anatomi-
methods that can reveal normal myelin ( e.g., cally by tracing the retrograde transport of
the Weigert method ) as well as myelin that dle en / yme horseradish peroxidase ( HRI ).
is undergoing degeneration ( e.g., the Marchi These data agree that the fibers of the
procedure). A careful analysis of sections sP> nodialamic tracts arise contralaterally in
dl sP I1td cord (Tom cells in laminae 1 and V ,
stained with such methods can yield useful ° '
and to a lesser extent from cells in laminae IV,
information about the location and relative
size of different spinal cord tracts in humans VI, and VII of the posterior and intermediate
( Figs. 11.2-11.4). Evidence of degeneration horns ( 4, 215, 216 ). After large HRP injection
in the posterior columns also can be detected *n du‘ mon ey thalamus, the largest number
^
in Nissl stained sections because relatively of spinothalamic neurons is found in con -
dense gliosis occurs in areas of degenerated tralateral lower lumbar segments ( 9 ). For
fibers ( Fig. 11.5). It must be realized, how - each rcSion ot the sPinal cord ' ipsiIateral la -
ever, that the histologic methods that can
be applied to the study of human material
,
beled spinothalamic neurons constitute about
d < ' ot du‘ totld nurr> ber ot retrogradely la -
are much less powerful than the various ex - keled neurons. Neurons that form the
perimental techniques that are currently spinothalamic tracts constitute a heteroge-
used in animal studies. For instance, the neous ced population that varies in size,
Marchi method ( 126 ) does not provide infor - shape, and number among the different seg-
mation concerning the termination of degen - ments and spinal laminae. Spinothalamic
erated fibers and often produces deceiving fibers cross in the anterior white commissure
artifacts (see chapter 5 ). and collect contralaterally into three more or
less distinct bundles termed anterior spinotha -
lamic , lateral spinothalamic , and spinoceri' i-
cothalamic tracts.
ANTERIOR SPINOTHALAMIC TRACT
. y
m .
Jplx
Fibers forming the anterior spinothalamic
tract ascend in the anterior and anterolateral
mm. funiculi and are somatotopically arranged, so

that those arising from sacral and lumbar seg-
ments are most lateral and those from tho-
racic and cervical segments are most medial
’ ‘ ( Figs. 11.4 and 11.6). A small number of un -
crossed fibers also occur, but these fibers are
not illustrated in Figure 11.6. The anterior
. x' spinothalamic tract is reduced in size at
medullary levels because some fibers, or col -
. laterals, project to the nuclei of the reticular
formation. The spinothalamic component of
Figure 11.5. Section through the fifth cervical spinal this tract becomes closely associated with the
segment In a rhesus monkey following multiple cervical medial lemniscus in the pons and midbrain ,
dorsal rhizotomies on the right and section of the 05 dor - At midbrain levels, the anterior spinothalam -
sal root on the left . Intense gliosis sharply outlines the fas-
ic tract consists of two components ( 98).
ciculus cuneatus on the right, while more restricted glio-
sis on the left occupies the area of degenerated C5 Fibers of the larger lateral component termi -
dorsal root fibers (Nissl stain) . nate in caudal parts of the ventral posterolat-
cortex Arm Hand (postcentral gyrus )
Corpus callosum
III Ventricle Axons of neurons
Thalamus in posterior limb of
internal capsule
Internal capsule -
Vent posterolateral
,
nucleus ( VPL)
Superior colliculus
MIDBRAIN Substantia nigra
Spinotectal tract
PONS v/;
- Anterior spinothalamic tract
Trigeminal nerve
*Pp
| o
O
and medial lemniscus
MEDULLA
Nucleus gracilis
:
MEDULLA
Axon of neuron
decussating to ascend Pyramid
in medial lemniscus
C8
Collaterals of neuron I- > Axons of ascending fibers

in spinotectal tract
T 12
L 1 po I
Neuron I
(dorsal root ganglion cell) *
'i
L3
o
Tactile receptor
(Meissner's corpuscle) Axons of neuron crossing in
@3 anterior white commissure to
. '
1
ascend in anterior spinothalamic
tract
Axon of anterior horn cell
terminating in motor end plates
.
Figure 11.6. Anterior spinothalamic (red) and the spinotectal ( black ) tracts These tracts arise from cells in multiple
laminae of the spinal gray at all levels. The largest number of spinothalamic fibers appear to arise from cells in lami-
. .
nae I IV and V contralaterally The anterior spinotholamic tract conveys impulses associated with "light touch. " the
sensation produced by stroking glabrous skin with a wisp of cotton The spinotectal tract ascends in close association
with the anterior spinothalamic tract, but terminates in deep layers of the contralateral superior colliculus and In parts
of the periaqueductal gray This tract conveys nociceptive impulses . Letters and numbers indicate segmental spinal
levels
eral, pars caudalis ( VPL, ), thalamic nucleus. spinothalamic system are far more complex
Fibers of the medial component of the tract than classic descriptions suggest . Unilateral
project into the periaqueductal gray and bi - anterolateral cordotomy produces (a ) ipsilat-
laterally in the intralaminar thalamic nuclei. eral degeneration in the VPL, nucleus, ( b ) bi -
Axons reaching the VPL nucleus of the thala - lateral degeneration in certain intralaminar
mus terminate somatotopically upon neurons nuclei, and (c ) bilateral degeneration in a pos-
which in turn project to the postcentral gyrus terior thalamic nucleus. These anatomical ob-
(somesthetic area ) of the cerebral cortex . servations, confirmed by electrophysiologic
Fibers of the anterior spinothalamic tract studies ( 167, 173, 232 ), indicate that the body
convey impulses associated with what is surface is represented in an orderly but dis-
called "light touch," a sensation that is pro- torted somatotopic fashion in the VPL, nu -
voked by stroking skin, devoid of hair cleus and reveal that cells of the VPL, nucleus
( glabrous skin ), with a feather or wisp of cot - are related to small contralateral receptive
ton . This sensation supplements deep touch fields. In the posterior thalamic nucleus, cells
( pressure) and discriminative tactile sense are activated from large receptive fields, both
conveyed in the posterior white columns. Be- ipsilaterally and contralaterally.
cause tactile sensation is transmitted centrally Recent anatomic investigations in various
by both the posterior white columns and the species, including nonhuman primates, have
anterior spinothalamic tracts, clinically this led to a more unified view of the spinotha-
sensory modality is of limited value in local - lamic afferents than the one presented earlier.
izing injuries of the spinal cord . In fact, injury These studies suggest that the spinothalamic
to the anterior spinothalamic tract produces tracts in the anterolateral quadrant of the
little, if any, disturbance in tactile sensibility. spinal cord contain primarily axons of lamina
V cells, which respond to both innocuous and
LATERAL SPINOTHALAMIC TRACT noxious stimuli. Axons of lamina I cells,
which respond to noxious mechanical or
This tract is closely related to the anterior thermal stimuli, course more dorsally in the
spinothalamic tract but is of greater clinical dorsolateral quadrant . The spinothalamic
importance because it transmits impulses pathway in nonhuman primates is said to en-
concerned with pain and thermal sense ( Fig. compass a continuous fiber bundle that ex-
11.7). Its component fibers are more concen- tends dorsally to include a region of the lat-
trated than those in the anterior spinothala - eral funiculus where fibers project primarily
mic tract, and it contains more fibers that pro- to posterior thalamic nuclei (187). Whether or
ject directly to the thalamus (97). Posterior not the same organization prevails in humans
horn neurons, principally those in laminae I remains to be determined .
and V, give rise to most of these fibers that Unilateral section of the lateral spinotha-
first cross in the anterior white commissure lamic tract produces a complete loss of pain
before ascending in the contralateral lateral and thermal sense ( analgesia and ther-
funiculus as the lateral spinothalamic tract ( 4, moanesthesia ) on the opposite side of the
215). Fibers of this tract cross obliquely to the body beginning about one or two segments
opposite side, usually within one or two below the level of the lesion ( Fig. 11.27 ). The
spinal segments. They lie medial to fibers of anesthesia involves the superficial and deep
the anterior spinocerebellar tract ( Figs. 11.4 portions of the body wall, but not the viscera,
and 11.25). They are somatotopically orga - which appear to be represented bilaterally.
nized in a manner similar to those of the ante- The anogenital region is not markedly af -
rior spinothalamic tract . There is an incom- fected with unilateral lesions. After a variable
plete segregation of fibers concerned with period there is often some return of pain and
pain and thermal sense; fibers related to ther- thermal sensibility, due perhaps to the pres-
mal sense tend to be posterior to those related ence of uncrossed spinothalamic fibers. Such
to pain. In the brainstem , this tract sends pain impulses also may ascend by shorter re-
branches into the reticular formation while lays along spinospinal and spinoreticular
the main fibers terminate in the VPL, nucleus pathways.
of the thalamus ( Fig . 11.7 ). In certain instances, bilateral surgical sec-
Section of the spinothalamic tract (antero- tion of the lateral spinothalamic tracts (cor-
lateral cordotomy ) in monkeys ( 29, 30, 135) dotomy ) is performed at slightly different
indicates that the thalamic projections of the levels on selected patients to relieve pain and

cortex Arm Hand (postcentral gyrus)
Corpus callosum Axons of neurons

Thalamus in posterior limb of
internal capsule
Internal capsule -
Vent, posterolateral
nucleus ( VPL)
MIDBRAIN
Substantia nigra
Crus cerebri
PONS
Medial lemniscus
Reticular formation
MEDULLA
C8 Lateral spinothalamic
tract
Neuron I (o
(dorsal root ganglion cell) Sacral fibers
Temperature Lumbar fibers
Pain —^ Thoracic fibers
*
Cervical fibers
Pam receptors ( free nerve
endings in skin of o Dorsolateral fasciculus
dermatomes T4 ( zone of Lissauer)
C 8 and T 4
o
Cells of substantia gelatinosa
Cold receptor in L3 and nuc. centrodorsalis
skin of dermatome
L3
Heat receptor in o
skin dermatome S2
S2 CiSS5 -- Axons crossing to opposite
side in anterior white commissure
Figure 11.7. Lateral spinothalamic tract (red) The cells of origin of the lateral spinothalamic tract appear to be
.
largely in laminae I IV, and V of Rexed Fibers of this tract usually cross to the opposite side within one segment In the
anterior white commissure. The lateral spinothalamic tract has a more complex termination In the thalamus than indi-
cated here, conveys Impulses associated with pain and thermal sense, and has a somatotoplc lamination, Letters
and numbers indicate segmental spinal levels.
produce a complete and more enduring movement, two- point discrimination, and vi -
sensory loss. The spinothalamic and bration are lost on the same side as the lesion
trigeminothalamic pathways both may be de- ( Fig . 11.27).
stroyed by one laterally placed lesion in the
medulla or midbrain, where these two tracts SPINOCERVICOTHALAMIC TRACT
occupy a superficial position ( Figs. 11.7 and
13.30 ). Interruption of both tracts at medulla Experimental studies in the cat, which ap-
levels results in a loss of pain and thermal pears to lack an uninterrupted spinothalamic
sense over the face contralaterally and over tract terminating in the VPL, nucleus of the
the body ipsilaterally, whereas mesen- thalamus ( 4, 25, 38 ), suggest that the spi -
cephalic tractotomy produces a thermoanal - nocervicothalamic tract may serve as its ho-
gesic loss over the face and body all on the mologue ( 58, 59, 139, 140, 210, 211 ). Cells in
side opposite to the lesion. lamina IV of the posterior horn at all spinal
It is evident from the foregoing that the levels give rise to uncrossed fibers that as-
sensory impulses brought in by the dorsal cend in the dorsolateral funiculus ( 58, 210 ).
roots are organized in the spinal cord into These cells in the posterior horn are mono-
two main systems: discriminative (epicritic) synaptically activated by dorsal root afferents
and affective ( vital , protopathic). The former that respond chiefly to low threshold cuta -
are related to the long fibers of the posterior neous stimuli ( 108, 123). Spinocervical cells
white columns and the latter to the shorter give off several collaterals before their axons
root fibers and the anterolateral white col- enter the ipsilateral dorsolateral funiculus;
umns. Discriminative sensibility carried by other collaterals, which course back to the
the longest fibers remains uncrossed in the posterior horn , are emitted as the fibers as-
spinal cord . Pain and thermal impulses, ini- cend to the lateral cervical nucleus. The spi-
tially conveyed bv the short fibers in the zone nocervical fibers terminate in a profuse
of Lissauer, may synapse one or more times plexus of fine collaterals in the lateral cervical
before reaching cells that give rise to fibers nucleus ( Figs. 10.26 and 11.8). The lateral cer -
crossing in the anterior white commissure vical nucleus is a longitudinal cell column , lat -
that form the lateral spinothalamic tract . eral to the posterior horn, in the lateral fu -
This distribution of afferent impulses ac- niculus of the upper three cervical segments
counts for the curious sensory dissociation of the cat's spinal cord ( 189). This nucleus is
occurring in the hemisection of the spinal present in a variety of species, including hu -
cord ( Brown-Sequard syndrome), where mans, although it is most prominent in carni -
there is loss of pain and thermal sense on the vores ( 217). Cells of the lateral cervical nu -
opposite half of the body below the level of cleus are somatotopically organized ( 60).
the lesion , while the sense of position and They give rise to fibers that cross in the ante-
Lateral cervical
wm m nucleus
y.
m
I
w
mm.
Figure 11.8. Section through the first cervical segment of the cat spinal cord demonstrating the lateral cervical nu
cleus Cell of the lateral cervical nucleus receive fibers of the spinocervical tract, considered the feline equivalent of
the spinothalamic tract . Fibers arising from cells in the lateral cervical nucleus cross In the upper cervical spinal seg-
ments and ascend to the thalamus in association with the medial lemniscus (cresyl violet stain)
rior white commissure at Cl and C2 levels the caudal half of the colliculus (see Chapter
and ascend in association with the medial 14). The functional significance of the spino-
lemniscus to the thalamus, where they end in tectal tract is unknown, but evidence sug -
a restricted part of the VPL nucleus ( 24, 59, gests that it may be part of a multisynaptic
108, 137). Retrograde transport studies with pathway transmitting nociceptive impulses
HRP in the cat indicate that virtually all cells (135). The intermediate and deep layers of the
in the lateral cervical nucleus project to the superior colliculus receive multiple sensory
contralateral thalamus and terminate somato- inputs while projections to the superficial lay-
topically (59). In contrast, similar studies in ers are all related to the visual system.
monkeys indicate that only one-third of the
cells in the lateral cervical nucleus project to Cerebellar Afferents
the thalamus, the rest of the neurons sending
their axons to the midbrain ( 205). There also POSTERIOR SPINOCEREBELLAR TRACT
are indications that the dorsal column-medial
This uncrossed tract, which ascends along
lemniscal pathway and the spinocervicotha-
the posterolateral periphery of the spinal
lamic projection may be functionally linked ,
cord ( Figs. 11.3, 11.4, 11.9, and 11.25), arises
because some spinocervical collaterals end in
from the large cells of the dorsal nucleus of
the dorsal column nuclei and some cells of
Clarke. Posterior root afferent fibers reach the
the dorsal column nuclei project to the lateral
nucleus directly and after ascending and de-
cervical nucleus (58).
scending in the posterior columns (44, 77,
Impulses conveyed via the spinocervi- 114, 203) ( Fig. 10.25). The cells of the dorsal
cothalamic tract reach the cortex earlier than
nucleus of Clarke give rise to large fibers that
those transmitted via the dorsal column-
ascend in the posterolateral part of the lateral
medial lemniscal pathway (148). Its integrity
is essential for the earliest portion of the corti-
funiculus (i.e., lateral to the corticospinal
tract ). In the medulla, fibers of this tract be-
cal evoked potential in somatic sensory areas
come incorporated in the inferior cerebellar
I and II (7), and , according to Oscarsson and
Rosen (163), this pathway also activates the peduncle ( Figs. 2.26 and 2.32), enter the cere-
bellum, and terminate in both rostral and
motor cortex. Single units of the spinocervi-
caudal portions of the vermis (75). In the an-
cothalamic tract show spontaneous activity
terior vermis, fibers end in Larsell's lobules 1
and respond to hair movement and thermal
to IV ( Fig. 15.1 ); posteriorly, fibers terminate
stimuli with a uniformly low threshold . They
are activated by tactile stimuli from relatively mainly in parts of the pyramis and parame-
dian lobule. These cerebellar cortical areas
restricted receptive fields, but additional acti-
vation results from pressure and pinching the represent mainly the hindlimb. Thus, the pos-
terior spinocerebellar tract, which conveys
skin. The spinocervical tract, containing
2000-3(XX) fibers, 10-14 p.m in diameter, is the impulses from the periphery to the cerebel-
lum, is an uncrossed disynaptic pathway
most rapidly conducting pathway in the fe-
line spinal cord . Anatomic studies suggest
formed by the axons of spinal ganglion cells
( neurons I ) and those of the dorsal nucleus of
that the spinocervical tract may convey im-
Clarke ( neurons II ).
pulses related to painful stimuli and also
plays a role in integration of motor functions. Impulses relayed to the cerebellum via the
posterior spinocerebellar tract arise from
Spinotectal Tract muscle spindles, Golgi tendons organs, and
pressure receptors. Neurons of the dorsal nu-
Cells of origin of the spinotectal tract lie in cleus of Clarke receive monosynaptic excita-
laminae I and V of the posterior horn. Fibers tion mainly via group la, lb, and group II af -
of this crossed tract ascend in the anterolat- ferents (159). The synaptic linkage between
eral part of the spinal cord ( Figs. 11.6 and group I afferents and the dorsal nucleus of
11.25) in close association with the spinotha- Clarke allows transmission of impulses at
lamic fibers (8, 174). At midbrain levels fibers high frequency. Fibers of the posterior spi-
of the spinotectal tract project medially into nocerebellar tract have conduction velocities
the intermediate and deep layers of the supe- ranging from 30 to 110 m / sec (116, 159). Exte-
rior colliculus and lateral regions of the peri- roceptive impulses, also transmitted via the
aqueductal gray. In the contralateral superior posterior spinocerebellar tract, are related to
colliculus, the crossed spinal afferents termi- touch and pressure receptors in skin and
nate somatotopically in an orderly fashion in slowly adapting pressure receptors. The pos-
Cerebellorubral fibers
Dentatothalamic fibers
Dentatoreticular fibers
Decussation of superior
Anterior spinocerebellar tract
on surface of superior cerebellar
—x cerebellar peduncle
peduncle
UPPER PONS Medial lemniscus
Vermis on cerebellum
Post spinocerebellar fibers
,
Dentate nucleus in inf . cerebellar peduncle

Sup. cerebellar peduncle
Middle cerebellar
peduncle
PONS
Cuneocerebellar tract
Accessory cuneate
nucleus
MEDULLA
Ant spinocerebellar —^
tract (axon of neuron II)
Neuromuscular spindle
C4 ( trapezius M )
Post , spinocerebellar tract

(axons of neuron II)
»
Neuromuscular spindle
( ext . dig. communis M. )
C8
Nucleus dorsalis -
(of Clarke)
Cell column neuron II
L3 Golgi tendon organ

(quadriceps femoris M )
Dorsal root ganglion cells
(neuron I)
S2 Golgi tendon organ
W ( Hamstring MM. )
Figure 11.9. Anterior ( red) and posterior ( blue) spinocerebellar tracts and the cuneocerebellar tract ( black ) The
posterior spinocerebellar tract arises from cells of the dorsal nucleus of Clarke and is uncrossed It conveys Impulses
arising from muscle spindles and Golgi tendon organs. Fibers of the anterior spinocerebellar tract are crossed and
.
arise from cells in parts of laminae V, VI and VII, Fibers of this tract are activated by impulses from Golgi tendon or -
gans The cuneocerebellar tract, arising from cells of the accessory cuneate nucleus in the medulla, is considered the
upper limb equivalent of the posterior spinocerebellar tract . This tract is uncrossed An uncrossed rostral spinocerebel-
lar tract (not shown) is considered the upper limb equivalent of the anterior spinocerebellar tract in the cat . Letters
and numbers indicate spinal level.
terior spinocerebellar tract is somatotopically bellar vermis in lobules I to IV ( 76, 165, 236).
organized at spinal levels and in its cerebellar Experimental studies show that the majority
terminations (see Chapter 15). Recent double of fibers of this tract in the cat terminate con -
retrograde labeling studies in the rat have re- tralaterallv, about 10% end ipsilaterally and
vealed that spinocerebellar projections ar- about 15%, after branching, end both ipsilat -
borizing in the anterior and posterior lobes of erally and contralaterally. The axon terminals
the cerebellum arise largely from the same of the anterior spinothalamic tract in the ante-
neurons in the spinal cord ( 21 ). This high de- rior lobe of the cerebellum are concentrated
gree of axonal branching suggests that the in very characteristic longitudinal zones par -
rostral and posterior regions of the cerebel - allel to the midsagittal plane ( 236).
lum receive common information from spi- Fibers of the anterior spinocerebellar tract
nocerebellar fibers. None of the impulses con - are less numerous than those of the posterior
veyed by this tract reach conscious levels. Im- spinocerebellar tract , are uniformly large
pulses transmitted bv this tract are utilized in (11-20 (jLin ), have conduction velocities of
the fine coordination of posture and move- 70-120 m / sec, and are virtually all crossed .
ment of individual limb muscles. Like the posterior spinocerebellar tract , it is
concerned with the transmission of impulses
ANTERIOR SPINOCEREBELLAR TRACT mainly from the lower extremity. Cells that
give rise to the anterior spinocerebellar tract
This tract ascends along the lateral periph -
receive monosynaptic excitation from group
ery of the spinal cord anterior to the posterior lb afferents from Golgi tendon organs whose
spinocerebellar tract, and posterior to the site receptive fields often include one synergic
of emergence of ventral root fibers ( Figs. 11.3,
muscle group at each joint of the lower limb
11.4, and 11.9 ). The tract makes its first ap- (159). Fibers of this system convey impulses
pearance in lower lumbar levels of the cord, concerned with coordinated movement and
but its cells of origin do not constitute a dis-
posture of the entire lower limb.
crete entity such as the dorsal nucleus of
Clinically, it is virtually impossible to de-
Clarke. Fibers of the anterior spinocerebellar termine the effects of injury to the spinocere-
tract were considered by Cooper and Sher- bellar tracts, because other spinal tracts usu -
rington ( 50) to arise in lumbar spinal seg-
ally are involved. No loss of tactile or
ments from cells in the periphery of the ante- kinesthetic sense results from such lesions,
rior horn , known as "spinal border cells" or
since the information projected to the cerebel-
the nucleus ( vrieornualis anterior. Anatomic in- lum does not enter the conscious sphere.
vestigations in various species reveal that
fibers of the anterior spinocerebellar tract CUNEOCEREBELLAR TRACT
arise from cells in part of the posterior (dor-
sal ) and intermediate horns ( laminae V, VI , The dorsal nucleus of Clarke is not present
and VII ). Cells giving rise to this tract extend above C8 and dorsal root fibers above this
from coccygeal and sacral spinal segments as level ascend ipsilaterally. These fibers, which
far rostrally as the LI segment ( 76, 78, 87, 129, convey impulses from muscle afferents
236 ). Morphologically, these neurons are al- ( group la ) and Golgi tendon organs ( group
most impossible to distinguish from motor lb ), terminate somatotopically upon cells of
neurons in Nissl preparations of normal the accessory cuneate nucleus , a group of large
spinal cord . cells in the dorsolateral part of the medulla
This pathway to the cerebellum is com - with cytologic features similar to those of the
posed of two neurons: (a ) neuron I in the dorsal nucleus of Clarke ( Figs. 11.9 and 12.8).
spinal ganglia , and ( b ) neuron II in the scat- The accessory cuneate nucleus in the monkey
tered cell groups at the base of the anterior receives afferents via the dorsal roots from T7
and posterior horns in lumbar, sacral, and to Cl ( 203) which terminate in an overlap-
coccygeal spinal segments. Fibers of neuron II ping systematic fashion . Cells of the acces -
cross in the spinal cord and ascend peripheral sory cuneate nucleus give rise to the cuneo-
to the fibers of the lateral spinothalamic tract. cerebellar tract, the upper limb equivalent of
At upper pontine levels, the tract enters the the posterior spinocerebellar tract . Fibers of
cerebellum by coursing along the dorsal sur- this tract known as posterior external arcuate
face of the superior cerebellar peduncle ( Fig. fibers, enter the cerebellum as a component of
11.9 ). The majority of the fibers of this tract the inferior cerebellar peduncle, and termi-
terminate contralaterally in the anterior cere- nate ipsilaterally in lobule V of the cerebellar
cortex. These cerebellar afferent fibers are dis- and flexor reflex afferents, both with wide re-
tributed to the forelimb area of the intermedi - ceptive fields.
ate zone in the anterior lobe and to forelimb The spino-olivary pathways appear to consti -
areas of the pyramis and paramedian lobule tute another component of the spinocerebel -
( Fig. 15.1 ). As for the anterior spinocerebellar lar circuitry ( 36 ). The two best defined spino-
tract , there is a high degree of axonal collater- olivary pathways have been designated as
alization of the cuneocerebellar fibers to both the posterior and anterior spino-olivary tracts
the anterior and posterior cerebellar regions (161, 162, 164 ). Fibers of the posterior spino-
( 22 ). The cuneocerebellar tract is considered olivary tract ascend in the posterior white
to be the upper limb equivalent of the poste- columns to the nuclei gracilis and cuneatus.
rior spinocerebellar tract. The posterior column nuclei relay impulses
to parts of the accessory olivary nuclei. The
OTHER SPINOCEREBELLAR TRACTS multiple anterior spino-olivary tracts ascend
contralaterally in the anterior funiculus and
In carnivores, another spinocerebellar
terminate upon portions of the dorsal and
pathway, the rostral spinocerebellar tract , has medial accessory olivary nuclei . Fibers con -
been described as the forelimb equivalent of
tributing to the spino-olivary tracts arise from
the anterior spinocerebellar tract (159, 160,
all levels of the spinal cord , are somatotopi-
162, 165). The cells of origin are rostral to the
callv organized and are activated by cuta -
column of Clarke in the cervical spinal cord neous afferents and group lb afferents from
and they give rise to an uncrossed tract that
Golgi tendon organs. In the cat, the cells of
ascends in the anterior part of the lateral fu - origin of anterior spino-olivary tracts lie in
niculus and enters the cerebellum via both in -
laminae IV and V and in medial regions of
ferior and superior cerebellar peduncles. This
laminae VII and VIII at lower lumbar levels
tract appears to arise principally from the (10). The accessory olivary nuclei which re-
large neurons of the centrobasal nucleus lo- ceive the spino-olivary systems, give rise to
cated in lamina VI of the cervical enlarge- crossed olivocerebellar fibers which project
ment ( 131, 169, 221 ). This tract resembles the
mainly to the anterior lobe of the cerebellum .
anterior spinocerebellar tract , except that it is
Brodal ( 34 ) has referred to these spino-
largely uncrossed . Fibers of the rostral spi- olivary-cerebellar linkages as the indirect
nocerebellar tract terminate more rostrally .
spinocerebellar pathways
than those of the posterior and anterior spi-
nocerebellar tracts. They arborize principally
in lobules IV and V of the anterior lobe and in Spinoreticular and Other
lobules VI and VII and the paramedian lobule Ascending Fibers
( 221 ).
SPINORETICULAR FIBERS
Another , smaller, crossed cervicospinocere-
bellar pathway arises from an interrupted col - A considerable number of spinoreticular
umn of cells in the upper cervical spinal cord fibers, arising from cells in the posterior horn
(Cl to C4 ), known as the central cervical nu - ( 31 , 134, 141 , 193), ascend in the anterolateral
cleus (Fig. 10.26) (61, 132 , 133 ) . This pathway part of the spinal cord and are distributed to
conveys impulses from upper cervical spinal widespread regions of the brainstem reticular
segments to the cerebellum . formation ( Fig . 11.10). In the medulla , these
Thus, in addition to the posterior and ante - fibers are predominantly uncrossed and ter-
rior spinocerebellar tracts, related primarily minate chiefly upon cells of the nucleus retic-
to the hindlimbs and caudal parts of the ularis gigantocellularis and parts of the lat -
body, there are two equivalent tracts, the cu - eral reticular nucleus (186). The lateral
neocerebellar and the rostral spinocerebellar, reticular nucleus of the medulla ( Fig. 12.7) is
that relay sensory information from the fore- known to project to specific portions of the
limbs and rostral parts of the body (159 ). The cerebellum, indicating that some fibers in this
posterior spinocerebellar and cuneocerebellar pathway are concerned with the transmission
tracts are similar and convey information of exteroceptive impulses to the cerebellum.
from muscle spindles, tendon organs and Large cells of the nucleus reticularis giganto-
touch and pressure receptors in the skin . The cellularis project to spinal levels as well as to
anterior spinocerebellar and rostral spi - more rostral regions of the brainstem . Spi -
nocerebellar tracts are similar in that they noreticular fibers passing to pontine levels
convey impulses from tendon organ afferents are distributed bilaterally and are less numer-
Superior colliculus Ascending reticular projections

to intralaminar thalamic nuclei
and hypothalamus
Red nucleus
MIDBRAIN
Interior colliculus Ascending reticular fiber system
Tegmentum of midbrain
Medial lemniscus
Pontine reticular formation

(nucleus reticularis Collateral endings in
pontis oralis) reticular formation
Ascending collateral fibers

Trigeminal nerve
PONS
Pontine reticular formation
(nucleus reticularis
pontis caudalis) — - Collateral endings in
reticular formation
- Facial ( VII) nerve
- Abducens ( VI) nerve
Medullary reticular formation
(nucleus reticularis
gigantocellularis) - Ascending collateral fibers
Descending nucleus and
tract of trigeminal nerve
MEDULLA Lateral reticular nucleus
Hypoglossal ( XII) nerve
Pontine reticulospinal fibers
Medullary reticulospinal Ascending spinoreticular

fibers fibers
Figure It . 10. Ascending and descending reticuldr fibers systems Ascending spinoreticular projections and collater -
als are shown on the right ( blue) In this system, collaterals are given otf at various brainstem levels and the pathway is
augmented by rostrally projecting reticular fibers Pontine reticulospinal fibers (red) are uncrossed and originate
largely from the nucleus reticularis pontis caudalis. Medullary reticulospinal fibers ( black ), predominantly uncrossed,
arise from the nucleus reticularis gigantocellularis. Descending fibers from these sources are not topographically orga-
nized or sharply segregated in the spinal cord.
1 1 Spinal Cord: Fiber Tracts 383
ous than those terminating in the medulla . lion fibers of which some 700,000 are myeli -
Most of these fibers end in the nucleus reticu - nated (109-111 ). Nearly 90% of these fibers
laris pontis caudalis (32). A smaller number
of spinoreticular fibers have been found in
—
are between 1 1 gm in diameter; remaining
fibers range from 5-22 pm in diameter, but
the reticular formation in the region of transi- only about 3.5% of these are above 20 pm .
tion from pons to mesencephalon (155). Func- Fibers of the corticospinal system arise from
tionally, spinoreticular fibers represent a cells in the deeper part of lamina V in the pre -
component of a polysynaptic system , which central gyrus (area 4 ), the premotor area (area
plays a significant role in behavioral aware- 6 ), the postcentral gyrus (areas I , 2, 3a , 3b )
ness, modification of motor and sensory ac- and adjacent parietal cortex (area 5) (52, 92 ).
tivities, and in the modulation of electrocorti- The corticospinal tract is a complex fiber sys-
cal activity. tem arising from multiple cortical areas, and
only a small part of it originates from the
OTHER ASCENDING FIBER SYSTEMS giant pyramidal cells of Betz in the precentral
In addition to the ascending fiber systems
gyrus (area 4 of Brodmann ) ( Fig. 20.10).
These cells have been estimated to number
mentioned in preceding sections, several
between 34,000 and 40,000 in one hemi -
other ascending pathways have been de-
sphere. They are a major source of large
scribed . While the existence of these anatomic
fibers ( 10-20 pm ) in the corticospinal tract
pathways seems certain , relatively little is (109, 112 ). The more numerous finer fibers
known of their functional significance.
come largely from cortical regions other than
Among those are the spinovestibular fibers , the primary motor cortex. The premotor
which project largely upon the dorsal part of
areas collectively comprise more than 60 % of
the lateral vestibular nucleus and to parts of
the cerebral cortex of the frontal lobe that
the inferior vestibular nucleus that do not re-
ceive primary fibers. These fibers ascend ipsi - projects to the spinal cord in nonhuman pri -
mates (64 ). Like the primary motor cortex,
laterally in the spinal cord from levels as far each of the premotor areas contains local re-
caudally as lumbar segments (180). Many
fibers of this tract are partially intermingled
gions that have a high density of corti -
cospinal neurons. These findings indicate that
with those of the posterior spinocerebellar
a substantial component of the corticospinal
tract. Spinopontine fibers have been described
system originates from the premotor areas in
as terminating upon pontine nuclei. It has
the frontal lobe. Through their direct access
been suggested that these fibers may transmit
to the spinal cord , each of these premotor
exteroceptive impulses to the cerebellum
( 226).
areas has the potential to influence the gener -
ation and control of movement indepen -
dently of the primary motor cortex. These
DESCENDING SPINAL TRACTS findings raise questions about the utility of
The descending spinal tracts are con - viewing the primary motor cortex as the
"upper motor neuron" for the central control
cerned with somatic and visceral motor func-
tion , the modification of muscle tone, seg- of movement (64 ).
mental reflexes, and the modulation of Cells of origin of the corticospinal system
central transmission of sensory impulses. The are arranged in strips or clusters that vary in
largest and most important tracts arise from size in different cortical areas ( Fig. 11.11 ). The
the cerebral cortex; all other descending axons of these cells converge in the corona ra -
spinal tracts arise from localized cell groups diata , enter the internal capsule, and descend
in the three lowest segments of the brainstem. to form the crus cerebri at midbrain levels
( Figs. 11.11 and 11.12 ). As this large tract de-
Corticospinal System scends in the ventral part of the infratentorial
brainstem , its fibers pass close to the emerg-
These tracts consist of fibers that (a ) arise ing root fibers of cranial nerves III , VI , and
from cells within the cerebral cortex, ( b) pass XII . In the medulla , the fibers form the mas-
through the medullary pyramid , and ( c) de- sive pyramids. At the junction of the medulla
scend into the spinal cord . They constitute and spinal cord , the corticospinal tract under -
the largest and most important descending goes an incomplete decussation and divides
fiber system of the human neuraxis (145). In into three separate tracts: ( a ) the large lateral
humans, each tract is composed of over 1 mil - corticospinal tract (crossed ), ( b ) the small an -
i
Internal capsule ,
l
posterior limb
\V
'
L\
Internal capsule,
anterior limb
Pyramid
Anterior corticospinal-
tract
Lateral corticospinal
tract
Figure 11.11 . Lateral and anterior corticospinal tracts (reef) showing their regions of origin and course These tracts
arise from cells of various sizes in the deep parts of lamina V.
terior corticospinal tract ( uncrossed ), and (c) uted to part of laminae IV, V, VI, and VII. In
the relatively minute uncrossed anterolateral monkeys, as well as in rats, a number of
corticospinal tract ( Fig. 11.12 ). Between 75% fibers synapse directly with anterior horn
and 90% of the fibers in the corticospinal tract cells or their processes in lamina IX (12, 113).
decussate at caudal medullary levels and The anterior corticospinal tract or direct cor-
enter the posterior part of the lateral funicu- ticospinal tract ( bundle of Tiirk ), formed from
lus where they form the lateral corticospinal a smaller portion of pyramidal fibers, de-
tract ( Figs. 11.12-11.15). Fibers of this tract lie scends uncrossed into the spinal cord , and
medial to the posterior spinothalamic tract occupies an oval sector adjacent to the ante-
and lateral to the fasciculus proprius ( Figs. rior median fissure ( Figs. 11.11-11.15). This
11.15 and 11.16). tract is distinguishable mainly in cervical seg-
The lateral corticospinal tract descends the ments. It is particularly well -developed in
length of the spinal cord , gives off fibers to humans and apes, but shows considerable
the spinal gray matter at all levels, and pro- variation because the proportion of decussat -
gressively diminishes in size at more caudal ing pyramidal fibers is not constant (220).
levels. In lower lumbar and sacral spinal seg- Most fibers of this tract cross at upper cer -
ments, where the posterior spinocerebellar vical spinal levels in the anterior white
tract is absent, fibers of the lateral corti - commissure and terminate bilaterally upon
cospinal tract reach the posterior (dorsal) sur- neurons in lamina VII . It appears chiefly con -
face of the spinal cord . Fibers of the crossed cerned with motor neurons that innervate the
corticospinal tract enter the spinal gray mat- muscles of the upper extremities and the
ter in the intermediate zone and are distrib- neck.
Corticospinal tract the posterior horn and the intermediate gray.

Demyelination in the lateral corticospinal
tract can be detected readily in Weigert -
stained preparations ( Figs. 11.14-11.16), but
this stain is not sensitive enough to reveal the
small number of fibers in the anterolateral
corticospinal tract.
Tract- tracing studies with various tracers,
J7 °
“ !
% including the lectin Phaseolus vulgaris- Leuco-
agglutin ( PHA- L ), indicate that fibers from
^ the precentral motor cortex terminate exten-
sively in lamina VII and in dorsolateral parts
of lamina IX, while fibers from somatosen-
Medullary sory cortex (areas 1, 2, 3, and 5) terminate in
pyramid overlapping zones in parts of the posterior
Lateral
horn ( 12, 53, 113). Although the majority of
corticospinal corticospinal fibers terminate upon internun-
tract cial neurons in lamina VII, a significant num -
2% ber of fibers establish direct synaptic contact
with motor neurons in the anterior horn (102,
90% 113).
8% Corticospinal neurons in the motor cortex
have multiple axonal branches that project to
-
.^ Anterior
corticospinal
different spinal segments (3, 102, 113, 199,
202). Corticospinal neurons with axonal col -
\ tract laterals terminating at different spinal levels
are distributed over wide areas of the motor
cortex . Multiple collateral branches of the cor-
ticospinal axons explain (a ) why a small HRP
injection in the spinal gray matter retro-
- Uncrossed gradely labels widely scattered projection
lateral neurons in the motor cortex, and ( b) why a
corticospinal small lesion in the motor cortex produces cor-
ticospinal degeneration distributed over
many segments. Collaterals of individual cor-
ticospinal axons project to multiple motor
neuronal pools in the cervical and lumbar en-
largements innervating different muscles.
Corticospinal axons exert multiple influences
upon different groups of spinal neurons in
widely separated spinal segments. Interest -
Figure 11.12. Decussation of the human corticospinal ingly, widely divergent corticospinal axons
tract ( red ) Approximately 90% of the corticospinal tract that branch to multiple motor neuronal pools
crosses in the lower medulla to form the lateral corti - have been shown to mediate activity in func-
cospinal tract . Of the fibers which do not decussate in
the medulla, approximately 8% form the anterior corti - tionally related muscle groups ( 102). Such a
cospinal tract which descends in the ventral funiculus divergence in the terminal arborization of
Most of these fibers cross in cervical spinal segments The corticospinal axons may play a crucial role in
small number of fibers in the uncrossed lateral corti - the coordinated control of specific subsets of
cospinal tract remain uncrossed
muscles.
Cortical areas giving rise to the corti -
Fibers of the anterolateral corticospinal tract cospinal tract also provide major inputs to
(15) are uncrossed , of fine caliber, and de- other motor-related structures, such as the
scend in a more ventral position in the lateral striatum , the pontine nuclei, and the red nu -
funiculus than those of the crossed lateral cleus. The question as to whether single corti-
corticospinal tract ( Fig. 11.12). These fibers re- cal neurons project to one or more of these
main uncrossed and terminate in the base of sites is still a matter of controversy. Recent
Lea Trunk Arm Motor cortex

(precentral gyrus)
Ant . limb of Pyramidal cells

internal capsule
Claustrum Fibers to lower extremity
External capsule Fibers to trunk
Putamen Fibers to upper extremity
Cortex of insula
Globus pallidus Post limb of internal capsule
,
Genu of internal capsule Corticospinal tract

MIDBRAIN Temporopontine tract
Crus cerebri
Oculomotor (III) nerve Frontopontine tract
PONS
Longitudinal fibers in
basilar portion of pons
Abducens nerve
OOi
MEDULLA
- •
Pyramid
Hypoglossal nerve
MEDULLA
Pyramidal decussation
Lateral corticospinal tract— Anterior corticospinal tract

(crossed-axons of neuron I) „
-
t (uncrossed-axons of neuron I)
To motor endings
in MM. of forearm
and hand , •>
Internuncial cell-neuron II
To motor endings :
in intercostal and
Jif
•\ Ventral root fiber
segmental back
MM. L4
To motor endings in vt - J Anterior horn cell-neuron III
gluteus medius and A To sacral segments of cord
tibialis anterior MM
c
Figure 11.13. Lateral and anterior corticospinal tracts (red), which are the principal descending motor pathways
concerned with skilled, voluntary motor activity Letters and numbers indicate corresponding segments of the spinal
cord.
Lateral
croticospinal
tract
-,r
Posterior
spinocerebellar
tract -nj
Lateral
Anterior
fasciculus proprius
corticospinal
tract
Figure 11.14 Transverse section through the cervical enlargement of an individual that has sustained a vascular le-
sion of one medullary pyramid. The lateral corticospinal tract on the left and the anterior corticospinal tract on the
side of the lesion are degenerated and demyelinated (Weigert ' s myelin stain).
Fasciculus
gracilis Fasciculus
Posterior cuneatus
spinocerebellar
Lateral
corticospinal tract
Anterior
Ventral corticospinal tract
roots
Figure 11.15. Section through the cervical enlargement of spinal cord of a 7 -8-month human fetus The corticospinal
.
tracts are unmyelinated at this stage and hence are unstained. S. G., substantia gelatinosa Z.L . zone of Lissauer
(Weigert ' s myelin stain)
Lateral
corticospinal
tract
Lateral
fasciculus
Rubrospinal proprius
tract
Vestibulospinal
tract
Figure 11.16 . Section through the fourth lumbar segment of a human spinal cord that had been accidentally
crushed in the lower cervical region some time before death The degenerated long descending tracts are un-
stained Note that the lateral corticospinal tract reaches the lateral periphery of the spinal cord at this level and the
vestibulospinal tract lies on the anterior surface of the cord (Weigert s myelin stain).
tract-tracing studies in the rat reveal that motor activity of the upper limbs compared
there is a considerable overlap of cortical to that of the lower limbs.
neurons projecting to these four sites (3). Fur- Immunocytochemical studies in the rat,
thermore, after injections of different retro- combined with retrograde tracing methods,
grade tracers in the striatum, the pontine nu - suggest that the amino acid glutamate
clei, the red nucleus, and the spinal cord , and / or aspartate may be the excitatory trans-
more than 98% of the cortical projection neu- mitter in corticospinal neurons (73). Approxi-
rons were single-labeled while less than 2% mately 30% of identified corticospinal neu -
were double-labeled . No triple- or quadru - rons in layer V were positive for either
ple-labeled neurons were observed (3). glutamate or aspartate, and 50 % of these neu -
Hence, cortical motor neurons in the rat ap- rons were immunoreactive for both sub-
pear to project individual, rather than collat - stances.
eral , axons to these four motor-related struc- The corticospinal tract is universally re-
tures. This finding indicates that the garded as the descending pathway most con-
corticofugal motor system is highly ordered cerned with voluntary, discrete, skilled
in rodents. movement. Lesions destroying portions of
Some physiologic and anatomic studies this tract at any level result in variable de-
suggest a somatotopical organization in the grees of paresis ( i.e., paralysis). Such lesions
monkey in which fibers from the precentral usually are associated with ( a ) initial loss of
gyrus pass to epi-axial motor neurons, but muscle tone (atonia ), ( b) hyperactive deep
not axial motor neurons ( 20, 104, 105, 115, tendons ( myotatic) reflexes, (c) loss of super-
182, 183). The contralateral projection is to ficial and cremasteric reflexes, and (d ) the ap-
neurons innervating distal (chiefly ) and prox- pearance of the Babinski sign. The sign of
imal limb muscles. The ipsilateral cortical Babinski is an abnormal plantar response,
projection is to motor neurons innervating which consists of extension of the great toe
proximal limb muscles. It has been estimated and fanning of the other toes on stroking the
that about 55% of all pyramidal fibers end in lateral or outer border of the sole of the foot
the cervical cord , 20% in the thoracic, and with a blunt instrument (13). The normal
25c/i in the lumbosacral segments ( 229 ). The plantar response is a brisk flexion of all toes.
greater number of fibers terminating at cervi- The Babinski sign is interpreted to mean in-
cal levels may reflect the fine control that the jury of the corticospinal tract, but it is not an
corticospinal system exerts upon the complex infallible sign, for it can be elicited in the
newborn, the sleeping or intoxicated adult, or the medial longitudinal fasciculus, various
following a generalized seizure. Likewise, the autonomic descending projections, and the
initial atonia seen after a lesion of the corti- monoaminergic pathways. The fastigiospinal
cospinal tract is replaced after a period of projection is also briefly reviewed in this
days, or sometimes weeks, by spasticity. The section .
affected muscles gradually become resistant
to passive movement (see Chapter 20). TECTOSPINAL TRACT
Paralysis of both arm and leg on the same
side is termed hemiplegia . The term para- Fibers of this tract arise from neurons in
plegia denotes paralysis of both legs, while the deeper layers of the superior colliculus,
quadriplegia refers to paralysis of all four sweep anteromedially around the periaque-
extremities. ductal gray , cross in the dorsal tegmental decus -
sation , and descend near the median raphe
Tracts Originating in Brainstem anterior to the medial longitudinal fasciculus
( Figs. 11.17 and 11.18). At medullary levels,
All major descending spinal tracts, other tectospinal fibers become incorporated in the
than the corticospinal tract, arise from the medial longitudinal fasciculus. In the older
brainstem . Three descending spinal tracts literature, tectospinal fibers are referred to as
—
arise from the midbrain the tectospinal,
rubrospinal, and interstitiospinal tracts. The
the predorsal bundle. In the spinal cord , tec -
tospinal fibers, located in the anterior funicu -
other tracts originating in the brainstem are lus near the anterior median fissure, descend
the vestibulospinal and reticulospinal tracts, only through cervical levels ( Fig . 11.25). The
Superior colliculus
Red nucleus
cerebri
Corticospinal
tract
Substontio nigra
Tectospmol 1roct
Rubrospinal tract
csznr
.
Figure 11.17. Rubrospinal ( red) and the tectospinal { blue) tracts. The rubrospinal tract arises somatotopically from
cells of the red nucleus, crosses in the ventral tegmental decussation, and descends to spinol levels where fibers ter -
minate in parts of laminae V, VI, and VII of Rexed Tectospinal fibers arise from cells in deep layers of the superior col-
.
liculus cross in the dorsal tegmental decussation, and descend In association with the medial longitudinal fasciculus.
. .
Fibers of the tectospinal tract are distributed to parts of laminae VIII VI and VII only in cervical spinal segments.
Optic 1 :• 3 4 5
radiation
Lateral
/
j
a i
1 v m Auditory radiation
geniculate /i
body y'" 0 Medial geniculate body
Tectospinal and
Optic tract
Dorsal tegmental
decussation
'
N
m• /
tectobulbar tracts
Red nucleus
Oculomotor (III) nerve n Ventral tegmental decussation

Spinotectal tract
Trochlear (IV) nerve- Lateral lemniscus
inferior colliculus
Medial lemniscus
MIDBRAIN
Medial longitudinal
Decussation of sup. fasciculus
cerebellar peduncle
Tectospinal and — Rubrospinal and

tectobulbar tracts rubroreticular tracts
PONS Middle cerebellar

peduncle
Facial ( VII) nerve
Abducens ( VI) nerve
Tectobulbar fibers Rubroreticular fibers

Vagus ( X ) nerve — Lateral reticular nucleus
MEDULLA
Nucleus ambiguus
Hypoglossal nerve Rubrospinal tract
( axons of neuron I)
C8 Internuncial cell-neuron II
Ventral root nerve fibers

T7 (axons of neuron III)
Figure 11.18. Course of the rubrospinal (red) and tectospinal ( blue) tracts. Crossed rubrobulbar fibers project to parts
of the facial nucleus (not shown) and to the loteral reticular nucleus of the medulla (rubroreticular fibers). Uncrossed
rubrobulbar fibers (not shown) descend in the central segmental tract and termindte in the dorsal lamella of the ipsi-
lateral principal olivary nucleus Tectospinal fibers descend initially ventral to the medial longitudinal fasciculus. At
medullary levels, these fibers become incorporated in the medial longitudinal fasciculus . Fibers of the tectospinal
.
tract descend only to lower cervical spinal segments. Numbered midbrain structures include I the brachium of the
. . . . . .
superior colliculus: 2 the pretectal area 3 commissure of the superior colliculus 4 spinotectal tract: and 5 collicular
fibers from the lateral lemniscus.
majority of the fibers terminate in the upper and ventrolateral parts of the nucleus. Tho-
four cervical spinal segments in laminae VII , racic spinal segments receive fibers that origi-
VIII , and parts of lamina VI (5, 151, 168). nate from intermediate regions of the nu -
None of these fibers terminate directly upon cleus. Rubrospinal fibers descend the length
alpha ( a ) motor neurons. The tectospinal of the spinal cord and terminate in the lateral
tract mediates reflex postural movements in half of lamina V , lamina VI , and dorsal and
response to visual and, perhaps, auditory central parts of lamina VII (80, 151, 152, 200 ).
stimuli . These fibers terminate on somata and den -
The superior colliculus also gives rise to drites of large and small cells within these
fibers distributed bilaterally in the mesen- laminae ( 152). Since rubrospinal fibers do not
cephalic reticular formation and to medial end directly upon anterior horn cells, their fa -
regions of the contralateral pontine and cilitation of gamma ( y ) motor neurons is me-
medullary reticular formation (5). These diated by spinal intemuncial neurons.
fibers are referred to as tectobulbar fibers and In their descent through the brainstem,
their function is discussed in Chapter 14. collateral fibers of the rubrospinal tract are
given off to the cerebellum ( 56 ), the facial nu -
RUBROSPINAL TRACT cleus (54 ), and the lateral reticular nucleus of
the medulla ( 54, 66, 80, 127, 138, 223). The
Fibers of this tract arise from cells of the parvicellular part of the red nucleus also
red nucleus, a well -defined , oval-shaped gives rise to uncrossed rubrobulbar fibers
structure in the central part of the midbrain ( 222) that project to dorsal parts of the princi -
tegmentum ( Figs. 11.17, 11.18, 14.1, and 14.6 ). pal inferior olivary nucleus ( 57, 66, 138, 175,
The red nucleus consists of a rostral parvicel - 223).
lular part and a caudal magnocellular part, The red nucleus receives fibers from the
which vary in size in different animals. In cerebral cortex and the cerebellum . In the cat
monkeys, three distinctive types of neurons and monkey, corticorubral fibers from the
are found in the red nucleus: (a ) large giant "motor" cortex project bilaterally to the par-
neurons with coarse, evenly distributed , vicellular part of the nucleus and ipsilaterally
Nissl granules which characterize the magno- to the magnocellular division ( 79, 106, 190,
cellular part, ( b) medium -sized triangular 218). These projections are somatotopically
neurons with prominent nucleoli and a Nissl organized with respect to origin and termina -
substance that does not form distinct gran- tion . The synaptic linkage of corticorubral
ules, which characterize the parvicellular and rubrospinal fibers together constitute a
part , and (c) small neurons, found in both somatotopically organized , disynaptic, non -
magnocellular and parvicellular parts, which
are achromatic and have scant cytoplasm ( 48,
pvramidal pathway between the motor cor -
tex and particular spinal levels. All parts of
99, 100, 188, 194 ). In the cat , the rubrospinal the red nucleus receive crossed cerebellar ef -
tract arises from cells of all sizes in the caudal ferent fibers via the superior cerebellar pe-
-
three fourths of the nucleus (179). In the duncle. Fibers from the interposed nucleus
monkey , the rubrospinal tract arises largely (equivalent to globose and emboliform nu -
from the magnocellular region which occu - cleus in humans ) relate portions of the cere-
pies the caudal third of the red nucleus (96,
106, 128, 157, 175).
bellar cortex somatotopically with the mag -
nocellular part of the red nucleus (55, 69,
Rubrospinal fibers cross completely in the 128). Stimulation of cells in the red nucleus
ventral tegmental decussation , and descend to (86, 176, 177, 196 ) produces excitatory postsy -
spinal levels, where they lie anterior to, and naptic potentials in contralateral flexor < <
partially intermingled with, fibers of the lat- motor neurons, and inhibitory postsynaptic
eral corticospinal tract ( Figs. 11.17, 11.18, and potentials in extensor a motor neurons. The
11.25). Fibers of the rubrospinal tract are so - most important function of the rubrospinal
matotopically organized , meaning that cells tract concerns control of muscle tone in flexor
in particular parts of the nucleus project se - muscle groups ( 128).
lectively to defined spinal levels (179). Fibers
projecting to cervical spinal segments arise VESTIBULOSPINAL TRACT
from dorsal and dorsomedial parts of the red
nucleus, while fibers projecting to lum - The vestibular nuclei constitute a cytologic
bosacral spinal segments arise from ventral complex in the floor of the fourth ventricle of
both the pons and medulla. The four major

nuclei of this complex ( i .e., lateral, medial, su -
/ Thalamus
perior, and inferior nuclei ) (35) receive affer-
ent fibers from the vestibular nerve and the
cerebellum which are distributed differen-
tially ( Figs. 11.19, 11.21, and 13.18). The
vestibulospinal tract , the principal descend -
ing spinal pathway from this complex, arises
j principally from the lateral vestibular nucleus
(or Deiters' nucleus) (1, 33, 34, 41, 153). The
N
Cerebellar lateral vestibular nucleus consists of a discrete
Vert
peduncles collection of giant cells in the lateral part of
Vestibular the complex near the entry of the vestibular
nerve root nerve root. Practically all cells of the lateral
IMTST 4 vestibular nucleus contribute fibers to the
formation of this tract , which descends
L the length of the spinal cord in the anterior
part of the lateral funiculus ( Figs. 11.19 —
Vestibular nuclei Vestibulospinal 11.21 ) .
tract
The vestibulospinal tract, like the rubro-
spinal tract, is somatotopically organized (35,
Medial longitudinal fasciculus
181 ). Cells in dorsolateral parts of the vestibu -
lar nucleus project to lumbosacral spinal seg-
Figure 11.19. Spinal projections from the vestibular nu- ments and cells in rostoventral regions pro-
clei The vestibulospinal tract ( blue) arises only from cells
of the lateral vestibular nucleus. This tract is uncrossed, ject mainly to cervical spinal segments.
somatotopically organized, and concerned with the fa- Somatotopic features are somewhat blurred
cilitation of extensor muscle tone Vestibular fibers de- by the observation that fibers of the tract
scending In the medial longitudinal fasciculus (red) arise give off collaterals that innervate several
largely from the medial vestibular nucleus and are
.
mainly uncrossed S indicates superior vestibular nu-
spinal segments, particularly in the enlarge-
cleus. L indicates the lateral vestibular nucleus: and I ments. The vestibulospinal tract has a three-
and M Indicate the inferior and medial vestibular nuclei. to four-fold stronger influence on cervical
Figure 11.20. Section through the upper cervical spinal segments in a rhesus monkey demonstrating labeling of
fibers (white area) in the vestibulospinal tract lying along the ventromedial border of the spinal cord Autoradi-
ographic tract -tracing method
Vestibular nuclei IV Ventricle

Medial Abducens ( VI) nucleus
Superior
Lateral
PONS-MEDULLA
Inferior cerebellar
JUNCTION
peduncle
Spinal nucleus of
trigeminal (V) nerve Middle cerebellar
peduncle
Facial ( VII) nerve —
and nucleus Vestibular nerve
Nucleus of superior
olive
Medial lemniscus
Vestibular nuclei
Medial Pyramid
Inferior Inferior cerebellar
peduncle
MEDULLA
Medial lemniscus Inferior olivary nucleus
Pyramid
MEDULLA
Spinal accessory ( XI)

Anterior gray column nerve
Medial longitudinal fasciculus Vestibulospinal tract
( vestibular component ) (axons of neuron I, uncrossed)
C3
Motor end plates in
Anterior horn cell-neuron III trapezius and scalene MM.
Ventral root nerve fiber
T4
Motor end plates in
— intercostal and segmental
back MM .
L3
Motor end plates in
quadriceps femoris M
S2
Motor end plates in
gastrocnemius M.
.
Figure 11.21. Vestibulospinal tract ( blue) and descending vestibular fibers In the medial longitudinal fasciculus ( red)
Fibers of the vestibulospinal tract have a somatotopic origin in the lateral vestibular nucleus, descend the length of
the spinal cord, and terminate predominantly in lamina VIII of Rexed. Descending vestibular fibers in the medial longi-
tudinal fasciculus arise from the medial vestibular nucleus. In the lower brainstem, these fibers are bilateral, but in the
cervical spinal cord they are ipsilateral. Letters and numbers indicate segmental spinal levels.
and lower lumbar segments than on thoracic the spinal cord . It also has been shown that
spinal segments. Fibers of the vestibulospinal electrical stimulation of points in the lateral
tract in cervical segments give off collaterals vestibular nucleus produces increases in ex-
that enter laminae IX and adjacent parts of tensor muscle tone which may be localized to
VII and Vlll ( 153, 201 ). Synaptic contacts are forelimb or hindlimb, depending upon the
made with interneurons and with proximal position of the electrode within the nucleus
dendrites and somata of large motor neurons. (178). These physiologic findings confirm the
Physiologic evidence indicates monosynaptic anatomically described somatotopical origin
excitation of motor neurons in the lum- of fibers in the lateral vestibular nucleus. Fol-
bosacral region and direct connection with y - lowing stimulation of the lateral vestibular
motor neurons. nucleus in the cat, excitatory postsynaptic po-
Vestibular influences, and certain cerebel- tentials can be recorded intracellularly from
lar influences, upon spinal cord activity are extensor motor neurons, while the effects on
mediated by the vestibulospinal tract . Pri- flexor motor neurons are insignificant (197,
mary vestibular fibers terminate differentially 233). Excitatory vestibulospinal influences
and selectively upon cells in all four major di- upon extensor muscles can be observed at
visions of the vestibular nuclear complex rest and during locomotion (158). Stimulation
( 208, 225). Projections to the lateral vestibular of the lateral vestibular nucleus during loco-
nucleus are restricted to its rostroventral part motion enhances the activity of extensor
and represent predominantly input from the muscles during the stance phase of the step.
utricle. Electron microscopic findings indicate Modulation of vestibulospinal neurons with
that primary vestibular fibers end upon locomotor rhythm occurs only when the cere-
perikarya and spines of proximal and distal bellum is intact. Anatomic data suggest that
dendrites of cells of all sizes in the lateral these facilitatory effects are mediated both
vestibular nucleus (144). The cerebellum pro- monosynaptically and disynaptically via in -
vides a large number of afferent projections terneurons in laminae Vll and VIII that influ -
to the vestibular nuclear complex. These ence extensor a motor neurons, particularly
fibers are derived from (a ) the "vestibular those innervating limb muscles. The anterior
part" of the cerebellum ( i.e., the nodulus, the lobe of the cerebellum inhibits neurons in the
uvula and the flocculus), ( b) the fastigial nu - lateral vestibular nucleus and thus may exert
clei, and (c) the anterior lobe of the cerebel- a controlling influence upon labyrinthine ac-
lum (143, 224, 227, 228). "Vestibular parts" of tivation.
the cerebellum project fibers to regions of all Fibers from the medial vestibular nucleus
vestibular nuclei in a pattern similar to that of project toward the midline and turn caudally
primary vestibular fibers, except that the pro- in the medial longitudinal fasciculus of both
jection to the lateral vestibular nucleus is sides. The fibers continue into the medial part
scant (33). Fastigial projections to the vestibu - of the anterior funiculus of the spinal cord .
lar nuclei are crossed and uncrossed , nearly They influence cervical motor neurons so that
symmetric, and end mainly in ventral por- the head moves in such a way as to assist in
tions of the lateral and inferior vestibular nu- maintaining equilibrium and fixation of gaze.
clei (19). Cerebellovestibular fibers from the The medial longitudinal fasciculus is dis-
anterior lobe of the cerebellum, representing cussed in more detail later.
Purkinje cell axons, are somatotopically
arranged and terminate only in dorsal parts RETICULOSPINAL TRACTS
of the lateral and inferior vestibular nuclei
( 143, 224 ). It is apparent that vestibular influ - Two relatively large regions of the brain-
ences upon the spinal cord are mediated stem reticular formation give rise to fibers
largely by the vestibulospinal tract. that descend to spinal levels. One of these re-
The lateral vestibular nucleus exerts facili- gions is in the pontine tegmentum while the
tatory influences upon the reflex activity of other lies in the medulla . Hence, it is proper
the spinal cord and spinal mechanisms which to refer to these as the pontine and medullary
control muscle tone. This, perhaps, is best ex- reticulospinal tracts ( Figs. 11.10 and 11.22).
emplified in experimental decerebrate ani- The pontine reticulospinal tract arises from
mals by the reduction of rigidity which fol- aggregations of cells in the medial pontine
lows lesions in the lateral vestibular nucleus tegmentum referred to as the nuclei reticularis
or interruption of the vestibulospinal tract in pontis caudalis and oralis (32, 34, 156, 213). The
PONS
Pontine reticular
formation
MEDULLA ^
; Medullary reticular
formation
tV
^
T
*35
Pontine
reticulospinal
tract
Medullary reticulo-
spinal tract
C8
• i
\f n
Figure 11.22. Reticulospinal tracts indicating their regions of origin, course, and terminations. Pontine reticulospinal
fibers (red) terminate in lamina VIII and ddjacent parts of lamina VII. Medullary reticulospinal fibers (black) terminate
.
chiefly in laminae VII but some end in lamina IX
caudal pontine reticular nucleus begins in the The pontine reticulospinal tract is almost
caudal pontine tegmentum and extends ros- entirely ipsilateral and descends chiefly in the
trally to the level of the motor trigeminal nu- medial part of the anterior funiculus ( i.e., sul -
cleus. This nucleus contains a number of comarginal area ) ( Fig. 11.22 ). Pontine reticu -
giant cells, in addition to various types of lospinal fibers are more numerous than those
smaller cells. The oral pontine reticular nu - arising in the medulla and descend the entire
cleus occurs in more rostral parts of the me- length of the spinal cord where they termi-
dial pontine tegmentum and extends into the nate in lamina VIII and adjacent parts of lam-
caudal mesencephalon . Giant cells are found ina VII ( Fig. 11.22 ). A few pontine reticu -
only in the more caudal parts of this nucleus. lospinal fibers cross at spinal levels in the
Reticulospinal fibers arise from cells in all anterior white commissure. A large propor-
parts of the nucleus reticularis ponds cau - tion of pontine reticulospinal fibers give off
dalis, but only from the caudal part of the nu - collaterals to more than one level of the
cleus reticularis ponds oralis. More than half spinal cord , suggesting they are involved in
of the large cells in the caudal pontine reticu - activities at multiple spinal levels. Stimula -
lar nucleus project fibers to spinal levels ( 213). tion of the pontine reticulospinal pathway
evokes both monosynaptic and polysynaptic terminate are similar to those in which
excitation of motor neurons supplying axial vestibulospinal fibers end ; both of these sys-
and limb muscles, with direct effects tems are considered to convey facilitatory im -
strongest upon axial muscles, particularly pulses. Likewise, medullary reticulospinal
those in the neck. fibers terminate in portions of the spinal gray
The medullar }/ reticulospinal tract arises laminae that also receive fibers from corti-
from the medial two-thirds of the medullary cospinal and rubrospinal tracts.
reticular formation (32, 95). The largest num- Experimental studies indicate that stimu -
ber of fibers arise from the nucleus reticularis lation of the brainstem reticular formation
$i$antoccllularis , lying dorsal to the inferior can (a ) facilitate or inhibit voluntary move-
olivary complex and lateral to the parame- ment, cortically induced movement, and re-
dian region ( Fig. 11.22). As the name of this flex activity; ( b ) influence muscle tone via the
nucleus implies, it is composed of character- 7 motor system; (c) affect phasic activities as-
istic large cells, but , in addition , it contains sociated with respiration; (d ) exert pressor or
many medium- and small-sized cells. Fibers depressor effects on the circulatory system;
of the medullary reticulospinal tract project and (e) exert facilitating and inhibiting influ -
bilaterally (both crossed and uncrossed ) to ences on the central transmission of sensory
spinal levels and mainly descend in the ante- impulses. Areas of the medullary reticular
rior part of the lateral funiculi ( Figs. 11.10 and formation from which medullary reticu -
11.22 ). Fibers crossing to the opposite side do lospinal fibers arise, correspond to regions
so in the medulla ( 17) and are less numerous from which inhibitory effects have been ob-
than uncrossed fibers. Some fibers of the tained ( 6, 32, 171, 172, 213). Facilitatory effects
medullary reticulospinal tract descend the are obtained from far larger rostral regions of
entire length of the spinal cord . Reticu- the reticular formation. The reticular forma -
lospinal fibers from the pons and medulla are tion can influence muscle tone by acting upon
not sharply segregated in the spinal cord . 7 motor neurons, which innervate the con -
Medullary reticulospinal fibers terminate tractile portions of the muscle spindle (68,
chiefly in lamina VII and , to a lesser extent, in 74 ). It is largely by this mechanism that the
laminae VIII and IX ( 17, 150, 151 ) ( Fig. 11.22 ). reticulospinal systems modify tendon reflex
Medullary reticulospinal fibers terminate in activity .
parts of the gray spinal laminae that also The brainstem reticular formation receives
receive fibers from the rubrospinal and corti - inputs from many sources, but direct corti -
cospinal tracts. Two components of the med - coreticular projections are particularly abun-
ullary reticulospinal tract have been identi- dant. Corticoreticular fibers arise from wide-
fied physiologically: ( a ) long projections spread areas of the cortex although the
that provide collaterals to multiple spinal greatest number originate from the "motor
levels, and ( b) short projections to cervical area." These fibers terminate in two fairly re-
segments arising mainly from dorsolateral stricted regions of the reticular formation,
regions of the nucleus reticularis gigantocel - one in the pons and one in the medulla (192).
lularis. Corticoreticular fibers are distributed bilater-
Reticulospinal fibers, arising in both the ally with some crossed preponderance. The
pons and medulla, largely terminate upon termination within the reticular formation
the somata and dendrites of internuncial neu- corresponds to those regions that give rise to
rons, although some medullary projections the reticulospinal tract . Thus, the synaptic
end directly upon motor neurons. Most im - linkage of corticoreticular and reticulospinal
pulses from the reticular formation that influ - fibers forms a pathway from the cortex to
ence 7 motor neurons probably are mediated spinal levels. There is no evidence of a soma-
at segmental levels by internuncial neurons totopic arrangement within this system (32 ),
in laminae VII and VIII (67, 68 ). Anatomi- whose function is examined in Chapters 12
cally , neither the pontine nor the medullary and 13.
reticulospinal tract are somatotopically orga -
nized , although physiologic data suggest MEDIAL LONGITUDINAL FASCICULUS
that localized regions of the pontine and
medullary reticular formation may exert their The posterior part of the anterior funiculus
major influence at particular spinal levels. Re- contains a composite bundle of descending
gions in which pontine reticulospinal fibers fibers that originates from different nuclei at
various brainstem levels. This composite descending in the ventral part of the lateral
bundle is known as the medial longitudinal fas- funiculus, project into the anterior gray horn .
ciculus ( MLR. Spinal portions of this bundle In the cat these fibers have been identified as
represent only a part of the brainstem tract far caudally as lower cervical spinal segments
designated by the same name. Descending ( 234 ) . Fastigial neurons projecting contralat-
fibers in the spinal medial longitudinal fasci - erally to cervical spinal segments can be acti-
culus arise from the medial and inferior vated by labyrinthine and somatic stimuli,
vestibular nuclei ( vestibulospinal fibers ), the but the significance of this pathway in motor
pontine reticular formation ( reticulospinal control remains unknown.
fibers ), the superior colliculus ( tectospinal
fibers ), and the interstitial nucleus of Ramon Autonomic Pathways
v Cajal ( interstitiospinal fibers). The medial
longitudinal fasciculus forms a well-defined The spinal cord contains descending auto-
tract only in cervical spinal segments, but nomic fibers that terminate upon visceral cell
component fiber systems have been shown to groups ( i.e., intermediolateral cell column
descend to sacral levels ( Figs. 11.19, 11.21, and sacral preganglionic cell groups ) that in -
and 11.25). Fibers arising from the medial nervate smooth muscle, cardiac muscle, and
vestibular nucleus are predominantly ipsilat- body viscera . The principal nuclei giving rise
eral in the spinal cord and terminate upon to descending autonomic fibers are ( a ) several
portions of laminae VII and VIII ( 33, 43, 124, regions of the hypothalamus, ( b) visceral nu -
149 ). Physiologic studies suggest that these clei of the oculomotor complex, (c) the locus
fibers convey monosynaptic inhibitory influ - coeruleus and adjacent areas, and (d ) por-
ences directly to upper cervical motor neu - tions of the nucleus of the solitary tract ( Fig.
rons ( 2, 235). This unusual direct pathway 11.23). Additionally, some neurons in the
appears to play a role in the labyrinthine reg- reticular formation are concerned with vis-
ulation of head position . The largest compo- ceral activities. These include some noradren -
nent of the spinal medial longitudinal fasci - ergic neuronal groups in the ventrolateral re-
culus, the pontine reticulospinal tract, was gions of the medulla and pons that receive
described earlier ( Fig. 11.22 ). The intersti - inputs from rostral autonomic structures and
tiospinal tract arises from a small mesen- project fibers to the spinal cord via a relay in
cephalic nucleus lateral to the medial longitu - the reticular formation. Hypothalamic neu -
dinal fasciculus and oculomotor complex. rons projecting to spinal levels include cells
Fibers of this tract terminate in parts of lami- in (a ) paraventricular nucleus, ( b ) lateral and
nae VII and VIII at all spinal levels. Fibers of posterior hypothalamic areas, (c) supramam-
the interstitiospinal tract are uncrossed, de- millary nucleus, and ( d ) dorsomedian nu -
scend in the most posterior part of the ante- cleus (94, 107, 195 ). Fibers from these hypo-
rior funiculus near the anteromedian fissure, thalamic nuclei project to visceral nuclei in
and terminate in dorsal parts of lamina VIII the medulla as well as to the spinal cord ( Fig.
and neighboring parts of lamina VII ( 151, 11.23). Direct hypothalamic-spinal fibers de-
207). scend in the lateral funiculus and terminate
upon cells of the intermediolateral cell col -
FASTIGIOSPINAL FIBERS umn in thoracic, lumbar, and sacral seg-
ments. These uncrossed fibers appear to di -
Although the cerebellum has been consid - rectly influence preganglionic sympathetic
ered to exert its influences upon spinal activi - and parasympathetic neurons. It should be
ties solely via relay nuclei in the brainstem, noted that hypothalamic regions giving rise
some evidence suggests that one of the deep to spinal projections receive, in turn , a signifi -
cerebellar nuclei projects directly'
to cervical cant input from cells scattered in the spinal
spinal levels (19, 72, 130, 212, 234 ) . Fasti - cord ( 23, 47, 93).
giospinal fibers arise from cells in all parts of Although the visceral nuclei of the oculo-
the fastigial nucleus, cross the midline within motor complex project large numbers of pre-
the cerebellum and emerge via the uncinate ganglionic parasympathetic fibers into the
fasciculus. Fibers descend ventral to the third nerve, these neurons also project di-
spinal trigeminal tract and are partially inter - rectly to spinal levels ( 120, 121, 193). De -
mingled with fibers of the vestibulospinal -
scending fibers from the Edinger Westphal
tract at some levels. In the spinal cord , fibers nucleus contribute fibers to the posterior col -
Anterior Paraventricular
commissure nucleus
Posterior + Pineal body
hypothalamus Mammillary body
Lateral
hypothalamic
nucleus
Hypophysis -
Oculomotor
HYPOTHALAMUS
visceral nuclei
MIDBRAIN
Hypothalamic spinal Oculomotor spinal

projections projections
Locus ceruleus Trochlear (IV) nerve
ISTHMUS
Dorsal motor nucleus

ot the vagus ( X) nerve
Nucleus solitarius
MEDULLA
Spinal projections ot Hypoglossal ( XII)

nucleus solitarius nerve
Phrenic nerve nucleus

C 3, C 4 , & C 5 Spinal projections of
locus ceruleus
T 12
Anterior horn and
intermediate gray
Figure 11.23. Descending autonomic projections to spinal cord Projections from hypothalamic nuclei (parvicellular
paraventricular nucleus, lateral and posterior hypothalamic areas) descend to terminate upon cells of the ipsilateral
intermediolatera! column in thoracic and upper lumbar spinal segments (blue) Hypothalamic nuclei are shown in a
sagittal plane. Parasympathetic visceral neurons in the oculomotor supply Intrinsic ocular structures and project fibers
to the spinal cord that terminate in parts of laminae I and V (green). At isthmus levels, cells of the pigmented locus
coeruleus give rise to descending noradrenergic fibers that reach the spinal cord and terminate in parts in the ante-
rior horn and the intermediate gray (red) . Cells In the ventrolateral part of the nucleus solitarius project crossed fibers
.
to the phrenic nucleus (C3, C4 and C5) and to parts of the anterior horn in thoracic and spinal segments ( black ).
Noradrenergic projections to the spinol cord from the ventrolateral pontine tegmentum (cell group A5) are shown in
Figure 11.24
umn nuclei and spinal projections that de- modulate sensory input , especially that re-
scend to lumbar levels ( Fig . 11.23). In the lated to nociceptive stimuli .
spinal cord , these fibers course in the lateral Cells in the ventrolateral part of the soli -
funiculus ajfcl terminate in lamina 1 and parts tary nucleus ( Fig . 11.23) project to cervical
of lamina V ( 121 ) . It has been suggested that and thoracic spinal segments ( 117). The soli -
these descending spinal projections may tariospinal tract is predominantly crossed
and terminates in the region of the phrenic acids, such as glycine (84 ), GABA (90, 91 ), as-
motor neurons at C3-C5 levels and the ante- partate, and glutamate (146), and ( b) neuroac-
rior horn and intermediolateral cell column at tive peptides, such as thyrotropin releasing
thoracic levels ( Fig. 10.21 ). Fibers of this tract hormone ( TRH ) and substance P (11, 146 ).
provide excitatory inputs to phrenic and in - Furthermore, serotoninergic medullary raphe
spiratory motor neurons (45, 63, 65, 209 ). neurons that project to the spinal cord are
Descending reticulospinal tracts that origi- known to coexpress several of these amino
nate in regions of medullary and pontine acids or neuroactive peptides.
reticular formation concerned with respira - The descending serotoninergic projections
tory and cardiovascular control are also part are believed to be involved in several spinal
of the autonomic pathways to the spinal cord cord functions, such as control of motor neu -
( see Chapters 12 and 13). rons and autonomic activities ( 51 ), and mod -
ulation of pain (16, 18, 184 ).
Monoaminergic Systems
CATECHOLAMINERGIC PROJECTIONS
SEROTONINERGIC PROJECTIONS
A small pigmented nucleus in the upper
Brainstem neurons which utilize serotonin pons, known as the locus coeruleus ( Figs.
-
(5 hydroxytryptamine, 5- HT ) as a transmitter 13.33-13.35) was demonstrated to synthesize,
and project to the spinal cord are largely con- store, and release the neurotransmitter norep-
fined to nuclei raphe pallidus, obscurus and inephrine ( also termed noradrenaline) ( 49 ).
magnus in the caudal medulla (27). These nu- This relatively small nucleus, which corre-
clei correspond respectively to groups Bl , B2, sponds to the catecholaminergic group A 6 of
and B3 in the nomenclature of Dahlstrom and Dahlstrom and Fuxe (62 ), distributes fibers
Fuxe (62 ). Additionally, axonal branches of a widely in the neuraxis and is regarded as a
limited number of serotoninergic neurons in principal source of norepinephrine. Data
the dorsal raphe nucleus (group B7) and adja- based upon axonal transport methods com-
cent midbrain reticular formation also reach bined with immunocytochemistry brings
the cervical part of the spinal cord ( 28). The detailed information on the organization of
serotoninergic fibers originating in these nu - noradrenergic projections to the spinal cord .
clei descend principally in the lateral funicu - Noradrenergic fibers from the locus coeruleus
lus and arborize along the entire length of the and its ventral extension, the subcoeruleus area
spinal cord and in both the anterior ( ventral ) ( group A 6v ), descend in the anterior and
and posterior ( dorsal ) horn (17, 28, 147). In lateral funiculi, are largely uncrossed , and
the posterior horn , serotoninergic fibers ar - arborize in the anterior horn and the ven -
borize more profusely in laminae I and II tral half of the posterior horn ( laminae
than in other laminae, and this dense inner- IV , V , and VI ) ( Fig . 11.23) ( 154, 170, 185,
vation is particularly obvious at the levels of 204 , 230, 231 ) . A large proportion of the
cervical and lumbar enlargements (147). In coeruleospinal neurons in the cat coexpress
the anterior horn, a dense plexus of sero- the opiate peptide methionine-enkephalin
toninergic fibers occurs at the levels of the ( 239 ) . The noradrenergic cells of the locus
medial and lateral motor neuronal groups coeruleus complex do not appear to pro -
(lamina IX ). These fibers form close pericellu - ject to the intermediolateral column ( 154,
lar contacts with the somata and proximal 231 ). In the anterior horn, noradrenergic
dendrites of the large motor neurons (101 ). In coeruleospinal fibers form conventional
the intermediate gray of the spinal cord , sero- synapses upon motor neurons ( 85) and are
toninergic fibers profusely arborize around , believed to augment the somatomotor out -
and synaptically contact sympathetic pregan- put, at least in part , via an ot -1 -adrenore-
glionic neurons of the intermediolateral col- ceptor- mediated excitation of motor neu -
umn ( 14 ). rons ( 71 ) .
In the lower medulla , serotoninergic neu - Two other noradrenergic cell groups, one
rons projecting to the spinal cord are in - in the caudolateral portion of the pontine
termingled with several other spinally- tegmentum ( group A7) and the other in the
projecting neurons that contain different ventrolateral region of the medullary reticu -
neurotransmitters. This chemically heteroge- lar formation (group A5), give rise to fibers
neous population of spinally- projecting cells that descend to the spinal cord . Noradrener-
comprises neurons that contain (a ) amino gic fibers from the A 5 group form the lateral
Brain stem
A5 catecholamine
Facial cell group
colliculus
— Intermediolateral
column
cell
Internuncial neurons
Figure 11.24. Spinal projections from the pontine catecholamine cell group A5. Noradrenergic fibers from this cell
group descend ipsilaterally, but are distributed bilaterally to the Intermediolateral cell column and internuncial neu-
rons In thoracic spinal segments. Preganglionic and postganglionic sympathetic fibers project to the cardiovascular
system
tegmental system , which directly innervates the A7 group are important components of
cells of the intermediolateral column ( 46, 119, the descending neuronal system that modu -
122 ) ( Fig. 11.24). Electrical stimulation of this lates nociception (40, 89 ).
neuronal group produces marked increases Other catecholaminergic inputs to the
in arterial blood pressure (118). This nucleus spinal cord derive from a group of adrena-
is considered as part of a brainstem vasomo- line- producing neurons located in the ventro-
tor center, whose effects on sympathetic pre- lateral portion of the caudal medulla and
ganglionic motor neurons are mediated via a termed group Cl by Hokfelt and colleagues
noradrenergic synapse upon cells in the inter- (82). These neurons project massively to cells
mediolateral column ( Fig. 11.24). In contrast, of the intermediolateral column (83, 88), but
neurons of group A 7 provide the major nora
drenergic innervation of laminae I to IV in the
- their function remains unknown.
posterior horn. Electrical stimulation of this INTRINSIC SPINAL FIBERS

nucleus has an antinociceptive effect that is
mediated by spinally projecting noradrener- A certain number of dorsal root afferent
gic neurons ( 237). These findings indicate fibers make monosynaptic connections with
that pontospinal noradrenergic neurons in anterior horn cells (70, 81, 206). In most in-
Fasc . septomarginalis Fasc . gracilis

Fasc. interfasciculis — — Fasc . cuneatus
Fasc . dorsolateralis
Lat. corticospinal tr.
Post spino-
,
cerebellar tr.
Lat . spino-
thalamic tr.
Rubrospinal tract
— Ant. spino-
cerebellar tr.
Medullary
reticulospinal tr. - Spinoolivary tr.
Vestibulospinal tr. Spinotectal tr .
Pontine reticulospinal tr. -Ant. spinothalamic tr .
Tectospinal tr. Med . longitudinal fasc .
— Ant. corticospinal tr.
Ascending pathways
Descending pathways
Figure 11.25 . Ascending and descending pathways of the spinal cord Two different types of hatched areas are
used to differentiate ascending from descending pathways. The fasciculus proprius system ( shaded areas ) and dorso-
lateral fasciculus contain both ascending and descending nerve fibers
stances, however, these first afferents synapse collaterals, and many terminals of ascending
on central or internuncial neurons ( interneu - dorsal root fibers are also part of the spin-
rons ) interposed between the afferent and ef - ospinal fiber system . Impulses entering the
ferent neurons. These interneurons then send cord at any segment may travel along these
their axons to the motor cells of the same seg- fibers to higher or lower levels before synaps-
ment , or to higher and lower segments, for ing directly or through internuncial neurons
the completion of various intersegmental re- with the anterior horn cells ( Fig. 10.24 ). These
flex arcs. Axons of spinal interneurons ascend shorter fiber systems forming part of the in -
or descend in the white columns of the same trinsic reflex mechanism of the spinal cord
side, or pass to the white matter of the oppo- are of major importance in a variety of re-
site side. All these ascending and descending flexes. Most long and myelinated spinospinal
fibers, crossed and uncrossed, which begin fibers are found in the interfascicular and
and end in the spinal cord and connect its septomarginal bundles, whereas unmyeli -
various levels, constitute the fasciculi proprii nated , or group C, axons and some thin
or spinospinal fasciculi of the spinal cord ( Figs. group A myelinated spinospinal axons occur
10.7 and 11.25). Long descending axons arise in the dorsolateral tract (or Lissaucr' s tract ).
ipsilaterally from lamina I and bilaterally The spinospinal fibers are found in all fu -
from laminae V, VII and VIII ( 151 ) . The
largest number of long descending fibers
—
niculi posterior, anterior, and lateral. They
occupy the area adjacent to the gray matter
arise from cells in laminae VII and VIII . and lie between the gray matter and the pe-
Fibers crossing to the opposite side decussate ripherally placed long tracts. They are most
at levels of cell origin . Descending branches numerous in the anterolateral white columns.
of axons in lamina I may be implicated in In the posterior funiculus, they form a nar-
modulation of sensory input, while neurons row zone along the posterior commissure
in laminae VII and VIII may influence motor and adjacent portions of the posterior horn .
neurons at more caudal levels of the spinal In general, the shortest fibers lie nearest the
cord . gray matter and connect adjacent segments
The descending root fibers of the interfas- while the longer fibers lie more peripherally.
cicular and septomarginal bundles and the These tracts and the major ascending and de-
scending spinal pathways are diagrammed in suprasegmental control by impulses trans-

Figure 11.25. mitted via descending spinal systems ( Fig.
11.25).
UPPER AND LOWER MOTOR NEURONS Injury or disease of the anterior horn cells
or their projecting axons results in weakness
One of the most important concepts in or paralysis of the muscles innervated by
neurologic diagnosis rests upon distinguish - these fibers, loss of muscle tone, and prompt
ing the abnormalities of motor function atrophy of the denervated muscle. Weakness
which result from pathologic involvement of , or paralysis , occurring in affected muscles,
or injury to, the upper or lower motor neu - bears a direct relationship to the extent and
ron . This relatively simple, yet frequently severity of the lesion. Since the anterior horn
puzzling, distinction forms one of the corner- cells that innervate a single muscle extend
stones of clinical neurology. The ability to longitudinally through several spinal seg-
distinguish upper and lower motor neuron ments, and since several such cell columns
lesions constitutes the first step in attempting exist at each spinal level, a lesion confined to
to localize the site of a neural lesion that man - one spinal segment will cause weakness, but
ifests itself by disturbances of normal motor not complete paralysis, in all muscles inner-
function . Once the site of the neural lesion vated by this segment. Complete paralysis
has been established , the clinician can begin will occur only when the lesion involves the
to consider the pathologic processes which column of cells in several spinal segments
might be responsible ( 42 ). that innervate a particular muscle, or the ven-
tral root fibers that arise from these cells. Be-
Lower Motor Neurons cause most of the appendicular muscles are
innervated by fibers arising from parts of
The anterior horn cells are regarded as the three spinal segments, complete paralysis of a
prototype for all motor neurons. These cells muscle resulting from a central lesion in the
and their axons, which project via the ventral anterior horn indicates involvement of sev-
root to striated muscle, constitute the eral spinal segments. Furthermore, because
anatomic and physiologic unit commonly re- neighboring cell columns are likely to be af -
ferred to as the final common motor pathway fected at each level, such a lesion usually pro-
or the lower motor neuron. The concept of duces paralysis in muscle groups, rather than
the lower motor neuron is not limited to the in individual muscles.
spinal cord , even though it is most frequently Since the lower motor neuron consists of
used in that context. Cells of the motor cra - the anterior horn cells and their axons, which
nial nerve nuclei ( N . Ill , IV , V , VI , VII , IX , X, innervate striated muscle, it becomes neces-
XI , and XII ), which provide innervation for sary to distinguish the motor deficits that
skeletal muscles of the head and neck, also occur as a consequence of lesions in spinal
must be classified as lower motor neurons, segments from those which occur in ventral
even though these nuclei form discontinuous roots, spinal nerves and peripheral nerves. A
cell columns in the brainstem . lesion in ventral root fibers usually produces
The segmental input to the lower motor motor deficits similar to those resulting from
neuron is profuse, both direct and indirect, destruction of anterior horn cells. At certain
and largely, but not exclusively, ipsilateral. levels ( i .e., thoracolumbar and sacral ), section
Muscle spindle afferents (group la ) project di- of the ventral root fibers produces additional
rectly to the lower motor neuron ( Figs. 10.23 autonomic deficits, which might not accom -
and 10.30 ), while afferents from most other pany anterior horn cell lesions at the same
receptors, including the Golgi tendon organ level ( Fig. 11.26 ). Lesions of mixed spinal
( Fig. 10.30), influence the lower motor neuron nerves produce motor and sensory deficits
indirectly via internuncial neurons. Afferent that correspond to those of combined dorsal
inputs from stretch receptors ( i .e., muscle and ventral root lesions. While the motor
spindle and Golgi tendon organ ) activate ip- deficit corresponds almost exactly to that
silateral cell groups in the spinal cord , while seen with pure lesions of the ventral root,
afferent impulses from other sensory recep- sensory disturbances and loss follow a der-
tors are distributed by multisynaptic circuits matomal distribution and tend to be less ex-
to both sides of the spinal cord . The lower tensive because of overlapping innervation
motor neuron also is under powerful indirect characteristic of dermatomes ( Figs. 8.10-8.12 ).
Fasciculus gracilis Fasciculus cuneatus
Lateral corticospinal tract Lower cervical
Fasciculus cuneatus Posterior spinocerebellar tract

i i i
i
Posterior spinocerebellar tract Upper thoracic
• i l l'
i i i !
I
5 I
I
I
Spinal ganglion
2 Lower thoracic
|:r.
Anterior spinocerebellar tract
Sympathetic ganglion
i
Fasciculus gracilis
Spinal nerve
Upper lumbar
Lateral spinothalamic tract'^^

^^J^^^—V^ 'Ventral
^
X
root
Figure 11.26. Degeneration resulting from certain lesions of the spinal nerves, spinal roots, and spinal cord Sites of le-
sions are indicated by small black wedges. Dorsal and ventral root fibers, peripheral nerve fibers, fibers in the posterior
white columns and short relays are in black: ascending spinal tracts are blue: and the corticospinal tract Is red A le-
sion of the dorsal root. 1. at upper lumbar levels produces degeneration (.dashed lines ) in the posterior and anterior
gray horns (not shown) and in parts of the fasciculus grocilis No degeneration Is present in other ascending spinal
tracts because degeneration does not pass beyond the synapse A lesion of a spinal nerve as at 2 produces periph-
eral degeneration ( dashed lines) in somatic motor, sensory, and postganglionic sympathetic fibers. A lesion of the
ventral root at site 3 produces degeneration in somatic motor and preganglionic sympathetic fibers. A lesion at 4 pro-
duces degeneration only in somatic motor fibers distal to the lesion. The lesion at 5 destroys the lateral funiculus and
produces ascending degeneration ( dashed lines) in the posterior and anterior spinocerebellar tracts ( blue) and In the
spinothalamic tracts (only the lateral spinothalamic tract ( blue) is shown here) above the level of the lesion This lesion
also produces descending degeneration in the corticospinal tract ( red) below the level of the lesion. Although other
spinal tracts which would degenerate are not indicated, the same principle applies
With a peripheral nerve lesion, the muscle drawal of streams of impulses transmitted to
paralysis and sensory loss correspond to the muscles that normally maintain a state of
distribution of the particular nerve ( Figs. 8.11 variable, but sometimes sustained , contrac-
and 8.12 ). tion in some of the muscle units. Reflexes in
Loss of muscle tone, hypotonia , is a charac- the affected muscles are diminished or lost
teristic and constant finding in lower motor ( areflexia ) in lower motor neuron lesions be-
neuron lesions. Flaccidity of the affected cause the reflex arc is interrupted ( Fig . 10.30) .
muscles is evidenced by greatly diminished In this type of lesion, the effector mechanism
resistance to passive movement . This reduc- is destroyed .
tion in muscle tone results from the with- Although paralysis, hypotonia , and are-
404 Section IV Spina! Cord
flexia occur almost immediately following a importance of the corticospinal system and
lower motor neuron lesion, atrophy or mus- the previously poorly defined functional in-
cle wasting does not become evident for 2 or fluences of descending nonpyramidal fiber
3 weeks. Muscle atrophy develops gradually, systems. Recent anatomic and physiologic
and in time is obvious on inspection. Why data concerning descending nonpyramidal
muscles deprived of their innervation atro- fiber systems make it necessary to modify
phy and degenerate is not adequately under- this venerable rule of thumb and to consider
stood . It seems likely that the morphologic the concept of the upper motor neuron in its
and functional properties of muscle are de- broadest sense. Descending impulses, trans-
pendent upon transmitter substances pro- mitted to spinal levels by a group of hetero-
vided by the terminals of motor nerve fibers. geneous tracts, are concerned mainly with (a )
Atrophy, of the type seen in lower motor mediation of somatic motor activity, (b) con-
neuron disease, does not result from depriv- trol of muscle tone (c) maintenance of posture
ing anterior horn cells of afferent impulses and equilibrium, (d ) suprasegmental control
from either suprasegmental or segmental lev- of reflex activity, (e) control of visceral and
els ( 214). autonomic activities, and (0 modification of
In certain diseases of the lower motor neu- sensory input.
ron, the muscles exhibit small, localized , Lesions involving upper motor neurons, at
spontaneous contractions known as fascicula- a wide variety of locations and resulting from
tions . These muscle twitches, visible through many different kinds of pathologic processes,
the skin , represent the discharge of groups of produce paralysis, alterations of muscle tone,
muscle fibers innervated by nerve fibers aris- and reflex activity. Lesions destroying upper
ing from a single lower motor neuron. Fascic- motor neurons are rarely selective, usually
ulations occur asynchronously in different incomplete, and frequently involve adjacent
parts of various muscles and are thought to pathways and nuclear structures. The degree
be due to a triggering of motor unit dis- of paresis (i.e., incomplete loss of muscle
charges that occur within the cell body of the power ) or paralysis does not bear a direct re-
motor neuron. Fasciculations of this type are lationship to the size of the lesion, or to the
interpreted as a disease process attacking the extent of involvement of the corticospinal
lower motor neurons in the anterior gray tract (110). Destruction of upper motor neu -
horn. Fasciculations commonly are seen in rons may result from vascular disease,
amyotrophic lateral sclerosis, occasionally in trauma, neoplasm, and infectious and degen-
acute inflammatory lesions of peripheral erative diseases. Unilateral lesions in the cere-
nerves, but rarely when anterior horn cells bral hemisphere and brainstem produce con-
are rapidly injured or destroyed , such as in tralateral paralysis, usually hemiplegia.
acute poliomyelitis. Spinal lesions, most commonly the result of
The term fibrillation , frequently misused as trauma, are usually bilateral, and either result
the equivalent of the term fasciculation refers in paraplegia or quadriplegia , depending
to the small (10-200 p.V ) potentials of 1-2 upon the cord level involved .
msec duration that occur irregularly and Immediately after an upper motor neuron
asynchronously in electromyograms of den- lesion in the cerebral hemisphere or brain-
ervated muscle. These spontaneous dis- stem, the paralyzed limbs contralateral to the
charges cannot be observed through the skin lesion usually are flaccid and the myotatic re-
and produce no detectable shortening of flexes are depressed or absent. After variable
muscles. periods, the myotatic reflexes reappear in an
exaggerated form in the paralyzed limbs. The
Upper Motor Neurons superficial abdominal reflexes, elicited by
stroking the skin over the abdomen, and the
All of the descending fiber systems that cremasteric reflexes in the male, disappear on
can influence and modify the activity of the the side of the paralysis. The plantar re-
lower motor neuron constitute the system of sponse, elicited by stroking the sole of the
upper motor neurons ( Fig. 11.25). This is a foot, becomes extensor ( Babinski sign ).
more inclusive definition than that used by After a variable period of time, muscle
many clinicians who equate upper motor tone in the affected limb gradually returns
neurons solely with the corticospinal system. and ultimately exceeds that of the normal
The narrower concept has become a rule of side. This exaggeration of muscle tone is re-
thumb because of the overwhelming clinical ferred to as hypertonicity or spasticity . The in-
crease in tone is not exhibited by all muscles from unilateral lesions in the brainstem or
-
of the affected limbs. Spasticity selectively in cerebral hemisphere produce contralateral
volves the antigravity muscles. In the affected disturbances of motor function . Unilateral
upper extremity, spasticity is present particu - brainstem lesions involving upper motor
larly in the adductors and internal rotators of neurons frequently damage motor cranial
the shoulder, in the flexors of the elbow, nerves on the side of the lesion .
wrist, and digits, and in the pronators of the The concept of the upper and lower motor
forearm. In the affected lower extremity, neuron constitute one of the basic corner
spasticity develops in the adductors of the stones of clinical neurology and the simple
hip, the extensors of the hip and knee, and in distinctions outlined above must be consid -
the plantar-flexors of foot and toes. Spasticity ered in the neurologic examination of every
is relatively easy to describe but extremely patient .
difficult to define. Descriptively, spasticity is
characterized by (a ) increased resistance to
LESIONS OF THE SPINAL CORD AND
passive movement , ( b ) extraordinarily hyper - NERVE ROOTS
active myotatic (deep tendon ) reflexes that
exhibit a low threshold , a large amplitude, an Determination of the origin, course, and
enlarged reflexogenous zone, and a briskness termination of most spinal cord pathways
much greater than normal, and (c) the pres - from the study of normal Weigert- and Nissl-
ence of clonus (125). Clonus is a manifestation stained sections is virtually impossible, but
of the exaggerated stretch reflex in which the such preparations provide valuable informa -
contractions of one muscle group are suffi - tion concerning spinal cord organization and
cient to stretch antagonistic muscle groups cytoarchitecture. Secondary or Wallerian de-
and initiate myotatic responses in that muscle generation in nerve fibers (severe from cell
group. Clonus has a tendency to perpetuate bodies), studied in sections stained by the
itself in a synchronized manner. In some in- Marchi, Nauta , or other silver impregnation
stances, the threshold for this extreme exag - techniques, provided valuable information
geration of the myotatic reflex is so low that concerning the course and termination of
passively moving a limb may initiate it. fiber bundles in human materials ( Fig. 11.26).
The paralysis, which may appear complete Lesions in nerve fibers also produce alter -
at the onset of an upper motor neuron lesion, ation of the cell bodies giving rise to these
tends to become less severe in time. Even the fibers, and these changes can be detected in
weakness tends ultimately to involve one -
Nissl stained sections within a few days.
limb more than the other. The motor func - These cell changes, referred to as retrograde
tions affected most are those associated with cell changes, are characterized by swelling
fine, skilled movements. Gross movements, and distortion of the perikaryon, eccentrically
and those which involve a whole limb, are placed nuclei, and dissolution of Nissl sub-
least affected and show considerable restitu - stance. Retrograde cellular changes provide
tion. Atrophy of the type seen with lesions of precise data concerning the cell of origin of
the lower motor neuron does not occur with particular fiber bundles. The most convincing
upper motor neuron lesions. However, after a data concerning spinal pathways, however,
period of years some atrophy of disuse behave been derived from tract - tracing studies
comes evident. undertaken in animals. These investigations
Many hemiplegic patients, in time, recover were made possible with the advent of meth-
considerable motor function . Those that be- ods principally based on the physiologic
come ambulatory have a characteristic gait . principle of axoplasmic flow. The various
The paralyzed leg is circumducted at the hip neurobiologic tools currently available for
en bloc and swung forward , because of the studying neuronal morphology and connec -
difficulty in flexing the knee. The foot is plan- tions were described in Chapter 5.
tar-flexed and the toe of the shoe is dragged
in a characteristic circular fashion . The arm
on the affected side is flexed at the elbow and Root Lesions
wrist , the forearm is pronated , and the digits DORSAL ROOT LESIONS
are flexed . The arm usually is held close to
the body, but if the arm is swung at all in Section of the dorsal roots ( dorsal rhizo-
walking, it moves primarily at the shoulder. tomy ) abolishes all input supplied by these
Upper motor neuron syndromes resulting roots and interrupts segmental reflex arcs
( Fig. 11.26). Because of extensive overlap of to the smooth muscle of the eye and levator
dermatomes in the periphery, destruction of palpebrae muscle results in a triad of clinical
one dorsal root does not result in detectable symptoms known as Horner' s syndrome
sensory loss. If multiple dorsal roots are sec
tioned , for example C5 to Tl , cutaneous sen-
- (Chapter 9 ). This syndrome usually is accom-
panied by altered sweating on the face. In
-
sibility will be lost (anesthesia ) or greatly im such a case, secondary ( Wallerian ) degenera -
paired ( hypoesthesia ), in the C6, C7, and C8 tion results in somatic and visceral efferent
dermatomes, but input from stretch receptors fibers; postganglionic neurons and their
entering all five dorsal roots will be abol
ished . As a consequence, muscle tone and
- processes remain intact .
If a mixed nerve is injured distal to the
myotatic reflexes will be absent in most of the junction of the dorsal and ventral root (2, in
muscles of the upper extremity. Although the Fig. 11.26), the combined sensory and motor
muscles can be contracted because the ventral losses enumerated earlier will be present . It
root remains intact , the deafferented extrem - should be noted that if such combined nerve
ity is virtually useless due to loss of cuta - lesions are extensive, they may be followed
neous and kinesthetic sense. Monkeys with by trophic changes in the skin (smooth -
such rhizotomies do not use the deafferented ness, dryness ) and in capillary circulation
limb for walking, climbing, or grasping (142, (cyanosis). These trophic alterations presum-
157, 219). ably are due to the loss of peripheral vasomo-
tor and afferent nerve fibers.
Spinal cord degeneration resulting from
multiple dorsal rhizotomies (C5 to Tl ) is dis-
tributed more profusely at the level of the
sectioned roots to portions of the posterior Spinal Cord Transection
horn, to selected cell groups within lamina COMPLETE SPINAL CORD TRANSECTION
VII , and parts of lamina IX . Particularly pro-
fuse ascending and descending degeneration Such a transection results in immediate
is present in the ipsilateral fasciculus cunea - loss of all neural functions below the level of
tus. No ascending degeneration is present in the lesion. There is a complete loss below the
other ascending spinal tracts, because these level of the lesion of (a ) all somatic sensation,
tracts arise from cell groups within the spinal ( b ) all motor function, (c) all visceral sensa -
cord . In other words, degeneration is limited tion , (d ) all reflex activity, (e) all muscle tone,
to the primary afferent fibers and does not and ( f ) thermoregulatory control. This com -
involve intrinsic spinal neurons or their plete cessation of all neural function in the
processes. A representation of degeneration isolated spinal cord caudal to the lesion is
resulting from section of a single lumbar dor- called spinal shock and persists for 1-6 weeks
sal root is shown at 1 in Figure 11.26. (average 3 weeks) in humans. The termina -
tion of the period of spinal shock is heralded
VENTRAL ROOT LESIONS by the appearance of the Babinski sign. A
fairly orderly sequence of events follows
Injury or section of the ventral root pro -
which vary in duration . The various phases
duces a lower motor neuron paralysis of the involved in the recovery of function in the
muscle units innervated by the particular isolated human spinal cord have been care-
root ( 4, in Fig. 11.26). If the lesion involved fully analyzed (103). These phases in recov -
thoracic or upper lumbar ventral roots, pre- ery of neural function are (a ) minimal reflex
ganglionic sympathetic fibers also would be activity (3-6 weeks ), ( b ) flexor spasms (6-16
interrupted (3, in Fig. 11.26). Thus, destruc- weeks), (c) alternate flexor and extensor
tion of the C8 spinal ventral root would spasms (after 4 months), and (d ) predomi -
partly paralyze the small muscles of the hand nant extensor spasms (after 6 months). The
( via median and ulnar nerves ), whereas a le -
phase of minimal reflex activity is character-
sion of both ventral roots C8 and Tl would ized by weak flexor responses to nociceptive
produce a complete flaccid paralysis and at -
stimuli, which begin distally and progres-
rophy of these muscles ( Fig. 8.17). The inclu -
sively involve proximal muscle groups in the
sion of ventral root Tl in the injury would extremities. During this period the Babinski
also interrupt many of the preganglionic vis -
sign can be obtained bilaterally, but the mus-
ceral efferent fibers en route to the superior cles are flaccid and the deep tendon reflexes
cervical sympathetic ganglion ( Figs. 10.23 cannot be elicited .
and 11.30 ). Loss of these visceral motor fibers The phase of flexor muscle spasms is charac-
terized bv increasing tone in the flexor mus - the sacral cord (S2, S3, S4), leads to loss of rec-
cles and by stronger flexor responses to noci- tal motility . There are reflex spasms of the ex -
ceptive stimuli , which progressively involve ternal anal sphincters and fecal retention.
more proximal muscle groups. It is during Defecation occurs involuntarily after long in -
this phase that the so-called triple flexion re- tervals. If cord segments S2, S3, and S4 are
sponse of Sherrington is first seen . This in- destroyed ( conus medullaris syndrome ), there is
volves flexion of the lower extremity at the a permanent paralysis of the external sphinc -
hip, knee, and ankle in response to a rela - ter and fecal incontinence ( Fig . 9.11 ). When
tively mild nociceptive stimulus. The most these sacral segments are involved there is, in
exaggerated form of this reaction is the innss addition, paralytic incontinence and usually
reflex in which a relatively mild and some- bladder distension, impotence, and perianal
times nonspecific stimulus results in power- or saddle anesthesia. However, normal sen -
ful bilateral triple flexion responses. These sory and motor function is retained in the
responses are characterized by repeated dis - lower extremities. Bladder disturbances usu -
charge of motor units throughout the caudal ally occur in three phases after cord transec-
part of the spinal cord . The mass reflex ap- tion . At the outset there is always urinary re-
pears to be due to the spread of afferent im- tention , due to paralysis of the muscular
pulses from one cord segment to the next and bladder wall (detrusor muscle), and spasm of
dispersion of impulses in such a manner as to the vesicle sphincter. Two or 3 weeks later
cause motor units to continue to fire after the ( range 2 days to 18 months ) the second phase
exciting stimulus has been withdrawn. The or overflow incontinence is observed . An inter-
mass reflex is distressing to the patient be- mittent dribbling of urine during this phase is
cause it is almost impossible to control . This due to gradual hypertrophy of the detrusor
reflex becomes less severe about 4 months smooth muscle. The muscle overcomes the
after spinal transection %vhen extensor muscle resistance of the external sphincter for short
tone gradually begins to increase. During this periods of time. Continued hypertrophy of
phase both flexor and extensor muscle the bladder wall eventually permits the blad -
spasms occur, but within a relatively short der to expel small amounts of urine automati-
time extensor muscle tone predominates. It cally, providing bladder infections have not
may be so great that the patient can momen- intervened . This is the third phase, known as
tarily support his weight in a standing posi- automatic micturition . Such automatic activity
tion (103). of the bladder is poor if lumbar spinal cord
Examination of the patient 1 year after segments are involved, and absent ( paralytic
complete spinal cord transection reveals ( a ) incontinence) when the sacral segments are
marked extensor muscle tone, ( b) spasticity, destroyed . The incontinence problem usually
(c) hyperactive myotatic reflexes, (d ) sus - is handled by a system of tidal drainage,
tained clonus, (e) bilateral Babinski signs, ( f ) which automatically fills and empties the
loss of the superficial abdominal and cremas- bladder at regular intervals.
teric ( male) reflexes, and (g ) loss of all sensa- Degeneration resulting from a complete
tion and voluntary motor function below the transection of the spinal cord follows a well-
level of the lesion. Spasticity is characterized established pattern . Above the level of the
by increased tone in the antigravity muscles lesion ascending tracts will degenerate ( Fig.
(extensors in the lower extremity and flexors 11.2 ) while, below the lesion level, they re-
in the upper extremity ), increased resistance main intact ( Fig. 11.16 ). The reverse is seen
to passive movement, and a sudden reduc- in the descending tracts. Considerable de -
tion in tone as the limb is flexed or extended generation usually is present in nearly all
passively. The abrupt melting away of mus - systems in the immediate vicinity of the le-
cle tone, referred to as the knife-clasp phenome- sion . By studying spinal cord sections above
non , is due to disynaptic inhibition of exten
sor or flexor motor neurons caused by
- and below the level of the lesion, it is possi
ble to predict fairly closely the level of the
-
stimulating Golgi tendon organs in passively lesion .
stretching the involved muscles.
Bladder and bowel functions are disturbed SPINAL HEMISECTION
in all transections of the cord , for they are no
longer under voluntary control . Interruption Spinal cord hemisection is less common
of descending autonomic fibers, particularly than complete cord transection . When pre-
those en route to parasympathetic nuclei in sent it produces a Brown- Sequard syndrome , a
Posterior white column

( ipsilateral symptoms
below level of lesion )
Lesion
Txn
Lateral spinothalamic tract

( bilateral loss of pain and
temperature in segment (s) of
lesion , contralateral loss
of these sensory modalities
Intact fibers
Lateral
spinothalamic
Ventral root fibers Degenerated
tract
( ipsilateral lower motor fibers
neuron syndrome in
segments of lesion
Lateral
( ipsilateral upper motor
Intact anterior
neuron syndrome below spinothalamic
level of lesion)
Anterior spinothalamic tract

( ipsilateral light touch present
below level of lesion but diminished )
Figure 11.27. Degeneration associated with a spinal cord hemisecflon. Such a lesion produces the Brown-Sequdrd
syndrome. The mojor degeneration occurs on the side of the lesion with ascending tracts degenerated above the le-
sion and descending tracts degenerated caudal to it . If the lesion involves only one spinal level, contralateral degen-
eration would be minimal and confined to crossed fibers drising from the involved segment . Arrows indicate direction
of Impulse conduction, while broken lines indicate degenerated tracts
highly characteristic clinical entity which is on the side of the lesion and conforms to the
instructive for teaching purpose ( Fig. 11.27). same principle as described for complete
This type of lesion is not associated with a pe- spinal cord transection (5, in Fig. 11.26 and
riod of spinal shock, and the neurologic dis- Fig. 11.27). However, if the lesion involves
turbances are different . On the lesion side of several spinal segments, a small amount of
the cord , the following are found below the degeneration may be detected in the con-
lesion site: (a ) an upper motor neuron syn- tralateral spinothalamic tracts, and in the an-
drome, ( b) greatly impaired discriminatory
tactile sense, (c) loss of kinesthetic sense, and
terior spinocerebellar tract, if the lesion in
volves lumbar spinal segments.
-
( d ) reduced muscle tone. At the level of the Complete and incomplete transections of
lesion there usually is bilateral impairment of the human spinal cord may result from mis-
pain and thermal sense and variable degrees sile wounds or fracture-dislocation of verte-
of lower motor neuron involvement depen- brae. Similar damage may follow ischemic
dent on the size of the lesion. Contralateral to necrosis due to occlusion or interruption of
the lesion there is loss of pain and tempera - radicular arteries that supply the vulnerable
ture sensibility, usually beginning one or two upper thoracic segments ( Fig. 4.1) of the
segments below the level of the lesion . Sen - spinal cord ( 26, 136, 240). Neoplasms also
sory disturbances contralateral to the lesion may compress the spinal cord and secondar-
are due to interruption of crossed ascending ily compromise the blood supply. In such
fibers of the spinothalamic tracts. spinal cord lesions, the symptoms are severe
The spinal degeneration seen in the and the complications are numerous, regard -
Brown-Sequard syndrome is almost entirely less of the level of injury.
11 Spinal C o r d: Fiber Tracts 409
Spinal Cord Syndromes of the disease. Fasciculations (i.e., involun-

tary twitching of muscle fascicles) in affected
AMYOTROPHIC LATERAL SCLEROSIS muscles can be observed and felt by the pa -
This spinal cord disease involves both tient and the examiner. Myotatic irritability of
upper and lower motor neurons. It is a pro- affected muscles persists until atrophy is
gressive degenerative disease of unknown complete. Late in the course of this progres-
etiology which occurs with greatest fre- sive disease, functional disturbances of the
quency in the 5th and 6th decades of life, and bladder and bowel may appear due to injury
is characterized by degeneration and de- descending fibers en route to lumbar and
myelination of the corticospinal tracts and sacral segments of the cord ,
degeneration of anterior horn cells bilaterally
at some segmental levels. When degeneration C O M B I N E D SYSTEM DISEASE
of anterior horn cells begins in the cervical re-
gion ( Fig. 11.28), the disease manifests itself This disease represents the neurologic
by progressive muscular atrophy in the manifestations of pernicious anemia . It in-
upper extremities, usually in the small intrin- volves degenerative changes in peripheral
sic hand muscles, and spastic weakness of the nerves and in the central nervous system . The
muscles of the trunk and lower extremities, anemia and the degenerative changes in the
Muscular weakness usually is symmetric and nervous system result from a deficiency of vi-
becomes generalized in the terminal phases tamin B12. A defect in gastric secretion de-
Lateral corticospinal tract
Descending autonomic fibers

from higher levels
B i l a t e r a l lower m o t o r
neuron syndrome of all
s k e l e t a l m m. s u p p l i e d b y
anterior horn cells within
s e g m e n t s o f l e s i o n.
(e. g. s m a l l m m. o f h a n d)
Bilateral upper motor neuron

syndrome of cord segments
May result in symptoms
of visceral disturbance
(e g. b l a d d e r, r e c t u m )
Lesion 1 1
C 2E H - T I
Figure 11.28. Spinal cord pathology In amyotrophic lateral sclerosis, a syndrome that involves both upper and lower
motor neurons Although the upper motor neuron lesion may involve all spinal levels, lower motor neuron involvement
initially may be localized at particular levels Arrows Indicate direction of impulse conduction and broken lines indi-
cate degenerated nerve fibers.
prives these patients of an enzyme specifi- SYRINGOMYELIA

cally required for absorption of vitamin B12.
Peripheral nerves and spinal tracts undergo This is a chronic disease characterized
varying degrees of degeneration . The degen- pathologically by long cavities, surrounded
eration in the spinal cord appears to affect by glial elements, that develop in relationship
especially the posterior white columns and to the central canal of the spinal cord . These
the corticospinal tracts, but it is not confined cavities may extend into the medulla (sy-
to these systems ( Fig. 11.29 ). Patients have ringobulbia ). Syringomyelia probably is re-
both sensory and motor disturbances. The lated embryologically to an abnormal closure
sensory disturbances include numbness and of the central canal. Incomplete closure of the
tingling, “ pins and needles" sensation , loss central canal may leave cavities around
of position sense, and loss of vibratory sense. which a secondary gliosis develops. Charac-
These sensory disturbances are greatest in teristically syringomyelia involves the lower
distal portions of the extremities and tend to cervical and upper thoracic regions of the
be symmetric. There is little impairment of spinal cord . The affected region of the spinal
tactile, thermal , or pain sense. Weakness in cord is enlarged and transverse sections re-
the lower extremities is common, and the veal a large irregular cavity containing a clear
gait may be spastic and ataxic. The myotatic or yellow fluid .
reflexes in the lower extremities usually are The hallmark of this disease is an early im-
reduced while those in the upper extremity pairment, or loss, of pain and thermal sense
are normal. The sign of Babinski can be with preservation of tactile sense. This selec-
elicited bilaterally . Moderate muscular wast- tive loss of pain and thermal sense, fre-
ing usually occurs in the late stages of the quently noted first in the hands and forearms,
disease. results from interruption of decussating sen-
Biloteral posterior white column syndrome

( loss of discriminatory sense ; conscious
proprioception; locomotor ataxia , etc .
t
3
' J- Posterior spinocerebellar tract
( may be partial or total )
Descending autonomic fibers

from higher centers
Lateral corticospinal tract

involved on both sides ( bilateral
cvm - Ti upper motor neuron syndrome
in segments below level of lesion )
Figure 11 29 Spinal degeneration seen in combined system disease, a neurologic manifestation of pernicious ane-
mia. Ascending fibers in the posterior columns and descending systems in the lateral funiculus are affected early but
other tracts and peripheral nerves may be involved. Spinal degeneration is fairly symmetric. Arrows and broken lines
indlcdte fiber systems which degenerate In the syndrome The extent of degeneration in the posterior spinocerebellar
tract is variable.
sory fibers ( i.e., spinothalamic tracts ) in sev- that have crossed in spinal cord segments ei-
eral consecutive segments. This kind of sen- ther above or below the area of the lesion . In
sory loss is referred to as a "dissociated sen - this case, the lateral extension of the cavity
sor)' loss" because other forms of sensation also destroys the anterior ( ventral ) gray horn
are preserved . Later the cavity may enlarge in and nerve fibers passing through it ( Fig.
a lateral, posterior, cranial, or caudal direc- 11.30 ). A patient with such a lesion would
tion, destroying adjacent fiber tracts or gray have symptoms and signs of a unilateral
matter. An example of such a case is illus - lower motor neuron lesion and a Horner's
trated in Figure 11.30. Here the lesion inter- syndrome, in addition to the classic sensory
rupts the crossing fibers of the lateral disturbances. These neurologic findings aid
spinothalamic tract in spinal segments C8 in localizing the lesion to spinal segments C8
and Tl . Axons distal to the lesion are sepa - and Tl .
rated from their cells or origin and undergo
degeneration ( broken lines in Fig. 11.30). De- OTHER SPINAL SYNDROMES
struction of these crossing fibers from both
sides of the spinal cord results in a bilateral There are many varieties of spinal cord le-
loss of pain and thermal sense in the distribu - sions and syndromes in addition to those
tion of spinal nerves and dermatomes of C8 briefly described previously. Tabes dorsalis ( lo-
to Tl . All pain and temperature fibers of Tl comotor ataxia ) is a central nervous system
are destroyed , but some of the C8 fibers are form of syphilis which produces degeneration
spared inasmuch as a few fibers ascend in the in the central processes of dorsal root ganglion
dorsolateral tract ( Lissauer's tract ) and cross cells. This results in extensive demyelination
in the C7 spinal segment. This type of lesion and degeneration of fibers in the fasciculus
results in a "dissociated sensory loss" as de - gracilis. There is no unanimity of opinion as to
scribed earlier. The remainder of the lateral why the degenerative lesions in tabes dorsalis
spinothalamic tract contains normal fibers have this selective character. The principal
To dilator smooth muscle

fibers of iris
Postganglionic symp . nerve fiber
Lateral spinothalamic
\ Superior cervical symp ganglion
tracts
i Middle cervical symp ganglion
! '• /!/ ) ^ Interrupted preganglionic symp nerve

fiber ( produces ipsilateral Horner ’ s
syndrome )
Lesion
A csm- Ti \
Bilateral loss of pain
and temperature within
\
segments of lesion . These

r. c>
—
Ipsilateral lower motor neuron
4 lesion in distribution of spinal
nerves CHH - TI ( muscles of
forearm and hand )
Inferior cervical sympathetic

ganglion
sensory modalities are

preserved above and
below lesion .
Figure 11.30. Syringomyelia with lateral extension of the cavity into anterior gray horn of spinal cord Arrows show di-
rection of impulse conduction and broken lines indicate degenerate nerve fibers .
symptoms of tabes are attributable to degener- Multiple sclerosis is a demyelinating disease

ation and irritation of dorsal root fibers. Sen- of unknown etiology characterized by widely
sory loss, impairment of position and vibra - disseminated lesions in the central nervous
tory sense, radicular pains, and paresthesias system . This disease, which affects young
all are related to involvement of dorsal root adults, frequently involves the white matter
fibers. Ataxia and difficulty in walking are re- of the brain and spinal cord, but there is noth -
lated to loss of position and kinesthetic sense. ing selective about the location of the lesions.
The patient compensates for these deficits by Early manifestations of the disease are fol -
walking on a broad base with eyes directed to lowed by conspicuous improvement , but re-
the ground . Muscle tone is greatly reduced lapses are a striking and constant feature of
and the myotatic reflexes in the lower extremi - the disorder .
ties are greatly diminished or absent .
References 12. Asanuma H, Zarzecki P, of the rat cerebellum Brain Res

Jankowska E , Mongo T, Marcus S. -
1991;556:297 302.
1 Akaike T. Neuronal organization Projection of individual pyramidal 23. Blomqvist A , Berkley KJ . A re-
of the vestibulospinal system in the
cat Brain Res 1983, 259:217-227.
tract neurons to lumbar motoneu -
ron pool of the monkev . Exp Brain
examination of the spino-reticulo
diencephalic pathway in the cat .
-
2. Akaike T, Fanardjian VV , Ito M , -
Res 1979;34:73 89. -
Brain Res 1992;379:17 31 .
Ohno T. F.lectrophysiological 13. Babinski ). Sur le reflexe cutane 24 . -
Boivie J . Terminations of the cervi
analysis of vestibulospinal reflex plantaire dans certaines affections cothalamic tract in the cat : an ex-
pathways of rabbit . II . Synaptic ac- organiques du systeme nerveux perimental study with silver im-
tions upon spinal neurones. Exp central. C K Soc Biol ( Paris ) pregnation methods. Brain Res
-
Brain Res 1973;17:497 515. -
1896;48:207 208. -
1970;19:333 360.
3. Akintunde A , Buxton DF. Origins 14 . Bacon SJ , Zagon A , Smith AD. 25. Boivie J . The terminations of the
and collateralization of corticospinal , Electron microscopic evidence of a spinothalamic tract in the cat : an
corticopontine, corticorubral and monosynaptic pathway between experimental study with silver im -
corticostriatal tracts: a multiple ret - cells in the caudal raphe nuclei and pregnation methods. Exp Brain
rograde fluorescent tracing study. sympathetic preganglionic neu - -
Res 1971;12:331 353.
Brain Res 1992;586:208 218.- rons in the rat spinal cord. Exp 26. Bolton B. The blood supply of the
-
4 . Albe Fessard D. Levante A . Lam - Brain Res 1990;79:389-602. human spinal cord . ) Neurol Psy -
our Y . Origin of spinothalamic I 3 Barnes S. Degenerations in hemi - chiatry 19392 IV 118
tract in monkeys. Brain Res 1974 ; plegia : with special reference to a 27. Bowker RM , Weslund KN , Coulter
65:503-509.
5. Altman J , Carpenter MB. Fiber pro-
ventrolateral pyramidal tract , the JD. Origins of serotonergic pro -
accessory fillet and Pick's bundle jections to the spinal cord in
jections of the superior colliculus
in the cat . J Comp Neurol 1961 ;
- . .
Brain 1901;24:463 501
16. Basbaum Al , Clanton CM Fields
-
rat : an immunocytochemical retro
grade transport study . Brain Res
-
116:157-178. -
HI.. Opiate and stimulus produced 1981;226:187- 199.
6. Amoroso EC, Bell FR, Rosenberg analgesia: Functional anatomy of 28. Bowker RM , Westlund KN , Coul -
M . The relationship of the vasomo- medullospinal pathways. Proc ter ) D Serotonergic projections to
tor and respiratory regions in the Natl Acad USA 1976; the spinal cord from the midbrain
medulla oblongata of the sheep. J 73:4683-4688. in the rat: an immunocytochemical
Physiol ( Lond ) 1954;126:86-95. 17. Basbaum AI , Clanton CH , Fields and retrograde transport study
7. Andersson S. Projection of differ- III.. Three bulbospinal pathways Neurosci Lett 1981 ;24:221 -226.
ent spinal pathways to the second from the rostral medulla of the cat: 29. Bowsher D. Termination of the
somatic sensory area in cat . Acta an autoradiographic study of pain central pain pathway: the con -
Physiol Scand 1962;56(Suppl 194 ) : modulating systems. J Comp Neu - scious appreciation of pain. Brain
-
1 74. rol 1978;!78: 2(19-224 1957;80:606-622.
8. Antonetty CM, Webster KE. The 18. Basbaum Al , Ralston DD, Ralston 30. Bowsher D. The termination of sec -
organization of the spinotectal pro- IIJ . Bulbospinal projections in the ondary somatosensory neurons
jection : an experimental study primate: a light and electron mi - within the thalamus of Macaca mu -
in the rat . ) Comp Neurol croscopic study of a pain modulat - latto: an experimental degeneration
-
1975;163:449 465. ing system. I Comp Neurol study. J Comp Neurol 1961;
9. Apkarian AV , Hodge CJ . Primate -
1986;230:311 323. 177:213-227.
spinothalamic pathways: 1. a quan - 19. Batton RR 111, Javaraman A, Rug - 31 . Brodal A . Spinal afferents to the
titative study of the cells of origin giero D, Carpenter MB. Fastigial lateral reticular nucleus of the
of the spinothalamic pathway . ) efferent projections in the monkey: medulla oblongata in the cat: an
Comp Neurol 1989;288:447-473. an autoradiographic study . J Comp experimental study . J Comp Neu -
10. Armstrong DM , Schild RF. Spino- Neurol 1977;174:281-306. -
rol 1949;91:259 295.
olivary neurons in the lumbo- 2D. Bernhard CC, Bohm E. Cortical 32. Brixial A .. The reticular formation
sacral cord of the cat demonstrated representation and functional sig - of the brain stem . Anatomical as -
by retrograde transport of horse- nificance of the corticomotoneu - pects and functional correlations.
radish peroxidase. Brain Res ronal system . Arch Neurol Psychi - Springfield . IL: Charles C. Thomas,
1979;168: 176-179. atry 1934;72:473-302. 1937
11. Arvidsson U, Ulfhake B, Cullheim 21. Berretta S, Perciavalle V, Poppele 33. Brixial A . Anatomy of the vestibu -
-
-
S, et al . Thyrotropin releasing hor-
mone ( TRH ) like immunoreactiv -
RE. Origin of spinal projections to
the anterior and posterior lobes of
lar nuclei and their connections. In :
Komhuber Mil , ed MandKx > k of
ity in the grey monkev ( Macaca fas
cicularis ) spinal cord and medulla
- the rat cerebellum. J Comp Neurol
1991;303:273-281 .
sensory physiology: vestibular sys-
tem . Vol . 6. Berlin: Springer- Ver -
oblongata with special emphasis 22. Berretta S, Perciavalle V, Poppele lag, 1974:239-352.
on the bulbospinal tract. J Comp RE. Origin of cuneate projections 34. Brodal A. Neurological anatomy in
-
Neurol 1992;322:293 310. to the anterior and posterior lobes relation to clinical medicine. 3rd
ed . New York: Oxford University ropharmacologv. 6th ed . New corticospinal projections from the
Press, 1981. York: Oxford University Press, premotor areas in the frontal lobe.
35. Brodal A , Pompeiano O, Walberg 1991. |Neurosci 1991;11:667 689. -
F. The vestibular nuclei and their .
50 Cooper S, Sherrington CS. Gower's .
65 Duron B Postural and ventilatory
connections, anatomy and func- tract and spinal border cells. Brain functions of intercostal muscles.
tional correlations. Springfield , IL: 1940;63:123-134. Acta Neurobiol Exp ( Wars/ )
Charles C. Thomas, 1962 . 51. Coote Jll . Bulbospinal serotonergic 1973;33:355 380.-
36. Brodal A, Walberg F, Blackstad T. pathways in the control of blood 66. Edwards SB. The ascending and
Termination of spinal afferents to pressure. | Cardiovasc Pharmacol descending projections of the red
inferior olive in cat J Neurophvsiol 1990/ 1 5: 33-41 . nucleus in the cat: an experimental
1950;13:431-454 . 52. Coulter JD, Ewing I , Carter C. Ori - study using an autoradiographic
37. Burton H , Loewy AD. Projections gin of primary sensorimotor corti - tracing method . Brain Res 1972;
to the spinal cord from medullary cal projections to lumbar spinal 48:45-63.
somatosensory relay nuclei , j cord of cat and monkey. Brain Res 67. Eldred E, Fujimori B. Relations of
-
Comp Neurol 1977; 173:773 792. -
1976;103:366 372. the reticular formation to muscle
38. Busch HI M An anatomical analy - 53. Coulter JD, Jones EG . Differential spindle activation . In: Jaspers I III ,
sis of the white matter in the brain distribution of corticospinal projec- Proctor I .D, Knighton RS, Noshay
stem of the cat |Thesis|. University tions from individual cyloarchitec- WS, Costello RT, eds Reticular for -
of Leiden . Leiden : Van Gorcum , tonic fields in the monkey. Brain mation of the brain . Boston: l ittle,
1961. Res 1977;129*335 340 . Brown and Company , 1958:
39. Caine DB. Pallis CA . Vibratory 54 Courville |. Rubrobulbar fibers to 275-283.
sense: a critical review . Brain the facial nucleus and the lateral .
68. Eldred F., Granit R Merton PA
1966;89:723-746. reticular nucleus ( nucleus of the Supraspinal control of the muscle
.
40. Carlton SM Honda CN , Willcock
son WS, et al . Descending adrener -
- lateral funiculus ): an experimental
study in the cat with silver impreg -
spindles and its significance. J
Physiol ( Lond ) 1953;122:498 523. -
gic input to the primate spinal cord nation methods. Brain Res 69. Flumerfelt BA , Otabe S, Courville
and its possible role in modulation 1966;1:317-337. |. Distinct projections to the red
of spinothalamic cells. Brain Res 55. Courville J . Somatotopical organi- nucleus from the dentate and inter -
1991;543:77-90. zation of the projection from the posed nuclei in the monkey. Brain
41. Carpenter MB. Fiber projections nucleus interpositus anterior of the Res 1973;50:408-414 .
from the descending and lateral cerebellum to the red nucleus: an 70. Foerster O, Gagel O, Sheeman D.
vestibular nuclei in the cat . Am J experimental study in the cat with Veranderungen an den Endosen
Anat 1960;107:1-22. silver impregnation methods. Exp im Riickenmark des Affen nach
42. Carpenter MB. Upper and lower Brain Res 1966;2:191-215. I linterwurzeldurschschneidung. Z
motor neurons. In : Downey JA, 56. Courville J , Brodal A . Rubrocere - Anat Entwickl -Gesch 1933; 101:
Darling RC , eds. Physiological bellar connections in the cat: an ex - -
553 565.
basis ot rehabilitation medicine. perimental study with silver im - 71. Fung SJ, Manzoni D, Chan JY, Pom -
Ch. 1 . Philadelphia : W . B. Saun - pregnation methods. J Comp peianoC ), Barnes CD . Locus aieruleus
.
ders 1971:3-27. Neurol 1966;126:471-485. control of spinal motor output. Prog
43. Carpenter MB, Ailing FA , Bard DS. 57. Courville J , Otabe S. The rubro-oli - -
Brain Res 1991;88:395 409.
Lesions of the descending vestibu - varv projection in the Macaque: An 72. Fukushima K , Peterson BW,
lar nucleus in the cat . J Comp Neu - experimental study with silver im- Uchino Y , Coulter JD, Wilson VJ .
rol 1960;114:39-50. pregnation methods. J Comp Neu - Direct fastigiospinal fibers in the
44 . Carpenter MB. Stein BM , Shriver -
rol 1974;158:494 497 cat . Brain Res 1977;126:538-542.
|E. Central projections of spinal 58. Craig AD Jr . Spinal and medullary 73. Giuffrida R , Rustioni A . Glutamate
dorsal roots in the monkey. II . input to the lateral cervical nu - and aspartate immunoreactivity in
Lower thoracic, lumbosacral and cleus. J Comp Neurol 1978; corticospinal neurons of rats. J
coccygeal dorsal roots. Am J Anat 181:729-743. Comp Neurol 1989;288:154-164 .
1968;123:75- 118. 59. Craig AD Jr, Burton II . The lateral 74 . Granit R . Receptors and sensory
45. Caverson MM , Ciriello J , Calaresu cervical nucleus in the cat : perception. New Haven , CT: Yale
FR . Direct pathw'av from cardio- Anatomical organization of cervi - University Press, 1955.
vascular neurons in the ventrolat - cothalamic neurons. J Comp Neu - 75. Grant G . Projection of the external
eral medulla to the region of the in - rol 1979;185:329-346. cuneate nucleus onto the cerebel -
termed iolateraI nucleus of upper 60. Craig AD Jr, Tapper DN. Lateral lum in the cat: an experimental
thoracic cord : an anatomical and cervical nucleus in the cat: Func- study using silver methods. Exp
electrophysiological investigation tional organization and character - Neurol 1962;5:179-195.
in the cat . I Aut Nerv System istics. J Neurophysiol 1978; 76. Grant G . Spinal course and soma -
-
1983;9:451 475.
46. Clark FM , Proudfit HK . The pro-
-
41:1511 1534.
61 . Cummings JF, Petras JM . The ori -
totopically localized termination of
the spinocerebellar tracts: an ex -
jection ot noradrenergic neurons in gin of spinocerebellar pathways. I . perimental study in the cat .
the A7 catecholamine cell group to The nucleus cervicalis centralis of Acta Physiol Scand 1962;56(SuppI
the spinal cord in the rat demon - the cranial cervical spinal cord. J 193 ) 1 (5
strated by anterograde tracing Comp Neurol 1977;173:655-692. 77. Grant G , Rexed B. Dorsal spinal
combined with immunocytochem - 62. Dahlstrom A, Fuxe K . Evidence for root afferents to Clark 's column.
istry . Brain Res 1991 ;547:279-288 the existence of monoamine con - - Brain 1958;81 :567-576.
47. differ KD, Burstein R . Giesler GJ taining neurons in the central ner - 78. I la 11, Liu CN . Cell of origin of the
|r Distributions of spinothalamic, vous system . I . Demonstration of ventral spinocerebellar tract. J
spinohypothalamic, and spinote- monoamines in the cell bodies of Comp Neurol 1968;13:185 205. -
lencephalic fibers revealed by an - brainstem neurons. Acta Physiol 79. Hartmann-von Monakow K , Akert
terograde transport of PHA L in - Scand I 964;62(Suppl 232 ): 1 -55. K , Kiinzle H . Projections of the
rats. I Neurosci 199|; 11 :852 -868. 63. Dampney RAL, Czachurski I , precentral and premotor cortex to
48 Conde F, Conde IL Etude de la Dembowsky K , Goodchild AK , the red nucleus and other mid -
morphologie des cellules du noyau Seller II . Afferent connections and brain areas in Mnanu fnsaculnris .
rouge du chat par la methode de
-
Golgi Cox. Brain Res 1973;
spinal projections of the pressor re
gion in the rostral ventrolateral
- Exp Brain Res 1979;34:91 105. -
80. I linrnan A , Carpenter MB. Efferent
53:249-271. medulla of the cat .| Aut Nerv Sys - fiber projections of the red nucleus
49. Cooper JR , Bloom FE, Roth Rll. tem 1987;20:73-86. in the cat. J Comp Neurol
The biochemical basis of neu - 64. Dum RP, Strick PL. The origin of 1959;113:61-82.
81 . Hoff EC. Central nerve terminals in the medullary reticular forma - hemispherectomies on the fiber
in the mammalian spinal cord and tion and raphe nuclei projecting to components of the pyramids. |
their examination by experimental thoracic, lumbar and sacral seg - -
Comp Neurol 1945;83:113 119 .
degeneration. Proc R Soc Ser B ments of the spinal cord in the cat . 112. Lassek AM , Rasmussen C» L . The
-
1932;111:175 188 Anat Embryol ( Berlin ) 1991 ; human pyramidal tract: a fiber and
82. Hokfelt T. Fuxe K , Goldstein M , Jo- -
183:151 163. numerical analysis. Arch Neurol
hansson O. Immunohistochemical 96. Keller AD, Hare WK . The Psychiatry 1939,42:872-876
evidence for the existence of rubrospinal tracts in the monkey: 113. Liang FY , Morel V, Wiesendanger
adrenaline neurons in the rat brain. effects of experimental section. M , Rouiller EM . Corticomotoneu -
Brain Res 1974 ,66:235-251. Arch Neurol Psychiatry 1934; ronal connections in the rat : Evi -
83. I lokfelt T, Johansson O, Goldstein
M . Central catecholamine neurons
-
32:1253 1272.
97. Kerr FWL. Neuroanatomical sub -
-
dence from double labeling of mo
toneurons and corticospinal axon
-
as revealed by immunohistochem - strates of nociception in the spinal arborizations. J Comp Neurol
istry with special reference to cord . Pain 1975;1:325-356. 1991 ;311:356-366.
adrenaline neurons. In : Bjdrklund 98. Kerr FWL. The ventral spinothala - 114 . Liu CN. Afferent nerves to
A , Hokfelt T, eds. Handbook of mic tract and other ascending sys- Clarke's and the lateral cuenate
chemical neurtwnatomv. Vol. 2. tems of the ventral funiculus of the nuclei in the cat. Arch Neurol Psy -
Part 1: Classical transmitters in spinal cord. J Comp Neurol chiatry 1956;75:67-77.
the CNS. Amsterdam : Elsevier, -
1975;159:335 356.
99. King )S, Bowman Mil , Martin GF.
115. Liu CN , Chambers WW . An exper-
1984;157 276 imental study of the corticospinal
84 . Holstege JC, Bongers CM . A The red nucleus of the opossum system in the monkey ( Macaui mu -
glvcinergic projection from the ( DitUiphis nuirsupialis virginiam ): a latto ): the spinal pathways and
ventromedial lower brainstem to light and electron microscopic preterminal distribution of degen -
spinal motoneurons. An ultrastruc- studv . J Comp Neurol 1971 ; erating fibers following discrete le-
tural double labeling study in rat 143:157-184. sions of the pre- and postcentral
Brain Res 1991;566: 308- 315 100. King JS, Schwyn RC , Fox CA . The gyri and bulbar pyramid . J Comp
85. Holstege JC , Bongers CM . Ultra - red nucleus in the monkey ( Mduim Neurol 1964;113:257-284 .
structural aspects of the coeruleo- mu Inthi ): a Golgi and an electron 116. Llovd DPC, McIntyre AK . Dorsal
spinal projection. Prt »g Brain Res microscopic study' . 1 Comp Neurol column conduction of group I
-
1991;88:143 156. 1971;142:75-108. muscle afferent impulse's and their
86 Kongo T, Jankowska E , Lundberg .
101. Kojima M , Takeuchi V Goto M , relay through Clarke's column . J
A . The rubn »spinal tract . I . Effects Sano Y. Immunohistochemical Neurophysiol 1950;13:39 54.-
on alpha -motor - neurons innervat - study on the localization of sero - 117. Loewv AD, Burton H . Nuclei of
ing hindlimb muscles in cats Exp tonin fibers and terminals in the the solitary tract: efferent projec -
Brain Res 1969;7:344- 364 . spinal cord of the monkey (Macuci? tions to the lower brain stem and
87. I lubbard II Oscarsson O. Localiza - .
fuscata ) Cell Tissue Res spinal cord of the cat . J Comp Neu -
tion of the cell btKlies of the ventral -
1983;229:23 36. rol 1978; 181 :421 -450.
spiniKerebellar tract in lumbar 102. Kuang R K a l i l K. Branching pat - 118. Loewy AD, Gregorie EM , McKellar
segments of the cat . I Comp Neu - terns of corticospinal axon arbors S, Baker RP. Electrophvsiological
rol 1962;118:199-204 in the rodent. J Comp Neurol evidence that the A5 cate-
.
88. Jeske 1 McKenna KE. Quantitative -
1990;292:585 598. cholamine cell group is a vasomo-
analysis of bulbospinal projections 103. Kuhn RA . Functional capacity of tor center. Brain Res 1979;
from the rivstral ventrolateral the isolated human spinal cord . 178:196-200.
medulla: Contribution of Cl - Brain 1950;75:1-51 . 119. Loewv AD, McKellar S, Saper CB.
adrenergic and nonadrenergic neu - 104. Kuvpers HGJM . Central cortical Direct projections from the A 5 cat -
rons. J Comp Neurol 1992; projections to motor and somato - echolamine cell group to the inter -
324:1 -13 sensory cell groups. Brain mediolateral cell column . Brain
89. Jones SL. Descending noradrener- -
1960;83:161 184. -
Res 1979;174:309 314 .
gic influences on pain . Prog Brain 105. Kuvpers HGJM , Brinkman I Pre- 120. Loewy AD, Saper CB. Edinger-
Res 1991;88:381-394. central projections to different Westphal nucleus: Projections to
90 Jones SL, Light AR . Serotoninergic parts of the spinal intermediate the brain stem and spinal cord in
medullary raphespinal projection zone in the rhesus monkey. Brain thecal . Brain Res 1978;150:1-27 .
to the lumbar spinal cord in the rat:
a retrograde immunohistochemical
-.
Res 1970;24:29 48.
106. Kuvpers HGJM Lawrence IXi .
121. Loewy AD, Saper CB, Yamodis
ND. Re-evaluation of the efferent
study. J Comp Neurol 1992; Cortical projections to the red nu - projections of the Edinger - West -
322:599-610. cleus and the brain stem in the rhe - phal nucleus. Brain Res
91 . Jones BE , Holmes CJ , Rodriguez -
Veiga E, Mainville L. GABA syn --
sus monkev. Brain Res 1%7;
-
4:151 188.
-
1978;141:153 159.
122. Loewy AD, Wallach JH , McKellar
thesizing neurons in the medulla : 107. Kuvpers HGJM , Maisky VA . Ret - S. Efferent connections of the ven -
- -
their relationship to serotonin con rograde axonal transport of horse - tral medulla oblongata in the rat .
taining and spina llv projecting radish peroxidase from spinal cord Brain Re's Rev 1981;3:63 80.-
neurons in the rat . J Comp Neurol to brain stem cell groups in the cat 123. Lundberg A . Ascending spinal
-
1991;313:349 367. Neuroscience 1975;1:9-14 . hindlimb pathways in the cat. In:
92. Jones EG , Wise SP. Size, laminar 108. Lindgren S, Nordwall A, Eccles JC, Schade JP, eds. Progress
and columnar distribution of effer- Wengstrdm C. The location of the in brain research. Vol . 12. Physiol -
ent cells in the sensory- motor cor - thalamus relay in the spino cer - - ogy of spinal neurons. Amsterdam:
tex of monkeys. | Comp Neurol -
vico lemniscal path . Acta Physiol Elsevier, 1964:135-165.
-
1977;175:391 438. Scan 1965;65: 164-175. 124 McMasters RE , Weiss AH , Carpen -
.
93. Katter JT, Burstein R . Giesler C J |r .
The cells of origin ot the spinohv -
109. Lassek AM . The human pyramidal
tract. II . A numerical investigation
ter B Vestibular projections to the
nuclei of the extraocular muscles:
pothalamic tract in cats. I Comp of the Betz cells of the motor area degeneration resulting from dis-
-
Neurol 1991;303:101 112. Arch Neurol Psychiatry 1940; crete partial lesions of the vestibu -
94 . Kausz M . Distribution ot hypothal - 44:718-724. lar nuclei in the monkey . Am J
amic neurons projecting to the tho- 110. Lassek AM . The pyramidal tract: Anat 1966;118:163-194.
racic and sacral spinal segments in its status in medicine. Springfield , 125. Magoun HW, Rhines R . Spasticity:
the cat . J Hirnforsch 1990; IL: Charles C. Thomas, 1954 . -
the stretch reflex and extrapvrami -
-
31,697-703. 111 . Lassek AM , Evans JP. The human dal systems. Springfield , IL:
95. Kausz M . Arrangement ol neurons pyramidal tract. XII . The effect of Charles C. Thomas, 1947.
126. Marchi M, Algeri G. Sulle degener- thalamic and related tract. Acta 155. O' Leary JL, Kerr FWL, Gold ring S.
azioni discendenti consecutive a le - Psychiatr Neurol Scand 1951; The relation between spinoreticu -
sioni sperimentale in diverse zone 26:371-396. lar and ascending cephalic sys-
della corteccia cerebrale. Riv Sper 142. Mott FW, Sherrington CS. Experi - tems. In: Jaspers Mil , Proctor LI ).
Freniat Med Leg Alien Ment ments upon the influence of sen - Knightton , R5, et al ., eds. Reticular
1885; 11:492 494.-
127. Marlin GF, Dom R. Rubrobulbar
sory nerves upon movement and
nutrition of the limbs. Proc R Soc
formation of the brain. Boston: Lit -
tle, Brown and Company ,
projections of the opossum ( Didcl - 1895;57:481-488. 1958;187-201.
fdtiu virgitiiann ). | Comp Neurol 143. Mugnaini F., Walberg F. An experi - 156. Olszewski J , Baxter D. Cytoarchi -
1970;139:199-214. mental electron microscopical tecture of the human brain stem .
128. Massion J . The mammalian red nu - study on the mode of termination Philadelphia: J .B. Lippincott, 1954 .
cleus. Physiol Rev 1967;47:383-436. of cerebellar corticovestibular fi - 157. Orioli FL, Mettler FA . The
129 Matsushita M Spinocerebellar pro- bres in the cat lateral vestibular nu - rubrospinal tract in Maaica mulatto.
jections from the lowest lumbar cleus ( Deiters' nucleus ). Exp Brain J Comp Neurol 1956;106:299-318.
and sacral-caudal segments in the Res 1967;4:212-236. 158. Orlovsky GN . Activity of vestibu -
- lospinal neurons during locomo-
cat , as studied by anterograde
transport of wheat germ agglu
-
tinin horseradish peroxidase. J
-
144 . Mugnaini E, Walberg F, Hauglie
Hanssen E. Observations on the
fine structure of the lateral vestibu-
tion
-
Brain Rea l972tf 6£5 9&
159. Oscarsson O. Three ascending
Comp Neurol 1988;274:239-254. lar nucleus ( Deiters' nucleus ) in tracts activated from group I affer -
130. Matsushita M , Hosoya Y. The loca - the cat. Exp Brain Res ents in forelimb nerves of the cat .
tion of spinal projection neurons in 1967;4:146-186. Prog Brain Res 1964;12:179-196.
the cerebellar nuclei (cerebel - 145. Nathan PW, Smith MC. Long de- 160. Oscarsson O. Functional organiza -
lospinal tract neurons) of the cat: a scending tracts in man . I. Review -
tion of the spino and cunecxere-
study with the horseradish peroxi - of present knowledge. Brain bellar tracts. Physiol Rev
dase technique .
Brain Res 1955;78:248-303. - .
1965;45:495 522
1978;142:237-248. 146. Nicholas AP, Pieribone VA, 161 . Oscarsson O. Termination and
131 . Matsushita M . Hosoya Y , Ikeda M . Arvidsson U, Hokfelt T. Seroto- functional organization of a dorsal
Anatomical organization of the nin-, substance P- and glutamate / spino-olivocerebellar path . Brain
spinocerebellar system in the cat as aspartate-like immunoreactivities Res 1967;5:531-534.
studied by retrograde transport of in meduUo-spinal pathways of rat 162. Oscarsson O. Functional organiza -
horseradish peroxidase. I Comp and primate. Neuroscience 1992; tion of spinocerebellar paths. In :
Neurol 1979; 184:81-106. 48:545-559. Iggo A , ed . Handbook of sensory
132. Matsushita M, Ikeda M . The cen- 147. Nieuwenhuys R . Chemoarchitec- physiology. Vol . 2. Berlin:
tral cervical nucleus as cell origin ture of the brain. Berlin : Springer - -
Springer Verlag, 1973:339-380.
of a spinocerebellar tract arising Verlag, 1985. 163. Oscarsson O, Rosen I . Short - la -
from the cervical cord : a study in 148. Norrsell U, Voorhoeve P. Tactile tency projections to the cat's cere-
the cat using horseradish peroxi- pathways from the hindlimb to the bral cortex from skin and muscle
dase Brain Res 1975;100:412-417. cerebral cortex in cat . Acta Physiol afferents in the contralateral fore-
133. Matsushita M , Ikeda M, Hosoya Y. Scand 1962;54:9-17. limb. J Physiol ( U»nd ) 1966;
The location of spinal neurons 149. Nyberg- Hansen R Origin and ter - 182:164-184.
with long descending axons ( long mination of fibers from the 164 Oscarsson O, Sjdlund B. The ven -
descending propriospinal tract vestibular nuclei descending in the tral spino-olivocerebellar system in
neurons ) in the cat: a study with medial longitudinal fasciculus: an the cat. I . Identification of five
the horseradish peroxidase tech - experimental study with silver im - paths and their terminations in the
nique. J Comp Neurol 1979; pregnation methods in the cat . J cerebellar anterior lobe. Exp Brain
-
184:63 80.
134. Mehler VVR , Feferman ME, Nauta 150.
C omp Neurol 1964;122:355-368.
Nyberg- Hansen R . Sites and mode
-
Res 1977;28:469 486.
165. Oscarsson O, Uddenberg N . Iden -
WJG. Ascending axon degenera - of termination of reticulospinal tification of a spinocerebellar tract
tion following anterolateral cordo- fibers in the cat: an experimental activated from forelimb afferents
tomy in the monkey . Anat Rec study with silver impregnation in the cat . Acta Physiol Scand
1956;124:332-333. methods. J Comp Neurol 1965; -
1964;62:125 136.
135. Mehler WB, Feferman ME, Nauta 124:71-99. 166 Patterson IT, Chung K , Coggeshall
WJH . Ascending axon degenera - 151. Nyberg- Hansen R. Functional RE . Further evidence for the exis-
tion following anterolateral cordo - organization of descending tence of long ascending unmyeli -
tomy : an experimental study in the supraspinal fibre systems to the nated primary afferent fibers
monkey - Brain 1960;83:718 750. - spinal cord : anatomical observa - within the dorsal funiculus: Effects
136. Mettler FA . Neuroanatomy. St. tions and physiological correla - of capsaicin. Pain 1992;49:117- 120.
Louis: C.V. Mt >sbv, 1948. tions. Ergeb Anat Entwickl-Gesch 167. Perl ER , Whitlock DG. Somatic
137. Millar I . Topography and receptive 1966;39:1-48. stimuli exciting spinothalamic pro -
fields of ventroposterolateral thala - 152. Nyberg- Hansen R , Brodal A. Sites jections in thalamic neurons in the
mic neurones excited by afferents and mode of termination of cat and monkey. Exp Neurol
projecting through the dorsolateral rubrospinal fibres in the cat : an ex - 1961;3:256-296.
funiculus of the spinal cord . Exp perimental study with silver 168. Petras JM . Cortical, tectal and
Neurol 1973;41:303 313 - .
138. Miller RA. Strominger LN . Efferent
impregnation methods. J Anat
-
1964,98:235-253.
tegmental fiber connections in the
spinal cord of the cat. Brain Res
connections of the red nucleus in -
153. Nyberg Hansen R , Mascitti TA . 1967;6:275-324.
the brain stem and spinal cord of Sites and mode of termination of 169. Petras JM, Cummings JF. The ori -
1973;152:327-346.
-
the rhesus monkey J Comp Neurol fibers of the vestibulospinal tract in
the cat: an experimental study with
gin of spinocerebellar pathways. II
The nucleus centrobasalis of the
139 Morin F. A new spinal pathway for silver impregnation methods. J cervical enlargement and the nu -
cutaneous impulses . Am J Physiol Comp Neurol 1964;122:369 387. - cleus dorsalis of the thoracolumbar
1955;183:245 252. - 154 . Nygren LG, Olson L. A new major spinal cord . J Comp Neurol
.
140. Morin F Catalano JF. Central con- projection from the locus 1977;173:693-716.
nections of a cervical nucleus ( nu - coeruleus: the main source of nor - 170. Picket VM, Segal M. Bloom, FE. A
cleus cervicalis lateralis ) of the cat . adrenergic nerve terminals in radioautographic study of the ef -
J Comp Neurol 1955;103:17 32. - the ventral and dorsal columns of ferent pathways of the nucleus
141 Morin F. Schwartz HG, O' Leary JL. the spinal cord . Brain Res locus coeruleus. J Comp Neurol
Experimental study of the spim >- 1977;132:85-93. 1974;155:15-42.
171. Pitts RF. The respiratory center primate dorsal spinothalamic tract; MB . Central projections of spinal
and its descending pathways. J evidence for a specific termination dorsal roots in the monkey I. Cer -
Comp Neurol 1940;72:605 625.- in the posterior nuclei ( Po / SG ) of vical and upper thoracic dorsal
172. Pitts RF, Magoun IIW , Ranson SW . the thalamus. Pain 1992; -
roots. Am ) Anat 1968;123:27 74.
Localization of the medullary res - -
48:107 118. 204. Sluka KA , Westlund KN . Spinal
piratory centers in the cat . Am J 188. Reid JM, Gwvn DG , Flumerfelt BA . projections of the locus coeruleus
Physiol 1939;126:673-688. A cytoarchitectonic and Golgi and the nucleus subcoeruleus in
173. I’oggio GF, Mountcastle VB. A study of the red nucleus of the rat . the Harlan and the Sasco Sprague -
study of the functional contribu - J Comp Neurol 1975;162:337-362. Dawley rat . Brain Res 1992;
tions of the lemniscal and 189. Rexed B, Brodal A . The nucleus -
579:67 73.
spinothalamic systems to somatic cervicalis lateralis: a spinocerebel - 205. Smith MV , Apkarian AV . Thalami -
sensibility . Bull Johns Hopkins lar relay nucleus. J Neurophvsiol cally projecting cells of the lateral
Hosp 1960;106: 266-316. 1951;14:399-407. cervical nucleus in monkey. Brain
174 Poirier I .J , Bertrand C . Experimen - 190. Rinvik E, Walberg F. Demonstra - -
Res 1991 ;555:10 18.
tal and anatomical investigation of tion of a somatotopically arranged 206. Sprague ) M , Ha II . The terminal
the lateral spinothalamic and spi - cortico-rubral projection in the cat: fields of dorsal root fibers in the
notectal tracts. J Comp Neurol an experimental study with silver lumbosacral spinal cord of the cat ,
1955;102:745-757. methods. J Comp Neurol 1963; and the dendritic organization of
175. Poirier LJ , Bouvier G . The red nu - 120:393-407. the motor nuclei . In : Eccles jC,
cleus and its efferent nervous path - 191 . Rose JE, Mountcastle VB. Touch Schade JP, eds. Progress in brain
ways in the monkey , J Comp Neu - and kinesthesis. In : Fields J , ed . research . Vol. 2. Organization of
roll 966;128:233- 244 . Handbook of physiology. Sec. I , the spinal cord . Amsterdam: Else-
176. Pompeiano O. Sulle riposte postu - Vol . I : Neurophysiology. Ch . 17. vier, 19*4;121V152.
rali alia stimolazione elettrica del Washington , DC: American Physi- 207. Staal A . Subcortical projections on
nucleo rosso nel gatto decerebrato. -
ological Society, 1959:387 429. the spinal gray matter of the
Boll Soc Ital Biol Sper 1956; 192. Rossi GF, Brodal A . Corticofugal cat . The Hague: Koninkl Druk,
32:1450-1451 . fibers to the brain stem reticular -
Lankhout lmmig NV , 1 % l .
177. Pompeiano O. Analisi degli effetti formation : an experimental study 208. Stein BM , Carpenter MB . Central
della stimolazione elettrica del nu - in the cat . J Anat 1956;90:42-62. projections of portions of the
cleo rosso nel gatto decerebrato. 193. Rossi GF, Brodal A . Terminal dis- vestibular ganglia innervating spe-
Rend Accad Naz Lincei Cl Sci Fis tribution of spinoreticular fibers in cific parts of the labyrinth in
Mat Nat 1957;22:100-103. the cat . AMA Arch Neurol Psychi - the rhesus monkey . Am ) Anat
178. Pompeiano O. Organizzazione so- -
atry 1957;78:439 453. 1967;120:281-318.
matotopica delle risposte flessorie 194 . Sadun A A , Pappas GD. Develop - 209. Sterling P, Kuypers HGJM .
alia stimolazione elettrica del nu - ment of distinct cell types in the Anatomical organization of the
cleo di Deiters nel Gatto cerebrato. -
feline red nucleus: a Golgi Cox and brachial spinal cord of the cat II .
Arch Si Biol ( Bologna ) 1960; electron microscopic study. I The motoneuron plexus. Brain Res
44:497-51 .
179. Pompeiano O, Brodal A . Experi -
Comp Neurol 1978;182:315-366.
195. Saper CB, Loewy AD, Swanson
-
1967;4:16 32.
210. Taub A . Local , segmental and
mental demonstration of a somato - LW , Cowan WM . Direct hypothal - supraspinal interaction with a dor -
topical origin of rubrospinal fibers amo-autonomic connections. Brain solateral spinal cutaneous afferent
in the cat. J Comp Neurol
1957;108:225-251 196. Sasaki K,
-
Res 1976;117:305 312
Namikawa A,
system.
10:357-374.
Exp Neurol 1964;
180 . Pompeiano O, Brodal A . Spi -
novestibular libers in the cat: an
Hashiramoto S. The effect of mid -
brain stimulation upon alpha mi >-
211 . Taub A , Bishop 1*0. The spinocer
vical tract: Dorsal column linkage,
-
experimental study . J Comp Neu - toneurones in lumbar spinal cord . conduction velocity, primary affer -
-
rol 1957;108:353 382. Nippon Seirugaku Zassi I 960; ent spectrum . Exp Neurol 1965;
181 Pompeiano O, BrixJal A . The origin -
3:303 316. 13:1-21.
of the vestibulospinal fibre's in the 197. Sasaki K , Tanaka T, Mori K . Effects 212 . Thomas DM, Kaufman RP,
cat : an experimental -anatomical of stimulation of pontine and bul - Sprague JM , Chambers WW . Ex -
study, with comments on the de- bar reticular formation upon spinal perimental studies of the vermal
scending medial longitudinal fasci - motoneurons of the cat . Jpn J Phys- cerebellar projections in the brain
culus. Arch ltal Biol 1957; iol 1962;12:45-62. . ' tern of the cat ( fastigiobulbar
95:166 195. 198. Schoenen J , Grant G. Spinal cord: -
tract ), j Anat 1956;90:371 385.
182. Preston JB, Whitlock DG . Precen - connections. In: Paxinos G, ed . The 213. Torvik A , Brodal A . The origin of
tral facilitation and inhibition of human nervous system. Ch . 4 . reticulospinal fibers in the cat : an
spinal motoneurons. J Neurophvs - New York: Academic Press, experimental study. Anat Rec
iol 1960;23:154-170. 1990:77-92. -
1957;128:113 137.
183. Preston JB, Whitlock DG. Intracel - 199. Shinoda Y, Arnold A , Asanuma H. 214 . Tower SS. Function and structure
lular potentials recorded from mo- Spinal branching of corticospinal in the chronically isolated lum -
toneurons following precentral axons in the cat . Exp Brain Res bosacral spinal cord of the dog. J
gyrus stimulation in primate. J -
1976;26:215 234. Comp Neurol 1937;67:109-131.
Neurophysiol 196 l ;24:91 - 100 2 H . Shinoda Y, Ghaz C, Arnold A .
( ) 215. Trevino DL, Carstens E. Confirma -
184 . Proudfit HK , Anderson EG . Mor - Spinal branching of rubrospinal tion of the location of spinothala -
phine analgesia : blockade by raphe axons in the cat . Exp Brain Res mic neurons in the cat and monkey
magnus lesions. Brain Res 1975; -
1977;30:203 218. by the retrograde transport of
98:612-618. 201 . Shinoda Y, Ohgaki T, Futami T. horseradish peroxidase. Brain Res
.
185. Proudfit HK Clark FM . The priv - The morphology of single lateral 1975;98:177-182.
jections of locus coeruleus neurons vestibulospinal tract axons in the 216. Trevino DL, Coulter JD, Willis
to the spinal cord . Prog Brain Res lower cervical spinal cord of the WD . Location of cells of origin of
1991;88:123-141 . cat l Comp Neurol 1986; spinothalamic tract in lumbar en -
186 Rajakumar N , Hrycyshyn AW , 249:226-241. largement of the monkey. J Neuriv-
Flumerfelt BA Afferent organiza - 202. Shinoda Y , Yamaguchi T , Futami physiol 1973;36: 750-761
tion of the lateral reticular nucleus T. Multiple axon collaterals of sin - 217. Truex KC , Taylor MJ , Smythe MQ,
in the rat : an anterograde tracing gle corticospinal axons in the cat Gildenberg PL. The lateral cervical
study . Anat Embryol ( Berl ) spinal cord . J Neurophysiol nuclei of cat , dog and man J Comp
!992;185:25 17 1986;55:425-448. Neurol 1970;139:93-104.
187. Ralston HJ III , Ralston DD. The 203. Shriver JE, Stein BM , Carpenter 218. Tsukahara N , Toyama K , KOsaka
K . Electrical activity of red nucleus 227. Walberg F, Jansen J . Cerebellar cor - 235. Wilson VJ , Yoshida M . Mono -
neurones investigated with micro-
.
electrodes Exp Brain Res 1967;
ticovestibular fibers in the cat . Exp
- .
Neurol 1961;3:32 52
synaptic inhibition of neck moto
neurons by the medial vestibular
-
4:18-33. 228. Walberg F, Pompeiano O, Brodal nucleus. Exp Brain Res 1969;
219. Twitchell TE. Sensory factors in A, Jansen J . The fastigiovestibular 9:365-380.
purposive movement . J Neuro- projection in the cat: an experimen - 236. Xu Q, Grant G . The projection of
physiol 1954;17:239 252.- tal study with silver impregnation spinocerebellar neurons from the
220. Verhaart WJC, Kramer W . The un- methods. J Comp Neurol 1962; sacrococcygeal region of the spinal
crossed pyramidal tract . Acta Psy - 118:49-75. cord in the cat . An experimental
chiat Neurol Scand 1952; 229. Weil A , Lassek A. A quantitative study using anterograde transport
27:181-200. distribution of the pyramidal tract of WGA - HRP and degeneration.
221 . Voogd j, Feirabend HKP, Schoen in man. Arch Neurol Psychiatry Arch Ital Biol 1990;128:209-228.
JHR. Cerebellum and precerebellar 1929;22:495-510. 237. Yeomans DC, Clark FM, Paice JA ,
nuclei. In : Paxinos G, ed . The 230. Westlund KN, Bowker KM , Ziegler Proudfit UK Antinociception in -
human nervous system. Ch . 14 . MG, Coulter JD. Origins and ter - duced by electrical stimulation of
New York: Academic Press, minations of descending noradren - spinally projecting noradrenergic
1990:321-386. ergic projections to spinal cord of neurons in the A7 catecholamine
222. Walberg F. Descending connec - monkey. Brain Res 1984;292:1-16. cell group of the rat . Pain
tions to the inferior olive: an exper - 231 . Westlund KN, Coulter JD. De- -
1992;48:449 461 .
imental study in the cat . J Comp scending projections of the locus 238. Yoshida A , Sessle BJ , Dostrovsky
Neurol 1956;104:77-173. coeruleus and subcoeruleus / me- JO, Chiang CY. Trigeminal and
223. Walberg F. On the termination of dial parabrachial nuclei in mon - dorsal column nuclei projections to
rubrobulbar fibers: experimental key: axonal transport studies and the anterior pretectal nucleus in
observations in the cat . J Comp
Neurol 1958;110:66-73.
—
dopamine hydroxylase
munocvtochemistry . Brain Kes Rev
im- the rat. Brain Res 1992;590:81-94 .
239. Zhuo H, Fung SJ, Reddy VK ,
224. Walberg F. Cerebellovestibular re- 198Q2 235 264 Barnes CD. Immunohistochemical
lations: anatomy. Prog Brain Res 232. Whitlock DG, Perl ER . Thalamic- evidence for coexistence of methio-
1972;37:361-376. projections of spinothalamic path - -
nine enkephalin and tyrosine hy -
225. Walberg F, Bowsher D, Brodal A . ways in monkey . Exp Neurol droxylase in neurons of the locus
The termination of primary 1961;3:240-255. coeruleus complex projecting to
vestibular fibers in the vestibular 233. Wilson VJ , Peterson BW . Periph - the spinal cord of the cat. J Chem
nuclei in the cat: an experimental eral and central substrates of -
Neuroanat 1992;5:1 10.
study with silver methods. J Comp vestibulospinal reflexes. Physiol 240. Zulch KJ . Mangeldurchblutung an
Neurol 1958;110:391 -419. Rev 1978;58:80-105. der Grenzzone zweer Gefassgebi -
226. Walberg F, Brodal A . Spinopontine 234. Wilson VJ, Uchino Y, Susswein A, ete als Ursache bisher ungeklarter
fibers in the cat: an experimental Fukushima K. Properties of direct Ruckenmarksschadigungen . Dtsch
study. J Comp Neurol 1953; fastigiospinal fibers in the cat . Z Nervenheilk 1954;172:81-101 .
99:251-288. Brain Res 1977;126:543-546.
Section V
Brainstem and Cerebellum
12
Medulla
The medulla ( myelencephalon ), the most niscus, (0 the gradual replacement of spinal
caudal segment of the brainstem, represents a fibers in the zone of Lissauer by fibers of the
conical, expanded continuation of the upper spinal trigeminal tract, and (g) the develop-
cervical spinal cord . Externally, the transition ment of cranial nerve nuclei.
from the spinal cord to the lower medulla is
gradual, without sharp demarcation. The SPINOMEDULLARY TRANSITION
caudal limit of the medulla is rostral to the
highest rootlets of the first cervical spinal Transverse section at the junction of the
nerve at about the level of the foramen mag- spinal cord and the medulla ( Fig. 12.3) resem -
num. Above the level of transition, the ble those of the upper cervical spinal seg-
medulla increases in size and its external fea- ments. The substantia gelatinosa has in-
tures become distinctive. Changes in the ex- creased in size, and coarse descending fibers
ternal appearance of the medulla are due of the spinal trigeminal tract, which replace
chiefly to structural rearrangement and de- spinal fibers in the zone of Lissauer, are
velopment of structures peculiar to the found lateral to it. These fibers arise from
medulla. The development of the fourth ven- cells of the trigeminal ganglion, enter the
tricle causes structures previously located brainstem at pontine levels, and descend cau-
posteriorly to be shifted posterolaterally, dally in the posterolateral part of the brain -
while the appearance of the pyramids on the stem as far as the second cervical segment
anterior surface partially obliterates the ante- ( Fig. 12.9). The substantia gelatinosa gradu -
rior median fissure. The oval eminences pos- ally becomes the spinal trigeminal nucleus at
terolateral to the pyramids, produced by the high cervical levels, and this nucleus retains
inferior olivary nuclei, give the medulla the same relative position and size through-
above the zone of transition a characteristic out the medulla . Descending trigeminal
configuration. The gross features of the brain- fibers terminate directly, or by collaterals, in
stem are shown in anterior and posterior parts of the spinal trigeminal nucleus.
views in Figures 12.1 and 12.2. A conspicuous increase in the gray matter
Internally, changes in the transition from surrounding the central canal is evident ( Figs.
the spinal cord to the medulla are the follow- 12.3 and 12.4). The lateral corticospinal tract
ing: (a ) the development of the fourth ventri- has become clearly separated from the medial
cle, representing the rostral continuation of longitudinal fasciculus by its passage into the
the central canal of the spinal cord, ( b) the de- posterior part of the lateral funiculus. It is bro-
cussation of the medullary pyramids (decus- ken into a number of obliquely or transversely
sation of the corticospinal tract ), (c) the termi- cut bundles, between which are strands of
nation of the fasciculi gracilis and cuneatus gray matter. A few fibers of the spinal portion
upon their respective nuclei and the decussa- of the spinal accessory nerve can be seen arch-
tion of the internal arcuate fibers to form the ing posterolaterally to emerge from the lateral
medial lemniscus, (d ) the replacement of but- aspect of the spinal cord between the dorsal
terfly-shaped central gray matter of the spinal and ventral roots ( Fig. 12.3). Axons of somatic
cord by large cellular aggregations interlac- motor neurons in the anterior horn emerge as
ing fibers constituting the reticular formation, ventral root fibers of the first cervical spinal
(e) the termination of the ascending first nerve. Rostrally these cells extend into the
order fibers contained in the fasciculi gracilis lower medulla ( Fig. 12.6) where they consti-
and cuneatus upon their respective nuclei, tute the supraspinal nucleus (89). Fiber tracts in
and the decussation of the internal arcuate the white matter have the same arrangement
fibers to form the second order medial lem- as in cervical spinal segments.
421
422 Section V Brainstem and Cerebellum
Optic nerve
Optic chiasm 2 Anterior perforated substance
Infundibulum
Optic tract
Oculomotor nerve
Mammillary body Crus cerebri
Trochlear nerve - Trigeminal nerve

Pons
Facial nerve
Abducens nerve
Vestibulocochlear nerve
Glossopharyngeal nerve
) Vagus nerve
Hypoglossal nerve Spinal accessory nerve
Pyramidal decussation Ventral root C|
Figure 12.1. Anterior aspect of the medulla, pons, and midbrain
Corticospinal Decussation into the anterior funiculus of the spinal cord

( Figs. 11.12 and 11.14). In a graded series of
The most conspicuous features of the spi- ascending sections, the corticospinal decussa-
nomedullary transition ( Figs. 12.4 and 12.5) tion is seen in reverse sequence.
are the decussation of the corticospinal tracts, The corticospinal decussation forms the
the first appearance of the nuclei of the poste- anatomic basis for the voluntary motor con-
rior columns, and the development of the trol of one-half of the body by neuronal sig -
medullary reticular formation. The central nals from the contralateral cerebral cortex.
gray matter has increased in size and lies Injury of this tract anywhere above the decus -
mostly dorsal to the central canal. sation may cause upper motor neurons paral -
Fibers in the medullary pyramid cross the ysis of the contralateral extremities. For rea-
midline in large fascicles anterior to the cen- sons that will be clear when the motor cortex
tral gray matter and project posterolaterally is studied, the consequences of lesions con -
across the base of the anterior horn . Interdigi- fined to axons of the corticospinal tract in the
tating bundles, often of unequal size, project medullary pyramid have been of great inter-
downward and posteriorly so that in trans- est. Due to the nature of the blood supply of
verse sections most of the bundles are cut the region, it is rare in humans to encounter a
obliquely. The crossed fibers of the corti- lesion limited to the pyramid , and the motor
cospinal tract, which account for as much as deficit is usually a contralateral paresis spar-
90% of all corticospinal fibers, descend as the ing the face ( medial medullary syndrome). In
lateral corticospinal tract in the posterior part those rare cases with relatively little damage
of the lateral funiculus ( Figs. 11.11-11.13). beyond the pyramid , the paresis usually is
Fibers of the anterior corticospinal tract retain accompanied by spasticity after an initial pe -
their original position and project uncrossed riod of flaccidity (165). In monkeys, it is pos-
12 Medulla 423
m Ventricle
Stria medullaris
Pineal body Habenula
Pulvmar Brachium
Superior colliculus
Lateral geniculate
body
- Inferior colliculus
Cerebellar peduncles
Colliculus
Superior — Superior
—
Middle
Inferior
Inferior
Trochlear n
Lateral aperture
Vestibular area
Medial eminence Stria medullaris ( HZ vent )
Facial colliculus
Tuberculum
Triqonum Cuneatus
Vagi Gracilis
Hypoglossi
Fasciculus
Obex —' '
Cuneatus
Post intermediate sulcus Gracilis
\
^
Post median sulcus

Figure 12.2. Posterior aspect of the brainstem with the cerebellum removed
sible surgically to interrupt the pyramid with

minimal damage to the adjacent medulla
—
12.4 12.7). This nucleus is capped dorsolater-
ally by descending fibers of the spinal trigemi-
( 65,195, 208) . In these studies, there was a nal tract , which terminate in corresponding
modest impairment of contralateral limb parts of this nucleus. The anterior horn, still
movement , most noticeable in the distal limb recognizable at this level, contains groups of
joints, and hypotonia . The major deficit was motor neurons which contribute fibers to the
inability to individually move the fingers of first cervical and the spinal accessory nerves.
the contralateral upper limb to pick up small On the medial border of the anterior horn lies
objects. However, if about 30% of the pyrami- the medial longitudinal fasciculus, which is
dal tract fibers remain intact, it is possible shifted laterally by the fibers of the corti -
with time and retraining to overcome the cospinal decussation ( Figs. 12.4 and 12.5). On
deficits of finger movement. The enduring the ventral and lateral borders of the anterior
deficit is loss of hand contact orienting re- horn are fibers of the vestibulospinal tract .
sponses and reflex sensory- motor adjust- The gray matter between the spinal trigemi-
ments ( 175). nal nucleus and the anterior horn has lost its
At the spinomedullary transition , the sub- definite continuity and consists of a few cells
stantia gelatinosa of the cervical spinal cord scattered among fiber bundles. Fibers present
becomes the spinal trigeminal nucleus ( Figs. in this area are corticospinal fibers and short
Fasciculus cuneatus \ Fasciculus gracilis
,
— Dorsolateral fasciculus
Dorsal root
' Posterior
Substantia gelatinosa A
<
V
r ft spinocerebellar tract
N XI
Sm
Central gray Li
: t ,4
Anterior
m- 1
trS,<f
y' hJ
;
Lateral
corticospinal tract
spinocerebellar tract * J
fc -vs
Spinothalamic tracts Ventral root C 1
' Vestibulospinal tract
Corticospinal decussation
/ Medial longitudinal fasciculus
Figure 12.3. Transverse section through the junction of spinal cord and medulla Some of the most caudal decussat -
ing fibers of the corticospinal tract can be seen passing into the posterior part of the lateral funiculus. The structure la-
beled substantia gelatinosa also contains cell groups of the spinal trigeminal nucleus (Weigett s myelin stain)
Fasciculus gracilis
Nucleus gracilis
Spinal trigeminal tract
Fasciculus cuneatus
Spinal trigeminal nucleus Nucleus cuneatus
Central gray Posterior

spinocerebellar tract
Anterior N . XI
spinocerebellar tract —
Spinothalamic tracts 7 — Supraspinal nucleus

*
' Vestibulospinal tract
Corticospinal decussation
Medullary pyramid
Figure 12.4. Transverse section of the medulla through the decussation of the corticospinal troct (Weigert s myelin
stain)
12 Medulla 425
intersegmental fibers, comparable to those in laterally by fibers of the fasciculus gracilis. At

the fasciculi proprii . This area of intermin- progressively higher levels, increasing num-
gled gray and white matter is the most caudal bers of fibers terminate in these nuclei. The
part of the brainstem reticular formation. nuclei increase in size ( Fig. 12.6 ) while the
fasciculi correspondingly decrease ( Fig . 12.7).
Posterior Column Nuclei At levels through the caudal part of the infe-
rior olivary complex, the entire fasciculus
In the posterior white columns, nuclear gracilis and most of the fasciculus cuneatus
masses have appeared in the fasciculi gracilis were replaced bv their respective nuclei ( Figs.
and cuneatus. These are the nuclei of the pos- 12.7 and 12.8).
terior funiculi, known respectively as the nu - The overall appearance of the posterior
cleus gracilis and nucleus cuneatus . The long ( dorsal ) column nuclei in humans (144, 151 ) is
ascending branches of the cells in the dorsal similar to that observed in macaque monkeys
root ganglia , coursing in the posterior funicu- (62, 63). In both , the middle regions contain
lus (clinically called the posterior columns ), discrete clusters of neurons outlined by
terminate upon these nuclei ( Figs. 11.1 and bands of myelinated fibers. Studies with his-
12.2 ). At these levels, the fasciculus cuneatus tochemical methods for the mitochondrial en -
is massive and only a small caudal part of the zyme cytochrome oxidase show that the cell
nucleus cuneatus protrudes into the ventral clusters have more of the enzyme and , pre-
part of the fasciculus ( Figs. 12.4 and 12.5). The sumably, higher metabolic activity than the
nucleus gracilis is larger, occupies a more surrounding regions. The details of the par-
central position and is capped dorsally and cellation pattern of the nuclei in humans and
Post, spinocerebellar
Fasciculus gracil is
tract
Spinal nucleus and
/ Nucleus gracil i s
Fasciculus cuneatus
tract of N 33
Nucleus cuneatus
Central
spinothalamic •
tract Rubrospinal
tract
Ventral Vestibulospinal
Pyramidal
tract
decussation
Medial longitudinal
fasciculus
Ant. spinocerebellar tract
Figure 12.5. Transverse section of the medulla through the upper part of the corticospinal decussation (Weigert ' s
myelin stain).
Nucleus gion characterized by scattered cells occur-

cuneatus ^ M . ring singly or in small clusters (117, 161, 187).
M-i r *
“ ““
Reticular
Ascending dorsal root fibers project somato-
topically to the nucleus gracilis ( 38, 56, 60, 77,
204 ). According to Hand ( 77), lumbosacral
formation
dorsal root fibers exhibit a somatotopic lami-
— Cells of nation chiefly in the "cell nest" region, while
central gray terminations in the reticular region are dif -
fuse with intersegmental overlap (97). Cer-
Anterior horn
cells of first
tain physiologic studies in the cat suggest
Nucleus of cervical root that neurons in the nucleus gracilis exhibit
spinal tract (supraspinal rostrocaudal differences with respect to the
of N. V nucleus) size of the peripheral receptive fields, which
Figure 12.6 . Transverse section through the medulla of supply afferent input ( 72, 124 ), and segrega -
1 -month infant at about same level as in Figure 12.4 (cretion of sensory modality ( 56, 70, 109, 153,
syl violet stain, with cell groups blocked in). 207). Rostral portions of the nucleus ( i.e.,
reticular region ) are said to be related to deep
pressure and joint movement, while the "cell
monkeys are quite comparable, suggesting nest" and caudal regions of the nucleus are
the significance of the parcellation is the same related to hair and skin receptors.
(97). Other physiologic data (108), based upon
In the nucleus gracilis, three cytologically single neuron analysis of posterior column
distinct regions have been recognized: (a ) a nuclei, provide no evidence of rostrocaudal
reticular region rostral to the obex character- differentiation in terms of either somatotopy
ized by a loose organization of cells, ( b) a or modality segregation . The latter finding
"cell nest" region caudal to the obex charac- supports experimental studies (134, 157)
terized by cell clusters, and (c) a caudal re- which indicate that (a ) the somatotopic orga-
Central gray
Nucleus cuneatus
Nucleus gracilis
Accessory cuneate
Spinal tract nucleus
and nucleus
of NI External arcuate
fibers
Internal arcuate
fibers
Dorsal sensory
nucleus of vagus
Spinothalamic
—
Hypoglossal
nucleus
tract Reticular
formation
Spinocerebellar
tracts;
posterior Lateral reticular
anterior nucleus
Medial long .
fasciculus —. Inferior olivary
nucleus
Medial accessory Arcuate nucleus

Olive
Pyramid
Decussation of
medial lemniscus
Figure 12.7. Transverse section of the medulla through the decussation of the medial lemniscus (Weigert s myelin
stain).
12 Medulla 427
Cuneate nucleus '"''' Nucleus gracilis

^
A c c e s s o r y c u n e a t e ,x
nucleus Commissural
nucleus of N X
Dorsal Motor
nucleus of N X
Spinal
of
nucleus
N . 3Z — Hypoglossal nucleus
Nucleus reticularis
Nucleus ambiguus v e n t r a Ii s
Lateral reticular Medial accessory
olivary nucleus
nucleus
Pyrami d
Inferior olivary
nucleus
Figure 12.8 . Transverse section through medulla of 1 -month infant about the same level as in Figure 12.7 (cresyl violet
stain, with cell groups blocked in)
nization of the posterior columns and the me- angular and multipolar cells receive afferents
dial lemniscus is maintained at the level of primarily from proximal parts of the limb
the posterior column nuclei, and ( b ) neural el- and trunk, and appear related to larger cuta -
ements devoted to kinesthesis and tactile neous receptive fields. These studies sug-
sense are intermingled in a single and mutual gested that dorsal root fibers have a dual ter-
somatotopic pattern . Studies in the monkey mination with some fibers ending in cell
indicate that lower thoracic, lumbar, and clusters and others among basal triangular
sacrococcygeal dorsal roots project in over - cells.
lapping somatotopic fashion throughout the A systematic study of dorsal root projec-
rostrocaudal extent of the nucleus gracilis tions to the cuneate nucleus in the monkey
( 38). Zones of the nucleus gracilis receiving has shown that (a ) fibers from spinal seg-
terminals from fibers of the dorsal roots are ments Cl through T1 terminate in both exclu -
organized so that (a ) roots of the lumbar en - sive and overlapping zones, ( b) fibers from
-
largement project to irregular shaped areas in spinal segments C5 through C8 terminate in a
the central core of the nucleus; ( b) lower tho- central core region about which other dorsal
racic and upper lumbar roots project in serial root fibers terminate in oblique serial lami-
fashion to narrow, oblique laminae lateral to nae, (c) fibers from upper cervical spinal seg-
the core region; and ( c ) sacral and coccygeal ments (Cl through C4 ) terminate in ventro-
dorsal roots project in serial fashion to cres- lateral regions of the nucleus, and ( d ) fibers
cent -shaped laminae in dorsomedial parts of from lower spinal segments (T1 through T7)
the nucleus. The areas of terminal arboriza - terminate in dorsomedial regions of the nu -
tion in the nucleus gracilis are related to the cleus ( 177). Comparisons of the patterns of
size of the dorsal root and the number of as - dorsal root terminations in the two dorsal col -
cending fibers they contribute to the fascicu- umn nuclei in monkeys suggest that overlap-
lus gracilis. ping terminations are more extensive and ir -
The nucleus cuneatus also exhibits re- regular in the nucleus gracilis, and that there
gional differences in its cytoarchitecture (129, is less autonomous terminal representation of
144 ). Dorsal areas of the cuneate nucleus con- individual dorsal root fibers in the nucleus
tain clusters of round cells with bushy den- gracilis than in the nucleus cuneatus ( 38).
drites, while basal areas contain triangular,
multipolar, and fusiform cells with long, Decussation of the Medial Lemniscus
sparse dendrites ( 117). The round cell clusters
are believed to receive afferents principally In transverse sections of the medulla
from distal parts of the body and to be related above the corticospinal decussation ( Figs.
to small cutaneous receptive fields (117). Tri - 12.7 and 12.8 ), the nucleus gracilis reaches its
greatest extent, and practically all fibers of highest root. Upper thoracic dorsal root fibers
the fasciculus gracilis have terminated in por- (other than Tl ) exhibit greater overlap and
tions of the nucleus. A considerable number terminate in smaller zones in the lateral part
of fibers of the fasciculus cuneatus remain of the nucleus.
dorsal to the nucleus. From the nuclei gracilis Although fibers from parts of the fascicu -
and cuneatus, myelinated fibers arise which lus cuneatus terminate upon cells of the ac-
sweep ventromedially around the central cessory cuneate nucleus, these cells do not
gray matter. These fibers, known as internal contribute fibers to the formation of the me-
arcuate fibers , cross the median raphe and dial lemniscus. Cells of the accessory cuneate
form a well-defined ascending bundle, the nucleus give rise to uncrossed cuneocerebellar
medial lemniscus on the contralateral side. This fibers , which enter the cerebellum via the res-
large ascending fiber bundle can be readily tiform body, which is the major component of
followed through the brainstem to its termi- the inferior cerebellar peduncle ( Fig. 11.9).
nation in the ventral posterolateral nucleus The main cerebellar projection of the acces-
( VPL, ) of the thalamus ( Fig. 11.1 ). The medial sory cuneate nucleus is ipsilateral to parame-
lemniscus constitutes the second neuron of dian parts in the anterior lobe. The cuneo-
the posterior column pathway conveying cerebellar tract is regarded as the upper limb
kinesthetic sense and discriminative tactile equivalent of the posterior spinocerebellar
sense to higher levels of the neuraxis. The de- tract .
cussation of the medial lemniscus provides
part of the anatomic basis for sensory repre- Spinal Trigeminal Complex
sentation of half of the body in the contralat-
SPINAL TRIGEMINAL TRACT
eral cerebral cortex. Consequently, injury to
the medial lemniscus causes characteristic Afferent trigeminal root fibers, which
kinesthetic and tactile deficits on the opposite enter the brainstem at midpontine levels, de-
side of the body . scend in the dorsolateral part of the brain -
The accessory cuneate nucleus , located lat- stem as the spinal trigeminal tract ( Figs. 12.4,
eral to the cuneate nucleus at slightly more 12.5, 12.7, 12.9, 12.11, 12.12, and 12.26). These
rostral levels, is composed of large cells simi- fibers originating from cells of the trigeminal
lar to those of the dorsal nucleus of Clarke ganglion , have a definite topographic organi -
( Figs. 11.9, 12.7, and 12.8 ) . This nucleus is
considered the medullary equivalent of the
zation so that (a ) fibers of the mandibular di-
vision are most dorsal , ( b ) fibers of the oph-
dorsal nucleus ( 25, 150, 176). The two nuclei thalmic division are most ventral, and (c)
share these anatomic and functional features: fibers of the maxillary division are intermedi-
(a ) cells are morphologically similar with ec- ate ( Fig. 12.9 ). Some trigeminal root fibers
centric nuclei, ( b ) afferent fibers are derived from all divisions extend into upper cervical
from dorsal root ganglia , (c ) both nuclei give segments ( 100, 107, 164, 193) ( Fig. 12.9 ). As
rise to uncrossed cerebellar afferent fibers, this tract descends, it becomes progressively
and ( d ) both nuclei relay impulses from mus- smaller as fibers leave the tract and terminate
cle spindles, Golgi tendon organs, type II in the adjacent spinal trigeminal nucleus. The
muscle afferents, and cutaneous afferents tract contains general somatic afferent fibers
( 145, 146). Ascending fibers conveyed by the from the trigeminal nerve, as well as similar
fasciculus cuneatus and terminating in the ac- fibers from the vagus, glossopharyngeal, and
cessory cuneate nucleus are derived from the
same dorsal root ganglia as those projecting
facial nerves. These fibers descend in the dor -
somedial part of the tract for a considerable
to the cuneate nucleus, namely those of cervi- distance before terminating in the magnocel-
cal and upper thoracic spinal segments. As- lular division of the caudal part of the spinal
cending fibers in the fasciculus cuneatus ter- trigeminal nucleus (99, 101, 164, 193). A few
minate somatotopically in the accessory visceral afferent fibers descending in the dor-
cuneate nucleus (119, 177), and the pattern of sal part of the spinal trigeminal tract project
termination is similar to that disclosed in the medially to terminate in ventrolateral parts of
cuneate nucleus (177). Fibers from dorsal the nucleus solitarius (98, 100, 164, 193).
roots in cervical and upper thoracic spinal
segments that terminate in the accessory SPINAL TRIGEMINAL NUCLEUS
cuneate nucleus end in both exclusive and
overlapping zones; fibers from one dorsal This nucleus, which lies along the medial
root partially overlap the territory of the next border of the tract, extends from the level of
12 Medulla 429
Trigeminal
ganglion
Mesencephalic
Ophthalmic nucleus N V
division -^
Principal sensory
Maxillary division -• nucleus N V
Mandibular division -
— Spinal trigeminal
tract and nucleus
Spinal trigeminal
tract nucleus
Spinal cord
Mandibular
Maxillary Divisions
Ophthalmic
Figure 12.9. Topographic arrangement of fibers in the spinal trigeminal tract. Fibers with cell bodies in the trigeminal
ganglion enter the upper pons and descend caudally as far as C2. Throughout the length of the tract, mandibular
fibers are most dorsal and those of the ophthalmic division are most ventral. Fibers leave the spinal trigeminal tract to
synapse upon cells In the spinal trigeminal nucleus.
entry of the trigeminal root in the pons to the

second cervical spinal segment ( Figs.
Accessory
cuneate nucleus
^
13.29-13.31 ). Fibers from the spinal trigemi - STv
nal tract terminate upon cells of the nucleus
throughout its extent. Cytoarchitecturally the PTN
spinal trigeminal nucleus is subdivided into
three parts: (a ) pars oralis , which extends cau - i \
l l SCT
dally to the rostral pole of the hypoglossal
nucleus; ( b ) pars interpolaris, which extends
caudally to the level of the obex; and (c) pars
IV ;lli : II ; |
J j
caudalis, which begins near the level of the

obex and extends caudally as far as the sec- Reticular
ond cervical spinal segment (143). The caudal formation ,-
' *» i •
part of the spinal trigeminal nucleus has a cy-
tologic lamination similar to that of the poste- Spinothalamic
rior horn of the spinal gray matter ( Fig.
tracts
12.10). Four laminae are recognized : (a ) lam
ina I, corresponding to the posteromarginal
-
Inferior Lat. retie ,
zone; ( b ) lamina II, corresponding to the sub-

stantia gelatinosa; and (c) laminae III and IV,
which form the magnocellular layers ( 66-68,
106, 143). Fibers positive for substance P, as
ôlive nucleus
Figure 12.10. Laminar organization of the spinal trigemi-

nal nucleus. Lamina I adjacent to the spinal trigeminal
well as cells and fibers immunoreactive for tract (STv) Is called the marginal layer . Cells in lamina I
enkephalin, are present in laminae I and II resemble those of the posteromarginal nucleus at spinal
( Fig. 12.30). levels Laminae II corresponds to the substantia gelati-
Fibers in different parts of the spinal

.
nosa and laminae III and IV form the magnocellular sub-
division. PTN indicates the paratrigeminal nucleus and
trigeminal tract terminate in corresponding SCT the spinocerebellar tracts.
circumscribed sectors of the spinal trigeminal inal nuclei. This view surmises that afferents
nucleus. Fibers conveying impulses from the to the spinal trigeminal nucleus are distrib-
mandibular division terminate in dorsal parts uted following a sort of "onion skin pattern"
of the nucleus, while fibers of the ophthalmic ( 26 ). In essence, this concept implies that
division terminate in ventral parts of the nu - axons from facial sensory regions near the
cleus. A number of descending trigeminal midline, around the mouth and nose, project
fibers pass beyond the spinal trigeminal nu - rostrally in the caudal nucleus, whereas
cleus to terminate in dorsal parts of the retic- those from successively more lateral regions
ular formation and portions of the solitary of the face would supply more caudal parts
nucleus. Many neurons of the spinal trigemi- of the nucleus. This scheme of organization
nal nucleus give rise to an extensive axonal has important clinical value for localizing
plexus of small fiber bundles which lie adja- lower medullary and upper cervical cord le-
cent to the nucleus. These so-called "deep sions.
bundles" emit collaterals which effectively Secondary trigeminal fibers arise from
link different levels of the spinal trigeminal cells of the spinal trigeminal tract at multiple
nucleus (64 ). levels, cross through the reticular formation
Fibers in the spinal trigeminal tract convey to the opposite side, and ascend to thalamic
impulses concerned with pain, thermal, and levels in association with the contralateral
tactile sense from the face, forehead, teeth , medial lemniscus ( Fig. 13.30). These tri -
and mucous membranes of the nose and geminothalamic fibers constitute the sec -
mouth (55, 57, 159) ( Fig. 8.13). The spinal ond neuron in a sensory pathway from the
trigeminal tract and nucleus appear to be the face to the cortex. Other uncrossed fibers as-
only part of the trigeminal complex uniquely cend and descend on the same side, forming
concerned with the perception of pain and reflex connections with the motor nuclei of
thermal sense. Medullary trigeminal tractot - the hypoglossal, vagus, facial, and other cra -
omy ( i.e., section of the spinal trigeminal nial nerves ( Figs. 13.30 and 13.31 ). Other
tract ) markedly reduces pain and thermal trigeminal fibers (a ) terminate upon cells of
sense without impairing tactile sense (179 ). the reticular formation , ( b ) project to the cere-
Physiologic studies ( 159 ) indicate that the bellum via the inferior cerebellar peduncle
spinal trigeminal nucleus, pars caudalis, en- (36 ), or (c) establish reflex connections with
codes nociceptive information in the same multiple motor cranial nerve nuclei.
manner as the dorsal horn of the spinal cord. Groups of cells located lateral to the spinal
Cells are found which respond solely to oral trigeminal tract and embedded in the fibers
and facial nociceptive stimulation, as well as of the spinocerebellar tracts at the lateral edge
cells responding in a graded manner to a me- of the medulla form the yaratrigeminal nucleus
chanical stimuli of increasing intensity. The ( Fig. 12.10). Both cell bodies and fibers in the
cells responding to nociceptive stimulation neuropil show substance P-like immunoreac -
are located within the nucleus and also in the tivity. Additionally, the neuropil contains
subjacent reticular formation. Lesions in the many serotonin (5- hydroxytryptamine 5- HT)-
dorsolateral region of the medulla involving containing afferent axons (39, 40). The func -
the spinal trigeminal tract and adjacent tion of the paratrigeminal nucleus is not
spinothalamic tracts produce an alternating known . Since it receives afferent axons from
hemianalgesia and hemithermo-anesthesia of the intermediate nerve (12 ) and nucleus of
the face and the body. This condition , known the solitary tract (11), and sends efferent
as the lateral medullary syndrome (or Wallen- fibers to the gustatory region of the thalamus,
berg's syndrome), is characterized by dimin - it has been thought to represent a rostral ex-
ished pain and thermal sense in the face ipsi- tension of the portion of the nucleus of the
laterally (spinal trigeminal tract ) and over the solitary tract concerned with taste.
opposite side of the body and neck (anterolat - The arcuate nucleus lies on the anterior as -
eral system or ALS tracts ) ( Fig. 13.30). pect of the pyramid ( Figs. 12.7 and
There appears to be little overlap between 12.11-12.13). In rostral portions of the
the terminal territories of the main branches medulla , the nucleus enlarges considerably
of the trigeminal nerve in the spinal trigemi - ( nucleus precursorius pontis ) and appears to
nal nucleus. Evidence from clinical studies become continuous with the nuclei of the
have led to an interesting model regarding pons. Afferent fibers to this nucleus are de-
the somatotopic representation in the trigem - rived from the cerebral cortex, and its efferent
12 Medulla 431
EC Ventricle
Area postrema Dorsal long bundle
Nucleus gracilis
Nucleus cuneatus
Nucleus and Dorsal sensory

tract of nuc . of nerve X
solitary fasciculus
Descending nucleus
and tract of
trigeminal nerve
—
|
} — Accessory cuneote
nucleus
I Dorsal motor nuc.
of nerve X
Medial longitudinal
— Hypoglossal nucleus
fasciculus _ Nucleus ombiguus
Lateral reticular Root fibers of nerve XE

nucleus
Spinothalamic tracts
Internal arcuate
fibers Inferior olivary
nuclear complex
Amiculum of
inferior olivory
complex
Arcuate nucleus Medial lemniscus
Corticospinal tract
Figure 12.11. Transverse section of the medulla through the caudal part of the fourth ventricle, the area postrema
and the lower part of the inferior olivary complex (Weigert ' s myelin stain)
Choroid plexus
Dorsol long , fasciculus
Medial vest , nucleus
Inf . vest , nucleus
Dorsal sensory nuc . N. X
Vtntricl* Accessory
cuneote
Solitary fasciculus
Nucleus of solitary
—IS nucleus
Spinal tract
fasciculus 2 of N . 3Z and
Dorsal motor nuc. NX / Nucleus
Hypoglossal j» nucx — Olivocerebellar
fibers
~ Spinothalamic tr
Med . long. fasc .
Root fibers N . XH p Inferior olivary
f nucleus
Medial lemniscus ^ Central tegmental tr .
Root fibers N XIL

Pyramid
Arcuate nucleus
Medial accessory
olivary nucleus
Figure 12.12. Transverse section of the medulla through the inferior olivary complex rostral to that shown in Figure
.
12.11 Em X, emlnentia vagi. Em . XII eminentia hypoglossl (Weigert ' s myelin stain)
S p i n a l n u c l e u s of N . Y M e d i a l v e s t, n u c l e u s
\\ Accessory
cuneate nucleus
\ \ Nuc of fosc. Choroid plexus
\ \ solitarius
TV Ventricle
I Dorsal motor
n u c l e u s o f N . X.
Nucleus intercalatus
Pontobulbar
nucleus Hypoglossal nucleus
Nucleus of Roller
«8* Nucleus reticularis
gigantocellularis
I n f e r i o r v e s t. ' Paramedian reticular
nucleus nuclei
Dorsal accessory
Medial }
olivary nuclei
Lateral reticular
nucleus Inferior olivary nucleus
Pyramid
Nucleus ambiguus
Figure 12.13. Transverse section through midolivary region of the medulla (cresyl violet stain, with schematic repre-
sentation of the main cell groups)
fibers project as ventral external arcuate rophysin, oxytocin, and vasopressin , al-
fibers to the cerebellum . Fibers from this though these peptides cannot be demon-
small nucleus are thought to be crossed . strated within the area postrema. The area
postrema is an emetic chemoreceptor, sensi-
Area Postrema tive to apomorphine and intravenous digi-
talis glycosides ( 16, 17). Electrical activity in
Immediately rostral to the obex on each the region of the area postrema is altered by
side of the fourth ventricle is a small rounded intravenous administration of hypertonic so-
eminence, the area pwslrema ( Fig. 12.11 ), con- lutions ( 46), and lesions result in altered
taining astroblast-like cells, arterioles, sinu - Na ' / K excretion ratios in urine, which sug-
soids, and some apolar or unipolar neurons gest a transient potassium retention by the
( 20, 33). The area postrema is one of several kidney (181 ).
specialized ependymal regions (104) that lie
outside the blood -brain barrier, collectively INFERIOR OLIVARY COMPLEX
referred to as circumventricular organs ( Fig.
1.17). All the circumventricular organs, ex- The most characteristic feature of the
cept the area postrema, are unpaired and re- medulla is the inferior olivary complex ( Figs.
lated to portions of the diencephalon . Fibers 12.8, 12.11, and 12.12). The central canal has
of the solitary nucleus and spinal cord project opened into the fourth ventricle, and the roof
to the area postrema , which also harbor of this ventricle is formed by the inferior
axons and dendritic processes from nearby medullary velum and the tela choroidea and
regions of the medulla ( 45, 132, 197). The choroid plexus. The floor of the fourth ventri -
chemical anatomy of the region is complex, cle contains three eminences, which overlie
and a number of putative transmitters have cranial nerve nuclei. The most medial is the
been identified (138). For example, fields of hypoglossal eminence (or trigonum hypoglossi ),
terminals surrounding this area contain neu - overlying the nucleus of the hypoglossal
12 Medulla 433
nerve; an intermediate eminence (or trigonum of cells in the inferior olive would tend to dis-
wgi ) overlies the vagal nuclei. The most me- charge synchronously.
dial of the vagal nuclei is the dorsal motor The principal olivary nucleus is sur-
nucleus. The lateral part of the intermediate rounded by a dense band of myelinated
eminence overlies the nuclei of the solitary fibers, the amiculum olivae , comprised largely
fasciculus. The sulcus limitans, often an indis - of axons terminating in the nucleus. Descend -
tinct sulcus, passes through the intermediate ing fibers terminating upon cells of the infe-
or vagal eminence. Cranial nerve cell rior olivary complex arise from the cerebral
columns medial to the sulcus are efferent, cortex, the red nucleus, and the periaqueduc-
while those lateral to it are afferent ( Fig. tal gray matter of the midbrain , the inferior
12.14). The most lateral eminence overlies the vestibular nucleus, parts of the spinal trigem -
vestibular nuclei and is referred to as the area inal nucleus, and the contralateral cerebellar
vestibularis. ( Figs. 12.2 and 12.13). Internal ar - nuclei (131, 199, 203).
cuate fibers sweep ventromedially through Cortico-olivary fibers arise from frontal ,
portions of the reticular formation, decussate, parietal, temporal, and occipital cortex, de-
and enter the contralateral medial lemniscus. scend in most corticospinal fibers, and termi -
The medial lemnisci occupy triangular areas nate bilaterally, primarily upon the ventral
on each side of the median raphe, bounded lamella of the principal olive. Rubro-olivary
ventrally by the pyramids and laterally by fibers and fibers arising from the periaque-
the inferior olivary nuclei . Dorsal to the me- ductal gray matter of the midbrain enter a
dial lemnisci on each side of the median composite bundle known as the central
raphe are the medial longitudinal fasciculi tegmental tract, descend uncrossed , and ter-
( Figs. 12.11 and 12.12). The accessory cuneate minate in different portions of the principal
nucleus lies dorsolaterallv, posterior to the olive ( Figs. 12.33, 13.1, and 13.4 ) . Noradrener-
spinal trigeminal tract and nucleus. gic axons from the pons also reach the infe-
The inferior olivary complex is a convo- rior olive (180 ). Rubro-olivary fibers end in
luted gray band of cells which consists of the dorsal lamella while fibers from the peri -
three parts: (a ) the principal inferior olivary nu - aqueductal gray matter, interstitial nucleus of
cleus , appearing as a folded bag with the Cajal, nucleus of Darkschewitsch, and nearby
opening or hilus directed medially , ( b) a me- regions terminate in the rostral parts of the
dial accessory olivary nucleus located along the principal olivary nucleus, and in the medial
lateral border of the medial lemniscus, and and dorsal accessory nuclei ( 171, 203). Other
(c) a dorsal accessory olivary nucleus located brainstem projections to the olivary complex
dorsal to the main nucleus ( 19, 151 ). These originate in the medial and inferior vestibular
nuclei are composed of relatively small, nuclei (170), caudal part of the spinal trigemi-
round or pear-shaped cells with numerous nal nucleus, and the contralateral cerebellum
short branching dendrites, and appear to (13, 14 ) . Spinal projections to the inferior oli -
have glutamate as their excitatory transmit - vary complex terminate mainly in the acces-
ter. Axons of cells in the inferior olivary com - sory olivary nuclei. Fibers ascending in the
plex cross the median raphe, sweep postero- anterior spino-olivary tract (anterior funicu -
laterally, and enter the cerebellum via the lus ) synapse directly upon neurons in the
contralateral restiform body ( part of the infe - dorsal and medial accessory olivary nuclei.
rior cerebellar peduncle). Crossed olivocere- More than half of these fibers cross in the
bellar fibers constitute the largest single com- medulla . Spino-olivary fibers, ascending in
ponent of the restiform body ( Figs. 12.25, the posterior white columns, synapse upon
12.26, and 15.27). They project to all parts of cells in the rostral parts of the nuclei gracilis
the cerebellar cortex and to cerebellar nuclei and cuneatus, which , in turn, project to the
( 21 ). Fibers of this massive projection end as contralateral accessory olivary nuclei. All
climbing fibers in the cerebellar cortex (50, 59, parts of the dorsal column nuclei send axons
76). Climbing fibers exert a powerful excita - to the contralateral olivary complex, espe-
tory influence upon individual Purkinje cells, cially the dorsal accessory nucleus (13, 14 ).
resulting in bursts of action potentials called Spinal afferents to parts of the inferior olivary
complex spikes. Cells of the inferior olive complex constitute a link in spinocerebellar
have numerous gap junctions between den - circuitry resembling that of other spinocere-
drites (182 ) and are electrotonically coupled bellar tracts.
(120). This arrangement suggests that groups Fiber tracts in ventrolateral parts of the
reticular formation are pushed dorsally by dendrites are usually long and radiating,
the olivary nuclei. The anterior spinocerebel - characterizing the cells as being of the so-
lar, rubrospinal, and spinothalamic tracts are called isodendritic type (162 ). At one time,
located laterally between the restiform body the reticular formation was thought to consist
and the olivary complex. Fibers of the mainly of neurons with short axons. Golgi
vestibulospinal tract are scattered along the type II cells ( i.e., cells with short axons ) are, in
posterior surface of the inferior olive. Posteri- fact, scarce in the reticular formation, a find -
orly on each side of the medial raphe lie the ing that suggests that polysynaptic transmis-
medial longitudinal fasciculi, containing at sion of impulses probably is due to disper -
this level predominately descending fiber sion of impulses along collateral fibers. The
bundles of mixed origin . Descending fibers in organizational pattern of the reticular forma -
this tract are derived from certain vestibular tion suggests that single reticular neurons can
nuclei, portions of the brainstem reticular for- convey impulses both rostrally and caudally,
mation, and certain nuclei in the midbrain. may exert influence locally and at a distance,
The interstitial nucleus of Cajal ( intersti- and impulses can be conducted both rapidly
tiospinal tract) contributes a small number of ( primary axon ) and slowly ( via synapsing
fibers to the dorsomedial part of the medial collateral axons) (1, 173).
longitudinal fasciculus. Tectospinal fibers
from the superior colliculus form a loosely Major Subdivisions
organized group of fibers in the ventral part
of the bundle. The brainstem reticular formation begins
in the caudal medulla rostral to the corti -
MEDULLARY RETICULAR FORMATION cospinal decussation ( Figs. 12.6 and 12.7). The
lateral and ventral reticular nuclei are partic-
Definition ularly well-delineated at this level. The lateral
The term "reticular formation" refers to
reticular nucleus lies ventrolaterally in the cau -
portions of the brainstem core characterized
dal medulla and extends rostrally up to mi -
structurally by a wealth of cells of various dolivary levels ( Figs. 12.8 and 12.11 ). It can be
sizes and types, arranged in diverse aggrega - divided into three cytoarchitectonic parts:
tions, and enmeshed in a complicated fiber magnocellular, parvicellular, and subtrigemi -
network . This structure is well-developed in nal. The magnocellular part is oriented ven -
all vertebrates (51 ), and it forms the core of tromediallv within the nucleus, dorsal to the
the brainstem in humans. In a sense, the retic- inferior olive, and the parvicellular part lies
ular formation constitutes a matrix within dorsolateral to it (110, 198). Cells in the lateral
which "specific" nuclei and tracts are embed - reticular nucleus project axons to specific por-
ded . Anatomic studies indicate that the brain - tions of the cerebellar cortex and cerebellar
nuclei via the ipsilateral restiform body ( infe-
stem reticular formation , which extends from
rior cerebellar peduncle) (128). In turn , they
the medulla to the midbrain, can be subdi-
receive a topographically organized and
vided into regions having distinctive cytoar-
chitecture, fiber connections, and intrinsic or- highly convergent input from the spinal cord
via spinoreticular pathways (110). The lateral
ganization ( 24, 26, 127, 129, 144 ). Despite
these features, various subdivisions cannot be reticular nucleus also receives crossed de-
regarded as entirely independent entities, be- scending rubrobulbar axons (80, 202 ). Most
cause fiber connections provide innumerable cells in the lateral reticular nucleus respond
to stimulation over large peripheral receptive
possibilities for interaction between subdivi-
sions.
fields involving both fore- and hindlimbs
(166). Medial to the lateral reticular nucleus
Cytoarchitecture and dorsal to the caudal half of the inferior
olivary nucleus lies the ventral reticular nu -
Golgi studies indicate that almost all neu - cleus ( nucleus reticularis ventralis ) ( Fig. 12.8).
rons in the reticular core project axons in both By comparison to the lateral reticular nu -
rostral and caudal directions (173). Primary cleus, relatively little is known of the ventral
bifurcating axons are oriented longitudinally, reticular nucleus, except that it does not pro-
but collaterals pass in all directions and ter- ject to the cerebellum ( 26) .
minate in a variety of different endings. At midolivary levels, the gigantocellular
Many collaterals arborize about cells in both reticular nucleus ( nucleus reticularis gigantocel -
motor and sensory cranial nerve nuclei . The lularis of Olszewski and Baxter ( 144) ) occu -
12 Medulla 435
pies the area medial and dorsal to the rostral caudal and lateral portions of the medullary
half of the inferior olivary nucleus ( Fig. reticular formation . A considerable number
12.13). The latter nucleus is the rostral contin - of these fibers end in the caudal half of the
uation of the nucleus reticularis ventralis. As nucleus reticularis gigantocellularis, though
its name implies, it has characteristic large some project to more rostral portions of the
cells, but it also contains many medium- and reticular formation ( Figs. 11.10 and 12.13).
small -sized cells ( Fig. 12.13). This nucleus oc - Collaterals of spinothalamic fibers terminate
cupies the medial two-thirds of the reticular somatotopically upon cells of the lateral retic-
formation and extends to the medullary- pon
tine junction. Descending fibers from the gi-
- ular nucleus, a cerebellar relay nucleus ( 22,
26). Physiologic data indicate that exterocep-
gantocellular nucleus form the medullary tive impulses are relayed to the cerebellum
reticulospinal tract, which exerts an in - via this indirect spinocerebellar pathway ( 47).
hibitory effect upon spinal neurons (see Collateral fibers from second order sensory
Chapter II , and Figs. 11.10 and 11.22 ). The neurons of cranial nuclei, such as auditory,
other major nuclei of the medullary reticular vestibular, trigeminal, and visceral (solitary
formation are the parvicellular nucleus ( nu - fasciculus) nuclei, project to the parvicellular
cleus reticularis parvicellularis ) and the para - reticular nucleus. No collaterals of the medial
median nuclei . lemniscus terminate in any part of the brain -
The parvicellular reticular nucleus is a collec- stem reticular formation. Except for a modest
tion of small cells located posterolaterally, number of trigeminal fibers ( 36, 193), primary
medial to the spinal trigeminal nucleus, and sensory fibers do not appear to terminate in
anterior to the vestibular nuclei. This nucleus, the reticular formation .
occupying roughly the lateral third of the Corlicoreticular fibers originate from wide-
medullary reticular formation, has been re- spread areas of the cerebral cortex, but the
ferred to as the sensory part because it re- majority of these fibers arise from sensorimo-
ceives collaterals from secondary sensory tor areas (167 ). These fibers are both crossed
pathways ( 24, 26). The paramedian reticular and uncrossed, and most of them terminate
nuclei consist of several small nuclear groups in portions of the pons and medulla . Regions
that lie close to, and sometimes among, fibers of the brainstem reticular formation receiving
of the medial longitudinal fasciculus and the corticoreticular fibers are those which give
medial lemniscus ( Fig. 12.13). These neurons rise to reticulospinal fibers. These regions en-
project most of their fibers to the cerebellar compass the nucleus reticularis pontis oralis ,
vermis ( 23). the nucleus reticularis pontis caudalis , and the
In essence, the medullary reticular forma - nucleus reticularis 'gigantocellularis ( Figs. 11.10,
tion consists of three principal nuclear 11.22, and 12.13).
masses: (a ) a paramedian reticular nuclear Cerebelloreticular fibers terminate mainly in
group, ( b) a cetitral group ( i.e., the ventral retic- the paramedian reticular nuclei. These reticu -
ular and gigantocellular reticular nuclei ), and lar projections originate from the fastigial and
(c ) a lateral nuclear group consisting of the lat - dentate nuclei. Fibers from the fastigial nu -
eral reticular and parvicellular reticular nu - cleus reach the paramedian nuclei via the un -
clei. The raphe nuclei, consisting of several cinate fasciculus (35, 189), while fibers from
distinct groups of neurons, probably also be- the dentate nucleus pass via the crossed de-
long to the reticular formation but , because scending division of the superior cerebellar
they contain a multitude of serotoninergic peduncle ( 29, 37). Impulses from a wide vari-
neurons, they are described later with other ety of sources converge upon the reticular
chemospecific neuronal systems. nuclei . The maximal overlap of afferent fibers
from different sources occurs in the
Afferent Fibers medullary reticular formation, which gives
rise to a large number of long ascending and
The principal sources of afferents to the descending axons.
medullary reticular formation are (a ) the
spinal cord , ( b ) collateral fibers from second Efferent Fibers
order neurons of sensory cranial nuclei, (c)
the cerebral cortex, and (d ) the cerebellar nu - They arise from the medial two- thirds of
clei . the medullary reticular formation, which cor-
Spinoreticular fibers ascend in the anterolat - responds to the gigantocellular reticular nu -
eral funiculus ( 130, 169 ), and terminate in the cleus. This nuclear mass gives rise to both as-
cending and descending fibers. Ascending mation exerts its excitatory or inhibitory
fibers course in the central tegmental tract , are effects at both spinal and higher brainstem
uncrossed , and terminate mainly upon por- levels.
tion of the intralaminar and thalamic nuclei
(136) ( Fig. 13.4 ) . This system plays an impor-
ASCENDING AND DESCENDING TRACTS
tant role in the mechanism of arousal and
sleep. Descending fibers from this medial re- Ascending fibers of the medial lemniscus
gion of the reticular formation form the occupy an "L"-shaped area on each side of
medullary reticulospinal tracts, which are bi- the median raphe posterior to the pyramid
lateral but predominantly uncrossed (194 ) and medial to the inferior olivary complex
( Figs. 11.10 and 11.22). Other fibers, originat - ( Figs. 12.11, 12.12, and 12.25). The spinothala -
ing in the paramedian and lateral reticular mic tracts, which are part of the more global
nuclei, project, uncrossed, to specific portions anterolateral system ( ALS), have merged to
of the cerebellum. Fibers arising in the para- form essentially a single entity in the retro-
median reticular nuclei terminate largely in olivary area . These tracts appear considerably
the vermis of the anterior lobe ( 23), while smaller than at spinal levels, because an ap-
those from the lateral reticular nucleus end in preciable number of fibers terminate in the
the vermis, hemisphere, and flocculonodular lateral reticular nucleus and others have
lobule. passed medially into the gigantocellular retic-
The reticulospinal fibers have been the ular nucleus. The posterior spinocerebellar
subject of numerous anatomic and physio- tract has moved posteriorly at medullary lev-
logic studies, which yielded important infor- els and has become incorporated into the in-
mation on the organizational features of the ferior cerebellar peduncle ( Fig. 12.25). The an-
medullary reticular formation. For instance, terior spinocerebellar tract maintains a
anatomic studies of the origin of reticu - retro-olivary position in the medulla , and ul -
lospinal axons reveal both a rostrocaudal and timately enters the cerebellum by coursing
dorsoventral topographic arrangement (103, along the dorsal surface of the superior cere-
154, 155, 190, 210). In the spinal cord , reticu - bellar peduncle. About one- third of the fibers
lospinal axons from the pons form a medial of the rostral spinocerebellar tract enter the
tract in the ipsilateral ventromedial funiculus, cerebellum via the inferior cerebellar pedun-
and axons from the medulla form a lateral cle; all other fibers of this uncrossed tract
tract in the ipsilateral ventrolateral funiculus. enter the cerebellum in association with the
Medullary reticulospinal axons reaching tho- superior cerebellar peduncle (145).
racic and lumbar spinal segments arise from The medial longitudinal fasciculus lies an-
cells in the caudal and ventral medullary terior to the hypoglossal nucleus adjacent to
reticular formation, while axons to cervical the median raphe ( Figs. 12.11, 12.12, and
spinal segments originate from more rostrally 12.25). Descending fibers in this complex
located cells. Stimulation of the rostral and bundle are derived from various brainstem
dorsal parts of the nucleus reticularis gigan- nuclei. Vestibular fibers in this bundle arise
tocellularis and regions of the caudal pontine from the medial and inferior vestibular nu -
reticular formation produces monosynaptic clei. The pontine reticular formation con-
excitatory postsynaptic potentials in motor tributes the largest number of fibers descend -
neurons supplying the axial muscles of the ing in the medial longitudinal fasciculus.
neck and back ( 125, 150, 154, 155, 163, 183). Smaller groups of fibers arise from the inter-
Stimulation of the caudal and medial stitial nucleus of Cajal ( interstitiospinal tract )
medullary reticular formation produces disy- and the superior colliculus ( tectospinal tract ).
naptic and multisynaptic inhibitory postsy- Rubrospinal fibers, descending in retro-
naptic potentials in motor neurons at all lev- olivary position, project collaterals to the lat -
els. The medullary reticular formation can be eral reticular nucleus, a cerebellar relay nu -
divided into a dorsolateral facilitatorv region cleus. Uncrossed rubrobulbar fibers , arising
and a caudomedial inhibitory zone, which from rostral parts of the red nucleus, descend
both constitute the "effector" area of the in the central tegmental tract and end upon
medullary reticular formation. This effector cells in the dorsal lamella of the principal in-
area receives projections from cells in the par- ferior olivary nucleus. At midmedullary lev-
vicellular reticular nucleus, which serve " reels, fibers of the vestibulospinal tract are scat -
ceptive" or "associative" functions. The large tered in an area posterior to the inferior
effector area of the medullary reticular for- olivary complex. At more caudal levels, these
12 Medulla 437
fibers form a more compact bundle located in and uncrossed . At higher levels, the restiform
-
the retro olivary region. The medullary retic- body becomes covered laterally by fibers of
ulospinal tract is not evident at these levels, the middle cerebellar peduncle ( Figs. 12.33
but its cells of origin in the gigantocellular and 13.2 ).
reticular nucleus are present posteromedial On the posterolateral aspect of the inferior
to the inferior olivary complex ( Fig. 12.11 ). cerebellar peduncle, a small group of closely
The spinal trigeminal tract and nucleus oc- packed , medium-sized cells can be seen ( Fig.
cupy the same location as at more caudal lev- 12.13). These cells constitute the caudal por-
els. tion of the pontobulbar nucleus . At more rostral
levels, this cell column assumes a progres-
INFERIOR CEREBELLAR PEDUNCLE sively more ventral position, and at the junc -
tion of the pons and medulla it forms a fairly
This peduncle is a composite bundle that large cell mass ventral to the restiform body
contains fibers arising from cell groups in the and medial to the ventral cochlear nucleus
spinal cord and medulla that project to the ( Figs. 12.26 and 12.32 ). The cells of this nu -
cerebellum , as well as fibers interconnecting cleus resemble those in the ventral portion of
the vestibular nuclei and the cerebellum . The the pons and have been regarded as a caudal
inferior cerebellar peduncle is composed of extension of the pontine nuclei .
two major elements: (a ) a large restiform body ,
which contains many afferent fibers from dif - CRANIAL NERVES OF THE MEDULLA
-
ferent sources ( e.g., reticular formation , infe
rior olivary complex, trigeminal nuclei, nu - The schematic arrangement of the func-
cleus cuneatus, and spinal cord ), and ( b) a tional components of the cranial nerves of the
smaller juxtarestiform body , which contains medulla and the cell columns to which they
only cerebellovestibular and vestibulocere- are related are shown in Figure 12.14. This
bellar fibers. The restiform body is the large schema resembles that present in the spinal
bundle in the dorsolateral portion of the cord , although development of the fourth
medulla that is often referred to as the infe- ventricle has shifted somatic and visceral af -
rior cerebellar peduncle. The term inferior ferent regions laterally. The functional com -
cerebellar peduncle, however, should be re - ponents of a typical spinal nerve are four: (a )
stricted to the bundle that is formed at the general somatic afferent ( GSA ), ( b ) general vis-
base of the cerebellum bv the confluence of ceral afferent (GVA ), (c ) general somatic efferent
both juxtarestiform and restiform bodies. (GSE ), and (d ) general visceral efferent ( GVE ) .
Fibers entering the inferior cerebellar pe- Functional components of the cranial nerves
duncle assemble along the posterolateral bor- include the four types found in spinal nerves,
der of the medulla , dorsal to the spinal plus three additional special categories: ( a )
trigeminal tract and lateral to the accessory special somatic afferent (SSA ), ( b ) special visceral
cuneate nucleus. This bundle rapidly in- afferent (SVA ), and ( c) special visceral efferent
creases in size in the upper medulla by the (SVE ). Somatic efferent fibers in both spinal
addition of more fibers, and enters the cere- and cranial nerves belong to the general com -
bellum ( Figs. 12.25, 12.26, and 12.33). The ponent .
posterior spinocerebellar tract moves dorsally In the medulla , as in the spinal cord , the
and enters the restiform body directly. sulcus limitans divides afferent and efferent
Crossed olivocerebellar fibers, originating cell columns. Within the medulla special so-
from all parts of the inferior olivary complex, matic afferent (SSA ) cranial nerves in the
constitute, quantitatively, the largest group of medulla are represented by the auditory and
fibers that enter the inferior cerebellar pedun- vestibular components of the vestibulo-
cle ( Figs. 12.25, 12.33, and 15.27). Other cochlear nerve ( N . VIII ). General somatic af -
medullary nuclei projecting to the cerebellum ferent (GSA ) fiber components of cranial
via this peduncle are ( a ) the lateral reticular nerves V, VII , IX , and X enter the brainstem at
nucleus of the medulla , ( b ) the accessory different levels and descend in the spinal
cuneate nucleus, (c ) the paramedian reticular trigeminal tract. Fibers conveying taste (spe-
nuclei, ( d ) the arcuate nucleus, and (e) the cial visceral afferent (SVA ) ) and general vis-
perihypoglossal nuclei ( Figs. 12.13 and 12.25). ceral afferent (GVA ) impulses from compo-
Projections of the lateral reticular nucleus and nents of cranial nerves VII , IX , and X form a
the accessory cuneate nucleus are uncrossed; well -defined tract, the solitary fasciculus,
those from other relay nuclei are both crossed which is embedded in the solitary nucleus
Dorsal motor nuc n X

GSE cell column
Choroid plexus
GVE & SVE cell columns
12 Ventricle
"
GVA S SVA cell columns

Vestibular nuclei SSA 6 GSA cell columns
Inferior Vestibular nuclei
Medial - — SSA
Soinal trigeminal tract
Inferior and nucleus, GSA
cerebellar Vagus nerve
peduncle
SVA & GVA
Solitary fasciculus
and nucleus
Nucleus Sulcus limitans

ambiguus
Inferior olivary Hypoglossal nerve

nuclear complex GSE
Arcuate nucleus
Pyramid
Figure 12.14. Transverse section of the medulla showing Its basic features , Cell columns related to functional compo-
.
nents of the cranial nerve are Indicated on the right Functional components of cranial nerves are both general and
specldl The vestibular nuclei shown at this level (and auditory nuclei at higher levels) form the special somatic affer-
.
ent (SSA) cell columns. The spinal trigeminal nucleus forms the general somatic afferent (GSA) cell column and re-
.. .
ceives fibers from cranial nerves with this functional component (i e , N. V VII, IX, and X), Functional components of
.
the vagus nerve (except GSA) are shown in relation to particular nuclei The hypoglossal nucleus (and the nuclei of N .
.
VI IV, and III at higher brainstem levels) gives rise to general somatic efferent (GSE) fibers. Heavy clashes separate the
nuclei of the various cell columns on the right side.
( Figs. 12.11, 12.12, 12.15, 12.16, and 12.18). All fourth ventricle near the median raphe gives
of the these cell columns lie lateral to the sul - rise to general somatic efferent (GSE ) fibers
cus limitans ( Fig. 12.14 ). Ventromedial to the which innervate the muscles of the tongue.
sulcus limitans are the efferent cell columns. The general somatic efferent cranial nerve
The dorsal motor nucleus of the vagus nerve nuclei all lie near the median raphe and rela-
and the inferior salivatory nucleus of the tively close to the floor of the fourth ventricle
glossopharyngeal nerve give rise to general or cerebral aqueduct . Other nuclei, at more
visceral afferent (GVE ) fibers. Cells in the nu- rostral levels, belonging to this group are
cleus ambiguus, located in the ventrolateral the abducens, trochlear, and oculomotor .
reticular formation posterior to the inferior Schematic color-coded diagrams showing
olivary nuclear complex, give rise to special these nuclei and the intramedullary course of
visceral efferent (SVE ) fibers that pass periph- their fibers ( Figs. 12.15 and 12.16) help to un-
erally along cranial nerves XI, X, and IX ( Figs. derstand the organization of cranial nerves
12.15 and 12.16). These fibers innervate mus- and their various components. The general
cles of the pharynx and larynx derived from visceral efferent (GVE ) components ( para -
the third and fourth branchial arches ( i.e., sympathetic) forming parts of cranial nerves
branchiomeric muscles). Other motor nuclei, III , VII, IX , and X are indicated in Figures
having similar locations in the pons, supply 12.15 and 12.16.
special visceral efferent (SVE ) fibers to mus-
cles derived from the first and second Hypoglossal Nerve
branchial arches via cranial nerves V and VII,
respectively ( Figs. 12.15 and 12.16 ). The hy- The hypoglossal nerve ( N . XII ) is a general
poglossal nucleus located in the floor of the somatic efferent (GSE) cranial nerve that sup-
12 Medulla 439
Visceral nuclei N III
Somatic cell columns N III

Red nucleus
Trochlear nucleus
Mesencephalic
nucleus N V
Trigeminal nerve
Principal sensory
sensory nucleus N V
motor
Abducens nucleus
Solitary fasciculus
Salivatory nucleus
Inferior olivary complex
Dorsal motor nucleus N X
Hypoglossal nucleus
~ Nucleus ambiguus
N XII
Spinal part N XI Spinal trigeminal nucleus
Spinal nuclei N
Figure 12.15. Intramedullary course of the cranial nerves in a midsagittal view. The brainstem is represented as a hol-
low shell except for cranial nerve components General somatic (GSE) and special visceral (SVE) efferent compo-
nents of cranial nerves innervating striated muscles are shown in red General visceral efferent (GVE) components of
cranial nerves III. VII. IX and X. representing preganglionic parasympathetic fibers, are shown in yellow General so-
matic (GSA). general visceral (GVA), and special visceral (SVA) afferent components of the cranial nerves are in
blue
N III ( GVE ) x
N III IGSE )
Mesencephalic nucleus
and tract N V
Midbrain
Principal sensory nucleus N V

N IV ( GSEI
N V ( GSA )
N V ( GSAI
N V ( SVE )
Dorsal motor
Nucleus N VI ( GSE )
nucleus N X
Salivatory nuclei
Superior , Vestibular nuclear
Eons complex
Inferior N VII ( SVA )
N VII ( SVE )
( GVE ) N VIII ( vestibular . SSA )
N IX ( GVE ) N IX ( SVA. GVA )
( SVE ) N X ( GVA . SVA )
Medulla
Spinal trigeminal tract
N X ( SVE )
and nucleus
( GVE )
Solitary nucleus and fasciculus
N XI. cranial
root ( SVE )
Nucleus N XII ( GSE )
spinal root ( GSE )
Cl
Spinal cord
Cll Nucleus ambiguus
Figure 12.16. Infratentorial cranial nerves showing their nuclei of origin and termination, their intramedullary course,
and their functional components The cochlear nerve and nuclei are not shown . General somatic afferent (GSA)
components of the trigeminal nerve (N. V) are shown in light blue. General and special visceral afferent (GVA SVA)
.
components of the facial (N VII), glossopharyngeal (N. IX) and vagus (N X) nerves are shown in dark blue The .
vestibular nerve which differentially distributes special somatic afferent (SSA) fibers to the vestibular nuclear complex
is white. Similarities in the intramedullary course of fibers in the spinal trigeminal tract, the vestibular nerve root and the
solitary fasciculus are evident on the right . General somatic efferent (GSE) fibers from the oculomotor (N III) and
trochlear (N. IV) nuclei, and those of the spinal root of the accessory nerve (N. XI) are light red. Only contributions
from the first and second cervical segments to the spinal root of the accessory nerve are shown. Root fibers of the ab-
ducens (N. VI) and hypoglossal (N XII) nuclei, which exit ventrally and contain GSE fibers, are not shown. Special vis-
.
.
ceral efferent (SVE) fibers from the branchiomeric cranial nerves (N. V VII, IX, X and XI) are shown In light red . Gen-
eral visceral efferent (GVE) fibers, representing preganglionic parasympathetic components, of the oculomotor (N.
.
Ill), facial (N VII) glossopharyngeal (N IX), and vagus (N X) nerves are in dark red .
plies the somatic skeletal muscles of the the pyramid and the inferior olivary complex
tongue. It innervates the ipsilateral half of the ( Figs. 12.1, 12.11, and 12.12). The hypoglossal
tongue. The hypoglossal nucleus, composed nucleus receives numerous crossed and un-
of typical multipolar motor cells, forms a col- crossed fibers from neurons in the medullary
umn about 18 mm long that is located inter- reticular formation that form delicate
nal to the trigonum hypoglossi. It begins cau - plexuses around the cells of the nucleus. It
dal to the inferior olive and extends rostrally also receives direct projections from the "cor-
to the region of the striae medullares. Root ticobulbar" fiber system, which plays a cru-
fibers of this nerve emerge ventrally, pass cial role in the voluntary motor control of the
along the lateral margin of the medial longi- tongue. Other inputs from secondary glos-
tudinal fasciculus and the medial lemniscus, sopharyngeal, vagal, and trigeminal fiber sys-
traverse medial parts of the inferior olivary tems appear involved in reflex movements of
complex, and exit from the medulla between the tongue in response to stimuli from lin -
12 Medulla 441
Oculomotor nerve
Trigeminal
ganglion \ -rv Trochlear nerve
Trigeminal nerve
Abducens nerve
Facial nerve Cochlear and vestibular
Intermediate nerve components of N. VIII
Superior ganglion
Inferior ganglion — Spinal root N. XI

Cranial root N XI
Glossopharyngial
nerve *
Superior ganglion
Inferior ganglion
Vagus nerve
Figure 12.17. Brainstem and cranial nerves showing their peripheral ganglia
Area postrema
XII
Dorsal motor nucleus of X
Inferior /Solitary tract and nucleus
cerebellar peduncle
Spinal
trigeminal
tract and
nucleus
Nucleus Inferior
ambiguus
olive
Pyramid
.
Figure 12.18 A Major cell groups and tracts in the caudal medulla. The enclosed area in the dorsomedlal portion of
.
the diagram is shown in greater detail In B B Subnuclei forming the nucleus of the solitary tract which receive affer-
. .
ents from cranial nerves IX and X AP area postrema: Cun. n. cuneate nucleus: dlls, dorsolateral nucleus of solitary
. . . . .
tract; dnrs dorsal nucleus of solitary tract; Grac rt . gracile nucleus; ICN intercalated nucleus mTS medial nucleus of
. . .
solitary tract pTS, parvicellular nucleus of solitary tract; TS solitary tract; vlTS ventrolateral nucleus of solitary tract;
.
vnTS. ventral nucleus of solitary tract; X dorsal motor nucleus of vagus nerve: XII. hypoglossal nucleus
gual, oral, and pharyngeal mucous mem- form, respectively, the internal and external
branes. branches of the nerve ( Fig. 12.17). The cranial
In the gray matter surrounding the hy- part of the nerve arises from cells in the cau-
poglossal nuclei are several discrete nuclear dal pole of the nucleus ambiguus. Axons of
groups, collectively known as the perihy- these cells emerge from the lateral surface of
poglossal nuclei. These are the nucleus interca- the medulla caudal to the lowest filaments of
late , the nucleus prepositus , and the nucleus of the vagus nerve. Fibers of the cranial part of
Roller ( Figs. 12.13, 12.25, and 12.26). The nu- the accessory nerve join the vagus nerve to
cleus intercalatus, situated between the hy- form the inferior ( recurrent ) laryngeal nerve,
poglossal nucleus and dorsal motor nucleus which innervates the intrinsic muscles of the
of the vagus, is composed predominantly of larynx. This component of the accessory
small cells and a scattering of larger cells ( Fig. nerve innervates branchiomeric musculature
12.13). Rostral to the hypoglossal nucleus is and is regarded as a special visceral efferent
the nucleus prepositus ( Figs. 12.25 and 12.26), (SVE ) component .
which extends from the oral pole of the hy- The spinal portion of the accessory nerve
poglossal nucleus almost to the abducens nu- originates from a cell column in the anterior
cleus. It is composed of relatively large cells horn of the upper five (or six ) cervical seg-
and a few smaller cells resembling those of ments. Caudally cells of this column occupy a
the nucleus intercalatus, with which it is con- lateral process of the anterior horn, but at
tinuous at more caudal levels. The nucleus of higher levels they tend to assume a more cen-
Roller, composed of relatively large cells, lies tral position. Root fibers from these cells arch
ventral to the rostral pole of the hypoglossal posterolaterally to emerge from the lateral as-
nucleus and adjacent to its root fibers ( Fig. pect of the spinal cord between the dorsal
12.13). Immediately posterior to the hy- and ventral roots ( Fig. 12.3). Rootlets of the
poglossal nucleus is a small bundle of fibers spinal portions of the accessory nerve from
in the periventricular gray matter known as upper cervical segments unite to form a com-
the dorsal longitudinal fasciculus of Schutz mon trunk (external branch ) that ascends
(174) ( Figs. 12.11 and 12.12). This composite posterior to the denticulate ligaments, enters
bundle comprises both ascending and de- the skull through the foramen magnum, and
scending fibers and is considered to be vis- ultimately exits from the skull via the jugular
ceral in nature ( 30, 87, 105, 136, 137). foramen in association with the vagus and
Lesions of the hypoglossal nerve produce glossopharyngeal nerves ( Fig. 12.17). The
a lower motor neuron paralysis of the ipsilat- spinal part of the accessory nerve innervates
eral tongue muscles with loss of muscle tone the ipsilateral sternocleidomastoid and upper
and , ultimately, atrophy of the muscles. Due parts of the trapezius muscles. Although con-
to the paralysis of the genioglossus muscle, a tractions of the sternocleidomastoid muscle
muscle that effects protrusion of the tongue, turn the head to the opposite side, unilateral
the tongue will deviate to the side of the le- lesions of the spinal accessory nerve usually
sion when protruded . The intrinsic muscles do not produce any abnormality in the posi-
alter the shape of the tongue, while the ex- tion of the head. Weakness in turning the
trinsic muscles alter its shape and position. head to the opposite side against resistance,
Intramedullary lesions involving the pyra- however, is obvious. Paralysis of the upper
mid and the hypoglossal nerve (e.g., in cases part of the trapezius muscle is evidenced by
of vascular lesion of the anterior spinal (a ) downward and outward rotation of the
artery ) produce a combined upper and lower upper part of the scapula, and ( b) moderate
motor neuron syndrome referred to as inferior sagging of the shoulder on the affected side.
or hypoglossal alternating hemiplegia. This syn-
drome is characterized by (a ) a contralateral Vagus Nerve
hemiplegia ( upper motor neuron ), and (b) an
ipsilateral paralysis of the tongue (lower This complex mixed branchiomeric nerve
motor neuron ). ( N . X ) contains (a ) general somatic afferent
(GSA ) fibers distributed to cutaneous areas
Spinal Accessory Nerve back of the ear and in the external auditory
meatus, ( b) general visceral afferent (GVA )
The accessory nerve ( N. XI ) usually is di- fibers from the pharynx, larynx, trachea,
vided into cranial and spinal portions which esophagus, and thoracic and abdominal vis-
12 Medulla 443
cera , (c ) special visceral afferent (SVA ) fibers More numerous visceral afferent fibers of the
from taste buds in the region of the epiglottis, vagus nerve pass dorsomedially into the nu -
(d ) general visceral efferent (GVE ) fibers distrib-
uted to parasympathetic ganglia located near
cleus and tractus solitarius ( Figs. 12.14
12.16). Fibers entering the solitary fasciculus
—
the thoracic and abdominal viscera , and (e) bifurcate into short ascending and longer de-
special visceral efferent (SVE ) fibers that inner- scending components. Descending vagal
vate the striated ( branchiomeric) muscles of components in the solitary fasciculus gradu -
the larynx and pharynx. ally diminish in number as collaterals and
General somatic afferent fibers of the terminals are given off to the solitary nucleus.
vagus nerve arise from cells of the superior Some vagal visceral fibers descend caudal to
ganglion of the vagus nerve, located in, or the obex, where the solitary nuclei of the two
immediately beneath, the jugular foramen sides merge to form the commissural nucleus
( Fig. 12.17). Both general and special visceral of the vagus nerve ( Fig. 12.8). A number of
afferent fibers of the vagus nerve arise from descending vagal fibers decussate and enter
the larger inferior vagal ganglion ( nodosal the contralateral half of the commissural nu -
ganglion ). Afferent vagal fibers enter the lat- cleus ( 95, 96, 164 ).
eral surface of the medulla ventral to the infe- The fasciculus solitarius is formed by vis -
rior cerebellar peduncle by traversing the ceral afferent fibers contributed by the vagus,
spinal trigeminal tract and nucleus ( Fig. glossopharyngeal, and facial ( intermediate)
12.14 ). Cutaneous afferent fibers enter the nerves ( Figs. 12.15 and 12.16 ). Fibers convey -
dorsal part of the spinal trigeminal tract ing taste from the anterior two-thirds of the
along with similar general somatic afferents tongue ( via the chorda tympani ) and from
from other branchiomeric cranial nerves. the posterior third of the tongue ( glossopha -
Ventral posteromedial
nucleus ( VPMpc)
Parabrachial
nuclei
Solitary nuclear
complex
Nucleus ambiguus
Figure 12.19. Ascending projections of the solitary nuclear complex superimposed upon a posterior view of the
brainstem. The solitary nuclear complex receives special visceral afferent (SVA) fibers via the intermediate nerve and
.
both special and general visceral afferent (SVA SGA) fibers via the glossopharyngeal and vagus nerves Cells in ros-
tral parts of the nucleus solitarius project ipsilaterally via the central tegmental tract to the small-celled part of the
.
ventral posteromedial (VPMt ) nucleus of the thalamus. Caudal parts of the solitary nucleus which receive afferents
largely from the glossopharyngeal and vagus nerves project fibers rostrally to caudal parts of the solitary nucleus and
also project collaterals to the nucleus ambiguus. The solitary nuclear complex, the nucleus ambiguus the .
parabrachial nuclei and VPMK are shown in blue
ryngeal nerve) mainly terminate in rostral The lateral subnuclei form a column of
parts of the solitary nucleus. Portions of the larger cells which partially or completely sur-
Military fasciculus at the level of entry of the rounds the solitary fasciculus ( Figs. 12.12,
vagus nerve, and caudal to it , contain mainly 12.18, and 12.20). This part of the nucleus par -
general visceral afferent fibers, largely from allels the fasciculus throughout most of its
the vagus nerve (12). length. Rostrally it extends to the lower bor-
The nucleus solitarius can be divided on cy- der of the pons, while caudally its cells di-
toarchitectonic criteria into several parts: ( a ) a minish in number and are difficult to distin -
medial part , dorsolateral to the dorsal motor guish from reticular neurons. The enlarged
nucleus of the vagus; ( b) dorsomedial, dorso- rostral part of the solitary nucleus ( i.e., the
lateral, and ventrolateral subnuclei, which lateral part ) receives mainly special visceral
surround the tract us solitarius; and (c) a parvi- afferent ( taste) fibers from the facial ( interme-
cellular subnucleus lying between the medial diate) and glossopharyngeal nerves and is re-
nucleus and the area postrema ( Fig. 11.18). ferred to as the gustatory nuclei /s ( 135, 164 ).
Although there is some variation, this general The caudal and medial solitary nuclei receive
arrangement has been observed in carnivores most of the general visceral afferent fibers
and nonhuman primates and humans ( 12, 95, from the vagus nerve, along with some facial
121, 192 ). Cells of the medial part extend ros- and glossopharyngeal fibers. Although vis-
trally slightly beyond the dorsal motor nu- ceral afferent axons to the solitary nuclear
cleus of the vagus ( Figs. 12.20 and 12.21 ). This complex terminate over an extensive rostro
caudal portion of the structure, there is a vis-
-
part of the nucleus also extends caudal to the
fourth ventricle and merges with the corre- cerotropic pattern of endings within the sub-
sponding cell column on the opposite side to nuclei ( %). Alimentary tract afferents end in
form the commissural nucleus of the vagus the parvicellular nucleus (73), pulmonary af -
nerve ( Fig. 12.8) ( 193). ferents synapse in the ventrolateral subnu -
Lateral nucleus of
Medial nucleus of fasciculus solitarius
fasciculus solitarius
GZ Ventricle
"
Ependyma
Dorsal motor nucleus Fasciculus solitarius

of vagus nerve
Figure 12.20. The vagal nuclei in the floor of the fourth ventricle based upon a drawing of a Golgi preparation of
newborn cat . Efferent (preganglionic ) fibers from the dorsal motor nucleus of the vagus nerve are indicated by a
while b indicates fibers from the medial and lateral (sensory ) nuclei of the fasciculus solitarius forming secondary va -
goglossopharyngeal pathways. The medial nucleus of the fasciculus solitarius extends caudally to the fourth ventricle
and merges with corresponding cell group on the opposite side, forming the commissural nucleus of the vagus nerve
(Fig 12 8) The lateral nucleus of the fasciculus solitarius extends rostrally. increases in size and parallels the fasciculus
solitarius throughout most of its length
12 Medulla 445
dmnX '• /
",
%P
4 mm
i \
" 3
ap 2
> *
0 bex
\ Cu \ / Cu / /
\ : :g g; : :
Figure 12.21. Horizontal section through the medulla showing the solitary tract ( 75). medial, and ventrolateral nuclei
of the solitary tract (mnFS. vlTS). dorsal motor nucleus of vagus (dmnX). and the area postrema (ap) labeled with
horseradish peroxidase (HRP) following an injection into the right inferior (nodose) ganglion of X . Survival time was 48
hours The right side of the medulla is on the right side of the diagram and rostral is upward Interrupted lines represent
the position of sensory and motor fibers of X labeled with HRP reaction product . Dots indicate terminals of afferent
projections and solid triangles shown the location of retrogradely labeled cell bodies cu cuneate nucleus; g. gracile
,
nucleus. spV. spinal trigeminal nucleus.
cleus ( 121 ), and carotid sinus afferent endings nucleus concerned with gustatory sensation ,
are concentrated in the medial and dorsome- namely the ventral posteromedial nucleus,
dial subnuclei ( 147) ( Figs. 12.21 and 12.22). pars parvicellularis ( VPM[X ) ( 11, 191 ) ( Fig.
In terms of neurotransmitters, the solitary 12.19). Other secondary fibers form the soli -
nucleus is a highly heterogeneous structure. tary nucleus projecting to the hypoglossal
Neuropeptides identified within the various and salivatory nuclei mediate lingual and se-
subdivisions of the solitary nucleus include cretory reflexes. Projections from the solitary
enkephalin, somatostatin, substance P, chole- nucleus to the dorsal motor nucleus of the
cystokinin, and neuropeptide Y. These neu - vagus nerve, the phrenic nerve nucleus ( at
ropeptides are present , sometimes in various spinal segments C3 to C5), and anterior horn
combinations, in both cell bodies and afferent cells of thoracic spinal segments are involved
fibers. Cells in the solitary nucleus contain rein coughing and vomiting reflexes. The soli -
ceptors for many neuropeptides. Many of the tary nucleus also appears to project directly
same neuropeptides have been identified in to the hypothalamic paraventricular nucleus
relay nuclei of ascending visceral and gusta- ( 42, 43). This projection may play a role in
tory pathways at all levels of the neuraxis regulation of cardiovascular function, either
( 138, 156). The largest numbers of cell bodies by exerting control over vasopressin release
containing neuropeptides and catecholamine from the neural lobe of the pituitary or by ac-
are located in the region of the solitary nu - tivating spinal sympathetic preganglionic
cleus most concerned with visceral activities. neurons through axons of the paraventricular
Secondary fiber systems originating from nucleus that reach thoracic spinal segments.
the solitary nucleus project ipsilaterally to (a ) The solitary nucleus is a complex integra -
the nucleus ambiguus and the surrounding tion center subserving many diverse func-
reticular formation, ( b ) the parabrachial nu - tions (191 ). As seen earlier, the rostral part of
clei in the rostral pons, and ( c) the thalamic the nucleus is responsible for the processing
dorsal and ventral respiratory centers (31,

188). An interesting feature of medullary cells
projecting to the parabrachial nuclei is their
orientation along the radial penetrating blood
vessels (102 ).
Cells of the medullary "respiratory cen-
ters" are activated by vagal impulses and di -
rectly by changes in their chemical environ -
ment (COi accumulation , etc.). A medullary
vasomotor "center" consisting of separate
pressor and depressor zones is also believed
to be involved in the modulation of the car -
diovascular function , but this "center" re-
mains anatomically poorly defined . Recent
emphasis has been on the distributed neural
networks concerned with cardiovascular con -
trol . A group of noradrenergic neurons (des -
ignated A 3) located in the caudal pons be-
tween the superior olive and roots of the
facial nerve and projecting axons to the nu -
cleus solitarius, the nucleus ambiguus, the
dorsal motor nucleus of the vagus nerve, and
preganglionic sympathetic neurons in the
Figure 12.22. Medulla of a cat in which the inferior (no- thoracic spinal cord , appears to be part of one
dose) ganglion of nerve X was Injected with horseradish of these neural networks ( 122, 138). Some of
peroxidase The medulla was sectioned in the horizontal the projections of the A 3 cell group to other
plane. Rostral is toward the top. lateral is to the right Sur -
vival time was 48 hours Retrograde labeling is seen in
brainstem structures are illustrated in Figure
perlkarya of the dorsal motor nucleus of vagus ( dmnX ) 12.24.
and anterograde labeling occurs in the solitary nucleus The dorsal motor nucleus of the vagus nerve
and tract ( IS) Notice labeled fibers leaving the caudal is situated in the floor of the fourth ventricle
half of the solitary tract which is situated between TS and
dmnX In the lower half of the Figure (calibration bar. 500
posterolateral to the hypoglossal nucleus
( Figs. 12.11 , 12.13, and 12.14) . This column of
iim).
small spindle-shaped cells extends both ros-
trally and caudally beyond the hypoglossal
nucleus. Some larger cells in the nucleus con -
and relaying of gustatory sensations from the tain coarse chromophilic bodies and scattered
facial , glossopharyngeal, and vagus nerves melanin pigment. Cells of this nucleus give
(191, 206 ) . Thus, the rostral pole of the soli - rise to preganglionic parasympathetic fibers
tary nucleus corresponds to the human gus- (GVE ) ( Figs. 12.21 and 12.22). Axons of these
tatory nucleus of Nageotte (135) and the nu - cells traverse the spinal trigeminal nucleus
cleus ovalis of Olszewski and Baxter (144 ) and tract and emerge on the lateral surface of
( see also 141 ) . Furthermore, the nucleus of the the medulla between the olive and the resti -
solitary tract is coextensive with the physio- form body ( Figs. A.4 and A .5 in the atlas of
logically defined dorsal medullary respira - the human brain shown in Section VII ). The
tory "center" ( 94 ), which includes the nucleus dorsal motor nucleus contains relatively few
ambiguus and surrounding portions of the myelinated fibers, indicating that most of the
medullary reticular formation. terminals entering it are unmyelinated . These
Additional brainstem regions important are principally secondary fibers from the sen-
for the regulation of respiration are found in sory nuclei of the glossopharyngeal and
the pons. The medial parabrachial nucleus vagus nerves, and from visceral centers ( Figs.
and the adjacent nucleus of Kolliker Fuse
constitute the functionally defined "pneumo-
- 12.21-12.23). The dorsal motor nucleus of the
vagus is the vagal secretory secretomotor
taxic center ." An apneustic center was also center. Cells of the dorsal motor nucleus are
proposed , but has not been anatomically de- strongly immunoreactive to choline acetyl-
lineated . The parabrachial nuclei of the pons transferase (ChAT) ( Fig. 12.31 ). Destruction
receive afferent connections from the solitary of this nucleus greatly reduces insulin -in -
nucleus (94 ), and in turn project to both the duced secretion of gastric acid .
12 Medulla 447
3 • /
v
%
>•* « «Jfc t
, »
- 4 J
•4
*
J
i'dfnnj'i " V*. w >, ' »
<
;> ’ #
4. A *
-
'
V •
•
^
•<
•
m* ‘. '
•
-*JV
»
. .**
•
.*
Figure 12.23 . Medulla of cats in which the inferior (nodose) ganglion of nerve X was injected with either horseradish
peroxidase or trltiated amino acid. The brain was sectioned transversally . Dorsal is toward the top and the midline to
the left . In all photomicrographs, the rostrocaudal level Is 1 mm rostral to the obex A. Darkfleld photomicrograph The
Inferior ganglion was Injected with horseradish peroxidase 48 hours before the animal was prepared for histologic ex -
amination. Retrograde labeling is seen in the dorsal motor nucleus of X (dmnX ) and anterograde labeling is seen in
the medial nucleus of the solitary tract (mnTS) as well as dorsomedially in the area postrema (ap). Afferents fibers
from the mnTS are seen entering the dmnX and come into close contact with labeled perikarya (calibration bar 250 .
.
nm) B Darkfield photomicrograph The inferior vagal ganglion was injected with trltiated amino acid 5 days prior to
preparation for examination. In the upper right, the mnTS contains a high concentration of silver grains. The dmnX
also contains a grain concentration that is above background level (calibration bar. 250 |im). C. Brlghtfleld photomi-
.
crograph of exactly the same field as the one shown in B (calibration bar 250 |im).
ing projections
Facial (VII) nerve

Abducens ( VI) nerve
PONS A5 region
Superior olivary
nucleus
of vague nerve
Nuclei and
solitary tract
MEDULLA
Nucleus ambiguus
Hypoglossal ( XII) nerve
THORACIC Intermediolateral
SPINAL CORD cell column
Intercalated spinal
nucleus
Sympathetic
Vagus nerve ganglia
HEART
Figure 12.24. Descending projections of the A5 catecholamine cell group which lies lateral to the superior olivary nu-
cleus and projects to (a) medullary vasomotor areas, (b) preganglionic sympathetic neurons, and (c) Intercalated
spinal neurons Medullary nuclei receiving fibers from the A5 cell group Include (a) the nuclei of the solitary tract, (b)
the dorsal motor nucleus of the vagus nerve, (c) the nucleus ambiguus, and (d) the paramedian and medial
medullary reticular formation Inputs reaching cells of the intermediolateral cell column and Intercalated spinal neu-
rons project to postganglionic sympathetic neurons, which In turn project to the cardiovascular system Electrical
stimulation of the A5 cell group produces increases In systemic blood pressure and pulse pressure. Ascending projec -
tions from the A5 cell group have been described but not fully characterized
The nucleus ambiguus is a column of cells in posed of typical multipolar lower motor neu -
the reticular formation about halfway rostro- rons . Fibers from the nucleus arch dorsally ,
caudally between the spinal trigeminal nu - join efferent fibers from the dorsal motor nu -
cleus and the inferior olivary complex ( Figs. cleus of the vagus nerve, and emerge from
12.8, 12.11 , 12.13-12.16 ) . This nucleus, extend - the lateral surface of the medulla dorsal to the
ing from the level of the decussation of the inferior olivary complex ( Figs . 12.14-12.16 ) .
medial lemniscus to levels through the rostral Caudal parts of the nucleus ambiguus give
third of the inferior olivary complex, is com- rise to the cranial part of the spinal accessory
12 Medulla 449
nerve, while rostral parts of this cell column carotid sinus reflex ipsilaterally. As a rule,
give rise to glossopharyngeal special visceral visceral disturbances are not marked follow-
efferent fibers ( which innervate the stylopha - ing a unilateral lesion of the vagus nerve. A
ryngeus muscle). Special visceral efferent unilateral lesion of the recurrent laryngeal
fibers of the vagus nerve ( and those from the nerve will result in hoarseness of the voice
cranial part of the accessory nerve which re- and coughing attacks which in time diminish
join the vagus nerve) innervate the muscles of and disappear. The abductor muscles of the
the pharynx and larynx ( Figs. 12.14 and larynx are affected first.
12.16). The nucleus receives various projec- Bilateral lesions of the vagus nerve causes
tions, including corticobulbar (crossed and complete paralysis of the pharynx and lar-
uncrossed ) fibers involved in the voluntary ynx, and will result in death due to asphyxia
control of swallowing and phonation ( Fig. unless a tracheotomy is performed immedi -
12.27). The nucleus also receives impulses ately. Paralysis and atonia of the esophagus
from receptors in the pharyngeal and laryn- and stomach produce pain and vomiting. The
geal muscles, and from secondary vagal, heart rate becomes rapid and irregular due to
glossopharyngeal, and trigeminal fibers, removal of vagal inhibition. This condition is
Fibers in these three nerves convey impulses associated with marked dysphagia and
from the oral, pharyngeal, and respiratory dysarthria ,
mucosa that mediate various reflexes, such as
coughing, vomiting, and pharyngeal and la - Glossopharyngeal Nerve
ryngeal reflexes.
A unilateral lesion of the vagus nerve pro- This nerve ( N . IX ) is related closely to the
duces ipsilateral paralysis of the soft palate, vagus nerve, sharing common medullary nu -
pharynx, and larynx, which results in hoarse- clei and having similar functional compo-
ness, dyspnea , and dysphagia. During nents. Fibers of this nerve enter and emerge
phonation, the soft palate is elevated on the from the medulla at levels rostral to the
normal side and the uvula deviates to the rootlets of the vagus nerve, but like the vagus
normal side. The palatal reflex is lost on the nerve, they traverse the spinal trigeminal
lesion side. Anesthesia of the pharynx and tract and nucleus ( Figs. 12.14, 12.25, and
larynx results in an ipsilateral loss of the 12.26 ). The glossopharyngeal nerve is easier
cough reflex, while destruction of visceral to identify than the vagus nerve, because its
motor fibers of the vagus nerve abolishes the fibers form a single compact nerve root .
Medial vestibular nucleus Medial longitudinal fasciculus
Inferior vestibular I Nucleus prepositus

nucleus
Nucleus of fasciculus
..
& \ I 0
L
_ _
Dorsal cochlear nucleus
solitorius wmir Inferior cerebellar

SAL. peduncle
Spinal nucleus and ET’irv'

4- •
•
tract of trigeminal
^
z ' 1
nerve
— Ventral cochlear
nucleus
N IX
Olivocerebellar /
/
/
/
V
*
N IX
fibers : -k Anterior spinocerebellor troct
V
*
Amiculum of yv. Inferior olivary nuclear
inferior olive complex
Corticospinal tract Medial lemniscus

Arcuate nucleus
Figure 12.25. Transverse section of medulla of 1 -month infant through the cochlear nuclei and ninth nerve (Weigert s 1
myelin stain).
Medial vestibular nucleus

Nucleus prepositus Dorsal cochlear nucleus
Stria medullaris
Inferior vestibular
nucleus
Dorsal paramedian Inferior cerebellar
nucleus peduncle
Medial longitudinal _ Spinal trigeminal
fasciculus nucleus S tract
Tectospinal tract
Ventral cochlear
nucleus
Reticular formation N IX
Olivocerebellar
fibers
Medial lemniscus Spinothalamic tract
Central tegmental tr
( amiculum of olive)
Pyramid Inf olivary nucleus
Figure 12.26 Transverse section through the upper medulla at the level of the cochlear nuclei and the root fibers of
. .
the glossopharyngeal nerve. S lateral nucleus of the fasciculus solitarius Pb. pontobulbar nucleus (Weigert ' s myelin
stain).
Fibers of the vagus nerve enter and emerge (GVA ) fibers convey tactile sense, thermal
from the brainstem by a number of small sense, and pain from the mucous membranes
rootlets. The glossopharyngeal is a mixed of the posterior third of the tongue, the tonsil,
branchiomeric cranial nerve with these func- the posterior wall of the upper pharynx, and
tional components: (a ) general visceral afferent the Eustachian tube. Special visceral afferent
( GVA ) fibers, ( b) special visceral afferent (SVA ) fibers convey taste sensation from the poste-
fibers ( taste), (c) a few general somatic afferent rior third of the tongue. Visceral afferent
(GSA ) fibers, (d ) general visceral efferent (GVE ) fibers entering the posterolateral part of the
fibers, and (e) a small number of special vis- medulla are distributed to rostral portions of
ceral efferent (SVE ) fibers. Like the vagus the solitary fasciculus and its nucleus ( Fig.
nerve, it has two sensory peripheral ganglia , 12.25). Rostral and lateral parts of the nucleus
a small superior ganglion in the jugular fora- solitarius that receive fibers from the facial
men, and a larger extracranial inferior ( pe - (intermediate ) and glossopharyngeal nerves
trosal ) ganglion ( Fig. 12.17). The glossopharyn- constitute the "gustatory nucleus."
geal nerve also has a motor ganglion, the otic The carotid sinus nerve conveys impulses
ganglion , situated below the foramen ovale from the carotid sinus, a baroceptor located at
and medial to the mandibular division of the the bifurcation of the common carotid artery.
trigeminal nerve. Increases in carotid arterial pressure excite
Primary sensory neurons mediating gen- carotid sinus baroceptors and impulses are
eral somatic sense (GSA ) from cutaneous conveyed centrally by the glossopharyngeal
areas back of the ear lie in the superior gan- nerve to the nucleus of the solitary tract (147).
glion . Central processes of these cells enter Second order neurons in the solitary nucleus,
the spinal trigeminal tract and nucleus. Cell in turn, excite cells of the dorsal motor nu -
bodies of visceral afferent fibers lie in the in- cleus of the vagus nerve and bring about re-
ferior ganglion . General visceral afferent ductions in heart rate and arterial pressure
12 Medulla 451
via cholinergic pre- and postganglionic vagal the nucleus of the facial nerve and the rostral
fibers that act upon the sinoatrial and atri - end of the inferior olive. The cells on each
oventricular nodes, as well as atrial heart side of the midline can be considered "swal-
muscle. The carotid sinus reflex , involving lowing half -centers" which are coordinated
glossopharyngeal visceral afferents and vagal through extensive interconnections.
general visceral efferents, constitutes a mech- Swallowing can be readily initiated by
anism for the regulation of arterial blood stimulation of the endings of the internal
pressure. branch of the superior laryngeal nerve ( part
General visceral efferent fibers, arising of the vagus nerve). Stimulation of the maxil-
from the inferior salivatory nucleus , pass via lary division of the trigeminal nerve and of
the lesser petrosal nerve to the otic ganglion . the glossopharyngeal nerve can also trigger
Postganglionic fibers originating from the deglutition . Afferent neurons convey infor-
cells of the otic ganglion convey parasympa - mation from oropharyngeal receptive fields
thetic secretory impulses to the parotid to neurons in the lateral subnuclei of the soli-
gland . Cells of the inferior salivatory nucleus tary complex. Projections from the solitary
are scattered in lateral parts of the reticular nucleus to all the cranial motor nuclei in-
formation and can be positively identified volved have not been demonstrated anatomi -
immunocvtochemicallv by antiserum to cally, but it is likely that interneurons within
ChAT. the reticular formation are part of the reflex
Special visceral efferent fibers, as already circuit .
described , arise from rostral portions of the
nucleus ambiguus ( Figs. 12.15 and 12.16). CORTICOBULBAR FIBERS
These fibers, small in number, innervate the
stylopharyngeus muscle and perhaps por - Corticofugal fibers projecting to, and ter-
tions of the superior pharyngeal constrictor minating in, portions of the lower brainstem
muscle. are referred to as corticobulhar fibers . These
As the foregoing description indicates, the fibers arise mainly from cortex on both side
glossopharyngeal nerve is predominantly a of the central sulcus and project to (a ) sensory
sensory nerve and a nerve contributing pre- relay nuclei, ( b) parts of the reticular forma -
ganglionic parasympathetic fibers to the otic tion , and (c) certain motor cranial nerve nu -
ganglion. Isolated lesions of the glossopha - clei.
ryngeal nerve are rare. Disturbances associ- Sensory relay nuclei receiving corticobulbar
ated with lesions of the nerve include (a ) loss fibers include the nuclei gracilis and cunea -
of the pharyngeal (gag ) reflex, ( b) loss of the tus, the sensory trigeminal nuclei, and the nu -
carotid sinus reflex, and (c) loss of taste in the cleus of the solitary fasciculus ( 28, 111-117,
posterior third of the tongue. Glossopharyngeal 193, 200, 211 ). Corticobulbar fibers to the pos-
neuralgia resembles trigeminal neuralgia in terior column nuclei leave the corticospinal
that the excruciating paroxysmal pain may be tract and enter these nuclei by traversing the
triggered by seemingly trivial stimuli such as medial lemniscus or the reticular formation.
coughing or swallowing. The pain associated After unilateral cortical lesions, degenerated
with this syndrome radiates from the neck terminal fibers are distributed bilaterally to
into regions behind the ear. the posterior column nuclei, but are most nu -
Swallowing, or deglutition, is a complex merous contralaterally. There are suggestions
motor act which involves three identifiable of somatotopic projections between portions
neuroregulatory systems: (a ) buccopharyn- of the precentral and postcentral gyri and the
geal, ( b) esophageal, and (c) gastroesophageal nuclei gracilis and cuneatus, but considerable
(58). The effector neurons lie in the motor overlap also is evident (113). In rodents, pro-
nuclei of the trigeminal, facial, vagus jections from primary somesthetic cortex is
(amibiguus), and hypoglossal nerves. Unlike organized so that fibers from the forelimb
spinal motor cells, neurons in the cranial cortical area terminate in the nucleus cunea -
motor nuclei have no recurrent collaterals tus and those from the hindlimb area end in
which activate inhibitory interneurons. The the nucleus gracilis ( 211 ). In carnivores, corti-
neurons controlling the buccopharyngeal cobulbar fibers are distributed preferentially
phase of deglutition are located in the to portions of the dorsal column nuclei that
medullary reticular formation close to the contain loosely organized cells. Few fibers
midline and dorsal to the inferior olive. These from the cortex appear to terminate in "cell
cells are found between the caudal border of nest" regions, which receive ascending fibers
from spinal dorsal roots ( 117). Corticobulbar give rise to (a ) long ascending and descend -
fibers projecting to all trigeminal sensory nu - ing projections ( 27, 194), (b ) projections to the
clei and the nucleus solitarius are derived cerebellum ( 23, 47), and ( c) projections to cra -
from widespread cortical regions, with the nial nerve nuclei ( 173).
largest number arising from the frontopari- The motor cranial nerve nuclei innervating
etal region ( 28). Corticofugal fibers to the nu - skeletal muscles receive impulses from the
cleus solitarius terminate chiefly in its rostral cerebral cortex via corticobulbar pathways.
part , near levels where facial and trigeminal These fibers arise mainly from portions of the
afferents end . precentral gyrus and descend through the in -
Corticobulbar fibers, projecting to the pos- ternal capsule and brainstem in association
terior column and trigeminal sensory nuclei, with the corticospinal tract ( Figs. 2.12, 11.12,
are part of a complex mechanism whereby and 12.27). They constitute the upper motor
descending cortical impulses can modulate neurons for the motor cranial nerve nuclei .
the transmission of ascending sensory im- Most of the so-called corticobulbar fibers con-
pulses at the second neuron level . Both exci- veying impulses to motor cranial nerve nuclei
tatory and inhibitory effects upon these sen- are actually corticoreticular fibers. Neurons
sory relay nuclei can be produced by in the reticular formation serve to relay im-
stimulation of the cerebral cortex ( 70, 75, 79, pulses to motor cranial nerve nuclei . In non -
88). Excitatory and inhibitory actions appear primate species, it has not been possible to
to be exerted differentially upon portions of trace corticobulbar fibers to direct termina-
the nucleus gracilis that are distinguishable tions in motor cranial nuclei ( 111, 201, 211 ). In
on the basis of the size of the receptive field these animals, cortical influences upon motor
and sensory modality represented ( 70, 71 ). cranial nerve nuclei are mediated by corti-
Corticofugal inhibitory influences are princi- coreticular fibers and synaptically related
pally exerted in middle portions of the nu - reticular neurons projecting to the motor nu -
cleus, where individual cells responded to clei. This indirect system is supplemented in
movement of hair, light touch to foot pads, humans and nonprimates by corticobulbar
pressure at the base of a claw, or subcuta - fibers that project directly to particular motor
neous pressure. These cells exhibited small cranial nerve nuclei. Nuclei receiving these
receptive fields and were inhibited by stimuli direct corticobulbar projections are the
applied outside the physiologic receptive trigeminal, facial, hypoglossal, and
field ( i .e., surround inhibition ). Corticofugal supraspinal ( 112 ). These fibers are bilateral
excitatory effects were found mainly in ros- and nearly equal, except for those passing to
tral and deep parts of the middle region of parts of the facial nucleus, which are more
the nucleus, where individual cells re- abundant contralaterally ( Fig. 12.27). The
sponded principally to touch and pressure. more numerous corticoreticular fibers form
These cells with rather large receptive fields the basis of an indirect corticobulbar system
do not display the phenomenon of surround present in most mammalian species and in
inhibition . which neurons in the reticular core serve as
Corticoreticular fibers projecting to the internuncial elements. Direct corticobulbar
lower brainstem arise predominantly from fibers represent a parallel system that is par-
the motor, premotor and somesthetic cortical ticularly well -developed in humans and non-
areas ( 168). Fibers descend in association human primates.
with the corticospinal tract, leave the tract at The supranuclear innervation of motor cranial
various levels, and enter the brainstem reticu- nerve nuclei is largely bilateral and more com -
lar formation. The bulk of these fibers termi- plex than that present at spinal levels. Corti-
nate in two fairly circumscribed areas, one in cobulbar projections are bilateral to those cra -
the medulla and another in the pons. In the nial nuclei that innervate muscle groups that,
medulla , these fibers terminate in the area of as a rule, cannot be contracted voluntarily on
the nucleus reticularis gigantocellularis; in one side ( Fig. 12.27). These include the laryn-
the pons, most of the fibers end in the rostral geal, pharyngeal, palatal, and upper facial
pontine reticular formation ( nucleus reticular muscles. The same principle applies to the
pontis oralis). Corticoreticular fibers are dis- muscles of mastication and the extraocular
tributed bilaterally but with a slight contralat - muscles. Because unilateral stimulation of the
eral predominance ( 211 ). Regions of the retic- motor cortex produces isolated contraction of
ular formation, receiving corticofugal fibers, contralateral lower facial muscles, and unilat-
12 Medulla 453
.
Motor cortex for eye face,
mouth, pharynx, larynx, and
neck (lower precentral gyrus)
Ant. limb of
internal capsuleC /L-\_- —
Large pyramidal cells
of Betz ( upper motor
Claustrum neurons)
Cortex of insula
Putamen Corticobulbar tract in
Globus pallidus genu of internal capsule
Post, limb of internal
capsule Superior colliculus
MIDBRAIN
Medial lemniscus
Substantia nigra
Oculomotor (III) nerve
Crus cerebri
Trochlear (IV) nucleus

and nerve
MIDBRAIN Tegmentum of midbrain
Sensory and motor nuclei

trigeminal ( V) nerve p - Middle cerebellar
PONS peduncle
Lower motor neuron-

Ventral portion of pons
fiber in trigeminal ( V)
nerve
Facial ( VII) nerve

and nucleus Tegmentum of pons
PONS
Abducens ( VI) nerve -

of vagus and axon of Reticular formation
visceral efferent of medulla
neuron
Vagus nerve ( X )
Nucleus ambiguus
MEDULLA To motor endings in

sternomastoid and
trapezius mm.
Lower motor neuron in Anterior gray horn

spinal accessory ( XI) nerve ' -rf **
v ‘
Figure 12.27. "Corticobulbar " pathways in the brainstem. Fibers of this upper motor neuron pathway to the motor
cranial nerve nuclei arise in the cerebral cortex, pass caudally In the internal capsule, the crus cerebri, and the ven-
tral portion of the pons, and are distributed largely to neurons in the reticular formation bilaterally. Reticular neurons
conveying the impulses to the motor cranial nerve correspond to the intercalated on internuncial neurons found at
spinal levels. In human and nonhuman primates, this indirect system is paralleled by direct corticobulbar fibers distrib-
uted to the motor nuclei of the trigeminal, facial and hypoglossal nerves
eral lesions involving corticobulbar fibers prolonged periods of time, contractures may
produce paralysis only of contralateral lower appear in the muscles of the lips, tongue, and
facial muscles, cell groups of the facial nu - palate (78). Cranial nerves V, VU, and IX
cleus innervating the lower facial muscula- through XII may be involved , together or in
ture are regarded as receiving only crossed varying combinations, as a result of bilateral
corticobulbar fibers. The fact that unilateral interruption of the corticobulbar tracts cen-
stimulation of the motor cortex causes turn- trally ( Fig. 12.27 ) . Bilateral lesions involving
ing of the head to the opposite side has been "corticobulbar pathways" above pontine lev-
interpreted as indicating that corticofugal els usually are the result of extensive de-
fibers to nuclei innervating the sternocleido- myelinating disease, vascular disease, throm -
mastoid muscle probably are uncrossed , be- bosis, or neoplasms.
cause contraction of this muscle turns the
head to the opposite side. It seems likely that CHEMICAL ANATOMY
some uncrossed corticospinal fibers ( Figs.
11.13 and 11.14 ) project to spinal accessory As seen in Chapter 5, the functional orga -
cell groups innervating this muscle and the nization of the central nervous system is de-
upper part of the trapezius muscle, although pendent on transmitter molecules ( neurome-
direct fibers to these cells appear meager diators ) to convey neural information across
( 112 ). Eye movements elicited by electrical synapses. There are a large number of neuro-
stimulation of the cerebral cortex are always mediators recognized as having unique prop-
conjugate, indicating that the supranuclear erties in certain neural circuits and probably a
innervation of the nuclei of the extraocular great many more that remain to be identified .
muscles is bilateral. There are two major types of neuromediators:
Because the supranuclear innervation of ( a ) small- molecule transmitters, such as vari -
the motor cranial nerve nuclei is largely bilat - ous amino acids, biogenic amines, and acetyl -
eral, unilateral lesions interrupting cortico- choline, and ( b) neuroactive peptides belong-
bulbar fibers ( upper motor neuron ) produce ing to different families, such as tachykinins,
comparatively mild forms of paresis. Only opioids, and pancreatic polypeptides ( 48).
slight weakness of tongue ( genioglossus mus- Small-molecule transmitters can rapidly turn
cle) and jaw movements ( pterygoid muscles) the signals on or tiff as impulses arrive at the
contralateral to the lesions can usually be de- synapses, while neuroactive peptides can
tected . These are seen as modest deviation of modify signals, act over a different time
the tongue or jaw to the side opposite the le- course, influence neuronal metabolism, or
sion. However, marked weakness in the con- prepare cells for later neural events. A proper
tralateral lower facial muscles is evident with knowledge of the chemical coding of neurons
such lesions. Weakness of lower facial mus- and neuronal circuits is essential to under -
cles becomes obvious when the patient at - standing the anatomic and functional organi -
tempts to show the teeth , purse the lips, or zation of the central nervous system , compre-
puff out the cheeks. hension of a variety of neurologic diseases,
Pseudobulbar palsy results from bilateral and deciphering the nature of many drug ac-
lesions involving corticobulbar fibers. This tions. Immunohistochemical and in situ hy-
syndrome is characterized by weakness or bridization methods can reveal information
paralysis of muscles involved in swallowing, concerning the site and level of synthesis and
chewing, breathing, and speaking, and may storage of known or suspected neuromodula -
occur with relatively little paralysis in the ex- tors. Autoradiographic techniques can pro-
tremities. Loss of emotional control, charac - vide information concerning the localization
terized by inappropriate outbursts of laugh- of transmitter binding sites. Retrograde tract-
ing and crying, form an important part of the tracing methods combined with immunocy-
syndrome. These symptoms appear as the tochemistry make it possible to undertake de-
physiologic expression of rather extensive bi - tailed mappings of particular chemospecific
lateral lesions in the upper brainstem or at neuronal systems in the brain.
higher levels. Although there is marked pare- In the medulla , neuromediators of particu -
sis of the muscles of mastication and in the lar interest are: ( a ) the indolamine serotonin
muscles of the face, tongue, pharynx, and lar- (5-hydroxytrvptamine or 5-HT ), ( b ) various
ynx, these muscles do not atrophy, since the catecholamines, such as norepinephrine (or
lower motor neurons remain intact. After noradrenaline) and epinephrine (or adrena -
12 Medulla 455
line), (c) acetylcholine, and (d ) various neu - bulk of serotoninergic neurons in the medulla
roactive peptides, including substance P and lies within the raphe nuclei, some serotonin -
enkephalin . ergic neurons are scattered more laterally
among neurons of the reticular formation ( 40,
Serotonin and the Raphe Nuclei 54, 92, 148, 149, 158, 184, 192 ). Fibers originat -
ing from cells in the raphe nuclei are distrib-
Cell groups lying along the midline of the uted widely in the neuraxis and release sero-
medulla , pons, and midbrain collectively are tonin, as well as other neuromodulators, at
called the raphe nuclei. The major raphe nu - their terminals. Thus, the raphe nuclei may
clei of the brainstem are shown in Figure be viewed as a diffusely distributed multi -
12.28, a schematized midsagittal section of transmitter system . The serotonin neuronal
the brainstem . The raphe nuclei are not exclu - system can be considered as a component of
sively composed of neurons that use sero- the brainstem reticular formation, which has
tonin as a neurotransmitter . Neurons display - widespread and partly overlapping projec-
ing immunoreactivity to amino acids, such as tions.
-
y aminobutyric acid (GABA ) ( 41, 93) and In the medulla , serotoninergic neurons lie
glycine (85), as well as to neuropeptides, such in the nuclei raphe pallidus, raphe obscurus,
as substance P, enkephalin , cholecystokinin, and raphe magnus ( Fig. 12.28). These nuclei
and thyrotropin- releasing hormone, occur correspond respectively to groups Bl , B2, and
within the confines of the raphe nuclei (18, B3 of Dahlstrdm and Fuxe ( 54 ) . They give rise
138, 185). Certain serotoninergic neurons in principally to descending spinal projections.
the raphe nuclei coexpress other neuromedia - The raphe nuclei in the pons and midbrain
tors, particularly neuropeptides (3, 90), but are the sources of ascending projections that
also the excitatory amino acids aspartate and arborize profusely in the diencephalon and
glutamate (139 ). Furthermore, although the telencephalon . Cells in the nucleus raphe
.Pineal
ventricle
luperior colliculus
.Inferior colliculus
Periaqueductal gray
^
MIDBRAIN
Nucleus linearis
Dorsal raphe nucleus-^
Medial raphe nucleus"^
PONS
Nucleus raphe pontis
Nucleus raphe magnus
MEDULLA
Nucleus raphe pallidus IV ventricle
Nucleus raphe obscurui
\
Figure 12.28 . Midsagittal section of the brainstem indicating the positions of the raphe nuclei Nuclei in red project to
spinal levels, while those in blue have extensive projections to nuclei in the brainstem Projections to diencephalic
structures are most numerous from the dorsal and medial raphe nuclei and from the nucleus raphe pontis. The dorsal
and medial raphe nuclei also project widely to telencephallc structures.
magnus give rise to bilateral spinal projec- and II in caudal part of the spinal trigeminal
tions that descend in the dorsolateral funicu - nucleus and in the spinal cord (8, 10). Neuro-
lus and terminate principally in laminae I and mediators involved in the mediation of pain
II of the spinal posterior horn, and less abun- probably are multiple and appear to act upon
dantly in the intermediate gray matter and nociceptive interneurons, as well as neurons
anterior horn (9 ) ( Fig. 12.29). Portions of the that give rise to pain pathways ( i.e., anterolat -
motor nucleus of the facial nerve, the caudal eral tract neurons ).
part of the spinal nucleus of the trigeminal Medullary raphe nuclei also synapse di -
nerve, and the nucleus of the solitary tract re- rectly upon sympathetic preganglionic neu-
ceive a substantial serotonin innervation rons in the intermediolateral column (5), and
(184) . stimulation of medullary raphe nuclei pro-
Stimulation of nucleus raphe magnus produces inhibition of sympathetic pregan -
duces an analgesic effect by an inhibitory ac- glionic neurons (32). These findings indicate
tion upon nociceptive neurons in laminae 1 that the descending serotoninergic projec -
Vestibular nuclei IV Ventricle Inferior cerebellar
Inferior peduncle
Medial
Spinal trigeminal
Cochlear tract and nucleus
nerve
Nucleus raphe
Inferior olive magnus
Corticospinal
tract Middle cerebellar
peduncle
Pontine nuclei
PONTOMEDULLARY
JUNCTION Abducens ( VI)
nerve
CERVICAL
ENLARGEMENT
THORACIC
SPINAL CORD
Figure 12.29 . Spinal serotoninergic projections from the nucleus raphe magnus These projections are bilateral, de-
.. .
scend in the dorsal part of the lateral funiculus and terminate principally upon cells in spinal cord laminae I II and V
considered to receive nociceptive inputs. Large reticular neurons adjacent to the nucleus raphe magnus project
fibers ipsilaterally to the same laminae in the posterior horn, but are not serotoninergic . Both of these pathways are
considered links in an endogenous analgesia-producing system. Fibers from the nuclei raphe pallidus and obscurus
(not shown) descend in the ventral quadrant of the spinal cord.
12 Medulla 457
tions from the medullary raphe nuclei play a and the superficial layers of the posterior
role in the control of various autonomic horn of the spinal cord . These projections are
mechanisms, such as those involved in the ensured by noradrenergic neurons scattered
maintenance of blood pressure (49). throughout rostral regions of the lateral retic-
ular nucleus and adjacent reticular formation
(118). These ventrolaterally located noradren-
Catecholaminergic Neurons
ergic neurons form the groups A 5 and A7 of
Catecholamines present in significant con- Dahlstrom and Fuxe ( 54). The A5 cell group,
centrations in the medulla are norepineph- which lies lateral to the superior olivary com-
rine and epinephrine. The enzyme plex, sends noradrenergic fibers to medullary
--
dopamine |3 hydroxylase ( DBH ) transforms vasomotor centers, the intermediolateral cell
dopamine to norepinephrine, while the en- column at thoracic levels, and intercalated
zyme phenylethanolamine-n -methyltransfer- neurons at the same levels. These projections
ase (PNMT) converts norepinephrine to are collectively referred to as the lateral
epinephrine. Thus, DBH and PNMT are con- tegmental system. Medullary nuclei receiving
venient markers for noradrenergic and noradrenergic fibers from the A5 cell group
adrenergic neurons, respectively, and anti - include ( a ) the dorsal motor nucleus of the
sera raised against each of these enzymes vagus, (b) the nucleus ambiguus, (c) the nu-
allow a clear visualization of these two types clei of the solitary tract, and (d ) portions of
of catecholaminergic neurons. Specific anti- the medial medullary reticular formation. De-
sera to norepinephrine and to epinephrine scending projections to the spinal cord are re-
are also available, but their use requires par- layed via preganglionic and postganglionic
ticularly stringent technical conditions. Since sympathetic neurons to cardiovascular struc-
most brainstem catecholaminergic cell tures (123). The A7 cell group lies in the ven-
groups in primates are pigmented , this fea - trolateral portion of the pontine reticular for-
ture has been used as a criteria for the identi- mation medial to the lateral lemniscus and
fication of catecholaminergic neurons in gives rise to descending noradrenergic fibers
human brainstem (15). that terminate principally in the superficial
layers of the posterior horn of the spinal cord
(44). This descending noradrenergic system is
NORADRENERGIC CELL GROUPS
believed to be involved in the modulation of
The locus coeruleus (group A6 ), a blue- nociception (209).
black pigmented nucleus located at the upper Noradrenergic cells found in the lower
pons levels, is the largest collection of nora- part of the medulla and have been designated
drenergic neurons in the brain. This structure groups A1 and A2 by Dahlstrom and Fuxe
distributes noradrenergic fibers throughout (54). Cells of group A1 surround the nucleus
the central nervous system (138). Neurons in of the lateral funiculus and extend dorsome-
the ventral part of the locus coeruleus and dially into the lateral part of the medullary
in the subcoeruleus area give rise to descend- reticular formation . Cells of this group pro-
ing fibers that course in the lateral and ven- ject noradrenergic fibers to the solitary nu-
tral funiculi and arborize within nearly all cleus, the dorsal motor nucleus of the vagus
segments of the spinal cord (85, 138, 160). The nerve, the locus coeruleus, and the para-
coeruleospinal noradrenergic fibers terminate brachial nucleus in the pons. Cells of group
in the ventral parts of the posterior horn A 2 lie within the solitary nucleus, the dorsal
(laminae IV, V , and VI ), the intermediate gray motor nucleus of the vagus nerve, and the in-
matter, and the anterior horn. Through its no- tervening areas. Numerous cells of the A 2
radrenergic spinal projections, the locus group are found more caudally within the
coeruleus is believed to be involved in such confines of the area postrema . This dorsal
diverse functions as modulation of pain (91) medullary group provides a heavy bilateral
and control of spinal motor output (64). Fur- noradrenergic innervation to the solitary nu-
thermore, the coeruleospinal noradrenergic cleus. Cells in the A1 and A2 groups also give
fibers are likely to give collaterals to various rise to fibers that ascend toward the telen-
medullary structures, such as the inferior oli- cephalon (172).
vary complex (180). In primates, the Al , A5, and A7 groups
The locus coeruleus does not project sig- form a caudorostral continuum that extends
nificantly to the intermediolateral cell column throughout the lateral portion of the brain-
stem reticular formation (152). Caudal parts that they may play a role in the regulation
of this lateral tegmental nuclear complex are of blood pressure and respiration . The
connected with group A2 by strands of nora - medullary adrenergic neurons may also be
drenergic cells. Rostrally, a comparable involved in the modulation of spinothalamic
strand of noradrenergic cells forms a bridge cells ( 34).
between the locus coeruleus complex and the
A5-A7 groups. These intervening cells lie
Cholinergic Neurons
partly within the confines of the medial
parabrachial and Kolliker- Fuse nuclei, which Neurons containing acetylcholine ( ACh )
are considered as a "pneumotaxic center" in can be identified immunocytochemically
the medulla . The axons emerging from this with antisera raised against choline acetyl -
noradrenergic neuronal complex branch pro- transferase (ChAT), the enzyme that synthe-
fusely throughout the entire rostrocaudal ex- sizes ACh, or histochemically by visualizing
tent of the neuraxis (138). the hydrolytic enzyme acetylcholinesterase
( AChE ) (151, 178). While there is a general
ADRENERGIC NEURONS correspondence between ChAT immunoreac-
tivity and the presence of AChE, the hy-
Three groups of neurons displaying drolytic enzyme also is present in noncholin-
PNMT immunoreactivity occur in the lower ergic neurons, nerve fibers, and terminals,
portion of the medulla (83). By analogy with and is not considered a specific marker of
the nomenclature of Dahlstrom and Fuxe cholinergic neurons. As seen in previous
( 54 ), these groups have been designated as
chapters, ACh is released at the neuromuscu -
Cl , C2, and C3 (83). Cell group Cl , the largest lar junction, as well as at the terminals of all
of the three, lies lateral to the inferior olivary preganglionic neurons. All motor cranial nu -
complex and contains 69% of the total num- clei, all somatic spinal motor neurons, and all
ber of PNMT cells in the medulla . Cell group preganglionic autonomic neurons react posi-
C2 is located partly within and partly adja- tively to ChAT and are considered as cholin-
cent to the solitary nucleus and comprises ergic neurons. Postganglionic sympathetic
22% of the total number of PNMT cells. Cell neurons innervating the sweat glands also
group C3, which contains the remaining 9%> are cholinergic. In the medulla , cells of the
of the PNMT-immunoreactive cells, is com - hypoglossal nucleus, the dorsal motor nu-
posed of rather isolated elements inter- cleus of the vagus, and the nucleus ambiguus
spersed among the fibers of the medial longi- are all immunoreactive to ChAT ( Fig. 12.31 ).
tudinal fasciculus and scattered from the When thin sections of brain tissue are in-
level of the hypoglossal nerve to that of the cubated with a radioactive ligand , which
dorsal raphe nucleus (138). The Cl and C2 binds to ACh receptors with high specific ac-
cell groups form a rostral continuation of tivity, the general distribution of binding
groups A 1 and A2, respectively. sites can be observed in autoradiographs. The
Adrenergic fibers that emerge from the highest density of muscarinic acetylcholine
C1-C3 area ascend through the reticular for- receptors is found in the nucleus of the hy-
mation to the hypothalamus, where they poglossal nerve (cranial N. XII ) and nucleus
densely innervate the paraventricular nu- ambiguus ( cranial N. IX and X ), with some-
cleus (83, 138). The Cl and C2 nuclei also pro- what lower densities in the solitary nucleus
vide an adrenergic input to the ventral part of and lateral reticular nucleus. Still lower den-
the locus coeruleus, the solitary nucleus, the sity is observed in the dorsal motor nucleus
dorsal motor nucleus of the vagus nerve, and of the vagus nerve ( 205). In the medulla , nico-
the intermediolateral cell column in the tinic ACh receptors have their highest con-
spinal cord . Little is known of the central ac- centrations in the dorsal motor nucleus of the
tions of the adrenergic cells in the medulla . vagus nerve ( 2).
The dense innervation of the hypothalamic
paraventricular nucleus suggests that they
might be involved in the control of oxytocin Neuroactive Peptides
and vasopressin secretion, while the promi- OPIOID PEPTIDES
nent input to the solitary nucleus, the dorsal
motor nucleus of the vagus nerve, and the Immunocytochemical methods also have
sympathetic preganglionic neurons indicate been used to visualize cell bodies and termi -
12 Medulla 459
Figure 12.30. Immunocytochemlcal fea-

ture of the caudal spinal trigeminal tract
and nucleus in a monkey A. Fibers im-
I munoreactive for substance P in the spinal
trigeminal tract and in laminae I and II of
' the spinal trigeminal nucleus. B. Fibers and
cells in the spinal trigeminal nucleus
immunoreactive for leucine-enkephalin ,
Section were taken from the same animal.
X
nals containing the opiate peptides met- and enkephalinergic neuronal pathways is still in-
leu -enkephalin ( 4, 61, 82, 84, 156, 1%). In the complete. The morphine agonist properties of
medulla , cell bodies displaying enkephalin enkephalins (86) led to the analysis of the role
immunoreactivity occur in laminae II (sub- of enkephalinergic descending projections in
stantia gelatinosa layer ) and Ill of the caudal mechanisms of nociception and analgesia (7,
portion of the spinal nucleus of cranial N. V 8, 10). Other studies have suggested that
( Fig. 12.30). Other enkephalin-labeled cells enkephalins and related peptides may have
are found in the solitary nucleus and in a much broader functions, and it is now known
ventral cluster lying lateral to nucleus raphe that enkephalins and morphine bind to sepa-
magnus. Axons and terminals containing rate subclasses of opiate receptors. The orga -
enkephalins are generally seen in regions nization of descending pain control systems
containing labeled cell bodies. Additionally, is complex. Brainstem projections to the
enkephalinergic fibers form moderately spinal cord other than those arising from
dense terminal plexuses in the motor nuclei enkephalin-containing neurons in the
of the facial and hypoglossal nerves and in medulla have been shown to affect spinal
parts of the reticular formation (156 ). neurons which respond to noxious stimula-
The study of the functional significance of tion (74, 81, 126, 142).
Figure 12.31. Transverse sections through

the medulla of a monkey immunoreacted : £
with antiserum raised against the enzyme
choline acetyltransferase (ChAT), which is
considered a reliable market for choliner - • •
gic neurons . A Cholinergic neurons in the

.
hypoglossal nucleus ( X/f) the dorsal motor
.
nucleus of the vagus (DMN X) and the nu-
cleus amblguus (AM6) B. Cholinergic neu-
rons in the nucleus ambiguus
AMB :
'J
SUBSTANCE P OXYTOCIN AND VASOPRESSIN

Substance 1’ is a peptide of 10 amino acids A surprising finding emerging from stud -
present in several neural systems. About 2( )'/r ies of biologically important peptides in the
of the cell bodies in spinal ganglia contain brain, is the presence of posterior pituitary
substance I’. Fibers of these cells project via gland hormones in the brainstem and spinal
dorsal root filaments to terminate in laminae 1 cord . The nonapeptides oxytocin and vaso-
and II of the posterior horn ( Fig. 12.30) (also pressin are synthesized by cells in discrete
see Chapter 10). Similar numbers of subnuclei of the hypothalamus (see Chapter 17)
stance P-containing cell bodies are found in and transported along axons to terminals in
the trigeminal ganglion . Substance P-contain - the posterior lobe of the pituitary. Double-
ing cell bodies are small , and give rise to labeling experiments have demonstrated that
small, poorly myelinated fibers that encode the hypothalamic nuclei which innervate the
nociceptive information . Substance P pro- posterior pituitary gland contain separate
duces a prolonged excitation of central neu - subpopulations of cells with descending pro-
rons. In the medulla , terminals enriched with jections (186 ). The axons reaching the
substance P are found in the superficial lami- medulla contain mainly oxytocin and end in
nae of the caudal trigeminal nucleus, in the the solitary nucleus, dorsal motor nucleus of
solitary nucleus, and in some cells of the the vagus nerve, lateral reticular nucleus, and
raphe nuclei ( 32, 138, 136 ). Substance P also within lamina 1 ( marginal layer ) of the spinal
may coexist with other neuromediators in nucleus of N . V ( 133, 140). When oxytocin is
some neurons of the medulla . released into the circulation from the poste -
12 Medulla 461
rior lobe of the pituitary gland , it acts upon rostrodorsally. The fibers of this inferior cere-
smooth muscle of the uterus during parturi- bellar peduncle lie medial to the middle cere-
tion and upon myoepithelial cells of the bellar peduncle ( Fig. 12.33).
mammary gland during milk letdown. The In the floor of the fourth ventricle, the nu -
function of this peptide in the medulla is un- cleus prepositus lies medially in the position
known , but it is interesting to note that oxy- previously occupied by the hypoglossal nu -
tocin containing axon terminals are found in cleus. Lateral to this nucleus are the vestibu -
or near regions rich in catecholamine and lar nuclei ( Figs. 12.25 and 12.33). At this level,
enkephalin containing terminals. portions of the medial and inferior vestibular
nuclei are seen . The inferior vestibular nu -
MEDULLARY - PONTINE JUNCTION cleus lies adjacent to the medial surface of the
restiform body and is characterized by nu -
The fourth ventricle reaches its maximum merous, relatively coarse, myelinated fiber
width at the level of the lateral recesses ( Figs. bundles which course through it . These fibers
12.2, 12.32, and A.6). These lateral extensions coursing longitudinally in the axis of the nu -
of the fourth ventricle pass external to the in- cleus are descending primary vestibular
ferior cerebellar peduncle and the cochlear fibers and cerebellar efferent fibers. The me-
nuclei ( Fig. A.5). The lateral wall of each re- dial vestibular nucleus is highly cellular and
cess is formed by the peduncle of the flocculus , contains finer fibers, most of which are not
a part of the flocculonodular lobe of the cere- myelinated . In some preparations, myeli-
bellum lying close to the lateral surface of the nated fibers of the striae medullares of the
medulla ( Fig. 12.32 ). The cochlear nerve and medulla can be seen in the floor of the fourth
the dorsal and ventral cochlear nuclei , lie on the ventricle dorsal to the nucleus prepositus and
medial and rostroventral surfaces of the lat- the vestibular nuclei. These fibers arise from
eral recess. The restiform body has achieved the arcuate nucleus, pass dorsally in the
its maximum size, and fibers of the cochlear raphe, and project laterally in the floor of the
nerve curve around its lateral and superior fourth ventricle to the cerebellum.
surfaces. At slightly more rostral levels, Root fibers of the cochlear nerve , conveying
above the lateral recess, the inferior cerebellar impulses from the organ of Corti in the
peduncle enters the cerebellum by passing cochlea , enter the posterolateral margin of the
Emboliform
nucleus
Dentate
nucleus -r
Vermis
EZ Ventricle
Peduncle
of flocculus
Inf centrol
Pontobulbar - nucleus
nucleus
Flocculus -N TZir ( motor )
Cochlear
nerve
Ventral portion
Nm - of pons
Figure 12.32. Transverse section through the junction of medulla and pons in a 1 -month infant . Portions of the cere-
bellum containing large parts of the intracerebellar nuclei are attached. Structures In and around the tegmentum
are Identified in Figure 12.33 (Weigert ' s myelin stain).
Dorsal Lateral Dentate nucleus

cochlear Nucleus Medial vestibulor ^
nucleus prepositus vestibular nucleus - Peduncle of flocculus
^ ^
l / lnf. cerebellar peduncle
^lr» f. vestibular nucleus
Nucleus spinal troct N.Y
^
^ Spinal tract of N . Y
Ventral cochlear nucleus
Motor nucleus of N. 3ZH
—
~~ Vestibular nerve root
"'•' Fibers trapezoid body
Cochlear Ventral " Motor root N . 2E
nerve cochleor ,^ Ant. spinocerebellar
nucleus A
ond spinothalamic tracts
Pyramid Pons
Central tegmentol tract
Inferior olivary nucleus
Root fibers of N YL Medial lemniscus
Figure 12.33. transverse section of medulla of a 1 -month infant through caudal border of pons f c p Foramen
cecum posterior; MLF , medial longitudinal fasciculus (Weigerfs myelin stain).
upper medulla. Primary auditory fibers ter- the cerebellum, ( b) reduction in size and, ulti -
minate upon two nuclear masses, the ventral mately, disappearance of the inferior olivary
and dorsal cochlear nuclei . The dorsal cochlear complex, (c ) incorporation of the corti-
nucleus forms a prominence, the tuberculum cospinal tract within the ventral part of the
acusticum , along the lateral border of the pons, (d ) enlargement of the reticular forma -
rhomboid fossa ( Figs. 12.26, 12.33, and A .6 ). tion , and (e) appearance of cranial nerve nu -
Cells of the dorsal cochlear nucleus are small, clei and root fibers typical of this higher level .
ovoid, and fusiform , while those of the ven- Cranial nerves present at the junction of
tral nucleus are large, round cells with a medulla and pons are the abducens, cochlear,
dark-staining cytoplasm. Secondary auditory vestibular, and facial . The abducens nerve
fibers arising from the dorsal and ventral emerges at the lower border of the pons lat-
cochlear nuclei become apparent at more ros- eral to the pyramids. All other cranial nerves
tral brainstem levels. at this level are grouped together at the cere-
The inferior olivary complex is reduced in bellopontine angle , formed by the junction of
-
size at the medullo pontine junction, and the
accessory olivary nuclei disappear ( Fig.
medulla , pons, and cerebellum ( Fig. 12.17).
All of these nerves emerge from , or enter, the
12.32 ). Anterior to the olivary complex, the internal auditory meatus. The cochlear nerve
fibers of the pyramid are surrounded by pon- is the most caudal and lateral, while the facial
tine nuclei and some transverse fibers. The nerve is the most rostral and medial . The
medial lemniscus and medial longitudinal vestibular nerve lies between the cochlear
fasciculus occupy the same positions as at and facial nerves. These cranial nerves are de-
more caudal levels, although they are slightly scribed and discussed in the next chapter.
separated from the corresponding tract on In the upper medulla , the medial lemnis-
the opposite side by more fully developed cus reaches its full extent. It forms a vertical
nuclei in the median raphe. Other ascending band of heavily myelinated fibers on either
and descending tracts maintain the same rel - side of the raphe dorsal to the pyramids ( Fig.
ative positions as at lower medullary levels. 12.26). The formation and course of this tract
The junction of medulla and pons ( Figs. are shown in Figure 11.1. The lateral and ante-
12.32 and 12.33) is characterized by (a ) pas- rior spinothalamic tracts occupy a retro-oli -
sage of the inferior cerebellar peduncle into vary position ( Fig. 12.26). Corticobulbar fibers
12 Medulla 463
leave the pyramids and pass dorsally into the eases, neoplasms, and vascular pathology are
reticular formation ( Fig. 12.27); intercalated the most common . Demyelinating diseases
neurons lying in the reticular formation, in usually are disseminated and involve multi-
turn , project upon motor cranial nerve nuclei ple systems at different sites. Neoplasms tend
( 201 ). The medial longitudinal fasciculus, tec- to extend in the longitudinal axis of the brain-
tospinal, and tectobulbar tracts occupy an stem. Vascular lesions show great variation,
area dorsal to the medial lemniscus on each but often give rise to characteristic syn-
side of the median raphe. The tracts are par - dromes. The vascular syndrome most com -
tially separated by lighter-stained areas repre- monly seen in the medulla is attributed to oc-
senting the raphe nuclei. At somewhat higher clusion of the posterior inferior cerebellar
levels, this position is occupied by the inferior artery ( PICA ), a vessel that supplies struc-
central nucleus ( Figs. 12.32 and 13.4 ). Other tures in the posterolateral region . While it
descending tracts, such as the rubrospinal and seems likely that this syndrome may more
vestibulospinal, are difficult to distinguish in frequently result from the involvement of the
-
Weigert stainod material . vertebral artery and its smaller branches (6),
As the inferior cerebellar peduncle enters the symptoms and signs are similar and un-
the medullary core of the cerebellum, it is mistakable. Lateral medullary syndrome (or
covered externally by the fibers of the middle Wallenberg' s syndrome ) is characterized by (a )
cerebellar peduncle, which arise from the loss of pain and thermal sense in the ipsilat -
ventral part of the pons. The development of eral half of the face and the contralateral half
the ventral portion of the pons envelops the of the body, (b) nausea , (c) vertigo, (d ) distur-
medullary pyramids. The blind end of the an- bance of equilibrium, (e) persistent hiccup,
terior median fissure, overhung by the pons, and ( f ) dysphonia ( hoarse voice) (53). Distur-
is known as the foramen cecum posterior ( Fig. bances forming parts of this syndrome fre-
12.33). The attenuated rostral pole of the infe- quently can be correlated with the extent and
rior olivary nucleus is flanked laterally by the precise location of the medullary lesion. Dor-
fibers of the central tegmental tract, and me- solateral structures commonly involved in
dially and ventrally by the medial lemniscus. lateral medullary syndrome include ( a ) the
The medial lemniscus gradually becomes flat - spinal trigeminal tract and nucleus, (b) the
tened dorsoventrally and lies along the ven - spinothalamic tract, (c ) efferent fibers of the
tral border of the pontine tegmentum ( Fig. vagus and glossopharyngeal nerves originat-
11.1 ). The light -staining area separating the ing from the nucleus ambiguus, ( d ) parts of
medial lcmnisci and the medial longitudinal the inferior cerebellar peduncle, as well as
fasciculi is occupied by raphe nuclei . fiber systems projecting toward this pedun-
Lesions of the medulla or structures cle, and ( e) variable portion of the inferior
within it can be produced by a variety of cerebellar cortex. The blood supply of the
causes, but those due to demyelinating dis- medulla is discussed in Chapter 4 .
References and lower medulla . Brain Res modulating systems. J Comp Neu -
1977;124:53-67. rol 1978; 178:209-224.
1 . Adey VVR , Segundo JP, Livingston 5. Bacon SJ , Zagon A , Smith AD. 9. Basbaum Al , Fields HL . The origin
RB Corticofugal influences on in-
. Electron microscopic evidence of a of descending pathways in the
trinsic brain stem conduction in cat monosynaptic pathway between dorsolateral funiculus of the spinal
and monkev . J Neurophvsiol cells in the caudal raphe nuclei and cord of the cat and rat: further
1957;20:1-16. sympathetic preganglionic neu - studies on the anatomy of pain
2. Arimatsu V , Seto A . Amano T. An rons in the rat spinal cord . Exp modulation . J Comp Neurol
atlas of u -bungarotoxin binding Brain Res 1990;79:589-602. 1979;187: 513-532.
sites and structures containing 6. Baker AB . Cerebrovascular dis- 10 . Basbaum Al , Ralston DD, Ralston
acetylcholinesterase in the mouse ease. IX . The medullary blood sup- HJ . Bulbospinal projections if the
central nervous system . J Comp ply and the lateral medullar)' syn - primate: a light and electron mi -
Neurol 1981 ; 198:603-631 . drome Neurology 1961 ;11 :852-
. croscopic studv of a pain modulat -
3. Arvidsson U , Ulfhake B, Cullheim 861. ing system . J Comp Neurol
S, et al . Thyrotropin-releasing hor- 7. Basbaum Al , Clanton CH , Fields 1986;250:311-323.
mone ( TRH ) - like immunoreactiv - HL . Opiate and stimulus- produced 11 . Beckstead RM , Morse JR , Norgren
itv in the grey monkey ( Mtiaica fas - analgesia : functional anatomy of R . The nucleus of the solitary tract
cicularis ) spinal cord and medulla medullospinal pathways. Proc in the monkey : projections to the
oblongata with special emphasis Natl Acad Sri USA 1976;73: thalamus and brain stem nuclei . J
on the bulbospinal tract . J Comp 4685-4688. Comp Neurol 1980; 190:259-282.
-
Neurol 1992;322:293 310.
4 Atweh SF , Kuhar MJ . Autoradi -
8. Basbaum Al , Clanton CH , Fields 12. Beckstead RM , Norgren R . An au -
HL . Three bulbospinal pathways toradiographic examination of the
ographic localization of opiate re- from the rostral medulla of the cat : central distribution of the trigemi -
ceptors in rat brain . 1 . Spinal cord an autoradiographic study of pain nal , facial , glossopharyngeal and
vagal nerves in the monkey . J cofugal fibers to sensory trigeminal 43. Ciriello J , Calaresu FR . Monosy -
Comp Neurol 1979;184:455-472. nuclei and nucleus of solitary tract . naptic pathway from cardiovascu -
13 Berkley KJ , Hand PJ . Projections to J Comp Neurol 1956 ;106:527 555.- lar neurons in the nucleus tractus
the inferior olive of the cat. II 29. Brodal A, Szikla G. The termina- solitarii to the paraventricular nu -
Comparisons of input from the tion of the brachium conjunctivum cleus in the cat. Brain Res 1980;
gracile, cuneate and the spinal descendens in the nucleus reticu - -
193:529 533.
trigeminal nuclei. J Comp Neurol laris tegmenti pontis: an experi - 44. Clark FM, Proud fit HK . The pro-
1978;180:253-264 mental study in the cat . Brain Res jection of noradrenergic neurons
14 . Berkley KJ, Worden IG . Projections 1972 ;39:337-351 . in the A7 catecholamine cell group
to the inferior olive of the cat . I 30. Burgi S, Bucher VM . Markhaltige to the spinal cord in the rat
Comparisons of input from the Faserverbindungen im Himstamm demonstrated by anterograde trac -
dorsal column nuclei, the lateral der Katze. Berlin: Springer-Verlag, ing combined with immunocyto -
cervical nucleus, the spino-olivary 1950 chemistry. Brain Res 1991;547:
pathways, the cerebral cortex and 31 Bystrzycka EK . Afferent projec- 279-288.
the cerebellum . J Comp Neurol tions to the dorsal and ventral res- 45. Clemente CD, van Breemen VL.
1978;180:237-252. piratory nuclei in the medulla ob- Nerve fibers in the area postrema
15. Bogerts B. A brainstem atlas of cat - longata of the cat studied by the of cat, rabbit , guinea pig and rat .
echolaminergic neurons in man. horseradish peroxidase technique. Anat Rec 1955;123:65-79.
using melanin as a natural marker Brain Res 1980;185:59-66. 46. Clemente CD, Sutin J , Silverstone
J Comp Neurol 1981;197:63-80. 32. Cabot JB, Wild JM, Cohen DH. JT. Changes in electrical activity of
16. Borison HL, Wang SC. Functional Raphe inhibition of sympathetic the medulla on the intravenous in -
localization of central coordinating preganglionic neurons. Science jection of hypertonic solutions . Am
mechanisms or emesis in cat. J 1979;203:184-186. J Physiol 1957;188:193-198.
Neurophysiol 1949;12:305-313. 33. Cammermever J . Is the human 47. Combs CM . Bulbar regions related
17. Borison HL, Wang SC. Physiology area postrema a neuro- vegetative to localized cerebellar afferent im -
and pharmacology of vomiting. nucleus? Acta Anat ( Basel ) 1947; pulses. J Neurophysiol 1956;19:
-
Pharmacol Rev 1953;5:193 230. 2: 294-320. -
285 300.
18. Bowker RM , Westlund KN , Sulli - 34. Carlton SM , I londa CN, Wiilcock - 48. Cooper JR, Bloom FE, Roth RH .
van MC, Wilber JF, Coulter JD De- son WS, et al . Descending adrener - The biochemical basis of neu -
scending serotonergic, peptidergic gic input to the primate spinal cord ropharmacology . 6th ed . New
and cholinergic pathways from the and its possible role in modulation York: Oxford University Press,
raphe nuclei: a multiple transmit - of spinothalamic cells. Brain Res 1991
ter complex. Brain Res 1983; 1991 543:77-90. 49. CooteJH . Bulbospinal serotonergic
288:33-48. 35. Carpenter MB, Brittin GM , Pines J . pathways in the control of blood
19. Bowman JP, Sladek JR Morphol - Isolated lesions of the fastigial nu - pressure. J Cardiovasc Pharmacol
ogy of the inferior olivary complex clei in the cat . J Comp Neurol 1990;15:35-41.
of the rhesus monkey ( Macaco mu 1958;109:65-90. -
50. Courville J , Faraco Cantin F. On
Itittu ). J Comp Neurol 1973;152: 36. Carpenter MB, Hanna GR . Fiber the origin of the climbing fibers of
-
299 316. projections from the spinal trigem - the cerebellum : an experimental
-
20. Brizzee KR , Neal LM. A re evalua - inal nucleus in the cat. J Comp study in the cat with an autoradi -
tion of the cellular morphology of Neurol 1961;117:117-132. ographic tracing method . Neuro -
the area postrema in view of recent 37. Carpenter MB, Nova HR . Descend - science 1978;3:797-809.
evidence for a chemoreceptor func- ing division of the brachium con - 51. Cruce Wl.R, Newman DB. Evolu -
tion . J Comp Neurol 1954;100:
41-62.
junctivum in the cat : a cerebello-
reticular system . J Comp Neurol
—
tion of motor systems the reticu -
lospinal pathways. Am Zool
21 . Brodal A . Experimentelle Unter - 1 ^60 : 114: 295-305. -
1984;24:733 753.
suchungen ufaier die olivocerebel - 38. Carpenter MB, Stein BM , Shriver 52. Cuello AC, Kanazawa I. The distri -
lare Lokalisation . Z Gesamte Neu - JE. Central projections of spinal bution of substance P immunore-
rol Psychiatry 1940;169:1 - 153. dorsal roots in the monkey . II . active fibers in the rat central ner-
22. Brodal A . Spinal afferents to the Lower thoracic, lumbosacral and vous system . J Comp Neurol
lateral reticular nucleus of the coccygeal dorsal roots. Am J Anat 1978;178:129-156.
medulla oblongata in the cat: an 1968;123:75-118. 53. Currier RD, Giles CL, Dejong RN .
experimental study. J Comp Neu - 39. Chan - Palav V . Paratrigeminal nu - Some comments on Wallenberg's
-
rol 1949,91:259-295. cleus. II . Identification and interre- lateral medullary syndrome. Neu-
-
23. Brodal A . Reticulo cerebellar con -
nections in the cat: An experimen -
lations of catecholamine axons, in-
dolamine axons and substance P
rology 1961;11:778-791.
54. Dahistrom A , Fuxe K . Evidence for
tal study . J Comp Neurol 1953; immunoreactive cells in neuropil. J the existence of monoamine-con -
98:113-153. Neurocytol 1978;4:419-442. taining neurons in the central ner -
24 . Brodal A. The reticular formation 40. Chan - Palay V . Morphological cor- vous system. 1 Demonstration of
of the brain stem. Anatomical as- relates for transmitter synthesis, monoamines in the cell bodies of
pects and functional correlations. transport , release, uptake and ca- brain stem neurons. Acta Physiol
Springfield , IL: Charles C Thomas,
1957.
tabolism: a study of serotonin neu -
rons in the nucleus paragigantocel- .
55. Dawson NJ, Hellon RF Hubbard
—
Scand 1964;62(Suppl 232 ):1 55.
25. Brodal A . Die Verbindungen des lularis lateralis. In: Fonnum F, ed . JI . Cell responses evoked by tooth
Nucleus cuneatus extemus mil Amino acids as chemical transmit - pulp stimulation above the mar -
dem Kleinhirn beim Kaninchen ters. New York: Plenum Press, ginal layer of the cat's trigeminal
und bei der Katze: Experimentelle 1978:1-30. nucleus caudalis. J Comp Neurol
Untersuchungen . Z Gesamte Neu - 41 . Cho HJ , Basbaum A . GABAergic -
1980;193:983 994.
rol Psychiatry 1961 ;171:167-199. circuitry in the rostral ventral 56. Dykes RW , Rasmussan PD, Streta -
26. Brodal A . Neurological anatomy in medulla of the rat and its relation - van D, Rehaman NB. Submodality
relation to clinical medicine. 3rd ship to descending antinociceptive segregation and receptive field se -
ed . New York: Oxford University controls. J Comp Neurol 1991; quences in the cuneate, gracile,
Press, 1981. 303:316-328. and external cuneate nuclei of the
27. Brodal A , Rossi GF. Ascending 42. Ciriello J , Calaresu FR . Autoradi - cat . I Neurophvsiol 19H 2 ; 47
fibers in brain stem reticular for - ographic study of ascending pro - .389-416.
mation of cat . Arch Neurol Psychi - jections from cardiovascular sites 57. Dostrovsky JO, Hellon RF. The
atry 1955 ;74:68-87. in the nucleus tractus solitarii in representation of facial tempera -
28. Brodal A , Szabo T, Torvik A . Corti - the cat Brain Res 1980;180:448-453. ture in the caudal trigeminal nu -
12 Medulla 465
deus of the cat. J Physiol (Lond ) of the solitary tract in the cat . Neu - umn nuclei of cat , including an
1978;277:29-48 . road I ftt 1979; 14: 13- 17 analysis of pathways. J Neuro-
38 . Doty RW . Neural organization of 74 . Haber LH , Martin RF, Chatt AB, physiol 1961;24:499-509 .
deglutition . In : Gode CP. ed . Willis WD. Effects of stimulation in 89. Jacobsohn L . Uber die Kerne des
Handbook of physiology Vol. IV, nucleus reticularis gigantocellu - menschlichen Riichenmarks Ab-
Sect . 6 Washington, DC: American
. laris on the activity of spinothala - handlungen des konigl preuss
Physiological Society , 1968: 1861 - mic tract neurons in the monkey . Akademie der Wisscnschafte, 1908
39 .
1902.
Eccles JC, I to M , Szentagothai ) .
- .
Brain Rea 1978;153:163 168
75. Hagbarth KE, Kerr DIB. Central in -
72.
90 . Johansson O, I Iokfelt T, Pernow B,
The cerebellum as a neuronal ma - fluences on spinal afferent conduc- et al Immunohistochemical sup-
.
chine. New York: Springer- Verlag, tion . J Neurophysiol 1954; 17: port for three putative transmitters
1967. 295-307 . in one neuron : coexistence of 5 - hv -
60 . Ferraro A , Barrera SF.. Posterior 76 . Hamori J , Szentagothai J Identifi - droxytryptamine, substance P- and
column fibers and their termina - cation under the electron micro- thyrotropin releasing hormone-
tions in the Macacus rhesus. J Comp scope of climbing fibers and their like immunoreactivity in medul -
Neurol 1935;62:507-530. synaptic contacts. Exp Brain Res lary neurons projecting to the
61 . Finley JCW , Maderdrut |L , Petruz 1966; 1 :65-81 . spinal cord. Neuroscience I 981 ;6:
P. The immunocytochemical local - 77 . Hand I ’J . Lumbosacral dorsal root 1857- 1881 .
ization of enkephalin in the central terminations in the nucleus gracilis 91 . Jones SL. Descending noradrener-
nervous system of the rat J Comp
. of the cat: some observations on gic influences on pain . Prog Brain
Neurol 1981 ; 198:341-565. terminal degeneration in other Res 1991 ;88:381 - 394 .
62 . Florence SL, Wall JT, Kaas Jl 1 . The medullary sensory nuclei . J Comp 92. Jones BE , Friedman L . Atlas of cat -
somatotopic pattern of afferent Neurol 1966; 126: 136-156. echolamine perikarya, varicosities
projections from the digits to the 78 . Haymaker W . Bing's local diagno- and pathways in the brainstem of
spinal cord and cuneate nucleus in sis in neurological diseases. St. the cat . J Comp Neurol 1983;
macaque monkeys. Brain Res
'
Louis: C.V . Mosby, 1956:57-62; 215:382-3%.
1988;452: 388-392. 105-112. 93. Jones BE , Holmes CJ , Rodriguez-
63 . Florence SL , Wall JT, Kaas JH . So- 79 . Hemandez-Peon R , Hagbarth KE . Veiga E, Mainville L . GABA - syn -
matotopic organization of inputs Interaction between afferent and thesizing neurons in the medulla
from the hand to the spinal gray cortically induced reticular re- their relationship to serotonin - con -
and cuneate nucleus of monkeys sponses . J Neurophvsiol 1955; taining and spinally projecting
with observations on the cuneate 18:44-55 . neurons in the rat . J Comp Neurol
nucleus of humans. J Comp Neurol 80. Hinman A , Carpenter MB . Efferent 1991;313:349-367.
1989, 286:48-70. fiber projection of the red nucleus 94 . Kalia M Neuroanatomical organi -
,
64 . Fung SJ , Manzoni D, Chan JY , in the cat . J Comp Neurol zation of the respiratory centers.
Pompeiano O, Barnes CD. Locus 1959; 113:61 -82. Fed Proc 1977;36:2405-2411 .
coeruleus control of spinal motor 81 . Hodge CJ, Apkarian AV, Stevens 95 . Kalia M , Mesulam M - M . Brain
output . Prog Brain Res 1991 ; R , Vogel -Sang G, Wisnicki HJ . stem projections of sensory and
88:395-409 . Locus coeruleus modulation of motor components of the vagus
65 . Gilman S, Marco LA . Effects of dorsal horn unit responses to cuta - complex in the cat . 1. The cervical
medullary pyramidotomy in the neous stimulation . Brain Res vagus and nodose ganglion . J
monkey . 1 Clinical and electro- 1981 ;204:415-420. Comp Neurol 1980;193:435-465.
myographic abnormalities. Brain 82. Hokfelt T, Elde R , Johansson O, %. Kalia M , Mesulam M - M . Brain
1971 ;94:495-514 Terenius L , Stein L . The distribu - stem projections of sensory and
66 . Gobel S . Golgi studies of the sub- tion of enkephalin immunoreactive motor components of the vagus
stantia gelatinosa neurons in the cell bodies in the rat central ner - complex in the cat . II . Laryngeal ,
spinal trigeminal nucleus . 1 Comp vous system . Neurosci Lett tracheobronchial , pulmonary , car -
Neurol 1975;162:397-416. 1977;5:25-31 . diac , and gastrointestinal branches .
67. Gobel S. Golgi studies of the neu - 83 1 iokfelt T, Fuxe K , Goldstein M , Jo-
. J Comp Neurol 1980;193:467-508.
rons in layer 1 of the dorsal horn of hansson O . Immunohistochemical 97 . Kaas JH Somatosensory system
.
the medulla ( trigeminal nucleus evidence for the existence of In : Paxinos G, ed . The human ner -
caudalis ) . J Comp Neurol 1978; adrenaline neurons in the rat brain . vous svstem . Ch . 24. New York
180:375-394 . Brain Res 1974;66:235-251 Academic Press, 1990:813-844 .
68 . Gobel S. Golgi studies of the neu - 84 . Hokfelt T, Terenius T, Kuypers 98 . Kerr FWL. Structural relation of
rons in layer II of the dorsal horn HGJM , Dann O. Evidence for the trigeminal spinal tract to upper
of the medulla ( trigeminal nucleus enkephalin immunoreactivity neu - cervical roots and the solitary nu -
caudalis) . J Comp Neurol 1978; rons in the medulla oblongata pro- cleus in the cat. Exp Neurol
180:395-414 . jecting to the spinal cord . Neurosci 1961 ;4:134- 148.
69 Gobel 5, Purvis MB Anatomical Lett 1979;14:55-60. 99. Kerr FWL Facial , vagal and glos-
.
studies of the organization of the 85. Holstege JC, Bongers CM . A sopharyngeal nerves in the cat : af -
spinal V nucleus: the deep bundles glycinergic projection from the ferent connections . Arch Neurol
and the spinal V tract . Brain Res ventromedial lower brainstem to 1962;2:264-281 .
1972;48:27-44 . spinal motoneurons. An ultrastruc- 100. Kerr FWL . The divisional organi -
70. Gordon G, Jukes MGM . Dual orga - tural double labeling study in rat .
'
zation of afferent fibers of the
nization of exteroceptive compo- Brain Res 1991;566:308-315 . trigeminal nerve Brain 1 %3;86
.
nents of the cat's gracile nucleus. J 86. Hughes J , Smith T, KottaftitZ II , 721 -732.
Physiol ( Lond) 1964;173:263-290 . Fothergill L, Morgan B, Morris H . 101 Kimmel DL, Kimmel CB , Zarkin A .
71 . Gordon G, Jukes MGM Descend -
. Identification of two related pen - The central distribution of afferent
ing influences on the exteroceptive tapeptides from the brain with po- nerve fibers of the facial and vagus
organization of the cat's gracile tent opiate agonist activity . Nature nerves in the guinea pig. Anat Rec
nucleus . J Physiol ( Lond ) 1964; 1975;258:577-579. 1961 ;139:245 .
173:291 J19. 87. Ingram WR . Nuclear organization 102 . King GW . Topology of ascending
.
72. Gordon C , Paine PH . Functional and chief connections of the pri - brainstem projections to the nu -
organization in nucleus gracilis of mate hypothalamus. Proc Assoc cleus parabrachialis in the cat J
the cat . J Physiol ( Lond ) 1960; Res Nerv Ment Dis 1940;20: Comp Neurol 1980;191 :615-638 .
153 : 331 - 349 . 195 244 103. Kneisley LW , Biber MP, LaVail JH .
73. Gwyn DG , Leslie RA , Hopkins 88. Jabbur SJ , Towe AL . Cortical exci - A study of the origin of brain stem
DA Gastric afferent to the nucleus
. tation of neurones in dorsal col - projections to monkey spinal cord
using the retrograde transport in cat inferior olive. J Neurophysiol to the midbrain in the cat . Brain
method. Exp Neurol 1978;60:116- 197437:560-571. 195831:319-340.
139 121 Loewy AD, Burton H. Nuclei of 137. Nauta WJH . The central viscero -
104 . Koella WP, Sutin J . Extra blood
-
-
brain barrier brain structures. Int
- the solitary tract : efferent projec
tions to the lower brain stem and
- motor system: a general survey. In:
llockman CH, ed . Limbic system
Rev Neurobiol 1967;10:31-55. spinal cord of the cat. J Comp Neu - mechanisms and autonomic func-
105. Krieg WJS. The hypothalamus of rol 1978;181421 ^450. tion . Ch . 2. Springfield , IL: Charles
the albino rat . J Comp Neurol 122. Loewy AD, McKellar S. The neu - C. Thomas, 1972:21-33.
1932,55:19 89. -
106. Kruger L. Functional subdivision
roanatomical basis of central car- 1.38. Nieuwenhuys R . Chemoarchitec
diovascular control . Fed Proc ture of the brain . Berlin: Springer-
-
of the brainstem sensory trigemi - -
198039:2495 2503. Verlag, 1985.
nal nuclear complex. In : Bonica JJ , 123. Loewy AD, Wallach JH, McKellar 139. Nicholas AP, Pieribone VA,
-
Liebeskind JC, Albe Fessard DG, S. Efferent connections of the ven- Arvidsson U, 1 lokfelt T. Sero-
eds. Proceedings of the Second tral medulla oblongata in the rat . tonin-, substance P- and gluta-
World Congress on pain : advances -
Brain Res Rev 1981;3:63 80. mate / aspartate-like immunoreac-
in pain research and therapy . Vol 124 McComas A|. Responses of the rat tivities in medullo-spinal pathways
3. New York: Raven Press, dorsal column system to mech - of rat and primate. Neuroscience
1979:197-211. anical stimulation of the hind 1992;48:545-559.
107 Kruger L, Michel F. A morphologi - paw. J Physiol ( Lond ) 1%3;166: 140. Nilaver G, Zimmerman EA,
cal and somatotopic analysis of 435-445. Wilkins J , Michaels J , Hoffman D,
single unit activity in the trigemi - 125. Magoun HVV, Rhines R. An in- Silverman A-J . Magnocellular hy -
nal sensory complex of the cat. Exp hibitory mechanism in the bulbar pothalamic projections to the
Neurol 1962;5:139-156. reticular formation. J Neurophvsiol lower brain stem and spinal cord
108. Kruger L , Siminoff R , Witkovskv 1946;9:165-171 . of the rat Neuroendocrinologv
P. Single neuron analysis of dorsal 126. Martin RF, Haber LH, Willis WD. 1980;30:150-158.
Primary afferent depolarization of 141 . Norgren R . Gustatory system. In:
column nuclei and spinal nucleus
of trigeminal in cat . J Neurophvsiol
1961;24:333 349. -
identified cutaneous Fibers follow -
ing stimulation in medial brain
.
Paxinos C , ed . The human nervous
system. Ch. 25. New York: Aca -
109 Kuhn RA . Topographical pattern stem J Neurophvsiol 1979;42: -
demic Press, 1990:845 861 .
of cutaneous sensibility in the dor - 779-790. 142. Oliveras JL, Hosobuchi Y, Guil -
sal column nuclei of the cat . Trans 127. Martin GF, Holstege G, Mehler baud G , Besson JM . Analgesic elec -
Am Neurol Assoc 1949;74:227 230.
110. Kunzle H. The topographical or -
- WR . Reticular formation of the
pons and medulla. In: Paxinos G ,
trical stimulation of the feline nu -
cleus raphe magnus: development
ganization of spinal afferents to
the lateral reticular nucleus of the
ed . The human nervous system.
Ch. 8. New York: Academic Press,
of tolerance and its reversal by 5
HTP Brain Res 1978;146: 404-409.
-
cat . J Comp Neurol 1973;149: 1990:203-220.
—
103 117.
111 . Kuvpers HGJM. An anatomical
analysis of corticobulbar connec -
128. Matsushita M, Ikeda M . Projec-
tions from the lateral reticular nu -
cleus to the cerebellar cortex and
143. Olszewski J . On the anatomical
and functional organization of the
spinal trigeminal nucleus. | Comp
Neurol 1950;92:401 -413.
tions to the pons and lower brain nuclei in the cat. Exp Brain Res 144 . Olszewski J , Baxter D Cytoarchi -
stem in the cat. J Anal 1958; 1976;24:403-422. tecture of the human brain stem .
92:198-218. 129. Meesen H, Olszewski J . A cytoar - Philadelphia : J .B . Lippincott , 1954.
112. Kuypers HGJM. Corticobulbar chitectonic atlas of the rhomben - 145. Oscarsson O. Functional organiza -
connections to the pons and lower cephalon of the rabbit . Basel: S. -
tion of the spino and cuneocere -
-
brain stem in man : an anatomical Larger . 1949, bellar tracts. Physiol Rev 1965;
study . Brain 1958;81:364-388. 130. Mehler WR , Felerman ME, Nauta -
45:495 522.
113. Kuypers HGJM. Some projections WJG. Ascending axon degenera - 146. Oscarsson O. Functional organiza -
from the pen -central cortex to the tion following anterolateral cordot - tion of spinocerebellar paths . In:
pons and lower brain stem in mon - omy: an experimental study in the Iggo A, ed . Handbook of sensory
.
key and chimpanzee J Comp Neu - monkey. Brain 1956;83:718-750. physiology. Vol. 2. Berlin :
rol 1958;110:221 -256 . 131. Mettler FA . The tegmento-olivarv Springer -Verlag, 1973:339-380.
114 . Kuypers HGJM . Pericentral corti - and central tegmental fasciculi. J 147. Panneton WM, Loewy AD. Projec -
cal projections to motor and sen - Comp Neurol 1944;80:149-175. tions of the carotid sinus nerve to
sory nuclei . Science 1958;128: 132. Morest DK . Experimental study of the nucleus of the solitary tract in
662-663. the projections of the nucleus of the cat. Brain Res 1980;191:239-244.
115 Kuypers HGJM . Central cortical the tractus solitarius and the area 148. Parent A , Descarries L, Beaudet A.
projections to motor and somato - postrema in the cat . J Comp Neu - Organization of ascending sero-
sensory cell groups. Brain I 960; rol 1967;130:277-299. tonin systems in the adult rat
-
83:161 184 . 133. Morris R, Salt TE, Sofroniew MW , brain. A radioautographic study
116. Kuypers HGJM Hoffman AL . . Hill RG. Actions of microion- after intraventricular administra -
Beasley RM. Distribution of corti - tophoreticallv applied oxytocin, -
tion of |'H| 5 hydroxytryptamine
cal "feedback" fibers in the nuclei and immunohistochemical local- Neuroscience 1981;6:115-138.
cuneatus and gracilis. Proc Soc ization of oxytocin , vasopressin 149. Parent A, Poitras D, Dube, L. Com -
Exper Biol Med 1 %1;108:6.34-6.37. and neurophysin in the rat caudal parative anatomy of central
117. Kuypers HGJM , Tuerk JD. The dis- medulla. Neurosci Lett 1980;18: monoaminergic systems. In : Bjork -
tribution of cortical fibres within 163-168. lund A, Hokfelt T, eds. Handbook
the nuclei cuneatus and gracilis in 134 . Mountcastle VB, Powell TPS. Cen- of chemical neuroanatomv . Vol. 2.
the cat. J Anal 1964;98:143-162. tral nervous mechanisms subsen Part 1: Classical transmitters in the
118 . Levitt P, Moore RY. Origin and or - ing pt >sition sense and kinesthesis. CNS. Amsterdam: Elsevier, 1984:
ganization of brainstem cate
cholamine innervation in the rat . J
- Bull Johns Hopkins Hosp 1959;
105 ; 17.3-200.
409-433.
150. Pass IJ . Anatomic and functional
Comp Neurol 1979;186:505-528. 135. Nageotte J . The pars intermedia or relationship of nuc. dorsalis
119. |.iu CN . Afferent nerves to nervus intermedius of Wnsberg, ( Clarke’s column ). Arch Neurol
Clarke's and the lateral cuneate and the bulbo- pontine gustatory Psychiatry 1933;30:1025-1945.
nuclei in the cat . Arch. Neurol . nucleus in man . Rev Neurol Psv - 151. Paxinos G, Tork I , Halliday G,
Psychiatry 1956;75:67-77.
120. Llinas R, Baker R , Sotelo C. Elec -
-
chiatrv 1906;4:473 488.
136. Nauta WJH . Hippocampal projec-
Mehler WR Human homologs to
brainstem nuclei identified in other
trotonic coupling between neurons tions and related neural pathways animals as revealed by acetyl -
12 Medulla 467
cholinesterase activity. In : Paxinos ent input to the lateral reticular nu - 181 . Snyder RL Jr , Sutin J . Effect of le-
G, ed . The human nervous system . cleus of the cat . Exp Brain Res sions of the medulla oblongata on
Ch. 7. New York: Academic Press, 1973;18:242-255. electrolyte and water metabolism
1990:149-302. 167. Rossi GF, Brixial A . Corticofugal in the rat . Exp Neurol 1961 ;
152 . Pearson ) , Malliday G, Sakamoto fibers to the brain stem reticular 4:424-435.
-
N, Michel J P. Catecholaminergic formation: an experimental study 182. Sotelo C, Elinas R , Baker R . Struc-
neurons. In Paxinos G, ed . The in the cat . J Anat 1956;90:42-62. tural study of interior olivary nu -
human nervous system. Ch . 31. 168. Rossi GF, Brodal A. Spinal affer - cleus of the cat : morphological cor -
New York : Academic Press, 1990: ents to the trigeminal sensory nu - relates of electrotonic coupling. J
1023 1049 , clei and the nucleus of the solitary Neurophysiol 1974;37:541-559.
153. Perl ER. Whitlock DG, Gentry JR . tract . Confin Neurol 1956;16: 183. Sprague jM, Chambers WW Con -
Cutaneous projection to second - 321-332. trol of posture by reticular forma -
order neurons of the dorsal col - 169. Rossi GF, Brodal A . Terminal dis- tion and cerebellum in the intact ,
umn system . J Neurophysiol tribution of spinoreticular fibers in anesthetized, unanesthetized and
-
1962;25:337 353. the cat . AMA Arch Neurol Psychi - in the decerebrated cat . Am J Phys-
-
154 . Peterson BW. Reticulo motor path - atry 1957 78:439 433 iol 1954;176:52-64 .
ways: their connections and possi - 170. Saint-Cyr JA, Courville J . Projec- 184 . Steinbusch HWM . Distribution of
ble roles in motor behavior. In tion from the vestibular nuclei to -
serotonin immunoreactivity in the
Asanuma II, Wilson VJ , eds . Inte - the inferior olive in the cat : an au - central nervous system of the rat
gration in the nervous system. toradiographic and horseradish cell bodies and terminals. Neuro-
-
Tokyo: Igaku Shoin, 1979:185 200.
155. Peterson BW . Reticulospinal pro-
peroxidase study. Brain Res 1979;
-
165:189 201 .
science 1981 ;6:577-618.
185. Steinbusch HWM . Nieuwenhuys
jections to spinal motor nuclei . 171 . -
Saint Cyr JA , Courville J . Sources R . The raphe nuclei of the rat
Annu Rev Physiol 1979;41 :127-140. of descending afferents to the infe - brainstem : a cytoarchitectonic and
156 Pioro EP, Mai JK, Cuello AC Dis- rior olive from the upper brain immunohistochemical study. In :
tribution of substance P and
-
en kepha lin immunoreactive neu -
- stem in the cat as revealed by the
retrograde transport of horserad -
Emson PC, ed . Clinical neu -
roanatomy. New York: Raven
rons and fibers In : Paxinos G, ed . ish peroxidase. J Comp Neurol Press, 1983: 131-207.
The human nervous system . Ch. 1981;198:567-581 . 186. Swanson LW, Kuypers HCJM . The
32. New York: Academic Press, 172. Sawchenko PE, Swanson LW . The paraventricular nucleus of the hy -
-
1990:1051 1094. organization of noradrenergic pothalamus: cytoarchitectonic sub-
157 Poggio GF, Mountcastle VB A pathways from the brainstem to divisions and organization of prtv
study of the functional contribu - the paraventricular and supraoptic jeetions to the pituitary, dorsal
tions of the lemniscal and nuclei in the rat . Brain Res Rev vagal complex , and spinal cord as
spinothalamic systems to somatic 1982;4:275-325. demonstrated by retrograde fluo-
sensibility Bull Johns Hopkins 173. Scheibe! ME, Scheibel AB. Struc- rescence double-labeling methods.
Hosp 1960;106:266-316. tural substrates for integrative pat - J Comp Neurol 1980;194:555-570.
158. Poitras D, Parent A . Atlas of the terns in the brain stem reticular 187 Taber E. The cytoarchitecture of
distribution of monoamine-con- core. In: Jasper HH, Proctor I P, the brain stem of the cat . I . Brain
taining nerve cell bodies in the Knighton RS, et al., eds. Reticular stem nuclei of cat. J Comp Neurol
brain stem of the cat. J Comp Neu - formation of the brain. Ch. 2. 1961;116:27-70.
rol 1978;179:699-718. Boston: Little Brown & Company, 188 Takeuchi Y, Uemura M , Matsuda
.
159. Price DD Dubner R, Hu JW -
1958:31 55. K , Matsushima R, Mizuno N .
Trigeminothalamic neurons in nu - 174 . Schulz H . Anatomische Unter - Parabrachial nucleus neurons pro -
cleus caudalis responsive to tactile, suchungen uber den Faserverlauf jecting to the lower brain stem and
thermal and nociceptive stimula - im zentralen Hohlengrau und den the spinal cord : a study in the cat
tion of monkeys face. J Neurophys - Nervenfaserschwund in demsel - by the Fink - Heimer and the horse -
iol 1976;39:936-953. ben bei der progression Paralyse radish peroxidase methods . Exp
160. Proudfit HK, Clark FM . The pro- der Irren. Arch Psychiatr Nervenkr Neurol 1980;70:403-413.
jections of locus coeruleus neurons 1891;22:527-587. 189. Thomas DM , Kaufman RP,
to the spinal cord . Prog Brain Res 175. Schwartzman RJ . A behavioral Sprague JM , Chambers WW . Ex -
1991;88:123-141 . analysis of complete unilateral sec - perimental studies of the vermal
161 . Ramon y Cajal S. Histologie du tion of the pyramidal tract at the cerebellar projections in the brain
Systeme Nerveux de 1' Homme et medullary level in Mactica mulalta . stem of the ( fastigiobulbar tract ). J
des Vertebres. ( Azoulav L, trans.), Ann Neurol 1978;4:234-244 . Anat 1956;90:371-385.
Paris: Maloine, 1909, 1911 . ( Re- 176. Sherrington CS. Note on the spinal 190. Tohyama M, Sakai M, Salvert D,
printed , Consejo Superior de portion of some ascending degen - Touret M , Jouvet M . Spinal projec -
Investigadones Cientificas, Insti - erations | Phvsiol (Lond)
. 1893 tions from the lower brain stem in
tuto Ramon y Cajal , Madrid, 1972. ) 14 : 233 M2 the cat as demonstrated by the
162. Ramon - Moliner E, Nauta WJH. 177. Shriver JE, Stein BM, Carpenter horseradish peroxidase technique.
The isodendritic core of the brain MB. Central projections of spinal 1. Origins of the reticulospinal
stem. J Comp Neurol 1966;126: dorsal roots in the monkey. I . Cer - tracts and their funicular trajecto-
-
311 335. vical and upper thoracic dorsal ries. Brain Res 1979;173:383-403
163. Rhines R , Magoun HW. Brainstem roots Am | Anat 1968;123:27 74 191 Tork I, McRitchie DA , Rikard - Bell
facilitation of cortical motor re- 178. Shute CCD, Lewis PR . Choline- GC, Paxinos G . Autonomic regula -
sponse. J Neurophvsiol 1946,9. sterase-containing systems of the tory centers in the medulla oblon -
219-229. brain of the rat. Nature 1963,199: gata . In : Paxinos G, ed . The human
164 . Rhoton A I ., O'Leary J L, Ferguson 1160-1163. nervous system. Ch . 9. New York:
JP. The trigeminal, facial, vagal 179 Sjoqvist O. Studies on pain con - Academic Press, 1990:221-259
and glossopharyngeal nerves in duction in the trigeminal nerve: a 192 . Tork I , Hornung JP. Raphe nuclei
the monkey . Arch Neurol 1966; contribution to surgical treatment and the serotonergic System . In:
-
14:530 540. of facial pain . Acta Psychiat Neurol Paxinos G, ed . The human nervous
165 Ropper AH, Fisher CM , Kleinman Scand 1938;17(Suppl ):l -139. system . Ch . 30. New York: Aca -
GM . Pyramidal infarction in the 180. Sladek JR Jr , Bowman JP. The dis - -
demic Press, 1990:1001 1022.
medulla : a cause of pure motor tribution of catecholamines within 193. Torvik A . Afferent connections to
hemiplegia sparing the face. Neu - the inferior olivary complex of the the sensory trigeminal nuclei, the
rology 1979;29:91-95. cat and rhesus monkey. J Comp nucleus of the solitary tract and ad -
166. Rosen I, Scheid P. Patterns of affer - Neurol 1975;163:203-214 jacent structures: an experimental
study in the rat . J Comp Neurol the nuclei of the dorsal columns: terminals in the solitary nucleus. J
-
1956;106:51 142. an experimental study in the cat. Comp Neurol 1986;244:72-85.
194 . Torvik A , Brodal A . The origin of Brain 1957;80:273-287 207. Winter DL . N . gracilis of cat: Func-
reticulospinal fibers in the cat: an
experimental study . Anal Rec
201. Walberg F. Do the motor nuclei of
the cranial nerves receive corti -
tional organization and corticofu
gal effects. ) Neurophysiol 1965;
-
1957;128:113-137. cofugal fibres? An experimental 28:48-70.
195. Tower SS. Pyramidal lesion in the study in the cat . Brain 1957; 208. Woolsey CN , Gorska T, Wetzel A ,
monkey Brain 1940;63:36-90. 80:597-605. Erickson TC, Earls FJ, Allman JM.
196. Uhl GR, Goodman RR , Kuhar MJ . 202. Walberg F. On the termination of Complete unilateral section of the
Childers SR, Snyder SH . Immuno- rubrobulbar fibers: experimental pyramidal tract at the medullary
histochemical mapping of enkeph - observations in the cat . J Comp level in Macaco mulatto. Brain Res
alin containing cell bodies, fibers Neurol 1958;110:66-73. -
1972;40:119 124.
and nerve terminals in the brain 203. Walberg F. Descending connec- 209. Yeomans DC, Clark FM , Paice JA,
.
stem of the r it Brain Res 1979 tions from the mesencephalon to Proudfit HK . Antinociception in -
166:75-94 . the inferior olive an experimental
, duced by electrical stimulation of
197. Vigier D, Rouviere A. Afferent and study in the cat. Exp Brain Res spinally projecting noradrenergic
efferent connections of the area 1974;21:145-156. neurons in the A7 catecholamine
postrema demonstrated by the 204. Walker AE, Weaver TA Jr . The top- cell group of the rat. Pain 1992;
horseradish peroxidase method .
Arch ltal Biol 1979;117:325-339.
ical organization and termination
of fibers of the posterior columns
-
48:449 461.
210. Zemlan FP, Pfaff DW Topographi-
198. Walberg F. Lateral reticular nu - in Macaco mulatto . J Comp Neurol cal organization in medullary retic-
cleus in medulla oblongata in 1942;76:145-158. ulospinal systems as demonstrated
mammals: comparative-anatomi - 205. Wamsley JK, Lewis MS, Young WS by the horseradish peroxidase tech -
cal study - J Comp Neurol 1952; HI , Kuhar MJ . Autoradiographic nique. Brain Res 1979;174:161-166.
-
96:283 343. localization of muscarinic choliner- 211 Zimmerman EA , Chambers WW ,
199 Walberg F. Descending connec- gic receptors in rat brainstem. J Liu CN. An experimental study of
tions to the inferior olive: an exper - Neurosci 1981;1:176-191. the anatomical organization of the
imental study in the cat . J Comp 206. Whitehead MC. Anatomy of the cortico-bulbar system in the albino
-
Neurol 1956;104:77 173. gustatory system in the hamster: rat . J Comp Neurol 1964:123:
200. Walberg F. Corticofugal fibres to svnaptology of the facial afferent 301-324.
13
Pons
The pons is the adult derivative of the me- present in the floor of the fourth ventricle
tencephalon. It forms the rostral part of the throughout the caudal pons ( Fig . 13.2 ).
hindbrain . This portion of the brainstem con- The pontine reticular formation is more
sists of two distinctive parts: ( a ) a dorsal por - extensive than the medullary reticular forma -
tion , the pontine tegmentum, which is present tion, but occupies a similar region . The major
in all mammalian species, and ( b ) a ventral part of the pontine reticular formation is rep-
portion , referred to as the pons proper, which resented by the pontine reticular nuclei ( nu -
is particularly well-developed in primates clei reticularis pontis ( pars caudalis and pars
and becomes strikingly prominent in humans oralis); Figs. 13.1 and 13.28) ( 31, 191 ). The pars
( Figs, 13.1 and 13.2 ) . The pons also can be di - caudalis replaces the gigantocellular reticular
vided caudorostrally into three major seg- nucleus of the medulla and extends rostrally
ments: (a ) the caudal pons, which is charac- to the level of the trigeminal motor nucleus
terized by the presence of facial and ( Fig. 13.3). The pars oralis , present in more
abducens nerve and nuclei; ( b ) the midpons, rostral pontine levels, extends into the caudal
including the trigeminal nerve and its chief mesencephalon ( Fig. 13.28 ). The pontine
sensory and motor nuclei, and (c) the rostral reticular nuclei give rise to the pontine reticu -
pons also referred to as the isthmus of the lospinal tract ( Figs. 11.10 and 11.22 ). Lateral
hindbrain. to the pars caudalis is a small-celled reticular
nucleus ( parvicellularis ) similar to that de-
scribed in the medulla . The median raphe
CAUDAL PONS
contains the inferior central nucleus, which is
Dorsal Portion a rostral extension of the nucleus raphe mag-
nus, and the subependymal area near the
The pontine tegmentum is the rostral con - midline contains the nucleus of the medial em -
tinuation of the medullary reticular forma - inence and the dorsal paramedian nucleus
tion . It contains cranial nerve nuclei, ascend - ( Figs. 13.3 and 13.4 ) .
ing and descending tracts, and reticular The reticular formation posterolateral to
nuclei ( Fig. 13.1 ). Cranial nerve nuclei found the medial lemniscus contains a relatively
in the pons are those of cranial nerves V , VI , large discrete bundle known as the central
VII , and VIII . The ascending tracts in this part tegmental tract ( Figs. 13.1 and 13.4 ) . This is a
of the brainstem are similar to those found in composite tract consisting of descending
the medulla , except for the medial lemniscus. fibers from midbrain nuclei that project
The medial lemniscus, which is oriented ver- mainly to the inferior olivary complex, and
tically on each side of the median raphe in the ascending fibers from the lower brainstem
medulla , now assumes a nearly horizontal reticular formation that project to certain
position dorsal to the ventral part of the pons thalamic nuclei.
( Figs. 13.1 and 13.2 ). Crossing fibers of the The cerebellopontine angle, formed laterally
trapezoid body traverse ventral parts of the at the junction of pons, medulla, and cerebel -
bundle on each side. The medial longitudinal lum, contains root fibers of the vestibulo-
fasciculi ( MLF) are situated dorsally on each cochlear and facial nerves ( Figs. 13.2 and
side of the median raphe. The spinothalamic 13.6). Fibers of the cochlear nerve root pass
and anterior spinocerebellar tracts occupy dorsally, lateral to the inferior cerebellar pe-
positions in the anterolateral tegmentum. The duncle, to terminate upon cells in all divi -
spinal trigeminal tract and nucleus lie medial sions of both the dorsal and ventral cochlear
to the inferior cerebellar peduncle. The .
nuclei ( Fig. 12.33). Vestibular root fibers,
vestibular nuclei ( i.e., medial and lateral ) are
469
'
slight ' medial and rostral to those of the
Cerebellum
Cerebellar peduncles Ventricle EZ-
Vestibular nuclei
Superior
Superior
Inferior
Lateral
Middle
Spinal trigeminal
Nucleus
Tract
Nucleus reticularis
Dorsal H
pontis caudalis
pons
Central tegmental
tract
Nucleus N YU
Ventral
pons Superior olivary nucleus
Medial lemniscus
Lateral lemniscus
Corticospinal tract
Pontine nuclei
Trapezoid body
Figure 13.1. Transverse section of the pons at the level of the abducens nucleus The dorsal portion of the pons, con-
stituting the tegmentum, contains the reticular formation, cranial nerve nuclei, and ascending and descending
tracts The ventral portion of the pons contains the pontine nuclei, massive bundles of corticofugal fibers, and the
transverse fibers of the pons which form the middle cerebellar peduncle
Medial long fasciculus Abducens nucleus
Vestibular nuclei — Dentate nucleus

Lateral
Medial Cerebellar peduncle
Spinal trigeminal
—.
- Inferior
Middle
troct S> nucleus
Ventral cochlear
nucleus Superior olive
Facial nucleus
Medial lemniscus
( motor )
'•Trapezoid body
Vestibular nerve
Intermediate nerve
"" Corticospinol tract
Motor root NHU
Central tegmental tract

Figure 13.2. Slightly asymmetric transverse section through the pons of a 1-month infant Root fibers of the vestibular
and facial nerves are present on the left (Weigerts myelin stain)
13 Pons 471
Superior vest nucleus

,
Spinal nucleus Lateral vest nucleus

,
of N . Y
Nucleus of NM
Access , nuc . of N .IZH
Nucleus of the
medial eminence
Abducens nucleus
Dorsal paramedian
nucleus
Large cells nucleus
Small cells pontis }

reticularis
caudalis
i
y Pontine nuclei
\V
Superior olivary
nucleus
Nucleus of the
trapezoid body
Figure 13.3. Transverse section through the pons and pontine tegmentum of 3-month infant at about same level as
Figure 13 2 (Cresyl violet stain, with schematic representation of cell groups)
Inferior vestibular nucleus

Medial vestibular nucleus
Inferior cerebellar
peduncle Nucleus prepositus
Medial longitudinal
Ventral cochlear fasciculus
nucleus Tectospinal tract
Spinal trigeminal
Inf central nucleus
nucleus
Middle cerebellar - Medial lemniscus
peduncle
Spinal trigeminal
tract
^ Trapezoid body
Secondary cochlear Corticospinal tract

fibers
Pontine nuclei
Superior olive
Tronsverse pontine
fibers
Figure 13.4. Transverse section of the adult pons at the level of the emergence of the facial nerve root (Weigert s
myelin stain).

Dorsal cochlear
nucleus
Medial vest nucleus
,
Nucleus of N. 3ZI
Motor nucleus
N. m Medial long. fasc .
Inferior
cerebellar
peduncle
Spinal nucleus
N. 31
Spinal tract
N . 3£
Ventral
cochlear
nucleus
Vestibular
.
root ( N 3ZHL )
Motor root N. VTT
Secondary cochlear
fibers forming
trapezoid body tract body
Lateral lemniscus Pontine nuclei Medial lemniscus

and superior olive
Figure 13.5 . transverse section of left half of the pons and pontine tegmentum of a 3- year -old child whose brain
showed a complete absence of the left cerebellar hemisphere and middle cerebellar peduncle The origin of the
trapezoid fibers from the ventral cochlear nucleus is clearly shown Note fibers of the dorsal acoustic stria passing into
the tegmentum from the dorsal cochlear nucleus (Weigert ' s myelin stain)
Superior cerebellar
Trigeminal root peduncle
Oblique pontine
fibers
Abducens nerve
Facial nerve
Intermediate nerve
^^ liddle cerebellar
L / peduncle
V- Vestibular nerve
Cochlear nerve
Glossopharyngeal
nerve Acoustic tubercle
Inferior olive Pontobulbar body
Hypoglossal Vagal rootlets
rootlets
Figure 13.6. Lateral view of the cerebellopontine angle from a dissection of the brainstem and cerebellum
13 Pons 473
cochlear nerve, enter caudal portions of the visceral efferent (parasympathetic (GVE ) )
pons by passing between the restitorm body fibers. The larger motor root of the facial
and the spinal trigeminal tract ( Figs. 13.2 and nerve is the most rostral and medial cranial
13.5). Primary vestibular fibers are distrib- nerve in the cerebellopontine angle.
uted differentially within the vestibular nu -
clear complex in the floor of the fourth ventri - Ventral Portion
cle. A moderate number of vestibular fibers
project to specific parts of the cerebellum via The massive ventral part of the pons con -
the juxtarestiform body, which is part of the sists of orderly arranged transverse and lon -
inferior cerebellar peduncle ( Fig. 13.7). Ven - gitudinal fiber bundles intercalated between
tral to the vestibular nerve are the intermedi - large collections of pontine nuclei ( Figs. 13.1 ,
ate and facial nerves ( Figs. 13.2 and 13.5). The 13.3, and 13.4 ). Longitudinal fiber bundles
intermediate nerve contains mainly special coursing through central regions of the ven -
visceral afferent ( taste (SVA ) ) and general tral pons are ( a ) corticospinal, ( b ) corticobul -
Fastigial nucleus Emboliform nucleus

Globose nucleus Dentate nucleus
Inferior
cerebellar
peduncle
N. m
Middle
cerebellar
peduncle
Principal ~ nucleus
Lateral lemniscus of N SL
and superior olive
figure 13.7. Transverse section of the pons, pontine tegmentum and portions of the cerebellum at the level of the
abducens nuclei of a 1-month Infant (Weigert ' s myelin stain)
bar, and (c) corticopontine ( Figs. A.7-A .9 of fibers do not become myelinated until some
the human brain atlas shown in Section VII ). time after birth and are not distinguishable in
Corticospinal fillers traverse the ventral part brain sections of a 4-week infant stained by
of the pons, and in sagittal sections can be the Weigert technique ( Fig. 13.2). They are
traced into the medullary pyramids ( Figs. 2.24, shown in the adult pons in Figures 13.4,
2.26, 11.13, and A.28). These fibers display a 13.27, and 13.32.
compact arrangement at rostral and caudal The pontine nuclei are large, closely
pontine levels, but are broken into a number of packed cellular aggregations situated be-
small fascicles by transversely oriented pon - tween the transverse and longitudinal fibers
tine fibers in the middle regions of the pons. ( Fig. 13.3). In caudal regions, the cells form a
Corlicobulbar fibers separate from the corti - ring around the compact pyramidal tract ,
cospinal tracts and enter the pontine tegmen- which more rostrally is broken into smaller
tum. These fibers convey impulses that pass bundles by islands of pontine cells. In a gen -
to the motor cranial nerve nuclei directly and eral way, the cells may be grouped into lat -
via intercalated neurons. eral, medial , dorsal, and ventral nuclear
Corticopontine fibers , arising from frontal, masses ( Fig. 13.27). In the lateral groups, the
parietal, temporal, and occipital cortex, de- polygonal cells are relatively large- or
scend without crossing and terminate upon medium-sized ; in the paramedian region,
the pontine nuclei, between corticospinal and cells are smaller. Although the dendrites of
corticopontine tracts. Corticopontine fibers these cells ramify around adjacent cell bodies,
from the primary sensorimotor cortex appear their axons are mainly crossed and form the
to be somatotopically organized and end middle cerebellar peduncle ( or brachium
upon circumscribed regions of the pontine ponds). Among these cells are found curi -
nuclei ( 42 ). Each part of the cerebral cortex so ously shaped Golgi type II cells whose den -
far studied appears to give off fibers to sev - drites are beset with numerous hair-like
eral well -defined areas within the pontine nu - processes and whose short, branching axons
clei ( 43, 44 ). The pontine nuclei give rise to terminate in the vicinity of the cell body.
the transverse fiber bundles of the ventral Certain nuclei in the pontine tegmentum ,
pons, which cross the midline and enter the like the reticulotegmental nucleus, project
cerebellum via the middle cerebellar pedun- fibers into the ventral part okthe pons, which
cle ( Figs. 13.1 and 13.4 ). Transverse ponto- enter the cerebellum via the contralateral
cerebellar fibers cross above (superficial middle cerebellar peduncle ( Figs. 2.26, 13.28,
layer ) and below (deep layer ) the fascicles of 13.33, A .8, and A .9). The reticulotegmental
descending fibers. The ventral portion of the nucleus is regarded by some as a tegmental
pons may be considered as a massive relay extension of the pontine nuclei (130).
station in a disynaptic neuronal pathway
whereby impulses from the cerebral cortex VESTIBULOCOCHLEAR NERVE
are transmitted to the contralateral cerebellar
hemisphere. Additionally, a small number of The vestibulocochlear nerve ( N . VIII ) com -
fibers from the superior colliculus ( tectopon- prises two distinctive parts: (a ) the cochlear
tine fibers) descend ipsilaterally to terminate part concerned with audition , and ( b ) the
upon dorsolateral pontine nuclei (8). These vestibular part conveying impulses concerned
fibers, and fibers from the pontine nuclei, are with equilibrium and orientation in three-di -
considered to transmit optic impulses to re- mensional space. These two components of
stricted regions of the cerebellum . the vestibulocochlear nerve run together from
The corticopontocerebellar pathway is the internal auditory meatus to the cerebello-
quantitatively the most important route by pontine angle, where they enter the brainstem
( Figs. 12.1 and 13.6). Each of these nerves has
which the cerebral cortex can influence the
cerebellar cortex in a somatotopically orga- distinctive central nuclei and connections.
nized manner. The corticopontine fibers are
most numerous in the rostral pons, where Cochlea and Related Nerve and Nuclei
they form bundles difficult to distinguish COCHLEA
from the pyramidal tracts ( Fig. 13.32). Their
number gradually diminishes as fibers termi - The cochlea consists of a fluid -filled coil
nate in the pontine nuclei. The corticopontine tube of two and a half turns ( Fig . 13.8) that
fibers and the transverse pontocerebellar serves as the auditory transducer ( Fig. 13.9).
13 Pons 475
Anterior ' End of

semicircular duct saccule
Posterior
semicircular duct
Lateral
semicircular duct
\
Anterior
-Lateral |
Ampullae Superior I Vestibular
'
r
-
—-
- Inferior ) ganglia
Vestihular
nerve
Facial
nerve
/
‘Cochlear
Posterior ampullar / nerve
Utricle /
7 /
Saccule /
Ductus reuniens
/
Spiral ganglion
iochlea
Figure ) 3.8 . Labyrinthine and cochlear apparatus, their ganglia and nerves, with anatomic orientation The cochlea
has been rotated downward and laterally to expose the vestibular ganglia The divisions of the vestibular nerve were
separated by retracting the superior division proximal to its ganglion
The basilar and vestibular ( Reisner's) mem- specific sound frequencies. High frequencies
branes partition the cochlea to form the scala are perceived at the base of the cochlea and
vestibuli, the scala tympani, and the cochlear low frequencies at its apex . The basilar mem -
duct ( scala media ) ( Figs. 13.9 and 13.10) En -. brane has a stiffness that varies 100-fold from
one end to the other. It is narrowest and
ergy from sound reaching the tympanic
membrane is transmitted via the ear ossicles stiffest at the base of the cochlea and widest
to the scala vestibuli (oval window ) by the and most pliable near the helicotrema (118).
foot plate of the stapes. The membrane cover-
ing the round window located at the base of COCHLEAR NERVE AND NUCLEI
the scala tympani accommodates to hydrosta -
tic pressure changes. The organ of Corti , the The cochlear nerve originates from cells of
auditory transducer, lies in the cochlear duct the spiral ganglion situated about the modio-
and consists of one row of inner hair cells and lus of the cochlea that use glutamate as their
three rows of outer hair cells (223) ( Figs. principal neurotransmitter ( Figs. 13.9, 13.10,
13.9-13.11 ). The tectorial membrane, attached and 13.13). Peripheral processes of the bipo-
to the spiral limbus, overlies the hair cells lar cells of the spiral ganglion end in relation
( Fig. 13.10 ). The piston - like action of the to the hair cells of the organ of Corti ( Fig.
stapes transmits the energy of the sound 13.9). The central processes of ganglion cells
waves to the perilymph in the scala vestibuli. form the cochlear nerve, which enters the
Energy transmitted to the perilymph pro- brainstem lateral, dorsal, and slightly caudal
duces traveling waves in the basilar mem- to the vestibular nerve ( Figs. 12.33 and 13.13).
brane that moves from the base of the cochlea Fibers of the cochlear nerve terminate in two
to its apex ( 273). Displacement of the basilar cell masses on the lateral surface of the infe-
membrane in response to acoustic stimuli rior cerebellar peduncle, the ventral and dor-
causes bending of hair cells in contact with sal cochlear nuclei ( Figs. 12.25, 12.33, and
the tectorial membrane. Maximum displace- 13.12 ). These nuclei represent a more or less
ment of the basal membrane at different discontinuous cell mass, but they have distinc-
tances from the stapes can be correlated with tive cells and cytoarchitecture.
SCALA
VESTIBULI
COCHLEAR
Vestibular
DUCT
membrane
Internal spiral
sulcus Tectorial Cells of Vascular
membrane Hensen stria
Border cells
Cochlear gSp— Spiral

nerve ligament ]
Inner hair Outer hair Basilar \
cell cells membrane
Spiral
ganglion SCALA TYMPANI -
LB 94
Figure 13.9 Radial section through the cochlea showing the cochlear duct the basilar membrane the organ of
Corti, and the tectorial membrane The small diagram in the upper left is an axial section of the cochlea The area
enclosed in the rectangle is reproduced in detail in the large drawing.
The dorsal cochlear nucleus forms an emi- sal cochlear nucleus). This layer of conspicu -
nence on the most lateral part of the floor of ous cells gives the dorsal cochlear nucleus its
the fourth ventricle, known as the acoustic tu - distinctive lamination . The polymorphic layer ,
bercle. The acoustic tubercle lies dorsal to the the deepest and thickest of all three layers,
restiform body and forms the floor of the lat - contains a diverse population of cells, includ -
eral recess of the fourth ventricle ( Figs. 13.5 ing small granule cells, pyramidal cells, mul-
and 13.12 ). Cells of the dorsal cochlear nu - tipolar cells, and occasional giant cells ( 193).
cleus, in most mammals, are organized in In humans, these three layers are indistinct.
three distinct layers: (a ) molecular, ( b) The ventral cochlear nucleus is subdivided
fusiform , and (c) polymorphic ( 30, 194, 216, into anteroventral and posteroventral nuclei
257). The molecular layer , beneath the on the basis of topography, cytology, and
ependyma of the lateral recess, contains small functional characteristics ( Fig. 13.12 ). Each of
round neurons with scant cytoplasm which these subdivisions is tonotopically organized
often are clustered in islands. The fusiform and has an orderly sequential representation
layer is composed of evenly distributed pyra - of the auditory spectrum ( 225, 226). The an -
midal cells oriented radially ( i .e., with long teroventral cochlear nucleus lies in the most ros-
axes perpendicular to the surface of the dor- tral part of the cochlear nuclear complex be-
Figure 13 10. Radial section through the cochlea in human similar to Figure 13 9 Note the cells of the spiral ganglion
Figure 13.11. Cochlea of the rhesus monkey A. View of the basal coil of the cochlea with the tectorial membrane
( JM) reflected ( • 450) B Surface view of the hair cells of the cochlea after removal of the tectorial membrane ( JM)
. .
except for fragments attached to outer hair cells ( OHC) , IHC inner hair cells; HP head plate of inner pillar ( * 2100)
U / AsCZUtt the cochlear nuclei, bifurcate in an orderly se-

quence, and are distributed to both dorsal
and ventral cochlear nuclei ( 167). Primary au -
ditory fibers arborize in all parts of the
cochlear nuclear complex ( 178, 215, 289 ). As-
cending branches of the auditory nerve root
terminate in a rostrolateral to caudomedial
gradient in the anteroventral cochlear nu -
cleus chiefly upon spherical and globular
cells. Descending branches of the root termi-
nate in a ventral to dorsal pattern in the pos-
teroventral and dorsal cochlear nuclei. Fibers
in the posteroventral nucleus end upon glob-
ular, multipolar and octopus cells. Fibers to
the dorsal cochlear nucleus terminate upon
cells in the deep polymorphic layer and upon
the deep dendrites of pyramidal cells.
Figure 13.12. Cochlear nuclei from the lateral surface One of the characteristic features of the au -
of the brainstem of a cat Major divisions of the cochlear ditory system is the pattern of tonotopic lo-
.
nuclei are indicated Dc dorsal cochlear nucleus; Pv. calization evident at various levels. In the
posteroventral nucleus. Av. anteroventral nucleus cochlea, it has been shown that high tones are
Branches of central processes of the spiral ganglion cells
are distributed to all divisions of cochlear nuclei and in
received in the basal coils, while the apical
eoch division neurons responding to higher frequencies portion is sensitive to low frequencies (85,
are most dorsal Fiber 1 is derived from the middle turn of 263). Anatomic studies suggest that apical
the cochlea while fiber 2 comes from the basal turn, a cochlear fibers terminate in ventral parts of
represents cut edges of the inferior and superior cerebel-
the dorsal cochlear nucleus and in the ventral
lar peduncles; b is the cut edge of the middle cerebellar
peduncle; 5th n is the trigeminal nerve root. nucleus, while fibers from basal portions of
the cochlea end in the dorsal part of the dor-
sal cochlear nucleus (162, 197). Physiologic
tween the vestibular nerve root and the pe- evidence ( 224, 225), based upon microelec-
duncle of the flocculus. It is composed pri- trode studies of neuron frequency sensitivity
marily of ovoid or spherical cells that are in the cochlear nuclear complex, indicates
densely packed in rostral parts of the nucleus. that each major division possesses its own
In the posterior part of this nucleus, near the frequency sequence and that each division
entry zone of the cochlear root , cells are more seems to have a full tonal spectrum. The mul -
widely spaced and larger. This region also tiple tonotopic representation in all divisions
contains globular cells with eccentric nuclei of the cochlear nuclear complex is due to the
which bulge on the cell surface ( 13, 30, 193). orderly bifurcation and distribution of fibers
The posteroventral cochlear nucleus begins at throughout the complex. In all three divisions
the level of entrance of the cochlear root into of the cochlear complex, neurons responding
the brainstem and continues to the caudal tip to higher frequencies are dorsal, while those
of the cochlear complex, where it is capped responding to lower frequencies are ventral .
posteriorly by the dorsal cochlear nucleus Thus, the tonotopic localization in the
(30, 257 ) ( Fig. 13.12 ). Although the pos- cochlear nuclei is the reverse of that in the
teroventral cochlear nucleus contains several cochlea with high frequencies perceived in
distinct types of neurons, multipolar cells of dorsal regions and low frequencies in ventral
various sizes predominate, especially ros- regions.
trnlly (193). The caudal pole of this nuclear
subdivision contains octopus cells, so-called AUDITORY PATHWAYS
because most of the dendrites are gathered Secondary auditory pathways in the brain -
together on one side of the cell body. stem are complex, and many details concern -
ing their composition are uncertain. Most of
Auditory Fiber Systems the available information regarding these
PRIMARY AUDITORY FIBERS pathways is based upon studies in animals
( Fig. 13.13). Secondary auditory fibers arising
These fibers, representing the central from the three subdivisions of the cochlear
processes of cells in the spinal ganglion, enter nuclei are grouped into three acoustic striae:
13 Pons 479
D
Ul T ransverse
temporal gyrus
\J
Temporal
lobe
Superior colliculus
- fo
c
it Medial geniculate body
, »-
Commissure of the Brachium of the

inferior colliculus inferior colliculus
Inferior colliculus
Nucleus of lateral
lemniscus
B Medial lemniscus
Lateral lemniscus
Cochlear nuclei
dorsal pari —
ventral part — Inferior cerebellar
SsSlIfr peduncle
—
Spinal trigeminal
nucleus and tract
"or Superior olivary

^nucleus
Cochlea Spiral Cochlear Trapezoid Medial accessory
ganglion nerve body nucleus
Figure 13.13. Auditory pathways Primary auditory fibers arising from the spiral ganglion are in black Secondary au-
ditory fibers arising from the dorsal and ventral cochlear nuclei and forming the acoustic striae are in red Auditory
.
fibers arising from relay nuclei are in blue. A, medulla; S, level of inferior colliculus; C level of superior colliculus and
medial geniculate body; D, transverse section through the cerebral hemisphere.
(a ) a dorsal acoustic stria, (b) a small interme- medial lemniscus, cross the raphe, and
diate acoustic stria, and ( c) a ventral acoustic reach the dorsolateral border of the oppo-
stria ( 15). The three acoustic striae project to site superior olive, where they turn upward
auditory relay nuclei on both sides of the to form a longitudinal ascending bundle
brainstem (i.e., nuclei of the superior olivary known as the lateral lemniscus. Other trape-
complex and trapezoid body) and also con- zoid fibers terminate in the homolateral and
tribute fibers to the lateral lemniscus, the contralateral nuclei of the superior olive
principal ascending auditory pathway in the and the trapezoid body, two nuclear masses
brainstem. interposed in the secondary cochlear path-
The dorsal acoustic stria arises from the dor - way (Fig. 13.13). Fibers from these nuclei
sal cochlear nucleus, arches medially around join the lateral lemniscus of the same or the
the superior surface of the inferior cerebellar opposite side.
peduncle, and crosses the median raphe ven- The dorsal acoustic stria is larger than the
tral to the medial longitudinal fasciculus ( 256, intermediate stria and the ventral stria is
257). A few fibers in this stria appear to termi- larger than the other two combined. In their
nate in the contralateral lateral superior oli- passage through the tegmentum, there is a
vary nucleus, but the main bundle enters the diminution in the number of fibers in the var-
opposite lateral lemniscus directly ( Fig. ious striae due to terminations in the reticular
13.13). These fibers and their collaterals ter - formation, the superior olivary nuclei, and
minate in the contralateral ventral and dorsal the trapezoid nuclei. The superior olivary
nuclei of the lateral lemniscus and in the cen- and trapezoid nuclei (Fig. 13.5) give rise to a
tral nucleus of the inferior colliculus on the number of tertiary auditory fibers which as-
opposite side ( 256). cend mainly in the lateral lemniscus of the
The intermediate acoustic stria arises from same side ( 193, 255, 289). The lateral lemnis-
cells in the posteroventral cochlear nucleus, cus consists primarily of crossed secondary
courses dorsally through parts of the dorsal fibers contributed by the three auditory striae
cochlear nucleus and enters the tegmentum and tertiary fibers from the superior olive
by passing around the inferior cerebellar pe- and trapezoid nuclei. No direct fibers from
duncle ( 256). In the ipsilateral tegmentum, the cochlear nuclei ascend in the ipsilateral
these fibers approach the dorsal aspect of the lateral lemniscus ( 15). The number of ascend-
superior olivary complex where they are dis- ing fibers in the lateral lemniscus is small
tributed to retro-olivary and periolivary nu- compared with the total number of fibers
clear groups. Fibers of the intermediate arising from the dorsal and ventral cochlear
acoustic stria continue across the median nuclei.
raphe posterior to the trapezoid body to be The superior olivary complex is a cellular
distributed to retro-olivary and periolivary column, about 4 mm long, extending from
nuclei contralaterallv ( 256, 257, 287). None of the level of the facial nucleus to the motor
these fibers appears to terminate in the prin- nucleus of the trigeminal nerve. It is in con-
cipal nuclei of the superior olivary complex. tact ventrally with the lateral portion of the
Other fibers in the intermediate acoustic stria trapezoid body ( Figs. 13.3 and 13.5). It rep-
reach the contralateral lateral lemniscus and resents the most caudal relay in the audi-
terminate in the ventral nucleus of the lateral tory pathway where ascending fiber sys-
lemniscus and in the inferior colliculus ( 287). tems from the two sides converge ( 257).
Because the retro-olivary and periolivary nu- This nuclear complex is composed of ( a ) a
clei are known to give rise to fibers of the large lateral ( principal ) superior olivarv nu -
olivocochlear bundle that pass peripherally cleus, (b ) a small medial (accessory) supe -
to make synaptic contact with outer hair cells, rior olivary nucleus, and (c ) a few cell ag-
the posteroventral cochlear nucleus, which gregations referred to as preolivarv,
projects prominently to these nuclei, must retro-olivary, and periolivary nuclei. From
play a significant role in this modulating the region dorsal to the medial accessory
feedback system ( 257, 287). olivary nucleus a bundle of fibers, the pe-
The ventral acoustic stria arises from the duncle of the superior olive , passes dorsomedi-
ventral cochlear nucleus ( 260, 286), and ally toward the abducens nucleus ( Figs. 13.2
courses medially along the ventral border of and A .7). Binaural interaction in the supe-
the pontine tegmentum to form the trape- rior olivary complex plays an important role
zoid body ( Figs. 1.3.5 and 13.13). Many of in sound localization.
these fibers pass through or ventral to the The lateral superior olivary nucleus has a
13 Pons 481
conspicuous S-shaped configuration in carni- tegmentum, appears immediately rostral to

vores, but in monkeys and humans it is oval the lateral preolivary nuclei, and is sur -
with dorsal and ventral indentations ( Figs. rounded ventrally and laterally by fibers of
13.5 and 13.27) . The lateral superior olive in the lateral lemniscus. The dorsal nucleus of tlw
humans consists of about six clusters of cells lateral lemniscus appears at more rostral pon -
which do not present a sharply circumscribed tine levels and is composed of cell clusters
configuration ( 258 ). The medial superior olivary located within fascicles of the lateral lemnis-
nucleus forms a slender obliquely oriented cus ( Fig . 13.32 ). The oral pole of the dorsal
cell column medial to the lateral superior nucleus of the lateral lemniscus lies immedi -
olive, the dorsal tip of the cell column is clos- ately ventral to the inferior colliculus. The
est to the midline. Spindle-shaped cells of the dorsal and ventral nuclei of the lateral lem -
medial superior olivary nucleus emit den - niscus of both sides receive inputs arising
drites from both poles of the neurons. In ad - from the anteroventral cochlear nuclei ( 286 ).
dition to the main nuclei, there are other Other fibers ascending in the lateral lemnis -
smaller, diffusely arranged cell groups that cus probably contribute terminals or collat -
belong to the superior olivary complex. Dif - erals to these nuclei . The extent to which the
fusely arranged cells ventral to the superior nuclei of the lateral lemniscus contribute to
olivary complex are referred to as the preoli - the principal ascending auditory pathway is
vary nuclei , while cells dorsal to the main unknown , but it probably is substantial.
complex are designated as the retro-olivary When the lateral lemniscus reaches the mid -
cell group. The periolivary nucleus lies dorsal brain , most of its fibers terminate directly in
and medial to the medial superior olivary nu - the central nucleus of the inferior colliculus
cleus. ( 254, 301 ). Some fibers may reach the collicu -
The trapezoid body forms a conspicuous lus of the opposite side through the commis-
bundle of transverse fibers in the ventral sure of the inferior colliculi . The inferior col -
part of the pontine tegmentum ( Figs. 13.4, liculus give rises to fibers that project to the
13.5, and 13.27). These fibers arise princi - medial geniculate body of the thalamus via
pally from the ventral cochlear nucleus and the brachium of the inferior colliculus ( Fig.
sweep medially in a gentle arc toward the 13.13).
median raphe. Most of these fibers cross to Physiologic studies ( 228) suggest that
the opposite side, passing through or ventral some neurons of the inferior colliculus are
to the medial lemniscus, and reach the ven - sensitive to interaural time relationships of
trolateral portion of the tegmentum ( Fig. binaurally applied stimuli, while others are
13.5). Here they turn sharply in a longitudi - sensitive to small interaural intensity differ-
nal direction to form the principal ascending ences. These data indicate that certain neu -
auditory pathway, the lateral lemniscus ( Fig. rons in the inferior colliculus are concerned
13.13). The turn is made just dorsolateral to with the localization of a sound source.
the superior olivary complex ( Figs. 13.27 and It is obvious from this description that the
A .29 ). Cell aggregations scattered among the auditory pathway receives contributions
trapezoid fibers constitute the nuclei of the from a number of intercalated nuclear masses
trapezoid body . and has a more complex composition than
The lateral lemniscus , the principal ascend - sensory systems considered heretofore. There
ing auditory pathway in the brainstem, is also a considerable ipsilateral ascending
courses rostrally in the lateral part of the component consisting of ascending fibers
tegmentum . Initially, this bundle lies lateral arising mainly from the superior olivary com -
to the superior olivary complex ( Figs. 13.5 plex. It is difficult to state the number of neu -
and 13.13), but at isthmus levels its position rons involved in the auditory pathway from
is more dorsal ( Fig. 13.32 ). The lateral lem - the periphery to the cortex, but the principal
niscus ascends to midbrain levels, where the ones are (a ) cells of the spiral ganglion whose
fibers terminate in the inferior colliculus. In - central processes form the cochlear nerve, ( b )
terposed in the lateral lemniscus at isthmus secondary fibers from the dorsal and ventral
levels are the nuclei of the lateral lemniscus , cochlear nuclei which form the three auditory
which receive and contribute fibers to the striae and contribute primarily crossed fibers
main bundle. Two nuclei are distinguished : to the lateral lemniscus, ( c) the nuclei of the
a ventral nucleus and a dorsal nucleus. The superior olivary complex and the trapezoid
ventral nucleus of the lateral lemniscus , a com - body that contribute to the lateral lemnisci,
pact aggregation of cells in the ventrolateral ( d ) the nuclei of the lateral lemniscus which
receive and contribute fibers to the bundle of components of the olivocochlear bundle pro-
the same name, (e) the inferior colliculus ject peripherally from the brainstem to the
which receives fibers from the lateral lemnis - cochlea and form a pathway by which the
cus and projects via its brachium to the me- central nervous system may influence its own
dial geniculate body, and ( f ) the medial sensory input (108, 220 ). Electrical stimula -
geniculate body, which gives rise to geniculo- tion of the crossed olivocochlear bundle in
cortical fibers (auditory radiation ) that project the cat inhibits auditory nerve responses to
to the transverse temporal gyri of Heschl acoustic stimuli (114 ). Fibers of the olivo-
( Figs. 2.11 and 13.13) . Some crossed fibers in cochlear bundle originate from cholinergic
the dorsal and intermediate acoustic striae neurons surrounding the principal and acces-
may pass via the lateral lemniscus directly to sory superior olivary nuclei ( Fig. 13.15).
the medial geniculate bodv ( 256, 259, 297). Cochlear efferent fibers are best defined on
Most of the auditory impulses reaching the basis of their cells of origin into medial
the auditory cortex are conveyed by higher and lateral systems (121, 291 ). The medial
order neurons. Physiologic studies indicate a olivocochlear system originates from cells
definite tonotopic localization in the inferior medial, ventral, and rostral to the medial su-
colliculus ( 5, 176, 227, 289 ). Units of the cen- perior olive ( medial periolivary nucleus), is
tral nucleus of the inferior colliculus are char- composed of myelinated fibers, and project
acterized by sharp tuning and binaural re- bilaterally ( with contralateral dominance) to
sponses, while those in the pericentral and the outer hair cell region of the cochlea . The
external nuclei are very broadly tuned ( Fig. lateral olivocochlear system arises from cells
14.4 ). There is a systematic representation of lateral to the medial superior olive ( the lateral
the cochlea within the pericentral nucleus periolivary nucleus), contains unmyelinated
and a highly ordered representation of the fibers ( 264 ), and projects bilaterally ( with ip-
cochlea in the central nucleus of the inferior silateral dominance) to the inner cell region
colliculus. Isofrequency contours in the cen - of the cochlea. Crossed fibers of the olivo-
tral nucleus parallel cellular laminae with cochlear bundle project dorsomedially to-
low frequencies represented dorsally and ward the facial genu , cross the midline, and
high frequencies represented ventrally. In the are joined by uncrossed fibers ( Fig. 13.14 ).
medial geniculate body, low frequencies are Both crossed and uncrossed components of
perceived laterally and high frequencies are this efferent bundle emerge from the brain -
represented medially in the principal division stem via the vestibular nerve root (168). In
(3, 4, 289). Physiologic data concerning the the inner ear, these efferent fibers enter the
tonotopic representation of auditory im - cochlear nerv e via the vestibulocochlear anas-
pulses at the cortical level are discussed in tomosis, pass to the organ of Corti ( 219 ), and
Chapter 20. make synaptic contact with hair cells (146,
Because of the large number of interca - 239-241, 247-249 ). The efferent cochlear bun-
lated nuclei in the course of the auditory dle suppresses auditory nerve activity by in-
pathway ( i .e., superior olive, trapezoid nu - hibiting the receptivity of the end organ.
cleus, nucleus of the lateral lemniscus, infe - Other feedback mechanisms in the audi-
rior colliculus ), the cochlear reflex connec- tory system involve relay nuclei in the audi-
tions are exceedingly complex. It seems likely tory pathway ( 221 ). Fibers from the inferior
that all of the relay nuclei along the auditory colliculus, the nuclei of the lateral lemniscus,
pathway are involved to some degree in re- and the principal superior olive descend, or
flex circuits by which various motor phenom- pass distally, to relay nuclei. These pathways
ena occur in response to cochlear stimulation. differentially inhibit impulses concerned with
Experimental evidence suggests that a de- certain frequencies of the auditory spectrum
scending conduction system , from the audi- and in this way enhance frequencies not sub-
tory cortex to the cochlea ( 220), is associated ject to central inhibition . This phenomenon is
with the classical ascending auditory system . referred to as auditory sharpening.
Acoustic reflex mechanisms involve mid -
EFFERENT COCHLEAR BUNDLE dle ear muscles, such as the stapedius and
tensor tympani. The stapedius muscle, which
One of the most interesting cochlear reflex serves to dampen the oscillations of the ear
connections involves the olivocochlear bundle ossicles in response to high levels of acoustic
or the efferent cochlear bundle described by stimuli, is innervated by the facial nerve. Au -
Rasmussen ( 218, 219 ). Crossed and uncrossed ditory fibers from the superior olivary com-
Inferior cerebellar peduncle
IV Ventricle Vestibular nerve

Cochlear duct
Scala vestibuli
Scala tympani
Nucleus N
Spiral
ganglion
Superior olive Efferent cochlear bundle
Accessory olive
Figure 13.14 . Efferent cochlear fibers in the cat Crossed fibers of the olivocochlear bundle (red. a) arise from cells
dorsal to the accessory superior olivary nucleus, pass dorsomedially toward the floor of the fourth ventricle, and cross
to the opposite side. Uncrossed fibers of the olivocochlear bundle (red. b) arise from cells dorsal to the superior olivary
nucleus, join the crossed fibers, and pass peripherally in association with the vestibular nerve. Peripherally, efferent
cochlear fibers join the cochlear nerve via the vestibulocochlear anastomosis and are distributed to the hair cells of
the cochlea
«r. f-. Figure 13.15. Cochlear efferent neurons

identified by immunoreactivity to choline
acetyltransferase (ChAT) in the rhesus
monkey . A. A collection of ChAT-positive
neurons (.arrowhead) lying dorsal to the
superior olivary nucleus ( SO). B. The same
group of cochlear efferent neurons seen
.
at a higher magnification N VI abducens
nerve.
0.5 mm
100 fJm
483
plex ( 27) project bilaterally to stapedius oval window is thickened. Early in the course
motor neurons. Contractions of the stapedius of the disease patients with otosclerosis have
muscle, in response to loud sounds, serve to either a loss of appreciation of low tones, or a
diminish amplitude. Contractions of the ten - mild loss in the entire auditory range. Later
sor tympani muscle, innervated bv trigeminal there is a marked perceptual deficit for high
nerve fibers, also are initiated bv impulses tones. Tinnitus, without vertigo, is common ,
from the superior olivary complex. The ten - and many patients hear better in the presence
sor tympani muscles diminish the sensitivity .
of loud noises ( paracusis ).
of the tympanic membrane to sound bv tens-
ing the membrane. Labyrinth and Related Nerve and
Nuclei
LESIONS OF THE AUDITORY SYSTEM
LABYRINTH
Destruction of the cochlear nerve or the
cochlear nuclei causes complete deafness on The vestibular part of the inner ear con-
the same side. Among the more common dis- sists of three semicircular ducts, the utricle,
orders is the so-called acoustic neurinoma, a and the saccule ( Figs. 13.8 and 13.16 ). These
perineural fibroblastoma that arises from parts of the labyrinth are concerned with
cells of the Schwann sheath . Although this equilibrium and orientation in three-dimen-
benign tumor probably originates from the sional space, maintenance of equilibrium,
vestibular portion of the eighth nerve, loss of and modification of muscle tone. The semicir-
hearing with, or without, tinnitus usually is cular ducts, concerned with kinetic equilib-
the first symptom. Unilateral loss of hearing rium , are arranged at right angles to each
usually is gradual and may not be noticed by other and represent approximately the three
the patient until it is severe. In time, other planes of space. One end of each duct has a
cranial nerves almost invariably are involved , dilatation, the ampulla, containing a trans-
including the vestibular, trigeminal, and fa- versely oriented ridge, known as the crista
cial nerves. Since the secondary cochlear ampullaris . Columnar epithelium of the crista
pathways are both crossed and uncrossed , le- ampullaris is composed of neuroepithelial hair
sions of one lateral lemniscus or of the audi- cells that constitute the vestibular receptor
tory cortex cause a bilateral diminution of ( Fig. 13.20 ) . Each crista is covered by a gelati -
hearing ( partial deafness) that is most nous cupula that moves across the hair cells in
marked in the contralateral ear. Removal of response of movement of the endolymphatic
one temporal lobe causes an impairment of fluid . Angular acceleration causes displace-
sound localization on the opposite side, espe- ment of endolymphatic fluid and movement
cially as regards judgment of the distance of the cupula which stimulates the hair cells.
from which the sound is coming ( 204 ). Endolymphatic flow is greatest in the pair of
Conduction deafness due to disease of the semicircular ducts most nearly perpendicular
middle ear should be distinguished from to the axis of rotation.
nerve deafness. In conduction deafness, the The utricle and saccule together constitute
ossicular chain fails to transmit vibrations the so-called "otolith organ." They have a
from the tympanum to the oval window and similar patch of sensory epithelium known as
to the scala vestibuli and scala media ( i.e., the macula . The maculae are endowed with
cochlear duct) ( Fig. 13.9). When the ossicular hair cells in contact with a gelatinous mass
chain is broken , vibrations of the tympanum containing small calcareous concretions or
pass via the air of the middle ear to the round particles, the otoliths. The utricular macula re-
window. This is inefficient because it lacks sponds to changes in gravitational forces and
the impedance matching of the ossicular to linear acceleration in the long axis of the
chain and considerable sound energy is lost. body and convey impulses concerning the
Hearing loss due to interruption of the ossic- position of the head in space ( i.e., static equi-
ular chain ranges from 3(1 decibels for low librium ). The macula of the saccule is less
tones to 65 decibels in the middle range. Fixa - sensitive, but responds to linear acceleration
tion of the ossicular chain resulting from mid - in the ventrodorsal axis of the body .
dle ear infections, or otosclerosis, is more Anatomic studies ( 167, 252) demonstrate
common than interruptions of the ossicular that afferent nerve fibers from the saccular
chain . In otosclerosis , air conduction is im- macula do not join the cochlear nerve and
paired because the membrane covering the that they are distributed to the vestibular nu-
13 Pons 485
Anterior canal
Superior vestibular Lateral canal

ganglion
Utricle
Intermediate nerve
^ // j
Saccule
Facial nerve
Posterior canal
Vestibular
nerve
Inferior vestibular ganglion
Auditory nerve
Figure 13.16. Vestibular ganglia and peripheral branches innervating distinct portions of the labyrinth Cells in the su-
perior vestibular ganglion are arranged in a spiral fashion. Cells in the superior and distal portion of this ganglion inner -
vate the cristae of the anterior and lateral semicircular ducts. The brodder proximal part of the superior vestibular
ganglion contains cells which innervate the macula of the utricle. Cells of the inferior vestibular ganglion innervate
the macula of the saccule and the crista of the posterior semicircular duct . The superior and inferior vestibular gan-
glia are joined by an isthmus of cells The relationships between the facial, intermediate, vestibular, and auditory
nerves are shown on the left
clei in a manner similar to that of nerve fibers utricle. Cells of the smaller inferior vestibular
from the utricular macula and the semicircu - ganglion innervate the crista of the posterior
lar ducts. semicircular duct, and the macula of the sac-
cule ( 65, 144, 252 ). Vestibular root fibers en -
VESTIBULAR GANGLION AND NERVE ters the brainstem at the cerebellopontine
angle where fibers pass between the inferior
The maculae and cristae are innervated by cerebellar peduncle and the spinal trigeminal
cells of the vestibular ganglion (ganglion of tract. On entering the vestibular nuclear com -
Scarpa ), an aggregation of bipolar cells lo- plex, the fibers bifurcate into short ascending
cated in the internal auditory meatus. Most and long descending branches that terminate
cells of the vestibular ganglion have gluta - in the vestibular nuclei ( Figs. 12.16 and
mate as their neurotransmitter, but over 20 % 13.17-13.19 ). Some primary vestibular fibers
of the cells contain substance P ( 58). This gan - (i.e., root fibers) continue without interrup-
glion can be divided into superior and infe- tion to particular parts of the cerebellum .
rior vestibular ganglia, which are connected These fibers reach the ipsilateral half of the
by a narrow isthmus ( Figs. 13.8 and 13.16). cerebellum via the juxtarestiform body ( Fig.
The short peripheral processes of bipolar cells 13.7) and project mainly to the cortex of the
located in the ganglia go to the receptor cells nodulus, uvula and flocculus ( 34, 65).
of the maculae and cristae, while the longer
central processes form the vestibular nerve. VESTIBULAR NUCLEI
Cells of the superior vestibular ganglion in -
nervate the cristae of the anterior and lateral The vestibular nuclei lie in the floor of the
semicircular ducts, and the macula of the fourth ventricle and extend from levels ros-
VESTIBULAR NUCLEI VESTIBULAR GANGLIA
Superior
Lateral
Vestibular root
r . Anterior canal n
5%
Medial
Inferior ^ Lateral canal n

Utricular n
Saccular n
Post canal n
Figure 13.17 . Relationship between portions of the vestibular ganglia and central fibers projecting to parts of the
vestibular nuclear complex . The vestibular ganglia are shown in a modified transverse plane, while the vestibular
nerve root and the vestibular nuclear complex are drawn in a stylized fashion, as they would appear in horizontal
sections of the brainstem . Only the principal central projections of distinctive pdrts of the vestibular ganglia are
shown. Portions of the vestibular ganglia innervating the cristae of the semicircular ducts (red) project primarily to the
superior vestibular nucleus and rostral parts of the utricle project central fibers primarily to parts of the inferior and me-
dial vestibular nuclei. Fibers from portions of the inferior vestibular ganglion innervating the macula of the saccule
( blue), project mainly to dorsolateral parts of the inferior vestibular nucleus. Some cells in the vestibular ganglia pro-
ject fibers to parts of an vestibular nuclei, so that each part of the labyrinth has a unique as well as common protec-
.
tion within the vestibular nuclear complex.
tral to the hypoglossal nucleus to slightly be- cleus is characterized by bundles of longitu -
yond the level of the abducens nucleus. Nu - dinally oriented fibers, part of which are
clei of this complex are arranged into longitu- descending primary vestibular fibers. These
dinal columns. The lateral column consists of descending fiber bundles facilitate the delin-
three distinctive nuclei: the inferior, lateral, eation of the inferior and medial vestibular
and superior vestibular nuclei. The medial nuclei ( Figs. 12.26 and 13.4 ).
vestibular nucleus constitutes the medial cell The lateral vestibular nucleus ( Deiters' nu -
column (115) ( Figs. 13.17, 13.18, A.4, A.5, and cleus), located laterally in the ventricular
A .6). floor at the level of entrance of the vestibular
The inferior vestibular nucleus begins cau - nerve, extends rostrally to the level of the ab-
dally in the medulla, medial to the accessory ducens nucleus. This nucleus is composed of
cuneate nucleus, and extends rostrally medial multipolar giant cells with coarse Nissl gran -
to the level of entrance of the vestibular nerve ules. Although most of the cells of this nu -
( Fig. 13.4 ). This nucleus is composed mostly cleus are regarded as giant cells, considerable
of small- and medium-sized cells, except in variations in cell size are found ( Fig. 13.3).
its most rostral part, where large cells resem- The nucleus also contains varying types of
ble those of the lateral vestibular nucleus. In smaller cells. Cells of all sizes are intermin-
the ventrolateral and caudal parts of the nu - gled throughout the nucleus except in a small
cleus, a number of rather large cells form sev- dorsolateral protrusion that consists only of
eral densely packed groups. These cells medium-sized cells. There are some regional
( group f of Brodal and Pompeiano ( 36) ) are of differences in the relative number and size of
particular interest because they do not re- giant cells, which are most abundant in the
ceive primary vestibular fibers and many of caudal part of the nucleus. The giant cells in
them project fibers to the cerebellum. In fiber- the lateral vestibular nucleus have numerous
stained sections, the inferior vestibular nu - boutons on their soma , while small cells have
13 Pons 487
Thalamus
Oculomotor
nucleus
Vestibular
nuclei { Lateral
Superior
Trochlear
nucleus
\
Abducens
yf nucleus
\ N
/ Middle cerebellar
Vestibular root I peduncle
Interstitial nucleus Secondary

of vestibular nerve vestibulo - cerebellar
fibers
Vestibular
nuclei { Inferior
Medial
Medial longitudinal fasc . _ Vestibulospinal

(descending vestibular fibers) tract
Figure 13.18 . Principal fiber projections of the vestibular system. On the left, the relationships and spatial disposition
of the four main vestibular nuclei are indicated Among the afferent root fibers are the cells of the interstitial nucleus
of the vestibular nerve. Dotted areas in the vestibular nuclei represent the regions of the nuclear complex which re-
ceive the largest number of primary vestibular fibers. These areas are (a) the ventral half of the lateral vestibular nu-
.
cleus (b) the lateral part of the medial vestibular nucleus, (c) the dorsomedial part of the inferior vestibular nucleus,
and (d) the central part of the superior vestibular nucleus. On the right, secondary projections from some of the Indi-
vidual vestibular nuclei are shown. Fibers from the superior vestibular nucleus (red) ascend ipsilaterally in the medial
longitudinal fasciculus ( MLF ) and terminate In parts of the trochlear and oculomotor nuclei . Ascending projections
from the rostral part of the medial vestibular nucleus (.black ) to the nuclei of the extraocular muscles are predomi-
nantly crossed. A small number of uncrossed ascending fibers from lateral vestibular nucleus are not shown. Fibers
from caudal parts of the medial vestibular nucleus descending in the MLF are shown in black . The somatotopically or -
ganized vestibulospinal tract ( blue) arises only from the lateral vestibular nucleus . Secondary vestibulocerebellar
fibers ( black ) arise from caudal parts of the inferior and medial vestibular nuclei
relatively few boutons (180). Fibers of the its rostrocaudal extent. The mesencephalic
vestibular root traverse ventral parts of this and principal sensory nuclei of the trigeminal
nucleus. nerve are adjacent to the nucleus medially
The superior vestibular nucleus lies dorsal and ventrally, in its rostral two-thirds. The
and rostral to the lateral vestibular nucleus in rostral pole of the nucleus is difficult to de-
the angle formed by the floor and the lateral limit . Cells in the central region of the nu -
wall of the fourth ventricle ( Figs. 13.1 and cleus are large, stellate, and form clusters
13.7). The superior cerebellar peduncle (or (32), whereas those at the periphery are
brachium conjunctivum ) forms the dorsolat - smaller, round or spindle-shaped, and more
eral border of the nucleus throughout most of loosely distributed .
Vestibular Fiber Systems

PRIMARY VESTIBULAR FIBERS
These fibers project to all four vestibular

nuclei and to the interstitial nucleus of the
vestibular nerve, a collection of cells between
the entering vestibular root fibers. Upon en-
tering the vestibular complex, virtually all
fibers bifurcate into ascending and descend -
ing branches. Ascending branches project
mainly to the superior, lateral , rostral parts of
the medial vestibular nuclei ( Fig. 13.17). De-
scending branches provides fibers to the infe-
rior vestibular nucleus and collaterals to cau -
dal parts of the medial vestibular nucleus ( 46,
47, 236, 232, 278). Primary vestibular fibers
are distributed within all vestibular nuclei,
V s but some regions of each nucleus contain
L fewer endings. In the superior vestibular nu -
cleus, primary vestibular fibers terminate
B most profusely about large central cells but
extend into all peripheral regions. In the lat -
Figure 13.19 . A. Soggital section through the bn : eral vestibular nucleus, primary vestibular
in a rhesus monkey demonstrating transport of ( 5H) -la-
beled amino acids from the labyrinth to the vestibular fibers terminate only in the ventral regions
nuclei in an autoradiograph (Cresyl violet, dark field. ( 46, 47, 167, 232, 278 ) ( Fig 13.19 ) . These fibers
x 20) B Fastigial (F) and vestibular nuclei S. superior establish synaptic contact primarily with the
vestibular nucleus; L lateral vestibular nucleus. /. inferior soma and dendritic stems of small cells; the
vestibular nucleus. Art, medial vestibular nucleus Al-
though primary vestibular afferents proiect to all ipsilat -
giant cells receive fewer synaptic endings
eral vestibular nuclei, only the ventral half of the lateral from primary vestibular fibers (180). The me-
vestibular nucleus receives terminals from this source. dial vestibular nucleus receives primary
vestibular fibers throughout large regions of
its rostral part , but caudally, terminations are
The medial vestibular nucleus , the largest of mainly in lateral regions near the inferior
all four vestibular nuclei, is located medial to vestibular nucleus ( Fig. 13.17). Primary
the inferior and lateral vestibular nuclei in the vestibular fibers in the inferior vestibular nu -
floor of the fourth ventricle ( Figs. 13.4 and cleus end more profusely in dorsal regions
13.17). This nucleus extends from the oral ( Figs. 13.17 and 13.18) . The cristae of the
pole of the hypoglossal nucleus to the ab- semicircular ducts give rise to fibers that pro-
ducens nucleus and rostrally fuses with the ject primarily to the superior vestibular nu -
superior vestibular nucleus. It is composed of cleus and to rostral parts of the medial
-
small and medium-sized cells and contains vestibular nucleus. Cells of the superior
relatively few fibers. Dorsolaterally, some vestibular ganglion , which innervate the
larger cells resemble those of the lateral macula of the utricle, project almost exclu -
vestibular nucleus, although none are true sively to the ventral part of the lateral
giant cells. The medial and inferior vestibular vestibular nucleus ( Fig. 13.19 ). Cells of the in-
nuclei can be readily distinguished at all lev- ferior vestibular ganglion, which innervate
els in myelin -stained preparations because the macula of the saccule, give rise to central
bundles of longitudinally coursing fibers are fibers that descend and terminate mainly in
not present in the medial vestibular nucleus dorsolateral portions of the inferior vestibular
( Fig. 13.4 ). nucleus and in an accessory nucleus known
Besides the main vestibular nuclei, there as cell group "y" ( 46, 47, 39, 232). The intersti -
are several smaller accessory nuclei ( 32, 36, tial nucleus of the vestibular nerve appears
113), one of which consists of strands of cells distinctive in that this nucleus receive fibers
between the root fibers of the vestibular from all cell groups of the vestibular ganglia
nerve ( interstitial nucleus of the vestibular ( Fig. 13.18).
nerve ) ( Fig. 13.18). A small number of primary vestibular
13 Pons 489
fibers enter the cerebellum via the juxtaresti- relayed by the fastigial nuclei. The cortex of
form body. Most of these primary vestibulo- the cerebellar vermis projects upon the fasti-
cerebellar fibers traverse portions of the lateral gial nucleus, which in turn gives rise to a
and superior vestibular nuclei and terminate vestibular projection. Fastigial efferent fibers
in the cortex of the ipsilateral nodulus, uvula , follow a complex course, best described in re-
and flocculus ( 34 ). In monkeys, cells in all lation to other efferent systems from the cere-
parts of the vestibular ganglion project to the bellar nuclei (see Chapter 15). The fastigial
ipsilateral nodulus and uvula, where they nucleus projects bilaterally and nearly sym-
end as mossy fibers in the granular layer of metrically upon ventral portions of the lateral
cerebellar cortex (65). Cells of the vestibular and inferior vestibular nuclei ( 19, 55). Fasti-
ganglion that innervate the cristae of the an - gial efferent projections have excitatory influ -
terior and lateral ducts and the maculae of ences, probably mediated by glutamate.
the utricle and saccule have distinctive re- The vestibular nuclei do not appear to re-
gions of termination in the folia of the ipsilat - ceive descending fibers from the cerebral cor -
eral flocculus. Although a few primary tex, the corpus striatum, the superior collicu -
vestibular fibers may end in the dentate nu - lus, or the nuclei of the posterior commissure
cleus, there is no conclusive evidence that ( 214). Descending fibers from the interstitial
such fibers terminate in the fastigial nucleus. nucleus of Cajal project via the medial longi -
At least one study suggests that primary tudinal fasciculus to the medial vestibular
vestibulocerebellar fibers are confined largely nucleus. These fibers appear to be the only
to the ipsilateral nodulus and flocculus and descending vestibular afferent fibers arising
are relatively sparse ( 148 ). from cells within the brainstem .
Commissural projections from the con -
AFFERENT PROJECTIONS TO THE VESTIBULAR tralateral vestibular nuclei , principally the su-
NUCLEI perior and medial vestibular nuclei, have
major influences on vestibular function ( 50,
The vestibular nuclei receive a large num - 94, 111), 157, 175, 235). Vestibular neurons re-
ber of afferent fibers from sources other than ceiving inputs from ganglion cells innervat -
the vestibular ganglion ( 175). According to ing the cristae of the semicircular ducts have
Brodal ( 32 ), vestibular afferents from the inhibitory influences on contralateral vestibu -
cerebellum outnumber those from any other lar neurons via commissural projections.
source. Cerebellar projections to the vestibu - Vestibular neurons with inputs from gan -
lar nuclei arise from the following regions of glion cells innervating the maculae of the
the cerebellum: ( a ) the "vestibular part," ( b) otoliths exert contralateral excitatory influ -
the "spinal part," and ( c) the fastigial nucleus. ences via commissural projections.
The "vestibular part" of the cerebellum (or
vestibulocercbellum ), consisting of the floc - SECONDARY VESTIBULAR FIBERS
culus, nodulus, and ventral portion of the
uvula , projects ipsilaterally, chiefly to parts of The vestibular nuclei give rise to sec-
the superior and medial vestibular nuclei ondary fibers that project to specific portions
(10). The lateral vestibular nucleus receives of the cerebellum, to certain motor cranial
only a few afferents from this source. Projec- nerve nuclei, and to all spinal levels. These
tions from the "spinal part" of the cerebel - fibers are more widely dispersed within the
lum , represented mainly by the vermis of the neuraxis than any other special sensory sys-
anterior lobe, are ipsilateral to the dorsal part tem, probably because the vestibular system
of the lateral vestibular nucleus and the dor - is concerned with the maintenance of equilib-
sorostral part of the inferior vestibular nu - rium and orientation in three-dimensional
cleus ( 279 ). The latter projection somatotopi
callv links the forelimb region of the anterior
- space.
Secondary vestibulocerebellar fibers arise
lobe with the forelimb region of the lateral mainly from caudal portions of the inferior
vestibular nucleus. These fibers, representing and medial vestibular nuclei and project ipsi -
axons of Purkinje cells, are known to have a laterally to the cortex of the nodulus, uvula ,
monosynaptic inhibitory influence upon neu - and flocculus ( 41 ) ( Fig. 13.18). Vestibulocere-
rons of the lateral vestibular nucleus medi- bellar fibers, both primary and secondary,
-
ated by •y aminobulyric acid (GABA ) ( 68, 101, enter the cerebellum via the juxtarestiform
128). Indirect projections from "spinal parts" body . None of these fibers end in the fastigial
of the cerebellum to the vestibular nuclei are nucleus, but this nucleus projects to the
vestibular nuclei in a selective manner (19, 49, Some vestibular fibers descending in the MLF
55, 265, 280 ). synapse directly upon alpha (a ) motor neu -
Cells of the lateral vestibular nucleus give rons. Experimental evidence indicates that
rise to the somatotopically organized , un- these fibers exert direct inhibitory influences
crossed vestibulospinal tract, which descends upon cervical motor neurons ( 295). The supe-
throughout the length of the spinal cord in rior, lateral, and inferior vestibular nuclei do
the anterior and lateral funiculi ( Figs. 11.19, not appear to contribute descending fibers to
11.21, and 13.18). These fibers, arising from the MLF that reach spinal levels (50, 187, 213).
cells of all sizes within the nucleus, are soma- The MLF at spinal levels also contains
totopically organized ( 213). In the medulla , nonvestibular descending fibers from (a ) the
the vestibulospinal tract is a loosely orga- interstitial nucleus of Cajal ( interstitiospinal
nized bundle extending obliquely from the tract ), ( b ) the superior colliculus ( tectobulbar
region of the medial longitudinal fasciculus and tectospinal tracts, sometimes referred to
( MLF ) to the retro-olivary area . The dorsal as the predorsal bundle), (c) the pontine retic-
half of the lateral vestibular nucleus receives ular formation ( reticulospinal tract ), and ( d )
somatotopically organized inhibitory inputs more rostral brainstem nuclei projecting to
from the Purkinje cells in the anterior lobe particular portions of the inferior olivary
vermis, while ventral regions of the nucleus complex. The largest group of descending
receive crossed and uncrossed excitatory in- fibers in the MLF are the pontine reticu -
fluences from the fastigial nuclei (19, 55). lospinal fibers ( Figs. 11.10 and 11.22 ). Other
Fibers from the fastigial nucleus do not ap- pontine reticulospinal fibers descend more
pear to terminate upon large cells in the lat - ventrally to reach the anterior funiculus of
eral vestibular nucleus ( 280 ), while fibers the spinal cord ( Fig. 11.25).
from the cerebellar vermal cortex end princi - Ascending fibers in the MLF arise mainly
pally upon such cells ( 179, 279 ). Thus, the lat- from parts of the medial and superior
eral vestibular nucleus receives impulses vestibular nuclei ( 120, 251 ), are crossed and
from the vestibular nerve and various parts uncrossed , and project primarily to the nuclei
of the cerebellum, and conveys impulses to of the extraocular muscles (i.e., the abducens,
spinal levels that mediate responses in axial trochlear, and oculomotor ) (52, 170 ). Ascend -
and appendicular musculature ( 37). Impulses ing fibers from the medial vestibular nucleus
relayed to spinal levels via the vestibu- reach (a ) the abducens nucleus ( bilateral ), ( b)
lospinal tract have facilitating influences the contralateral trochlear nucleus, (c ) the
upon extensor muscle tone. contralateral intermediate cell column ( i .e.,
inferior oblique muscle), and (d ) the ipsilat -
MEDIAL LONGITUDINAL FASCICULUS (MLF) eral ventral nucleus ( i .e., medial rectus mus-
cle ) of the oculomotor complex ( Figs. 13.18
Fibers from all of the vestibular nuclei pass and 14.14 ). Large cells in central parts of the
medially in the region of the abducens nu - superior vestibular nucleus give rise to un -
cleus and enter the MLF. Vestibular fibers in crossed ascending fibers in the MLF distrib-
the MLF are both crossed and uncrossed , and uted to the trochlear and oculomotor nuclei.
many bifurcate into ascending and descend - Smaller cells in peripheral parts of the supe-
ing branches ( Figs. 11.19 and 13.18). rior vestibular nucleus project fibers to the
Descending vestibular fibers in the MLF oculomotor nucleus via a crossed ventral
projecting to spinal levels arise primarily, if tegmental pathway (outside the MLF), which
not exclusively, in the medial vestibular nu - has major influences on cells innervating the
cleus. These fibers, both crossed and un- opposite superior rectus muscle ( 56 ). Physio-
crossed at medullary levels, descend in the logically, crossed ascending vestibular projec-
MLF until they reach the pyramidal decussa - tions to the nuclei of the extraocular muscles
tion , where they shift ventrolaterally to enter have excitatory effects, while uncrossed fibers
the sulcomarginal region of the anterior fu - exert inhibition ( Fig 13.18).
niculus. In their course, they may project Additionally, the MLF contains an impres-
fibers into the lower brainstem reticular for- sive crossed ascending projection originating
mation . Although these fibers are present bi- from the abducens internudear neurons that
laterally in the medulla, at spinal levels al - terminate upon cells of the medial rectus sub-
most all fibers are ipsilateral. Some fibers division of the oculomotor nuclear complex
may descend as far as upper thoracic seg- ( 14, 54, 56, 120, 243, 250, 251 ) ( Fig. 13.25) . This
ments, but most fibers end at cervical levels. projection interrelates activities of the ab-
13 Pons 491
ducens nucleus neurons on one side with 89-91, 158, 164 ). Thalamic nuclei receiving
neurons of the oculomotor nucleus, which in - vestibular inputs also respond to somatosen -
nervate the medial rectus muscle on the op- sory signals, suggesting there is no exclusive
posite side. This pathway provides a neural representation of vestibular sense at thalamic
mechanism for simultaneous contractions of levels.
the lateral rectus muscle on one side and the
medial rectus muscle on the opposite side, EFFERENT VESTIBULAR SYSTEM
which are required for conjugate lateral gaze
( Fig. 13.22 ). Like the cochlea, the vestibular end organ
A small number of ascending fibers in the receives an efferent innervation that arises bi -
MLF bypass the oculomotor nucleus to termi- laterally and symmetrically from brainstem
nate in the interstitial nucleus of Cajal, a neurons (112, 116, 288 ). These cholinergic ef -
small group of neurons embedded in the ferent neurons lie along the lateral border of
MLF ( Figs. 14.16-14.18). The medial vestibu - the abducens nucleus and give rise to fibers
lar nucleus project to the opposite interstitial that pass peripherally with the vestibular
nucleus, while the superior vestibular nu - nerve on each side to innervate hair cells in
cleus provides terminals to the ipsilateral in - the cristae of the semicircular ducts and the
terstitial nucleus. maculae of the utricle and saccule (58) ( Figs.
Secondary vestibular projections to thala - 13.20 and 13.21 ). Efferent vestibular fibers
mic relay nuclei are bilateral, modest in num - have bilateral excitatory effects on each of the
ber, and end about cell clusters in the ventral five end organs of the labyrinth . It has been
posterolateral ( VPLC ) thalamic nucleus (24, postulated that the efferent vestibular fibers
Hair cells labyrinth
Type I Type II
Supporting
cells —
Nerve — Granulated
chalice nerve ending
Pons
Vestibular
IV afferents
Ventricle \
SCPJ
S •V - Efferent
L VI vestibular
' fibers
VII
Spinal
trigeminal
tract
f
/
,
\ rJL Nerve
Vestibular ganglion
Nucleus
\
N. VI
A
Figure 13.20. Efferent vestibular fibers (red) and their relationship to the hair cells of the labyrinth . Efferent cholinergic
vestibular fibers arise bilaterally from small groups of neurons along the lateral border of the abducens nucleus ( VO
(see Figure 13.21). emerge vid the vestibular nerve, and terminate in granulated nerve endings at the base of type I
and type II hair cells A. Transverse section of the pons at level of abducens nuclei. B Hair cells of the labyrinth. Effer -
ent vestibular fibers exert excitatory influences upon the hair cells, which may modulate their dynamic range. L lat-
eral vestibular nucleus; S. superior vestibular nucleus; SCP. superior cerebellar peduncle.
Figure 13.21. Vestibular efferent neurons

identified by their immunoreoctivlfy to
choline acetyltransferase (ChAT) in a rhe-
sus monkey A . Vestibular efferent neurons
.
( arrowhead) lying lateral to the cells of the
abducens nucleus ( VI) B. Higher magnifi -
cation of the same section, showing
vestibular efferent neurons and one popu-
lation of cells in the abducens nucleus
that are cholinergic
may modulate the dynamic range of afferents ments of the eyes. Section of the MLF rostral
to match expected acceleration . It is of inter- to the abducens nuclei abolishes these pri -
est that the efferent cochlear and vestibular mary oculomotor responses, but nystagmus
neurons are both cholinergic, but efferent still results from labyrinthine stimulation ( 22,
cochlear fibers are inhibitory and efferent 165, 166, 244 ), suggesting that pathways es-
vestibular fibers are excitatory ( Figs. 13.15 sential for nystagmus probably pass via the
and 13.21 ). reticular formation .
Labyrinthine stimulation , irritation , or dis-
Functional Considerations ease cause vertigo, postural deviation , un-
steadiness in standing and walking, devia -
Secondary vestibular fibers contained in tions of the eyes, and nystagmus. In some
the MLF play an important role in conjugate instances, nausea , vomiting, vasomotor
eye movements (73, 74, 99, 261 ). Selective changes, and prostration occur. The term ver -
stimulation of the nerve from the ampulla of tigo refers to a subjective sense of rotation, ei -
individual semicircular ducts produces spe- ther of the individual or his environment.
cific deviations of both eyes that are regarded This term should not be regarded as a syn -
as primary responses. Stimulation of the am- onym for dizziness or giddiness. The most
pullary nerve from the horizontal duct pro- prominent objective signs of vestibular in -
duces conjugate deviation of the eyes to the volvement is nystagmus , a rhythmic involun -
opposite side. Bilateral stimulation of the am- tary oscillation of the eyes characterized by
pullary nerve of the anterior ducts produces alternate slow and rapid ocular excursions.
upward movement of both eyes; similar bilat - By convention, the direction of the nystag-
eral stimulation of the ampullary nerve of the mus is named for the rapid phase, even
posterior ducts causes downward move- though the slow ocular excursion is the pri-
13 Pons 493
mary movement ( the rapid phase is the auto- lar adduction on attempted lateral gaze to the
matic reflex correction ). The nausea and vom- opposite size results from interruption of as-
iting which occur with motion sickness are cending fibers from the abducens internu -
mainly the result of stimulation of the utricle. clear neurons after they have crossed from
Since the labyrinths are antagonistic to each the opposite side ( 54 ) ( Fig. 13.22 ). Unilateral
other, the elimination of one causes the other lesions of individual vestibular nuclei in the
to be overactive until accommodation takes monkey do not produce dissociated ( i .e.,
place. dysconjugate ) eye movements ( 51, 170, 269 ).
Tests for vestibular function are based on Mechanisms governing equilibrium ( i.e.,
stimulation of the semicircular canals or maintenance of appropriate body position )
vestibular nerve endings by ( a ) the rotating and orientation in three-dimensional space
chair test ( Barany chair ), ( b) the caloric test are largely reflex in character and depend
( irrigation of the external auditory canal with upon afferent inputs from several sources
water of temperatures appropriate to induce ( 294 ). The most important of these are (a )
convection currents in the endolymphatic kinesthetic sense conveyed by the posterior
fluid ), and (c ) the galvanic test which stimu - column-medial lemniscal system from recep-
lates nerve endings directly. Following a pe- tors in joints and joint capsules, ( b ) impulses
riod of rotation in the Barany chair, the chair conveyed centrally by spinocerebellar sys-
is abruptly stopped , but the endolymphatic tems from stretch receptors in muscles and
fluid continues to circulate for a time. In this tendons, (c) the suprasegmental kinesthetic
postrotational phase, the slow phase of the sense provided by the vestibular end organ,
nystagmus, the deviation of the eyes, pos - and (d ) visual input from the retina . Among
tural deviation (standing), and past - pointing the sensory systems that contribute to the
are all in the direction of the previous rota- maintenance of equilibrium , the labyrinth
tion and can be correlated with the direction constitutes a highly specialized receptor that
of endolymphatic flow. The patient experi - is stimulated by the change of position or
ences a sensation of vertigo opposite to that changes in position of the head . When the
of the prior rotation ( 92 ). head is moved , either by contraction of the
Lesions involving the MLF rostral to the neck muscles or by shifting the body as a
abducens nuclei produce a disturbance of whole, the cristae are stimulated and effect
conjugate horizontal eye movements known compensatory reflex adjustments of the eyes
as intermiclcar ophthalmoplegia (69, 72, 245, and limb muscles needed for the particular
246 ). The salient features of this syndrome in movement ( kinetostatic reflexes ). As long as
cases with a unilateral MLF lesion are ( a ) the position of the head remains unchanged ,
paresis of ipsilateral ocular adduction on at - the new attitude is sustained by impulses
tempted lateral gaze to the opposite side, ( b) originating in the macula of the utricle. The
monocular horizontal nystagmus in the con- sustaining (static) reflexes are initiated by
tralateral abducted eye, and (c) no impair- gravitational forces acting upon the macular
ment of ocular convergence. The paresis of hair cells.
ocular adduction on attempted lateral gaze to The vestibulospinal tracts and descending
the opposite side occurs ipsilateral to unilat - fibers from the pontine reticular formation
eral lesions of the MLF ( Fig. 13.22 ). Bilateral exert a strong excitatory influence upon mus-
lesions of the MLF rostral to the abducens nu - cle tone, particularly extensor muscle tone.
clei result in dissociated horizontal eye move- Descending vestibular impulses in the MLF
ments on attempted lateral gaze to both the exert inhibitory influences upon cervical
right and left sides ( 22, 23, 233). In the bilat- motor neurons ( 295). Normally, muscle tone
eral syndrome, no ocular adduction is seen is maintained by a balance of inhibitory and
on attempted lateral gaze to either side. An facilitatory influences from higher centers, a
adequate explanation for the monocular nys- large part of which are mediated by the
tagmus seen in the abducting eye has eluded brainstem reticular formation . If the influ -
clinicians and basic science researchers. This ences of higher centers are removed in an ex-
syndrome has been produced in monkeys perimental animal , such as the cat , by tran-
( 62, 66 ) and occurs in humans, mainly as a section of the brainstem at intercollicular
consequence of brainstem vascular lesions or level ( i.e., between the superior and inferior
in association with demyelinating diseases, colliculi ), a condition known as decerebrate
such as multiple sclerosis. The paresis of ocu - rigidity develops. This condition is character-
Medial
rectus
Lateral
V -
rectus C . Right MLF syndrome
Attempted gaze to left
N . Ill 1 . Paresis of right ocular
adduction
2 . Monocular horizontal
nystagmus on left
B . Right lateral gaze paralysis

1 . Forced lateral gaze to
Midbrain
N III N. VI the left
2 . Inability to gaze to the
right
MLF
'
t
A Right lateral rectus palsy

Attempted gaze to the right
Figure 13.22. Lesions affecting conjugate horizontal gaze The lesion at A (red), involving the right abducens nerve
as It leaves the brainstem, produces a paralysis of the right lateral rectus muscle. In the eyes at A. the patient is at -
tempting to gaze to the right The right eye is somewhat adducted and the left eye is fully adducted. This patient
would experience diplopia on attempted right lateral gaze. The lesion in the abducens nucleus (8 ( red)) would de-
stroy lower motor neurons and abducens internuclear neurons whose axons enter the opposite MLF and ascend to
the ventral nucleus (which innervates the medial rectus muscle) of the oculomotor complex . A patient with such a le-
sion would have a right lateral gaze paralysis and both eyes would be forcefully directed to the left field of gaze A
unilateral lesion (red) in the right MLF ( blue) at C would interrupt axons of abducens internuclear neurons arising from
the left abducens nucleus. This lesion would produce dissociated horizontal eye movements. On attempted gaze to
the left, there would be a paresis of right ocular adduction (C) and monocular horizontal nystagmus In the left ab-
ducting eye. Indicated by arrows .
ized by tremendously increased tone in the mation and from the lateral vestibular nu-
antigravity muscles, due to an increased fir- cleus ( vestibulospinal tract ) remain active,
ing rate of muscle spindles by gamma ( y ) while inhibitory elements of the reticular for-
motor neurons. The increased firing rate of mation no longer function. Inhibitory regions
the muscle spindles afferents activates a of the reticular formation are considered to be
motor neurons that maintain the tonic state dependent upon descending impulses from
( Fig. 10.30 ). In this experimental preparation, higher levels, while facilitating regions of the
facilitatory pathways from the reticular for- reticular formation remain active. Midbrain
13 Pons 495
transection removes the input essential to the facial expression, the platysma , the buccina -
reticular inhibitory system but has little effect tor, and the stapedius muscles. The motor nu -
upon brainstem facilitating mechanisms. De- cleus of nerve VII forms a column of choliner-
cerebrate rigidity can be abolished, or dimin - gic multipolar neurons in the ventrolateral
ished , by a variety of different lesions, includ - tegmentum dorsal to the superior olivary nu-
ing section of the vestibular nerve, cleus and ventromedial to the spinal trigemi-
destruction of the vestibular nuclei, or section nal nucleus ( bigs. 13.1, 13.2, 13.23, and 13.24) .
of the vestibulospinal tract . Surgical section The facial motor nucleus is subdivided into
of several successive dorsal or ventral spinal dorsomedial, ventromedial, intermediate,
roots will abolish the phenomenon segmen- and lateral cell groups, each group innervat-
tally because either will interrupt the gamma ing distinct facial muscles (84, 1 %, 276 ). The
-
( y ) loop. dorsomedial cell group gives rise to the pos-
terior auricular nerve which innervates auric-
FACIAL NERVE ular muscles and the occipital muscle. The
ramus colli which innervates the platysma
The facial nerve ( N. VII ) and the interme- muscle arises from be ventromedial cell
diate nerve usually are discussed together al- group. Cells in the medial group are consid -
though they subserve separate functions ered to innervate the stapedius muscle ( 27).
( Figs. 13.1 and 13.2). Functional components The temporal and zygomatic branches of the
of these nerves include (a ) special visceral effer- facial nerve, related to the intermediate cell
ent (SVE, branchiomotor ) fibers, ( b ) general group, supply the frontalis, orbicularis oculi,
visceral efferent (GVE, parasympathetic) fibers, the corrugator supercilli, and the zygomati-
(c) special visceral afferent (SVA, taste ) fibers, cus. The lateral cell group gives rise to the
and ( d ) a few general somatic afferent (GSA, buccal branches which innervate the buccina-
sensory ) fibers. tor muscle and the buccolabial muscles. Com-
Special visceral efferent (SVE ) fibers of the parisons of the cell groups of the facial nu -
motor component innervate the muscles of cleus in animals and humans ( 276) reveal a
Lacrimal gland
T rigeminal
p salivatory
ganglion
nucleus
L- Motor nucleus
Major superficial N 3ZII
petrosal nerve
Nasal and ,
palatine _ . . 7 c Nucleus fasc
glands solitarius
Pterygopalatine /'
ganglion /7 Geniculate
Chorda
ganglion
\
tympani
Lingual nerve A
\
Fasc. solitarius
rSubmandibular gang .
^ Motor root NAZII
Submandibular gland
Sublingual gland
Figure 13.23. Functional components, organization, and peripheral distribution of the facial nerve. Special visceral
efferent fibers (motor) are shown in red . General visceral efferent fibers (parasympathetic) are in yellow, and special
.
visceral afferent fibers (taste) are in blue. A. 0 and C denote lesions of the facial nerve at the stylomastoid foramen,
distal to the geniculate ganglion, and proximal to the geniculate ganglion Disturbances resulting from lesions at
these locations are described in the text .
Root fibers N. VII

Ascending
Cerebellar peduncle
Inferior
Middle
Nucleus N VI
Spinal trigeminal
Nucleus
Tract
Central tegmental
tract Nucleus N. VII
Medial Superior olivary

lemniscus nucleus
Trapezoid
Lateral pontine
nuclei
Medial pontine nuclei Corticospinal tract

Figure 13 24 Transverse section of the adult pons through the abducens nucleus showing the root fibers of the ab
ducens and fdcial nerves (Weigert ' s myelin stain)
.
close correspondence, except tli it in humans
the lateral cell group ( buccolabial muscles) is
near the rostral pole of the abducens nucleus,
they make a sharp lateral bend around the
especially prominent while the medial cell rostral border of the abducens nucleus and
group is very small . A few muscle spindles pass ventrolaterally. In their emerging
have been described in facial muscles ( 29, course, these fibers pass medial to the spinal
275 ). The presence of muscle spindles sug- trigeminal complex, lateral to the superior
gests the existence of gamma ( y ) efferent olivary nucleus, and exit from the brainstem
fibers, and leads to the assumption that near the caudal border of the pons, at the
gamma ( y ) neurons are mixed with a neu - cerebellopontine angle ( Figs. 12.33, 13.1, 13.4,
rons in the facial nucleus. 13.6, and 13.7). Root fibers looping around
Efferent fibers from the facial motor nu- the abducens nucleus form the internal genu
cleus (SVE fibers ) emerge from its dorsal sur- of the facial nerve ( Fig. 13.27).
face and project dorsomedially into the floor The facial motor nucleus receives afferent
of the fourth ventricle. These fibers ascend fibers from a number of sources. Among
longitudinally medial to the abducens nu - these are (a ) secondary trigeminal fibers from
cleus and dorsal to the MLF ( Fig. 13.24 ), but the spinal trigeminal nucleus (61 , 217) in-
13 Pons 497
volved in corneal and other trigeminofacial column that extends from the medulla to the
reflexes, ( b ) direct corticobulbar fibers ( Fig. pons ( 76 ). Cells of the dorsal motor nucleus of
12.27), which project bilaterally, but with im- the vagus form the caudal portion of this col -
portant regional differences (131, 152), (c ) in - umn. Cells in more rostral regions are less
direct corticobulbar fibers, which convey im- compact and are distributed over a wide re-
pulses to the facial nucleus via relays in the gion of the reticular formation. In the pons,
reticular formation ( 152, 153, 277 ), and (d ) cells of this column lie between the nucleus of
crossed rubrobulbar fibers (83), which project the solitary tract and the facial motor nucleus.
only to cell groups ( i.e., dorsomedial and in- The overlapping origins of neurons con-
termediate ) innervating the upper facial mus- tributing to the glossopharyngeal and inter-
cles. Additionally, descending fibers from the mediate nerves raise a question concerning
mesencephalic reticular formation project ip- the appropriateness of a nomenclature that
silaterally to portions of the facial nucleus distinguishes separate salivatory nuclei as in -
(83). Secondary or tertiary auditory fibers, ferior and superior .
considered to reach the facial nucleus, are Preganglionic parasympathetic fibers from
thought to mediate certain acousticofacial re- the superior salivatory nucleus pass periph -
flexes. These reflexes include closing of the erally as a component of the intermediate
eyes in response to a sudden loud noise, and nerve, but near the external genu of the facial
contraction of the stapedius muscle to nerve they divide into two groups: ( a ) one
dampen the movements of the ear ossicles. group that passes to the pterygopalatine gan -
Studies of the neuronal organization of glion via the major superficial petrosal nerve,
acoustic middle ear reflexes indicate that and ( b ) another group that projects via the
pathways involved in the stapedius reflex chorda tympani and branches of the lingual
comprise three or four neurons: (a ) primary nerves to the submandibular ganglia ( Fig.
auditory neurons, ( b ) processes of cells of the 13.23). Synapses with postganglionic neurons
ventral cochlear nucleus which form the occur in the pterygopalatine and subman -
trapezoid body, and ( c ) neurons in the ipsilat- dibular ganglia . Postganglionic fibers from
eral and contralateral medial superior olivary the pterygopalatine ganglion give rise to se -
nucleus, which project to facial motor neu - cretory and vasomotor fibers that innervate
rons that innervate the stapedius muscle ( 27). the lacrimal gland and the mucous mem -
The intermediate nerve ( of Wrisberg ), which branes of the nose and mouth . Postganglionic
emerges at the cerebellopontine angle between parasympathetic fibers from the subman -
the facial motor root and the vestibular nerve dibular ganglion pass to the submandibular
( Fig. 13.2), contains afferent and general vis- and sublingual salivary glands.
ceral efferent fibers. Afferent fibers (SVA and
GSA ) arise from cells of the geniculate gan- LESIONS OF THE FACIAL NERVE
glion, located at the external genu of the facial
nerve ( Fig. 13.23). Special visceral afferent (SVA ) Lesions of the facial nerve ( Bell ' s palsy )
fibers convey gustatory sense ( taste ) from the produce paralysis of the ipsilateral facial
anterior two-thirds of the tongue via the muscles and other sensory and autonomic
chorda tympani nerve. Centrally, these fibers disturbances that depend upon the location
enter the solitary fasciculus and terminate and extent of the peripheral lesion . A com -
upon cells in the rostral part of the solitary nu- plete lesion of the motor part of the facial
cleus, sometimes referred to as the gustatory nerve as it emerges from the stylomastoid
nucleus. General somatic afferent (GSA ) fibers foramen ( A in Fig. 13.23) results in a complete
convey cutaneous sensory impulses from the paralysis of ipsilateral facial muscles. On the
external auditory meatus and the region back side of the lesion , the patient is unable to
of the ear; centrally these fibers enter the dor- wrinkle the forehead, close the eye, show the
sal part of the spinal trigeminal tract ( 20). teeth, purse the lips. The palpebral fissure is
General visceral efferent ( GVE ) fibers in the widened , the nasolabial fold is flattened , and
intermediate nerve arise from the superior the corner of the mouth droops. The corneal
salivatori/ nucleus , which consists of scattered reflex is abolished on the side of the lesion ,
cholinergic cells in the dorsolateral reticular but corneal sensation remains. A lesion distal
formation ( Figs. 12.15, 12.16, and 13.23). to the geniculate ganglion ( B in Fig. 13.23)
These preganglionic parasympathetic neu - produces the deficits associated with a lesion
rons are part of an uninterrupted dorsal cell at A but, in addition, produces impairment of
sublingual and submandibular salivary secre- unilateral lesion interrupting corticobulbar

tions, hyperacusis, and , frequently, loss of pathways results in paralysis of only the
-
taste in the anterior two thirds of the tongue
ipsilaterally . Salivary secretions are impaired
lower facial muscles contralaterally. A lesion
involving corticobulbar and corticospinal
due to interruption of preganglionic para- fibers in the internal capsule produces a con -
sympathetic fibers, and loss of taste is due to tralateral voluntary central type facial paraly-
interruption of SVA fibers. Hyperacusis results sis and a contralateral hemiplegia. Such a le-
from paralysis of the stapedius muscle, which sion never impairs taste, salivary or lacrimal
serves to dampen the oscillations of the ear secretions, or the corneal reflex.
ossicles and causes sounds to be abnormally Mimetic or emotional innervation of the
loud on the affected side. Lesions of the facial muscles of facial expression may be pre-
nerve proximal to the geniculate ganglion ( C served even in the presence of a voluntary
in Fig. 13.23) produce all of the disturbances central type facial palsy. In response to a gen -
described for lesions at A and H and, in addi- uine emotional stimulus, the muscles of the
tion , invariably result in complete loss of lower face will contract symmetrically.
taste over the anterior two- thirds of the Mimetic or emotional innervation of facial
tongue and impairment of ipsilateral lacrima- muscles is involuntary and is mediated by
tion . This lesion interrupts all SVA fibers as pathways that are independent of those aris-
they course centrally and all preganglionic ing from the cerebral cortex. While it is recog-
parasympathetic (GVE ) fibers cu route to both nized that these pathways are separate from
the pterygopalatine and submandibular gan - those mediating voluntary facial expression,
glia . Following a complete lesion proximal to their origin and course are unknown . Thus,
the geniculate ganglion, taste is permanently certain neural lesions can produce a mimetic
lost and no regeneration of sensory fibers facial paralysis without impairing voluntary
takes place. Preganglionic parasympathetic facial contractions. More extensive lesions
fibers may regenerate, but this frequently oc- can produce combined voluntary and
curs in an aberrant manner. Fibers that previ - mimetic facial palsies.
ously projected to the submandibular gan-
glion may regrow and enter the major ABDUCENS NERVE
superficial petrosal nerve. As a consequence
of this aberrant regeneration , a salivary stim- The abducens nerve ( N . VI ) arises from a
ulus may produce lacrimation (syndrome of collection of typical motor cells that forms a
"crocodile tears"). The true etiology of Bell's column, about 3 mm in length, in the lateral
palsy is poorly understood . It is assumed that part of the medial eminence of the fourth
most facial palsies of this type are due to ventricle ( Figs. 13.1 , 13.7, and 13.27). Together
compression of the nerve secondary to an un - with the internal genu of the facial nerve, it
explained swelling in the bony facial canal. forms the rounded prominence in the ventric-
Central types facial palsies involve cortico- ular floor known as the colliculus facialis ( Figs.
bulbar and corticoreticular fibers that directly 13.1 and 13.24). This motor nerve (GSE ) in -
and indirectly convey impulses to cells of the nervates the lateral rectus muscle, which
facial nucleus. Two types of central facial serves to abduct the eye. Root fibers of the ab-
paralysis, voluntary and mimetic, are recog- ducens nerve emerge from the medial aspect
nized . Voluntary central-type paralysis oc- of the nucleus and pass ventrally through the
curs contralateral to a lesion involving corti- pontine tegmentum lateral to the corti-
cobulbar fibers and affects only the muscles cospinal tract ( Figs. 13.1, 13.7, and 13.24 ).
of the lower half of the face, particularly They emerge from the brainstem at the cau -
those in the perioral region . Muscles of the dal border of the pons ( Figs. 12.1, 12.15, and
upper facial region concerned with wrinkling A .7). This slender nerve has a long intracra-
the forehead , frowning, and closing the eyes nial course and traverses the cavernous sinus
are not affected . The accepted explanation of and the superior orbital fissure en route to the
this upper motor neuron facial paralysis is lateral rectus muscle. In the cavernous sinus,
that corticobulbar fibers projecting to cell the abducens nerve lies close to the internal
groups of the facial nucleus innervating mus- carotid artery.
cles of the upper face and forehead are dis- The abducens nerve is unique among
tributed bilaterally, while those projecting to motor cranial nerves in that it contains two
cell groups that innervate the lower part of populations of neurons: ( a ) typical motor
the face are only crossed (131, 153). Thus, a neurons that project fibers via the nerve root
13 Pons 499
to innervate the lateral rectus muscle, and ( b) reticular formation, and the nucleus preposi-
internuclear neurons whose axons ( retained tus (111, 119, 171 ). Afferent fibers from the
within the brainstem ) cross the midline, as - medial vestibular nucleus are predominantly
cend in the contralateral MLF, and terminate ipsilateral and both populations of abducens
upon cells of the oculomotor nuclear complex neurons receive the same profile of disynap -
that innervate the medial rectus muscle of the tic excitation and inhibition from the
opposite side ( 14, 54, 55, 109, 120, 126, 243, labyrinth ( 14 ). Abducens nucleus afferents
250, 251 ) ( Fig. 13.25). Abducens internuclear from the paramedian pontine reticular formation
neurons, constituting 25-307, of the nucleus ( PPRF) and the nucleus prepositus hy-
( 250 ), are distributed throughout the nucleus, poglossi are uncrossed . Corticobulbar fibers
and are virtually impossible to distinguish convey impulses bilaterally to the abducens
from motor neurons in common stain ( 243). nucleus via intercalated neurons in the reticu -
Abducens motor neurons are immunocyto- lar formation ( Fig. 12.27 ).
chemically reactive to choline acetyltrans-
ferase (ChAT ) ( Fig. 13.21 ). Lesions of the Abducens Nerve
The abducens nucleus receives afferent in-
puts from the medial vestibular nucleus, the Lesions of the abducens nerve in the brain -
stem, or in its long intracranial course, cause
ipsilateral paralysis of the lateral rectus mus-
cle ( Fig. 13.22 ). Because contraction of the me-
dial rectus muscle on the affected side is un -
opposed , the eye is strongly adducted . The
contralateral eye is unaffected and can move
in all directions. The patient has diplopia (dou -
ble vision ) on attempting to gaze to the side
of the lesion . This impairment, called hori-
zontal diplopia, results because light reflected
by an object in the visual field does not fall
upon corresponding points of the two reti -
nae. The abducens nerve is the most fre-
quently injured cranial nerve. An isolated le-
sion of the sixth nerve has no neurologic
localizing value because of its long intracra-
nial course. If the lesion produces ipsilateral
horizontal diplopia and a contralateral hemi-
paresis, the lesion can be localized in the me-
dial pons where it involves root fibers of the
abducens nerve and part of the corticospinal
tract. This resulting syndrome is known as
middle alternating hemiplegia ( Fig. 12.27). Ipsi-
lateral horizontal diplopia combined with a
facial paralysis on the same side indicates a
lesion in the caudal pontine tegmentum in-
volving root fibers of the abducens and facial
nerves.
Lesions of the Abducens Nucleus

Discrete unilateral lesions of the abducens
Figure 13.25. Dark-field photomicrographs of (3H)
labeled amino acids injected into the right abducens
- nucleus produce a paralysis of lateral gaze to-
nucleus in a rhesus monkey showing transport via ward the side of the lesion . The syndrome of
abducens root fibers and the contralateral medial longi- lateral gaze paralysis differs from paralysis of
tudinal fasciculus ( A ) Isotope transported from ab- the lateral rectus muscle in that neither eye
ducens internuclear neurons via the medial longitudinal can be directed laterally toward the side of
fasciculus terminate in the medial rectus subdivision of
the opposite oculomotor complex ( B) The medial rectus
the lesion and that both eyes tend to be force-
subdivision in the caudol oculomotor complex are repre- fully and conjugately deviated to the oppo-
sented by cell groups designated a dnd b. site side ( Fig. 13.22 ). Ocular convergence usu -
ally is unaffected . Thus, the abducens nerve tine "center for lateral gaze" and the ab-
appears unique in that it is the only motor ducens nucleus probably constitute a single
cranial nerve in which lesions of the root entity (53-55, 63, 117, 120, 243, 250).
fibers and nucleus do not produce the same The localized region most concerned with
effect. vertical eye movements lies in the tegmental
Lateral gaze paralysis, due to discrete le- area rostral to the oculomotor complex in the
sions in the abducens nucleus, is caused by zone of transition between diencephalon and
( a ) destruction of motor neurons in the ab- mesencephalon ( 45). This zone, which con -
ducens nucleus, which results in paralysis of tains large cells lying among fibers of the
the ipsilateral lateral rectus muscle, and ( b) MLF and is distinct from the interstitial nu -
destruction of internudear neurons within cleus of Cajal , are referred to as the rostral in -
the abducens nucleus, that give rise to as- terstitial nucleus of the MLF ( RiMLF). Centers
cending fibers that project via the opposite for horizontal gaze ( i .e., the abducens nu -
MLF to the medial rectus subdivision of the cleus ) and vertical ( i.e., RiMLF) gaze are in-
contralateral oculomotor complex ( 54, 55, 63) terrelated by a collection of physiologically
( Fig. 13.18) . The paresis of ocular adduction defined neurons in the paramedian reticular
in the contralateral eye ( internudear ophthal- formation rostral to the abducens nucleus,
moplegia ), which forms part of the lateral called the paramedian pontine reticular for-
gaze paralysis, appears to be due to destruc- .
mation ( PPRF) Stimulation of the caudal
tion of abducens internudear neurons that regions of the PPRF produces conjugate hori-
are intermingled with cells whose axons form zontal deviation of the eyes, while stimula -
the abducens nerve root ( 66 ) ( Fig. 13.22 ). An- tion in rostral regions produces vertical eye
other , and more common , cause of anterior movements. Caudal parts of the PPRF project
internudear ophthalmoplegia ( as seen in
multiple sclerosis), is a lesion of the contralat -
fibers to the ipsilateral abducens nucleus
rostral regions of the PPRF project uncrossed
—
eral ascending fibers in the medial longitudi - fibers to the RiMLF, which ascend outside of
nal fasciculus originating from the PPRF and the MLF ( 45). The RiMLF in turn project to
going to the cells of the oculomotor nuclear the ipsilateral oculomotor nuclear complex.
complex controlling movement of the con - Lesions in the PPRF may cause paralysis of
tralateral medial rectus muscle. Experimental horizontal eye movements (caudal part ),
studies have shown that lesions limited to in - paralysis of vertical eye movements ( rostral
dividual vestibular nuclei do not produce part ), or both if extensive ( 21, 56).
paresis of ocular adduction (170 ).
TRIGEMINAL NERVE
Horizontal and Vertical Eye Movements
The trigeminal nerve ( N. V ) is the largest
All ocular movements, whether horizon - of all cranial nerves and contains both sen -
tal , vertical, or rotatory, require reciprocal ac- sory and motor components ( Figs. 12.1 and
tivity in the extraocular muscles producing 13.26 ). General somatic afferent (GSA ) compo-
these movements. Conjugate lateral gaze re- nents convey both exteroceptive and proprio-
quires simultaneous appropriate contractions ceptive impulses. Exteroceptive impulses of
of the lateral rectus muscle on one side and touch, pain , and thermal sense are transmit -
the medial rectus muscle of the opposite side. ted from ( a ) the skin of the face and forehead
The central neural mechanisms underlying ( Fig. 8.13), ( b ) the mucous membranes of the
conjugate eye movements are just beginning nose and mouth, (c) the teeth , and ( d ) large
to be understood ( 117). The observation that portions of the cranial dura. Deep pressure
paralysis of vertical or horizontal eye move - and kinesthesis are conveyed from the teeth,
ments can occur independently implies that periodontium, hard palate, and temporo-
there are separate anatomic sites at some dis- mandibular joint . Additionally, impulses are
tance from each other that generate vertical transmitted centrally from stretch receptors
and horizontal eye movements. Many conju - in the muscles of mastication. Special visceral
gate eye movements, however, have both efferent fibers (SVE, branchiomotor ) innervate
vertical and horizontal components so pre- the muscles of mastication, the tensor tym -
cisely synchronized that centers controlling pani, the tensor veli palatini, the mylohyoid ,
vertical and horizontal eye movements must and the anterior digastric muscles. Afferent
be functionally connected and coordinated . fibers constitute the sensory root , while effer-
Considerable evidence suggests that the pon - ent fibers form the smaller motor root.
13 Pons 501
Emboliform nucleus Dentate

nucleus
Fastigial nucleus
Globose nucleus
\
1
V
<v m rt
Juxtarestiform
body
Superior
Superior vest nuc,
Inferior
cerebellar
cerebellar
peduncle
-
f
peduncle
Middle
cerebellar
peduncle
'A
i r ,r
K 4 I
>' ' f
S .
A
/
Trigeminal * Po 11 s
nerve Lateral lemniscus
and superior olive
Figure 13.26. Transverse section through the pons, pontine tegmentum, and part of cerebellum at the level of the
roof of the trigeminal nerve in a I-month infant (Weigert ' s myelin stain)
Trigeminal Ganglion The maxillary branch supplies the upper lip,

lateral and posterior portions of the nose,
Afferent fibers, except those associated upper cheek, anterior portion of the temple,
with pressure and stretch receptors, have and mucous membranes of the nose. It also
their cell bodies in the large, flattened, cres- innervates the upper jaw, upper teeth , and
cent-shaped trigeminal ganglion ( Figs. 1.8, roof of the mouth to the palatopharyngeal
-
2.26, and 13.2*4 ). This semilunar shaped gan - arch. Sensory fibers of the mandibular branch
glion, located in a dural cleft on the cerebral are distributed to the lower lip, chin, poste-
surface of the petrous bone in the middle cra - rior portions of the cheek, temple, external
nial fossa , is composed of typical unipolar ear, lower jaw , lower teeth, cheeks, floor of
ganglion cells ( 268 ) ( Fig. 13.31 ). Peripheral the mouth , and anterior two- thirds of the
processes of these cells form the three main tongue. All three divisions of the trigeminal
divisions of the trigeminal nerve: ophthalmic, nerve contribute sensory fibers to the dura.
maxillary, and mandibular ( Fig. 13.30). The The dura of the posterior fossa is also inner-
first two are wholly sensory, whereas the vated by fibers from the tenth cranial and the
mandibular branch incorporates the entire upper three spinal nerves ( 145, 205 ).
motor root supplying the muscles of mastica - Central processes of trigeminal ganglion
tion . The ophthalmic branch innervates the cells form the large sensory root of this nerve,
forehead , upper eyelid , cornea , conjunctiva, which traverses the lateral part of the rostral
dorsum of the nose, and mucous membranes pons, to enter the tegmentum where many
of the nasal vestibule and the frontal sinus. fibers divide into short ascending and long
descending branches ( Figs. 12.16 and 13.31 ). in lamina I respond to nociceptive and ther-
Other fibers descend or ascend without bifur - mal stimuli; lamina II correspond to the sub-
cation ( 2% ). The short ascending fibers and stantia gelatinosa; and laminae 111 and IV
their collaterals terminate in the principal ( magnocellular layers ) correspond to the
sensory nucleus lying dorsolateral to the en - proper sensory nucleus. Fibers containing
tering fibers. The long descending branches substance 1’ terminate in lamina 1 and outer
form the spinal trigeminal tract , whose part of lamina II in the pars caudalis; cells
longest fibers reach the uppermost cervical positive for enkephalin are found in deeper
segments of the spinal cord; terminals and parts of lamina II . Throughout the nucleus
collaterals to the spinal trigeminal nucleus the face is represented in an upside down
are given off at route ( Fig. 13.31 ). fashion, with the jaw dorsal and the forehead
ventral ( 284 ). The pars oralis receives im -
Spinal Trigeminal Tract and Nucleus pulses predominantly from the internal struc -
tures of the nose and mouth. The pars inter -
Root fibers entering the spinal trigeminal polaris is related mainly to cutaneous facial
tract have a definite topographic organization regions, while the pars caudalis has large re-
(93, 142, 143, 298 ) . Fibers of the ophthalmic ceptive fields over the forehead, cheek, and
division are most ventral, fibers of the jaw. The peculiar "onionskin pattern" of ter -
mandibular division are most dorsal, and mination of afferents to the spinal trigeminal
those of the maxillary division are intermedi - nucleus and its relative clinical importance
ate ( Fig. 13.29 ). This inverted laminar were alluded to in Chapter 12.
arrangement of fibers results from medial ro- In addition to fibers of the trigeminal
tation of the trigeminal sensory root as it en- nerve and general somatic afferent fibers
ters the brainstem and persists throughout from other branchiomeric cranial nerves, the
the length of the tract. The tract extends from spinal trigeminal nucleus receives corticobul -
the level of the trigeminal root entry in the bar fibers (38, 93, 152, 156, 303). These fibers
pons to the uppermost cervical spinal seg- arise mainly from the frontal and parietal cor-
ments ( Figs. 13.29 and 13.30). Fibers of the tices and are predominantly crossed . Physio -
spinal trigeminal tract terminate upon cells of logic studies (88) indicate that corticobulbar
the spinal trigeminal nucleus, which forms a fibers projecting to the pars oralis and pars
long cell column medial to the tract . Ros-
trally, the nucleus merges with the principal
caudalis mediate both inhibitory and excita
tory effects. Observations suggest that in -
-
sensory nucleus, while caudally it blends into hibitory effects are presynaptic in nature.
the substantia gelatinosa of the first two cer- Lesions of the spinal trigeminal tract result
vical spinal segments. Fibers of the spinal in loss or diminution of pain and thermal
trigeminal tract project into that part of the sense in areas innervated by the trigeminal
spinal trigeminal nucleus immediately adja- nerve (95). Such lesions do not abolish tactile
cent to it (87). There is a sharp segregation of sense, because some neurons at all levels of
terminal fibers within parts of the nucleus the nucleus respond to tactile stimuli (149).
and virtually no overlap of fibers from the Tactile sense may be mediated by fibers that
different divisions of the nerve (87, 93, 142, bifurcate and send branches to both the
149 ). The spinal trigeminal tract also contains spinal trigeminal nucleus and the principal
small groups of GSA fibers from the facial, trigeminal nucleus. Clinically, there is no
glossopharyngeal, and vagus nerves, which doubt that pain and thermal sense are han-
occupy dorsomedial regions (141, 222, 266 ). dled entirely by the spinal trigeminal tract
Cvtoarchitecturallv the spinal trigeminal and nucleus, principally the pars caudalis,
nucleus has been subdivided into three parts -
while touch and two point discrimination are
( 190 ): (a ) a pars oralis extending caudally to in large part related to the principal sensory
the rostral third of the inferior olivary nu - nucleus ( Figs. 13.30 and 13.31 ). However,
cleus, ( b ) a pars interpolaris extending from physiologic studies ( 150, 284 ) indicate that it
the pars oralis to the decussation of the pyra- is extremely difficult to isolate and identify
mids, and (c ) a pars caudalis extending cau - neurons in the spinal trigeminal nucleus
dally as far as the second cervical spinal seg- uniquely concerned with pain.
ment . The laminar configurations within The composition, location, and relation-
caudal parts of the spinal trigeminal nucleus ships of the spinal trigeminal tract and nu -
consist of four layers and resemble those of cleus are of considerable diagnostic and sur-
the posterior gray horn at spinal levels. Cells gical importance. It should be noted that
13 Pons 503
virtually no overlap exists between the cuta- thalmic division terminate ventrally, fibers of
neous areas supplied bv the three peripheral the maxillary division are intermediate, and
divisions of the trigeminal nerve, in contrast fibers of the mandibular division are most
to the extensive overlap characteristic of dorsal (142, 143). Caudally this nucleus
spinal dermatomes (Fig. 8.13). Trigeminal merges with the pars oralis of the spinal
tractotomy (i.e., sectioning of the spinal trigeminal nucleus and the level of transition
trigeminal tract) can relieve various forms of is indistinct (Fig. 13.31 ). The principal sensory
facial pain including trigeminal neuralgia ( tic nucleus is populated by small to medium-
douloureux ) ( 237). This procedure eliminates sized, oval cells with relative large nuclei
or greatly reduces pain and thermal sense (Fig. 13.28). These cells have large receptive
without impairing tactile sense. Corneal sen- fields, show high spontaneous activity, and
sation remains, as does the corneal reflex, respond to a wide range of pressure stimuli
though it may not be as brisk ( 282, 290). with little adaptation ( 284).
Principal , Mesencephalic and Motor MESENCEPHALIC NUCLEUS

Nuclei This trigeminal nucleus forms a slender
PRINCIPAL SENSORY NUCLEUS cell column near the lateral margin of the cen-
tral gray matter of the upper fourth ventricle
This nucleus lies lateral to the entering and cerebral aqueduct ( Figs. 13.28-13.31).
trigeminal root fibers in the upper pons ( Figs. This nucleus, composed of large unipolar
13.27 and 13.31). Root fibers conveying im- neurons, extends from the level of the trigem-
pulses for tactile and pressure sense enter the inal motor nucleus to the rostral midbrain.
principal sensory nucleus and are distributed Most of its cells resemble those of the dorsal
in a manner similar to that described for the root ganglion but are encapsulated, often
spinal trigeminal nucleus. Fibers of the oph- have more than one process, and lie within
Motor nucleus
of N. 2 \
Motor root Superior cerebellar peduncle

of N 1
Mesencephalic tract of N. Y
Principal sensory
nucleus of N Y Nucleus of medial
eminence
Genu of N. YE
Medial Iona.
fasciculus
Trapezoid body
Medial lemniscus
Aberrant pyramidal
fibers
Deep pontine fibers
Corticospinal tract
Sensory root Superficial pontine fibers

Lateral lemniscus
Figure 13.27 . Transverse section through the pons and pontine tegmentum at the level of the entrance of the
trigeminal nerve in a 1 -month infant (Weigerts myelin stain).
of N 31
Motor nucleus Nucleus of
of N . 3£ medial eminence
Principal sensory
nucleus of N 3T
Nucleus reticularis
pontis oralis
Superior central
nucleus
Middle Reticulotegmental
cerebellar
peduncle nucleus
Pontine nuclei
Pontine nuclei
Superior olivary / ;:
nucleus
' /
"
Corticospinal tract
Figure 13.28. transverse section through the pons and pontine tegmentum at about the same level as in Figure
13.27 In a 1-month intant (Cresyl violet stain, with cell groups blocked in).
Trigeminal
ganglion
Mesencephalic
Ophthalmic nucleus N V
division
Principal sensory
Maxillary division- - nucleus N V
Mandibular division
Pons
Spinal trigeminal
tract and nucleus
Spinal trigeminal
Medulla
tract nucleus
Spinal cord
Mandibular
Maxillary Divisions
Ophthalmic
Figure 13.29. Topographic arrangement of the fibers in the spinal trigeminal tract The laminar arrangement of fibers
from the different divisions of the trigeminal nerve persists throughout its length, although fibers leave the tract at all
levels to terminate upon cells of the spinal trigeminal nucleus
13 Pons 505
Thalamus III Ventricle Cerebral cortex

(lower postcentral gyrus)
Sensory area ot face,

orbit , nose and mouth
Internal capsule
Globus pallidus
Axon of neuron III in
posterior limb of
0
internal capsule
MIDBRAIN
V
Vent posteromedial
,
nucleus
Dorsal trigeminal tract
Ventral trigeminal tract
(Trigeminothalamic)
0 ( Trigeminothalamic)
MIDBRAIN s
f
Mesencephalic nucleus ‘
of trigeminal ( V) nerve
Motor nucleus of
PONS trigeminal ( V ) nerve
Trigeminal nerve Principal sensory nucleus

of trigeminal ( V ) nerve
Neuron I in
N. V ganglion : Spinal trigeminal tract
\ :
Crossing axons of neuron II
Motorj
root Spinal trigeminal nucleus
V2 MEDULLA
V3
Crossing axons of neuron II
Spinal trigeminal nucleus Spinal trigeminal tract

fl
MEDULLA Axons of neuron II crossing
in lower medulla and upper
cervical cord (ser ondary
C2 pain and temperature fibers )
Sustantia gelatinosa
TUX Dorsolateral fasciculus
( zone of Lissauer)
Figure 13.30. Secondary trigeminal tracts The ventral trigeminal tract (red) conveys pain thermal, and tactile sense
,
These fibers originate from the spinal trigeminal nucleus, cross at various locations in the lower brainstem, and ascend
in association with the contralateral medial lemniscus Secondary trigeminothalamic fibers from the principal sensory
nucleus, conveying touch and pressure (.blue) ascend By two separate pathways Fibers from the ventral part of the
principal sensory nucleus of fhe trigeminal nerve (N. V) cross and ascend in association with the contralateral medial
lemniscus Fibers from the dorsomedial part of the same nucleus ascend uncrossed as the dorsal trigeminal tract
Both the ventral and dorsal trigeminal tracts project to the ventral posteromedial nucleus of the thalamus. The brain-
stem location of the ascending lateral spinothalamic tract is indicated in gray on the right side. The ophthalmic (VI).
.
maxillary (V 2) and mandibular (V3) divisions of the trigeminal nerve are identified. I . Free nerve ending. 2. thermal re-
.
ceptor , 3. Meissner ' s corpuscle; 4 neuromuscular spindle; 5, motor end plate in muscle of mastication
Principal sensory nucleus Trigeminal (V) motor

nucleus
Trigeminal ganglion
Trigeminal ( V) nerve
Trigeminal (V) motor
Ophthalmic (I)
root fibers
division
Maxillary (II) Facial ( VII) motor

division nucleus
Mandibular (III)
division
Secondary trigeminal
fibers
K
O' ,
I
Spinal tract
Hypoglossal ( XII)
f> (
v
nucleus
v
Trigeminal ( V )
5
spinal nucleus
Figure 13.31 . Trigeminal nuclei and some of the trigeminal reflex arcs
the central nervous system ( 201, 202 ). The found along the motor root appear related to
principal processes of these cells form a slen - the mesencephalic nucleus and are consid -
der sickle-shaped bundle, the nwscnceplmlic ered to convey impulses from stretch recep-
traet of the trigeminal nerve ( Figs. 13.27, 13.32, tors in the mylohyoid and diagastric muscles.
and A .8 ), which descends to the level of the Although most afferent fibers of the mesen -
trigeminal motor nucleus. Collaterals of these cephalic nucleus course peripherally with
processes enter the trigeminal motor nucleus, fibers of the motor root, experimental evi-
while the main fibers emerge as part of the dence (81 ) indicates that some fibers from this
motor root . Cells of this nucleus are consid - nucleus pass peripherally in all three divi -
ered to be primary sensory neurons that have sions of the trigeminal nerve.
been " retained " within the central nervous Connections of the mesencephalic nucleus
system . are more extensive than previously believed
Afferent fibers of the mesencephalic nu - ( 201 ). Some fibers leave the mesencephalic
cleus of the trigeminal nerve convey pressure tract and enter the white matter of the cere-
and kinesthesis sense from the teeth, peri - bellum , possibly connecting with the cerebel -
odontium, hard palate, and joint capsules (6, lar nuclei. Other fibers have been traced to
7, 81 , 82, 208). These fibers appear concerned the roof of the cerebral aqueduct, the base of
with the mechanisms that control the force of the cerebellum , and to the region of the supe-
the bite. The mesencephalic nucleus also re- rior colliculi .
ceives afferent impulses from stretch recep- It has been suggested that deep sensibility
tors in the muscles of mastication . Action po- of the lingual , facial , and extraocular muscles
tentials can be recorded in the mesencephalic is mediated by fibers of the fifth nerve ( 78,
nucleus in response to stretching the mastica- 79), and that impulses from muscle spindles
tory muscles ( 79, 82 ). Scattered ganglion cells in the extraocular muscles are conveyed by
13 Pons 507
Superior medullary velum Decussation of trochlear nerve

Mesencephalic root of nerveY
Trochlear nerve
Lateral lemniscus
Medial longitudinal
fasciculus f Nucleus of lateral lemniscus
Central tegmental tract Spinothalamic tracts
Sup cerebellar peduncle Medial lemniscus
Decussation of
sup cerebellar
peduncle
^ Transverse fibers of pons
Corticospinal and
corticopontine tracts
— ~ Pontine nuclei
Figure 13.32. Transverse section through the upper pons (Isthmus level) of an adult brain at the level of the decussa-
tion and exit of the trochlear nerve (Weigert ' s myelin stain)
the axons of specific cells in the trigeminal to reticular neurons, which in turn project to
ganglion ( 173). Cells in a part of the ganglion the motor nucleus ( Fig. 12.27).
that forms the ophthalmic division respond
with a sustained increase in discharge rate Secondary Pathways and Trigeminal
when the extraocular muscles are stretched.
Reflexes
These short latency responses are abolished
by section of the ophthalmic division of the SECONDARY TRIGEMINAL PATHWAYS
trigeminal nerve. Deep sensibility from the
face also is considered to be mediated by the These pathways originate from cells in the
trigeminal nerve, but the possibility remains principal sensory and spinal trigeminal nu -
that this may be supplemented by facial clei and project to higher levels of the brain-
nerve afferents. stem , the cerebellum, and spinal cord . Collat -
erals of these fibers provide numerous
MOTOR NUCLEUS projections to motor nuclei of the brainstem
involved in complex reflexes ( Fig. 13.31 ).
The motor nucleus of the trigeminal nerve Trigeminothalamic projections arise largely
forms an oval column of typical multipolar from cells in laminae I and IV of the pars cau -
motor cells medial to the motor root and the dalis and interpolaris of the spinal trigeminal
principal sensory nucleus ( Fig. 13.28). Fibers nucleus. Axons from cells in the spinal
from this nucleus exit from the brainstem me- trigeminal nucleus project ventromedially
dial to the entering sensory root , pass under - into the reticular formation, cross the median
neath the trigeminal ganglion, and become raphe, and ascend in close association with
incorporated in the mandibular division the contralateral medial lemniscus (60, 183,
( Figs. 13.30 and 13.31 ). The motor nucleus re- 242, 281 , 283) ( Fig. 13.30 ). These secondary
ceives collaterals from the mesencephalic trigeminal fibers terminate in a selective man -
root, which form a two- neuron arc for reflex ner about cells of the ventral posteromedial
control of the jaw muscles ( jaw- jerk reflex ). ( VPM ) nucleus of the thalamus ( 124 ). Crossed
Secondary trigeminal fibers, both crossed and axons from cells of the spinal trigeminal nu -
uncrossed , establish reflex connections be- cleus that ascend in the brainstem with the
tween the muscles of mastication and cuta- contralateral medial lemniscus form the ven -
neous regions, as well as with lingual and tral trigeminal tract ( ventral trigeminothalamic
oral mucous membranes. Some corticobulbar tract ).
fibers terminate directly and bilaterally upon Secondary trigeminal fibers from the prin -
trigeminal motor neurons, while others pass cipal sensory nucleus are both crossed and
uncrossed . Cells in the dorsomedial part of rior horn, contribute to a variety of reflexes,
the nucleus give rise to a small bundle of un - and link receptors in the trigeminal distribu -
crossed fibers which ascends close to the cen - tion with somatic and visceral effectors in the
tral gray matter of the midbrain and enters spinal cord .
the ipsilateral ventral posteromedial ( VI’M )
nucleus of the thalamus ( 48, 2b7 ) ( Fig. 13.3(1). TRIGEMINAL REFLEXES
These fibers form the dorsal trigeminal tract
-
( 197, 271 , 274, 281 , 247 ), and appear to be as Although secondary trigeminal fibers are
sociated in a unique way with the mandibu - involved in a large number of reflexes, the
lar division of the trigeminal nerve ( 142 ). corneal reflex is one of the most important.
Cells in the ventral part of the principal sen- Stimulation of the cornea with a wisp of cot -
sory nucleus of the trigeminal nerve give rise ton produces bilateral blinking and closing of
to a larger, entirely crossed bundle of the eyes. The blinking and closing of the eyes
trigeminothalamic fibers, which ascends in is effected by impulses reaching the facial nu -
association with the contralateral medial lem - clei on both sides. This reflex is mediated by
niscus, in a manner similar to that described secondary trigeminal fibers projecting bilater-
for the ventral trigeminal tract ( 197, 229, 267, ally to the facial nuclei. Following an injury to
281 , 283, 297 ). These crossed secondary the ophthalmic division of the trigeminal
trigeminal fibers also terminate in the VI’M nerve, corneal sensation and the corneal re-
nucleus of the thalamus. flex are lost on that side because the afferent
TrigeminocereMlar fibers arise from cells in limb of the reflex arc has been destroyed .
lamina IV in all parts of the spinal trigeminal Corneal sensation , however, remains on the
nucleus with the largest contribution origi- opposite side, and stimulation of that cornea
nating from rostral parts of the nucleus ( 124 ). will produce bilateral blinking and eye clo-
Additional trigeminocerebellar fibers come sure, indicating that the efferent limb ( facial
from cells in ventral portions of the principal nucleus and nerve ) of the reflex arc is intact .
sensory nucleus. These portions of the In patients with peripheral facial palsies,
trigeminal nuclei project uncrossed fibers to corneal sensation will be present on both
the paramedian lobule, the simple lobule, sides, but no corneal reflex can be elicited on
and posterior part of crus II. A large number the side of the lesion because the efferent
of these fibers enter the cerebellum via the in- limb of the reflex arc has been destroyed .
ferior cerebellar peduncle. Stimulation of the cornea on the side of the le-
As previously mentioned, the mesen- sion, however, will cause blinking and clo-
cephalic trigeminal nucleus is peculiar in that sure of the opposite eye (consensual re-
the primary sensory neurons that form this sponse).
nucleus lie in a brainstem nucleus rather than The numerous trigeminal secondary fibers
in the trigeminal ganglion. While there is con- that ascend and descend in the dorsolateral
vincing evidence that fibers from this nucleus part of the reticular formation give off termi -
convey impulses from pressure, joint, and nals or collaterals to various motor nuclei .
stretch receptors, the pathway by which these These projections provide a substratum for
impulses are transmitted centrally remains specific reflexes initiated by stimulation of
obscure. It has been hypothesized that the skin of the face, the oral and nasal mu -
processes of cells in the mesencephalic nu - cous membranes, and muscles, tendons, and
cleus may project to the cerebellum ( 201 , 298). bones of the jaw and face. Reflexes involving
Since a significant part of the input to this nu - secondary trigeminal fibers that project im -
cleus comes from stretch receptors, and impulses to cranial nerve nuclei include ( a ) the
pulses from most stretch receptors in other lacrimal or tearing reflex , in which corneal irri -
parts of the body are relayed to the cerebel - tation initiates impulses via trigeminal nerve
lum , this hypothesis is plausible. fibers that synapse upon neurons of the supe-
Trigeminospinal projections arise from cells rior salivatory nucleus ( parasympathetic) re-
in laminae I and III in all subdivisions of the sulting in lacrimation; ( b ) sneezing, in which
spinal trigeminal nucleus. Fibers from pars trigeminal impulses pass to the nucleus am-
caudalis and interpolaris are ipsilateral while biguus, to respiratory centers in the reticular
those from pars oralis are bilateral ( 124). formation, and to cell groups in the spinal
These descending projections may modulate cord (i.e., phrenic nerve nuclei and anterior
incoming sensory information in the poste- horn cells innervating the intercostal mus-
13 Pons 509
cles), which are paroxysmally activated; (c) cus, and closely associated with fibers of the
vomiting, in which trigeminal impulses pass trapezoid body, is the rostral pole of the su -
predominantly to vagal nuclei (i.e., dorsal perior olivary nucleus ( Fig. 13.26). Ventrolat -
motor, ambiguus and solitary ); and (d ) sali- erally, the lateral lemniscus is becoming a
vary reflexes in which secondary trigeminal well -defined bundle ( Fig. 13.27). The
fibers pass to the inferior salivatory nuclei. spinothalamic and anterior spinocerebellar
Secondary trigeminal fibers probably also tracts are located lateral to the medial lemnis-
pass to the hypoglossal nuclei and mediate cus and the medial longitudinal fasciculus is
reflex movements of the tongue in response located dorsally on each side of the median
to stimulation of the tongue and the mucous raphe. The central part of the pontine
membranes of the mouth . tegmentum contains the pontine reticular for -
The jaw- jerk , or masseter reflex, is a mono- mation . Longitudinally cut fibers of the facial
synaptic myotatic reflex. This reflex is elicited genu appear lateral to the medial longitudi -
by placing the examiner's index finger over nal fasciculus. Fibers of the central tegmental
the middle of the patient's chin ( mouth tract form a fairly discrete bundle in the retic-
slightly open ) and tapping gently with a re- ular formation dorsal to the lateral part of the
flex hammer. The response is a bilateral con - medial lemniscus ( Fig. 13.27).
traction of the masseter and temporal mus- The isthmus rhomhencephali is situated ros-
cles. This reflex involves stretch receptors in tral to the cerebellum and immediately cau -
the muscles of mastication, the mesen- dal to the midbrain ( Figs. 13.32, 13.33, and
cephalic nucleus, and collaterals from this nu - A .9). As in other parts of the brainstem, three
cleus that terminate in the motor trigeminal regions are distinguished , namely, a roof
nucleus. The jaw reflex is absent in peripheral plate, a tegmental region, and a ventral corti-
lesions of the trigeminal nerve. cally dependent part. The roof consists of a
thin membrane, the superior medullary velum .
This thin membrane, containing the decussat-
ROSTRAL PONS- ISTHMUS LEVEL
ing fibers of the trochlear nerve, forms the
Tegmentum roof of the most rostral part of the fourth ven-
tricle.
Transverse sections through the upper The tegmental region, ventral to the fourth
pons at the level of the trigeminal nerve root ventricle, is smaller than at caudal levels. The
( Figs. 13.26, 13.27, and A .8) reveal important more abundant central gray matter resembles
changes when compared with sections at that seen at mesencephalic levels. The lateral
lower pontine levels ( Figs. 13.2 and 13.4). The border of the central gray matter contains the
fourth ventricle is narrower, although its roof mesencephalic nucleus and tract of the
is still formed by the cerebellum . Within the trigeminal nerve. Ventral and medial to these
cerebellum portions of all the cerebellar nu - structures is the relatively large collection of
clei can be seen, and fibers of the inferior and pigmented ( melanin-containing ) cells of the
middle cerebellar peduncles enter the cere - locus coeruleus. Lateral to the central gray mat -
bellum close to each other ( Fig. 13.26). At ter are the fibers of the superior cerebellar pe-
slightly higher levels, the superior cerebellar duncle that have passed into the tegmentum
peduncle forms the dorsolateral wall of the and are shifting ventromedially to undergo a
fourth ventricle ( Fig. 13.27). The ventral por- complete decussation ( Fig. 13.32 ). Cells of the
tion of the pons is larger than at lower levels parabrachial nuclei lie adjacent to the superior
but still contains transverse and longitudinal cerebellar peduncle. The lateral lemniscus lies
fibers, as well as large masses of pontine nu - near the lateral surface of the tegmentum,
clei. Corticospinal and corticopontine tracts forming the major part of the external struc -
consist of numerous fiber bundles less com - ture known as the triyonum lemnisci. Groups
pactly arranged than in the caudal pons. of cells among its fibers constitute the nuclei of
Fibers within the raphe of the pons are proba - the lateral lemniscus , which are part of several
bly reticulocerebellar fibers arising from cells intercalated nuclei in the auditory pathway
in the pontine tegmentum. ( Figs. 13.13, 13.32, and 13.33) . Most fibers of
In the dorsal part of the pons, the medial the lateral lemniscus project rostrally and
lemniscus is located ventrally and is tra - enter the inferior colliculus. The medial lem -
versed in part by the transverse fibers of the niscus is a flattened band of ascending fibers
trapezoid body. Lateral to the medial lemnis- in the ventrolateral tegmentum . Fibers of the
Lateral parabrachial
nucleus Mesencephalic nucleus of NI
.
/
Nucleus of lateral Dorsal nucleus
lemniscus of raphe!
Locus ceruleus
Superior _
cerebellar
peduncle Medial long fasciculus
Reticular
formation if& Jli- Reticular
: -
formation
i
Superior central
t nucleus
fee. Reticulotegmentol
:
feSLOHififfl—
L --
nucleus
Pontine nuclei
Figure 13.33 . Transverse section through upper pons (isthmus level) of a 3-month infant (cresyl violet stain with cell
groups blocked in)
spinothalamic tract are located laterally near tinue directly to the ventral lateral nucleus of
the junction of the medial and lateral lem- the thalamus ( Figs. 15.21 and 16.13A ) . A rela -
nisci. Included in the medial lemniscus are tively small number of fibers of the superior
the secondary trigeminal fibers. The dorsal cerebellar peduncle descend lateral to the su -
trigeminal tract ascends in the dorsal part of perior central nucleus and terminate in the
the reticular formation, lateral to the medial pontine reticulotegmental nucleus and in the
longitudinal fasciculus ( Fig. 13.30). Thus, at medullary paramedian reticular nuclei ,
this level , the principal ascending sensory which project back to the cerebellum ( 39, 64 ).
pathways form a peripheral sTiell of fibers Thus, these descending cerebellar fibers ap-
that encloses most of the pontine tegmentum. -
pear to be part of a cerebello reticulo-cerebel -
The ventral part of the pons at the isthmus lar feedback loop ( Fig. 15.21 ).
level is larger than the tegmental part , but is Fibers of the anterior spinocerebellar tract
not as impressive as at midpontine levels ascend in the lateral part of the reticular for -
( Figs. 13.32, A .2b, and A .27). Corticospinal mation and accumulate on the lateral surface
and corticopontine tracts are broken up into of the superior cerebellar peduncle at upper
numerous small bundles surrounded by pon - pons levels ( Fig. 11.9 ). These fibers reverse
tine nuclei. their direction and enter the cerebellum by
coursing within the superior medullary
Superior Cerebellar Peduncle velum along the dorsolateral border of the
superior cerebellar peduncle. The majority of
The superior cerebellar peduncle (or the fibers cross to the opposite side within the
brachium conjunctivum ) arises from the den- cerebellum and terminate in the anterior lobe
tate, emboliform, and globose nuclei, and of the cerebellar vermis ( Fig. 15.1 ).
forms the most important efferent fiber sys- As fibers of the superior cerebellar pedun -
tem of the cerebellum. Fibers of this large cle move ventromedially toward their decus -
bundle ascend from the hilus of the cerebellar sation they divide the reticular formation into
nuclei into the dorsolateral part of the rostral medial and lateral parts ( Fig. 13.32 ). In the
pontine tegmentum . It initially forms a cres- lateral part is a fairly dense collection of cells
cent -shaped bundle dorsolateral to the fourth known as the pcdunculo HVitinc tegmental nu -
ventricle ( Fig. 13.26), but at more rostral lev- ^
cleus ( i.e., the pedunculopontine nucleus).
els of the isthmus it lies medial to the lateral Cells of this nucleus are partially traversed by
lemniscus ( Fig. 13.32 ). The superior cerebellar fibers of the superior cerebellar peduncle
peduncle decussates completely at midbrain ( Figs. 14.3 and 19.36), and some cerebellar
levels ( Figs. 13.32, 14.2, and 15.21 ). Some of axons give off collaterals that terminate
its fibers end in the red nucleus; others con- within the pedunculopontine nucleus
13 Pons 511
itself ( 125). Compact and diffuse portions of is not obvious that there are human horno-
this nucleus extend rostrally into the caudal logues to the numerous subdivisions de-
midbrain ( 192 ). This nucleus receives cortical .
scribed in the rat (200) L ells in the
projections from the precentral gyrus (154 ), parabrachial nuclei contain a large variety of
and descending fibers from the globus pal - neuromodulators. For example, cells and
lidus and substantia nigra (57, 67, 159, 184, fibers displaying immunoreactivity to either
198). The efferent projections of the peduncu - enkephalin or substance P occur in both the
lopontine nucleus are to the substantia nigra, medial and lateral parabrachial nuclei ( 211 ),
the subthalamic nucleus, and the thalamus. and some of these peptidergic neurons were
This nucleus is known to play an important shown to project to the dorsal raphe nucleus
role in the functional organization of the ( 207). One group of large cells, ventral to the
basal ganglia and in the modulation of the -
parabrachial nuclei, the Kiilliker Fuse nucleus ,
thalamocortical neuronal system . project to the nucleus of the solitary tract .
These neurons are associated with central
Parabrachial Nuclei mechanisms involved in the control of respi-
ration .
These nuclei consist of distinct groups of
neurons that surround medial and lateral re- Locus Coeruleus
gions of the superior cerebellar peduncle. The
lateral parabrachial nucleus receives input Near the periventricular gray matter of the
mainly from general visceral nuclei in caudal upper part of the fourth ventricle is an irregu -
regions of the nucleus solitarius. The medial lar collection of pigmented cells referred to as
parabrachial nucleus receives afferents from the locus coeruleus or nucleus pigmentosus pon-
the gustatory part of the nucleus solitarius. tis ( Figs. 13.33-13.35). The locus coeruleus in
Afferents from the nucleus solitarius ascend humans corresponds to group A6 disclosed
uncrossed in the brainstem. The medial in the rat by Dahlstrom and Fuxe (86 ). In hu -
parabrachial nucleus projects to the thala
mus, the hypothalamus, and the amygdala .
- mans, cells of this nucleus are partially inter-
mingled with those of the mesencephalic nu -
The lateral parabrachial nucleus innervates cleus of the trigeminal nerve, but the large
nuclei in the hypothalamus and amygdala globular neurons of the mesencephalic nu -
( 105). The parabrachial nuclei are less densely cleus extend further dorsally and rostrally at
populated in humans than in rodents, and it the margin of the central gray matter ( 203)
Figure 13.34 , Cell groups surrounding the
tom Mesencephalic
nucl N . V
periventricular gray at isthmus levels. Cells
of the locus coeruleus contain granules
composed of melanin pigment and high
concentrations of norepinephrine. Globu-
lar cells of the mesencephalic nucleus of
ill® Locus ceruleus

the trigeminal nerve (N V) are present
along the dorsal border of the locus
coeruleus and extend dorsally and ros-
trally at the margin of the central gray
Ventricle IV
#3
Figure 13.35. Neurons containing norepinephrine in the locus coeruleus ot the rat The norepinephrine containing
-
cells were reacted with glyoxylic acid which converts norepinephrine into a fluorescent chemical derivative that can
be viewed under the fluorescence microscope
13 Pons 513
( Figs. 13.24 and 13.34 ). Cells of the locus ( groups Cl and C2 ) ( 140, 210 ) and from
coeruleus are of at least two types: (a ) neighboring peptidergic neurons ( 143). These
-
medium si /ed oval or round cells with eccen -
tric nuclei and fairly large clumps of melanin
findings indicate that the locus coeruleus lies
within an extremely complex neurochemical
pigment granules, and ( b ) small oval cells environment .
with scant cytoplasm and no pigment (142, Major ascending projections from the
230). Ventrolateral to the locus coeruleus is a locus coeruleus pass rostrally through the
more diffuse collection of similar cells which midbrain lateral to the medial longitudinal
forms the nucleus subcoeruleus ( 142). fasciculus and ventrolateral to the central
Although the locus coeruleus is a rela - gray matter. In the caudal diencephalon, the
tively small structure, it can be identified main ascending bundle of noradrenergic
readily in gross sections of the brainstem be- fibers enters the medial forebrain bundle via
cause of its characteristic pigmentation and the mammillary peduncle and the ventral
location. The significance of this small , pig- tegmental area . These fibers accompany the
mented nucleus remained unknown until it medial forebrain bundle to and through the
was demonstrated by the formaldehyde-in - lateral hypothalamus. This ascending path -
duced fluorescence method ( 46 ) that its cells way continues rostrally to levels of the ante-
contained catecholamines, nearly all of which rior commissure where it divides into bun -
were norepinephrine ( Fig. 13.35) ( 4, 86, 151 , dles innervating the diencephalic and
184, 270 ). Since then , the noradrenergic na - telencephalic structures. The stria medullaris
ture of the locus coeruleus neurons has been component turns caudally to innervate mid -
repeatedly confirmed with various tech- line portions of the thalamus, while the stria
niques including immunocytochemical pro- terminalis component supplies the amyg-
cedures ( 77, 203). Unlike other brainstem no- daloid nuclear complex ( Fig. 13.36). Other ef -
radrenergic cells found as scattered neurons ferent fibers from the locus coeruleus pass via
in the lateral tegmentum (groups A 5 and A 7 the fornix to the hippocampal formation and ,
of Dahlstrom and Fuxe (86 ) ), the locus as a component of the cingulum bundle, to
coeruleus is a compact nucleus that projects the cingulate cortex, the subiculum, and the
fibers to portions of the telencephalon, dien- hippocampal formation . The most rostrally
cephalon , midbrain, cerebellum, pons, projecting fibers from the locus coeruleus
medulla , and spinal cord . Information con- pass from the medial forebrain bundle into
cerning the widespread projections of locus the external capsule which distributes fibers
coeruleus and the nucleus subcoeruleus were to the rostral , dorsal , and lateral cortex of the
obtained following studies undertaken in a frontal lobe. Smaller groups of fibers separat -
wide range of mammalian species and with a ing from the main bundle, which is referred
combination of different anatomic, histo- to as the dorsal catecholamine pathway, pro-
chemical, immunocytochemical, biochemical, ject into the periaqueductal gray matter and
and pharmacologic methodologies ( 28, 47, the periventricular grav matter of the third
107, 127, 135, 137, 138, 161 , 164, 172, 177, 186, ventricle. One of the most profuse projections
188, 184, 203, 204, 212, 270, 242 ). is to the thalamus where terminals are found
Immunocytochemical studies revealed in the intralaminar thalamic nuclei , the ante-
that noradrenergic cells of the locus coeruleus rior nuclear group, and the lateral geniculate
and subcoeruleus area are closely sur- body . In addition to these ipsilateral path -
rounded by, and partly intermingled with, ways, smaller numbers of fibers cross to the
neurons containing different types of neuro- opposite side via the tegmental decussation,
modulators, including acetylcholine and the posterior commissure, the supraoptic
-y-aminobutyric acid (GABA ) and various
neuroactive peptides ( 100, 133, 211 ). Further-
commissures, and the anterior commissure.
After decussating, these noradrenergic path -
more, a significant proportion of noradrener- ways have a distribution similar to those on
gic cells in the locus coeruleus and sub- the ipsilateral side.
coeruleus are known to contain neuroactive More than 10% of cells in the locus
peptides, such as enkephalin and neuropep- coeruleus innervate both the cerebral and
tide Y ( 106, 304). Also of interest is the cerebellar cortex. Noradrenergic fibers project
demonstration that noradrenergic cells in the to the cerebellar cortex via the superior cere-
locus coeruleus receive projections from bellar peduncle and terminate around I ’urk -
adrenergic neurons in the lower medulla inje cell somata and in the lower third of the
Occipital Frontal
lobe lobe
Accumbens
nucleus
Amygdala Septal and
diagonal
band nuclei
Spinal cord
Figure 13 W . Parasagittal section of the human brain showing the widespread arborization of ascending and de-
scending noradrenergic axons of the locus coeruleus The locus coeruleus provides a noradrenergic innervation that
covers the entire rostrocaudal extent of the neuraxis AC, anterior commissure; CB. cerebellum; CC, corpus callosum;
.
CD caudate nucleus; HIP. hippocampal formation. HYP. hypothalamus; LC. locus coeruleus. OF. olfactory tubercle;
TH. thalamus.
molecular layer (186, 2lW , 2W ). In the brain - synaptic relays in the thalamus ( 138). Retro-
stem, the locus coeruleus innervates the infe- grade 11 RP studies based upon transport of
rior and superior colliculi , primary sensory, the enzyme from a large number of sites
and association nuclei, as well as a portion of within the neuraxis suggest a regional topog-
the pontine nuclei (103, 147, 186 ). Both the raphy within the locus coeruleus ( 174 ). These
locus coeruleus and subcoeruleus project data imply that the locus coeruleus is com-
fibers to the spinal cord via the anterior and posed of several distinct subdivisions.
lateral funiculi , which innervate portions of Noradrenergic neurons in the lower brain -
the anterior and intermediate gray matter at stem consist of smaller collections of cells and
all levels. A high percentage of these fibers scattered neurons in the lateral tegmentum of
cross at segmental levels ( 71, 104, 155, 186, the pons and medulla (e.g., groups A5 and
188, 238). A7). These cell groups have projections to re-
The remarkable feature of the locus gions of the central nervous system that do
coeruleus projection is its wide distribution not receive fibers from the locus coeruleus.
throughout the neuraxis ( Pig . 13.36 ). With the Thus, despite the widespread nature of their
exception of the midbrain raphe serotonin projections, the locus coeruleus and the lat -
projection system , no other cell group of the eral tegmental groups appear to form com -
reticular formation has been shown to have plementary and specific neuronal systems.
such an extensive projection. The projection The locus coeruleus and its efferent projec-
of the locus coeruleus directly to the cerebral tions are considered to play a role in paradox-
cortex is unique in that it does not involve ical sleep, facilitation and inhibition of sen-
13 Pons 515
sory neurons, and control of cortical activa- smaller raphe nuclei of the pons and medulla
tion (11, 70, 134, 139, 163, 182, 231, 232 ). Addi - ( 254). Neurons in some raphe nuclei also
tionally, descending noradrenergic fibers contain noradrenaline, dopamine, GABA,
from the locus coeruleus may supply pregan- enkephalin, somatostatin, and cholecys -
glionic sympathetic neurons in the intermedi- tokinin (186 ). Furthermore, excitatory amino
olateral cell column at thoracic and upper acids ( e.g., glutamate and aspartate) and neu -
lumbar levels ( 122, 188). roactive peptides ( e.g., substance P,
enkephalin, and thyrotropin releasing hor-
Raphe Nuclei mone (TRH )) coexist with serotonin in some
cells within the raphe (132, 185 )
Both the pons and the medulla contain cell The principal ascending fibers arise from
groups in the median raphe which properly serotonin cell bodies located in the dorsal
belong to the reticular formation ( 40, 262), but raphe nucleus and in the superior central nu -
are the source of serotoninergic fiber systems cleus ( 12, 25, 26, 75, 186, 270, 272 ) . The major
widely distributed in the central nervous sys- ascending pathway from the rostral raphe
tem . The raphe nuclei of the medulla ( i .e., nu - nuclei passes through the ventral tegmental
cleus raphe obscurus, nucleus raphe pallidus, area (of Tsai ), medial parts of the fields of
and nucleus raphe magnus) are smaller and
less conspicuous than those seen in the pons
( Figs. 12.28 and 12.29) . The inferior central nu -
cleus appears in the median raphe at the junc-
tion of pons and medulla ( Fig. 13.4 ) and rep-
resents the rostral extension of the nucleus
raphe magnus. The nucleus raphe pontis con -
sists of several small cell groups, dorsal and
rostral to the inferior central nucleus. Despite
difficulties in reconciling data from cytoarchi-
tectonic analysis with those from serotonin
mapping studies, the nucleus raphe pontis
appears largely homologous to group B5 of
Dahlstrdm and Fuxe (86 ). The rostral exten-
sion of the pontine raphe nuclei is the superior
central nucleus (of Bechterew ) ( Figs. 13.28 and
13.33), a large aggregation of closely packed
small- and medium -sized cells that encom-
pass both groups B6 and B8 of Dahlstrdm and
Fuxe (86). This superior central nucleus is
also known as the median nucleus of the
raphe or, more simply, the median raplw nu -
cleus . Decussating fibers of the superior cere-
bellar peduncle pass through portions of the
superior central nucleus ( Fig. 13.32). On each
side of the midline, dorsal to the medial lon-
gitudinal fasciculus, is the dorsal nucleus of the
raphe ( Fig. 13.33). This paired nucleus corre-
sponds to group B7 and lies within the ante-
rior periaqueductal gray matter dorsomedial
to the dorsal tegmental nucleus ( of Gudden )
( Fig. 14.3).
Serotoninergic (5-hydroxytryptamine or 5-
HT ) neurons, identified first by the Falck-
Hillarp histofluorescence method and more
recently with immunocytochemical proce-
dures, are widely distributed in the raphe nu - Figure 13.37 . Dark - field photomicrographs of retro-
gradely labeled neurons in the nucleus raphe magnus
clei. The highest percentages of serotoniner- after injection of horseradish peroxidase (HRP) at the
gic neurons are found in the dorsal raphe level of the C2 spinal segment in a squirrel monkey ( A
nucleus and the lowest percentage in the x 80. B. x 200)
Forel , and joins the medial forebrain bundle dorsal motor nucleus of the vagus, the soli-
in the lateral hypothalamus. Fibers leaving tary nucleus, and the spinal trigeminal nu -
this main ascending bundle enter the sub- cleus ( pars caudalis). Spinal projections of
stantia nigra, the intralaminar thalamic nu - this nucleus are bilateral and descend in the
clei , the stria terminalis, the septum , and the lateral funiculus ( Figs. 11.23 and 12.29 ). These
internal capsule. The most rostral projections fibers terminate in the marginal zone ( lamina
terminate mainly in the frontal lobe, although I ), the substantia gelatinosa (lamina II ), and in
some fibers are distributed throughout the parts of laminae V, VI, and VII of the spinal
cerebral cortex. The dorsal nucleus of the gray matter (see Chapter 12 ). Because electric
raphe selectively innervates the substantia stimulation of the nucleus raphe magnus in -
nigra , the lateral geniculate body, the stria - hibits the discharge of neurons associated
tum , the pyriform lobe, the olfactory bulb, with nociceptive sensory input , it was sug-
and the amygdaloid nuclear complex (12, gested that this nucleus is linked to endoge-
160, 194, 253) ( Figs. 13.38 and 13.39 ). The su - nous analgesic mechanisms (16, 18, 98, 293).
perior central nucleus is particularly associ- This thesis is strengthened by the close corre-
ated with serotonergic fibers projecting to the spondence between the terminal projections
interpeduncular nucleus, the mammillary of this nucleus and opiate receptor binding
bodies, and the hippocampal formation. sites ( 206). Serotonin and the raphe nuclei
Other ascending fibers from these nuclei radi- also have been implicated in the regulation of
ate into the mesencephalic reticular forma- diverse physiologic processes such as the reg-
tion and the periventricular gray matter. As- ulation of sleep ( 139 ), aggressive behavior
cending projections from the caudal raphe ( 234 ), and a variety of neuroendocrine func-
nuclei are less numerous and distributed to tions ( 75, 302 ) .
the superior colliculus, the pretectum, and Structurally, the serotonin molecule is sim-
the nuclei of the posterior commissure. As- ilar to a portion of the larger ( / -lysergic acid
cending serotoninergic pathways from the diethylamide ( LSD ) molecule in that both
superior central nucleus project mainly to contain an indole nucleus. LSD is a hallucino-
mesolimbic structures, such as the hippocam- genic drug considered to be the prototype of
pus and septal nuclei , while the dorsal raphe a psychotomimetic drug ( i .e., a drug whose
nucleus has major projections to the basal effects mimic psychosis ) ( 77, 113, 300 ). It was
ganglia , including the striatum and substan - suggested that psychotic phenomenon might
tia nigra ( 12, 160) ( Fig. 13.38). Ascending probe due to either decreased amounts of brain
jections of cells in the raphe nuclei are mainly serotonin or the synthesis of an endogenous
ipsilateral, but axons give rise to abundant compound that antagonized the action of
collaterals with different terminations. serotonin in the brain . Microelectrode studies
Descending projections of the dorsal raphe demonstrated that LSD produced a specific
nucleus are modest, but they include fibers depression of activity in raphe neurons which
distributed to the locus coeruleus and the contain serotonin ( 1, 123). These observations
parabrachial nuclei ( 26). The superior central led to the hypothesis that LSD acts to depress
nucleus gives rise to descending projections the activity of serotoninergic neurons which
to ( a ) the cerebellum via the middle cerebellar through disinhibition, cause a release of ac-
peduncle, ( b ) the locus coeruleus, and (c ) tivity in neurons in the visual system, the lim -
large regions of the pontine reticular forma - bic system , and in many other brain areas ( 2).
tion ( Fig. 12.33). The mesencephalic and Destruction of serotonin neurons, inhibition
motor nuclei of the trigeminal nerve also re- of its synthesis, or blockade of its receptors
ceive serotoninergic afferents (80, 102 ). Nu - consistently produces an animal that is hy-
clei raphe pontis and raphe magnus have dif - persensitive to virtually all environmental
fuse projections in the brainstem and more stimuli and hyperactive in virtually all situa -
specific projections to the spinal cord ( Fig. tions. By a general inhibitory action in the
13.37). Autoradiographic studies have re- central nervous system , serotonin may serve
vealed that the nucleus raphe magnus pro- to modulate and maintain behavior within
jects primarily to structures concerned with specific limits. Studies indicate that as the
nociceptive and / or visceral afferent input overall level of motor activity or arousal in-
(17, 18 ). Structures receiving efferents from creases, so does the activity of serotoninergic
the nucleus raphe magnus, largely via the neurons. As an animal becomes quiescent
dorsal longitudinal fasciculus, include the and drowsy, the activity of these cells dimin -
13 Pons 517
SCP '
IV
Figure 13.38 . Serotonin-containing neurons in the dorsal raphe nucleus at low ( A ) and high ( B) power magnifica
tions. and noradrenaline- containing neurons in the locus coeruleus (C) of the squirrel monkey ( Saimiri sciureus) The
serotoninergic neurons were visualized immunohistochemically with an antibody directed against serotonin itself , The
noradrenergic neurons of the locus coeruleus were identified on the basis of their immunoreactlvity for tyrosine hy
droxylase. the rate-limiting enzyme in the synthesis of primary catecholamines. Most serotoninergic neurons lie in be-
tween the cerebral aqueduct ( AO) and the medial longitudinal fasciculus ( MLF) Some serotonin immunoreactive
neurons are also present in the central superior (median raphe) nucleus (CS) The locus coeruleus forms a compact
cell group lying near the surface of the fourth ventricle ( IV) and medial to the superior cerebellar peduncle ( SCP)
Fibers of the mesencephalic tract of the trigeminal nerve ( TMV ) traverse the locus coeruleus The arrows in B point to
some cells of the dorsal raphe nucleus that contain granular material indicating the presence of cholera toxin subunit
B (CTb) This tracer was injected into the striatum and transported retrogradely to cell bodies in the dorsal raphe
Serotonin-immunoreactivity was revealed with diaminobenzidin (DAB), which gives a diffuse brown reaction, whereas
CTb was visualized with a nickel intensification procedure (NiDAB), which gives a dark blue, granular reaction prod-
uct Scale bars 500 jim (A , C) and 25 jim (B)
Occipital Frontal
lobe
Accumbens
nucleus
Amygdala Septal and
diagonal
band nuclei
Figure 13.39 . Parasagittal section of the human brain showing the widespread arborization of ascending and de-
scending serotoninergic axons of the raphe nuclei. The caudally located raphe nuclei protect primarily to lower
medulla and spinal cord, while the rostrally located ones give rise to ascending projections that arborize profusely
.
throughout the thalamus, hypothalamus, and cerebral hemispheres AC anterior commissure; CB. cerebellum, CC,
. .
corpus callosum; CD caudate nucleus; HIP hippocampal formation; HYP. hypothalamus; OF, olfactory tubercle; PD.
nucleus raphe dorsalis; RMa nucleus raphe magnus; RMe. nucleus raphe medlanus; RO. nucleus raphe obscurus;
. .
RPa nucleus raphe pallidus; TH thalamus
ishes. Neurons of the raphe fire slowly as an in the mechanism of what is called slmv wave
animal enters sleep, and during rapid eye sleep, a state characterized by the posture of
movement ( REM ) sleep the cells stop firing. sleep, myotic pupils, and cortical electrical ac-
These findings suggest that , under the influ - tivity (electroencephalogram or EEG ) which
ence of hallucinogenic drugs, the individual displays spindles and slow waves. Addition-
is fully awake but the brain serotonin system ally, serotoninergic neurons may have effects
is depressed and behaving as it does during upon the cells of the locus coeruleus that trig-
sleep ( 129 ). ger what is called paradoxical sleep (70, 139 ).
Investigations indicate that both serotonin Paradoxical sleep occurs intermittently after
-
and norepinephrine containing neurons in variable periods of slow wave sleep and is
the reticular formation play roles in the active characterized by (a ) abolition of antigravity
mechanisms that control sleep states (139 ). muscle tone, ( b) reductions in blood pressure,
Sleep is not a single phenomenon. Sleep bradycardia , and irregular respiration , (c )
states can be quantitatively measured and bursts of REM, and (d ) an EEG that resembles
correlated with biochemical, pharmacologic, the waking state. Bilateral lesions of the locus
and structural alterations. Inhibition of sero- coeruleus in animals cause a selective sup-
tonin synthesis, or total destruction of sero- pression of paradoxical sleep for about 2
toninergic neurons in the raphe system, leads weeks, after which it returns to nearly the
to insomnia . Serotonin seems to be involved normal range.
13 Pons 519
RETICULAR FORMATION tralaminar thalamic nuclei . Impulses passing

to these thalamic nuclei profoundly influence
Two relatively large nuclear masses, the the electrical activity of broad areas of the
nucleus reticularis pout is caudal is and oralis , cerebral cortex.
compose the bulk 1 the pontine reticular for- Other reticular nuclei present at pontine
mation . The pars caudalis, which replaces the levels are the reticulotegmental and central
gigantocellular reticular nucleus of the superior nuclei ( Figs . 13.28, 13.32, and 13.33 ) .
medulla , extends rostrally to levels of the The reticulotegmental nucleus lies near the
trigeminal motor nucleus. The pars oralis ex- median raphe dorsal to the medial lemniscus
tends rostrally into the caudal mesen - and is regarded as a tegmentally displaced
cephalon where its precise boundary is indis- pontine nucleus ( 33 ) ( Fig . 13.28 ) . This nucleus
tinct ( Fig . 13.28 ) . Cells of the pontine reticular receives projections from the cerebral cortex
formation give rise to uncrossed reticu - and the cerebellum ( 39, 64 ) and , in turn, pro-
lospinal fibers, which in the brainstem de- jects massively to the cerebellum ( 35 ) . Thus,
scend as a component of the MLF. Other cells the reticulotegmental nucleus is regarded as
give rise to fibers that ascend as part of the an important relay in cortical and cerebellar
central tegmental tract ( Fig . 13.32 ) . Many cells motor circuits. The superior central nucleus
have dichotomizing axons that project develops in the median raphe and enlarges at
branches both rostrally and caudally . As- isthmus levels, where it is referred to as the
cending pontine reticular fibers project via median nucleus of the raphe ( nucleus raphe
the central tegmental tract to parts of the in- medianus).
References cephalon . Acta Physiol Scand croscopic study of a pain modulat -

-
1966;67:313 326. ing system J Conip Neurol
1 Aghajanian GK , Foote W'E, Sheard 10. Angaut 1', Brodal A . The projection 1966250:311 |23
H Lysergic acid diethylamide , of the "vestibuIocerebel1um" onto 19. Batton RR III . Javaraman A , Rug -
sensitive neuronal units in the the vestibular nuclei in the cat. giero D, Carpenter MB . Fastigial
midbrain raphe. Science 1968;161 . Arch Ital Biol 1967;105:441^ 79. efferent projections in the monkey:
706-708. 11 . - *
Aston Jones G, Chiang C, Alexin - an autoradiographic study. J Comp
2. Aghajanian GK , Maigler MJ , Ben- sky T. Discharge of noradrenergic Neurol 1977; 174 : 281 -306.
nett JL . Amine receptors in the locus coeruleus neurons in behav - 20. Beckstead RM , Norgren R . An au -
-
CNS. 111. 5 hydroxytrvptamine in ing rats and monkeys suggests a toradiographic examination of the
.
brain. In: Iverson LL Iverson SD, role in vigilance. Prog Brain Res central distribution of the trigemi -
Snyder SI I , eds. I landbook of psy - -
199138:501 520. nal , facial, gl » »sHopharyngeal and
chopharmacologv . 6 th ed . New 12. A / mitia EC, Gannon PJ . The pri - vagal nerves in the monkey. I
York: Plenum Press, 1975:63-96. mate serotoninergic system: a re- Comp Neurol 1979;184:455 472. -
3. Aitkin LM , Webster WR . Tono - view of human and animal studies 21 Bender MB, Shan /er S. Oculomo -
topic organization in the medial and a report on Macaca fasdculnns . tor pathways defined bv electrical
geniculate bodv of the cat . Brain In : Fahn S, ed Advances in neurol - stimulation and lesions in the brain
-
Res 197126:402 405. ogy. Vol. 43. New York: Raven stem of the monkey. In: Bender
4 Aitkin LM , Webster WR . Medial Press, 1986:407-468. MB, ed . The oculomotor system.
geniculate Nuly of the cat : organi - 13. Bacsik RD, Strominger NIL. The cy- New York: Harper and Row,
zation and responses to total stim - toarchilecture of the human an- 1964:81-140.
uli of neurons in the ventral divi - teroventral cochlear nucleus. J 22. Bender MB. Weinsten FA Effects
sion . | Neurophvsiol I 972;35: -
Comp Neurol 1973;147:281 290. of stimulation and lesion of the
365-380. 14 Baker R, Highstein SM . Physiologi - median longitudinal fasciculus in
5. Aitkin LM, Webster WR , Veale JL, cal identification of interneurons the monkey . Arch Neurol & Psy -
Crosby DC Inferior colliculus. I and motoneurons in the abducens chiatry 1944;52: 106 113.
Comparison of response properties nucleus. Brain Res 1975;91 :292- 23. Bender MB, Weinstein FA The
of neurons in central , pericentral 298. syndrome of the median longitudi -
and external nuclei of adult cat. J 15. Barnes WT, Magoun IIW , Kanson nal fasciculus Proc Assoc Res
6.
Neurophvsiol 1975;38: l 196- 1207.
Allen , YVF. Application of the
SW. The ascending auditory path -
way in the brain stem of the mon - 24.
-
Nen Men! Mi 195028:414 420
Blum IS, Day MJ , Carpenter MB,
Marchi method to the study of the key . J Comp Neurol 1943;79: Gilman S. Thalamic components of
radix mesencephalica trigemini in 129-152. the ascending vestibular system.
the guinea pig. J Comp Neurol 16. Basbaum Al . Opiate and stimulus- I xp \ » •11 r » > 1 1979 • < i 587 < '• 1
1919;30:169- 216. produced analgesia : functional 25. Bobillier P, IVlit jean F, Sal vert D,
7. Allen WF. Identification of the cells anatomy of a medullospinal path - Ligier M , Seguin S Differential
and fibers concerned in the inner - way. Proc Natl Acad Sci USA projections of the nucleus raphe
vation of the teeth . J Comp Neurol -
1976;73:4685 4688. dorsalis and mu leus raphe cen -
H.
-
1925;39:325 343.
Altman |, Carpenter MB Fiber pro-
17. .
Basbaum Al , Clanton CM Fields
III.. Three bulbospinal pathways
tralis as revealed by autoradiogra
phy . Brain Res 1975;85:205-210.
-
jections of the superior colliculus from the rostral medulla of the cat: 26. Bobillier P, Seguin S, Pet it jean F,
in the cat. J Comp Neurol 1961 ; an autoradiographic study of pain Sal vert D, Touret M Jouvet M . The
116:157-178. modulating systems. J Comp Neu - raphe nuclei of the cat brain stem:
9. -
Anden N E, Dahlstrrim A , Fuxe K , rol 1978;178:209-224 . a topographical atlas of their effer -
Larsson K , Olson L, Ungersttn.lt U .
Ascending monoamine neurons
18. Basbaum Al, Ralston DD, Ralston
MJ. Bulbospinal projections in the
ent projections as revealed by au
toradiography Brain Res 1976;
-
to the telencephalon and dien - primate: a light and electron mi - 113:449 - 486
27 Borg I On the neuronal organiza - rimotor cortex. Exp Brain Res neurons in the monkey identified
tion of the acoustic middle ear re- 1988;5:212- 237. by immunocytochemical methods.
flex : a physiological and anatomi - 43 Brtxlal IV The corticopontine pro- Brain Res 1987:408:275-280.
cal study . Brain Res 1973;49: jection from the visual cortex in the 59 . Carpenter MB, Cowie R | . Connec-
101—123. cat . I The total projection and the tions and txrulomotor projections
28 Bowden DM , German DC , Poynter projection from area 17. Brain Res of the superior vestibular nucleus
VVD An autoradiographic, semi - 1972;34:297- 317. and cell group "y." Brain Res
stereotaxic mapping of major pro- 44 . Brtxlal IV I he corticopontine pn>- 1485;338:285- 287.
jections from locus coeruleus and jection from the visual cortex in the 80. Carpenter MB, I lanna GR . Fiber
adjacent nuclei in Mnnicn nwinI In . cat . II . The projection from areas 18 projections from the spinal trigem-
Brain Res 1978;145:257- 278. and 19 Brain Res 1972;39:319-335. inal nucleus in the cat . I Comp
29. Bowden REM, Mahran ZY . The 45. Biittner U, Btittner-Ennever ) A, Neurol 1961;117:117- 132.
functional significance of the pat - I lenn V . Vertical eye movement re- 81 . Carpenter MB, Hanna GR . Effects
tern of innervation of the muscle lated unit activity in the rostral of thalamic lesions upon cerebellar
quadratic labii superioris of the mesencephalic reticular formation dyskinesia in the rhesus monkey I
rabbit , cat and rat . | Anat 1456; of the alert monkev. Brain Res Comp Neurol 1982;119: 127- 148.
MO 217 227. 1977;130:239- 252. 82 . Carpenter MB. McMasters RE , Dis-
.30. Brawer |R , Mortal DK , Kane EC . 46. Carleton SC. Carpenter MB. Affer - turbances of conjugate horizontal
The neuronal architecture of the ent and efferent connections of the eye movements in the monkey. II .
cochlear nucleus of the cat . J Comp medial. inferior and lateral Physiological effects and anatomi-
Neurol 1474; 155:251- 300. vestibular nuclei in the cat and cal degeneration resulting from le-
31 Brodal A . The reticular formation monkey. Brain Res 1483;278:29- 51 . sions in the medial longitudinal
ol the brain stem. Anatomical as- 47. Carleton SC, Carpenter MB. Distri- fasciculus. Arch Neurol 198.3;8:
pects and functional correlations. bution of primary vestibular fibers 347-388.
Springfield, 1L: Charles C. Thomas, in the brain stem and cerebellum 8.3. Carpenter MB, McMasters RE,
IMS7. of the monkev . Brain Res 1484; I lanna GR. Disturbances of conju -
32 Brtxlal A Anatomy of the vestibu - 244 :281 - 298. gate horizontal eye movements in
lar nuclei and their connections. In: 48. Carpenter MB. The dorsal trigemi - the monkey . I Physiological effects
Kornluiber Mil, ed. I iandbook of nal tract in the rhesus monkev. ) and anatomical degeneration re-
sensory physiology: vestibular sys- Anat 1957;91:82-40. sulting from lesions of the ab-
tem Vol. n Berlin: Springer - Ver - 49 Carpenter MB. Lesions of the lasti - ducens nucleus and nerve. Arch
lag. 1974:239-352. gial nuclei in the rhesus monkev. Neurol 196.3;8:23l 247.
33. Brtxlal A . Brtxlal IV The organiza - Am J Anat 1954; 104 : 1- 34. 84 . Carpenter MB, Nova HR Descend -
tion of the nucleus reticularis 50. Carpenter MB. Fiber projections ing division of the brachium con-
tegmenli pontis in the cat in the from the descending and lateral junctivum in the cat : a cerebello-
light of experimental anatomical vestibular nuclei in the cat . Am ) reticular system. J Comp Neurol
studies of its cerebral cortical affer- Anat 1980;107:1-22. 1960;114:295-305.
ents Exp Brain Res |97 l;13;40- | 10 51 Carpenter MB. The ascending 85 Carpenter MB, Stein BM, Peter IV
34 . Bnxlal A , I loivik B Site and mtxle vestibular system and its relation- Primary vestibulocerebellar fibers
of termination of primary ves- ship to conjugate horizontal eye in the monkey: distribution ol
tibulocerebellar fibres in the cat movements. In: Wolfson R |, ed libers arising from distinctive cell
Arch Ital Biol 1964;102:1 - 21 . The vestibular system and its dis- groups of the vestibular ganglia
35. Brodal A , lansen | The pontocere- ease's. Philadelphia: University of Am J Anat 1472;135:221- 250.
bellar projection in the rabbit and Pennsylvania Press, 1988:88-98. 88. Carpenter MB, Strominger NL. The
. i it | C omp Neurol I946;84:31 I 18 52. Carpenter MB. Upper and lower medial longitudinal fasciculus and
38. Brtxlal A , Pompeiano O. The motor neurons. In: Downey JA , disturbances of conjugate horizon-
vestibular nuclei in the cat . | Anat Darling RC . eds. Physiological tal eye movements in the monkey.
1957;91:438-454. basis of rehabilitation medicine. I Comp Neurol 1485; 125:41-88.
17. Brodal A , I’ompeiano O, Walberg Ch 1 Philadelphia: VY B
. .
Saun- 87. Carpenter MB, Strominger NL. Ef -
I The vestibular nuclei and their ders, 1471:3-27. ferent fibers of the subthalamic nu-
connections, anatomy and func - 53 Carpenter MB. Central oculomotor cleus in the monkey : a comparison
tional correlations. Springfield, II pathways. In Bach- y-Rita P. ed. of the efferent projections ol the
c fortes i Ihomas, 1%2. The control of eye movements. Ch. subthalamic nucleus, substantia
38. Brtxlal A , Szabo T, Torvik A . Corti- 4 . New York: Academic Press, nigra and globus pallidus. Am )
cofugal libers to sensory trigeminal 1471:87- 103. Anat 1987, 121 :41-72.
nuclei and nucleus of solitary tract. 54 Carpenter MB, Batton RR III Ab- 88 Chan - Palav V . Cerebellar dentate
I Comp Neurol 1456; 108:527-555. ducens intemuclear neurons and nucleus: organization, cytology
34 Brtxlal A , Szikla G. The termina- their role in conjugate horizontal and transmitters . Berlin: Springer-
tion of the brachium conjunctivum gaze | Comp Neurol 1480; 184; Verlag, 1977.
descendens in the nucleus reticu- 141- 209. 89. Christoff N. Anderson PL
laris tegmenti pontis: an experi- 55. C arpenter MB, Batton RR 111. Con- Nathanson M, Bender MB. Prob-
mental study in the cat . Brain Res nections of the fastigial nucleus in lems in anatomic analysis of le-
1472;39:337-351. the cat and monkey. Exp Brain Res sions of the median longitudinal
44 ) . Brtxlal A , Taber E. Walberg E The 1482;(5uppl 8 ): 25(C295. fasciculus . AM A Arch Neurol
raphe nuclei of the brain stem in 56. Carpenter MB, Carleton SC . Com - 1960;2:293- 304.
the cat . II Efferent connections | parison of vestibular and abducens 70. Chu N- S, Bloom FF.. Norepineph-
Comp Neurol 1%0;114:239 259 projections to the medial rectus rine-containing neurons: changes
41 . Brodal A . Torvik A . Uber den Ur - subdivision of the oculomotor in spontaneous discharge patterns
sprung der sekundaren vestibulo- complex in the monkey. Brain Res during sleeping and waking. Sci-
cerebellaren Fasern bei der Katze 1483;274:144 144. ence 1973;179:908-910.
Fine experimentell-anatomische 57. Carpenter MB, Carleton SC, Keller 71 C lark EM. Proudfit I IK. The pro-
Studie Arch I ’svchiatr 1457; 145 IT , Conte P Connections of the jection of locus coeruleus neurons
550- 587. subthalamic nucleus in the mon- to the spinal cord in the rat deter -
42 Brodal IV Ihe corticopontine pro- kev Brain Res 1481;224:1 29. mined by anterograde tracing com -
jection in the cat . I. Demonstration 58. Carpenter MB, Chang L, Pereira bined with immunoeytochemistrv
of a somatotopically organized AB, llersh LB, Bruce G, Wu ) Y . Brain Res 1941 ,538 : 231 245
projection from the primary senso- Vestibular and ax'hiear efferent 72. Cogan IX i, Kubik CS, Smith Wl .
13 Pons 521
. .
Lnil itiT il internuclear ophthalmo- monoamines in the cell btxlies ot tyric acid ami glutamate decar-
.
plegia : report of eight clinic il case's brain stem neurons. Acta Physiol boxylase in the inhibitory Purkinje
with one postmortem study . Arch Scand W64;62(Suppl 232 ):1 -55 axons terminals in the cat . Brain
Opthalmol 1950;44:783-796 87. Darian -Smith I , Mayday G. Soma - Res 1973;54.||5 127
-
73. Cohen B. Vestibulo ocular rela - totopic organization within the 102 Fort P, Luppi I ’ll . Sakai K , Sal vert
--
tions. In : Bach y Rita P, ed . The brain stem trigeminal complex ot D, Jouvet M Nuclei of origin
control of eye movements. New the cat . Exp Neurol 1960, 2:290 309 ot mom vi minergu , peptidergic,
York Academic Press, 1971:
-
103 135.
88. -
Darian Smith I , Yokota T. Corti
cofugal effects of different neuron
- cholinergic afferents to the cat
trigeminal motor nucleus: a dou -
74 . Cohen B, Su / uki Jl , Bender MB. types within the cat's brain stem ble-labeling study with cholera -
Eye movements from semicircular activated by tactile stimulation ot toxin as a retrograde tracer J
nerve stimulation in the cat . Ann the face. | Neurophysiol 1966; C omp Neurol 1990;101:262-275.
Otol Rhinol Farvngol 1964;73: 29:185-206. 103 Fritschv |M, Gr / anna R . Distribu -
-
153 169. 89. Deecke I , Schwarz DWF, Fredrick - tion ot locus UHTUICUS axons
75. Conrad LCA , Leonard CA, Plait son ) M. The vestibular thalamus in within the rat brainstem demon -
DVV . Connections of the median the Rhesus monkey. Adv Otorhi - strated by I liiiwlus rul$art> leuco
’ -
and dorsal raphe nuclei in the rat : nolarvngol 1973;19:210-219. agglutinin anterograde tracing in
an autoradiographic and degener - 90. Deecke L, Schwarz DWF, Fredrick - combination with dopamine-beta -
ation study. | Comp Neurol son |M . Nucleus ventropostenor hydroxylase immunofluorescence
1974;t56:179 206
76. Contreras R|, Come/ MM, Nor -
inferior ( VPI ) as the vestibular
thalamic relay in the Rhesus mon - 104 Fritschv |M. Gr / anna R fX*mon-
—
J Comp Neurol 199( 1 ;293:616 31
gren R . Central origins of cranial key . I . Field potential investigation stration ot two separate descend -
nerve parasympathetic neurons in Exp Brain Res 1974;20:88- 100 ing noradrenergu pathways to the
the rat I Comp Neurol WHO; 91 Deecke L , Schwarz DWF, Fredrick - rat spinal cord evidence lor an in -
-
190:373 394. son JM. Vestibular responses in the tragriseal trajectory of lixus
77. Cooper |R , Bloom Ft , Roth RIF rhesus monkey ventroposterior coeruleus axons in the superficial
The biochemical basis of neu - thalamus. II . Vestibulopropriocep- layers of the dorsal horn. | C omp
ropharmacology . 6th ed . New tive convergence at thalamic neu - Neurol 1990 ; 29| 553 82
York : Oxford University Press, rons. Exp Brain Res !977;30: lt )5. Fulwiler C E , Sapor CB. Subnuclear
1991. -
219 232. organization ot the efferent con -
78. Cooper S, Daniel PY1, Whitteridge 92. Dejong RN . The neurological ex - nections of the parabrachial nu -
D. Nerve impulses in the brain - amination . 4 th ed . New York : cleus in the rat Brain Res Rev
stem of the goat: short latency re- Harperand Row, W79. 1984;7:229-259
sponses obtained by stretching the 93. Dodd |, Kelly JP. Trigeminal sys - .
106. Fung S| Zhuo II , Manzoni D,
extrinsic eye muscles and the jaw tem . In: Kandel ER , Schwartz |ll . .
Reddy VK Barnes CD. Coeru -
muscles j Physiol ( Lond ) W53;
,
Jessell TM, eds. Principles of lospinal cells containing neuropep -
-
120:471 490. neural science. 3rd ed . Ch. 45. New tide Y in the cat . Peptides
79. Cooper S, Daniel PM , Whitteridge -
York: Elsevier, 1991:702 710. 1991 ;12:739-743
D. Nerve impulses in the brain - 94 . Dow RS. The fiber connections of 107. Fuxe K . Evidence tor the existence
stem of the goat: responses with the posterior part of the cerebellum of montvimino neurons in the cen-
long latencies obtained by stretch - in the rat and cat . J Comp Neurol tral nervous system IV. Distribu -
ing the extrinsic eye muscles. I 1936;63:527-548. tion ot momvimine nerve terminals
80.
Physiol il oitd) 1953/120:491 51 •
Copray JC, Liem RS, Ter Horst C J , . 95. .
Dubner R , Bennett CJ . Spinal and
trigeminal mechanisms of niRecep-
m the central nervous system. Acta
Physiol Stand l 965;64(Suppl 247 ):
van Willigen JD. Origin , distribu - tion. Annu Rev Neurosci |983;6: 37-120.
tion and morphology of serotoner - 381 4 is . 108. Gacek RR . The efferent cochlear
gic afferents to the mesencephalic 96 Falck B, Hillarp NA . Thieme G. bundle in man . Arch Otolaryngol
trigeminal nucleus of the rat . Neu - Torp A . Fluorescence of cate - 1961;74:690-694
*
-
rosci Lett 1991;121.97 101 cholamines and related com - 109. Gacek RR . Fixation of brain stem
81. Corbin KB Obsc» rvations on the pounds condensed with formalde- neurons projet ting to the oculomo-
peripheral distribution of fibers hyde. | Histochem Cytochem tor nucleus in the cat. Exp Neurol
arising in the mesencephalic nu - 1962;10:348-354 . 1977;57:725-749
cleus tit the fifth cranial nerve | 97. Eel ten DL, Sladek |R |r. 110. Gacek RR . Fixation of commis-
Comp Neurol W40;73: I 53 177 Monoamine distribution in pri - sural neurons m the vestibular nu -
82. Corbin KB, I larnson F. Function of mate brain V . Monoa minergu nu - clei of the cat Exp Neurol 1978;
the mesencephalic root of the fifth clei: anatomy, pathways and lixal 59:479-491 .
cranial nerve. I Neurophysiol 1940; organization . Brain Res Bull 111 . Gacek RR . Fixation ot abducens
3:42.3-435. 1983;10:171-284. afferent neurons in the cal . Exp
83. Courville |. Kubrobulbar fibres to 98 Fields ML , Basbaum Al , Clanton Neurol I 979;64 142 353
the facial nucleus and the lateral
reticular nucleus ( nucleus ot the
CH , Anderson SD. Nucleus raphe
magnus inhibition of spinal cord
.
112 . C acek RR , Fvon M The Itxali /a -
tion of vestibular efferent neurons
lateral funiculus ): an experimental dorsal horn neurons. Brain Res in the kitten with horseradish per -
study m the cat with silver impreg - 1977;126:441 -454 . oxidase Acta Otolaryngol (Stockh )
nation methixls Brain Res 1966; 99. Fluur E . Influences of semicircular 1974;77:92- 101
1 :317-337. ducts on extraocular muscles. Acta 113. Gaddum I I I , llameed KA . Drugs
84 Courville J . The nucleus of the fa - Otolaryngol (Stockh ) 1959; 149 which antagonize 5- hvdroxvtrvpt -
cial nerve: the relation between cel - I 46 . amine. Br I Pharmacol 1954 ;9;
lular groups and peripheral 100. Ftxior M , Gores TJ , Palkovits M -
240 248.
branches of the nerve. Brain Res Immunohistochemical study on 114 Galambi >s R Suppression ot audi
Woivi 338 354 the distribution til neuropeptides lory nerve activity by stimulation
85. Crowe SJ . Symposium on tone lo- within the pontine tegmentum of efferent fibers to cochlea . | Neu -
calization in the cochlea . Ann Otol particularly the parabrachial nuclei rophysiol 195n.19 240-248.
Rhinol Larvngol 19.35,44:737-837. and the locus coeruleus of the 113 Gerrits NM Vestibular nuclear
86 Dahlstrbm A . Luxe K . Evidence for human brain . Neuroscience 1992, .
complex. In : Paxinos G ed . The
the existence of monoamine con - - 46:891-908. human nervous system. Ch . 26.
taining neurons in the central ner - 101 . Fonnum F , Walberg F . An estimate New York: Academic Press,
vous system . I . IX’monstration ot ot the concentration of •y -aminobu - |990;86.3 888
116. Goldberg |M , Fernandez C. Effer- Deiters neurones. Experientia trigeminal nerve. Brain 1963;
ent vestibular system in the squir - 1464;20:515. 86:721-732.
rel monkey: an anatomical location 129. Jacobs BL, Trulson ME. Mecha - 143. Kerr FWL, Kruger LI . Schwass . -
and influence on afferent activity . J nisms of actions of LSD. Am Sci .
mann HO Stern R . Somatotopic
Neurophysiol I 480;43:986- 1025. 1979;67:396-404. organization of mechanoreceptor
117. Golberg ME, Howard MF, Gouras 130. Jacobsohn L. Uber die Kerne des units in the trigeminal nuclear
P. The iK ular motor system . In :
'
menschlichen Himstamms. Ab- complex of the monkey. I Comp
Kandel FR , Schwartz jl I, Jesse11 handlungen der kdnigl . Preuss Neurol 1468;134: 127-144
TM, eds. Principles of neural sci - Akademie der Wissenschaften, 144. KevetterGA , Perachio AA . Distrib-
ence 3rd ed . Ch. 43. New York: El - 1904;1 : 1 -70. ution of vestibular afferents that
sevier , 1991;660-678. 131. Jenny AB, Saper CB. Organization innervate the sacculus and poste -
118. Goldstein M . The auditory periph - of the facial nucleus and corticofa - rior canal in the gerbil ) Comp
ery . In: Mountcastle VB, ed . Med - cial projection in the monkey: a re - Neurol 1486;234: 410 -424
ical physiology. 12th ed . Gh . 64 . St consideration of the upper motor 145. Kimmel DL. Innervation of the
Louis: C . V . Mosbv, I 4O8;1465- neuron facial palsv. Neurology spinal dura mater and dura mater
1448. 1987;37:930-939. of the posterior cranial fossa . Neu -
119. Graybiel AM . Direct and indirect 132. Johansson O, Hokfelt T, Pernow B, -
rology 1961;9:800 804.
preoculomotor pathways of the et al . lmmunohistochemical sup - 146. Kimura R , Wersall J . Termination
brainstem : an autoradiographic port for three putative transmitters of the olivo-cochlear bundle in re-
study of the pontine reticular for - in one neuron: coexistence of 5- hv - lation to the outer hair cells of the
mation in the cat . J Comp Neurol droxytrvptamine, substance P- and organ of Corti in guinea pig Acta
1477;175:37-78. thrvrotropin releasing hormone- Otolaryngol (Stockh ) I 462;55:
120. Graybiel AM , Hartwieg FA . Some like immunoreactivity in medul - -
11 32.
afferent connections of the oculo- lary neurons projecting to the 147. Klepper A , 1 lerbert 11. Distribution
motor complex in the cat: an exper - spinal cord . Neuroscience 1981;6: and origin of noradrenergic and
imental study with tracer tech - -
1857 1881. serotonergic fibers in the cochlear
niques Brain Res 1974;81 :543 551 . 133. |ones BE. Noradrenergic locus nucleus and inferior colliculus of
121. Guinan II , Warr WB, Norris BE. coeruleus neurons: their distant the rat . Brain Res 1441 ;557: 140-201 .
Differential olivocochlear projec - connections and their relationship 148. Kortc GE, Mugnaini E The cere-
tions from the lateral versus me- to neighboring ( including choliner - bellar projection of the vestibular
dial zones of the superior olivary gic and GABAergic ) neurons of the nerve in the cat . I Comp Neurol
complex | Comp Neurol 1983; central gray and reticular forma - 1474;184 : 265-278.
221 :358 370. tion . Prog Brain Res 1941;88: 15-30. 144. Kruger L, Michel F. A morphologi -
122. Guyenet PG. Central noradrener - 134 . Jones BE , Bobillier P, Pin C, Jouvet cal and somatotopic analysis of
gic neurons: the autonomic con- M . The effects of lesions of cate- single unit activity in the trigemi -
nection Prog Brain Re> 1491;88: cholamine-containing neurons nal sensory complex of the cat. Exp
365-380. upon monoamine content of the Neurol 1462;5:134-156.
123. I laigler 11|, Aghajanian GK . Lyser - brain and EEC and behavioral 150. Kruger L, Michel F. Reinterpreta -
gic acid diethylamide and sero- waking in the cat. Brain Res tion of the representation of pain
tonin : a comparison of effects on 1973;58:157-177. based on physiological excitation
serotonergic neurons and neurons 135. Jones BE , Friedman L. Atlas of cat - of single neurons in the trigeminal
receiving serotonergic input . J echolamine perikarya , varicosities sensory complex. Hxp Neurol
Pharmacol Exp Ther 1974 ;188: and pathways in the brainstem of -
1962;5:157 178.
688-699. .
124 llayashi II , Sumino R , Sessle B|
the cat . J Comp Neurol 1983;
215:382-396.
Functional organization of trigemi - 136. Jones BE, Halaris AE, Mcllhany M ,
.
151 . Kuhar MJ , Roth RH Aghajanian
C K . Synthesis of catecholamines in
the locus coeruleus from 'll - tvro-
nal subnucleus interpolates: ninri - Moore RY . Ascending projections sine in viw. Biochem Pharmacol
ceptive and innocuous afferent in - of the locus coeruleus in the rat . 1. 1972;21 : 2280-2282.
puts, projections to thalamus, Axonal transport in central nora - 152. Kuypers HGJM. An anatomical
cerebellum, and spinal cord , and drenaline neurons. Brain Res analysis of corticivbulbar connex-
descending modulation from peri - 1977;127:1-22. ions to the pons and lower brain
aqueductal gray. J Neurophysiol 137. Jones BE, Harper ST, Halaris AF.. stem in the cat I Anat 1958;
-
1984;51:890 905. Effects of locus coeruleus lesions 92: 198-218.
125 Hazrati l .- N , Parent A . Projection upon cerebral monoamine content , 153. Kuypers HGJM. Corticobulbar
from the deep cerebellar nuclei to -
sleep wakefulness states and the connexions to the pons and lower
the pedunculopontine nucleus in response to amphetamine in the brain-stem in man: an anatomical
the squirrel monkey. Brain Res cat . Brain Res 1977;124:473-496. study . Brain 1958;81:364- 388.
1492;585:267-271 . 138. Jones BE , Moore RY. Ascending 154. Kuypers HGJM , Lawrence IX .
126 I lighstein SM . Abducens and Ocu - projections of the locus coeruleus Cortical projections to the red nu -
lomotor internuclear neurons: rela - in the rat . II. Autoradiographic cleus and the brain stem in the rhe-
tion to gaze. In: Baker R, Berthoz study Brain Res 1977;127:23-53. sus monkey. Brain Res |9f >7; 4 :
A, eds Control of gaze by brain 139. Jouvet M . Biogenic amines and the 151-188.
stem neurons: developments in states of sleep. Science 1969; 155. Kuypers HGJM , Maisky VA . Ret -
neuroscience. Vol. I . Amsterdam : 163:32-41. rograde axonal transport ot horse-
Elsevier, 1977;153 162. 140. Kachidian P, Astier B, Renaud B, radish peroxidase from spinal cord
127. I lokfelt T, Johansson O, Goldstein Bosler O. Adrenergic innervation to brain stem cell groups in the cat .
M . Central catecholamine neurons of noradrenergic locus coeruleus Neuroscience Lett 1975; 1 :4-14
as revealed by immunohisU »chem-
istry with special reference to
neurons. A dual labeling immuno
cytochemical study in the rat . Neu -
- 156. Kuypers HGJM , Tuerk DJ . The dis
tribution of cortical fibres within
-
adrenaline neurons. In : Bjorklund -
rosci Lett 1490; 109:23 29. the nuclei cuneatus and gracilis in
.A Hokfelt T, eds. Handbook of 141 . Kerr FWL. Structural relation of the cat . ) Anat I 9<>4 ;48: I 4.V|62.
chemical neuroanatomy. Vol . 2. the trigeminal spinal tract to upper 157. Ladpli R , Brodal A . Experimental
Part I : Classical transmitters in the cervical roots and the solitary nu - studies of commissural and reticu -
CNS . Ch . 5. Amsterdam : Elsevier, cleus in the cat . Exp Neurol lar projections Irom the vestibular
1984: 157 276. 1961;4:134- 148. nuclei in the cat. Brain Res
128 . Ilo M , Yoshida M . The cerebellar - 142. Kerr FYVL . The divisional organi- 1968;8:65-96.
evoked monosynaptic inhibition of zation of afferent fibers of the 158. Lang W, Buttner - Ennever |A . But -
13 Pons 523
tner U. Vestibular projections to encephale du rat. Brain Res 1972; and primate. Neuroscience 1992;
the monkey thalamus: an autoradi - 3<vl 9-35. 48:545-559.
ographic study. Brain Res 1979; 173. Vlanni E, Bortolami R , Desole C. 186. Nieuwenhuys R . Chemoarchitec-
177:3-17. Eye muscle proprioception in the ture of the Brain Berlin: Springer -
159. Larsen KD, McBride RL. The orga - semilunar ganglion . Exp Neurol Verlag, 1985.
nization of feline entopeduncular 1966;16:226-236. -
187. Nyberg llansen R Origin and ter -
nucleus projections: anatomical 174. Mason ST, Fibiger 11C. Regional mination of fibers from the
studies. J Comp Neurol 1979; topography within noradrenergic vestibular nuclei descending in the
IH4:293-308. locus coeruleus as revealed by ret - medial longitudinal fasciculus: an
160. Lavoie B, Parent A . Immunohisto - rograde transport of horseradish experimental study with silver im -
chemical study ol the serotoniner - peroxidase. J Comp Neurol pregnation methods in the cat . I
gic innervation of the basal ganglia 1979;187:703-724. C omp Neurol 1964;122:355-368.
in the squirrel monkey . J Comp 175. Mehler WR , Rubertone ) A. 188. Nygren LG. Olson I A new major
Neurol 1990;299:|-16. Anatomy of the vestibular nucleus projection from the locus
161 . Levitt P. Moore RV. Origin and or - complex. In : Paxinos G, ed . The rat coeruleus: the main source of nora -
ganization of brainstem cate- nervous system. Vol . 2. Chap. 9. drenergic nerve terminals in the
cholamine innervation in the rat . I Sydney, Australia: Academic ventral and dorsal columns of the
Comp Neurol 1979;186505 528 Press, 1985:185-219. spinal cord . Brain Res 1977;1.32:
162 . Lewv FH, Kobrak H . Neural pro- 176. Merzenich MM, Reid MD Repre - 85 93
jection of cochlear spirals on pri - sentation of the cochlea within the 189 Olsen L, Luxe K On the projec -
mary acoustic centers. Arch Neu - inferior colliculus of the cat . Brain tions from the locus coeruleus no-
163.
-
rol Psychiatry 1936;35:839 852.
Lidbrmk P. The effects ot lesions of
Res 1974;77:397 115-
177. \1iH » re RY , Card P. Noradrenaline-
radrenaline neurons the cerebellar
innervation. Brain Res 1971;28:
ascending noradrenaline pathways containing neuron systems. In : 165-171.
on sleep and waking in the cat . Bjorklund A , Hbkfelt T, eds. Hand - 190. Olszewski J On the anatomical
Brain Res I 974;74: 19~l0. btH *k of chemical neurixinatomv. and functional organization ol the
164 . Liedgren SRC , Milne AC, Rubin Vol . 2. Part 1: Classical transmitters .
spinal trigeminal nucleus |Comp
AM , Schwarz DWF. Tomlinsen m the CNS. Ch . 4 . Amsterdam: El - Neurol 1950;92:40 l 413.
RD. Representation of vestibular -
sevier , 1984:123 156. 191 . Olszewski J . Cytoarchitecture of
afferent ** in somatosensory thala - -
178. Moskowitz N, Liu J C. Central pro- the human reticular formation . In :
Delafresnaye |F, ed . Brain mecha -
mic nuclei of the squirrel monkey jections of the spiral ganglion of
( Saimiri 'kinreus ). J Neurophysiol the squirrel monkey . I Comp Neu - nisms and consciousness- Oxford :
1976;39:601-612. -
rol 1972;144:335 344. Blackwell Scientific Publications,
165 Lorente de No R . Die Labyrmthre - 179. Mugnaini E, Walberg F. An experi - 1954;54-80.
flexe auf die Augenmuskeln nach mental electron microscopical 192. Olszewski J , Baxter D. C ytoarchi-
einseitiger Labyrinthextirpation study on the mode of termination tecture of the human brain stem .
nebst einer kurzen Angabe uber of cerebellar corticovestibular fibre Philadelphia : J . B Lippincott , 1954.
den N erven mechanism us der in the cat lateral vestibular nucleus
( Deiters' nucleus ) . Exp Brain Res
193. Osen KK The intrinsic organiza -
vestibularen Augenbewegungen. tion of the cochlear nuclei in the
Vienna: Urban and Schwarzen- -
1967;4:212 236. cat. Acta Otolaryngol (Stockh )
berg, 1928. 180. Mugnaini E , Walberg F, Brodal A . 1969;67:352-359
166 . Lorente de No R . Ausgewahlte Mode of termination of primary 194 . Osen KK Cyhwrchitecture of the
Kapitel aus der vergleichenden vestibular fibres in the lateral cochlear nuclei in the cat .|Comp
Phvsiologie des Labyrinthes: die vestibular nucleus: an experimen - Neurol 1%9;1.36 453-484.
Augenmuskelreflexe beim Kan - tal electron microscopical study in 195. Pammer C , Gores T, Palkovits M.
inchen und ihre Grundlagen the cat. Exp Brain Res 1967; Peptidergic innervation of the
-
Ergebn Physiol 1931;32:73 242. 4: 187-211. locus coeruleus cells in the human
181 Mugnaini E, Walberg F, Mauglie- brain Brain Res 1990 15 247 255
167. Lorente de No R . Anatomy of the
eighth nerve: the central projection
of the nerve endings of the internal
Hanssen E. Observations on the
fine structure of the lateral vestibu -
^
19f » . Papez JW. Subdivisions of the fa -
cial nucleus. | Comp Neurol 1927;
ear. Laryngoscope 1933;43:1-38. lar nucleus ( Deiters' Nucleus ) in 43:159- 191.
168. Luk GD, Morest DK , McKenna the cat. Exp Brain Res 1967; 197 Papez JW, Rundics W . The dorsal
NM . Origins of the cri>ssed olivo- 4:146-186. trigeminal tract and the centre me -
cochlear bundle shown by an acid 182. Nakai Y , Takaori S. Influence of dian nucleus ol Luys. J Nerv Ment
phosphatase method in the cat. norepi neph ri ne-con ta ini ng neu - Dis 1937;85:509 519
Ann Otol Rhinol Larvngol 1974 ; rons derived from the locus 198 Parent A, De Bellefeuille L. Organi -
83:382-391. coeruleus on lateral geniculate zation of efferent projections from
169 McBride RL, Sutin |. Projections of neuronal activities of cats. Brain the internal segment of the globus
the locus coeruleus and adjacent Res 1974;71 :47-60. pallidus in primate as revealed by
pontine tegmentum in the cat J 183. Nauta Wjl I . Kuypers HCJM. Some fluorescence retrograde labeling
-
Comp Neurol 1976;165:265 284. ascending pathways in the brain method Brain Res 1982;245
170 McMasters RE, Weiss Al I , Carpen - stem reticular formation . In : Jasper 201-213.
ter MB. Vestibular projections to MIL Proctor LP, Knighton RS, et 199 Parent A, Descarries L, Beaudet A .
the nuclei of the extraocular mus- al . , eds. Reticular formation of the Organization ol ascending sero -
cles: degeneration resulting from brain . Henry Ford lh >spital Inter - tonin systems in the adult rat
discrete partial lesions of the national Symposium . Ch. 1 . Boston : brain A radioautographic study
vestibular nuclei in the monkey. Little, Brown and Company , 1958 after intraventricular administra -
Am|Anat 1966; 118:164-194 3 -
tion of pll| 5 hydroxytryptamine
171 Maciewicz R|, Eagen K. Kaneko 184 . Nauta WIN , Mehler WR . Projec - Neuroscience 1981 ,6:115-138.
CRS, Highstein SM. Vestibular and tions of the lentiform nucleus in 200. Paxinos G, Fork I . Halliday G,
medullary brain stem afferents to .
the monkey Brain Res 1966;1: Mehler WR . Human homologs to
the abducens nucleus in the cat. 3-42. brainstem nuclei identified in other
Brain Res 1977;123:229-240 185. Nicholas AP, Pieribone VA , animals as revealed by acetyl -
172. Maeda T, Shimuzu V Projections Arvidsson U , Hbkfelt T. Serotonin , cholinesterase activity . In : Paxinos
ascendantes du locus coeruleus et substance P- and glutamate / aspar - .G ed . The human nervous system.
d 'autres neurones aminergiques tate-like immunoreactivities in Ch . 7. New York Academic Press,
pontiques au niveau du pros- medullo-spinal pathways of rat 1990,149- 302.
201 Pearson AA The development and 216 Powell TI*S, Krulkar SD. Transneu - which may be relevant to localiza -
conncctions of the mesencephalic ronal cell degeneration in the audi - tion of a sound source. J Neurtv-
root ol the trigeminal nerve in tory relay nuclei of the cat I Anal physiol 1066;20:288-314.
man .|Comp Neurol 1040;00: 1 16- |062;06 240 268 , 220. Russell GV . The dorsal trigemino -
202 Pearson AA Further observations 217 Ramon y Cajal S. Histologic du thalamic tract in the cat: reconsid -
on the mesencephalic nn > t of the Systeme Nerveux de 1' Homme et ered as a lateral roticulo- thalamic
trigeminal nerve. | Comp Neurol des Vertebres. ( Azoulay L, Trans. ) system of connections. ) Comp
1040;01 :147- 104 . Paris: Maloine,1000, 1011 Neurol 1054;101:237-264.
203. Pearson j , I lallidav G , Sakamoto ( Reprinted ,Conscjo Superior de 230. Russell GV. The nucleus locus
N, Michel IP. Catecholaminergic Investigaciones Cientificas, Insti - coeruleus ( dorsolateralis teg-
Neurons. In : Paxinos G , ed . The tuto Ramon v Cajal . Madrid , 1072. ) menti ) . Tex Rep Biol Med 1035;13:
human nervous system . Ch . 31 218. Rasmussen GL. The olivary pe- 030 -088.
New York : Academic Priss, duncle and other fiber projections 231 Sakai K Physiological properties
1000.1023-1040. of the superior olivary complex . | and afferent connections of the
204 . IVntield VV , Evans |. Functional de- Comp Neurol|046;84 : 141 -210. locus coeruleus and adjacent
fects produced by cerebral lobec - 210 Rasmussen GL. Further observa - tegmental neurons involved in the
tonnes PrtK ASMK Res Nerv Ment tions of the efferent cochlear bun - generation of paradoxical sleep in
Dis 1034 , 13 352 - 377 dle |Comp Neurol 1053;00:61-74 the cat . Prog Brain Res 1091;
203 IVntield VV . McNaughton I Dural
headache and innervation of the
22tV Rasmussen GL . Efferent fibers of
the cixhlear nerve and cochlear
-
88: 31 15.
232. Sasa M , Takaori S. Influence of the
dura mater . Arch Neurol Psychia - nucleus In Rasmussen GL, Win - UKUS coeruleus on transmission in
try 1040;44 : 43-75. dle WE, eds. Neural mechanisms the spinal trigeminal nucleus neu -
206. Pert CB, Kuhar MJf Snyder SH . of the auditory and vestibular sys- -
rons Brain Res 1073;55:203 208
Autoradiographic IcKalization ot .
tems Ch, 8 Springfield, II 233. Shan /er S, Wagman III , Bender
the opiate receptor in rat brain Charles C. Thomas, 1060:105-115 MB. Further observations on the
Life S i 1075; 16:1840- 1854 . 221 Rasmussen GL . Anatomic relation - median longitudinal fasciculus
207. Petrov T . Ihamandas I I I . Krukoff ships of the ascending and de- Trans Am Neurol Assoc 1050;
Tl . Characterization of peptidergic scending auditory systems. In : 84 : 14-17.
efferents from the lateral Field VVS, Alford BR , eds Neuro - 234 Sheard Mil. The effect of PCPA in
parabrachial nucleus to identified logical aspects of auditory and behavior in rats : relation to brain
neurons in the rat dorsal raphe nu -
cleus . | C hem Neuroanat 10U 2;
vestibular disorders Ch . I Spring -
held , II t haries t ihomos,
-
serotonin and 5 hydroxyindole
acctic acid . Brain Res 1060;15;
-
5: 367 373. 1064 : 1 14 . 524 - 528.
208 Pfaffmann C . Afferent impulses 222. Rhoton AL, O’ Leary JL, Ferguson 235 Shima / u 11 , Precht W . Inhibition of
from the tooth resulting from a vi - |P. The trigeminal , facial, vagal central vestibular neurons from the
bratory stimulus. | Physiol ( l .ond ) and glossopharyngeal nerves in contralateral labyrinth and its me-
1030,-07:220- 232. the monkey. Arch Neurol diating pathway . J Neurophvsiol
200. Picket VM , Segal M . Bloom I E . A 1066;14:530-540. -
1066;20:467 402.
radioautographic study of the ef - -
223 Rivera Dominguez M , Agate l||r, 2.36 Siegborn I , Grant G Brain stem
ferent pathways of the nucleus Noback CR . Scanning electron mi - projections ol different branches of
locus coeruleus ) Comp Neurol crocopy of the spiral organ of the vestibular nerve. An experi -
1074 ; 155:15-42 Corti of the adult rhesus monkey. mental study by transganglionic
. -
210. Pieribone VA Aston Jones G . Brain Res 1073.65 150- 164 transport of horseradish peroxi -
Adrenergic innervation of the rat 224 Rose |l Organization of frequency dase in the cat I The horizontal
nucleus locus coeruleus arises pre- sensitive neurons in the ctnhlear ampullar and utricular nerves.
dominantly from the Cl adrener - complex of the cat . In : Rasmussen Arch Ital Biol 1083;121:237-248
gic cell group in the rostral GL, Windle WF, eds. Neural mech - 237 SfiKjvist O. Studies on pain con -
medulla Neuroscience 1001 ;41: anisms of the auditory and duction in the trigeminal nerve: a
525- 542. vestibular systems. Ch. 0. Spring- contribution to surgical treatment
211 I’ioro I P, Mai |K , Cuello AC . Dis - field , II.: Charles C. Thomas, ot facial pain . Acta Psychiat Neurol
tribution of substance P- and 1060 116- 136 Scand 1038; l 7(Suppl ): I - 130.
- .
enkephalin immunoreactive neu - 225. Rose |E Galambos R , Hughes |R 238 Stuka KA , Westlund KN . Spinal
rons and fibers In : Paxinos G , ed Microclectrode studies of the projections ot the UKUS coeruleus
The human nervous system . Ch. ciKhlear nuclei of the cat Bull and the nucleus subciKruleus in
32 . New York: Academic Press, Johns Hopkins Hosp 1050;104: the Harlan and the Sasco Sprague-
|000;|05 M 004 . :n 23 i . Dawley rat . Brain Res 1002;
212 Poitras I ), Parent A . Atlas of the 226. Roc* |F, Galambos R , Hughes |R 570:67-73.
distribution of monoamine-con - Organization of frequency sensi - 230 Smith CA . Innervation of the organ
taining nerve cell bodies in the tive neurons in the cochlear com - of Corti. In : lurato S, ed . Subnucro-
brain stem ot the cat I Comp Neu - plex ot the cat In : Rasmussen GL, scopic structure of the inner ear .
rol 1078; 170:600-718. Windle WF. eds. Neural mecha - Oxford : Pergamon , 1067: 107- 131
213. Pompeiano O, Brodal A . The origin nisms of the auditory and vestibu - 240 Smith CA, Rasmussen GL. Recent
of the vestibulospinal fibres in the lar systems. Chap. 10. Springfield , -
observations on the olivo cochlear
-
cat : an experimental anatomical II.: Charles C. Thomas, 1060; bundle. Ann Otol Rhinol Larvngol
study, with comments on the de - 116-136. |063;72:480 507.
.
scending medial longitudinal faci - 227 Rose JE Greenwood DB, Golberg 241 Smith CA , Rasmussen GL. Degen -
cuius. Arch Ital Biol 1057;03 JM. Hind IE . Some discharge char - eration in the efferent nerve end -
166- 105. acteristics of single neurons in the ings in the ciKhlea after axonal sot -
214 Pompeiano O, Walberg F De
scending connections to the
- inferior colliculus of the cat . I .
Tonotopical organization , relation 242 Smyth GF The systemization and
-
lion . ) Cell Biol 1065;26:63 77.
vestibular nuclei: an experimental

studv in the cat . I Comp Neurol
-
of spike counts to tone intensity ,
and firing patterns ot single ele -
central connections of the spinal
tract and nucleus of the trigeminal
1957;108 165 302 ments. ) Neurophvsiol I 063;26: nerve. Brain 1030 ,62 : 41-78.
215. Powell TI *S, Cowan WM . An ex -203 320. - . 243 Spencer Rl , Sterling P An electron
perimental study of the projection 228 Rose IE, C ross NB, Geisler IK , microscopic study of motonou -
ol the anhlea I Anat |062;06 I Imd IF.. Some neural mechanisms rones and interneurones in the cat
260 284 in the inferior colliculus ot the cat abducens nucleus identified bv ret -
13 Pons 525
rograde intraaxonal transport of 259. Strominger NL, Nelson I R , Trigeminus. Jahrb Psychiat Neurol
horseradish peroxidase. | C omp Doughterty VVJ . Second order au - -
1911;32:107 148.
Neurol 1977; 176:65-86. ditory pathways in the chim - 275. Voss II Zahl und Anordnung der
244 Spiegel EA Experimentalstudien panzee. | Comp Neurol 1977; Muskelspindeln in den oberen
am Nervensvstem: XV. l \* r Mech - 172.449- 466. Zungenbeinmuskeln, im M.
anism us des labyrintharen Nystag - 260. Strominger NL, Strominger Al. As - trapezius und M latissimus dorsi .
mus Z I lals- Nasen -Ohrenheilk cending brain stem projections ol Anat Anz 1956; 10.4:443-446
245.
-
1929;25:200 217.
Spiegel FA , Sommer I Neurology
the anteroventral cochlear nucleus
in the rhesus monkey. J Comp
-
276. Vraa - jensen Cl Mu* motor nu -
cleus of the facial nerve, with a sur -
of the eye, ear, nose and throat . Neurol 1971;143: 217-242. vey of the efferent innervation of
New York: Grime & Stratton , 261 . S/entagothai J . The elementary the facial muscles [Thesisl Copen -
1944.667. -
vestibulo ocular reflex arc J Neu * hagen : Ejnar Munksgaard , 1942
246 Spiller WG . Ophthalmoplegia in - rophysiol 1950;13:395 407. - 277. Walberg F. IX > the motor nuclei of
ternuclearis anterior: a ease with 262. Taber F, Brodal A, Walberg F The the cranial nerves receive corti-
necropsy. Brain 1924, 47:545 457 raphe nuclei of the brain stem in cofugal fibres * An experimental
247. Spoendlin I I I I . The organization ol the cat . I Normal topography and study in the cal . Brain 1957,
the cochlear receptor. Adv Otorhi - cvtoarchitecture and general dis- 80:597-605.
nolarvngol 1966; 1.4:1 -227. cussion . J Comp Neurol I 960; 278. Walberg F, Bowsher D, Brodal A
248. Spoendlin Mil The innervation of 114: 161- 187. The termination of primary
the cochlear receptor In : Moller 264. Tasaki I . Nerve impulses in indi - vestibular fibers in the vestibular
AR , ed . Basic mechanisms in hear - vidual auditory nerve fibers of nuclei in the cal an experimental
ing. New York: Academic Press . guinea pig | Neurophvsiol 1954 ; study w i t h silver methods |Comp
197.4;185-234 . 17:97-122. Neurol 1958;110:391 419
249. Spoendlin HH , Gacek RR . Electron 264 . Terayama Y , Yamamoto K Olivo- 279. Walberg F, Jansen I (. erebellar cor -
microscopic study of the efferent cochlear bundle in the guinea pig ticovestibular libers in the cal Exp
and afferent innervation of the cochlear after central transection ot Neurol I 46l ;3:32 52 .
organ of C orti in the cat . Ann Otol
'
the crossed bundle: Electron mi - 280. Walberg F, Pompeiano O, Brodal
Rhinol l .arvngol 1963;72:660-686. croscopic study on origin and dis- .
A Jansen J . The fastigiovestibular
250. Steiger ll - J , Biittner- Fnnever I Re- tribution of unmyelinated efferent projection in the cat an experimen -
lationship between motoneurons fibers by axonal degeneration . Acta tal study with silver impregnation
and intemuclear neurons in theab- Otolaryngol (Stockh ) 1971:72: methods J Comp Neurol 1962 ;
ducens nucleus: a double retro- -
385 396. 118:49-75.
grade tracer study in the cat. Brain 265. Thomas DM , Kaufman RP, 281 . Walker AF. The origin , course and
Res 1978;148: 181 - 188. Sprague JM , Chambers VVW . Ex - terminations of the secondary
251 . Steiger H I . Buttner - Fnnever JA perimental studies of the vermal pathways of the trigeminal nerve
Oculomotor nucleus afferents in cerebellar projections in the brain in primates. | Comp Neurol
the monkey demonstrated with stem of the cat ( fastigiobulbar -
1939;71 :59 89.
horseradish peroxidase. Brain Res -
tract ).| Anat 1956,90:371 -385. 282 . Walker AH Anatomy , physiology
1979;160:1 - 15. 266. Torvik A , Afferent connections to and surgical considerations of the
252 . Stein BM, Carpenter MB. Central the sensory trigeminal nuclei , the spinal tract of the trigeminal nerve
projections ot portions of the nucleus of the solitary tract and ad - J Neurophysiol I939;2t234 248
vestibular ganglia innervating spe- jacent structures: an experimental 283. Walker AF . Somatotopii localiza -
cific part of the labyrinth in the studv in the rat . J Comp Neurol tion of spinothalamic and sec -
rhesus monkey. Am ) Anat -
1956;106:51 142. ondary trigeminal tracts in mesen -
1967:120:281 418. 267. Torvik A The ascending fibers cephalon . Arch Neurol Psychiatry
253. Steinbusch HWM. Distribution of from the main trigeminal sensory 1942;48:884-889
serotonin - immunoreactivity in the nucleus: an experimental study 284 . Wall PD, Taub A Four aspects of
central nervous system of the rat — in the cat . Am J Anat 1957;100: the trigeminal nucleus and a para -
cell bodies and terminals. Neuro- 1-15. dox . J Neurophysiol 1962;25:
science 1981;6:577-618. 268. Truex RC. Morphological alter - 110-126.
254 Steinbusch HWM , Nieuwenhuys ations in the Gasserian ganglion 285. Wallenberg A Die second a ren
R. The raphe nuclei of the rat cells and their association with Bahnen aus dem trontalen sensi -
brainstem: a cytoarchitectonic and
immunohistochemical study. In
senescence in man. Am | Pathol
1940; 16: 255-268.
ble!? Trigeminus Kerne des Kan
inchens . Anat Anz
-
I 905;26:
'
.
Emson IX ed . Chemical neu - 269. Uemura T, Cohen B. Effects of 145- 155
roanatomy . New York : Raven vestibular nuclei lesions on 286. Warr VVB. Fiber degeneration fol -
Press, 1983131 207. vestibulo-ocular reflexes and pos- lowing lesions in the anterior ven -
255. Stotler VVA An experimental study ture in monkeys. Acta Otolaryngol tral cochlear nucleus of the cat . Exp
of the cells and connections of the (Stockh ) 1973;315: 1-71. Neurol 1906;14 : 453-474
superior olivary complex of tin
cat . J Comp Neurol |954;98:
- 270. Ungerstodt U . Stereotaxic mapping
of the monoamine pathways in the
287. Warr WB. Fiber degeneration fol -
lowing lesions m the posteroven-
256.
-
401 423.
Strominger Nl The origins, course
rat brain . Acta Phvsiol Scand
-
1971;367(Su ppl ):1 48.
tral cochlear nucleus of the cat. F.xp
Neurol 1969;23:140- 155.
and distribution of the dorsal and 271 . Verhaart WJC. The tractus trigemi - 288. Warr WB. Olivocochlear and
intermediate acoustic striae in the nalis of Wallenberg. Acta Psychiat vestibular efferent neurons of the
-^
Rhesus monkey . I Comp Neurol Neurol Scand 1954 90 269 279 feline brain stem : their location ,
1973;147:209 234 272. Vertes RP A PHA L analysis of as - morphology and number deter -
257. Strominger NL The anatomical or - cending projections of the dorsal mined by retrograde axonal trails
ganization of the primate auditory raphe nucleus in the rat . | Comp port and acetylcholinesterase his -
pathways. In : Noback CR , ed . Sen - -
Neurol 1991;313:643 668. tochemistry . | C o m p Neurol
273. Von Bekesy G . Experiments in
sory systems of primates New
York: Plenum Publishing Co.,
1978;53-9|.
hearing. New York: McGraw Hill,
1960.
- .
1975; 161 : 159-182
289. Webster WR , C arey LJ . Auditory
system In : Paxinos G, ed . The
258 Strominger NL, Hunvitz JL. 274. Von Economo CF. L' ber disso/ i - human nervous system Ch 27
Anatomical aspects of the superior ierte Fmphindungslahmung bei New York Academic Press,
Ponstumoren und iiber die zen -
olivary complex . | Comp Neurol
1976;170:485-498. tralen Bahnen des sensiblen
1990:889 944
.
290. Weinberger I M , ( rant FC . Experi -
cnees wilh intramedullary tractot - rons bv the medial vestibular nu - ders. Proc Natl Acad Sci USA
omy 111. Studies in sensation. Arch cleus. Exp Brain Res 1 %9;9: 1954;40:228-231 .
-
Neurol Psychiatry 1942;48:355 381. 365-380 . 301. Wool lard HH , Harpman JA . The
291 . White IS, Warr WB. The dual ori - 29n. Windle WF. Non - bifurcating nerve -
connections of the inferior collicu
gins of the olivocochlear bundle in fibers of the trigeminal nerve. J lus and dorsal nucleus of the lat -
the albino rat . ) Comp Neurol Comp Neurol 1926;40:229-240. eral lemniscus. J Anat 1940;
1983;219:203- 214 297. Winkler C . Opera omnia . Vols 74:441 -458.
292. Wiklund L, Leger L, Persson VI . 1 -10. Haarlem, The Netherlands 302. Wurtman RJ . Brain monoamines
Monoamine cell distribution in the . -
E.F. Bohn 1918 1933. and endocrine function. Neurosci
cat brain stem . A fluorescence his- 298. Woodburne RT. A phylogenetic Res Program Bull 1971;9: 177- 297.
tochemical study with quantifica - consideration of the primary and 303. Zimmerman EA , Chambers WW,
tion of indolaminergic and locus secondary centers and connections Liu CN . An experimental study of
coeruleus cell groups. J Comp of the trigeminal complex in a se- the anatomical organization of the
-.
Neurol 1981;203:613 647.
293. Willis WI), Haber LH Martin RF
ries of vertebrates. J Comp Neurol
1936;65: 403-501.
cortico-bulbar system in the albino
rat. I Comp Neurol I 964; I 23:
Inhibition of spinothalamic tract 299. Woodward D) , Moises HC, Water - 301-324.
cells and interneurons by brain - house BD, Yeh HH, Cheun ) E The 304 Zhuo H , Fung SJ , Reddy VK ,
stem stimulation in the monkey. ) cerebellar norepinephrine system: Barnes CD. Immunohistochemical
Neurophysiol 1977;40:988-981 inhibition , modulation , and gat - evidence tor coexistence of methio-
294 . Wilson V ) , Mclvill Jones Ci . Mam - ing. Prog Brain Res 1991;88: nine-enkephalin and tyrosine hy -
malian vestibular physiology. New 331-341 droxylase in neurons of the locus
York . Plenum Press, 1979 34 X4. Woolev DW, Shaw E . A biochemi - coeruleus complex projecting to
295. Wilson V|. Yoshida M Monosy
naptic inhibition of neck motoneu -
- cal and pharmacological sugges -
tion about certain mental disor -
the spinal cord of the cat . J Chem
Neuroanat 1992;5:1 -10.
14
Midbrain
Tin* midbrain, or mesencephalon, is the part of the pons become smaller and at more
smallest and least differentiated division of rostral levels undergoes a reorganization as
the brainstem. Like other parts of the brain - the massive crura cerebri appear ( Figs. 14.3
stem , the midbrain can be divided into three and 14.6 ). In some sections, portions of the
parts: (a ) a dorsal part , the tcdum or heavily pigmented substantia nigra are evi -
quadrigeminal plate , lying dorsal to the cere- dent dorsal to the most rostral pontine nuclei.
bral aqueduct, ( b) a central part, the tegmen- Fibers of the lateral lemniscus, located near
tum , representing the rostral continuation of the lateral surface of the tegmentum, migrate
the pontine tegmentum, and (c) a ventral dorsally and enter the inferior colliculus.
part , the massive crura cerebri or cerebral pe - These fibers envelop the inferior colliculus
duncles , containing descending cortical pro- and form its capsule ( Figs. 14.2 and 14.3).
jections. The cerebral aqueduct, surrounded
by the central gray substance ( i.e., periaque- Inferior Colliculi
ductal gray ), separates the tectum from the
tegmentum ( Fig. 14.1 ), whereas the substan - These paired ovoid cell masses of the cau -
tia nigra , a darkly pigmented nucleus, sepa - dal tectum can be divided into three parts: ( a )
rates the midbrain tegmentum from the crus an ovoid cell mass called the central nucleus,
cerebri ( Figs. 14.1 , A .10, and A .27 in the Atlas ( b) a thin dorsal cellular layer, the pericentral
of the Human Brain, Section VII ). Two cranial nucleus, referred to as the cortex, and (c ) an
nerve nuclei, the trochlear and the oculomo- external nucleus that surrounds the central
tor, lie near the midline, ventral to the peri- nucleus laterally and ventrally ( 126, 188, 269,
aqueductal gray. The midbrain contains im- 288, 342, 343).
portant relay nuclei of the auditory and The central nucleus of the inferior colliculus
visual systems, along with pathways interre- appears fairly homogeneous in Nissl and
lating higher and lower portions of the neu - myelin stained preparations. In Golgi prepa -
raxis. The principal nuclear masses and fiber rations, it can be subdivided into a smaller
pathways of the midbrain are described as dorsomedial division composed of large cells
they appear at caudal or inferior collicular and a large ventrolateral division of medium
level and at rostral or superior collicular and small cells with a laminar arrangement
level. ( Fig. 14.4). In the ventrolateral division of the
central nucleus, laminae form an overlapping
CAUDAL MIDBRAIN onion -like series of concentric shells, most of
which are incomplete except for those closest
The transition from the isthmus to the to the center of curvature. The thickness of
midbrain is associated with changes mainly the laminae is determined by the dendritic
in the tectum and tegmentum ( Figs. 13.32, ramifications of fusiform and bitufted cells
13.33, 14.2, 14.3, A .9, and A .10). The major that represent the principal cell types in these
changes that characterize this transition can layers ( 269, 288). These laminae provide the
be summarized as follows: (a ) the rostral basis for the tonotopic organization of neu -
fourth ventricle narrows and becomes the rons in the central nucleus. Each of these lam -
cerebral aqueduct, ( b ) the superior medullary inae correspond to an isofrequency contour.
velum is replaced by two rounded emi- Multipolar and large neurons have dendrites
nences, the inferior colliculi, (c) fibers of the which cross one or more laminae and may
superior cerebellar peduncles move ventro- form the basis for interactions between lami -
medially and begin to decussate, and (d ) the nae ( 258, 348). A large proportion of neurons
tegmentum is reduced in size. The ventral in the central nucleus are GABAergic ( 339 ).
527
Superior colliculus
Central gray
Cerebral aqueduct
Tegmentum
Brachium inf colliculus
Medial lemniscus
Red nucleus
Lateral pes lemniscus
TemporoN
Parieto Pontine
Occipito f ibers
Corticospinal tract
Corticobulbar fibers
cerebri
Substantia nigra Frontopontine fibers
Medial pes lemniscus
Figure 14.1 Transverse section through the rostral midbrain MLF. medial longitudinal fasciculus
Commissure of the
Cerebral aqueduct inferior colliculus
Inferior colliculus
Central gray ^
N .IV
Parabigeminal area
MLF ^ , Lateral lemniscus
Superior cerebellar i Central tegmental
peduncle tract
Medial lemniscus
Decussation
sup . cerebellar
peduncle
Transverse
pontine
fibers
Pontine nuclei :
Lateral
Medial
Figure 14.2 transverse section of the adult midbrain through the inferior colliculus Large fascicles of corticospinal
and corticopontine fibers (unlabeled), cut in cross-section, are located among the bundles of transverse pontine
fibers (Weigert ' s myelin stain )
14 Midbrain 529
Inferior colliculus Mesencephalic

nucleus of N Y
Pedunculopontme
tegmental nucleus L o c u s ceruleus
Mesencephalic Dorsal tegmental

reticular nucleus
formation
Trochlear nucleus
inter peduncular
nucleus
F o r a m e n cecum
Substantia anterior
nigra
Pontine nuclei
Figure 14.3 Transverse section through inferior colliculi of the midbrain in a 3-month infant (Cresyl violet stain with
schematic representation of main cell groups )
Superior colliculus
Pericentral nucleus
Central nucleus
External
nucleus
Inferior
colliculus
i
|
- Lateral
lemniscus
Cerebral aqueduct Central
gray
A B
Transverse
Superior colliculus
Pericentral
nucleus
Central
nucleus
Inferior colliculus
External
nucleus 1
Superior cerebellar
Nucleus of \
lateral lemniscusV • —
JL
\
- Lateral
lemniscus
peduncle
D
Sagittal
Figure 14.4 Transverse ( A and B) and sagittal (C and D) sections through the inferior colliculus outlining the nuclear
.
subdivisions The pericentral nucleus is indicated in red and the external nucleus in blue The central nucleus in white
shows contours of the laminae in the ventrolateral division. Black dashes indicate the division of the central nucleus
into the large-celled dorsomedial part and the ventrolateral laminated part . Laminae In the central nucleus repre-
sent a given frequency band across the width of the nucleus and form the basis for the tonotopic organization of
neurons The disc -shaped laminae in dorsal regions are not as thick and represent the lower frequencies High- fre -
quency octaves are represented ventrally .
The pericentral nucleus is a thin sheet of the central nucleus, which course parallel to
densely packed cells extending over the dor- its laminae.
sal and posterior surfaces of the inferior col- Most cells of the inferior colliculus re-
liculus ( Fig. 14.4 ). This nucleus overlies both spond to binaural stimulation, and many
major divisions of the central nucleus, and its cells encode information about sound local -
lateral border is continuous with the external ization with specific spatiotemporal dis-
nucleus (343). Although the pericentral nu
cleus has been described as having a layered
- charge patterns. A definite tonotopic localiza -
tion is present within the central and
"cortical" structure, Golgi studies suggest pericentral nuclei of the inferior colliculus (5,
only a predominance of certain cell types at 258, 345). Neurons in the central nucleus of
different depths of the nucleus. This nucleus the inferior colliculus are arranged in a lami-
is composed of spiny and aspiny cells. Small nar pattern that represents different fre-
spiny neurons are found at all depths in the quency bands. Isofrequency contours parallel
pericentral nucleus, while large spiny neu- the cellular laminae, which are tilted ven -
rons, overlying the large-celled division of trallv, laterally, and down rostrally. Most
the central nucleus, project axons into it . units respond to binaural stimuli . Advance-
Large aspiny neurons are fusiform or multi- ment of an electrode from dorsal to ventral in
polar; dendrites of multipolar neurons extend the inferior colliculus consistently gives a se-
throughout the depth of the pericentral nu - quence of frequencies from low to high in the
cleus, and their axons project toward the -
central nucleus. The disc shaped laminae rep-
brachium of the inferior colliculus. The resenting the lowest frequencies ( i.e., dorsal
largest cells are in deepest parts of the nu - regions ) are not as thick or as extensive as
cleus. those representing middle and high frequen -
The external nucleus is composed of cells of cies ( i .e., ventral region ). The frequency rep-
various sizes, similar to those found in the resentation in the central nucleus reflects the
central nucleus but less densely packed ( 342 ). proportional representation of frequencies
This nucleus appears almost continuous with along the cochlear partition, in which low fre-
the pericentral nucleus but is traversed by quencies are perceived at the apex of the
fibers of the lateral lemniscus and the cochlea and high frequencies at the base. The
brachium of the inferior colliculus ( Fig. 14.4 ). central nucleus of the inferior colliculus is a
Physiologic studies indicate that the external tightly organized structure bearing specific
nucleus is not an auditory relay nucleus like relationships to the cochlea with elements
the central nucleus, but a nucleus related pri- sharply tuned to different frequencies. Small
marily to acousticomotor reflexes ( 4, 5). sections of the basilar membrane of approxi-
The inferior colliculus is the major brain- mately equal lengths are represented across
stem auditory relay, transmitting impulses individual anatomically defined cellular lam-
from the lateral lemniscus to the medial inae within the nucleus ( 258). This tonotopic
geniculate body, which in turn projects to the organization, which has been confirmed with
primary auditory cortex . Ascending auditory anatomic, electrophysiologic, and metabolic
fibers in the lateral lemniscus project to both -
( 2 deoxyglucose) methods ( 417, 418), applies
dorsomedial and ventrolateral divisions of only to the ventrolateral division of the cen -
the central nucleus of the inferior colliculus. tral nucleus.
Fibers entering the ventromedial division of The pericentral nucleus demonstrates
the inferior colliculus course along the length some evidence of a tonotopic organization in
of each laminae following its curvature. As which high frequencies are located externally
fibers traverse these laminae they establish and low frequencies are found near the mar-
synaptic contact with collicular neurons. The gins of the central nucleus (5). This nucleus
dorsomedial division of the central nucleus contains units with broad tuning characteris-
receives commissural connections from the tics, the majority of which receive only a con-
corresponding region of the opposite inferior tralateral monaural input. Axons of neurons
colliculus and bilateral projections from the in the pericentral nucleus project to areas
auditory cortex . The pericentral nucleus also around the ventral division of the medial
receives bilateral inputs from the auditory geniculate body, which in turn project to non-
cortex and ascending projections from the primarv auditory cortex (370). The overall be-
dorsal nucleus of the lateral lemniscus. Cells havior of units in the pericentral nucleus and
of the pericentral nucleus project fibers into their monaural input suggest that cells in this
14 Midbrain 531
nucleus may serve to direct auditory atten - with the superior colliculus in processing vi -
tion . The external nucleus probably is not an sual information .
auditory relay nucleus like the central nu -
cleus of the inferior colliculus; this nucleus is Trochlear Nerve
related primarily to acousticomotor reflexes
( 4, 417). The nucleus of the trochlear nerve ( N. IV )
Efferent fibers from the ventromedial di- is a small compact cell group at the ventral
vision of the central nucleus of the inferior border of the periaqueductal gray, which rep-
colliculus project via the brachium of the in - resents a small caudal appendage to the ocu -
ferior colliculus to the ventral laminated lomotor complex indenting the dorsal surface
part of the medial geniculate body ( 188, 219, of the medial longitudinal fasciculus ( Figs.
267, 322, 342, 417). Cells in the dorsal divi - 14.3 and 14.5). Root fibers emerging from the
sion of the central nucleus and in the peri - nucleus curve dorsolaterally and caudally
central nucleus send fibers to the dorsal part near the margin of the periaqueductal gray ,
of the medial geniculate body. Thus, the decussate completely in the superior
dorsal division of the central nucleus and medullary velum, and exit from the dorsal
the pericentral nucleus of the inferior col - surface of the brainstem caudal to the inferior
liculus, which receive fibers from the audi- colliculus ( Figs. 2.25, 2.26, 12.2, 13.32, 14.2,
tory cortex but not from the lateral lemnis - 14.3, and A.9). Peripherally the slender nerve
cus, ultimately send impulses back to the root curves around the lateral surface of the
secondary auditory cortex via the dorsal brainstem, passes between the superior cere-
part of the medial geniculate body ( 219 ). bellar and posterior cerebral arteries, as do
Cells of the ventral part of the medial genic - the fibers of the oculomotor nerve, and enters
ulate body project tonotopically upon the the cavernous sinus ( Fig. 4.11 ) . This cranial
primary auditory cortex ( 51, 206 ). nerve innervates the superior oblique muscle
that serves to intort the eye when abducted ,
Parabigeminal Area and depress the eye when adducted (see
Table 14.1 ). Lesions involving the trochlear
Ventrolateral to the inferior colliculus and nerve alone are unusual, and detection of re-
lateral to the lateral lemniscus is a fairly well- sulting disturbances of extraocular move-
defined zone known as the parabigeminal area ment by inspection is difficult . Diplopia re-
( Fig. 14.2). It is composed mainly of sulting from such a nerve lesion is vertical
obliquely, or transversely, running fibers, and maximal on attempted downward gaze
among which are scattered groups of cells to the opposite side. Patients with trochlear
constituting the parabigeminal nucleus. This nerve lesions complain especially of difficulty
small oval nucleus in the lateral midbrain in walking downstairs. Tilting of the head to
contain cholinergic neurons (group Ch 8 the opposite side, seen in some patients with
( 260) ) and receives a substantial projection trochlear nerve lesions, is a posture which
from the superficial layers of the superior col- compensates for the weakness of ocular intor-
liculus, which has a visuotopic organization tion on the lesion side ( 76 ).
(145, 148, 362 ). Cells of each parabigeminal
nucleus project bilaterally upon superficial Tegmental and Interpeduncular Nuclei
layers of the superior colliculi and show a re-
gional organization . Rostral parts of the nu- The periaqueductal gray ( PAG ) surround -
cleus project contralaterally and cells in cau- ing the cerebral aqueduct contains several
dal parts of the nucleus project to the nuclear groups. The mesencephalic nucleus
ipsilateral superior colliculus (97, 150). Cells of the trigeminal nerve and the pigmented
of the parabigeminal nucleus respond briskly cells of the locus coeruleus occupy lateral re-
and consistently to visual stimuli , can be acti- gions at isthmus levels (see Chapter 13). The
vated by both moving and stationary light raphe region contains the dorsal nucleus of the
spots, and have receptive fields similar to raphe or dorsal raphe nucleus , which is greatly
those of the superficial layers of the superior expanded at caudal midbrain levels. The dor-
colliculus ( 362 ). The parabigeminal nucleus sal raphe nucleus is flanked laterally by the
has a representation of the entire contralat- dorsal tegmental nucleus ( of Gudden ) ( Figs.
eral visual field and at least the central part of 12.28, 13.33, and 14.3). This dorsal raphe nu -
the ipsilateral field . This nucleus functions cleus, composed mainly of small cells dorso-
Commissure of inferior colliculus
nferior colliculus
Central entral nucleus

gray -
/ Brachium of
inferior colliculus
Cerebral
aqueduct —
Central tegmental
Trochlear
tract
nucleus v
Dorsal
nucleus
of raphe <
Medial
» / lemniscus
-Crus
cerebri
Substantia
lecussation superior cerebellar peduncle
Figure 14 5 Right dorsal quadrant from a transverse section through the rostral part of the inferior colliculus
(Welgert ' s myelin stain.)
Table 14.1. Origin of Root Fibers to Extraocular Muscles
C RANIAL NERVE MUST IFSUTI IED COURSE OF FIBERS ACTION OF MUSCLE
Oculomotor ( III! Medial rectus Uncrossed Adduct eye

Interior rectus
Inferior oblique
Uncrossed
Uncrossed
-
IX prcss eye when eye is abducted
Elevate eye when eye is adducted
Superior rectus Crossed Elevate eye when eye is abducted
Levator palpobrac Crossed and Raise upper eyelids
uncrossed
Trochlear < IV ) Superior oblique Crossed Depress eye when eye is adducted ;
intort eye when eve is abducted
Ahducens ( VI ) lateral rectus Uncrossed Abduct eye
medial to, and between , the trochlear nuclei, den ). These cells appear as a rostral continua -
has been called the supratrochlear nucleus tion of the superior central nucleus of the pons.
( 241 ). Although the dorsal nucleus of the These nuclei usually are designated together
raphe and the dorsal tegmental nucleus are as the superior central nucleus or the median
adjacent to each other, only cells in the dorsal raphe nucleus . Fibers from both dorsal and
raphe nucleus utilizes serotonin as a neuro- ventral tegmental nuclei ascend to the mam -
transmitter . Ventral to the medial longitudi - millary bodies, the lateral hypothalamic
nal fasciculus and lateral to the raphe are the areas, and the preoptic and septal areas ( 155,
cells of the ventral tegmental nucleus (of Gud - 280 ). These fibers travel in the dorsal longitudi -
14 Midbrain 533
nal fasciculus (of Schiitz ), a small but complex ( 24, 25). The region has been implicated in
pathway in ventromedial PAG, the mammil- central analgesic mechanisms, vocalization ,
lary peduncle , and some continue rostrally in control of reproductive behavior, aggressive
the medial forebrain bundle ( Fig. 17.14 ). behavior, and mechanisms of upward gaze.
As seen in Chapter 13, serotonin-contain- Afferents to the periaqueductal gray arise
ing neurons have been located in pontine and from the hypothalamus, the brainstem retic-
mesencephalic raphe nuclei ( Fig. 13.38). ular formation, the raphe nuclei, the locus
These cell groups have been identified as the coeruleus, and the spinal cord . Many of
dorsal raphe nucleus (group B7), the median these regions receive reciprocal projection
raphe nucleus (superior central nucleus, from the periaqueductal gray . Neurons in
group B8 ), and the lateral cell group ( B9 ) ( 86 ). the periaqueductal gray are immunoreactive
Detailed anatomic and biochemical studies in to enkephalin , substance P, dynorphin,
various species, including nonhuman pri - cholecystokinin, neurotensin, serotonin, and
mates, reveal that cell groups B7 and B8 give somatostatin, and single neurons often con -
rise to two distinct but overlapping ascend - tain several neuropeptides ( 283). The role of
ing serotoninergic systems (16, 38, 39, 132, the periaqueductal gray in brainstem anal -
198, 230, 231, 268, 289, 296, 379, 394 ). Despite gesic mechanisms received considerable at -
several species variations in the organization tention . Ventrolateral regions of the peri-
of ascending serotoninergic systems (16, 198, aqueductal gray appear the most effective
283, 398), there is a consensus regarding the -
sites for stimulation produced analgesia .
respective contributions of the dorsal and Microinjections of morphine in the ventral
median raphe nuclei to the serotoninergic in- periaqueductal gray produce pronounced
nervation of the forebrain . The dorsal raphe analgesia in rodents.
nucleus projects to the periaqueductal gray The interpeduncular nucleus is a collection
and gives rise to fibers that ascend in the me- of medium-sized , multipolar, slightly pig-
dial forebrain bundle and that project to the mented cells, that lie dorsal to the interpe-
substantia nigra, the hypothalamus, the in- duncular fossa ( Fig. 14.3). This nucleus,
tralaminar thalamic nuclei, the lateral genicu - which is prominent in most mammals but
late body, the striatum, the amygdaloid nu - comparatively small in humans, receives
clear complex, and broad regions of the fibers from the habenula via the fasciculus
frontal cortex. The median raphe nucleus retroflexus ( Figs. 16.5 and 17.14 ) . A large pro-
projects fibers to the midbrain reticular for - portion of the habenulo-interpeduncular
mation , the hypothalamus, including the fibers, particularly those terminating in the
mammillary bodies, the septal area , the en - core of the interpeduncular nucleus, derive
torhinal cortex, and the hippocampal forma - from the cholinergic neurons of the medial
tion . The median raphe nucleus and , to a habenular nucleus (group Ch 7 (260)). In ro-
lesser extent , the dorsal raphe nucleus, give dents, the interpeduncular nucleus is subdi -
rise to descending fibers projecting to the vided into multiple subnuclei whose neurons
cerebellum , the locus coeruleus, the reticular display various combinations of small- mole-
formation of the lower brainstem, and the cule neurotransmitters and neuroactive pep-
raphe nuclei of the pons and the medulla tides, including substance P, enkephalin,
( 39 ). The predominant postsynaptic action of cholecystokinin, vasoactive intestinal pep-
serotonin in the forebrain is inhibition, al - tide, and somatostatin ( 163). Fibers of the fas-
though excitation is also frequently seen ciculus retroflexus, bypassing the interpe-
( 198 ). These opposite effects of serotonin on duncular nucleus, are distributed to the
forebrain neurons may be explained by the superior central nucleus, the dorsal tegmental
existence of a wide variety of serotoninergic nucleus, and the periaqueductal gray ( 279 ).
receptors. Three major families of serotonin- The dorsal tegmental nucleus also receives
,
ergic receptors (5- HT , 5- HT2, and 5- HT , ) are fibers from the mammillary bodies via the
now well -characterized , and other receptors mamillotegmental tract and is closely related
are being discovered as a result of extensive to the dorsal longitudinal fasciculus ( Fig.
application of molecular biology techniques 17.16 ). Although the prevailing direction of
to the cloning of new receptor families. conduction in this bundle appears to be as-
The midbrain periaqueductal gray ( PAG ) cending, it contains some descending ele-
consists of dense collection of relatively ments, but few of these reach pontine levels.
small cells surrounding the cerebral aque - These pathways are part of a complex system
duct , which is functionally heterogeneous whereby impulses related to the limbic sys-
tern , concerned primarily with visceral and part of the tectum ( Figs. 14.6-14.8), ( b) the
behavioral functions, are projected to mid - oculomotor nuclei form a V-shaped complex
brain nuclei. ventral to the periaqueductal gray and root
fibers of the oculomotor nerve emerge from
ROSTRAL MIDBRAIN the interpeduncular fossa ( Figs. 14.1, 14.6,
and 14.16), (c) the red nuclei, surrounded by
Transverse sections of the rostral midbrain fibers of tire superior cerebellar peduncle, oc-
appear strikingly different from those cupy the central tegmental region ( Figs. 14.1,
through the inferior colliculus in that (a ) the 14.6, and 14.13), and (d ) the substantia nigrae
flattened superior colliculi form the rostral achieve their maximum size ventral to the
Oculomotor nucleus
\ caudal centrol nucleus Superior colliculus

Nucleus of Darkschewitsch
1 lateral somatic
cell column Brachium of
inferior colliculus
Spinotholomic tract
Centrol tegmental
Medial lemniscus tract
-'Medial long. fasc .
Red nucleus
Strionigrol fibers
Crus cerebri
Ventral tegmental Root fibers

decussation N m Interpeduncular
nucleus
Interpeduncular
fossa
Figure 14.6 Transverse section of odult midbrain through the level of the oculomotor nerve (Weigert s myelin stain.)
Commissure of Stratum zonale

superior colliculus
Stratum cinereum
Stratum opticum
Stratum griseum
mediate
Stratum album mediale

Stratum griseum profundum
Cerebral aqueducl
Stratum album profundum
Central gray
Figure 14.7 Cellular lamination and organization of the superior colliculus based upon Golgi preparations from a
human fetus
14 Midbrain 535
Stratum griseum mediate

Stratum album mediate
Stratum opticum Commissure
Stratum cinereum .
Stratum
.
\r
5 v,
*iV: i
'f .
»y
- r- y
" i
Cerebral
zonale aqueduct
C
-'. V 'V festV^ 1: Central gray
Brachium of \ Stratum griseum profundum

superior colliculus
Stratum album profundum
Figure 14.8 Myelinated fiber structure of the superior colliculus based upon Weigert -stained sections
tegmentum and dorsal to the crura cerebri. and white layers ( Figs. 14.7 and 14.6 ). From
Fibers of the brachium of the inferior collicu - the surface inward these layers are ( a ) the
lus lie on the lateral surface of the tegmentum stratum zonale ( mainly fibrous ), ( b) the stratum
at this level ( Fig. 14.6). The medial lemniscus cinereum (outer gray layer ), (c) the stratum op-
appears as a curved bundle dorsal to the sub- ticum (superficial white layer ), and (d ) the
stantia nigra and lateral to the red nucleus. stratum lemnisci consisting of middle and
Fibers of the spinothalamic and spinotectal deep gray and white layers (stratum griseum
tracts lie together medial to the most dorsal medium, stratum album medium, stratum
part of the medial lemniscus. griseum profundum, and stratum album pro-
fundum ) ( Figs. 14.7 and 14.8 ) . The stratum
Superior Colliculi zonale is composed of fine nerve fibers aris-
ing mainly from the occipital cortex and en-
The superior colliculi are flattened , lami - tering through the brachium of the superior
nated eminences that form the rostral half of colliculus. Among the fibers are small, mostly
the tectum ( Figs. 2.25, 2.26, 14.6, and A . l 1 ). In horizontal cells with tangentially or centrally
nonmammalian vertebrates, the optic tectum , directed axons. The stratum cinereum con -
a structure homologous with the mammalian sists of radially arranged cells whose den -
superior colliculus, has a complex laminated drites pass peripherally and whose axons
organization resembling that of the cerebral project inward . The larger cells lie deepest.
cortex and is the primary termination of the The stratum opticum is composed mainly of
optic tract . Beginning with reptiles, the im- fibers from the ganglion cells of the retina
portance of the superior colliculus in visual and corticotectal fibers arising from the visual
discrimination progressively diminishes as cortex. These fibers enter the stratum opticum
an increasing number of optic fibers establish via the brachium of the superior colliculus
more extensive connections with the thala- and pass into the superficial and middle gray
mus and cortex . In humans, the superior col - layers. Corticotectal fibers from the frontal
liculi have become reduced in size and serve lobe ( Brodmann 's area 8) reach superficial
primarily as reflex centers, influencing the and middle layers of the superior colliculus
position of the head and eyes in response to via a transtegmental approach and are
visual, auditory, and somatic stimuli ( 142 ). thought to participate in mechanisms related
The superior colliculus is concerned primar- to saccadic eye movements ( 222, 223). The
ily with the detection of the direction of stratum lemnisci composed of medium - and
movement of objects in the visual fields ( 383), large-sized stellate cells, receives heteroge-
and facilitates visual orientation, searching, neous inputs from diverse sources, most of
and tracking. Cells in deeper layers of the su- which are somatosensory and auditory.
perior colliculus appear to respond to audi - These deep layers of the superior colliculus
tory, somatic, and visual stimuli, sometimes receive afferents from ( a ) the spinal cord ( i.e.,
separately and sometimes in different combi- spinotectal tract ), ( b ) somatosensory relay nu -
nations ( 142 ). clei ( i .e., nucleus cuneatus, lateral cervical nu -
Each colliculus consists of alternate gray cleus, and spinal trigeminal nucleus), (c ) cate-
cholaminergic and serotoninergic neurons in dominant, a finding that contrasts with the
the locus coeruleus and raphe nuclei ( 272 ), equal representation of the two eyes in the
( d ) the inferior colliculus and a variety of au - lateral geniculate body and the striate cortex.
ditory relay nuclei , (e) the cerebellar nuclei, Corticotectal fibers arise from portions of the
and ( f ) the substantia nigra and various parts frontal, temporal, parietal, and occipital
of the brainstem reticular formation (97, 124, lobes. The most substantial and highly orga -
188, 201, 257). nized projection arises from the visual cortex
The superficial layers of the superior col- and reaches the superior colliculus via the
liculus receive most of their input from the brachium of the superior colliculus ( 124 , 125,
retina and visual cortex , and are concerned 225, 420). These fibers enter the stratum op-
with detection of movement of objects in the ticum and pass into the superficial and mid -
visual field , whereas the deep layers receive dle grav layers. Fibers from the retina enter
inputs from multiple sources and have via the same route and appear to terminate in
anatomic and physiologic characteristics of the same layers. Although retinal and visual
the brainstem reticular formation. Superficial cortical projections to the superior colliculus
layers of the superior colliculus project pri- are similar, there are important differences:
marily to vision related nuclei, while interme- retinal projections are bilateral and greatest
diate and deep layers project to diverse re- contralaterally, while striate cortical projec-
gions related to head and eve movements (8, tions are unilateral. Anatomic data indicate
68, 124 , 148, 169, 188 ). However , despite mor- that portions of the visual cortex and superior
phologic, connectional, and biochemical dif - colliculus related to particular regions of the
ferences, the superficial and deep layers of retina are interconnected . Thus, essentially
the superior colliculus are intimately linked the same cells of the superior colliculus re-
with each other in a spatial registration . ceive distinct , but related, inputs from gan -
glion cells of the retina and the striate cortex
( Fig. 14.9). Afferents to the superficial lami-
AFFERENT PROJECTIONS
nae also arise from the parabigeminal area .
The superior colliculus receives afferents Corticotectal fibers from the frontal lobe,
from the retina , the cerebral cortex, brainstem particularly the frontal eye field ( Brodmann 's
nuclei , and the spinal cord . area 8), terminate in the middle gray layer,
Retinotectal fibers leave the optic tract ros- the stratum opticum, and the stratum zonale
tral to its principal termination in the lateral ( 223) . These fibers reach the superior collicu -
geniculate body and project to the superior lus throughout via a transtegmenta1 ap-
colliculus via its brachium. Fibers come from proach and are thought to participate in
homonymous portions of the retina of each motor mechanisms related to eye move-
.
eye but crossed fibers are most numerous.
Thus, the contralateral homonymous halves
ments. Cells in superficial layers respond to
visual stimuli, while cells in the middle gray
of the visual field are represented in each su - layers discharge prior to the onset of saccadic
perior colliculus ( Fig. 14.9 ). Optic tract fibers eye movements. The auditory cortex projects
project to all parts of the superior colliculus to deep layers in caudal parts of the superior
(85, 187). The upper quadrants of the con - colliculus that receive no visual input (90 ).
tralateral visual field are represented in me- Brainstem afferents to the superior colliculus
dial parts of the superior colliculus; the lower arise from the inferior colliculus and a num -
quadrants are related to lateral regions of this ber of auditory relay nuclei (97, 188, 322, 393).
structure. The contralateral peripheral visual Projections to deep layers of caudal parts of
field is represented in the caudal two- thirds the superior colliculus arise mainly from the
of the superior colliculus, while central re- external and pericentral nuclei of the inferior
gions of the visual field ( i.e., within 10° of the colliculus. Other auditory relay nuclei pro-
fovea ) are represented rostrallv . The region of jecting fibers to the superior colliculus in -
the retina corresponding to the optic disc ( the clude the ventral nucleus of the lateral lem -
blind spot ) has been identified near the center niscus and the nuclei of the trapezoid body.
of the superior colliculus ( 149, 168, 187, 188 ). Commissural fibers coursing in the commis -
Retinal ganglion cells projecting to the supe- sure of the superior colliculus ( Figs. 14.7 and
rior colliculus are of the Y and W cell tvpes 14.8) primarily relate deep and intermediate
( see Chapter 16 ) . In the superior colliculus, gray layers in the rostral halves of the supe-
representation of the contralateral eye is rior colliculi ( 96). Additionally, this bundle
14 Midbrain 537
Upper quadrants Macular area
Lower quadrants
• \
/ \
t
Temporal retina - Nasal - I \
retina
Optic nerve
Optic chiasm
/ Optic tract
Superior
colliculi Lateral geniculate
b body
Brachium of
superior colliculus
V
Inferior
colliculi
Right
occipital
cortex
Calcarine
sulcus
Figure 14.9 Projections of the retinae and striate cortex upon the superior colliculi in the rhesus monkey Retinotectal
fibers from the ipsilateral temporal and contralateral nasal halves of the retinae, which subserve the contralateral
homonymous visual field, project to the superior colliculus . Cells in portions of the retinae concerned with the con-
tralateral peripheral visual field project to the posterior two-thirds of the superior colliculus. Upper quadrants of the
contralateral peripheral visual field ( solid blue and red) are represented in medial region of caudal parts of the supe -
rior colliculus, while lower quadrants of the contralateral peripheral visual field ( blue and red stripes) are represented
.
in lateral regions. Portions of the retinae concerned with central vision (i e., within 10° of the fovae centralis, blue and
red dots) are represented in the rostral third of the superior colliculus. Although retinotectal fibers arise from portions of
.
the retina of each eye crossed fibers are most numerous. Corticotectal fibers from the striate cortex, shown on the
right, project to all parts of the superior colliculus via Its brachium. There is a correspondence in the superior colliculus
of retinotectal and corticotectal terminations that represent both central and peripheral parts of the visual field
contains some fibers projecting to noncorre - vey visual information to the extrastriate cor-
sponding areas of the colliculus and some tex via the pulvinar. It also has been shown
decussating elements of both tectal and non - that cells in the most superficial layers of the
tecta! origin . The pars reticulata of the sub - superior colliculus in primates project upon
stantia nigra projects fibers to the deep and the dorsal lateral geniculate body (167) and to
intermediate layers of the caudal two-thirds the parabigeminal nucleus (28). Most of the
of the superior colliculus (58). Many of these tectogeniculate fibers terminate in intralaminar
GABAergic neurons have dichotomizing geniculate regions adjacent to the magnocel-
axons that also project to the thalamus ( 20, 30, lular layers, which are thought to contain in-
302). These connections appear related to terneurons. Thus, visual pathways to the cor-
motor functions, since all brainstem and tex via the superior colliculus and the lateral
spinal afferents arise from deep layers. geniculate body are not entirely separate. The
Spinotectal fibers projecting to the deep lay- deep layers of the superior colliculus also
ers of the superior colliculus are not numer- give rise to ascending fibers that project to the
ous. Although some somatosensory input to posterior and intralaminar thalamic nuclei
the superior colliculus arises from cells in the (169). Cells in the intermediate and deep col-
dorsal horn ( lamina IV ), the major inputs are licular layers project to both motor and sen-
from the posterior column nuclei ( particu- sory nuclei. These collicular projections in-
larly the nucleus cuneatus) and all parts of clude the pretectum, the paramedian pontine
the spinal trigeminal nuclear complex (97). reticular formation ( PPRF), and the rostral in -
Regardless of the locations of the cells of ori- terstitial nucleus of the medial longitudinal
gin , somatosensory input to the deep layers fasciculus ( RiMLF) involved in subcortical
of the superior colliculus is topographically control of eye movements.
organized with the head represented ros- Descending tectofngal fibers arising from in-
trally, the forelimbs posterolaterallv, and the termediate and deep layers of the superior
remainder of the body posteromedially (104, colliculus can be grouped into uncrossed tec-
378). The somatotopic representation is dis- topontine and tectobulbar tracts, and crossed
torted in that regions related to the head and tectobulbar and tectospinal projections.
forelimb are unusually large. Uncrossed tectopontine and tectobulbar fibers
As the preceding discussion indicates, the project to the ipsilateral dorsolateral pontine
superior colliculus can be partitioned into nuclei, the lateral part of the reticulotegmental
two zones: (a ) the superficial layers, which re- nucleus, and the nucleus reticularis pontis
ceive primarily visual afferents, and ( b) deep oralis (8, 166, 169, 188, 210). Additionally , deep
layers, which receive a heterogeneous multi- layers of the superior colliculus project fibers
modal input. Although the superficial layers to the cuneiform nucleus and the external nu -
of the superior colliculus have projections cleus of the inferior colliculus. Superficial lay-
distinct from that of all deeper layers, they ers of superior colliculus give rise to a substan-
also project to the deep layers (166). tial ipsilateral projection to the parabigeminal
nucleus, a structure that has bilateral region-
EFFERENT PROJECTIONS ally organized projections to the superior col-
liculus (150, 166). The dorsolateral region of
In general, the superficial layers give rise the pontine nuclei, which receives fibers from
to ascending fibers and the deep layers pro- the superior colliculus, also receives inputs
ject descending fibers to nuclei in the brain- from the visual and auditory cortex (48, 125).
stem and spinal cord. This collection of pontine nuclei projects to
Tectothalamic fibers , arising from superficial lobules VI and VII of the cerebellar vermis (46)
layers of the superior colliculus, project ipsi- and are responsive to visual, auditory, and so-
laterally to the pulvinar, the dorsal and ven- matosensory stimuli (359).
tral lateral geniculate nuclei, and the pretec- Tectoreticular fibers project profusely and
tum (8, 26, 28, 68, 148, 169, 188). The pulvinar bilaterally to dorsal regions of the midbrain
receives the most extensive projection from reticular formation. Some tectofugal fibers
the superficial layers of the colliculus and , in enter the accessory oculomotor nuclei (i.e.,
turn, projects upon extrastriate cortical areas the nucleus of Darkschewitsch and the inter-
(areas 18 and 19) (27, 28, 140). Thus, the su- stitial nucleus of Cajal), but none appear to
perficial layers of the superior colliculus give enter the oculomotor complex (8, 250, 292,
rise to tectothalamic fibers, part of which con- 329, 392).
]4 Midbrain 539
Crossed tectobulbar and tectospinal fibers de- stimuli flashed on and off within the recep-
cussate in the dorsal tegmental decussation at tive field . In the superior colliculus, the pre-
midbrain levels and descend near the median ferred directional selectivity is parallel to the
raphe ( Fig. 11.18). At medullary levels these horizontal meridian of the visual field and to-
fibers become incorporated within the medial ward the periphery of the visual field . Thus,
longitudinal fasciculus. Tectospinal fibers units in the left superior colliculus have re-
continuing to cervical spinal segments de- ceptive fields in the right visual field and re-
scend in the medial part of the anterior fu - spond best to stimuli moving from left to
niculus ( Fig. 11.25). In the brainstem, this right. Cells in the superficial layers of the su-
crossed projection is referred to as the predor - perior colliculus are most responsive to small
sal bundle. Fibers from this bundle project to moving objects.
the reticulotegmental nucleus and to both In animals in which the visual cortex has
rostral and caudal portions of the pontine been removed , cells of the superior colliculus
reticular formation ( 166). At medullary lev- lose their directional sensitivity to moving
els, crossed tectobulbar fibers terminate in objects in the visual field ( 419 ). While in the
parts of the medial accessory olivary nucleus normal animal cells in the superior colliculus
( i.e., nucleus (3). Tectospinal fibers descend - can be driven by stimuli to either eye, follow-
ing only to cervical spinal segments terminate ing ablations of the visual cortex, these cells
in laminae VII and VIII ( 285). respond only to stimuli in the contralateral
eye. Thus, the superior colliculus cannot per-
FUNCTIONAL CONSIDERATIONS form its normal function as a detector of spe-
cific movements within the visual field when
Each superior colliculus receives a visual deprived of input from the visual cortex.
input related to the contralateral visual field . Stimulation of the superior colliculus re-
Additionally, it receives an ipsilateral projec- sults in contralateral conjugate deviations of
tion from the visual cortex concerning only the eyes ( 13, 384 ), even though this structure
the contralateral visual field . These two sys- has no projections to the nuclei of the extraoc -
tems are precisely and topographically orga - ular muscles. Part of these responses may be
nized at all levels. Unilateral lesions of the su - mediated by collicular projections to (a ) the
perior colliculus in a variety of animals rostral interstitial nucleus of the medial longi-
produce ( a ) relative neglect of stimuli in the tudinal fasciculus ( RiMLF), which projects to
contralateral visual field , ( b) deficits in per- specific subdivisions of the ipsilateral oculo-
ception involving spatial discriminations and motor complex (61 , 377), or ( b ) the pontine
tracking of moving objects, (c ) heightened re- paramedian reticular formation ( PPRF),
sponses to stimuli in the ipsilateral visual which projects to the ipsilateral abducens nu -
field , and (d ) no impairment of eye move- cleus ( 54 ) and the RiMI.F. Although the PPRF
ments ( 374, 375). These disturbances undergo has no direct connections with the oculomo-
considerable attenuation in time, but indicate tor complex, impulses relayed via abducens
that the superior colliculus contributes to the internuclear neurons can influence subdivi -
coordination of head and eye movements sions of the oculomotor nuclear complex ( 59 ).
used to localize and follow visual stimuli. Electrical stimulation of the superior col -
Physiologic studies in the cat indicate that liculus in alert monkeys also elicits short -
the collicular receptive fields are two to four latency saccadic eye movements ( 340, 356).
times larger than the receptive fields in the vi - The amplitude and direction of these sac-
sual cortex. A receptive field in the visual sys- cades are a function of the site stimulated
tem is defined as that region of the retina (or within the superior colliculus. Medial regions
visual field ) over which one can influence the of the colliculus are associated with upward
firing of a particular ganglion cell ( 220). The components, while lateral regions have
receptive field consists of a central circular re- downward components ( 373). Chronic micro-
gion and a concentric surround . Most collicu - electrode recordings in the intermediate and
lar cells respond only to moving stimuli, and deep layers of the superior colliculus have
three-fourths of these cells show directional shown maximal discharges of neurons prior
selectivity (85, 383). These cells respond well to eye movements in particular directions.
to movement in one direction, but poorly, or These studies indicate that the superior col -
not at all, to movement in the opposite direc- liculus is involved in coding the location of
tion , and are nonresponsive to stationary an object relative to the fovea and in eliciting
saccadic eye movements that produce foveal of the pretectal region include (a ) the nucleus
acquisition of the object ( 373). The GABAer- of the optic tract, ( b ) the sublentiform nu -
gic projections to the superior colliculus play cleus, (c) the nucleus of the pretectal area , ( d )
a crucial role in the control of saccadic eye the pretectal olivary nucleus, and (e) the prin -
movements. The visuotopic order of the elec- cipal pretectal nucleus ( 14, 66, 208, 221 ). The
trophysiologic response properties of neu - nucleus of the optic tract consists of a plate of
rons in the intermediate layers of the superior large cells along the dorsolateral border of
colliculus to which the substantia nigra pro- the pretectum at its junction with the pulv -
jects, and the matching of visual receptive inar ( Fig. 14.10). The pretectal olivary nucleus
fields of superior colliculus neurons and ni- ( or olivary nucleus of the superior colliculus )
gral neurons that innervate them, suggest a forms a sharply delimited cell group at levels
visuotopic ordering of nigral neurons related through caudal parts of the posterior com-
to eye movements (178-181 ). The superficial missure ( Fig. 14.11 ), whereas the sub-
laminae of the superior colliculus also play an lentiform nucleus forms a crescent-shaped
important role in the extrageniculate visual -
group of small- and medium sized cells me -
pathways related to depth perception. dial to the nucleus of the optic tract . The nu -
cleus of the pretectal area occupies a dorso-
Pretectal Region medial part of the pretectum throughout its
extent, while the principal pretectal nucleus
This region lies immediately rostral to the lies ventral to the sublentiform nucleus and
superior colliculus at levels of the posterior its boundaries are difficult to distinguish .
commissure ( Figs. 14.10 and 16.4 ). Several The pretectal nuclei receive fibers from the
distinctive cell groups within this region ap- optic tract, the lateral geniculate body , certain
pear related to the visual system. The nuclei areas of the cortex, and probably from the
NPCm
Figure 14.10 Brainstem transverse section through the most compact portion of the posterior commissure (PC) At
this level, the nucleus of the optic tract ( NOT), the sublentiform nucleus (Si), the nucleus of the pretectal area (NPA).
and the nuclei of the posterior commissure (NPC) are well - developed The anterior median nucleus (AM) is present,
but the dorsal visceral nuclei ( VN) of the oculomotor complex have not separated into medial and lateral cell
.
columns INC. interstitial nucleus of Cajal. ND. nucleus of Darkschewitsch, NPC ,. nucleus of posterior commissure, pars
.
magnocellularis; NPC,. nucleus of posterior commissure, pars principalis. III oculomotor nerve
14 Midbrain 541
sate ventral to the cerebral aqueduct ( Fig.

14.16 ). Because of the complex crossed and
uncrossed projections to the visceral nuclei of
oculomotor nerve, only relatively large le-
sions involving multiple structures in the pre-
tectum impair the pupillary light reflex.
Posterior Commissure
The transition from midbrain to dien -
cephalon is marked dorsally by the posterior
commissure ( Figs. 2.28, 14.10, 14.11, 14.12A ,
and 14.15B ) . This small commissure lies dor-
sal to the periaqueductal gray and rostral to
the superior colliculi at the point of transition
between the cerebral aqueduct and the third
Figure 14 11 Myelin - stained section at junction of pre ventricle. As fibers of the posterior commis-
tectum and superior colliculus in the rhesus monkey . BSC. sure fan out laterally, they are surrounded by
.
brachium of the superior colliculus. CSC commissure of
cells that collectively form the nuclei of the pos -
.
the superior colliculus ON. pretectal olivary nucleus, PC . terior commissure ( Fig . 14.10) ( 64 ) . Identified
posterior commissure, SC. superior colliculus (Weil stain )
elements in the posterior commissure include
fibers from (a ) the pretectal nuclei, ( b ) the nu -
posterior thalamic nuclei ( 124, 125, 136, 137, clei of the posterior commissure, ( c ) the inter-
176, 190, 309, 353). The pretectal region is stitial nucleus of Cajal , and ( d ) the nucleus of
considered to be principal midbrain center in - Darkschewitsch ( Fig. 14.17). Fibers from the
volved in the pupillan/ li lit reflex ( 245, 246, pretectal olivary nucleus ( Figs. 14.10 and
327). ^ 14.11 ) cross in the commissure to the same
Fibers from the pretectal olivary nucleus, nucleus on the opposite side and give collat -
which receives both crossed and uncrossed erals to the visceral nuclei of the oculomotor
retinofugal fibers, cross in the posterior com - complex ( Fig. 14.16 ). Lesions in the posterior
missure and project to specific components of commissure reduce, but not eliminate, the
the visceral nuclei of the oculomotor complex consensual pupillary light reflex ( 247) and do
( Fig. 14.16 ) (66, 377 ). Fibers from the nuclei of not affect the pupillary light reflex as mea -
the posterior commissure, projecting bilater- sured in infrared pupillograms ( 66 ). Lesions
ally to other visceral nuclei , partially decus- in the nuclei of the posterior commissure, in -
m o im
. ,v a.-*.*.
• ' * -
w
•V
••
I
- --
•r ’ Zf
v*
• _ <-
* >• S •
»,
•4
HNHHRTE B
Figure 14.12 Subcommissural organ in the rhesus monkey A. Position of the structure in the roof ot the aqueduct be-
neath the posterior commissure B. Difference between the tall columnar cells of the subcommissural organ and the
.
cells of the ependyma (Nissl stain * 16; 100.)
'
terrupting fibers from the interstitial nuclei of gested that it may serve as a volume receptor
Cajal, produce bilateral eyelid retraction and (134), play an important role in control of salt
impairment of vertical eye movements ( 61 ). and water balance (133, 253), and be con-
The subcommissural organ is a modified cerned with thirst and water intake. The sub-
ependymal plate in the roof of the cerebral commissural organ is the only midbrain
aqueduct immediately beneath the posterior structure not included in the blood -brain bar-
commissure ( Figs. 1.17 and 14.12 ). This rier.
periventricular organ , which is recognized as
circumventricular and appears to have a se-
cretory function, consists of ciliated columnar Oculomotor Nerve
cells ( 421 ). The secretory product of these OCULOMOTOR NUCLEAR COMPLEX
cells, in all species except human, is con -
densed to form a strand of proteinaceous ma - The oculomotor nuclear complex is a col-
terial ( Reissner's fiber ) that extends through lection of cell columns and discrete nuclei
the aqueduct, the fourth ventricle and into that (a ) innervate the inferior oblique and the
the spinal canal. Cells of the subcommissural superior, medial, and inferior rectus muscles,
organ are different than the usual ependymal ( b ) supply the levator palpebrae muscle, and
cells in that they have projections into the (c) provide preganglionic parasympathetic
ventricular lumen covered with protruding fibers to the ciliary ganglion ( Fig . 14.14 and
microvilli, an abundance of rough endoplas- Table 14.1 ). Functional components of the
mic reticulum and microtubules. These cells nerve are categorized as general somatic effer-
also show pinocytotic vesicles near the cell ent ( GSE ) and general visceral efferent (GVE ).
surface ( 77 ). These data, based upon scanning This complex lies ventral to the central gray
and transmission electron microscopy, sug- matter in the midline in a V-shaped trough
gest that cells of the subcommissural organ formed by the diverging fibers of the medial
are active in secretion and possibly in absorb- longitudinal fasciculus ( MLF). It extends
ing substances from the cerebrospinal fluid . from the rostral pole of the trochlear nucleus
The function of this subcommissural organ in to the upper limit of the midbrain ( Figs. 14.6,
human is unknown, but it has been sug- 14.10, and 14.13). The nuclear complex con-
Externol , middle and deep

gray layers of superior colliculus
Mesencephalic
Mesencephalic / nucleus of N 3T
reticular
formation Cerebral aqueduct
Periaqueductal gray
Peripeduncular Dorsal tegmental

nucleus nucleus
Dorsal nucleus
of lateral cell
column of N . Ill
Caudal centrol nucleus
of oculomotor complex
Ventral nucleus
of lateral cell
column of N. ITT
Large cells
Reticular zone Small cells
} red nucleus
/ l substantia
Compact zone J nigra
Figure 14.13 Transverse section through superior colliculi of midbrain in a 3-month infant (Cresyl violet stain with the
main cell groups schematically blocked ,)
14 Midbrain 543
sists of paired lateral somatic cell columns, The caudal central nucleus is a midline so-
midline and dorsal visceral nuclei, and a dis - matic cell group found only in the caudal
crete midline dorsal cell group called the cau - third of the complex ( 414). This nucleus gives
dal central nucleus. rise to crossed and uncrossed fibers that in -
The lateral somatic cell columns is composed nervate the levator palpebrae muscle ( Figs.
-
of large motor type neurons that innervate 14.13 and 14.14 ).
the extraocular muscles ( 413). The dorsal cell Visceral nuclei of the oculomotor nuclear
column (or nucleus) innervates the inferior complex consist of two distinct nuclear
rectus muscle, the intermediate cell column groups, which are in continuity rostrally. The
innervates the inferior oblique muscle, and Edinger-Westphal nucleus ( Figs. 14.10, 14.14,
the ventral cell column supplies fibers to the and 14.15A ) consists of two slender columns
medial rectus muscle ( Fig. 14.14 and Table of small cells dorsal to the rostral three-fifths
14.1 ). Although major representation of the of the somatic cell columns. In transverse sec-
medial rectus muscle is in the ventral cell col- tions through the middle third of the com-
umn, a discrete collection of cells in dorsal re- plex, each of these paired columns divides
gions also innervate this muscle. Root fibers into two smaller cell columns, which taper
arising from these cell columns are un- and gradually disappear. Rostrally the cell
crossed . A cell column medial to both the column of the Edinger- Westphal nucleus
dorsal and intermediate cell columns, re- merge in the midline dorsally and become
ferred to as the medial cell column, provides continuous with the visceral cells of the ante-
crossed fibers that innervate the superior rec- rior median nucleus. Cells of the anterior me-
tus muscle. dian nucleus lie in the raphe between por-
Intermediate Viscerol nuclei

column
Dorsal nucleus
Caudal
central Ventral nucleus
nucleus T rochlea
— Superior oblique
@
Right lateral aspect x Superior rectus
;
Levator^
palpebrae ' Lateral rectus
Medial rectus /
Interior rectus
Inferior oblique
Dorsal aspect
ISV
V
Caudal third Rostal third Rostral pole
Figure 14.14 Localization of the extraocular muscles within the oculomotor nuclear complex, based upon studies in
the rhesus monkey Cell columns composing the complex are shown in lateral , dorsal, and transverse views through
various levels. The visceral motor ( parasympathetic) cell columns are shown in black . The ventral nucleus ( blue) inner -
vates the medial rectus muscle, while the dorsal nucleus ( red) innervates the inferior rectus muscle The intermediate
cell column ( yellow ) innervates the inferior oblique muscle, while the cell column ( white) medial to the dorsal and in-
termediate cell columns innervates the superior rectus muscle . The caudal central nucleus ( lined) supplies fibers to
the levator palpebrae superioris. Fibers innervating the medial rectus, inferior rectus, and inferior oblique muscles are
uncrossed Fibers supplying the levator palpebrae muscle are both crossed and uncrossed, while those to the supe -
rior rectus muscle are crossed The drawing in the upper right shows the positions of the extraocular muscles in relation
to the globe and the bony orbit .
aqueduct ( 66). Although the visceral nuclei of

the oculomotor nuclear complex ( i.e., the
Edinger-Westphal and anterior median nu -
clei ) have been considered to supply pregan-
glionic parasympathetic fibers only to the cil -
iary ganglion, retrograde transport studies
demonstrate that these visceral neurons also
project to the lower brainstem , the cerebel-
lum, and spinal cord ( 69, 226, 239, 240, 386 ).
Descending fibers from distinctive visceral
nuclei of the oculomotor complex project to
the posterior column nuclei and Rexed's lam -
inae 1 and V as far caudally as lumbar spinal
segments ( Fig. 11.23).
The so-called central nucleus of Perlia has
been regarded as a midline cell group con-
cerned with ocular convergence. There has
been great difficulty in identifying this nu -
cleus in humans and monkeys ( 74, 415, 416),
and its function remains in doubt.
Root fibers of the oculomotor nerve pass
ventrally in numerous small bundles, some of
which traverse the red nucleus. Ventrally, the
fibers converge and emerge from the interpe-
duncular fossa on the anterior aspect of the
midbrain ( Figs. 2.9, 2.26, and 12.1 ). Visceral
fibers emerge with rootlets in the rostral part
of the oculomotor nerve. Spreading of the
root fibers through and around the red nu -
Figure 14.15 A . Sagittal section through the oculomo- cleus is an expression of the intraradicular ex-
tor complex slightly removed trom the midline in a rhesus pansion of the red nucleus during embry-
monkey The continuity of the anterior median ( AM ) and
dorsal visceral cell columns ( VN) is evident Other nuclei
ologic development ( Fig. 14.6).
.
identified are DCC dorsal (somatic) cell column; VCC .
.
ventral (somatic) cell column; ICC intermediate (so- ACCESSORY OCULOMOTOR NUCLEI
.
matic) cell column, CCN caudal central nucleus; IN.
Grouped under this designation are three
.
trochlear nucleus; and SIN supratrochlear (dorsal
raphe) nucleus (Nisst stain, 20 ) B . Parasagittal section
* nuclei closely associated with the oculomotor
through the posterior commissure (PC) and the medial complex. These nuclei are the interstitial nu -
longitudinal fasciculus (MLF). demonstrating the relation-
ships between the nucleus of Darkschewitsch (ND) the . cleus of Cajal, the nucleus of Darkschewitsch,
interstitial nucleus of Cajal ( INC), and the red nucleus and the nuclei of the posterior commissure.
( RN) FRF indicates fasciculus retroflexus (Nissl stain. < 20 ) The interstitial nucleus (of Cajal ) is a small
collection of multipolar neurons situated
among, and lateral to, the fibers of the Ml.F in
tions of the rostral lateral somatic cell the rostral midbrain ( 326) ( Figs. 14.10, 14.12A ,
columns ( Figs. 14.10 and 14.16). Both the 14.15B, and 14.18). In humans, the interstitial
Edinger-Westphal and the anterior median nucleus contains about 75% of small - to
nuclei give rise to uncrossed preganglionic medium-sized polymorph cells and 25% of
parasympathetic fibers that emerge with so- large polygonal neurons dispersed through -
matic root fibers and project to the ciliary out the nucleus (35). The smaller neurons are
ganglion (50). The anterior median nuclei and believed to be key integrative elements while
the lateral visceral cell column receive fibers large neurons are thought of as projection
from the contralateral pretectal olivary nuclei elements. The interstitial nucleus receives
which cross in the posterior commissure ( 377) projections from the superior and medial
( Fig. 14.16 ) . The anterior median and medial vestibular nuclei, the pretectum, the frontal
visceral cell columns receive bilateral projec- eye fields, and the fastigial nucleus. Efferent
tions from the nuclei of the posterior commis- fibers from the interstitial nucleus cross in the
sure which partially decussate ventral to the ventral part of the posterior commissure and
14 Midbrain 545
NPCF
ON
Figure 14.16 Transverse section of the midbrain through the posterior commissure, showing the course and termina -
tions of afferents projecting to the visceral nuclei of the oculomotor complex The pretectal olivary nucleus (ON) re-
.
ceives direct bilateral retinal projections Projections of the pretectal olivary nucleus (red) partially cross ventral to the
.
cerebral aqueduct and terminate in the medial visceral cell column (MVCQ and the anterior median nuclei ( AM)
Other efferents from the pretectal olivary nuclei cross in the posterior commissure and end in the lateral visceral cell
column ( LVCC) and the anterior median nuclei. Commissural connections interrelate the pretectal olivary nuclei.
. . .
CSC commissure of the superior colliculus; INC interstitial nucleus of Cajal; NPC nuclei of the posterior commissure;
.
NPCf nucleus of the posterior commissure, pars infrocommissuralis.
are distributed to all somatic cell columns of mentioned earlier. Cells of these nuclei lie
the contralateral oculomotor complex, except dorsolateral and dorsal to the central gray
the ventral ones (61 ). Additionally, the nu - matter, and have connections with the pretec-
cleus projects fibers bilaterally to the tal and posterior thalamic nuclei. In the mon -
trochlear nuclei and ipsilaterally to the me- key, interruption of fibers in the posterior
dial vestibular nucleus (321 ) and spinal cord commissure in the midline does not impair
( i .e., interstitiospinal tract ) ( Fig. 14.17 ) . This the pupillary light reflex, but lesions involv-
nucleus is concerned with slow rotatory and ing the nuclei of the posterior commissure
vertical eye movements and smooth pursuit and crossing fibers from the interstitial nuclei
eye patterns. It also plays a role in the control of Cajal produce bilateral eyelid retraction
of head movements and posture (120 ). and impairment of vertical eye movements.
The nucleus of Dcirksclteu' itsch is formed by
small cells which lie inside the ventrolateral AFFERENT CONNECTIONS OF THE
border of the central gray matter, dorsal and OCULOMOTOR COMPLEX
lateral to the somatic cell columns of the ocu -
lomotor complex ( Figs. 14.10, I 4.12 A , 14.15 B, Although no direct corticobulbar fibers
and 14.18). The nucleus projects to the nuclei reach the oculomotor complex, impulses
of the posterior commissure, but does also from the cerebral cortex are conveyed to
project fibers into the oculomotor nuclear reticular neurons, which relay these impulses
complex or the lower brainstem ( 377). to the complex. Direct projections to the ocu -
The nuclei of the posterior commissure consist lomotor nuclear complex arise from parts of
of collections of cells intimately associated the vestibular nuclei, the interstitial nucleus
with fibers of the posterior commissure, as of Cajal, abducens internuclear neurons .
OCULOMOTOR COMPLEX
ROSTRAL
00 DCC
VCC
MIDDLE MCC
CCN
CAUDAL
TROCHLEAR NUCLEI
3 C? ,ST
MLF.
^
Figure 14.17 Degeneration resulting from a lesion (red) in the right interstitial nucleus of Cajal (INC) The lesion de-
stroyed (a) cells which give rise to fibers that cross in the ventral part of the posterior commissure and fibers which de-
.
scend in the ipsilateral MLF and (b) fibers from the opposite interstitial nucleus which have crossed in the posterior
commissure and traverse the lesion en route to the oculomotor complex . Fairly symmetric differential degeneration
(red stippling) in the oculomotor complex was greatest in the intermediate (ICC) and medial cell columns ( MCC) .
somewhat less profuse in the dorsal cell columns ( DCC). and absent in the ventral cell columns ( VCC) and in the cau-
dal central nucleus (CCN) Degeneration in the trochlear nuclei was bilateral but was greatest ipsilaterally . Fibers of
.
the interstitiospinal tract ( 1ST) were concentrated in the dorsomedial part of the MLF . ND nucleus of Darkschewitsch,
. . .
PC posterior commissure RN red nucleus
parts of the perihypoglossal nuclei , the ros- part of the posterior commissure and pass to
tral interstitial nucleus of the MLF ( RiMLF ) , all somatic cell columns, except the ventral,
and the pretectal olivary nucleus. The supe- on the opposite side ( Fig . 14.17 ) ( 57, 61 ) . Sec-
rior colliculus does not project directly to the ondary fibers arising from the medial and su -
oculomotor complex, but it innervates parts perior vestibular nuclei project to the oculo-
of the periaqueductal gray close to the oculomotor nuclear complex via the MLF ( 377) .
motor nuclei . The interstitial nucleus of Cajal Projections from the medial vestibular nu -
gives rise to fibers that cross in the ventral cleus via the MLF are bilateral , while those
14 Midbrain 547
Nucleus of
Darkschewitsch
Cerebral
Interstitial
nucleus of Cajal
Medial
longitudinal
fasciculus
Figure 1 4 . 1 8 Relationships of the nucleus of Darkschewitsch and the interstitial nucleus of Cajal to the central gray
matter (surrounding the cerebral aqueduct) and the medial longitudinal fasciculus ( b. collateral fibers terminating in
the nucleus of Darkschewitsch. a. fibers leaving this nucleus) Based upon Golgi preparations from a newborn kitten
from the superior vestibular nucleus via this vertical eye movements, particularly in a
bundle are ipsilateral. Fibers from peripheral downward direction . Cells in the RiMLF are
parts of the superior vestibular nucleus, not activated in short bursts before vertical eye
contained in the MLF, cross in the caudal movements occur in response to vestibular or
midbrain and project to the superior rectus optokinetic stimuli. The RiMLF receives
and inferior oblique subdivisions of the ocu - input from the superior vestibular nucleus
lomotor complex. These vestibulo-oculomo - via the MLF and uncrossed projections from
tor connections serve to integrate the receptor the paramedian pontine reticular formation
activities of the labyrinth and visual systems ( PPRF), which ascend outside the MLF. Cells
which provide information concerning orien - of the RiMLF project ipsilaterally to the ocu -
-
tation in three dimensional space. Abducens lomotor complex and terminate mainly in the
internuclear neurons give rise to axons that inferior rectus subdivision . Thus, the PPRF
ascend in the contralateral MLF and termi - projects fibers to both the principal center for
nate selectively upon cells of the opposite me - conjugate horizontal eye movements, the ab-
dial rectus subdivision of the oculomotor ducens nucleus, and the established center
complex (53, 59). These internuclear projec - for vertical eye movement, the RiMLF
tions from the abducens to the oculomotor (52 ) . These findings indicate that paralysis of
nucleus underlie the neural mechanism re- conjugate horizontal and vertical eye move -
sponsible for conjugate horizontal gaze. ments can occur independently, yet a mecha -
The nucleus prepositus, which receives an nism exists that integrates horizontal and
input from the flocculus (7, 18, 118), projects vertical components of conjugate eye move-
ipsilaterally to the oculomotor nuclear comments ( 141 ).
plex (122, 151, 377), and may be concerned
with vertical eye movements (18, 59, 118). Pupillary Reflexes
Physiologically, the projection from the nu -
cleus prepositus appears related to upward Light shone on the retina of one eye causes
eye movements. both pupils to constrict . The response in the
The rostral interstitial nucleus of the MLF eye stimulated is called the direct pupillary
( KiMLF), situated among the fibers of the light reflex , while that in the opposite eye is
MLF rostral to the oculomotor complex at the known as the consensual pupillary light reflex.
junction of the mesencephalon and the dien - Pathways involved in the pupillary light re-
cephalon, appears uniquely concerned with flex are not entirely known but involve ( a )
axons of retinal ganglion cells that pass via the side of the neck, and in association with
the optic nerve, optic tract, and brachium of severe pain and extreme emotion. Impulses
the superior colliculus to the pretectal area; related to pain probably reach cells of the in -
( b ) axons of pretectal neurons that partially termediolateral cell column in upper thoracic
cross in the posterior commissure and termi- (C8 to Tl ) spinal segments ( Fig. 11.23) that
nate bilaterally in visceral nuclei of the oculo- give rise to preganglionic sympathetic fibers
motor complex ( Fig. 14.16); (c ) preganglionic that convey impulses to the superior cervical
fibers from the visceral nuclei that course ganglion . Postganglionic fibers from the su-
with fibers of the third nerve and synapse on perior cervical ganglion pass via blood ves-
cells in the ciliary ganglion ( Fig. 9.1 ); and (d ) sels to dilatator muscles fibers of the iris ( Fig.
postganglionic fibers from the ciliary gan - 11.30).
glion that project to the sphincter of the iris. A Horner' s syndrome usually results from
Cells of the pretectal olivary nucleus receive interruption of descending autonomic path -
fibers of the optic tract and project bilaterally ways that course in the dorsolateral tegmen-
to the visceral nuclei of the oculomotor com- tum at all the brainstem levels caudal to the
plex. In humans, direct and consensual pupil- hypothalamus. This syndrome may also
lary light reflexes are equal ( 241 ). The term occur as a consequence of interrupting de-
anisocoria is used to denote pupillary inequal - scending autonomic fibers in the brainstem or
ity . The principal central lesions producing cervical spinal cord and with lesions involv-
anisocoria involve efferent pathways from ing either preganglionic or postganglionic
the oculomotor complex. sympathetic fibers to the superior cervical
The acconnnodalion-convergence miction oc- ganglion . The syndrome is characterized by
curs when gaze is shifted from a distant ob- miosis, pseudoptosis, apparent enophthal-
ject to a near one. This reaction involves (a ) mos, and dryness of the skin over the face. If
contractions of both medial recti muscles for Horner's syndrome is the result of a brain-
convergence; ( b) contraction of the ciliary stem lesion, the pupil shows relatively little
muscles, which relaxes the suspensory liga - dilatation to adrenaline. If the provocative le-
ment of the lens and cause the lens to assume sion involves postganglionic sympathetic
a more convex shape; and (c) pupillary con- fibers, adrenaline produces mydriasis and
striction . In this reflex , retinal impulses must eyelid retraction on the affected side due to
first reach the visual cortex and be relayed via denervation sensitivity (76).
corticofugal fibers to brainstem centers. Corti-
cofugal fibers involved in this response reach LESIONS OF THE THIRD NERVE
the superior colliculus and pretectal region
and are relayed to the oculomotor complex. Complete lesions of the third nerve pro-
Although under normal circumstances ac- duce an ipsilateral lower motor neuron paral -
commodation always is accompanied by ysis of the muscles supplied by the nerve.
pupillary constriction , certain central nervous There is a complete ptosis (dropping ) of the
system lesions can impair or abolish the eyelid , due to paralysis of the levator palpe-
pupillary light reflex without affecting ac- bral muscle. The eye is deviated laterally (ex-
commodation . Such lesions occur with cen- ternal strabismus ) due to paralysis of the
tral nervous system syphilis ( tabes dorsalis ) oculomotor-innervated muscles and the un -
in which the pupils are small ( miosis ) and do opposed action of the intact lateral rectus
not react to light but react to accommodation. muscle. The pupil is fully dilated ( mydriasis)
This is the Argyll - Robertson pupil. The precise and there is a loss of the pupillary light reflex
location of the responsible lesion is unknown. as well as a loss of lens accommodation . Loss
In intense illumination, contraction of the of the pupillary light reflex and accommoda -
pupil may be accompanied by closure of the tion results from the interruption of visceral
eyelids, lowering of the brow, and general efferent fibers. Lesions involving the oculo-
contractions of the face, designed to shut out motor nerve and corticospinal fibers in the
the maximal amount of light . In so far as they ventral part of the midbrain result in an ipsi -
are not volitional , these reflex movements lateral oculomotor paralysis and a contralat-
probably are mediated through the superior eral hemiplegia , which clinically are known
colliculi and the tectobulbar tracts. as Weber' s syndrome. This syndrome, also
The central pathways for pupillary dilata - known as superior alternating hemiplegia , is a
tion are not entirely known , but dilatation oc- midbrain equivalent of similar syndromes oc-
curs reflexly on shading the eyes, scratching curring from lesions of the pons ( i.e., middle
14 Midbrain 549
alternating hemiplegia ) with involvement of The nucleus extends from the caudal dien -
the abducens nerve and the corticospinal cephalon to the decussation of the superior
tract and the medulla ( i.e., inferior alternating cerebellar peduncle. The red nucleus is tra -
hemiplegia ) with involvement of the hy- versed in its oral part by fibers of the fascicu -
poglossal nerve and the pyramid . lus retroflexus ( Fig. 16.4 ), in its central part by
rootlets of the oculomotor nerve, and in its
MIDBRAIN TEGMENTUM caudal and lateral regions by fibers of the su -
perior cerebellar peduncle.
The midbrain tegmentum, the region ven - Since the classic comparative studies of
tral to the cerebral aqueduct and dorsal to the Hatschek ( 172 ), it has been customary to rec-
substantia nigra, contains the trochlear and ognize magnocellular and parvicellular por -
oculomotor nuclei, the mesencephalic reticu - tions of the red nucleus. The magnocellular
lar formation, the red nuclei, and many scat - part tends to occupy caudal parts of the struc-
tered collections of cells. The most conspicu - ture, it is more extensive in lower mammals
ous structure in the midbrain tegmentum at and has been considered as the cell group
the level of the superior colliculus is the red which gives rise to the rubrospinal tract. The
nucleus. small-celled , or parvicellular, portion forms
the bulk of the nucleus ( Fig. 14.13). Its devel -
Red Nucleus opment parallels the growth of the cerebellar
TOPOGRAPHY AND CYTOARCHITECTURE nuclei, particularly the dentate nucleus. Be-
tween cells of the nucleus are numerous
The red nucleus is characterized by its small bundles of myelinated fibers which
pinkish-yellow color, due to its high degree give a punctate appearance to the nucleus in
of vascularization, its central position, and its transverse sections. These are primarily fibers
capsule formed bv fibers of the superior cere- of the superior cerebellar peduncle which tra -
bellar peduncle. In transverse sections, the verse the nucleus and terminate in parts of it .
red nucleus appears oval, but in sagittal sec- Cytologic studies of the red nucleus in the
tions it has an elliptical shape with a blunt monkey reveal three distinctive types of neu -
oral and a tapered caudal pole ( Fig. 14.19 ). rons (a ) large multipolar neurons 50-90 jim
Lateral geniculate
Pulvinar Superior colliculus
Medial geniculate
Crus cerebri Subthalamic nucleus

Substantia nigra Red nucleus
Figure 14.19 Transverse section through the rostral midbrain, demonstrating the manner in which diencephalic nu -
clei surround dorsal and lateral portions of the midbrain. (Weigert ' s myelin stain.)
in diameter with prominent nucleoli and a lowed by enhanced excitability of interposed

cytoplasm containing coarse Nissl granules neurons whose discharges result in depolar-
( magnocellular part ); ( b ) medium-sized cells, ization of red nucleus neurons ( 400 ). Cerebel -
20-30 jcm in diameter, with a triangular or lar cortical inhibition is mediated via y -
fusiform shape (parvicellular part ); and (c) aminobutyric acid (GABA ) while the effect of
small achromatic neurons, 10-15 gm in diam - cerebellar nuclei are likely to be mediated
eter, found in all parts of the nucleus ( 214, bv the excitatory amino acid glutamate (78,
215). Golgi preparations in the monkey have 283).
provided details concerning these neurons. Corticorubral projections arise from pre-
Giant neurons have star-shaped, ovoid, or central and premotor cortex ( 106, 170, 203,
elongated cell bodies with prominent somatic 225, 276, 337). Both of these areas project so-
spines. Dendrites of these cells radiate in all matotopically upon cells of the red nucleus.
directions and have a few isolated spines. Projections from the medial part of area 6 ( the
Medium-sized neurons, largely representing supplementary motor area ( M-ll )) are crossed
cells of the parvicellular part of the nucleus, and end in the magnocellular region of the
have shorter, less robust dendrites with nucleus. Projections from the precentral
branching collaterals. Small neurons have motor cortex to the magnocellular part of the
delicately branched dendrites and short red nucleus are ipsilateral and correspond to
axons. the somatotopic origins of the rubrospinal
fibers, as originally suggested by Pompeiano
CONNECTIONS and Brodal ( 320 ). These fibers have a somato-
topic linkage and , together with the rubro-
Afferent fibers projecting to the red nu - spinal tract ( crossed ), constitute a disynaptic
cleus are derived from two principal sources, pathway whereby impulses can be conveyed
the cerebellar nuclei and the cerebral cortex. from the "motor" cortex to spinal levels. Cor-
Fibers from both of these sources terminate ticorubral fibers form asymmetric synapses
somatotopically within the red nucleus. mainly with distal dendrites and dendritic
Fibers of the superior cerebellar peduncle, spines in the red nucleus ( 203, 276). Electro-
arising from the dentate, emboliform, and physiologic studies reveal that both cortical
globose nuclei, undergo a complete decussa- and cerebellar inputs converge upon the
tion in the caudal midbrain, and enter and same rubrospinal neurons, where they exert a
surround the contralateral red nucleus. Fibers complementary influence (138, 139). Addi-
and collaterals from the dentate nucleus ter- tionally, part of the cortical and cerebellar in -
minate in the rostral third of the red nucleus fluence upon neurons of the red nucleus is
of the opposite side ( parvicellular part ) (81, mediated through a large pool of inhibitory
107), while fibers from the emboliform and interneurons that regulate the levels of ex-
globose nuclei (anterior and posterior inter- citability of rubrospinal neurons (325).
posed nuclei ) project somatotopically upon Descending rubral efferent fibers cross in
the caudal two-thirds of the nucleus ( Figs. the ventral tegmental decussation and project to
15.21 and 15.22). The latter connection links (a ) the interposed nuclei of the cerebellum ,
paravermial regions of the cerebellar cortex ( b ) the principal sensory and spinal trigemi-
to the magnocellular part of the red nucleus nal nuclei, (c) part of the facial nucleus, ( d )
that in turn project somatotopically to spinal several medullary relay nuclei, and (e) the
levels ( Fig. 11.18). Two decussations are in- spinal cord (80, 83).
volved , that of the superior cerebellar pedun - Kubrobulbar projections are both crossed
cle and that of the rubrospinal tract. The cere- and uncrossed. Crossed rubrobulbar fibers
bellar afferent fibers form asymmetric project to the principal sensory nucleus of the
synapses mainly with the soma and proximal trigeminal nerve, and some of these fibers ex-
dendrites in the red nucleus ( 276 ). Physio- tend caudallv into the pars oralis of the spinal
logic interrelationships between the cerebel- trigeminal nucleus (94, 252, 263). At more
lar cortex, the interposed nuclei and the red caudal levels, fibers separating from the
nucleus indicate that excitatory influences of rubrospinal tract enter the lateral aspect of
the interposed nuclei upon the large cells of the facial nucleus and terminate in dorsome-
the red nucleus are suppressed by stimula- dial and intermediate cell groups whose neu -
tion of the cerebellar cortex. Cortical inhibi- rons innervate musculature of the upper part
tion , mediated by Purkinje cell axons, is fol- of the face (80, 82, 94, 263). Rubrobulbar fibers
14 Midbrain 551
ending upon motor neurons of the facial nu - matodendritic domain , whereas that from the
cleus probably are not involved in the neural cerebral cortex terminates more distally . In
mechanism of mimetic facial innervation, respect to rubral neurons themselves, evi-
since this phenomenon involves predomi- dence from lesion experiments in rodents in -
nantly perioral facial muscles. In the medulla , dicates that rubrospinal neurons also utilize
crossed rubrobulbar fibers end in the lateral an excitatory amino acid , most probably as-
reticular nucleus, the accessory cuneate nu- partate, as an excitatory transmitter ( 29 ). In
cleus, and the nuclei gracilis and cuneatus contrast, local interneurons in the red nucleus
(80, 94, 252, 412 ). appear to exert their inhibitory effect upon
Rubrospinal fibers in the cat arise chiefly, rubral projection neurons via GABA ( 325,
but not exclusively, from cells of all siz.es in 357). In fact, the strong motor impairment
the caudal three-fourths of the red nucleus produced by injection of GABA antagonists
( 320, 341, 425) . Cells in dorsomedial parts of into the red nucleus suggests an important
the nucleus project fibers to cervical spinal functional role for the GABAergic interneu -
segments, while cells in ventral and ventro- rons. Principally under the control of cortical
lateral locations project to lumbosacral spinal afferents, these GABAergic interneurons can
segments. Fibers passing to thoracic regions modulate the level of activity of rubrospinal
of the spinal cord arise from intermediate neurons and participate in the control of
parts of the red nucleus. Cervical spinal seg- motor behavior ( 357 ).
ments receive the largest number of rubro-
spinal fibers. In the monkey, rubrospinal FUNCTIONAL CONSIDERATIONS
fibers arise almost exclusively from the cau-
dal magnocellular part of the nucleus ( 225). Stimulation of the red nucleus in the de-
Recent electrophysiologic studies in the cat cerebrate cat results in (a ) excitatory postsy -
revealed the existence of direct monosynaptic naptic potentials in the contralateral flexor a
effect of rubrospinal neurons upon spinal motor neurons, and ( b) inhibitory postsynap -
motor neurons innervating muscles of the tic potentials in contralateral extensor a
forelimbs, whereas the same neurons do not motor neurons. These observations suggest
receive such monosynaptic input from the that the rubrospinal tract transmits impulses
cerebral cortex ( 119 ). that facilitate flexor muscle tone. Recent elec-
Uncrossed descending rubral efferents trophysiologic evidence reveal that rubro-
from the parvicellular part of the nucleus spinal neurons may influence also the dy-
enter the central tegmental tract and project namic and static y motor neurons ( 205).
to the dorsal lamella of the principal inferior Because of somatotopic relationships be-
olivary nucleus. These fibers are referred to tween the interposed nuclei of the cerebellum
as rnbro-olivary and constitute part of a feed - and the red nucleus (81, 83), stimulation of
back system to the cerebellum (94, 263, 314, these nuclei in decerebrate animals produces
412 ). No fibers from the red nucleus project to flexion in the ipsilateral limb muscles ( 242,
thalamic nuclei . 318, 319). These responses are ipsilateral be-
cause both fiber systems involved are crossed
( i.e., the superior cerebellar peduncle and the
NEUROTRANSMITTERS
rubrospinal tract ) ( Fig. 15.22 ). Thus, the red
Recent immunohistochemical studies have nucleus appears to act in close conjunction
shed light on the neurotransmitters involved with the motor cortex and the cerebellum for
in the neuronal circuitry centered upon the the control of motor behavior ( 71 , 254 ).
red nucleus. For instance, there is strong evi-
dence for the fact that afferents from lx> th LESIONS OF THE RED NUCLEUS
cerebral cortex and cerebellar nuclei excite
rubral neurons by using excitatory amino Lesions involving the midbrain tegmen -
acids, most likely glutamate, as a neurotrans- tum and the red nucleus unilaterally produce
mitter ( 78, 182, 283). The excitatory influence ( a ) ipsilateral oculomotor disturbances, and
of these two inputs are mediated , at least in ( b ) contralateral motor disturbances of an in -
part , by receptors of the N-methyl - D-aspar- voluntary nature ( i .e., tremor, ataxia , or cho-
tate ( NMDA ) type ( 36, 165). As mentioned reiform movements). This combination of
earlier, however, input from the cerebellum disturbances is known as the syndrome of
terminate preferentially in the proximal so- Benedikt . Experimental evidence suggests the
contralateral abnormal involuntary motor ac- terograde tract -tracing studies have revealed
tivity is due primarily to involvement of that collaterals from the superior cerebellar
crossed fibers of the superior cerebellar pe- peduncle innervate cells of the pedunculo-
duncle ( 55, 56, 195, 275, 324, 406 ). pontine nucleus (173). This finding suggests
that the pedunculopontine nucleus may act
as a functional interface between the basal
Reticular Formation ganglia and the cerebellum for the control of
CYTOARCHITECTONIC DIVISIONS motor behavior.
The nuclei cuneifortnis and subcuneiformis
The midbrain reticular formation is less lie ventral to the tectum and dorsal to the
extensive than that of the pons. This term pedunculopontine nucleus. The nucleus
usually is used to designate structures dorsal cuneiformis extends throughout the rostro-
and lateral to the red nucleus. According to caudal extent of the midbrain where it lies di-
detailed cytoarchitectonic studies ( 290, 291 ), rectly ventral to the superior and inferior col -
the principal reticular nuclei of the midbrain liculi (95). This nucleus increases in size at
reticular formation are (a ) the nucleus more rostral levels and merges with the pre-
tegmenti pedunculopontinus ( pedunculo- tectum . Most of the nucleus is composed of
pontine nucleus ), ( b ) the nucleus cuneiformis, small- and medium-sized oval or fusiform
and (c) the nucleus subcuneiformis. cells. The nucleus subcuneiformis lies ventral
The pedunculopontine nucleus lies in the lat- to the nucleus cuneiformis. Descending fibers
eral part of the midbrain tegmentum ventral from the cuneiform nucleus cross in the ven-
to the inferior colliculus ( Fig. 14.3). The nu - tral tegmental decussation and project to ter-
cleus consists of two parts, a compact part lo- minations in the reticulotegmental nucleus,
cated dorsolaterally and a small-celled dif - the medial pontine and medullary reticular
fuse part located ventrally ( 291 ). Fibers of the formation, the nucleus raphe magnus, and in
superior cerebellar peduncle traverse por- parts of the facial nucleus ( 95). Some fibers
tions of the nucleus as they course ventrome- also end in parts of the medial accessory oli-
dially toward their decussation. The pedun- vary nucleus. Ascending projections of the
culopontine nucleus appears to receive cuneiform nucleus are to the pretectal nuclei,
inputs from multiple sources that include (a ) the nuclei of the posterior commissure, the
the cerebral cortex ( 170, 225), ( b ) the medial posterior hypothalamus, the zona incerta,
( or internal ) pallidal segment ( 67, 213, 281, and the paraventricular and the caudal in-
295, 371 ), and ( c ) the pars reticulata of the tralaminar thalamic nuclei ( 98 ). The wide-
substantia nigra ( 21, 60, 196, 265, 302). Projec- spread connections of the midbrain reticular
tions of the pedunculopontine nucleus are formation are considered to mediate the var -
mostly ascending, with the largest number of ied somatic and visceral responses elicited by
fibers projecting to the pars compacta of the electrical stimulation of this region . These re-
substantia nigra and the subthalamic nucleus. sponses in the cat can be integrated into elab-
A small number of fibers project to the me- orate defense or attack behavior character-
dial pallidal segment ( 21, 60, 89, 161 , 197, 234, ized by pupillary dilatation, widening of the
350, 372 ). A large proportion of the cells in palpebral fissures, flattening of the ears, and
the pedunculopontine nucleus are im- aggressive and vicious behavior (189, 361 ).
munoreactive for choline acetyltransferase
(ChAT ). They correspond to the Ch5 group or
FUNCTIONAL CONSIDERATIONS
sector, as defined by Mesulam, et al . ( 260 ),
and are known to project to the thalamus The anatomic organization of the brain -
( 174, 293, 381 , 422 ) and various basal ganglia stem reticular formation has been described
components, particularly the substantia nigra regionally. In the medulla and pons, four
( 143, 234 , 235, 259 ) . Cells displacing im - zones are recognized: ( a ) a median zone con-
munoreactivity for other transmitters, includ - taining nuclei of the raphe, ( b ) the parame-
ing glutamate ( 75, 233, 235) , are also present dian reticular nuclei, ( c ) a medial zone re-
in the pedunculopontine nucleus. The pedun- garded as an "effector" area , and (d ) a
culopontine nucleus also lies in a region of smaller lateral region referred to as the "sen -
the mesopontine tegmentum from which sory" or "receptive" part because it receives
walking movements can be elicited on electri - collaterals from secondary sensory pathways.
cal stimulation ( 123). Furthermore, recent an- In the medulla , the paramedian reticular nu -
14 Midbrain 553
clei project mainly to the cerebellum. The "ef - duced by stimulation of the rostral and dorsal
fector" zone, which is coextensive with the parts of the nucleus reticularis gigantocellu -
giant cell area of the reticular formation, Iaris, or of the nuclei reticularis pontis cau -
gives rise to both ascending and descending dalis and oralis, presumably could reach
fibers. The "sensory" zone, coextensive with spinal levels by direct reticulospinal fibers
the parvicellular area, projects its axons me- originating in these nuclei . Descending poly-
dially into the "effector" area . The pontine synaptic pathways would appear to mediate
reticular formation has essentially the same facilitatory effects obtained from regions of
zones, although the "sensory" portion is the midbrain and diencephalon, which have
smaller and clearly evident only in the caudal no direct reticulospinal projections.
pons. Descending influences of the brainstem
The reticular formation comprises neurons reticular formation are not limited to inhibi -
that are not part of the major nuclear groups tion and facilitation of somatic motor func-
of the brainstem. It may be considered as a tions. Inspiratory and vasodepressor effects
rostral extension of the interneuronal net- can be obtained from the gigantocellular re-
work of the spinal cord , but is considerably gion in the medulla , while expiratory effects
more extensive ( 344 ). It is composed of neu - are obtained from the parvicellular region .
rons whose axons are widely distributed Vasopressor effects are evoked from lateral
within the neuraxis (355). The axon of reticu - reticular regions that projects noradrenergic
lar neurons not only descends to the spinal fibers to spinal levels (see Chapter 13). Al -
cord , but also ascends to the thalamus and though nearly all parts of the central nervous
hypothalamus. The brainstem reticular for- system are capable of exerting detectable in -
mation is involved in (a ) regulation of mus- fluences upon the heart and blood vessels,
cles reflexes, ( b) coordination of autonomic the primary vasomotor control center is lo-
functions, (c ) modulation of pain sensation, cated laterally in the reticular formation of
and (d ) behavioral arousal. the pons and medulla . Transections of the
brainstem as far caudal as the lower third of
Descending Reticular Neuronal Systems the pons have no significant effect upon arter-
ial pressure. Successively more caudal tran -
Early experimental studies demonstrated sections produce (a ) a drop in blood pressure
that electrical stimulation of the caudal and and ( b ) a reduction in the discharge of cardiac
medial "effector" zone of the medullary retic - accelerator impulses ( 19 ). The bulbar pressor
ular formation inhibits most forms of motor and depressor areas constitute a central car-
activities, such as myotatic reflexes, flexion diovascular mechanism that reflexively regu -
reflex, extensor muscle tone, and cortically in- lates blood pressure and the parameters of
duced movements ( 248, 249 ). Regions of the the heart rate. In the intact animal, a normal
medullary reticular formation from which in - arterial pressure is dependent on the bulbar
hibitory responses are obtained correspond pressor area . A group of noradrenergic neu -
roughly to the area of the gigantocellular part rons (group A 7) (see chapter 12 ), located in
that gives rise to medullary reticulospinal the caudal pons and rostral medulla , sends
fibers ( 399 ). Stimulation of the rostral and axons to the nucleus of the solitary tract, the
dorsal part of the nucleus reticularis giganto- nucleus ambiguus, and preganglionic sympa -
cellularis produces monosynaptic excitatory thetic neurons in the intermediolateral cell
postsynaptic potentials in motor neurons column of the thoracic spinal cord . These
supplying axial muscles in the neck and back. noradrenergic neurons are part of a neural
A far larger region of the brainstem reticu - network related to the regulation of the car -
lar formation facilitates reflex activity and diovascular system.
cortically induced movements. This facilita - The region surrounding the nucleus of the
tory area extends rostrally from the upper solitary tract is coextensive with the physio-
medulla into caudal regions of the dien- logically defined dorsal medullary respira -
cephalon . Bilateral facilitatory effects can be tory "center." A ventral medullary respira -
evoked throughout this extensive region of tory "center" includes the nucleus ambiguus
the reticular formation . The facilitatory re- and the surrounding reticular formation . Ad -
gion of the reticular formation includes many ditional brainstem regions important in the
areas from which no direct reticulospinal control of respiration are the " pneumotaxic
projections arise. Facilitatory effects pro- center" found in the pons near the medial
parabrachial nucleus and an "apneustic cen- an ascending direction to influence the elec-
ter," which remains poorly defined . The trical activity of the cerebral cortex ( 273). The
parabrachial nuclei receive input from the pioneer investigations of Hans Berger ( 31, 32)
nucleus of the solitary tract and , in turn , pro- indicated that in humans and other mammals
ject to both dorsal and ventral respiratory wakefulness, sleep, alertness, and relaxation
"centers" in the medulla . The "pneumotaxic were characterized by strikingly different
center" periodically releases the inhibition of electroencephalographic patterns. Wakeful -
the "apneustic center." ness and alertness are characterized by fast
Stimulation of inhibitory and facilitatory low-voltage activity, while at least one form
regions of the reticular formation can de- of sleep is associated with the appearance of
crease or increase the rates of discharges from slow high-voltage waves.
the muscle spindles via y -efferent fibers. A Fundamental insight into the underlying
part of the effects exerted upon a motor neu- brain mechanisms was provided by Frederic
rons may result from the firing of y-efferents, Bremer ( 43) who compared the electroen -
which indirectly influence these neurons cephalograms ( EEC ) of animals following
through the y -loop, as suggested by the pio- high spinal transections ( encephale isole ) and
neering studies of Granit and his colleagues decerebration (i.e., transection of the mid -
(146) ( Fig. 10.30). Granit and Kaada ( 147 ) brain at the intercollicular level, cerveau isole ).
demonstrated that repetitive electrical stimu - In the encephale isole preparation , the EEC
lation of the facilitating regions of the brain - displayed the waking pattern, while in the
stem tegmentum increased the efferent dis - cerveau isole preparation, the EEC exhibited
charge of y motor neurons and increased the a pattern characteristic of the sleeping state.
rate of discharge from the muscle spindle. On These experiments pointed to a potent as-
the other hand, inhibition of the y discharge cending electrotonic influence generated in
was produced bv stimulating the medullary the lower brainstem . While it was well -
inhibitory region. These data suggest that a known that a variety of different stimuli
large part of the excitation of « motor neu - could change the EEG from a synchronized
rons results from firing of the y-efferents, pattern ( i .e., sleep state), to a desynchronized
which are actively controlled by the reticular one ( i.e., alert state), the puzzling feature was
formation. The inhibition of extensor muscle how impulses channeled in the classic as-
tone in a decerebrate animal by stimulation of cending pathways could exert such broad
the medullary reticular formation ( 393) is a and diffuse electrotonic changes in the cere-
dramatic example of this potent influence. bral cortex. The observations that stimulation
The discovery that the activity of the mus - of the brainstem reticular formation could ac-
cle spindle could be modified by descending tivate and desynchronize the EEG and pro-
reticular projections suggested that the retic - duce behavioral arousal without discharging
ular formation might affect the initiation and the classic lemniscal pathways suggested the
transmission of other sensory impulses. Hag - concept of a second ascending system ( 273).
barth and Kerr (160 ) demonstrated that This second ascending system , exerting pow-
synaptic transmission of sensory impulses in erful influences upon broad regions of the
the spinal cord could be depressed by stimu - cerebral cortex has become known as the as-
lation of the reticular formation . Likewise, cending reticular activating system.
potentials evoked in the posterior column nu - Interruption of the long ascending specific
clei following stimulation of the posterior sensory pathways in the brainstem does not
columns could be depressed or abolished by prevent impulses ascending in the reticular
stimulation of the reticular formation. There activating system from provoking their char-
is now ample evidence that this phenomenon acteristic EEG arousal response (116, 273,
occurs in the case of noxious stimuli, as de- 376). Lesions in the rostromedial midbrain
scribed in Chapter 13. tegmentum abolish the EEG arousal reaction
elicited by sensory stimulation ( 113, 243, 244 ),
Ascending Reticular Neuronal Systems even though long ascending sensory path -
ways are intact . Thus, two functionally
The seminal work of Giussepe Moruzzi distinct pathways must project to the di-
and Horace Magoun in the late 1940s led to encephalon: (a ) long ascending sensory path -
the discovery that the facilitatory region of ways, the lemniscal system , concerned with
the brainstem reticular formation also acts in specific sensory modalities ( i.e., medial lem-
14 Midbrain 555
niscus, lateral lemniscus, spinothalamic dantly to two regions of the brainstem reticu -
tracts, and secondary trigeminal projections) lar formation: (a ) the nucleus reticularis pon-
that end upon specific thalamic nuclei, and tis oralis, and ( b) the nucleus reticularis gi-
( b ) the ascending reticular activating system , gantocellularis ( 347).
which receives collaterals from the surround - Although physiologically the reticular for-
ing specific systems and conveys impulses mation behaves as if it consisted of a chain of
via the reticular core. Physiologically, the as- neurons that fire successively, the reticular
cending reticular activating system is re- formation does not contain short-axoned ,
garded as a multineuronal , polysynaptic Golgi type II cells ( 355 ). Cells in the "effector"
system within which collaterals conveying reticular regions that give rise to long ascend -
impulses of a "nonspecific" nature related to ing fibers in the reticular core appear to form
wakefulness and arousal. the structural basis of the ascending reticular
It must be made clear, however, that the activating system ( 47). Rapidly conducted
passive view of sleep as a functional deaf - impulses in the reticular core are transmitted
ferentation regulated by the ascending reticu - by the main long-ascending axons, while
lar activating system , which has dominated slowly conducted impulses are conveyed by
sleep research for many years, is no longer collaterals or by multisynaptic pathways in-
tenable. Experiments, conducted again by volving laterally dispersed collaterals. The
Morru / i and his colleagues in the late 1950s, main long-ascending pathway in the brain -
questioned the unitary view of the nonspe- stem reticular formation appears to be the
cific reticular activating system. These inves- centra! tegmental tract ( Figs. 13.4, 13.24, and
tigators showed that when brainstem transec- 13.32 ), a large composite bundle that also
tions are performed at midpontine level , just contains descending fiber systems ( 45, 280 ) .
a few millimeters caudal to the midbrain cuts This bundle occupies a large part of the bul -
of Bremer, the animals could not sleep. This bar tegmentum, but at mesencephalic levels it
suggests that the rostral reticular formation is displaced dorsally so that its fibers occupy
contains a population of neurons whose ac- a position adjacent to the central gray and
tivity is required for wakefulness, whereas dorsal to the red nucleus ( Fig. 14.6 ). At dien -
the caudal brainstem reticular formation con- cephalic levels, the central tegmental tract
tains neurons that are necessary for sleep. Al - projects principally to the rostral intralaminar
though there is still much uncertainty as to nuclei of the thalamus. Ascending projections
where exactly in the brainstem these two from medial regions of the midbrain reticular
functionally opposite neuronal populations formation projecting to the hypothalamus are
are located , electrophysiologic studies con- distinct from those contained in the central
firmed the existence of active sleep- inducing tegmental tract ( 280 ). These projections are
neurons in the brainstem reticular formation represented largely by three bundles: ( a ) the
( 382 ). Thus, sleep must be viewed as an active dorsal longitudinal fasciculus ( of Schiitx ) sit -
and rhythmic neural process. uated ventrally in the central gray matter; ( b )
The cerebral cortex also plays a role in al - fibers of the mammillary peduncle, which
tering the state of consciousness and alertness originate in the medial tegmental region ( Fig .
by influencing reticular neurons that mediate 17.14 ) and terminate in the mammillary body
the arousal responses ( 44, 114, 200 ). Such a and lateral hypothalamus ( 279 ); and ( c ) the
role has been suggested by the well -known medial forebrain bundle, which contains cer-
arousal effect of psychic stimuli. Areas of the tain ascending components from several
cerebral cortex from which the arousal re- sources.
sponses can be obtained by nonconvulsive The central reticular core may be regarded
electrical stimulation include loci on the or- as a common system of neurons with multi-
bitofrontal surface, the frontal convexity, the ple relays, which are discharged equivalently
sensorimotor cortex, the posterior parietc>-oc- by all sensory systems projecting collaterals
cipital cortex, the superior temporal gyrus to it . Such a common system is not involved
and the cingulate gyrus. Corticoreticular in the conscious perception of any sensory
fibers, which originate from all parts of the modality, but is concerned with afferent func-
cerebral cortex, convey excitatory impulses to tions common to all types of sensory experi-
the reticular neurons, whose ascending dis- ence, namely, alerting and attracting atten -
charges participate in the arousal response. tion . The nonspecific sensory impulses
Corticoreticular fibers project most abun - ascending in the reticular activating system
appear to sharpen the attentive state of the levels. In contrast, cerebral oxygen uptake in -
cortex and create optimal conditions for the creases above normal during the rapid eye
conscious perception of sensory impulses me- movement ( REM ) phase of sleep, whereas it
diated by the classical pathways. decreases below normal resting levels in
coma ( 212). Thus, coma may be defined as a
Clinical Notes nonsleep loss of consciousness that lasts for
an extended period ( 211 ). Within the range of
In humans, lesions of the brainstem often this definition , different levels of uncon-
produce disturbances of consciousness that sciousness, including lethargy, loss of sensa -
range from fleeting unconsciousness to deep tion , stupor, and coma, can be distinguished
and sustained coma . In all forms of disturbed clinically based on the degree of indifference
consciousness due to brainstem lesions, there exhibited by the patient to various external
is a loss of crude awareness. With lesions of stimuli. Stupor is a state in which someone is
the lower brainstem, unconsciousness usu - responsive only to shaking, shouting, or nox
ious stimuli, whereas coma refers to a state of
-
ally is accompanied by respiratory and
cardiovascular disturbances and , often, total unresponsiveness ( 211 ).
increased muscle tone. The loss of conscious- At all levels of the brainstem, liability to
ness frequently is sudden, and depression of unconsciousness is related to the rapidity
vital functions leads to extreme states. Le- with which the lesions develop. Lesions asso-
sions of the upper brainstem most commonly ciated with hemorrhage produce sudden un-
produce hypersomnia characterized by mus- consciousness and coma. Slowly developing
cular relaxation, slow respiration, and an lesions, such as tumors, may not disturb con -
EEC pattern showing large amplitude slow sciousness for a considerable period of time
waves. The level of unconsciousness usually ( 312 ). Although there is no center particularly
is not deep, and some patients can be aroused concerned with consciousness, there are indi-
briefly. If the patient develops decerebrate cations that the functional integrity of the
rigidity, there is usually coma, but these phe- brainstem reticular formation is essential for
nomena are not always correlated. A variant its maintenance. A healthy cerebral cortex
of hypersomnia seen with upper brainstem cannot by itself maintain the conscious state.
lesions is referred to as akinetic mutism (coma
vigil ). In this variant, the EEC pattern resem - Neurotransmitters
bles that associated with slow-wave sleep,
but eye movements remain normal. Many pa - The brainstem reticular formation is a neu -
tients with such lesions survive for months in rochemically highly heterogeneous structure.
this state. As described in Chapter 13, it harbors neu -
It was once common to postulate a contin- rons that contain serotonin , noradrenaline, or
uum of consciousness that ranged from atten - acetylcholine. Additionally, many of these
tion , alertness, relaxation, and drowsiness, neurons coexpress other neuromediators,
to sleep, stupor, and coma . It was generally particularly neuroactive peptides. The nora -
believed that the level of excitation in the as- drenergic neurons lie principally within lat -
cending reticular activating system deter- eral portions of the reticular formation,
mined the level of consciousness. As men- whereas serotoninergic neurons are mostly
tioned earlier, however, the discovery of the confined to the median raphe nuclei. The
extraordinary amount of neural activity that cholinergic neurons abound particularly
characterizes sleep led to abandonment of the within central portions of the reticular core.
idea of a neurophysiologic continuum from These three groups of chemospecific neu -
quiescence to excitation ( 211 ). The lack of a ronal systems provide ascending projections
direct continuity between the various states to the thalamus, including projections that
of consciousness is best exemplified by the terminate within the intralaminar nuclei .
differences that exist between sleep and Thus, the effects of the ascending reticular ac-
coma . Sleep and coma differ behaviorally by tivating system is likelv to be mediated bv
their arousal threshold or relative reversibil - various neurotransmitters, whose complex
ity . They can also be easily distinguished interplay at target-site levels remains to be
physiologically. Sleep is a highly active neu - elucidated. Among these different neuro-
rologic state during which cerebral oxygen transmitters, serotonin has been the subject of
uptake does not decline from normal waking innumerable studies (198, 199 ). This in-
14 Midbrain 557
dolamine is believed to play an important greater than in any other order and reaches
role in the modulation of various state-de- maximum intensity in humans ( 42, 251, 405).
pendent behaviors mediated through both In humans, pigmented cells do not appear in
the ascending reticular activating system and the substantia nigra until the fourth or fifth
the limbic system . Hallucinogenic drugs, year of life and the amount of melanin within
such as lysergic acid diethylamide ( LSD ), de- each neuron increases significantly with age.
press the serotoninergic system and the re- Caudally, neurons of the pars compacta ex-
lease of inhibition results in hypersensitivity tend as far as the retrorubral area ( RRA ) where
to environmental stimuli and hyperactivity in they become intermingled with fibers of the
a brain otherwise behaving as if it were lateral lemniscus. Lateral to the substantia
asleep. Numerous drugs used to treat psy- nigra , a layer of small cells, the pcripeduncular
choaffective disorders also act principally nucleus , caps the dorsal surface of the crus
upon serotoninergic neurons of the reticular cerebri ( Fig. 14.13).
formation (78). The topographic relationship between the
pars compacta and the pars reticulata of the
substantia nigra varies greatly among
SUBSTANTIA NIGRA
species, and the exact boundary between the
Cytoarchitecture two major nigral subdivisions is not always
easy to trace. In fact, the basis for subdividing
The substantia nigra lies dorsal to the crus the substantia nigra into two (or three ) dis-
cerebri, ventral to the midbrain tegmentum, tinctive parts has been questioned in ultra -
and extends throughout the length of the structural studies ( 334 ). Likewise, there is, at
midbrain ( Figs. 14.1 , 14.3, 14.6, 14.13, and present, no consensus regarding classification
14.19 ). It is rudimentary in fish and amphib- of neurons of the substantia nigra in mam -
ians, makes its definite appearance in reptiles mals. However, most investigators agree that
and birds, expands significantly in mammals, this structure contains a certain proportion of
and reaches its greatest development in pri-
mates, particularly humans (294 ). Since the
—
small neurons ( 10 12 pm ) with short axons,
which are believed to be interneurons (Golgi
early studies of Mingazzini ( 264 ) and Sano type II cells) (112, 359), and a much larger
( 352), this structure is commonly divided into number of projection (Golgi type I ) neurons
two parts: (a ) the pars compacta (SNc), a cell- with medium -sized to large cell bodies. In ro-
rich zone comprising numerous densely dents, the small interneurons are said to rep-
packed neurons that contain melanin pig- resent approximately 10 % of the total neu -
ments, and ( b) the pars reticulata (SNr ), a cell- ronal population in the SNc and 40 % of the
poor zone whose neurons are enmeshed in SNr (156 ). The large output neurons ( 25-40
the dense fiber network of the striatonigral pm ) abound in the SNr where they are em-
fibers. A third part , the pars lateralis (SN1), bedded in a neuropil of fine unmyelinated
comprising fibers and neurons dorsolateral fibers, whereas the medium -size ( 15-25 pm )
and rostral in the most fibrous region of the projection neurons are closely grouped in the
substantia nigra , is also recognized by some SNc but separated from one another by thin
authors ( 111, 113, 315). The pars compacta of astrocytic sheaths.
the substantia nigra can be further divided In cats, all nigral neurons have a promi-
into dorsal and ventral tiers (102 ). Neurons in nent rough endoplasmic reticulum and nu -
the dorsal tier are few in number, have medi- merous free ribosomes, but the larger neu -
olaterally oriented dendrites, and merge me- rons are much richer in cytoplasmic
dially with similar neurons in the ventral organelles than the smaller ones (17, 334 ). In
tegmental area ( VTA ), a tegmental region con - monkeys, nigral neurons display a wide vari-
taining scattered cells of various sizes, many ety of shape and sizes, with diameter ranging
of which are pigmented . In contrast, neurons from 12-99 pm, and no significant difference
in the ventral tier are extremely abundant, has been noted between the large- and
have dorsoventrally oriented dendrites, and medium-sized neurons ( 359). Quantitative es-
form typical cell columns that impinge timates reveal that the total number of neu -
deeply upon the underlying pars reticulata rons in the substantia nigra is much greater in
( Fig. 14.20A ). Most pigmented cells occur in macaque monkeys ( N = 73,508) than in cats
the ventral tier of the substantia nigra . The in- ( N = 38,366 ) and rats ( N = 22,532 ). The neu -
tensity of the pigmentation in primates is rons of the SNc type are by far the most abun-
Figure 14 20 Dopamine immunoreactive neurons of the substantia nigra pars compacta in ttie squirrel monkey A .
.
Low power view of the substantia nigra to illustrate the dopaminergic neurons in the ventral tegmental area ( VTA )
and in the substantia nigra pars compacta (SNc) The dotted line indicates the approximate limit between the dorsal
and ventral tiers of the SNc Note the columns of dopaminergic neurons belonging to the ventral tier of the SNc that
Impinge deeply upon the underlying the substantia nigra pars reticulata (SNi ) The location of the substantia nigra
pars lateralis ( SNI ) is also Indicated. B and C. Higher power views of dopamine-immunopositive neurons lying in the
ventral tier of the SNc Note numerous long immunoreactive dendrites forming a dense bundle oriented dorsoven-
. .
trally (6), and shorter dendrites arborizing in the viscinlty of the cell body (Q CP cerebral peduncle: N III oculomotor
nerve rootles Scale bars equals 0.5 mm in A 125|im in B and 25 |im in C
14 Midbrain 559
dant, accounting for 85% of the total nigral rise to the so-called mesolimbocortical dopamin -
population in monkeys, 58% in cats, and 44 % ergic system, whose fibers arborize principally
in rats ( 315). In humans, the total number of in the ventral striatum, including the nucleus
SNc cells amounts to about one-half million accumbens and the deep layers of the olfac-
( 162, 405). tory tubercle, the amygdala , and the pre-
In Golgi preparations, nigral neurons dis- frontal cortex ( 37, 236 ) ( Fig . 14.21 ). Some
play long radiating, smooth dendrites that dopaminergic neurons in the VTA and dorsal
branch infrequently ( Fig. 14.20 B, C ) . The den- tier of the SNc also project directly to the pal -
dritic fields of the SNc neurons are oriented lidum, where they arborize principally
primarily in a dorsoventral direction , while within the internal pallidal segment ( 236,
those of the SNr neurons have a rostrocaudal 366). Many of the dopaminergic neurons of
direction . The most ventral region of the SNr the VTA contain the neuroactive peptide
contains neurons with dendrites oriented cholecystokinin (360 ), but midbrain dopami-
mostly parallel to the crus cerebri . Further - nergic neurons containing either dopamine
more, intracellular injections studies reveal and cholecystokinin appear to give rise to
that many SNc and SNr neurons give rise to distinct projections to the prefrontal cortex in
dense collateral arborizations ( 294 ). The monkeys (287). Besides its action at striatal
axons of nigral cells branch not only within levels, dopamine can be released into the sub-
the dendritic field of the parent cell but also stantia nigra itself by dendrites of the nigro-
in quite remote regions of the substantia striatal dopaminergic neurons ( 72, 238). Fur-
nigra . The axon collaterals are one of the most thermore, electrotonic coupling is known to
important intrinsic features of the medium - exist between nigrostriatal dopaminergic
sized and large nigral neurons, and may facil- cells but not between SNr cells (144 ). Such
itate complex integration of neuronal output electrical communication between SNc neu -
within the substantia nigra . Some of the in
trinsic collaterals also terminate on dendrites
- rons appears to be involved in modulating
burst firing and in synchronizing dopamine
of the parent cell, forming true autaptic release.
synapses , or autapses, that could play an im- The human substantia nigra contains nu -
portant role in the self -regulation of nigral merous fibers and axon terminals displaying
neurons ( 294 ). The dendrites of nigral neu- immunoreactivity for GABA, substance P, or
rons are covered with boutons that increase enkephalin. Dynorphin is another neuroac-
in number with distance from the soma . The tive peptide that abounds at substantia nigra
majority of these boutons are of type I, with levels (128). The GABAergic fibers arborize
pleomorphic vesicles and symmetric junc- profusely in the SNr, whereas fibers display-
tion , and originate in the striatum ( 334, 359 ). ing immunoreactivity for either substance P
or enkephalin are distributed in the SNr, as
Chemoarchitecture well as in the ventral tier, of the SNc ( 311 ).
Substance P- positive fibers occur in large
The two major divisions of the substantia number in the substantia nigra of rats, cats,
nigra can be readily distinguished from one and primates, whereas enkephalinergic fibers
another on the basis of their neurotransmitter are much more abundant in the substantia
content. The neurons of the SNc contain high nigra of primates than in that of rats and cats
concentrations of dopamine ( Fig. 14.20), as (194 ) ( Fig. 14.22) . In humans, the distribution
first demonstrated with histofluorescence of enkephalinergic fibers is not as extensive
techniques (9 ), whereas those of the SNr dis- as that of substance P- positive fibers, suggest-
play GABA and GAD immunoreactivity (274, ing that specific peptidergic pathways differ-
286, 368). entially innervate the substantia nigra (157,
Collections of dopaminergic neurons of 311 ). Peptidergic fibers at the substantia nigra
the SNc, VTA , and RRA correspond respec - levels display a typical arrangement termed
" woolly " fibers ( 158 ) . Woolly fibers are com -
tively to groups A9, A10, and A8 of
Dahlstrom and Fuxe ( 15) (86 ). Cells of the posed of an unstained core ( the dendrite of a
SNc and RRA give rise to the massive nigros- nigral cell ) ensheathed in a dense plexus of
triatal ( mesostriatal ) dopaminergic system , thin beaded fibers ( the substance P- or
whose fibers arborize profusely in most of the
caudate nucleus and putamen, except their
-
enkephalin positive fibers ) (157, 311 ). In ac-
cordance with experimental findings from
most ventral portions. Cells in the VTA give animal studies, neuropathologic data clearly
Occipital Frontal
lobe
- Accumbens
nucleus
Amygdala Septal and
HIP diagonal
Midbrain
band nuclei
- Pons
Medulla
Spinal cord
Figure 14.21 Comparison ot the ascending projections arising from the dopaminergic neurons in the substantia
nigra pars compacta ( SNc ) and in the ventral tegmental area ( VTA ) transposed on a parasagittal section of the
. . .
human brain. AC, anterior commissure; CB cerebellum; CD caudate nucleus HIP, hippocampal formation; HYP hy- .
. .
pothalamus; HB, habenula OT, olfactory tubercle; TH thalamus.
-
indicate that both substance P and enkeph - the putamen and are known as striatonigral
alin - positive fibers in the human substantia fibers.
nigra originate from the striatum. For exam -
ple, in both striatopallidal infarction (310) STRIATONIGRAL FIBERS
and 1 luntington 's disease ( 100, 330) there is a
marked decrease of nigral peptidergic inner- These fibers ( 270, 349, 410 ) are topographi -
vation . The substantia nigra also displays nu - cally organized ( Fig. 14.23), but their exten -
merous serotonin-immunoreactive fibers and sive nature, organization, and regions of ter-
terminals, particularly in the SNr ( 230 ). The mination were not appreciated until the
dorsal nucleus of the raphe appears to be the anterograde degeneration studies of Voneida
principal source of this serotoninergic inner - and Szabo ( 387-389). These investiga-
( 411 )
vation ( 49, 60, 92, 230). tions indicated that, in primates, fibers from
the head of the caudate nucleus project to the
Afferent Connections rostral third of the substantia nigra and have
a mediolateral correspondence in primates.
Afferents to the substantia nigra arise Fibers from the putamen project to the caudal
mainly from the striatum (caudate nucleus two-thirds of substantia nigra , with dorsal re-
and putamen ), the lateral ( or external ) seg- gions of the putamen related to lateral parts
ment of the globus pallidus, the subthalamic of the nigra , and ventral regions related to
nucleus, the dorsal raphe nucleus, the pedun- medial parts of the nigra. More recent studies
culopontine nucleus, and the cerebral cortex. with highly sensitive anterograde tracers
Quantitatively the largest numbers of nigral (127, 175, 298 ) have confirmed that there is an
afferents arise from the caudate nucleus and inverse topographic relationship between
14 Midbrain 561
Figure 14.22 Transverse sections through the middle third of the substantia nigra in a rat , cat , and squirrel monkey
comparing the distribution of substance P (SP)- and enkephalin (EN/O-lmmunoreactive fibers The hatched areas rep-
.
resent dense networks of fine immunoreactlve fibers, the small dots Illustrate more scattered coarse fibers. CP cere-
. . .
bral peduncle; SNc substantia nigra pars compacta; SNr substantia nigra pars reticulata; III oculomotor nerve
rootlets
striatal cells of origin and their termination onto neurons in most of the extent of the sub-
sites in the substantia nigra. They also re- stantia nigra and ventral tegmental area
vealed that fibers from both putamen and (159). While most of the striatonigral fibers
caudate nucleus form multiple terminal fiber are regarded as terminating onto GABAergic
plexuses that are distributed throughout the neurons in the SNr, some striatal fibers termi -
rostrocaudal and mediolateral extent of the nate also onto dopaminergic neurons in the
substantia nigra (127, 298). Furthermore, neu - SNc. Even in the SNr, GABAergic and pep-
rons located in ventral portions of the stria - tidergic striatal fibers synapse upon the long,
tum , including the nucleus accumbens and ventrally oriented dendrites of the dopamin -
the deep layers of the olfactory tubercle, ap- ergic SNc neurons ( 41, 308). Striatonigral
pear to project in a highly divergent manner fibers arise from multitudinous medium-
CD
/• . p
A/ A ' Pul
'
SCO
'V v CM ~ J '
\ VLo ,
i
> O Nigrostriatal fibers

O —< Slrionigral fibers
Figure 14.23 Striatonigral feedback system In a sagittal plane. Strlatonigral fibers project topographically upon cells
-
of the substantia nigra pars reticulata (SNr) and have y -aminobutyric acid (GABA) as their neurotransmitter . Cells of
the substantia nigra pars compacta (SNc) give rise to reciprocally arranged nigrostriatal fibers which convey
. . .
dopamine to specific loci within the striatum. AC anterior commissure CD caudate nucleus; CM centromedian nu- .
. .
cleus; ICO inferior colliculus; GPe, external segment of globus pallidus; ML medial lemniscus; GPL internal segment of
. . .
globus pallidus; OT. optic tract; PPN. pedunculopontine nucleus; Pul pulvinar: PUT putamen; SCO superior colliculus;
. . . . .
SN substantia nigra S7N subthalamic nucleus VA ventral anterior nucleus; VLo, ventral lateral thalamic nucleus,
. .
pars oralis Zl zona incerta.
sized (12-20 pm) neurons with spiny den- whereas striatal fibers terminate largely in the
drites ( medium spiny neurons ) scattered more distal dendritic domain of SNr neurons.
throughout the caudate nucleus and putamen Thus, the pallidonigral projection allows the
( 49, 154 ), and establish symmetric types of striatum to influence the same SNr neurons
synapses on the soma, dendritic trunks, or by acting directly on their distal dendrites
dendrites of nigral cells in the SNr. The stria- and indirectly on their cell bodies via a relay
tonigral fibers use GABA as their major in the lateral (or external ) pallidal segment
small - molecule transmitter , but also coex- ( 298).
press either substance P, enkephalin , and
dynorphin , or a combination thereof (128, SUBTHALAMONIGRAL FIBERS
294 ). While GABA is known to be inhibitory,
substance P is considered to be excitatory. These fibers were demonstrated by both
The precise role of opiate peptides at substan - anterograde and retrograde transport studies
tia nigra levels remains to be defined . in primates ( 58, 277, 303, 365). They form sev -
eral terminal fiber plexuses in the SNr ( 216),
PALLIDONIGRAL FIBERS but the exact relationship with the multiple
terminal plexuses formed by the striatonigral
These fibers were identified in a number of fibers remains to be established . Fluorescent
animals by retrograde transport studies ( 49, double-labeling studies suggest that in the rat
154, 209). They are considered GABAergic virtually all cells in the subthalamic nucleus
and arise from the lateral (or external ) palli- project axons to both the substantia nigra and
dal segment. They terminate in the form of the globus pallidus ( 403). Similar studies in
typical basket -like arrangements around the primates reveal that only about 10% of the
cell bodies of SNr neurons ( 299), with large subthalamic nucleus neurons project to both
terminal boutons making symmetric SNr and globus pallidus (297). Subthalamoni -
synapses. The pallidonigral projection ap- gral fibers terminate in the form of large bou -
pears particularly well -developed in rodents, tons that make asymmetric synapses with
and pallidonigral fibers were shown to con- dendrites and cell bodies of SNr neurons and
verge with striatonigral fibers upon the same display glutamate immunoreactivity (336).
SNr neurons (364). The pallidonigral input Thus, the subthalamic nucleus appears to
appears to complement the striatonigral af - exert a glutamate-mediated excitatory influ -
ferent in that pallidal fibers arborize mostly ence upon SNr neurons which can serve to
in the proximal somatodendritic domain , counteract the strong GABA - mediated action
14 Midbrain 563
of the striatonigral and pallidonigral fibers its terminals form asymmetric synaptic con -
upon the same neurons. tacts with both cell bodies and proximal
dendrites of SNc dopaminergic neurons ( 40,
RAPHE -NIGRAL FIBERS -
143, 235, 255, 256, 259 ). An increase in the ac
tivity of the SNc cells is observed after either
These fibers use serotonin as their major electrical stimulation of the pedunculopon -
neurotransmitter and arise principally from tine nucleus or exogenous application of
the dorsal raphe nucleus and less abundantly acetylcholine and nicotine ( 284 , 354 ). These
from the median (central superior) raphe nu - results indicate that the substantia nigra is a
cleus of the midbrain ( 2, 16, 91, 121, 198, 230, site of cholinergic transmission and suggest
271, 296, 304, 379, 380). They arborize pro- that acetylcholine and dopamine interact at
fusely in the SNr and much more lightly in nigral levels as they do at striatal levels
the SNc ( 230 ). In rodents, the raphe- nigral ( 235). In addition to ChAT-positive neurons,
projection is largely composed of collaterals the pedunculopontine nucleus also contains
of the raphe-striatal pathway ( 403), appears neurons displaying immunoreactivity for
to be strictly ipsilateral ( 404 ), and contains a
significant number of nonserotoninergic ele-
glutamate ( 75, 233), and some of these gluta -
matergic neurons can be labeled following
ments (88, 380 ). In primates, the exact cellular injection of retrograde tracers into the sub-
origin and the degree of collateralization of stantia nigra ( 235). Furthermore, recent
the raphe-nigral projection remain to be in- studies in monkeys reveal that injection of
vestigated . Ultrastructural studies in pri - anterograde tracers in the pedunculopontine
mates reveal that both synaptic and nonsy - nucleus label terminal boutons that form
naptic axonal varicosities occur in the asymmetric synapses with dopaminergic
neuropil of the substantia nigra, although SNc neurons and display glutamate im -
synapses with specific junctional appositions munoreactivity ( 70). These findings indicate
appear to predominate ( 271, 304 ). The axonal that the pedunculonigral projection in pri -
varicosities exhibiting junctional appositions mates has a dual cholinergic / glutamatergic
were reported to be of the asymmetric type nature ( 235).
( 177, 282, 304 ), and some of these serotoniner -
gic synapses occur on dopaminergic neurons CORTICONIGRAL FIBERS
in both SNc ( 282 ) and VTA (177). These find -
ings indicate that serotonin can alter the ac- These fibers have been a matter of much
tivity of nigrostriatal dopaminergic neurons controversy over the years, their existence
by acting directly at the level of the SNc- VTA being alternatively demonstrated and denied ,
complex ( 230 ). Indeed , despite the fact that sometimes even by the same group of investi -
serotoninergic synapses at nigral levels are of gators ( 332, 338). However, recent retrograde
the asymmetric type, which is usually indica - and anterograde labeling studies provide
tive of excitatory effect, electrical stimulation rather convincing evidence for the existence
of the dorsal nucleus of the raphe predomi - of corticonigral fibers ( 49, 222, 351 ). These
nantly produces inhibition of spontaneous fibers arise principally from the prefrontal
activity in single neurons of the substantia cortex and terminate preferentially within the
nigra (92). This discrepancy could be ex- ipsilateral SNc, with lighter innervation of
plained by the type(s) of receptors upon the SNr, SNI, VTA, and RRA (351 ). Lesions of
which serotonin acts at nigral levels. In pri - the frontal cortex in the cat produce a signifi-
mates, the action of serotonin at the substan- cant decrease of glutamate concentrations at
tia nigra level is likely to be mediated , in part, nigral levels (218), which suggest that corti -
,
by 5- HT receptors, which are the most abun- conigral fibers may use this excitatory amino
-
dant 5 HT receptors subtypes in this brain acid as a neurotransmitter.
area (305, 306, 385).
Efferent Connections
PEDUNCULONIGRAL FIBERS
In respect to its efferent projections, the
These fibers arise in the pedunculopon - substantia nigra can be considered as a dual
tine nucleus and terminate principally in the structure ( 294 ). Whereas the SNc is in some
SNc ( 197, 234, 265, 371, 396 ). There is ample way locked in a closed reciprocal loop with
evidence that the pedunculonigral projec - the striatum ( Fig. 14.23), the SNr has highly
tion is, at least in part , cholinergic, and that divergent projections and is considered , to-
gether with the medial (or internal ) pallidal antibodies directed either
studies with
segment , as one of the major output nuclei of against dopamine itself (15), or against tyro-
the basal ganglia ( Fig. 14.24 ). sine hydroxylase, the rate-limiting enzyme in
the synthesis of dopamine ( 236), have re-
NIGROSTRIATAL FIBERS vealed the organization of the ascending ni
grostriatal dopaminergic system in primates.
-
They were first demonstrated by retro- The nigrostriatal dopaminergic fibers arise
grade cellular degeneration in the substantia from the cell bodies of the SNc, the RRA, and
nigra following cerebral ablations that in - the lateral part of the VTA . These fibers accu -
cluded portions of the striatum ( 407). Subse- mulate dorsomedially to the rostral portion
quent studies showed that the retrograde cell of the substantia nigra, where they form a
changes in the substantia nigra could be cor- massive bundle that courses through the pre-
related with the extent of striatal injury (103, rubral field and ascend along the lateral as-
262). Attempts to trace nigrostriatal fibers in pect of the medial forebrain bundle in the lat -
Marchi preparations indicated that nigral ef - eral hypothalamus. Some ventrally located
ferent fibers ascended and entered both seg- fibers run throughout the rostrocaudal extent
ments of the globus pallidus, but none could of the preopticohypothalamic area and can be
be followed into the caudate nucleus or puta - followed up to the olfactory tubercle,
men ( 261 , 262, 328, 346 ). These data suggest whereas other fibers turn laterodorsally to in-
that nigrostriatal fibers become poorly myeli - vade the caudate nucleus.
nated in the globus pallidus. At more rostral levels in the lateral hypo-
Even though the fluorescent histochemical thalamus, many fiber fascicles detach them-
technique clearly demonstrated nigrostriatal selves from the main bundle and sweep later-
projections ( 10, 402 ), the Nauta silver impreg- ally to reach the globus pallidus and the
nation method failed to provide evidence of a putamen. At pallidal levels, most fibers des-
substantial projection ( 1 , 62, 67). Investiga- tined to the striatum ascend within the inter-
tions of nigral efferent projections using rela - nal and external medullary laminae, as well
tively short survival times and more sensitive as along the inner border of the internal cap-
silver impregnation techniques demonstrated sule, thus avoiding the core of the pallidal
nigrostriatal projections in both the cat and complex. In the striatum, the fibers break into
monkey (65, 266 ). Immunohistochemical a multitude of thin axonal varicosities that
SCO
VAmc ICO
\ PAG \
RN
i
— . ~ PPN VI)
Nr SCP
'1
Pons Medulla
Figure 14 24 Efferent pro|ections of the substantia nigra pars reticulata (SNr) as seen in sagittal sections These
.
GABAerglc neurons give rise to nigrothalamic. nigrotectal and nigrotegmental projections. Collectively, these fibers
represent part of the output system of the basal ganglia by virtue of their input from spiny striatal neurons Nigrothala-
.
mic fibers project to medial parts of the ventral lateral nucleus (1/i.m) (not shown), the magnocellular part of the ven-
tral anterior nucleus ( VAmc), and parts of the mediodorsal nucleus (MD) Of the fibers projecting to the middle and
deep layers of the superior colliculus (SCO), 20-30% represent collaterals of nigrothalamic fibers About 60% of the
cells in the SNr projecting to the thalamus have collaterals that project to the pedunculopontine nucleus ( PPN) CM,
.
centromedian thalamic nucleus: F fornix. H Forel' s field. Hb. habenular nucleus, ICO inferior colliculus: MD.
. . . . . .
mediodorsal nucleus MM, mammillary body OT optic tract PAG periaqueductal gray: RN red nucleus: SCP supe- .
.
rior cerebellar peduncle: V( abducens nucleus: III oculomotor nerve
14 Midbrain 565
are rather uniformly scattered along the ros- atal projection neurons with highly specific
trocaudal extent of the striatum, but appear ,
D and D2 receptor agonists and antagonists
slightly more numerous in the ventral stria- so as to develop more effective treatment for
tum than in the dorsal striatum . Zones con- motor and psychoaffective disorders.
taining relatively few axonal varicosities em- Striatonigral and nigrostriatal fibers ap-
bedded in a matrix of dense terminal labeling pear to form a closed feedback loop in which
occur in the striatum, particularly in the head striatonigral fibers form the afferent limb and
of the caudate nucleus ( 236). These zones of nigrostriatal fibers constitute the efferent
weak dopaminergic innervation appear to limb. This reciprocal arrangement is evident
correspond to the striatal patches or "strio- in that HRP injected into the striatum is trans-
somes" that are embedded in a dense exported retrogradely from the axon terminals
trastriosomal matrix, both forming two to cells of the SNc, and anterogradely via stri -
anatomically and neurochemically distinct atal neurons to the SNr ( 278, 367) ( Fig. 14.25).
striatal compartments (152) (see Chapter 19 Retrograde transport studies of HRP in the
for further details). cat and monkey provide data concerning the
Nigrostriatal dopaminergic fibers termi- topographic organization of nigrostriatal pro-
nate upon striatal projection neurons, where jections ( 390, 391 ). The projections of the SNc
they make symmetric synaptic contacts prin- to the striatum are organized in all principal
cipally on the neck of dendritic spines (117). planes. The rostral two-thirds of the substan-
Thus, the striatal dopaminergic input appears tia nigra is related to the head of the caudate
ideally located to modulate the influence of nucleus, while neurons projecting to the
the corticostriatal fibers, which terminate putamen are located posteriorly. An inverse
upon the head of the spines of medium-sized relationship exists dorsoventrally between
striatal projection neurons. the substantia nigra and the caudate nucleus,
Until recently, it was believed that so that ventral parts of the pars compacta
dopamine mediates its effects by interacting project to dorsal regions of the caudate nu -
with two receptor subtypes, which have been cleus and dorsally situated neurons in the
designated D, and D: on the basis of different nigra pass to ventral regions of the caudate
biochemical, electrophysiologic, and pharma - nucleus. Lateral and posterior regions of the
cologic properties (84, 207, 331 ). The cloning nigra are related to dorsal and lateral parts of
of putative D,, D4, and D3 receptor subtypes, the putamen. There is also a mediolateral cor-
however, implies that there is even greater respondence between the cells of the substan -
heterogeneity within the dopamine receptor tia nigra and regions of fiber termination in
family (78). In general, D, and D; receptors the striatum.
have opposite effects on biochemical systems. Other levels of organization are superim-
,
For example, activation of D receptor in- posed upon this crude topographic arrange-
creases adenyl cyclase and cAMP production, ment. For example, fluorescent retrograde
whereas D2 receptor inhibit, or have no effect double-labeling studies in primates reveal
on, this enzyme. These two receptor subtypes that nigral projections to the caudate nucleus
can interact to produce additive or synergis- and to the putamen arise from separate neu -
tic effects, which may explain the wide vari- rons that form closely interdigitated clusters
ety of effects on behavior and movement-rein the SNc (301 ) ( Figs. 14.26 and 14.29). Other
lated functions noted with the use of different studies in rodents show that cells in the dor-
dopamine agonists. Recent evidence obtained sal tier of the SNc and adjoining VTA project
in the rat suggests that D2 receptors are pref - mainly the matrix compartment of the stria -
erentially located on striatal neurons that tum, whereas those in the ventral tier project
contain enkephalin and project to the lateral to the striatal patches or striosomes (see
(or external ) pallidal segment, while D, re- Chapter 19). In turn, neurons in the striatal
ceptors abound on striatal neurons that pro- matrix project principally to the SNr, while
ject to the medial (or internal ) pallidal seg- those in striatal patches innervate the dorsal
ment and the SNr and contain substance P tier of the SNc (128, 130). Neurons located in
and dynorphin (128, 129). This concept of a the dorsal tier of the SNc and projecting to
differential distribution of dopamine recep- the striatal matrix compartment are enriched
tors at striatal levels has important functional with the calcium binding protein calbindin
implications. Among other things, it raises D-28 k, whereas those lying in the ventral tier
the possibility of pharmacologically acting and projecting to the striosomes are largely
specifically upon one or the other type of stri- devoid of such a protein ( 128). A similar, al -
c
Figure 14 25 Features of the anterograde and retrograde labeling observed at the level of the substantia nigra
after injection of wheat germ agglutinin-horseradish peroxidase conjugated (WGA -HRP) in the caudate nucleus on
the right (A) and in the putamen on the left side (B C and D) in squirrel monkeys A and B. Some retrogradely labeled
nigral cells on the caudate-injected side (A) and putamen-injected side (B) as they appear under darkfield illumina-
tion The bundle of anterogradely labeled nigrostriatal axons is partially visible in the upper portion of each photomi-
crograph Note that labeled cells are more closely packed on the putamen-injected side (B) than on the caudate-
injected side ( A) C and D. Typical clusters of retrogradely labeled nigral cells lying within a dense terminal field of
putamenonigral fibers, as seen under brightfield illumination Scale bars equal 250 jim
beit less distinct , arrangement appears to the ventral anterior nucleus ( VAmc ) and the
exist in primates ( 204, 227 ) . These findings in- paralaminar part of the mediodorsal nucleus
dicate that the striatonigrostriatal loop is not ( MDpl ) (58, 191, 193, 333 ) . In their course ,
organized in a strict point -to-point manner. these fibers closely parallel the mammil-
lothalamic tract (63, 65, 67 ). Cells of the SNr
NIGROTHALAMIC FIBERS constitute an important component of the
output system of the basal ganglia bv virtue
They arise from GABAergic cells of the of their linkage with the striatonigral fibers.
SNr and project to the magnocellular part of In primates, nigrothalamic fibers terminate in
14 Midbrain 567
/ o
u&. spferrvpl
» .;.
'" y O
ojo '
0
B
CP V o
l
Figure 14.26 Transverse sections through the rostral ( A) and middle ( B) third of the substantia nigra of the squirrel
monkey illustrating the mosaic -like distribution of the pars compacta ( SNc ) neurons projecting to the caudate nu-
cleus (open circles) and the putamen ( filled circles), as seen after injection of one fluorescent retrograde tracer in the
.
caudate nucleus (CD) and another in the putamen ( PUT) on the same side of the brain. CP cerebral peduncle: SNr .
.
substantia nigra pars reticulata, III oculomotor nerve rootlets.
thalamic motor nuclei, which do not receive portion of the SNr coextensive with the SN 1,
afferents from any other part of the basal gan - as defined by certain investigators ( 111 ).
glia nor from the cerebellum ( 192, 193, 307). These neurons project to the middle gray lay-
Fluorescent retrograde double-labeling stud - ers of the caudal two-thirds of the ipsilateral
ies indicate that nigrothalamic fibers have superior colliculus, and appear topographi -
significant numbers of collaterals that project cally organized ( 153, 183, 201, 335) ( Fig.
to the superior colliculus and the mesopon- 14.27). Projections of nigrotectal fibers are to
tine tegmentum ( 20, 302 ) ( Figs. 14.24, 14.28, portions of the superior colliculus that re-
and 14.29 ). ceive inputs not related to the visual system
and contain large neurons giving rise to the
NIGROTECTAL AND NIGROTEGMENTAL tectospinal pathway. Electrophysiologic and
FIBERS fluorescent retrograde double- labeling stud -
ies reveal that a significant proportion of the
Nigrotectal fibers arise only from cells of the SNr neurons projecting to the superior col -
SNr, particularly those located in the lateral liculus also project to the thalamus ( If , 12, 20,
tural reflexes. These abnormal movements in -

clude (a ) tremor ( rhythmic, involuntary, oscil -
latory movements of a body part ), ( b ) athetosis
(slow, writhing movements involving pri -
marily the distal part of the limb), ( c ) chorea
( rapid , flick-like movements of the limbs and
facial muscles), (d ) batlism ( violent, flailing
movements primarily involving proximal
parts of the limb ), and (e) dystonia ( a persis-
tent posture of a body part that can result in
grotesque movements and distorted posi-
tions of the body ) (79). Parkinson's disease
( paralysis agitans), one of the best character -
ized disorders of the basal ganglia , usually
comprises (a ) a rhythmic tremor at rest, ( b )
increased muscle tone or rigidity, and (c) a
slowness in the initiation of movement ( aki -
nesia ) as well as in the execution of move-
Figure 14.27 Darkfield photomicrograph of an autora
diograph demonstrating nigrotectal terminations Nigro-
ment (bradykinesia ). The Parkinsonian syn -
drome may have different etiologies such as
tectal fibers arise from cells in the substantia nigra pars
reticulata (SNr) and terminate in the deep and middle idiopathic Parkinson 's disease, progressive
gray layers of the superior colliculus supranuclear palsv, striatonigral degenera -
tion, and postencephalitic Parkinsonism.
However, idiopathic Parkinson 's disease
302 ). Nigrotectal fibers play an important role ( PD ) is by far the most common of all degen -
in the control of oculomotor activities, partic- erative forms of Parkinsonism . Multisystem
ularly in the initiation of saccadic ( rapid ) eye degeneration Parkinsonisms account only for
movements ( 178-181 ). about 15‘>; of all forms ( 202).
Ni$rote$mental fibers arise also from The neuropathologic hallmark of Parkin -
GABAergic neurons of the SNr and project son 's disease is a massive loss of pigmented
principally to the pedunculopontine nucleus cells of the substantia nigra and ventral
( 21, 60 ). A large proportion of SNr neurons, tegmental area first noted by Tretiakoff ( 401 ),
up to 60% , project collaterals to both thala - and later confirmed by Foix ( 108), Foix and
mus and pedunculopontine nucleus ( 20, 302). Nicolesco (109), and llassler ( 171 ) ( Fig. 14.30 ).
As mentioned , cells of the pedunculopontine The cell loss in the substantia nigra ranges
nucleus receive inputs from multiple sources, from 50-85%, whereas it appears more vari -
including the cerebral cortex, the medial (or able in the ventral tegmental area ( 202 ). The
internal ) pallidal segment, and the cerebel - nigral cell loss is currently accompanied by
lum. In turn, neurons of the pedunculopon - massive reactive gliosis. Furthermore, degen -
tine nucleus project back to the substantia erating nigral neurons were found to display
nigra, where they terminate, not on GABAer- cytoskeletal abnormalities, such as cytoplas -
gic neurons of the SNr that innervate them , mic inclusion bodies first described bv Lewy
but on the dopaminergic nigrostriatal neu - ( 237) and referred to as Leuu/ bodies (110 ).
rons of the SNc. Thus, the nigrotegmental Since the pigmented dopaminergic cells are
fibers are part of a nigrotegmentonigral feed - the major target of the neuronal degenerative
back loop that, as is the case for the nigrostri - processes involved in Parkinson's disease,
atonigral loop, involves the two major subdi- the main biochemical feature of this disease is
visions of the substantia nigra. a marked decrease of striatal dopamine
concentrations, as first observed by Oleh
Neuropathology Hornykiewicz and his colleagues (99,
184-186). However, the dopaminergic neu -
The substantia nigra is involved in some of ronal systems do not degenerate to the same
the most prominent basal ganglia diseases, degree. The nigrostriatal ( mesostriatal ) sys-
characterized by involuntary movements tems is more severely affected than the
( dyskinesia ), poverty or slowness of move - mesolimbocortical system and the striatal
ment , and disorders of muscle tone and pos- dopaminergic denervation is more prominent
14 Midbrain 569
Figure 14.28 Transverse sections through

the middle third of the substantia nigra in
VA / VL ( o) the squirrel monkey summarizing the distri-
*• o o PPN ( •) bution of retrogradely labeled neurons In
•* o
two typical coses in a series of double-la-
* *
** '
°* beling experiments with retrograde fluo-
° **
I
o rescent tracers. This study was designed to
*
* SNC \ study the cellular origin and degree of ax
* o
* *o * o
' onal collateralization of the SNr efferent
° * projections in primates A . Results ob-
o
o
tained after injections of one tracer in the
o ventral anterior / ventral lateral thalamic
*° •
* *o
SNr nuclei (VA / VL ) and the other in the pe -
0
o* * dunculopontine nucleus (PP/V) B Results
'.
t
\*
. o . 00
o
obtained after injections in the VA / VL nu-
° *O * *
*v •
• * **
o' -• '
«
• clei and the superior colliculus (SCO) The
. ;0 0 -
double-labeled cells are represented by
* *
O 4 '
• • • .
asterisks CP. cerebral peduncle SNc sub-
* * .
stantia nigra pars compacta SNr. substan -
CP * .
tia nigra pars reticulala; III oculomotor
nerve rootlets
o
o o VA / VL ( o )
oo o o
o o o \ SCO (•)
o
o o o
'
o
° o o •
o o
* o
•• ;
* ° o SNC \
• • o
o
0 *0 •° -
1
•' ,
I
I
/;
I
.**
O o
* °“ SNr '
° ^- x
* o o I
• •1 \
\
I
0
°* * . \
0 0
O
• o °
• •o
o '
- - -« 0
CP
in the putamen than in the caudate nucleus left unmetabolized systemically to enter the
the striatal dopamine de-
( 3, 99, 186 ) . Overall, brain where the desired decarboxylation to
pletion is directly proportional to the cell loss dopamine can occur ( Fig. 1.15). Although L-
in the substantia nigra ( 33). dopa therapy has been hailed as the most sig-
An effective treatment for Parkinson's dis- nificant treatment of Parkinson's disease, this
ease is the oral administration of large doses drug does not alter the course of the disease.
-
of L dihydroxyphenylalanine ( L dopa or lev
odopa ), a precursor of dopamine, which
- - Additionally, many patients become refrac
tory or suffer side effects (e.g., hallucinations,
-
-
passes the blood brain barrier. The effective- nausea ) after treatment with L-dopa for sev -
ness of L-dopa can be enhanced by the use of eral years. Thus, new approaches have been
a peripheral decarboxylase inhibitor, which used to overcome the limitations of L dopa -
prevents systemic decarboxylation of L-dopa therapy. One involves the transplantation of
to dopamine. Thus, adequate L-dopa will be fetal dopaminergic cells into the striatum (93,
B #
g f
*
Figure 14.29 Fluorescence photomicrographs showing various features of the retrograde labeling in the substantia
nigra of the squirrel monkey after double-labeling experiments A. A typical cluster of pars compacta neurons pro-
jecting to the striatum, as seen after injection of Evans blue ( fS) in the putamen B. One of the few cells in the pars
reticulata that was retrogradely labeled after injection of True blue (JB) in the putamen The arrow points to the initial
axon segment C One of the rare double-labeled cells visualized in the pars compacta after injection of Nuclear yel-
low (NY ) in the putamen and Fast blue (FS) in the caudate nucleus NY is confined to the nucleus, which displays a
bright yellow -green fluorescence, whereas TB is revealed by the dull blue appearance of the cytoplasm of the neu-
ron. D. High power view of nlgrostriatal neurons in the pars compacta retrogradely labeled with EB injected into the
putamen (same animal as in A) E . Some of the numerous double-labeled neurons seen in the lateral sector of the
pars reticulata after injection of NY into the superior colliculus and FB into the ventral anterior / ventral lateral (VA / VL)
thalamic nuclei
14 Midbrain 571
SNc
•% . * *
Figure 14 30 Number and distribution of neurons displaying (a) tyrosine hydroxylase ( TH) immunoreactivity (open or
ctes). (b) calbindin (CaBP) immunoreactivity ( asterisks), and (c) both TH and CaBP ( filled circles ) in the middle third of
the substantia nigra/ ventral tegmental area complex in two cynomolgus monkeys ( Macaca fascicularis) The animal
in A was normal, whereas the one in B was rendered parkinsonian by the systemic administration of the neurotoxin
MPTP Note the massive loss of TH-immunoreactive neurons in the ventral tier of the substantia nigra pars compocta
and the relative sparing of TH /CaBP-immunoreactive neurons in the dorsal tier of the SNc in the parkinsonian monkey
Each symbol represents five cells CP. cerebral peduncle. SNc. substantia nigra pars compocta; SNr. substantia nigra
.
pars reticulata; III oculomotor nerve rootlets
424). Fetal nigral neurons can be successfully neurons of the substantia nigra and can pro-
incorporated into the adult striatum, where duce a typical Parkinsonian syndrome in
they can serve as a permanent intrinsic both human and nonhuman primates ( 73,
source of dopamine. Such grafts can alleviate 217, 228, 229 ) gives further support to the hy -
experimentally induced behavioral deficits in pothesis that an environmental toxin may
rats, but the clinical usefulness of these trans- play a role in the development of Parkinson 's
plants in humans is still being debated . disease.
Lesions of the substantia nigra in rats, cats, This availability of such a specific neuro-
and monkeys result in a marked depletion toxin has allowed the development of highly
of striatal dopamine together with motor ab- valuable primate models of Parkinson's dis -
normalities ( 23, 313, 316, 317, 402 ). Recently, ease ( 22 ), as well as the study of molecular
the discovery that the meperidine analog mechanisms involved in neuronal cell death.
- - -
1- methy1 4- phenyl 1,2,5,6 tetrahydropyrid in In monkeys rendered Parkinsonian after sys-
( MPTP) is highly toxic to the dopaminergic temic injection of MPTP, the major loss of ni -
grnl dopaminergic neurons occurs in the ven - tremity; the larger middle region contains
tral tier of the SNc, where most pigmented fibers concerned with the upper extremity;
neurons are located (131 , 232, 3( H ), 358). Bv and the most medial fibers of the central re-
comparison , dopaminergic neurons in the gion are associated with the musculature of
dorsal tier of the SNc and in the VTA are less the face, pharynx and larynx. The extreme
severely affected . Interestingly, neurons that medial and lateral portions of the crus cerebri
are less severely affected are those that ex- contain corticopontine fibers . Frontopontine
press both tyrosine hydroxylase and the cal- fibers are medial, while corticopontine fibers
cium binding protein calbindin D-28k, from the temporal, parietal, and occipital cor-
whereas neurons that degenerate massively tices are located laterally ( Fig. 14.1 ).
are those that express tyrosine hydroxylase The corticospinal fibers in the internal cap-
only ( Fig. 14.3(1). Likewise, pigmented neu - sule are largely confined to a compact region
rons devoid of calbindin immunoreactivity in the caudal part of the posterior limb of the
degenerate massively, whereas nonpig- internal capsule ( 34, 101 , 135, 164, 363). Soma -
mented neurons expressing calbindin are rel- totopical organization of fibers destined for
atively spared in cases of human idiopathic particular segmental levels appears relatively
Parkinsonism ( 423). These findings indicate crude. These data suggest that the somato-
that, by virtue of its capacity of binding large topic arrangement of corticospinal fibers in
quantities of free calcium ions, calbindin may the crus cerebri probably is much less precise
protect nigral dopaminergic neurons from than commonly depicted. In humans, corti-
neurodegenerative processes. Current studies cospinal fibers probably account for only 1
involving animal models of Parkinson's dis- million of the 20 million fibers in the crus
ease should bring novel information regard - cerebri; the remaining fibers are largely corti -
ing the use of various growth factors and dif - copontine (397).
ferent neuroprotective molecules as possible Besides these named tracts, there often are
cures for Parkinson 's disease and other neu - two fiber bundles which descend partly
rodegenerative d isorders. within the crus cerebri and partly in the re-
Other complex interrelationships between gion of the medial lemniscus, known as pcs
dopamine, GABA, and acetylcholine suggest lemnisci. The medial or superficial pes lemniscus
that both the striatum and the substantia detaches itself from the lateral portion of the
nigra may be involved in the neural mecha- crus cerebri, winds ventrally around the crus,
nisms responsible for choreoid dyskinesia in and forms a semilunar fiber bundle medial to
Huntington 's disease, which is characterized the frontal corticopontine tract ( Fig. 14.1 ). At
by a marked striatal atrophy due to a severe lower levels, the fibers leave the crus cerebri,
loss of GABAergic projection neurons in the pass dorsally through the substantia nigra,
striatum (6). Much remains to be learned and descend in or near the ventromedial por-
about neurotransmitter alterations in various tion of the medial lemniscus. The lateral or
multisystemic disorders, such as progressive deep pes lemniscus detaches itself from the dor-
supranuclear palsy and striatonigral degener- sal surface of the crus, runs for some distance
ation , which are characterized by motor in the lateral portion of the substantia nigra,
deficits similar to those encountered in then turns dorsally and descends in the re-
Parkinson's disease. gion of the medial lemniscus ( Fig. 14.1 ). Cer-
tain authors (87, 409) regarded these bundles
CRUS CEREBRI as aberrant corticospinal fibers which during
phylogenesis became separated from the
The most ventral part of the midbrain con - main tract by the increasing development of
tains a massive band of descending corticofu - the dorsal pontine nuclei. According to
gal fibers, the crus cerebri . According to Dejer- Kuypers ( 224), fibers of the pes lemnisci can
ine (87), the medial three-fifths of the crus be traced caudally through the pons to the
cerebri contain somatotopically arranged cor - level of the pyramidal decussation. A number
ticospinal and corticobulbar fibers . Other au - of these fibers are distributed to the tegmen-
thors ( 105, 323, 408) indicate that much tum of the pons and medulla . These fibers,
smaller portions of the central part of the crus undoubtedly corticobulbar, appear to project
cerebri contain these fibers. In the classic mainly into the reticular formation. Few, if
view , fibers in the most lateral part of the cen- any, of these fibers pass directly to motor cra -
tral region are concerned with the lower ex- nial nerve nuclei ( Fig. 12.27).
14 Midbrain 573
References monkey CSaimiri scmreus ). ) Comp hitlii ) : an autoradiographic study

Neurol 19H8;267:489 - 306. Brain Res 1976;108:1 24
1 . Afifi A , Kaelber VVW . Efferent con - 16 . Azmitia EC, Gannon Pj. The pri - 2H. Beneven to LA , Standage C» l *. The
nections ot the substantia nigra in mate serotoninergic system: A re - organization of the projection of
the cat Exp Neurol 1965;!1 : view of human and animal studies the retinorecipient nuclei of the
474-482. and a report on Miumn fascicuforis . pretectal complex and layers of the
2. Aghajanian GK , Kuhar MJ , Roth In : Fahn S, Marsden CD, Van superior colliculus to the lateral
Rl I . Serotonin -containing neuronal Woert MIL eds. Myoclonus. Ad - pulvinar and medial pulvinar in
perikarya and terminals: differen - vances in neurology. Vol. 43. New the macaque monkey. I Comp
tial effects of p-chlorophenylala - York : Raven Press, 1986:407 468. Neurol I 983;2 I 7:307 146.
nine. Brain Res 1973;54:85-101 . 17. .
Bak II , Choi WB liassler R, 29 Benson CC, Chase* MC, Potashner
3. Agid Y, Javov- Agid F, Ruberg M. Usunoff KG , Wagner A . Fine struc - SJ . Decreased release of D aspar - -
Biochemistry of neurotransmitters tural synaptic organization of the tate in the guinea pig spinal cord
in Parkinson's disease*. In : Marsden corpus striatum and substantia after lesions of the red nucleus. I
CD, Fahn S, eds. Movement disor - nigra in rat and cat . In : Caine C, Neurochem 1991;56:1174 1183.
ders. Vol. 2. London : Butterworths, .
Chase TN Barbeau A, eds. 30. Bentivoglio M . Van Her Kooy I ).
4.
1987: 166-230.
Aitkin EM , Gates GR, Phillips SC.
Dopaminergic mechanisms. Ad
.
vances in neurology Vol . 9. New
- .
Kuypers HCJM . The organization
ot the efferent projections ol the
Responses of neurons of the infe-
rior colliculus to variations in 18
-
York: Raven Press, 1975:15 41.
Baker K . Anatomical and physio-
substantia nigra in the rat : a retro-
grade fluorescent double-labeling
sound -source azimuth . J Neuro- logical organization ot brain stem study. Brain Res IW; 174: 1 -17.
phvsiol 1984 ;52: 1 -17. pathways underlying the control 31 . Berger 14. Leber das Elek -
5. Aitkin EM . Webster WR , Veale JE . of gaze. In : Baker R , Berthoz A , trenkephalogramm des Menschen
Crosby IX Interior colliculus. I eds. Control of gaze by brain stem Arch Psvchiatr Nervenkr I 929;87:
Comparison of response proper - neurons: developments in neuro- -
327 570.
ties of neurons in central , pericen - science. Vol. I . Amsterdam: Else- 32 . Berger H. Ueber das Elek -
tral and external nuclei of adult vier, 1977,207-222. trenkephalogramm des Menschen.
cat . J Neurophysiol 1975,38: I 1# Bard P. Regulation of the systemic J Psychol Neurol 1940;40:160 179. -
-
1196 1207. circulation. In : Mountcastle VB, cd . 44. Bernheimer IL Birkmaver VV ,
h. Albin RE , Young AB, Penney ) B |r. Medical physiology. 12 th ed Vol. I lornykiewicz Of Jellinger K , Seit -
The functional anatomy of basal
ganglia disorders Trends Neurosci
I , Ch. 11. St. Louis: C.V . Mosby
1968: 178-208.
. elberger F Brain dopamine and
the syndromes of Parkinson and
1989.12:366-375. 20. Beckstead RM . Long collateral Huntington . I Neurol Sci 1974;
7. Alley KR, Baker R, Simpson II Af - branches ol the substantia nigra 20:415-433.
ferent* to the vestibulocerebellum pars reticulata axons to thalamus, 44 . Bertrand GL, Blundell |, Musella R
and the origin of the visual climb- superior colliculus and reticular Electrical exploration of the inter -
ing fibers in the rabbit . Brain Res formation in monkey and cat. Mul - nal capsule and neighboring striu
J 975j9fc582 589 tiple neuronal labeling with fluo- tu res during stereotaxic proce-
8. .
Altman J , Carpenter MB Fiber pro - rescent dies. Neuroscience 1984; dures. J Neurosurg I 965;22:
jections of the superior colliculus 10:767-779. 333-343.
in the cat. I Comp Neurol 1961 ; 21. Beckstead RM , Domesick VB, .45, Bianchi K . Gioia M . Accessory ocu -
-
116:157 178. Nauta WJII . Efferent connections lomotor nuclei of man. II . The in -
9. Anden \ - F., Carlsson A,
Dahlstrdm A , Fuxe K , I lillarp N -A,
of the substantia nigra and ventral
tegmental area in the rat . Brain Res
.
terstitial nucleus ot Caj il : a Nissl
and Golgi study. Acta Anal ( Basel )
Larsson K . Demonstration and |979; I 75 : M 217 I W|; l 42:357- 4h 5.
mapping out of nigro- neostrialal 22. Bedard PJ, Boucher R , Gomez - Billard IM Daniel ll . Pumain K
,
dopamine neurons. Life Sci 1904 ; Mancilla B, Blanchette P. Primate Sensitivity of rubrospinal neurons
-
3:523 530. models of Parkinson's disease. In: to excitatory amino acids in the rat
10. Anden N - E, Dahlstrdm A , Fuxe K , Boulton A , Baker G. Butterworth red nucleus in vivo. Neurosci Lett
Larsson K , Olson L, Ungerstedt U . R. eds. Neuromethods. Vol . 21 . 1991;134:49-52.
Ascending monoamine neurons Animal models of neurological dis- 37. Bjorklund A , Lindvall Cl Dopa -
to the telencephalon and dien -
cephalon . Acta Physiol Scand
ease, I. Totowa, N ): Humana Press,
1992:159- 173.
-
mine containing systems in the
CNS. In : Bjorklund A , Hokfelt T,
1966;67:313 326. - 23. Bedard PJ , Larochelle L, Parent A , ills. I landbook of chemical neu -
11 . Anderson ME, Yoshida M . Elect ro
phvsiological evidence for branch
-- Poirier LJ . The nigrostriatal path -
way: a correlative study based on
roanatomy. Vol . 2. Part 1 : Classical
transmitters in the CNS. Ch. 4.
ing nigral projections to the thala - neuroanatomica! and neurochemi - Amsterdam : Elsevier, 1984:35-122.
mus and the superior colliculus. cal criteria in the cat and monkev . 38. Bobillier P, Petit jean F, Salvert I ).
Brain Res 1977;137:361-364. Exp Neurol 1969;25:363-377. l .igier M , Seguin s Differential
12. Anderson ME, Yoshida M . Axonal 24 Beit / A ) . The midbrain periaque - projections of the nucleus raphe
branching patterns and location of ductal gray in the rat . I . Nuclear dorsalis and nucleus raphe cen -
nigrothalamic and nigrocollicular volume, cell number, density, ori - tralis as revealed by autoradiogra-
neurons in the cat. I Neurophvsiol
1980,43:883-895.
entation and regional subdivisions.
I Comp Neurol 1985;237:443 459 - 40 . ^ -
phy, Brain Res 1975 5:205 210.
Bobillier P, Seguin S, Pctitjcan F,
13. Apter |T. Eye movements follow - 25. Beitz AJ , Shepard RD. The mid - Salvert D, Touret M, Jouvet M . The
ing strychnmi / ation of the supe- brain periaqueductal gray in the raphe nuclei ot the cat brain stem:
rior colliculus of cats. I Neurophvs- rat . II . A Golgi analysis. J Comp a topographical atlas of their effer -
iol 1946;9:73-86. Neurol 1985;237:460 475.- ent projections as revealed by au -
14. Aronson ER , Papez JW. Thalamic 26. Benevento I .A , Fallon JH. The as- toradiography . Brain Res |97h ;
nuclei of Pithecus ( Macacos ) rhe- cending projections of the superior 113:449-486.
sus. II . Dorsal thalamus. Arch Neu - colliculus in the rhesus monkey 40. Bolam IP, Francis C M , Henderson
rol Psychiatry 1934;32:27-44. ( Maaica nwlnttn ). | Comp Neurol Z. Cholinergic input to dopaminer -
15 -
Arsenault M Y , Parent A , Seguela -
1975;160:339 362. gic neurones in the substantia
P, Descarries L. Distribution and 27 Benevento LA , Re/ ak M . The corti - nigra: a double immunocvtochemi -
morphological characteristics of cal projections of the inferior pulv - cal study . Neuroscience I 99|;4 I :
-
dopa m i ne i mmu noreact i ve neu - inar and adjacent lateral pulvinar 48.3-494
rons in the midbrain of the squirrel in the rhesus monkev ( Miittim inn 41 . Bolam PJ, Smith Y The GABA and
substance P input to dopaminergic ized lesions ot the red nucleus. | tamatergic inputs from the pedun-
neurones in the substantia nigra of Comp Neurol 1956;105:195-250. culopontine nucleus to the mid -
the rat Brain Res 1990;529: 57-78. 3b. Carpenter MB. Functional relation- brain dopaminergic neurons in pri-
42 Braak 11, Braak E. Nuclear configu- ships between the red nucleus and mate's: a light and electron
ration and neuronal types of the the brachium conjunctivum. Physi- microscopic study . Soc Neurosci
nucleus niger in the brain of the ologic study ot lesions of the red Abstr 1993,19:1437.
human adult . Hum Neurobiol nucleus in monkeys with degener - 71. Cheney PD, Fetz HE Mewes K .
1986;5:71-82. ated superior cerebellar brachia. Neural mechanisms underlying
43. Bremer E. l/ activite cerebrale au Neurology 1937;7:427-437. corticospinal and rubrospinal con -
cours du sommeil et de la narcose: 37. Carpenter MB. Central oculomotor trol ot limb movements. Prog Brain
contribution a I'etude du mecan- -
pathways. In: Bach-y Rita P, ed.
The control of eye movements. Ch.
Res 1991;87:213-232.
72. Cheramy A, Leviel V, Glowinski J.
isme du sommeil. Bull Acad R
Med Belg 1937;2:68-86 4. New York: Academic Press, Dendritic release of dopamine in
44 . Bremer F, Terzuolo C. Contribu- 1971:67-103, the substantia nigra Nature 1981;
tion a I'etude des mecanismes 58. Carpenter MB. Anatomy ot the 289:337-342.
physiologiques du maintien de
I'activite vigile du cerveau: interac-
corpus striatum and brainstem in-
tegrating systems. In: Brooks VB,
73. Chiueh CC, Burns RS Markey SP, .
Jacabowitz DM, Kopin IJ. Primate
tion de la formation reticulee et de ed. Handbook of physiology. Sec . model of Parkinsonism: selective
I’ecorce cerebrale dans le processus I: The Nervous System. Vol. II: lesion of nigrostriatal neurons by
du reveil. Arch Int Phsyiol Biochim Motor control. Ch. 19. Washington, I - methyl - 4 -phenyl-l,2,3,6- tetrahv -
|934;62:I57 178 IX': American Physiological Soci- dropvridine prikluces an ex -
45. Brodal A . The reticular formation ety, 1981:947-993. trapyramidal syndrome in rhc*sus
ot the brain stem. Anatomical as- 39. Carpenter MB, Batton RR III. Ab- monkeys. LifeSci 1983;36:213-218.
pects and functional correlations. ducens internuelear neurons and 74 . Clark WEE. The mammalian IK U -
.
Springfield. II CharlesC Thomas, their role in conjugate horizontal lomotor nucleus . I Anat 1926;60:
1957 gaze. | Comp Neurol 1980; 189: 426-448
46. Brikial A , Jansen |. The ponto-cere- 191 209 73. Clements |R, Grant S. Glutamate-
bellar projection in the rabbit and 60. Carpenter MB, Carleton SC, Keller like immunoreactivity in neurons
cat . | Comp Neurol 1946;K4:3I 118 |T, Conte P. Connections of the of the laterodorsal tegmental and
47. Brikial A , Rossi GF Ascending subthalamic nucleus in the mon- pedunculopontine nuclei in the rat .
libers in brain stem reticular for - key Brain Res 1981;224:1 29 Neurosci Lett 1990;120:70-73.
mation of cat . Arch Neurol Psychi - 61. Carpenter MB, llarbison JW, Peter 76. Cogan DC. Neurology of the ocu -
atry 1955;74:68- 87. IV Accessory oculomotor nuclei in lar muscles. 2d ed Springfield, II
.
48. Briki il P. The corticopontine pro- the monkey. Projections and effects Charles C. Thomas, 1936.
jection from the v isual cortex in the ot discrete lesions. J C omp Neurol .
77. Collins P Woolam DHM. The ven-
cat .I The total projection and the 1970;140:131-134. tricular surface of the subcom-
projection from area 17. Brain Res .
62. Carpenter MB McMasters Rl IAl - misural organ: a scanning and
1972 9:297 3|7
^
49. Bunney BS, Aghajanian GK The
stons ot the substantia nigra in the
rhesus monkey : efferent fiber de-
transmission electron microscopic
study. ) Anat 1979;129:623-631.
precise localization of nigral affer - generation and behavioral obser- .
78 . Cooper |R Bloom HE Roth RH .
ents in the rat as determined by a .
vations Am | Anal I9b4;ll4 : The biochemical basis of neu-
retrograde tracing technique. Brain 293-320. ropharmacology. 6th i*d. New
Re's 1976;117:42.3-1.35. .
63. Carpenter MB Nakano K. Kim R York: Oxford University Press,
30. Burde RM, l.ik* wy AD. Central ori - Nigrothalamic projections in the 1991
gin ot oculomotor parasvmpathetic monkey demonstrated by autora - 79. Cote L, Crutcher MD. The basal
neurons in the monkey . Brain Res diographic techniques. J Comp ganglia. In: Kandel ER, Schwartz
1980;198:4 34 -4.39 Neurol 1976;165:401-416 JH, jessell TM, eds. Principles of
51 Burton II, lorn's EG. The posterior 64 Carpenter MB, Peter P. Accessors neural science. 3rd ed Ch . 42 New
thalamic region and its cortical oculomotor nuclei in the monkey.| York: Elsevier, 1991:647-659.
projection in new’ world and old Hirnforsch 1970 / 71,12:403-418. 80. Courville j. Rubrobulbar fibres to
world monkeys. | Comp Neurol 63. Carpenter MB, Peter P. Nigrostn- the facial nucleus and the lateral
1976;168:249- 302 atal and nigrothalamic fibers in the reticular nucleus ( nucleus of the
52 Buttner U, Buttner - Ennever |A, rhesus monkev. I Comp Neurol lateral funiculus): an experimental
Ilenn V. Vertical eye movement re- -
1972,144:93 116. study in the cat with silver impreg-
lated unit activity in the rostral 66. Carpenter MB, Pierson RJ. Pretec - nation methods. Brain Res 1966;
mesencephalic reticular formation tal region and the pupillary light 1:317-337.
of the alert monkey. Brain Res reflex: an anatomical analysis in 81. Courville |. Somatotopical organi -
1977;130:239-252. the monkev. I Comp Neurol zation of the projection from the
53 . Buttner-Ennever | Pathways Irom 1973;149**271-300. nucleus interpositus anterior of the
the pontine reticular formation to 67. Carpenter MB, Strominger \ l Ef - cerebellum to the red nucleus: an
structures controlling horizontal ferent fibers of the subthalamic nu - experimental study in the cat with
and vertical eye movements in the cleus in the monkey: a comparison silver impregnation methods. Exp
monkey. In: Baker R. Berthoz A, of the efferent projections of the Brain Res 1966;2: 191 -215.
eds Control of gaze by brain stem subthalamic nucleus, substantia 82. Courville J. The nucleus of the fa -
neurons: developments in neuro- nigra and globus pallidus. Am | cial nerve: the relation between
science. Vol. 1. Amsterdam: Ellse- Anal 1967;121:41-72. cellular groups and peripheral
vier, 1977:89-98. 68. Casagrande VA , Harting JK , Hall branches of the nerve. Brain Res
.
54 . Buttner-Ennever JA Henn V . An WC, Diamond IT. Superior collicu - 1966;1:338-354.
autoradiographic study of the lus of the tret* shrew : a structural .
83 . Courville J. BHK1 II A . Rubro-cere-
pathways from the pontine reticu - and functional subdivision into su- bellar connections in the cat: an ex-
lar formation involved in horizon- perficial and deep layers . Science perimental study with silver im-
tal eye movements. Brain Ri*s 1972;177: 444-447 pregnation methods. J Comp
1976; 108:155- 164 69 Castiglioni A|, Callaway MC, Neurol 1966;126:471 483. -
55. Carpenter MB. A study ot the red Coulter |D Spinal projections from 84 . Creese I, Eraser CM. Receptor
nucleus in the rhesus monkey. the midbrain in the monkev . I biochemistry and methodology:
Anatomic degenerations and phys- Comp Neurol 1978;178:329- 346 dopamine receptors. Vol. 8. New
iologic effects resulting Irom local- .
70. Charara A , Smith Y Parent A . Glu- York: Liss, 1987;I - 245.
14 Midbrain 575
85. Cynader M, Berman N . Receptive - trapyramidalen Systems. Klin nates. Brain Res Bull 1985; 14 :
field organization of monkey supe- Wochensch 1960;38:1236 1239. - 349-367.
rior colliculus. I Neurophvsiol 100. Emson PC, Arregui A , Clement- 114 French JD, 1 lemandez - Peon R , Liv -
197235:187-201. lones \ . Sandberg BEB , Kossor \1 ingston RB . Projections from cortex
86 Dahlstrom A , Fuxe K . Evidence for Regional distribution of methio - to cephalic brain stem ( reticular
the existence of monoamine-con- nine enkephalin and substance P- formation ) in monkey. J Neuro-
taining neurons in the central ner - liki immunoreactivity in normal
* physiol 1955;18:74-95.
vous system. I Demonstration of human brain and in Huntington 's 115 French JD, Magoun IIW . Effects of
monoamines in the cell bodies of disease. Brain Res 1980;199: chronic lesions in central cephalic
brain stem neurons. Acta Physiol -
147 160. brain stem of monkeys. Arch Neu -
Scand l %4;62(Suppl 232 ): 1 - 55. 101 . Englander RN , Netsky MG , Adel - rol Psychiatry 1952;68:591-604 .
87 Dejerine J . Anatomic des centres man LS. Location of human py - 116 French |D, Verzeano M, Magoun
nervcux . Vol . 2. Paris. |. Rueff , ramidal tract in the internal IIVV . An extralcmnisca! sensory
88.
1901 .
Descarries L, Berthelet E, Garcia S,
—
ca psule a na tom ica I
Neurology 1975:25:823 826.
ev id ence.
-
system in the brain . Arch Neurol
Psychiatry 1953;69:505-518
Bcaudet A . Dopaminergic projec - 102. Fallon JH , Loughlin SE . Substantia 117. Freund TF, Powell JE, Smith AD
tion from nucleus raphe dorsalis to nigra . In : Paxinos G, ed . The Rat Tyrosine hydroxylase- immunore-
neostriatum in the rat . I Comp nervous system. Vol. 1. Sydney, active boutons in synaptic contacts
Neurol 1986:249:511 520. Australia ; Academic Press, 1985: with identified striatonigral neu -
89. DeVito II . Anderson ME. Walsh 353 374 rons, with particular reference to
KE . A horseradish peroxidase 103 Ferraro A. Contributa speri men tale dendritic spines. Neuroscience
study of afferent connections of the alio studio della substantia nigra 1984:13:1189- 1216.
globus pallidus in Mncncn nmlalla . normale e dei suoi rapporti con la 118 Fuchs A . Role of the vestibular and
Exp Brain Kes 1980;38:65-73. corteccia cerebrate e con il corpo reticular nuclei in the control of
90. Diamond IT, Jones EG, Powell striato. Arch Gen Neurol Psychia - gaze: reticular, propositus and
TPS. The projection of the auditory
cortex upon the diencephalon and 104 ^. Schneps. SF Wilson PC,
try 1925 :26 117
Finlay BL ,
other internuclear neuronal activ -
ity. In : Baker R , Berthoz A , eds.
brain stem in the cat . Brain Kes .
Schneider GE Topography of vi - Control of ga /e by brain stem neu -
-
I %9;15:305 340. sual and somatosensory projec - rons: developments in neuro-
91 . Dray A . Serotonin in the basal gan - tions to the superior colliculus of science. Amsterdam: Elsevier,
glia : Functions and interactions the golden hamster. Brain Res 1977:341 - 348.
with other neuron pathways. I 1978, 142:223-235. 119 Fuji to Y , Imai T, Aoki M Monosy -
Physiol (Paris) 1981,77:393 403 105. Flechsig P. Einige Bemerkungen naptic excitation of motoneurons
92 . Dray A , Davies|, Oakley NK , Ton - liber die Untersuchungsmethoden innervating forelimb muscles fol -
groach P. Velluceci S. The dorsal der Grosshirnrinde, insbesondere lowing stimulation of the red nu -
and medial raphe projections to des Menschen. Arch Anat Entwickl cleus in cats. Neurosci Lett
the substantia nigra in the rat : elec - Gesch 19()5;337 444 . - 1991;127:137-140.
trophysiological, biochemical and 106. Flumerfelt BA. An ultrastructural 120. Fukushima K The interstitial nu -
behavioural observations. Brain investigation of afferent connec- cleus of Cajal and its role in the
Res 1978;151 : 431 -442. tions of the red nucleus in the rat . J control of movements of head and
93 Dunnett SB. Bjorklund A . Mecha - Anat 1980;131:621-633. eyes. Prog Neurobiol 1987;29
nisms of function of neuronal 107. Flumerfelt BA , Otabe S, Courville 107-192.
grafts in the adult mammal - |. Distinct projections to the red 121 Fuxe K Evidence for the existence
ian brain I Exp Biol 1987;132: nucleus from the dentate and inter - of monoamine neurons in the cen -
265-289. posed nuclei in the monkey. Brain tral nervous system . IV . Distribu -
94 Edwards SB . The ascending and
descending projections of the ret!
Res 1973;50:408 414. -
108 Foix C. Les lesions anatomiques de
tion of monoamine nerve terminals
in the central nervous system . Acta
nucleus in the cat : an experimental la maladie de Parkinson. Rev Neu - Physiol Stand 1965;64(Suppl 247)
study using an autoradiographic rol ( Paris) 1921;37:593 600. - 37-120.
tracing method . Brain Res 1972; 109 Foix C, Nicolesco J . Les noyaux 122 . Gacek RR . Location of brain stem
-
48:45 63. gris centraux et la region neurons projecting to the oculomo -
95. Edwards SB . Autoradiographic mesencephalo-sous-optique suivi tor nucleus in the cat . Exp Neurol
studios of the projections of the d un appendice sur I'anatomie 1977;57: 725-749
midbrain reticular formation: de
scending projections of the nucleus
- pathologique de la maladie de
Parkinson. Paris: Masson , 1925.
123. -
Garcia Kill E. The pedunculopon -
tine nucleus. Prog Neurobiol
cuneiformis.|Comp Neurol 1975; 110. Forno 15. The Lewy body in 1991;36:363-389.
161 :341 - 358. Parkinson 's disease. In : Yahr MD, 124 Garev LJ . Visual system . In Paxi -
96 Edwards SB. The commissural pro - Bergmann KJ , eds. Parkinson's nos Ci , ed . The human nervous sys -
jection of the superior colliculus in Disease. Advances in neurology. tem . Ch . 28. New York: Academic
the cat. I c bmp Neurol 1977;173: Vol 45 New York : Raven Press . Press, 1990:945-977.
23 40 1986:35-43. 125. Carey LJ, Jones EG , Powell TI »S
.
97 Edwards SB Ginsburgh CL, Ill Francois C, Percheron G, Yelnik J Interrelationships of striate and ex -
Henkel CK , Stein BE. Sources of Localization of nigrostriatal , ni- trastriate cortex with the primary
subcortical projections to the supe - grothalamic and nigrotectal neu - relay sites of the visual pathway . I
rior colliculus in the cat. I Comp rons in ventricular coordinates in Neurol Neurosurg Psychiatry
Neurol 1979;184:309-330. macaques. Neuroscience 1984 ;13: 1968;31 :135-157.
98. Edwards SB, De Olmos JS. Autora -
diographic studies of projections of 112.
6 l - 7h .
Francois C, Percheron C, Yelnik J ,
126. Geniec P, Morest DK . The neu
ronal architecture of the human
-
the midbrain reticular formation: I leyner S. Demonstration of the ex - posterior colliculus. Acta Otolaryn -
ascending projections of nucleus istence of small local circuit neu - gol ISuppll (Stockh ) I 971;295: 1 33.
cuneiformis. J Comp Neurol rons in the Golgi-stained substan- 127. Gerten CR. The neostriatal mosaic:
1976;165:417-432. tia nigra . Brain Res 1979; 172: I. Compartmental organization of
99. Ehringer II , llornykiewicz D. 160 164 . projections from the neostriatum
Verteilung von Noradrenalin und 113. Francois C, Percheron Ci, Yelnik I , to the substantia nigra in the rat . |
Dopamin ( 3-hydroxytyramin ) im I leyner S. A histological atlas of Comp Neurol 1985;236: 454 -476.
Gehirn des Menschen und ihr Ver - the macaque ( Macaca nwlntln ) sub- 128 Gerfen CR . The neostriatal mosaic:
halten bei Erkrangkungen des Ex stantia nigra in ventricular coordi - Multiple levels of compartmental
.
organization in the bas il ganglia . stantia nigra from the pedunculo- zation of the ventral striatal effer -
Annu Rev Neurosci 1992; 15; pontincand laterodorsal tegmental ent projection in the rhesus mon-
285-320 . nuclei. Neuroscience 1989;28: key : an anterograde tracing studv.
129 Gerfcn CR, Engber TM, Mahan EC, 611-623. J Comp Neurol 1990)293: 282- 298
el al. D, and D_> dopamine recep- 144 Grace AA . Bunney BS. Intracellular 160. I lagbarth KE. Kerr DIB. Central in -
tor-regulated gene expression of and extracellular elcctrophvsiol- fluences on spinal afferent conduc-
slrialonigral and striatopallidal ogv of nigral dopaminergic neu- tion. J Neurophysiol 1954 ;17:
neurons. Science 1990)250: 1429- rons 3. Evidence for electrotonic 295- 307.
1492. coupling. Neuroscience 1983;10: 161 . Ilallanger AE, Warner BH. As-
130. Gerfen CK . Herkenham M, 333- 348. cending projections from the pe-
Thibaull |. The neostriatal mosaic. 145. Graham j . An autoradiographic dunculopontine tegmental nucleus
II . Patch- and matrix -directed study of the efferent connections of and the adjacent mesopontine
mesostriatal dopaminergic and the superior colliculus in the cat . J tegmentum in the rat . J Comp
non-dopaminergic systems. J Neu- Comp Neurol 1977;173:629-654. Neurol 1988;274:48V515.
rosci 1987;7:3915- 3934. 146. Granit R . Receptors and sensory 162. Halliday GM, Tbrk J. Comparative
131. German DC, Dubach M , Askari S, perception. New Haven, CT: Yale anatomy of the ventromedial mes-
Speciale SG, Bowden DM . 1 - University Press, 1955. encephalic tegmentum in the rat,
niet hv I - 4 - phenyl - 1 ,2,3,6- tetrahy 147. Granit R, Kaada BR . Influence of cat, monkey and human . | Comp
dropvridine- induced I’arkinsonia n stimulation of central nervous Neurol 1986;252:423-445.
syndrome in Macaca fascicufans: structures on muscle spindles in 163. Ilamill C»S, Olschowska | A , Eenn
which midbrain dopaminergic cat. Acta Physiol Scand I 952;27: NJ, Jacobowitz DM . The subnu-
neurons are lost ? Neuroscience 130 160. clear distribution of substance P,
1988.24: 161- 174 . 148. Graybiel AM. Some extragenicu- cholecystokinin, vasoactive intesti-
132. Geyer MA , Puerto A , Dawsey VVJ , late visual pathways in the cat. In- nal peptide, somatostatin, leu-
Knap S, Bullard WP, Mandell A| vest Ophthalmol 1972;11:322-332. enkephalin, dopamine-—hydroxy-
Histologic and enzymatic studies 149 . Graybiel AM. Anatomical organi- lase, and serotonin in the rat
ol the mesolimbic and mesostriatal zation of retinotectal afferents in interpeduncular nucleus. J Comp
serotoninergic pathways. Brain Res the cat: an autoradiographic studv. Neurol 1984;226:580- 596
1976; 106:241 256. Brain Res 1975;96:1- 24 164 . Hanaway J , Young RK . Localiza-
133. Gilbert GJ. The subcommissural 150. Graybiel AM . A satellite system of tion of the pyramidal tract in the
organ Neurology I 960; 10: 138— 142. the superior colliculus: The para- internal capsule of man. | Neurol
I 34 Gilbert GJ, Glaser GH. On the ner - bigeminal nucleus and its projec- Sci 1977;34:63-70.
vous system integration of water tion to the superficial collicular 165. Harris NC, Davies J . Cortically
and salt metabolism. Arch Neurol lavers Brain Res 1978)145 65 374 evoked excitatory synaptic
19hl;5:179- |9n ^
151 Graybiel AM, I lartwieg EA . Some mission in
trans-
the cat red nucleus is
133. Gillingham I ) Small localized sur - atterent connections of the oculo- antagonized bv D- AP5 but not by
gical lesions of the internal capsule motor complex in the cat . an exper - D- AI *7. Brain Res 1992;594:
in the treatment of dyskinesia . imental study with tracer tech- 176- 180.
Coniin Neurol I 962;22:.38V 392. niques. Brain Res 1974 ;81 543- 551 . 166 Karting |K Descending pathways
13< > Giolli RA , Guthrie MD. Organiza 152. Graybiel AM, Ragsdale C Jr. Ilistiv- from the superior colliculus: an au-
tion til subcortical projections of vi - chcmically distinct compartments toradiographic analysis in the rhe-
sual areas I and II in the rabbit : an in the striatum of human, monkey sus monkey ( Mncaai mu hi tin ). |
experimental degeneration study. I and cat demonstrated by acetyl - Comp Neurol 1977;173:583-612.
Comp Neurol 1971 ; 142:351- 37b. cholinesterase staining. Prix Natl'
167. Ilarting JK . Casagrande VA ,
137. Giolli RA , Tigges J. The primary Acad Sci USA 1978;75:5723-5726. Weber |T. The projection ot the pri -
optic pathways and nuclei of pri- 153. Graybiel AM, Sciascia TR . Origin mate superior colliculus upon the
mates . In: Noback CR, Montagna and distribution of nigrotectal dorsal lateral geniculate nucleus:
W , ids. The primate brain, ad - fibers in the cat. Neurosci Abstr autoradiographic demonstration of
vances in primatology. Vol. I Ch. 1975;1 :271. intralaminar distribution of tecto-
2 . New York Appleton-Century - 154. Grofova I . The identification of geniculate axons. Brain Res 1978;
Crotts, 1970: 29- 54 striatal and pallidal neurons pro- 150:59V 599
138. Giuffrida R , l.i Volsi G, Perciavalle jecting to substantia nigra : an ex - 168. Ilarting | K , Guillen RW . Organi -
V . Influences ol cerebral cortex and perimental study by means of ret - zation of the retinocollicular path -
cerebellum on the red nucleus tit rograde axonal transport of way in the cat . J Comp Neurol
the rat . Behav Brain Res 1988; horseradish peroxidase Brain Res 1976; 166: 13 V 144.
28: 109- 111 . 1975;91:286- 291 . 169 Karting JK. Hall WC, Diamond IT,
139 Giuffrida R , Palmed A , Rattaele R . 155. Guillery RW . Degeneration in the Martin GF. Anterograde degenera -
Ricca G. Sapien / a S. Convergence posterior commissural fornix and tion study ol the superior collicu-
pattern of cortical and interposital the mammillary peduncle of the lus in Tiifhiui y / js: evidence tor a
influences on rubrospinal neurons rat . J Anat 1956,-90:350-370. subdivision between superficial
ol the cat. Behav Brain Res 156. Gulley RE, Wind RE. The fine and deep lavers. J Comp Neurol
| 988;28: 113- 1 In. structure of the neurons in the rat 1973;148: 361- 386.
140. Glendenning KK . Hall A , Dia | - substantia nigra . Tissue C ell 1971; 170. I iartmann Von Monakow K , Akert
mond IT, Hall YVC. The pulvinar 3:675-690. K. Kunzle H Projections of the
nucleus of Galileo scuc alcnsis . | 157. Haber SN , Groenewegcn III The precentral and premotor cortex to
Comp Neurol 1975;161 419-45g. ^ interrelationship of the distribu- the red nucleus and other mid -
141 . Goldberg ME. Eggers IIM, Gtiuras tion ot neuropeptides and tyrosine brain areas in Miiaica fascicular is.
P The ocular motor system. In: hydroxylase immunoreactivity in Exp Brain Res 1979;34:91- 105.
Kandel ER , Schwartz jll, Jessell the human substantia nigra. | 171 . Hassler R Zur Pathologic der
TM, ids . Principles of neural sci- Comp Neurol 1989;290:53-68. Paralysis agitans und der pt >sle-
ence. 3rd ed . Ch . 43. New York: El - 158. Haber SN, Nauta WJH. Ramifica- nenzephaIit ischen Parkinsonis -
sevier. 1991 :660-678. tions of the globus pallidus in mus. J Psychol Neurol 1938;
142. Gordon B. The superior colliculus the rat as indicated by patterns 48:387-476
of the brain. Sci Am 1972; ol immunohistochemistry . Neuriv 172. Ilatschek R . Zur verglcichenden
227:72-82. science 1983;9: 245- 260 Anatomic dcs Nucleus ruber
143. Gould E, Wool! NJ, Butcher LI.. 159. Haber SN , Lynd E , Klein C, Groe- tegmenti. Arb Neurol Inst Wiener
Cholinergic projections to the sub- newegen HJ Topographic organi- Umv 1907,15:89- 135.
14 Midbrain 577
-
173. Hazrati L N , Parent A. Projection tal fibers in macaque monkey : an Parkinson 's disease. In : Marsden
from the deep cerebellar nuclei to autoradiographic study . Brain Res CD, Fahn S, eds. Movement disor-
the pedunculopontine nucleus in
the squirrel monkev. Brain Res 188.
*
-.
1975,%:25 40
Huerta ME, I Lif ting JK. The mam -
ders . Vol . 2. London : Butterworths,
1987: 124- 165.
1992;585:267-271. malian superior colliculus: studies 203. Jenny AB, Smith JM , Bernardo KL,
174. Heckers S, Geula C, Mesulam M - of its morphology and connections. Woolsey TA . Distribution of motor
M. Cholinergic innervation of the In: Vanegas 11, ed . Comparative cortical neuron synaptic terminals
human thalamus: dual origin and neurology of the optic tectum . on monkey parvocellular red nu -
differential nuclear distribution . I New York: Plenum , 1484:687-733. cleus neurons. Somatosens Mot
Comp Neurol 1992;325:68-82. 184. Ilunsperger RW . Affektreaktionen Res 1991;8:23-26.
175. lledreen JC, DeLong MR. Organi- auf elektrische Rei / ung im llirn - 204. -
Jimenez Castellanos J , Graybiel
zation of the striatopallidal , stria - stamm der Kart /e. I lelv Physiol AM . Evidence that histochemically
tonigral, and nigrostriatal projec - Pharmacol Acta 1456, 14:70-42. distinct zones of the primate sub-
tions in the macaque. J Comp PM ). Hutchins B, Weber JT . The pretec- stantia nigra pars compacta are re-
Neurol 1991;304:569-595. tal complex of the monkey: a rein - lated to patterned distributions of
17h . Hendrickson AM, Wilson ME, vestigation of the morphology and nigrostriatal projection neurons
Toyne MJ . The distribution of optic retinal terminations. J Comp Neu - and striatonigral fibers Exp Brain
nerve fibers in Mnaicn multi I hi . rol 1985232:425 442 Res 1989;74:227-238.
Brain Res 1470;23:425 -427. 141 . Ilinsky I A , Jouandest MJ , Gold * 205. Johansson 11. Rubrospinal and
177. Herve I ), Picket VM , Job Til , -
man Rakic l *S. Organization of the rubrobulbospmal influences on dy -
Beaudet A . Serotonin axon termi - nigrothalamocortical system in the namic and static gamma motoneu -
nals in the ventral tegmental area rhesus monkey. J Comp Neurol rones . Bchav Brain Res 1988,
of the rat : Fine structure and -
1485;256:315 330. 28:97-107.
synaptic input to dopaminergic 142 . -
Ilinskv IA , Kultas llinsky K . Sagit - 206. Jones KG. The thalamus . New
neurons. Brain Res 1487;435:71 83. - tal cytoarchitectonic maps of the York: Plenum , 1985.
178 Hikosaka O, Wurtz RH. Visual and Munmi mulatto thalamus with a re- 207. Kabebian JW, Caine DB Multiple
oculomotor functions of monkey vised nomenclature of the motor receptors for dopamine. Nature
substantia nigra pars reticulata . I . related nuclei validated by obser - 1979;277:93-96 ,
Relation of visual and auditory re - vation on their connectivity. I 208 . Kanaseki T, Sprague JM . Anatomi -
sponses to saccades. j Neurophvs
-
iol 1483;44:1230 1252.
- 143.
Comp Neurol 1487;262:3-31 3tvi.
.
Ilinsky I A , Tourtelotte WC , Kultas -
cal organization of pretectal nuclei
and tectal laminae in the cat . J
174. I tikosaka O, Wurtz R! I Visual and llinsky F. Anatomical distinctions Comp Neurol 1974 ;158:319 338.
oculomotor functions of monkey between the two basal ganglia af - 2( W. Kanazawa I , Emson IV , Cuello
substantia nigra pars reticulata li , ferent territories in the primate AC . Evidence for the existence of
Visual responses related to fixation motor thalamus. Stereotact Fund -
substance P containing fibers in
of gaze. | Neurophvsiol 1483; Neurosurg 1493;60:62-69. striatonigral and pallido nigral -
44:1254-1287. 144 Inagaki S, Parent A . Distribution of pathways in rat brain . Brain Res
ISO. Hikosaka O, Wurtz RH . Visual and substance P and enkephalin - like 1977;119: 447-453.
oculomotor functions of monkey immunoreactivity in the substantia 210. Kawamura K , Brodal A . The tecto-
substantia nigra pars reticulata . III . nigra of rat, cat and monkey. Brain pontine projection in the cat : an ex-
Memory-contingent visual and Res Bull I 984;1 fc319 129 perimental anatomical study with
saccade responses. | Neurophvsiol 195. Ingram WR , Ranson SW . Effects of comments on pathways for tele-
1483,44:1268-1284 . lesions in the red nuclei in cats. ceptive impulses to the cerebellum .
181. I tikosaka O. Wurtz Rl I . Visual and Arch Neurol Psychiatry 1932;28: J Comp Neurol 1973;149:371 390. -
oculomotor functions of monkey 483-512. 211. Kelly DD. Disorders of sleep and
substantia nigra pars reticulata . IV . 1 %. Jackson A , Crossman AR . Basal consciousness. In: Kandel ER,
Relation of substantia nigra to su - ganglia and other afferent projec- Schwartz 111, Jessell EM , eds . Prin -
perior colliculus. | Neurophvsiol tions to the peribrachial region in ciples of neural science. 3rd ed . Ch .
-
1483;44:1285 1301. the rat: a study using retrograde 52 New York : Elsevier, 1991:
182. Houk JC . Rod nucleus: role in and anterograde transport of 805-819.
motor control . Curr Opin Neuro - horseradish peroxidase*. Neuro - 212. Ketv S. Sleep and the energy me-
biol 1441;1:610-615 science 1981 ;6:1537-1549. tabolism of the brain. In:
183. Hopkins DA, Niessen LW. Sub- 197. Jackson A, Crossman AR . Nucleus Woltenholme GEW, O'Connor M ,
stantia nigra projections to the tegmenti pedunculopontinus: ef - eds . The nature of sleep. Boston:
reticular formation , superior col
liculus and central gray in rat , cat ,
- ferent connections with special ref -
erences to the basal ganglia , stud - 213.
Little, Brown, 1960:375 381 .
Kim R , Nakano K , Jayaraman A ,
and monkev . Neurosci Lett 1476; ied in the rat by anterograde and Carpenter MB Projections of the
-
2:253 254.
Hornykiewicz O. Dopamin ( 3- 1 Iv -
retrograde transport of horserad - globus pallidus and adjacent struc -
184 . ish peroxidase. Neuroscience 1983; tures: an autoradiographic study
droxytyramin ) in Zentralnerven - 10:725-765. in the monkey. J Comp Neurol
system und seine Beziehung zum 148. Jacobs BL, Azmitia EC. Structure 1476;164: 26.3 289.
-
Parkinson Syndrom des Men - and functions of the brain sero - 214 . King JS, Bowman Mil , Martin GF.
schen. Dtsch Med Wochensch tonin systems. Physiol Rev 1942; The red nucleus of the opossum
1462;87:1807-1810. 72:165-229. ( Dilit' lphis marsupiali* viryiniima): a
185. Hornykiewicz ( 3. Dopamine ( 3- 144. Jacobs BL, Tnilson ME. Mecha- light and electron microscopic
Hvdroxytyramine) and brain func- nisms of action of LSD. Am Sri study. J Comp Neurol 1471;
tions. Pharmacol Rev 1466; 18: -
1979,67:346-404. 143: 157-184 .
425-464. 200. Jasper HH , Ajmone- Marsan C, 215. King JS, Schwyn RC , Fox CA. The
186. Hornykiewicz O, Kish SJ . Bio- Stoll J . Corticofugal projections to red nucleus in the monkey ( Maiacu
chemical pathophysiology of the brain stem . Arch Neurol Psy - muInthi ): a Golgi and an electron
Parkinson 's disease. In : Yahr MD, chiatry 1952;67:155-171. microscopic study.|Comp Neurol
Bergmann KJ , eds. Parkinson's 201 . Javaraman A , Batton RK III , Car - 1971; 142:75-108.
Disease. Advances in neurology. penter MB. Nigrotectal projections 216. Kila II, Kitai ST. Efferent projec -
Vol. 45. New York: Raven Press
1486: 14-34 .
. in the monkey: an autoradi -
ographic study. Brain Res 1977;
tions of the subthalamic nucleus in
the rat: a light and electron micro-
187. Hubei Dll , Le Vay S, Wiesel TN . 135:147-152. scopic analysis. | Comp Neurol
Mode of termination of retino tec - - 202. Jellinger K . The pathology of 1487;260:435-452.
217. Kopin l|. Markey SP. MPTP toxic- normal and Parkinsonian mon - 249. Magoun IIVV , Rhinos R . Spasticity:
ity: implications for research in
Parkinson’s disease. Annu Rev
keys. Neuroreport 1991;2:601 604.
233. Lavoie B. Parent A . The peduncu
- -
-
the stretch reflex and extrapyrami -
dal systems. Springfield , IL:
Neurosti 1988;11:81 96 --
218. Komhuber J , Kim J S, Komhuber
. lopontine nucleus in the squirrel
monkey. Topographical organiza -
Charles C. Thomas, 1947.
250. Marburg O, Warner F). The path -
ME, Komhuber HU . The cortico - tion of cholinergic, monoaminergic ways of the tectum (anterior col -
nigral projection: reduced gluta - and glutamatergic neurons in the liculus ) of the midbrain in cats. J
mate content in the substantia mesopontine tegmentum. | Comp Nerv Ment Dis 1947;106:415-446.
nigra following frontal cortex abla - Neurol 1994;344:190-209. 251. Marsden CD. Pigmentation in the
tion in the rat . Brain Res 1984; 234 . Lavoie B, Parent A . The peduncu - nucleus substantiae nigrae of
322:124-126 . lopontine nucleus in the squirrel mammals. J Anat 1961#>.256-261.
*
219. Kudo M , Niimi k Ascending pri> - monkey Projections to the basal 252. Martin C» F, Dom R Rubrobulbar
jections of the inferior colliculus on ganglia as revealed by anterograde projections of the opossum ( Dtiicl
the medial geniculate body in the -
tract tracing methods. I Comp fthiu rirtfiniiimi ). ) Comp Neurol
cat studied by anterograde and ret - Neurol 1994;344:210 231 .- 1970;139:199- 214
rograde tracing techniques. Brain 235. Lavoie B, Parent A . The peduncu - 253. Martin JB, Reichlin S, Brown
Res 1978;153:113 117.- lopontine nucleus in the squirrel GM . Clinical neuroendocrinology
220. Kuftler SW . Discharge patterns monkey. Cholinergic and gluta - Philadelphia : FA . Davis, 1977:
and functional organization of matergic projections to the sub - 229 246
mammalian retina . 1 Neurophysiol stantia nigra . J Comp Neurol 254 . Martin JH, Ghez C. Red nucleus
-
1953;16:37 68. 1994; 344:232-241 and motor cortex: parallel motor
221 . Kuhlenbeck 11, Miller RN . The pre- 236. Lavoie B, Smith Y, Parent A . systems for the initiation and con -
tectal region of the human brain . J Dopaminergic innervation of the trol of skilled movement. Behav
Comp Neurol 1949;91:369-408. basal ganglia in the squirrel mon - Brain Res 1988;28:217-223.
222. Kun / le II , Akert K Efferent con - key as revealed by tyrosine hy- 255. Martinez- Murillo R , Villalba RM.
nections of cortical Area 8 ( frontal droxylase* immunohistochemistry. Rodrigo|. Electron microscopic lo-
eye held ! in Muaua famicularia: a I Comp Neurol 1989;288:36-52. calization of cholinergic terminals
reinvestigaturn using the autoradi - 237. Lewy FH. Zur pathologischen in the rat substantia nigra: an im-
ographic technique. J Comp Neu -
rol 1977;173: 147- 164
Anatomie der Paralysis agitans.
Dtsch Z Nervenheilkd |913;50:
munocytochemical study. Neu
rosci Lett 1989;%:121-126.
-
223. Kunzle H , Akert K , Wurtz RH. -
50 55. 256. Martinez- Murillo R , Villalba RM ,
Projections of area 8 ( frontal eye 238. Limas R . Greenfield SA , Jahsen H -
Montero Calballero Ml. Rodrigo j
field ) to superior colliculus in mon -
key: an autoradiographic study .
Electrophysiology of pars com - Cholinergic somata and terminals
pacta cells in the in vitro substantia in the rat substantia nigra : an im -
Brain Res 1976;117:487-492.
224 Kuypers HG|M. Corticobulbar
—
nigra a possible mechanism for
dendritic release. Brain Res 1984;
munohistochemical study with op-
tical and electron microscopic tech -
connexions to the pirns and lower 294:355-373. niques. ) Comp Neurol 1989;
brain stem in man: an anatomical 239. Loewy AD, Saper CB. Edinger - 281:397-416.
study Brain 1958;81 :364-388. Westphal nucleus projections to
, 257. Mehler WR , Feferman ME, Nauta
225. Kuypers HGJM, Lawrence DC . the brain stem and spinal cord in WJH. Ascending axon degenera -
Cortical projections to the red nu - the cat Brain Res 1978;150:1-27. tion following anterolateral cordot -
cleus and the brain stem in the rhe- 240. Loewy AD, Saper CB, Yamodis omy: an experimental study in the
sus monkey . Brain Res 1%7; ND. Re-evaluation of the efferent monkey. Brain 1960;83:718 750.-
4: 151 -188.
226 Kuypers HGJM, Maisky VA Ret -
projections of the Edinger West
phal nucleus. Brain Res 1978;
- - 258. Merzenich MM , Reid MD. Repre
sentation of the cochlea within the
-
rograde axonal transport of horse - 121 :153 159. - inferior colliculus of the cat . Brain
radish peroxidase from spinal cord 241 . Lowenstein O. Clinical pupillary Res 1974;77:397-415.
.-
to brain stem cell groups in the cat symptoms in lesions of the optic 259. Mesulam M M , Marsh D, Hersh L,
Neurosci Lett 1975; 1:9-14 nerve, optic chiasm and optic tract. Both well M Geula C. Cholinergic
227. Langer AF, Gravbiel AM . Distinct Arch Opthalmol 1954;52:385-403. innervation of the human striatum ,
nigrostriatal projection systems in - 242. Mattel L. Pompeiano O. Cerebellar globus pallidus, subthalamic nu -
nervates striosomes and matrix in control of flexor motoneurons. cleus , substantia nigra and red nu -
the primate striatum Brain Res Arch Ital Biol l%2;100:467-500. cleus. J Comp Neurol 1992;323:
-
1989;498:344 350. 243 Magoun IIVV. An ascending reticu - 252-268.
228. Langston JW , Fomo LS, Rebert CS, lar activating system in the brain 260. Mesulam M - M , Mufson EJ , Levey
Irwin I Selective nigral toxicity stem . Arch Neurol Psychiatry Al , Wainer BH Atlas of choliner -
after systemic administration of I - 1952;67:145-154 gic neurons in the forebrain and
methvl - 4 - phenyl - 1 ,2,5,6- tetrahy 244 Magoun HW . The waking brain . upper brainstem of macaque based
d ropy rid ine ( MPTP ) in the squirrel 2d ed. Springfield , IL: Charles C. on monoclonal choline acetyltrans-
monkey. Brain Res |983;292: Thomas, 1%3. ferase immunohistochemistry and
390-394 . 245. Magoun HW , Ranson SW . The acetylcholinesterase histochem -
229. Langston |W, Irwin 1. MPTP: Cur - central path of the light reflex: a istrv Neuroscience 1984 ; 12: 669-
rent concepts and controversies. study of the effect of lesions. Arch 606
Clin Neuropharmacol 1986;9: Opthalmol 1935;13:791 811. - 261 Mettler FA . Relation between
485-507. 246 Magoun HW , Ranson SW The af - pyramidal and extrapyramidal
2.34 Lavoie B, Parent A . Immunohisto-
) ferent path of the light reflex : a re - function . Proc Assoc Res Nerv
chemical study of the serotoniner- view of the literature. Arch Opthal - -
Ment Dis 1942;21 : 1 SO 227
gic innervation of the basal ganglia mol 1935;13:862-874. 262. Mettler FA . Extensive unilateral
in the squirrel monkey . I Comp 247 Magoun HW , Ranson SW , Mayer cerebral removals in the primate:
Neurol 199( );29M 1 - 16 LL. The pupillary light reflex after physiologic effects and resultant
231 . Lavoie B, Parent A . Serotoninergic lesions of the posterior commis- degeneration. J Comp Neurol
innervation of the thalamus in the sure in the cat . Am | Opthalmol 1943;79:185 243.-
primate: an lmmunohishKhemical 1935;18:624-630 26.3. Miller RA , Strominger NL. Efferent
study . J Comp Neurol I 9U 1 ; 248. Magoun HW , Rhmes R . An in - connections of the red nucleus in
312:1-18. hibitory mechanism in the bulbar the brainstem and spinal cord of
232. Lavoie B, Parent A . Dopaminergic reticular formation. J Nourophysiol the rhesus monkey |Comp Neurol
neurons expressing calbindin in 1946;9:165 171 . - 1973;152:327 346
14 Midbrain 579
264. Ming,17/ ini G. Sulla fina ^ trultur*i the granular reticulum . Brain Res 294 . Parent A .. Comparative neurobiol -
della substantia nigra Som- -
1475;85:373 384. ogy of the basal ganglia. New
meringii . Vol. 5. Atti R Acad l.incei 274. Nauta WJII. Hippocampal projec - .
York: Wiley I 486.
1888. tions and related neural pathways 295. Parent A, De Bellefeuille L. Organi -
265. Moon Edley S, Graybiel AM . The to the midbrain in the cat. Brain zation of efferent projections from
afferent and efferent connections 1458;81:314- 340. the internal segment of the globus
of the feline nucleus tegmenti pe- 280. Nauta WJH. Kuypers HGJM . Some pallidus in primate as revealed bv
dunculopontinus, pars compacta. J ascending pathways in the brain fluorescence retrograde labeling
Comp Neurol 1483;217:187-215. stem reticular formation . In. Jasper method . Brain Res 1482;245:
266. Moore RY , Bhatnagar RK , Heller HH, Proctor EP, Knighton RS, et 201 -213.
A . Anatomical and chemical stud - aE, eds . Reticular formation of the 246. Parent A, Descarries L , Beaudet A .
-
ies of a nigro neostriatal projection brain. Henry Ford Hospital Inter - Organization of ascending sero-
in the cat. Brain Res 1471; national Symposium. Ch. 1 . tonin systems in the adult rat
30:114-1.35. . -
Boston : l ittle Brown , 1458:3 30. brain . A radioautographic study
267. Moore RY , Goldberg JM . Ascend - 281 . Nauta WJH , Mehler WR . Projec- after intraventricular administra -
ing projections of the inferior col - tions of the lentiform nucleus in tion of |'111 5- hydroxvtrvptamine
liculus in the cat . J Comp Neurol
-
1463;121:104 136. 282.
the monkey. Brain Res 1466;1 :3 42.
Nedergaard S, Bolam JP, Green -
- Neuroscience 1481 ;6: 1 i 5-1 38.
297. Parent A , Bouchard C , Smith Y
268. Moore RY, I ialaris AE, Jones BE. field SA . Facilitation of a dendritic The striatopallidal and striatoni
Serotonin neurons of the midbrain -
calcium conductance by 5 hvdrox - gral projections: two distinct sys -
raphe: ascending projections. J vtryptamine in the substantia tems in primate Brain Res 1484 ;
Comp Neurol 1478;180:417-438. -
nigra . Nature 1988;333:174 177. -
303:385 340.
264. Morest DK. Oliver DL. The neu - 283. Nieuwenhuys R. Chemoarchitec- 298. Parent A , llazrati L - N . Multiple
ronal architecture of the inferior ture of the brain . Berlin: Springer- striatal representation at substantia
colliculus in the cat: defining the Verlag, 1485. nigra level in primate. J Comp
functional anatomy of the auditory 284 . Niijima K, Yoshida M . Activation Neurol 1444;344:305-320.
midbrain. | Comp Neurol 1484 ; of mesencephalic dopamine neu - 244. Parent A , llazrati L- N , Lavoie B.
222:204-236. rons by chemical stimulation of the The pallidum as a dual structure in
270. Morgan LR . The corpus striatum nucleus tegmenti pedunculoponti - primates. In : Bernardi G, Carpen -
Arch Neurol Psychiatry 1427, 18: nus pars compacta. Brain Res ter MB, Di Chiara G, Morelli M ,
-
495 548
271. Mori S, Matsumura T, Takino T , 285.
1988,451 :163-171 .
Nyberg- Hansen R Functional or -
Stanzione P, eds. The basal ganglia
III. New York: Plenum , 199 t ;81-88.
Sano Y. Eight and electron micro- ganization of descending 3< X). Parent A , Lavoie B. The hetero-
scopic studies of serotonin nerve supraspinal fibre systems to the geneity of the mesostriatal dopa -
fibers in the substantia nigra of the spinal cord: anatomical observa - minergic system as revealed in
rat , cat and monkey. Anat Embryol tions and physiological correla - normal and parkinsonian mon -
1487; 176: 13-18 tions. Frgeb Anat Entwickl -Gesch keys. In : Narabayashi H , Nagatsu
272. Morrison |H , Finite SL. Noradren - 1966;39: 1 -48. T, Yanagisawa Y , Mizuno Y, eds.
ergic and serotonergic innervation 286. Oertel VVH , Tappaz ML, Berod A, Parkinson 's disease: from basic re-
of cortical , thalamic, tectal visual -
Mugnaini E. Two color immuno - search to treatment . Advances in
structures in old and new world histochemistry for dopamine and neurology. Vol . 60 . New York :
monkeys | Comp Neurol I 486; GABA neurons in rat substantia -
Raven Press, 1443:25 33.
-
243:117 138. nigra and zona incerta . Brain Res 301. Parent A, Mackey A, LX* Belle-
273. Moruzzi G , Magoun 1 IVV . Brain Bull 1982;4:463-474. feuille L. The subcortical afferents
stem reticular formation and acti - 287. Oeth KM , Lewis DA . Cholecvs- to caudate nucleus and putamen in
vation of the EEG. F.lectroen- -
tokinin - and dopamine containing primate: a fluorescence retrograde
cephalogr Clin Neurophysiol mesencephalic neurons provide double labeling study. Neuro-
1949 I 455 173 distinct projections to monkey pre - -
science 1983; 10:1137 1150.
274. Mugnaini E , Oertel VVH . Atlas of frontal cortex . Neurosci Lett 302 . Parent A , Mackey A , Smith Y The
the distribution of GABAergic neu - 1442;145:87-92. output organization of the sub-
rons and terminals in the rat CNS 288. Oliver DL, Morest DK . The central stantia nigra in primate as revealed
as revealed by GAD immunohisto- nucleus of the inferior colliculus in by a retrograde double labeling
chemistrv . In : Bjorklund A , Hbkfelt the cat. J Comp Neurol 1984, method . Brain Res Bull 1983;
T, eds. Handbook of chemical neu - 222:237-264. 10:529-537.
roanatomy . Vol . 4 Part 1 GABA 284. Olpe H - R, Koella WP. The re- 303. Parent A , Smith Y . Organization of
and neuropeptides in the CNS. Ch . sponse of striatal cells upon stimu - efferent projections of the subthal -
10. Amsterdam: Elsevier, 1485: lation of the dorsal and median amic nucleus in primate as re -
4.36-545. raphe nuclei . Brain Res 1977;!22; vealed bv retrograde labeling
275. Mussen AT. Experimental investi - 357-360. methods. Brain Res 1987;436:
gations on the cerebellum. Brain 290. Olszewski J. Cytoarchitecture ot 296-310.
-
1427;50:313 344. the human reticular formation . In : 304. Pasik P, Pasik T, Holstein GR ,
276. Naus CG, Flumerfelt BA, Delafresnaye JF, ed . Brain mecha - Saavedra JP. Serotoninergic inner -
Hrycyshyn AW. An HRP - TMB ul - nisms and consciousness. Oxford : vation of the monkey basal gan -
trastructural study of rubral atfer- Blackwell 1954:54-80. glia : an immunocytochemical light
ents in the rat . J Comp Neurol 241 . Olszewski J , Baxter D. Cytoarchi - and electron microscopic study' . In :
-
1985 234:453 465
277. Nauta HJW , Cole M. Efferent pro -
tecture of the human brain stem
Philadelphia : J . B . Lippincott , 1434
McKensie JS, Kenm RF, Wilcock
LN , eds. The basal ganglia: struc -
jections of the subthalamic nu - 242. Papez JW, Freeman GL. Superior ture and function . New York:
cleus: an autoradiographic study colliculi and their fiber connections Plenum , 1484 115-129.
in monkey and cat. J Comp Neurol in the rat . J Comp Neurol 305. Pazos A, Probsl A , Palacios |M
1478;180: 1 -16. 1930;51:409-439. Serotonin receptors in the human
278. Nauta HJW , Kaiserman-Abramof 293. Pare D, Smith Y, Parent A , Steriade brain. III . Autoradiographic map -
IR, Lasek RJ . Electron microscopic M . Projections of brainstem core -
ping of serotonin 1 receptors. Neu -
observations of horseradish perox - -
cholinergic and non chol inergic roscience 1987;21 :97- 122.
idase transported from the cau - neurons ot cat to intralaminar and 306. Pazos A , Probsl A , Palacios JM
doputamen to the substantia nigra reticular thalamic nuclei . Neuro- Serotonin receptors in the human
in the rat : possible involvement of science 1488;25:69-86. brain . IV Autoradiographic map-
ping ot -
serotonin 2 receptors. Neu - studv in the cat . I Comp Neurol mu noreactivity: an electron micro -
roscience 1987;21 :123-139. 1957;108:463-302. scopic, immunogold analysis in the
307. Percheron G . The thalamic terri - 322. Powell EW , Hatton JB. Cingu - cat . J Chem Neuroanat 1993;
tory of cerebellar afferents and the loseptal projections in the squirrel 6:19-30.
lateral region ot the macaque thal - monkey. Brain Res 1969;%; 337. Kinvik E, Walberg F. Demonstra -
amus in stereotaxic ventricular co- -
310 316. tion of a somatotopically arranged
ordinates | Hirnforsch 1977;|8: 323. Quensel F. Uber den Stabkranz des -
cortico rubral projection in the cat:
373-400. menschlichen Stirnhirns. Folio an experimental study with silver
308 . Pickel VM. Chan J Sesack SR.
Cellular substrates for interac-
-
Neuro- biol 1910;4:319 334.
324 . Rademaker GGT. Die Bedeutung
methods J Comp Neurol 1963;
120:393-407.
tion between dynorphin terminals der roten Kerne und des ubrigen 338. Kinvik F., Walberg F. Is there a cor -
and dopamine dendrites in rat Mittehirns fur Muskeltonus, Kor - tico-nigral tract ? A comment bast'd
ventral tegmental area and sub - perstellung, und Labyrinthreflexe. on experimental electron micro-
stantia nigra . Brain Res I 993;602: -
Berlin : Springer Verlag, 1926: scopic observations in the cat.
273-289. -
64 222. Brain Res 1969;14:742-744
309 Pierson R|, Carpenter MB. Ana - 325. Ralston DD, Milrov AM . Inhibitory 339. Roberts RC , Ribak CE. GABAergic
tomical analysis of pupillary reflex synaptic input to identified neurons and axon terminals in the
pathways in the rhesus monkey. I rubrospinal neurons in MfffJlO) fit> brainstem auditory nuclei of the
C omp Neurol |974 ; I 58: 121 143 dcularis : an electron microscopic gerbil . J Comp Neurol |987;258:
310 Pioro I P. Hughes |T, Cuello AC . study using a combined immunt *- 267-280.
I t »ss ol substance P and GABA -gold technique and the ret - .340. Robinson DA . Eye movements
enkephalin immunoreactivity in rograde transport of WGA - HRP. J evoked by collicular stimulation in
the human substantia nigra after Comp Neurol 1992;320:97-109 the alert monkev. Vision Res
striatopallidal infarction. Brain Res 326. Ramon v Cajal S. Histologic du 1972;12:1793-1808.
1984:292:339 347 Systeme Nerveux de I'Homme et 341 . Robinson RC, llouk JC, Gibson
.
311 Pioro EP, Mai JK Cuello AC . Dis- des Vertebres. ( Azoulav L , trans ), AR . Limb specific connections of
tribution of substance P- and Parte: Maloine, 1909, 1911 the cat magnocellular red nucleus.
enkephalin - immunoreactive neu - ( Reprinted , Consejo Superior de J Comp Neurol 1987:237:533 377.
rons and fibers. In : Paxinos G , ed . Investigaciones Cientificas, Insti - 342 . Rockel AJ, Jones EG. The neuronal
The human nervous system. Ch. tuto Ramon v Cajal, Madrid , 1972. ) organization of the inferior collicu -
32. New York: Academic Press, 327. Ranson SW , Magoun HW . The lus of the adult cat . I. The central
-
1990:1031 1094. central path of the pupillo- con - nucleus. J Comp Neurol 1973;
312 . Plum F, Posner JB The diagnosis
of stupor and coma . 3rd ed. New
strictor reflex in response to light
Arch Neurol Psychiatry 1933;30:
-
147:11 60.
343 Rockel A ) , Jones EG. The neuronal
York Plenum , 1980. 1193-1204 . organization of the inferior collicu -
313 Poirier LJ . Experimental and histiv- 328. Ranson SW , Ranson SW Jr , Ranson lus of the adult cat . II . The pericen -
logical study of midbrain dyskine - M . Corpus striatum and thalamus tral nucleus. | Comp Neurol
sias. | Neurophvsiol |960;23: ol a partially decorticate monkey . 1973;149:301 - 334 .
534-551. Arch Neurol Psychiatry 194 L 46: 344 . Role l W , Kelly JP. The brain stem:
.
314 . Poirier LJ , Bouvier G . The red nu - 402-415. Cranial nerve nuclei and the
cleus and its efferent nervous path - 329. Rasmussen AT. Tractus tecto- monoaminergic systems. In : Kan -
ways in the monkey . |Comp Neu - spinalis in the cat . J Comp Neurol del HR, Schwartz JH, Jessell TM
eds. Principles of neural science.
.
rol 1966; 128:223- 244 . 1936;63:501-525.
315. Poirier L|, Giguere M , Marchand .
330. Reiner A Albin RL , Anderson KD, 3rd ed . Ch . 44 . New York: Elsevier .
R Comparative morphology of the D' Amato C|, Penney JB Jr, Young 1991 :683-699.
substantia nigra and ventral AB. Differential loss of striatal pro- .
345. Rose JE, Greenwood DB Goldberg
tegmental area in the monkey, cat jection neurons in I luntington's JM, Hind JE. Some discharge char-
and rat . Brain Res Bull 1983; disease. Proc Natl Acad Sci USA acteristics of single neurons in the
11 : 371 397 1988;85:3733-5737. inferior colliculus of the cat . I .
316. Poirier I I . Singh P, Boucher R , .
331 Richfield EK , Young A Penny IB Tonotopical organization , relation
.
Bouvier G Olivier A , Larochelle P |r . Comparative distribution of -
til spike counts to tone intensity ,
Effect i *l brain lesions on striatal dopamine D , and D: receptors in firing patterns of single elements. J
monoamines in the cat . Arch Neu - the basal ganglia of turtles, pi - Neurophysiol 1963:26:293 320.
rol 1967, 17:601 608. geons, rats, cats and monkeys. | 346. Rosegay II . An experimental in -
317. Poirier LJ , Sourkes TL. Influence of Comp Neurol 1987;262:446-463 vestigation of the connections be-
the substantia nigra on cate- -
332 Rinvik E . The cortico nigral projec - tween the corpus striatum and the
cholamine content of the striatum . tion in the cat: an experimental substantia nigra in the cat I Comp
Brain 1965;88: 181-192 . study with silver impregnation Neurol 1944;80:293- 310.
318. Pompeiano O. Organizzazione so - methods . J Comp Neurol 1966; 347. Rossi GF, Brinlal A . Corticofugal
matotopica delle riposte flessorie 126:241 - 254 . fibers to the brain stem reticular
alia stimolazione elettnca del nu - 333 Rinvik I Demonstration of nigro- formation. An experimental study
clei * interposito nel gatto decere- thalamic connections in the cat by in the cat. J Anal 1936;90:42-62.
brato. Arch Sci Biol ( Bologna ) retrograde axonal transport of 348. Roth GL, Aitkin LM , Anderson
1959;43:163-176. horseradish peroxidase. Brain Res RA , Merzenich MM Some features
319 Pompeiano O. Localizzazione delle -
1975;90:313 318. of the spatial organization of the
risposte estensorie alia stimo- 334 Rinvik E, Grofova I . Observations central nucleus of the inferior col -
lazione elettrica del nudeo inter - on the fine structure of the sub- liculus of the cat J Comp Neurol
posito nel gatto decerebrato. Arch stantia nigra in the cal F. xp Brain 1978;182:661-680.
Sci Biol ( Bologna ) 1960;44 : 473 -496. Res 1970;11 :229-248. 349. Rundles RW , Papez JW. Connec-
320. Pompeiano O, Brodal A . Experi - 335. Rinv ik E , Grofova I , Otlersen OP. tions between the striatum and the
mental demonstration ol a somato- Demonstration of the nigrotectal substantia nigra in a human brain
topical origin of rubrospinal libers and nigroreticular projections in Arch Neurol Psychiatry |937;38:
in the cat . | Comp Neurol 1957;
108:225-251 .
the cat by axonal transport of pro
tein . Brain Res 1976;112:388-394.
- 530-563.
350. Rve DB, Sapor CB, Lee HJ . Warner
321 Pompeiano O. Walberg F. De- 336 Kinvik E, Ottersen OP. Terminals BIT Pedunculopontine tegmental
scending connections to the of subthalamonigral fibres are en - nucleus of the rat : cytoarchitecture .
vestibular nuclei an experimental riched with glutamate-like im - cytochemistry, some extrapyranii -
14 Midbrain 581
ddl connections of the mesopon - ferent projections of the subthala - chemical and retrograde transport
tine tegmentum. | Comp Neurol mic nucleus in the squirrel monkey study J Physiol ( Paris) 1980;
1987 259:483-528. as studied with the PHA-L antero- 77: 157 174 .
351. Sakai ST. Corticonigral projections grade tracing method . J Comp .
381 Steriade M Biesold D Brain
from area 6 in the raccoon. Exp Neurol 1990;294:306-323. cholinergic systems. New York:
Brain Res 1988;73:498 504. -
352. Sano T. Beitrag / ur vergleichenden
366 Smith Y, Lavoie B, Dumas J , Parent
A . Evidence for a separate ni -
Oxford University Press, 1990.
382. Steriade M , McCarley RW Brain -
Anatomic der Substantia nigra , des gropallidal dopaminergic projec - stem control of wakefulness
Corpus luysii und der Zona in - tion in the squirrel monkev . Brain and sleep. New York : Plenum .
certa . Mschr Psvchiat Neurol Res 1989;482 : 381 386. 1990.
1910;27:110-127. 367. Smith Y , Parent A . Differential .
383 Sterling P Wickelgren BG. Visual
353. Scalia F. The termination of retinal connections of caudate nucleus receptive fields in the superior col -
axons in the pretectal region of and putamen in squirrel monkey liculus of the tat . J Neurophvsiol
mammals. J Comp Neurol 1972 ; ( Saint tn siiumts ) . Neuroscience 1969;32:1 - 15.
145:223-257 1986;18: 178-182. 384 Strvker MP, Schiller PII . Eye and
354 . Scarnati E, Proia A . Campana 368. Smith Y , Parent A, Seguela P.
E, Pacitti C. Pedunculopontine- Descarries L. Distribution of
head movements evoked by elec
trical stimulation of monkey supe-
-
evoked excitation of the substantia
nigra neurons in the rat . Brain Res
.
C A BAim mu noreactive neurons in
the basal ganglia of the squirrel
rior colliculus. Exp Brain Res
1975;23:103-112.
1984;304:351-361. monkey [ Saimiri saureus ).| Comp 385. Stuart AM , Mitchell IJ , Slater P.
.
355. Scheibel ME Scheibel AB St rue - -
Neurol 1987;259:50 65. Unwin III . P, Grossman AR. A
tural substrates for integrative pat - 369. Snider RS. Recent contributions to semi -quantitative atlas ol 5- hy -
terns in the brain stem reticular the anatomy and physiology of the -
droxytryptamine 1 receptors in the
core. In : Jasper HH. Proctor I P, cerebellum Arch Neurol Psychia - primate brain Neuroscience 1986;
Knighton RS, et al., eds. Reticular try 1950;64:196-219. 18:619-639.
formation of the brain . Ch . 2. 370. Sousa - Pinto A. Cortical projections 386. Sugimoto T, Itoh K , Mi / uno 11 Di -
Boston: l ittle Brown , 1958:31 55 of the medial geniculate KHIV in rect projections from the Edinger-
356. Schiller PH , Stryker M . Single unit - the cat . Adv Anal Embrvol Cell Westphal nucleus to the cerebel -
recording and stimulation in •supe- Biol 1973;48: 1 -42. lum and spinal cord in the cat: a
rior colliculus of the alert rhesus 371 . Spann BM , Grofova I . Nigrope- HRP study Neurosci Lett 1978;
monkev. I Neurophvsiol 1972;35: dunculopontine projection in the 9:17-22.
915-924. rat: an anterograde tracing study 387. S/abo J . Topical distribution of the
. .
357 Schmied A Almaric M, Dormont with P/WIJVO/MS I' ulgnri* leucoagglu - striatal efferents in the monkey .
JF, Farin D. GABAergic mecha - tinin ( PHA - L). J Comp Neurol Exp Neurol 1962;5:21- 36.
nisms in the cat red nucleus: effects 1991;311:375-388 388. S/abo |. The efferent projections of
of intracerebral microinjections of 372. Spann BM , Grofova I . Cholinergic the putamen in the monkey. Exp
muscimol and bicuculline on a and non-cholinergic neurons in the Neurol 1967; 19:463-476.
conditioned motor task . Exp Brain rat pedunculopon tine tegmental 389 S/abo J . Projections from the body
Res 1990;81:523-532. nucleus. Anat Embrvol 1992;186: of the caudate nucleus in the rhe-
358. Scheneider JS, Yuwiler A , Markam 215-227. sus monkev . Exp Neurol 1970;
CH . Selective loss of subpopula - 373. Sparks DL, Holland R. Guthrie BL 27:1-15.
tions of ventral mesencephalic Si /e and distribution of movement 390. S/ abo J . Distribution of striatal af -
dopaminergic neurons in the mon - fields in the monkev superior col - ferents from the mesencephalon in
kev following exposure to MPTP. liculus. Brain Res 1976;113:21-34. the cat. Brain Res 1980;188:3-21.
Brain Res 1987;411 :144-150. 374. Sprague JM . The superior collicu - 391 . S/ abo | Organization of the as-
359. Schwyn RC, Fox CA . The primate lus and pretectum in visual behav - cending striatal afferents in mon -
substantia nigra a Golgi and elec -
, ior. Invest Ophthalmol 1972; 11 : keys J Comp Neurol 1980; 189.
tron microscopic studv . J Hirn - 473-482. 307-321.
forsch 1974,15:95-126. 375. Sprague|M , Meikle Tl I Jr. The role 392. S/ entagothai |. The elementary
360. Seroogy KB, Dangaran K , Haycock of the superior colliculus in visu - -
vestibulo ocular reflex arc . J Neu -
JW , Fallon JH . Ventral mesen- ally guided behavior. Exp Neurol rophvsiol 1950;13:395 407.-
cephalic neurons containing both 1965; 11 : 115- 146 395 Tarlov EC, Moore RY. The tecto -
-
cholecystokinin and tyrosine hv - -
376. Star / I TE, WhitkHrk DG . Diffuse thalamic connections in the brain
droxvlase-like* immunoreactivities thalamic projection system in mon - of the rabbit . J Comp Neurol
project to forebrain regions. | key. J Neurophysiol I 952;15: 1973;126:403-422
Comp Neurol 1989;279:397 414 .
361 Sheard Mil , Flynn JP. Facilitation
- 449-468.
-
377. Steiger ll - J , Buttner Ennever JA
394 Ternaux JP, llery F, Bourgoin S,
Adrien J , Glowinski J , Hamon M
of attack behavior by stimulation Oculomotor nucleus afferents in The topographical distribution of
of the midbrain of cats Brain Res the monkey demonstrated with serotoninergic terminals in the
1967.4:324 333. horseradish peroxidase. Brain Res neostriatum of the rat and the can
.362. Sherk H . Visual response proper - 1979;160:1 -15. date nucleus of the cat . Brain Res
ties and visual field topography in 378. Stein BE, Magalhaes-Castro B . 1977;121:311 - 326.
the cats parabigeminal nucleus. Kruger L . Relationships between 395. Ter / uolo ( \ Ter / ian 11. Cerebellar
Brain Res 1978;145:375-379. visual and tactile representation in increase of postural tonus after
363. Smith MC . Stereotaxic operations cat superior colliculus. | Neun*- deafferentation and labyrinthec-
—
for Parkinson 's disease anatomi
cal observations. In : Williams D
-
.
physiol 1976;39:401-419.
379 Steinbusch HWM . Distribution of
tomv. | Neurophvsiol 1953;16
551-561 .
ed Modem trends in neurology serotonin-immunoreactivity in the 396. Tokuno 11, Mori /ami T, Kudo M .
Vol. 4 . London: Butterworths, central nervous system of the rat Nakamura Y A morphological evi -
1967:21 -52. cell bodies and terminals. Neuro - dence for monosynaptic projec -
364 Smith V , Bolam IP Convergence of science 1981;6:557-618. tions from tin * nucleus legmenti
synaptic inputs from the striatum 380. Steinbusch IIWM , Nieuwenhuvs pedunculopon tine pars compacta
and globus pallidus onto identified R , Verhotstad AAJ , Van der Koov ( TPC ) to nigrostriatal projection
nigrocollicular cells in the rat : a D. The nucleus raphe dorsalis of neurons Neurosci Left |988;85
double anterograde labelling
study . Neuroscience 1991 ;44:45-73.
the rat and its projection upon the
caudatoputamcn. A combined 397.
-
1 4.
Tomasch |. The numerical capacity
-
365. Smith Y , Ha / rati L N , Parent A . Ef - cvtoarchitectonic, immunohisto- of the human cortico- ponto-ccre -
tvllar system . Brain Re*s 1969; 407. Von Monakow C. Experimentelle human nervous system. Ch. 27.
13:476-484 . und pathologisch-anatomische Un- New York: Academic Press, 1990:
-
398 Tork I , Hornung J P. Raphe nuclei tersuchunger fiber die Haubenre- 889-944.
and the serotoninergic system . In : gion, den Sehhiigel und die Regio 418. Webster WR, Service J , Crewther
Paxinos G, ed . The human nervous subthalamica . Arch Psychiatr Ner- D, Crewther S. Iso-frequencv 2-DG
system . Ch . 30. New York: Acade
-
mic Press, 1990:1001 1022.
- -
venkr 1895;27:1 219.
408. Von Monakow C. Gehirnpatholo -
contours in the inferior colliculus
of the awake monkey . Exp Brain
399. Torvik A . Brixlal A . The origin of gie. 2d ed . Wien : Hdlde, 1905. Rc*s 1984;56:427-437.
reticulospinal fibers in the cat: an 409. Verhaart WJC. Die aberrierenden 419. Wickelgren BG, Sterling P. Influ -
experimental studv . Anal Rec Pyramidenfasern bei Menschen ence of visual cortex on receptive
1957;128:113-137. und Afen . Schweiz Arch Neurol fields in the superior colliculus of
400 Toyama K , Tsukahara N , Udo M. Neurochir Psychiatr 1935;36: the cat . ) Neurophvsiol 1969;
Nature of the cerebellar influences 170-190. 32:16-32.
upon the red nucleus neurons. Exp 410. Verhaart WJC. Fiber analysis of the 420. Wilson ME, Toyne M ) . Rctino tec - -
Brain Res 1968;4:292-309. basal ganglia . J Comp Neurol tal and cortico-tectal projections in
401 . Tretiakoff C. Contribution a l ’ e- 1950;93:425-440. Macaca mulatto. Brain Res 1970;
tude de I anatomopathologie du 411. Voneida TJ . An experimental
’
locus niger de Summering. These,

Universite de Paris, Number 293. -
of fibers arising in the head of cau
24:395-406.
.
study of the course and destination 421 . Wislocki C B, Leduc E. The cytol -
ogy and histochemistry of the sub -
Paris: Jouveet Cie, 1919. date nucleus in the cat and mon - commissural organ and Reissners
402 . Ungerstts.lt U . Stereotaxic mapping key . I Comp Neurol 1%0;115: fibers in rodents. J Comp Neurol
of the monoamine pathways in the
^
73 87.
rat brain . Acta Physiol Scand 412. Walberg F. On the termination of
1953 7515 543.
^
422. Woolf Nj, Harrison JB, Buchwald
-
(Suppl ) 1971;367: 1 48. rubrobulbar fibers: experimental JS. Cholinergic neurons of the pon -
403. Van der Koov D, I lattori T . Single observations in the cat . J Comp tomesencephalon. II Ascending
subthalamic nucleus neurons pro - Neurol 1958;110:66-73. anatomical projections. Brain Res
ject to both the globus pallidus and 413. Warwick R . Representation of the 1990;520:55-72.
substantia nigra in rat . J Comp
Neurol 1980;192:751-768.
extraocular muscles in the oculo
motor nuclei of the monkey. )
- 423. Yamada T, McGeer PL, Bairn -
bridge KG , McGeer EG . Relative
404 . Van der Kooy D, I lattori T. Bilater - Comp Neurol 1953;98:449-504. sparing in Parkinson 's disease' of
ally situated dorsal raphe cell bod - 414. Warwick R The identity of the substantia nigra dopamine neu -
ies have only unilateral forebrain posterocentral nucleus of Pane - -
rons containing calbindin D:sK .
projections in rat . Brain Res grossi . J Comp Neurol 1953;99: Brain Re's 1990;526:303-307.
-
1980;192:550 554. 599-612. 424 . Yurek DM , Sladek |R \ r Dopamine
405. Van Domburg PHMF, Ten Donke - 415. Warwick R . The ocular parasym- cell replacement : Parkinson's dis -
laar HJ . The human substantia pathetic nerve supply and its mes- ease*. Annu Rev Neurosci 1990;
nigra and ventral tegmental area. encephalic sources. ) Anal 1954 ; 13:415-440.
Adv Anat Embrvol Cell Biol 88:71 93 425. Houk JC, Gibson AR . Harvey CF,
1991;121:1-132. -
416. Warwick R . The so called nucleus Kennedy PR , van Kan PL. Activity
406. Von Economo CF, Karplus JP . Zur of convergence. Brain 1955;78: of primate magnocellular red nu -
Physiologie und Anatomic des 92-114 . cleusd related to hand and finger
Mittelhirn . Arch Psychiatr Ner- 417. Webster WR , Carey LJ . Auditory movements. Behav Brain Re's
-
venkr 1909;46:275 356. system. In : Paxinos G, ed . The 1988;28:201-206.
15
Cerebellum
REGIONAL ORGANIZATION cerebellar circuits for long periods of time. It

is currently thought that the function of the
The cerebellum derives its name from the cerebellum is modified by experience and
diminutive of the word cerebrum . It was con- that this structure plays an important role in
sidered by the ancient anatomists as a second , the learning of motor tasks.
smaller brain in its own right ( 173). The cere- The cerebellum is derived from ectoder-
bellum forms the roof of the fourth ventricle mal thickening about the cephalic borders of
and is the only region of the central nervous the fourth ventricle, known as the rhombic
system that spans the midline without inter- lip ( Figs. 3.12 and 3.14 ). Although the cerebel -
ruption . This structure has expanded during lum is derived from portions of the embry -
the course of human evolution (142, 227), but onic neural tube dorsal to the sulcus limitans
its basic neuronal circuits remained relatively and receives sensory inputs from virtually all
similar to what they are in all vertebrates. The receptors, it is not concerned with conscious
cerebellar cortex in humans has a total area of sensory perception . Sensory information
50,000 cm 2 versus 12 mm in the frog ( 26 ). transmitted to the cerebellum is used in the
This cortex folds into very deep folia ( leafs), automatic coordination of somatic motor
allowing this enormous surface to be packed function, the regulation of muscle tone, and
into a 300 cm ' volume. Because the cerebellar the maintenance of equilibrium. This meten -
cortex is very long in the rostrocaudal direc - cephalic derivative functions in a supraseg-
tion ( up to 1 meter in humans), most of the mental manner in that its integrative influ -
folding occurs in that direction. ence affects activities at all levels of the
The cerebellum occupies approximately neuraxis. The major influences of the cerebel -
10% of the total brain volume, but contains lum on segmental levels of the neuraxis are
approximately half of all the neurons in the mediated indirectly by relay nuclei of the
brain . These neurons form multiple, identical brainstem.
modules that compute neural information in Structurally, the cerebellum consists of (a )
a similar way throughout the cerebellum . The a superficial gray mantle, the cerebellar cortex ,
functional heterogeneity of the cerebellum ( b ) an internal white mass, the medullary sub-
derives from the fact that modules located in stance , and (c) four pairs of intrinsic nuclei em -
distinct areas of the structure process differ- bedded in the white matter ( Figs. 13.7, 13.26,
ent types of neural information deriving from and 15.19). The cerebellum is divided into a
specific sets of inputs (104 ). The cerebellum is median portion, the cerebellar vermis , and two
concerned with the coordination of somatic lateral lobes, referred to as the cerebellar hemi -
motor activity, the regulation of muscle tone spheres. In spite of a wealth of histologic detail
and mechanisms that influence and maintain concerning the structural organization of the
equilibrium. It acts as a "comparator" that cerebellum, precise anatomic localization
compensates for error in movement by com- within various lobules is difficult except in
paring intention with performance. The cere - gross specimens. Likewise, the precise identi-
bellum receives (a ) information about plans fication of cerebellar lobules, laminae, and
for movement (corollary discharge or internal folia in microscopic sections is difficult even
feedback ), ( b ) information about motor per - in serial sections. Detailed atlases of the cere-
formance (reafference or external feedback ), bellum in human (12 ) and nonhuman pri -
and (c) it projects to descending motor sys- mates ( 179 ) facilitate the microscopic study of
tem . The cerebellar afferents play a crucial cerebellar sections ( 272 ).
role in the functional organization of the cere- The cerebellar cortex is composed of nu -
bellum as certain classes of inputs can modify merous narrow laminae or folia , most of which
583
are oriented transversely . Five deep fissures perior semilunar lobule) and crus II ( inferior
divide the cerebellum into lobes and lobules. semilunar lobule ). The biventer lobule and the
All of these fissures can be identified in gross cerebellar tonsil lie between the prepyramidal
specimens as well as in midsagittal section and the posterolateral fissures in the cerebel -
( Figs. 2.30-2.33). The cerebellar fissures are lar hemispheres. The posterolateral fissure
( a ) the primnri/ , ( b ) the posterior superior , ( c ) separates the nodulus from the uvula in the
the horizontal , (d ) the prepyramidal , and ( e ) the cerebellar vermis.
posterolateral ( prenodular ). The primary fis- Embryologically, hodologically, and func-
sure is the deepest of all cerebellar fissures. tionally the cerebellum can be divided into
These fissures form the basis for all subdivi- three parts: the archicerebellum (or vestibulo-
sions of the cerebellum (164 ) ( Fig. 15.1 ). I’or- cerebellum ), the paleocerebellum ( or spin -
tions of the cerebellar vermis and hemi - ocerebellum ), and the neocerebellum (also
spheres located rostral to the primary fissure termed cerebrocerebellum or pontocerebel-
form the anterior lobe, whereas those be- lum ).
tween the primary and the posterolateral fis- The archicerebellum , represented largely by
sures constitute the posterior lobe. Portions of the nodulus , the paired flocculi , and their pe-
the cerebellum caudal to the posterolateral duncular connections ( i.e., the flocculonodular
fissure represent the flocculonodular lobe. lobe ) , is believed to be the oldest part of the
The various portions of the cerebellar vermis cerebellum . This division of the cerebellum is
are labeled bv names and serial Roman numer - most closely related to the vestibular system
als . The portion of the cerebellar hemispheres and is often related to as the vestibulocerebel -
between the primary and the posterior supe- lum ( 164 ) ( Fig. 15.1 ). The flocculonodular lobe
rior fissures is known as the simple lobule. The is separated from the corpus cerebelli bv the
ansiform lobule lies between the posterior su - posterolateral fissure, the first fissure to de-
perior fissure and the gracile lobule and is di - velop in the cerebellum .
vided by the horizontal fissure into crus I (su - The paleocerebellum ( i.e., the anterior lobe
Lingula
Anterior lobe Central lobule

I
Primary fissure
II , III
quadrangular, Posterior superior
IV lobule /
fissure
Culmen
Simple V Posterior
lobule quadrangulai
Declive lobule /
Superior
semilunar VI CRUS I
lobule FoliumVermis' VII
Posterior Horizontal
Tubgpyermiss
lobe Pyramis fissure
Inferior
semilunar VIII CRUS II
lobule
Uvula
Biventej
Gracile
lobule
lobule / IX
Prepyramidal
Paraflocculus fissure
X Posterolateral
fissure
Flocculonodular lobe Nodulus Flocculus
Figure 15 1 Fissures and lobules of the cerebellum Portions of the cerebellum caudal to the posterolateral fissure
( shaded area) represent the flocculonodular lobule (archicerebellum or vestibulocerebellum), while portions of the
cerebellum rostral to the primary fissure ( shaded area) constitute the anterior lobe (paleocerebellum or spinocerebel-
lum ) The neocerebellum (or cerebrocerebellum ) lies between the primary and posterolateral fissure . Roman numer
ats refer to portions of the cerebellar vermis only
15 Cerebellum 585
of the cerebellum ) lies rostral to the primary connections indicates that the cerebellum
fissure (169) ( Fig. 15.1 ). In nonmammalian serves as a major integrative center for the co-
vertebrates, the paleocerebellum forms the ordination of muscular activity. Before exam-
largest part of the cerebellum, while in hu - ining the afferent and efferent fiber systems
mans it constitutes a small subdivision which of the cerebellum , the structure of the cerebel -
receives impulses primarily from stretch re- lar cortex is considered .
ceptors via the spinocerebellar tract. It is the
part of the cerebellum most concerned with CEREBELLAR CORTEX
the regulation of muscle tone (184). Because
of its intimate connections with the spinal The cerebellar cortex is uniformly struc-
cord , it is often referred to as the spitiocerebel - tured in all parts and extends across the mid -
lum . line without evidence of a median raphe. The
The mvcerebellum ( i.e., the posterior lobe), cortex is composed of three well-defined lay-
phvlogeneticallv the newest and the largest ers containing five different types of neurons.
portion , includes all parts of the cerebellum These layers from the surface are (a ) the mol -
between the primary and posterolateral fis- ecular layer, ( b ) the Purkinje cell layer, and (c )
sures in both the vermis and the hemispheres the granular layer ( Figs. 15.2-15.4 ).
( Fig. 15.1 ) . This division of the cerebellum re-
ceives major inputs from the contralateral Molecular Layer
cerebral cortex via relays in the pontine nu -
clei, and is the part most concerned with co- The molecular layer contains two types of
ordination of somatic motor function . Be- neurons, dendritic arborizations of cells in
cause of its massive corticopontine input, it is deeper layers, and numerous thin axons
often referred to as the cerebrocerebellum (104) coursing parallel to the long axis of the folia
or pontocerebellum (32). ( Figs. 15.2, 15.4, and 15.5). This layer, whose
The cerebellum is attached to the medulla, cell density is relatively low , contains the bas-
the pons, and the midbrain by three paired ket cells in its inner portion and the stellate
cerebellar peduncles (see Chapter 2 for fur- cells in its outer portion ( Figs. 15.4 and 15.5).
ther details on the gross anatomy of the Dendrites of these two types of neurons are
cerebellum ). These compact fiber bundles confined to the molecular layer, as are the
interconnect the archicerebellum, paleo- axons of the stellate cells. Processes of both
cerebellum , and neocerebellum with the cells are oriented in a sagittal plane; that is,
spinal cord , brainstem, and higher levels of transversely to the long axis of the folia .
the neuraxis. The extensive nature of these Axons of the stellate cells make synaptic con -
Figure 15.2 Sections through a folium of a rhesus monkey cerebellar cortex A In this figure, the relative thickness of
the three cerebellar layers can be appreciated. Light spaces in the dark staining granular layer are the "cerebellar is-
lands' containing the glomeruli B A single row of Purkinje cells above the granular layer is shown (Nissl stain, »< 20.
* 50).
Basket cell
Purklnje cell
Granular cell
Glomerulus
Figure 15.3 Portions of the three layers of the human cerebellar cortex
Purkinje cell
Golgi cell
Granule cell
Parallel fibers Molecular

layer
Outer stellate cell
Purkinje cell
Purkinje cell dendrites layer
Golgi cell dendrites

Granular
Basket cell f layer
V
*
dendrite
axon 1 Glomerulus
•
White matter
Mossy fiber
1 e(
o 5'
Mossy fiber
Sagittal
/ Climbing fiber
Purkinje cell axons
Climbing fiber
Figure 15 4 Cerebellar cortex in sagittal and transverse planes showing cell ond fiber arrangements Purkinje cells
and cell processes (i.e . axons and dendrites) are shown in blue. Mossy fibers are in yellow and climbing fibers are
.
shown in red Golgi cells, basket cells, and outer stellate cells are in block . While the dendritic arborizations of Purkinje
cells are oriented in a sagittal plane, dendrites of Golgi cells show no such arrangement Layers of the cerebellar cor -
tex are indicated
15 Cerebellum 587
Outer stellate cell
FI *—
D
(
g'
m —
MH
Parallel fibers
o ,
- -
D
O
Q)
V t t m Ir
c
5 ill / '
t
C Basket cell
3
Q .
s Golgi cell i
ai
>>
o i
/ fiLx \
i S \
l
o
D
\
i — Purklnje cell axon
c
o j
O
>
Granule
cells
i
7 Deep cerebellar
nuclei
6
Climbing Lat. vest nuclei
fiber Mossy fiber
Figure 15.5 Cellular and fiber elements of the cerebellar cortex in the longitudinal axis of a folium. Excitatory (gluta-
matergic) inputs to the cerebellar cortex are conveyed by the mossy fibers ( yelloW) and the climbing fibers (red) The
broken line represents a glia lamella ensheathing a glomerulus that contains (a) a mossy fiber rosette, (b) several
granule cell dendrites, and (c) one Golgi cell axon. Axons of granule cells ascend to the molecular layer, bifurcate,
and form an extensive system of parallel fibers which synapse on the spiny processes of the Purkinje cells. Purkinje
cells and their processes are shown In blue. Climbing fibers traverse the granular layer and ascend the dendrites of
the Purkinje cells where they synapse on smooth branchlets . Arrows indicate the directions of impulse conduction,
Outer stellate and basket cells are shown in the molecular layer, but the axons of the basket cells that ramify around
Purkinje cell somata are not shown .
tacts with Purkinje cell dendrites ( Figs. 15.4 to 20 Purkinje cell widths and may contact as
and 15.5) . Basket cells , located in the deep many as 150 Purkinje cell bodies. Along its
parts of this layer near the Purkinje cell bod- course, the horizontal segment of a basket cell
ies ( Figs. 15.3-15.5), give rise to dendrites that axon emits groups of collaterals that descend
ascend in the molecular layer in some in- and embrace Purkinje cell soma and its initial
stances as far as 300 pm . The axons of basket segment . As many as 20-30 different basket
cells extend along the Purkinje cell layer at cells are believed to wrap their axon termi -
right angles to the direction of the parallel nals around each Purkinje cell soma , forming
fibers. They may spread over a distance equal a typical basket - like meshwork ( 20, 173) ( Fig .
15.4 ). The stellate and basket cells ( mean di - large primary dendrites which branch repeat -
ameter 5-9 jim ) may in fact belong to a single edly. In the depth of a furrow, the dendritic
class of neurons, it is estimated that stellate branches form a broad angle approximating
and basket cells are respectively 16 and 6 180°, while near the crest of a folium , den-
times more numerous than Purkinje cells dritic branches form more acute angles (89 ).
( 173) . The full extent of the dendritic arborization
Both cells are known to exert an inhibitory can be appreciated only in sagittal sections.
action upon the Purkinje cells, and y - Primary and secondary dendritic branches
aminobutyric acid ( GABA ) is likelv to serve are smooth, but tertiary dendritic branches
as the neurotransmitter of basket cells. The have spines that are short, thick, and rough .
basket cells also contain the enzyme that is These thick dendritic spines are referred to as
responsible for synthesizing nitric oxide spiny branchlets or gemmules (98) ( Figs. 5.9 and
( NO ), a highly toxic gas that is now believed 15.6). Larger dendritic processes bear stub-
to act as a neurotransmitter in several brain bier thorns or spines known as smooth branch-
areas, including the cerebellum ( 269). This lets. The combined surface area of the den-
enzyme, NO synthase, is identical to nicotin - dritic branchlets and spines of one Purkinje
amide adenine dinucleotide phosphate di - cell in monkeys is said to be about 200,000
-
aphorase ( NADPH diaphorase), an enzyme gnv ( 98). A synaptic area of such magnitude
that has been known for over 30 years and on each of 15 million cells indicates the com -
that can be easily visualized with a simple plexity and magnitude of the neural compu -
histochemical technique. The target for NO tation that occurs in the cerebellar cortex.
action is the soluble enzyme guanylvl cyclase. Purkinje cell axons are myelinated , pass
By activating this enzyme, NO induces through the granular layer and white matter,
marked increases in cCMP levels in the cere - and establish synaptic contacts with the cere-
bellum , as elsewhere in the brain. The cGMP bellar nuclei . Purkinje cell axons project to the
formed may then regulate protein kinases, cerebellar nuclei by the shortest direct route.
phosphodiesterases, and ion channels in These axons also give rise to recurrent collat -
Purkinje cells ( 269 ). Although the inhibitory erals ( Figs. 15.4 and 15.5), which establish ax-
neurotransmitter of stellate cells has not been osomatic contacts with Golgi type II cells in
decisively established , it could be taurine the granular laver (117). Purkinje cell axons
( 173, 201 ) . In addition to stellate and basket represent the sole output pathway of the
cells, the molecular layer contains the den - cerebellar cortex.
drites of Purkinje and Golgi type 11 cells and The unique feature of Purkinje cells is their
the transversely oriented axons of granule monoplanar shape. Both the dendritic arbors
cells ( i .e., parallel fibers ). and the axonal projections of Purkinje cells lie
in a single plane perpendicular to the major
Purkinje Cell Layer axis of the folia . Moreover, the planes of all
Purkinje cell dendrites in a given region are
-
This single cell layer consists of great parallel, so that the dendritic arrays of the
numbers of large flask-shaped cells relatively cells stack up in a highly ordered fashion .
uniformly arranged along the upper margin This remarkable orderly array determines, to
of the granular layer ( Figs. 15.2-15.5). Pur - a large extent, the nature and number of con -
kinje cells have a clear vesicular nucleus with tacts made with other kind of cells. Thus, par-
a deep-staining nucleolus and irregularly dis- allel fibers running perpendicular to the
tributed Nissl granules ( 212 ). They are among plane of the dendrites intersect a multitude of
the largest (about 50-80 pm in diameter ) and Purkinje cells, by the very manner in which
most numerous (approximately 15 x 10") neu - these elements are organized (173) . In Japan ,
rons in the central nervous system. A quanti - Masao Ito made the crucial discovery that the
tative study of the human cerebellum with Purkinje cells are inhibitory (134 ), and im-
stereologic techniques has estimated the munohistochemical studies indicate that
number of Purkinje cells to be as high as GABA is the neurotransmitter released at the
30.5 x 10" ( 6). Each cell gives rise to an elabo- synapse of these cells (96, 97, 201 , 210 ). Pur-
rate flattened, fan-like, dendritic tree oriented kinje cells also express various polypeptides,
at right angles to the long axis of the folia including motilin ( 67), nerve growth factor
( Figs. 15.4 and 15.5) ( 177). The dendritic tree receptor (197), insulin-like growth factor 1
arises from the neck of the cell as two or three ( IGF-1 ) ( 2), 0-thyroid receptor ( 222 ), and cal -
15 Cerebellum 589
Figure 15.6 A single Purkinje cell and its rich dendritic arborizations in the molecular layer . Golgi preparation ( •
300)
bindin D-28k ( 128 ). Some of these peptides Purkinjo cell comportments that are similar in
may play a crucial role in Purkinje cell matu- rodents, monkeys, and humans ( 24, 119, 171,
ration and maintenance. 219 ) (Fig. 15.8). This peculiar pattern of irn-
The Purkinje cells of the cerebellum were munostaining has been shown to be congru-
the first neurons to be identified ( 294 ) and the ent with the parasagittal / ones of termination
first neurons to be analyzed in microscopic of the olivocerebellar projections ( 119) and
detail. They are also the first class of neurons spinocerebellar projections arising from the
for which a specific immunologic marker, not central cervical nucleus ( 188 ). These findings
related to the biosynthesis of a neurotrans- suggest the existence of widespread chemical
mitter, has been identified. Guanosine 3 ',5 ' - and anatomic heterogeneity in the cerebellar
phosphate-dependent protein kinase (cGK ) cortex, particularly among the Purkinje cells.
antiserum is a specific marker for Purkinje
cells (79, 284) ( Fig. 15.7 ). Other immunologic Granular Layer
markers for Purkinje cells have been charac-
terized and many of these markers stain only This layer is composed of a vast number
subsets of Purkinje cells organized in densely packed small neurons, mostly small
parasagittal microzones separated by nonim- granule cells ( Figs. 15.2-15.5 and 15.9 ). The
munoreactive interzones (b7, 119, 188, 272,
284, 295). One intrinsic molecular marker of
number of these small neurons, about 10 ,
exceeds that of the entire cerebral cortex
"
particular interest is the polypeptide antigen (104 ). Granule cells are so tightly packed (3-7
zebrin I that is recognized by monoclonal million cells per cm ' ( 2b ) ) that residual space
(mab) antibody Q113. Zebrin I immunohisto- seems insufficient to accommodate their
chemistry reveals an array of parasagittal processes and fibers of passage These cells .
Figure 15.7 Sagittal section of the rat cerebellar cortex immunostained with an antibody to guanosine 3 \ 5 ' -phos-
phate-dependent protein kinase (cGK), a specific molecular marker for Purkinje cells. This immunologic marker is not
related to the biosynthesis of any neurotransmitters, but specifically labels all parts of the Purkinje cells.
are round or oval, 5-8 p. m in diameter, with dendritic domain (98, 99 ). This represents, by
aggregated chromatin granules near the nu - far, the largest synaptic input to any given
clear membrane. Granule cell nuclei appear central neuron. Each parallel fiber, extending
as naked nuclei because of the thinness of the about 3 mm from its bifurcation, has been es-
rimming cytoplasm and the absence of dis- timated to traverse the dendritic trees of up
crete Nissl granules ( 99). Each granule cell to 500 Purkinje cells ( 173, 255). The parallel
gives rise to four or five short dendrites with fibers of the granule cells also make "cross-
claw-like endings which terminate in the ing-over" synaptic contacts with the den-
"glomeruli" ( Figs. 15.5 and 15.9 ) . The scv drites of stellate, basket , and Golgi type II
called cerebellar islands are irregularly dis- cells in the molecular layer ( Fig. 15.5). The
persed spaces, which are free of granule cells granule cells are known to exert a glutamate-
but contain complex synaptic structures mediated excitatory influence upon its target
known as "glomeruli" ( Fig. 15.12). Axons of cells (106, 209, 210). They also contain signifi -
granule cells are unmyelinated fibers that as- cant levels of nitric oxide synthase or
cend vertically into the molecular layer and NADPH -diaphorase ( 269 ).
bifurcate into two branches which run paral- Golgi type II cells, found mainly in the
lel to the long axis of the folium. These fibers, upper parts of the granular layer, have vesic-
referred to as parallel fibers , are found ular nuclei, and definite chromophilic bodies.
throughout the molecular layer where they They are as numerous as the Purkinje cells
are oriented perpendicular to the sagittal fan - and their cell bodies have a diameter that
shaped dendritic expansions of the Purkinje ranges from 6-11 pan. Dendrites of these cells
cells ( 212 ) ( Fig. 15.4). extend throughout all layers of the cerebellar
Parallel fibers make multiple synapses on cortex, and arborizations are not restricted to
the spiny branchlets of Purkinje cells, princi - a single plane ( Figs. 15.4 and 15.5). Golgi cell
pally on the head of the spines. This type of dendrites are contacted by parallel fibers in
synaptic contact has been referred to as the the molecular layer, while their cell bodies re-
"cross-over" synapse (100, 114, 117). It is esti- ceive inputs from collaterals of climbing
mated that each Purkinje cell bears more than fibers and recurrent collaterals of Purkinje
100,000 dendritic spines and that about cells (117, 233). Golgi cells located in the deep
200,( XX ) parallel fibers projected through its portion of the molecular layer tend to be
15 Cerebellum 591
T
A . T T
^' V
f
** . 8 MSI# / .
a
i
:•.
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/3
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M
ti Jvi i
>
v
.' ,
JK
m **
r i
v;
i, ,
.
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§
4 0
t > *b* *»
•
'i •
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.
*
•*
~ ,>- \/
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*
/
/ f
As,:'. IX
. •
va«SS
iv /
v$- y
,v V
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•
Figure 15.8 Comparison of the band like distribution of (A) acetylcholinesterase (AChE) and (B) zebrin I on adjacent
frontal sections from the posterior lobe vermis of an adult rat. The presence of the antigen zebrin I was revealed with
the monoclonal antibody (mab) QII 3 Only Purkinje cells are stained and they are aligned to form a series of
parasagittal bands (P 1 -P7) in both the vermis and the hemispheres. The zebrin-posltive bands alternate with bands
devoid of immunostaining. This intrinsic molecular marker stains the soma, entire dendritic arbor, and axons of distinct
subsets of Purkinje cells that form typical parasagittal microzones that are congruent with the termination patterns of
spinocerebellar and olivocerebellar fibers, as well as with the distribution of AChE. The pattern of zebrin-positive bands
is particularly obvious in lobule VIII: the P I P2\ and P3 bands are labeled in B, and their AChE equivalent In A are in-
dicated with arrowheads.
' -
jw 4 i
Figure 15.9 Granule cells in the cerebellar cortex dis-

playing short dendrites with claw -like endings. Golgi
preparation ( 200)
*
smaller than those located more superficially

and they have dendrites that are largely con-
fined to the granular layer (89). Axons of
Golgi cells arborize profusely in the granular
layer and terminate on granule cell dendrites
Figure 15.10 Golgi (type II) neuron in the superficial
in cerebellar glomeruli, where they exert a
granular layer of the cerebral cortex immunostained for
GABA- mediated inhibitory action (173, 201 ) GABA These interneurons display more intense im-
( Fig. 15.10). munostaimng with antiserum to GABA than Purkinje cells
Cortical Inputs
Afferent fibers to the cerebellum convey the cerebellar nuclei, most likely via axon col -
impulses primarily to the cerebellar cortex. laterals of fibers that terminate in the cerebel -
These afferents form various tracts that enter lar cortex (195, 268). These projections acti-
mainly via the inferior and middle cerebellar vate neurons in the cerebellar nuclei and
peduncles and include the spinocerebellar, represent the primary cerebellar circuit ( 104 ).
cuneocerebellar, olivocerebellar, vestibulo- This primary circuit is then modulated by the
cerebellar, and pontocerebellar tracts, as well inhibitory action of the cerebellar cortex,
as numerous smaller bundles. Additionally, which is mediated by the Purkinje cells and
there are cerebellar association fibers that driven by the same excitatory inputs.
pass from one folium to adjacent folia and
others that connect different cortical regions MOSSY FIBERS
on the same side (86, 87, 208). Long- and
short-association fibers in the cerebellar cor- The mossy fibers , so-called because of the
tex are regarded as myelinated axonal collat- appearance of their terminations in the em-
erals of Purkinje cells (99). Within the cerebel - bryo, constitute the largest contingent of cere-
lar cortex, the afferent fibers lose their myelin bellar afferents. They originate from a variety
sheath and end either as mossy fibers or of central nervous system regions, including
climbing fibers. These two inputs use gluta - the vestibular nuclei, spinal cord , cerebellar
mate as a neurotransmitter ( 173, 201, 209, 210, nuclei, and the cerebral cortex via the ponto-
211 ), and their excitatory action determines cerebellar projection system, which is one of
the activity of the only cortical output system , the most massive pathways in the brain (78,
the Purkinje cells. Despite differences in ori- 173). These coarse fibers bifurcate repeatedly
gin , sites of termination, and functional roles, in the white matter, give off fine axon collat -
the mossy and climbing fibers both project to erals to cerebellar nuclei, enter the granular
15 Cerebellum 593
layer, and often provide branches to adjacent mal parts of Golgi cell dendrites. The center
folia . In the granular layer, fibers lose their of the glomerulus contains a single mossy
myelin sheath and emit many thin collaterals. fiber rosette with which the dendrites of
Fine lobulated enlargements occur along the about 20 different granule cells interdigitate
course of the branches and at their terminals ( Figs. 15.11-15.13). Axons of Golgi cells form
and are referred to as mossi/ fiber rosettes (114). a plexus on the outer surface of the granule
A single mossy fiber may have as many as 44 cell dendrites. The entire structure is en -
rosettes along its many branches ( Figs. 15.4, sheathed in a single glial lamella ( 20, 89 ). In
15.5, and 15.11 ) (99). Each mossy fiber rosette -
the glomerulus, the mossy fiber granule cell
forms the center of a cerebellar glomerulus. synapse is excitatory, while the Golgi axon-
In Golgi preparations, mossy fiber rosettes granulecell junction is inhibitory (91 ). Thus, a
appear as coiled, convoluted fibers ( Fig. cerebellar glomerulus is a synaptic cluster in
15.11 ) ( 99). At the ultrastructural level, nu - which two types of presynaptic fibers, mossy
merous synaptic vesicles, concentrations of fibers, and Golgi cell axons, enter into a com -
mitochondria, neurofilaments and neuro- plex relationship with one postsynaptic ele-
tubules are visualized within single rosettes ment , the granule cell dendrites. Golgi cells
( Fig. 15.13) (198, 212 ). function as a negative feedback to the mossy
A cerebellar glomerulus is a complex fiber-granule cell relay. The main excitatory
synaptic structure contained within the "cere- input to the Golgi cell is derived from the
bellar islands" of the granular layer ( Figs. parallel fibers ( Fig. 15.5).
15.4, 15.5, and 15.12 ). The glomerular com -
plex is a nodular structure formed by ( a ) one CLIMBING FIBERS
mossy fiber rosette, ( b) the claw-like dendritic
terminals of numerous granule cells, ( c) the The climbing fibers , whose name derives
terminals of Golgi cell axons, and ( d ) proxi - from the morphology of their terminations
figure 15.11 Mossy fiber rosettes in the granular layer of the monkey cerebellum as seen in a Golgi preparation.
Mossy fiber rosettes look like solid structures at a low magnification, but appear as coiled convoluted fibers at a higher
magnification ( x 850).
Mossy fiber rosette
Golgi ceil dendrite
Golgi cell axon
Granule cell dendrites
Glial capsule
Mossy fiber
Figure 15.12 Reconstruction of a cerebellar glomerulus based upon electron microscopic studies A cerebellar
glomerulus is formed by one mossy fiber rosette, the claw -like dendritic terminals of numerous granule cells ( red), and
terminals of Golgi cell axons ( yellow) Proximal parts of Golgi dendrites ( blue) also enter the glomerulus and establish
broad synaptic contacts with the mossy fiber rosette. The entire nodular structure is ensheathed in a glial capsule. In
this reconstruction, the glomerulus is shown in horizontal section, and In a schematic three-dimensional view .
upon Purkinje cells, have been the center of strips that interdigitate with unlabeled strips
great interest since their discovery by Ramon (17, 73, 78).
y Cajal in 1888, because of their remark - The climbing fibers ascend undivided
able one- to-one relationship with dendritic through the white matter of the cerebellum
branches of the Purkinje cell . These fibers and the medullary lamina of the folia , tra-
have been thought to be recurrent axonal col- verse the granular layer, and project beyond
laterals of Purkinje cells (175) or recurrent the Purkinje cell somata to reach the den-
axons of the cerebellar nuclei ( 62). There is drites of the Purkinje cells. These unmyeli-
now general agreement that climbing fibers, nated fibers divide into numerous branches
like mossy fibers, have exogenous origins and climb the dendritic arborization of the
( i.e., from nuclei outside of the cerebellum ). Purkinje cell ( Figs. 15.4 and 15.5). Climbing
Silver impregnation techniques originally fibers contact only the smooth branchlets of
suggested that most climbing fibers origi - Purkinje cell dendrites; they do not contact
nated from the inferior olivary complex ( 251 ). the spiny branchlets on which parallel fibers
This view was strengthened by electrophysi - synapse (99 ). Many climbing fibers form in -
ologic results which concluded that climbing fraganglionic plexuses immediately beneath
fibers originated only from the inferior oli- the Purkinje cell layer before turning upward
vary complex (63, 89, 254 ). Anterograde label - to be deployed over the dendritic arbor of a
ing studies indicate that nearly all climbing single Purkinje cell . Although collaterals of
fibers arise from the inferior olive and that climbing fibers may established contacts with
these fibers terminate in the contralateral as many as 10 adjacent Purkinje cells, each
cerebellar cortex in the form of thin sagittal Purkinje cell receives synaptic connections
15 Cerebellum 595
Figure 15.13 Cerebellar glomerulus in the monkey A mossy fiber rosette (Mf) with dispersed syndptic vesicles
( arroW ) is surrounded by granule cells (Gi ) Granule cell dendrites are Indicated by asterisks ( x 5600)
from only a single climbing fiber. In fact, the basket cell axons are restricted to dendritic
arborization of these thin collaterals ( 233) ap- shafts. Furthermore, collaterals of climbing
pears insignificant when compared with the fibers given off in the granular layer synapse
repeated and abundant synaptic contacts that directly upon the shafts of granule cell den -
a climbing fiber makes with the dendrites of drites and the somata of Golgi cells (69).
its own Purkinje cell (89). Collaterals of the
climbing fiber also make contact with stellate, MONOAMINERGIC AND CHOLINERGIC
basket, and Golgi cells (117, 233). Electron mi- INPUTS
croscopic evidence indicates that although
climbing fibers and basket cell axons partially Fluorescence histochemistry has revealed
overlap in their contact with portions of the a hitherto unrecognized fiber system in the
Purkinje cell dendritic tree, there are no cerebellar cortex that contains norepineph -
synaptic junctions between these fibers (68). rine (or noradrenaline) (124 ). These noradren-
Climbing fibers articulate primarily with the ergic fibers extend from the white matter into
smooth branchlets of the dendritic tree, while all layers of the cortex, are not restricted to
any particular plane, and are moderately con- throughout all cortical layers without special-
centrated in the Purkinje cell layer. This fiber ized junctions, and (c) pass directly to the
system arises chiefly from the locus coeruleus molecular layer where they bifurcate like par -
( Figs. 13.33-13.35, and 14.3) and less abun - allel fibers and synapse with cerebellar in -
dantly from catecholaminergic neurons in the terneurons (66 ). Serotonergic fibers differ
ventrolateral medulla and the rostral pons from noradrenergic afferents in the molecular
( 296 ). Cells in the caudal half of the locus layer in that they do not synapse upon Pur-
coeruleus were shown to arborize in the en - kinje cells.
tire cerebellar vermis, the flocculus, and the Evidence for a cerebellar cholinergic inner-
ventral paraflocculus ( 244 ). The brainstem vation derives from immunohistochemical
noradrenergic fibers appear to exert their in- studies with antibodies raised against the
fluence primarily on Purkinje cells ( 23, 202, acetylcholine synthesizing enzyme, choline
218), but also on GABAergic interneurons acetyltransferase (ChAT), in various species
( 289, 290) . Their activation produces a wide - including humans ( 19, 130, 133, 148, 149 ).
spread release of norepinephrine that hyper- Thin, finely beaded axons that display ChAT -
polariz.es the Purkinje cells. This form of inhi- immunoreactivity occurs in all cortical layers.
bition can be mimicked by the application of Furthermore, a selective ChAT labeling of
cyclic adenosine-3',5'- monophosphate ( AMP), some large mossy fibers rosettes is observed
and implies that norepinephrine may func- in the granular layer, particularly in cerebel -
tion by the activation of an electrogenic lar regions ( lobules 1, II , IX, and X , as well as
sodium pump similar to those in other cen -
tral neurons ( 173). An additional indepen -
-
flocculus ventral paraflocculus area ), which
are known to receive primary and secondary
dent action at low threshold is the enhance- vestibular afferents ( 19). These findings sug-
ment of GABA-mediated inhibition in the gest that a subset of vestibular projections to
cerebellar cortex, an effect that appears medi- the cerebellar cortex is cholinergic. Retro-
ated through [M noradrenergic receptors grade labeling studies have also identified the
( 289, 290). Hence, norepinephrine seems to pedunculopontine nucleus of the mesopon-
exert multiple modulatory functions in the tine tegmentum as a potential source of cere-
cerebellar cortex. bellar afferents ( 296). As seen in the preced -
There is also evidence for dopaminergic ing chapter, this nucleus is topographically
afferents to the cerebellar nuclei and to all related to the superior cerebellar peduncle
layers of the cerebellar cortex ( 213, 236). and is markedly enriched with cholinergic
Dopamine binding sites also exist in the cere- neurons ( group Ch 5). Hence, the pedunculo-
bellum as revealed by autoradiographic bind - pontine nucleus could be a major source of
ing studies undertaken with tritiated spiper - cholinergic input to the cerebellum.
one as ligand ( 213). The role of these
dopaminergic afferents, which appear to Basic Circuit Organization
originate from neurons located in the sub-
-
stantia nigra ventral tegmental area complex Geometric relationships of elements
of the ventral midbrain , is still unknown . within the cerebellar cortex have furnished
The raphe nuclei, which synthesize and re- many hypotheses concerning the functions of
- -
lease serotonin (5 hydroxytryptamine, 5 HT ), individual neurons. Physiologic studies indi-
project to all parts of the cerebellar nuclei and cate that (a ) climbing fibers exert a powerful
cortex (66, 152, 253, 265). The largest number excitatory influence on Purkinje cell den-
of serotonergic fibers appear to arise from the drites, ( b ) parallel fibers excite Purkinje cells
raphe nuclei of the pons and medulla (110,
252, and 296 ), although serotoninergic neu -
-
via "cross over" synapses, and ( c) stellate,
basket, and Golgi cells are inhibitory in-
rons located more laterally in the brainstem terneurons in the cerebellar cortex. Stellate
reticular formation also contribute to the cells exert inhibitory influence of dendrites of
cerebellar innervation (152 ). All parts of the Purkinje cells, whereas basket cell inhibition
cerebellar cortex receive afferents from the is affected by axosomatic synapses on many
raphe nuclei, with the most profuse projec- Purkinje cells in a sagittal plane. Golgi cells
tions passing to lobules Vll and X of the ver- inhibit afferent input to the cerebellar cortex
mis and to crus I and II ( 110). Axons of raphe -
at the mossy fiber granule cell relay in the
neurons (a ) terminate as mossv fiber rosettes glomeruli . Because Golgi cell axons reach
in the granular layer, ( b) terminate diffusely glomeruli throughout the depth of the cere-
15 Cerebellum 597
bellar cortex, they can inhibit mossy fiber Golgi cell axon . This mechanism depresses
input to parallel fibers. the activity in Purkinje cells on both sides of
The Purkinje cells are the sole output ele- the single Purkinje cell excited by the climb-
ments of the cerebellar cortex. They are under ing fiber. The widespread inhibitory influ-
the influence of three inhibitory interneurons ence exerted by a single climbing fiber ap-
( the stellate, basket, and Golgi cells) and one pears to be a device to silence the background
excitatory interneurons ( the granule cells). for a single Purkinje cell activated by a climb-
This relatively simple basic circuit is driven ing fiber volley (89).
by two major excitatory inputs, the climbing Mossy fiber impulses exert their synaptic
and the mossy fibers. Climbing fibers have a excitatory action solely within the cerebellar
direct, all-or-none, excitatory action on single glomerulus, where they excite granule cells
Purkinje cell (90, 92). This synaptic connec- whose axons ( the parallel fibers ) excite all
tion is one of the most powerful in the ner- cells with dendrites in the molecular layer
vous system. A single action potential in a (i.e., Purkinje, basket, stellate, and Golgi
climbing fiber elicits a gigantic excitatory cells). Impulses conveyed to dendrites in the
postsynaptic potential, which produces high molecular layer result in excitation of (a ) a
frequency burst of action potentials, called a narrow band of Purkinje and Golgi cells in
complex spike, in the Purkinje cell. In con- the longitudinal axis of the folia, and (b) bas-
trast, the mossy fiber input transmitted by ket and stellate cells whose axons extend
parallel fibers results in smaller excitatory sagittally ( transverse to the folia ) on each side
postsynaptic potentials. Spatial and temporal of the exited beam of parallel fibers ( Fig.
summation of these smaller postsynaptic po- 15.14). This geometric configuration results in
tentials is required for the Purkinje cell to excitation of a narrow band of Purkinje cells,
produce a single action potential, called a flanked on each side by Purkinje cells inhib-
simple spike (104). The mossy and climbing ited by basket and stellate cells (89, 93). By
fibers are modulated differently during nat- analogy to the surround inhibition in sensory
ural behaviors. Mossy fibers fire sponta- systems, the stellate and basket cell inhibition
neously at high rates, producing 50-100 sim- is thought to sharpen the boundaries between
ple spikes per second in Purkinje cells. active clusters of Purkinje cells, whereas
Sensory stimuli or voluntary movements in- Golgi inhibition provides temporal focusing
crease this firing even further. These mossy of the excitation (104).
fiber inputs are essential for controlling the The net result of the complex neural com-
firing of the Purkinje cell. In contrast, the neu- putation that occurs in the cerebellar cortex is
rons of the inferior olive that give rise to the a GABA-mediated inhibition conveyed by
climbing fibers fire at low and irregular rates, the axon of Purkinje cells (89, 134, 136-139).
and , on average, produce only one complex Thus, axons of Purkinje cells exert inhibitory
spike per second . Sensory stimuli or move- influence on cells with which they synapse,
ments elicit only one or two complex spikes, namely the cerebellar nuclei and portions of
suggesting that the climbing fibers are not in- the vestibular nuclei (82, 83, 85, 277). Collater-
volved in the direct control of motor behavior als originating from proximal portions of the
(104). Instead , because they can modulate the axon of Purkinje cells ( Fig. 15.4) exert in -
responsiveness of Purkinje cells to mossy hibitory influences on Golgi cells, which in
fiber inputs, the climbing fibers are likely to turn inhibit granule cells. This disinhibition
be involved in the learning aspect of cerebel- tends to release granule cells whose axons ex -
lar functions (134). cite Purkinje cells.
Climbing fibers reaching a given Purkinje
cell also have synaptic articulations with in- Neuroglia
hibitory interneurons, the Golgi, stellate, and
basket cells. Excitation of basket cells results While most of the neuroglial elements in
in inhibition of Purkinje cells on both sides of the cerebellar cortex are similar to those in
a single Purkinje cell receiving the main other parts of the central nervous system, the
branches of a climbing fiber. A single basket architectonics of the neuroglia bear definite
cell theoretically could inhibit 7 rows of about relationships to the three-layered neuronal
10 Purkinje cells. The excitation of Golgi cells structure ( Fig. 15.15). Each cortical layer has a
via climbing fibers results in the inhibition of different population of neuroglial cell types,
impulses reached by the ramifications of the and one type, the Golgi epithelial cell, is
Off -beam Purkinje cell

inhibited by stellate or
basket cell
/
Beam of parallel fibers
] excited by focal input:

on-beam excited
Purkinje cells
Basket cell
Purkinje cell
Figure 15.14 Dorsal surface of a folium showing that excitation of a beam of parallel fibers leads to excitation of a
central (on-beam) region of F urkinje cells and inhibition of surrounding (off -beam) Purkinje cells This type of inhibition
’
is mediated via the excitation of the inhibitory basket and stellate cells The dark area surrounding the excited beam
of parallel fibers indicates inhibitory effect.
unique to the cerebellar cortex ( Fig. 15.16). smooth branchlets of Purkinje cell dendrites
The cerebellar cortex contains both astrocytes from passing parallel fibers (99 ). This insula-
and oligodendrocytes. Astrocytes are primar- tion appears absent only where climbing
ily protoplasmic and have been divided into fibers come into synaptic relationship with
three classes: (a ) the Golgi epithelial cell, ( b) the smooth branchlets. These specialized glial
the lamellar or velate astrocyte, and (c ) the processes also may serve to confine transmit -
smooth astrocyte ( 212). The Purkinje cell ter substances to a particular synaptic site
layer contains modified astrocytes known as and in this way promote neuronal specificity
the Golgi epithelial cells ( 223), or Bergmann ( 217). The Golgi epithelial cell is characteristic
cells . These neuroglial cells are true satellites of the Purkinje and molecular layers and is
of Purkinje cells in that they lie directly not found elsewhere. Golgi epithelial cells,
against the surface of Purkinje cells and form Fananas cells and protoplasmic astrocytes of
a nearly complete sheath around them ( Fig. the cerebellar cortex probably are all variants
15.16). Purkinje cells also are surrounded by of a single cell type ( 212).
Fananas cells ( Fig. 15.15), which are similar to The lamellar astrocyte is found chiefly in
the Golgi epithelial cells and protoplasmic as- the granular layer, while the smooth astro-
trocytes ( 212, 248). Each Bergmann cell gives cyte may be found in any layer, but is most
rise to two or more processes which bifurcate common in the granular layer. Lamellar as-
and ascend in almost parallel lines to the pial trocytes are about the same size as granule
surface. These processes course perpendicu -
cells, have a bean-shaped nucleus and may
larly in the molecular layer and terminate at contain one or two nucleoli. The distribution
the surface of the cortex ( i.e., limiting glial and form of the glial processes of these cells
membrane) in conical expansions. These cells are unusual in that numerous lamellar neu -
resemble miniature candelabra with their roglial processes pass between adjacent gran -
branches either clustered or spread out in ule cells, dendrites, and axons, forming open
parasagittal planes. The neuroglial processes and confluent compartments. The number
of these cells lie between the dendritic ar- and extent of these processes is greater than
borizations of consecutive Purkinje cells might be expected . The lamellar processes
( 223). Electron micrographs indicate that the separate one glomerulus from another in the
ascending processes of neighboring Berg- cerebellar islands, and interweave with the
mann cells are interdigitated to form a dense dendrites and Golgi cell axons on the periph -
forest, rather than alternating palisades. ery of the glomeruli ( 212).
Processes of Bergmann cells insulate the Smooth astrocytes with long radiating
15 Cerebellum 599
. .
Figure 15.15 Arrangement of neuroglia cells in human cerebellar cortex f cells of Fananas; gl astroglia. hg( mi -
.
croglia; ogl ogl \ oligodendrocytes
Figure 15.16 Golgi epithelial cells in the rat cerebral cortex Purkinje cells are surrounded by Golgi epitheliol cells
whose somata bear ragged irregular appendages. Multiple processes of these glial cells extending upwards to the
pial surface in candelabra-fashion bear irregular leaf -like appendages which project horizontally . These cells cannot
be distinguished from Fahanas cells.
processes, found in the molecular and granu - tions to the cerebellar cortex, efferent fibers
lar layers, resemble stellate neuroglial cells, from the cerebellar cortex and , to a lesser ex-
but are much smaller. Processes of these cells tent, association fibers connecting the various
are kinky, contorted, and branch repeatedly. portions of the cerebellum. The corpus
Oligodendrocytes, seen throughout the cere- medullare is continuous with the three pe-
bellar cortex, are most numerous in the gran - duncles which connect the cerebellum with
ular layer and in the depths of the molecular the brain stem: ( a ) the inferior cerebellar pedun -
layer where myelinated fibers are found. cle , which connects with the medulla; ( b ) the
middle cerebellar peduncle , which connects with
CEREBELLAR NUCLEI the pons; and (c) the superior cerebellar pedun -
cle , which connects with the midbrain ( Figs.
Major Features 2.26 and 2.32 ). Medially and ventrallv , near
CORPUS MEDULLARE the roof of the ventricle, the corpus medullare
splits into two white laminae, inferior and su -
It is a compact mass of white matter, perior, which separate at an acute angle to
which is continuous from one hemisphere to form a tent-like recess (i.e., fastigium ) in the
the other and covered everywhere by the roof of the fourth ventricle ( Figs. 2.27, 2.28,
cerebellar cortex. It consists of afferent projec- and 2.33). The inferior medullary lamina ( or
15 Cerebellum 601
velum ) passes caudally over the nodulus and yond the cerebellum . Immunohistochemical
becomes continuous with the tela choroidea data suggest that glutamate and / or aspartate
and the choroid plexus of the fourth ventri- may be the excitatory transmitter of most
cle. Laterally , the inferior medullary velum cells in the cerebellar nuclei ( 201, 210, 228).
extends to the flocculi, forming a narrow Additionally, a significant proportion of the
bridge connecting these structures with the small neurons in the cerebellar nuclei are
nodulus. The largest part of the medullary GABAergic (101 ). Virtually all of these small
substance is continued rostrally , forming the GABAergic, presumably inhibitory, cells are
superior medullary velum ( Figs. 2.28 and projection neurons, and a significant propor-
2.32). The latter is a thin white plate joining tion of them project to the inferior olivary nu -
the two superior cerebellar peduncles. To- cleus ( 101 ). Purkinje cells, which provide the
gether, these structures form the roof and lat - only output from the cerebellar cortex, pro-
eral walls of the upper part of the fourth ven- ject in an orderly manner to the cerebellar nu -
tricle. clei, where they inhibit the excitatory (and
partly inhibitory ) output system that origi-
CEREBELLAR NUCLEI nates from the nuclear masses within the
white matter of the cerebellum .
Imbedded in the white matter of each half
of the cerebellum are four nuclear masses, the DENTATE NUCLEUS
cerebellar nuclei ( Figs. 13.7, 13.26, 15.18, and
This nucleus, the largest of the cerebellar
15.19). These cellular aggregates are often re-
ferred to as the "deep cerebellar nuclei," but nuclei, lies in the white matter of the cerebel -
because there exist no superficial cerebellar lar hemisphere close to the vermis ( Fig.
nuclei, the qualificative "deep" is avoided in 15.17). In transverse sections, this large nu -
the present account. All cerebellar nuclei cleus appears as a convoluted band of gray
matter having the shape of a folded bag with
originate from condensations of cells that mi-
the opening or hilus directed medially and
grate outward from the germinal neuroep-
ithelium of the fourth ventricle (155). The dorsally ( Fig. 15.19 ). Its resemblance to the in-
four cerebellar nuclei start to differentiate si- ferior olivary nucleus is obvious ( Fig. 15.18).
It is found as a definite nucleus only in mam -
multaneously at early developmental stages
and there is no evidence that individual cere- mals, and it becomes greatly enlarged in hu -
bellar nuclei differ with respect to ontoge- mans and the anthropoid apes. In both an -
netic origin or age. Although four distinct thropoid apes and humans, the dentate
nucleus can be divided into an older dorso-
cerebellar nuclei are recognized in most
mammals, prior to the investigations of medial portion (paleodentate) and a larger,
newer ventrolateral portion ( neodentate).
Snider ( 239) most authors described these nu - Cells in the ventrolateral region of the dentate
clei as a capriciously indented cell mass divis-
nucleus are smaller than those located dorso-
ible into three nuclei: ( a ) the medial ( fasti-
gial), ( b ) the interposed , and (c ) the lateral medially (170, 261 ). The nucleus is composed
( dentate ). Studies in the monkey distinguish mainly of large multipolar cells with branch -
ing dendrites. Axons of these cells acquire a
four cerebellar nuclei on the basis of fiber pat - myelin sheath while still in the nucleus and
terns, cellular morphology, and the size,
shape, and orientation of cells (76). The emerge from the cerebellum in the superior
cerebellar peduncle (170). Between these
strongest arguments supporting the existence
of four individual cerebellar nuclei are obser- large cells are small stellate cells whose axons
vations indicating that each nucleus has
arborize within the nucleus. Golgi studies of
the dentate nucleus in rats and monkeys re-
unique connections. The four cerebellar nu -
veal several varieties of large and small neu -
clei in humans, from medial to lateral, are the
rons and a segmentation of the nucleus into
fastigial, globose ( posterior interposed ), em - zones (66). Large dentate nucleus neurons
boliform ( anterior interposed ), and the den - have radiating tortuous dendrites bearing oc-
tate.
casional thorns. Large columnar neurons
NEUROTRANSMITTERS
have elliptical cell bodies with long twisting
dendritic branches, which arise from a pri-
Unlike Purkinje cells, neurons of the cere- mary trunk , and occur only in the two major
bellar nuclei are excitatory and project be- zones of the nucleus. Afferent fibers from the
White matter
Dentate Flocculus
nucleus
Medulla
Dentate
Pontine nucleus
projections
Superior cerebellar
B Pons peduncle
Figure 15.17 Dissections of the left dentate nucleus with portions of the cerebellar cortex and vermis intact A Dis-
section of the posterior surface of the cerebellum exposing the dentate nucleus B Dissection of the superior surface
of the cerebellum from above showing the left dentate nucleus in relationship to the isthmus (upper portion) of the
pons.
F’urkinje cells enter laterally and form a dense latter . It is composed of clumps of cells re-
fiber plexus, the amiculum , around the nu - sembling those of the dentate nucleus ( Figs.
cleus. 13.26 and 15.19). In most nonprimate mam-
mals, the globose and emboliform nuclei
EMBOLIFORM NUCLEUS form a continuous nuclear mass referred to as
the nucleus interpositus. Two parts of the nu -
-
This nucleus is a wedge shaped gray mass cleus interpositus have been distinguished:
situated close to the hilus of the dentate nu - (a ) an anterior nucleus interpositus, located
cleus and often is difficult to delimit from the rostrally close to the dentate nucleus, and be-
15 Cerebellum 603
Cerebellar cortex
White matter
Dentate nucleus
Inferior olive
Medulla
Figure 15.18 Transverse Weigert-stained section through the cerebellum and the medulla This photomicrograph
provides a comparison of the size and shape of the dentate nucleus and the inferior olivary nuclear complex
Emboliform nucleus Dentate nucleus
Fastigial nucleus Globose nucleus

Figure 15.19 Horizontal section through adult cerebellum showing portions of the cerebellar nuclei and the corpus
medullare (Cm) (Weigert ' s myelin stain).
lieved to be homologous to the emboliform of the fourth ventricle, and , in humans, is sec-
nucleus in humans, and ( b) a posterior nu- ond in size to the dentate nucleus ( Figs. 13.26
cleus interpositus, located more medially and and 15.19 ). The fastigial nucleus is character-
caudallv, and considered as the homologue ized by a population of densely packed cells
of the globose nucleus ( 76). of varying sizes. Large, medium , and small
cells are intermingled in dorsal parts of the
GLOBOSE NUCLEUS nucleus, while small cells predominate ven-
trally (76 ). Cell strands emerging from the lat -
This nucleus consists of one or more eral border of the nucleus extend ventrolater -
rounded gray masses lying medial to the em - ally towards the vestibular nuclei . Both large
boliform nucleus and lateral to the fastigial and small cells have dendrites radiating in all
nucleus ( Fig. 15.19). This nucleus contains directions which bear spines on distal
both large and small multipolar cells. branches ( 187). Dendritic fields of neurons
within the nucleus show extensive overlap,
FASTIGIAL NUCLEUS but there are no Golgi type II cells. Unlike the
other cerebellar nuclei, cells of the fastigial
This nucleus, the most medial of the cere- nucleus give rise to both crossed and un -
bellar nuclei, lies near the midline in the roof crossed axons; axons crossing to the opposite
side are most numerous in rostral regions of laterals to the cerebellar cortex (62, 223), con-
the nucleus ( 57). clusive evidence of this intrinsic cerebellar
pathway was provided only with the advent
Connections of axonal transport techniques (66, 109, 111,
260). Retrograde neuronal tracers injected
CORTICONUCLEAR PROJECTIONS into a localized region of the cerebellar cortex
in sin -
The largest number of afferent fibers to resulted in a profuse labeling of cells a
gle cerebellar nucleus , whereas injections of
cerebellar nuclei arise from Purkinje cells in
the cerebellar cortex and have GABA as their anterograde tracer into the cerebellar nuclei
labeled fibers terminating into the cerebellar
neurotransmitter. All parts of the cerebellar
cortex project upon the intrinsic nuclei. The cortex . Nucleocortical and corticonuclear pro-
work of Jan Jansen and Alf Brodal in Norway jections are reciprocally organized . Neurons
revealed that cerebellar cortical projections to in the cerebellar nuclei project back to the
the cerebellar nuclei form three rostrocaudal cerebellar cortical regions from which they
receive input ( 66, 80, 109, 111 , 239, 262 ). These
longitudinal zones: (a ) a medial or vermal
zone projecting to the fastigial nucleus; ( b) a reciprocal projections do not appear to be or -
- -
paravermal zone projecting to the interposed ganized in a strict point to point manner be-
nuclei; and (c ) a lateral or hemispheric zone cause projections from the cortex may not ter-
minate on cells that give rise to return cortical
projecting to the dentate nucleus (85, 143-145, ( 258). In primates, the nucleocorti -
projections
156, 272, 273). As seen earlier, these longitudi -
cal projections from the distinctive parts of
nal corticonuclear zones can be further subdi -
the dentate nucleus are more complex than in
vided into numerous parasagittal zones on
the basis of patterns of termination of various nonprimates . The neodentate ( ventrolateral )
projects to the lateral hemisphere, while the
brainstem afferents and on the heterogeneous
distribution of different molecular markers paleodentate
(dorsomedial ) has projections to
the vermis ( 262 ) . Axons of the cerebellar nu -
( 32, 119, 145, 272 ).
The medial cortical zone, comprising the clei projecting to the cerebellar cortex arise
vermis proper, projects in a strictly unilateral
from a heterogeneous population of cells,
manner to the fastigial nucleus ( 77, 115). similar to those that project to the thalamus
Fibers from the cortical lobules of the vermis and brainstem . Some cells in the dentate and
interposed nuclei have collateral axons that
project to the nearest region of the fastigial
nucleus which results in a sequential repre- project via the superior cerebellar peduncle to
sentation of the cerebellar vermis in the fasti -
the thalamus and inferior olive, as well as to
the cerebellar cortex ( 261 ) . Nucleocortical col -
gial nucleus. Each fastigial nucleus receives
afferents from a narrow band of Purkinje laterals terminate( in the granular layer of the
cerebellar cortex 260 ). Since the nucleocorti-
cells in the ipsilateral vermis in folia of lob-
ules I through X ( 57, 230 ). Information con - cal projection arises from axon collaterals of
cerebellar neurons, the same signals projected
cerning the paravermal and lateral longitudi -
nal cerebellar zones is less complete, but the to brainstem nuclei are fed back to the cere-
same principle appears to apply. Antero- bellar cortex. These collateral projections
grade tract tracing studies support the con - from the cerebellar nuclei represent a major
cept of three mediolateral zones projecting re- afferent system to the cerebellar cortex.
spectively to the fastigial, interposed and
dentate nuclei ( 22, 32, 80, 258). EXTRACEREBELLAR INPUTS
Although the Purkinje cells exert in-
NUCLEOCORTICAL PROJECTIONS hibitory influences on the cerebellar nuclei,
these nuclei maintain a high frequency excita -
The conceptual subdivision of the cerebel - tory discharge ( 134, 139, 140). It is presumed
lum into three sagittal zones ( 270), each con- that excitatory inputs from extracerebellar
sisting of a longitudinal strip of cerebellar sources overcome the tonic inhibitory output
cortex and the cerebellar nucleus to which its from the cerebellar cortex . The current thesis
Purkinje cells project, has been strengthened is that extracerebellar inputs to the cerebellar
by the observation that cells in the cerebellar nuclei provide the tonic facilitation which , at
nuclei send collaterals to the cortex in a spe - times, predominates over the cortical inhibi-
cific manner. While it has long been sus - tion and maintains the discharge of impulses
pected that the cerebellar nuclei provided col - directed towards brainstem nuclei (89 ).
15 Cerebellum 605
The dentate nucleus receives afferents ferent parts of the body are localized to par-
from (a ) the pontine nuclei, ( b ) the principal ticular parts of the cerebellum . As first shown
inferior olivary nucleus, (c) the trigeminal in the 1940s by Edgar Adrian in England and
sensory nuclei , (d ) the reticulotegmental nu - by Ray Snider in the United States, exterocep-
cleus, ( e) the locus coeruleus, and ( f ) the tive impulses (e.g., tactile sense, audition, and
raphe nuclei ( 66, 94 ). The largest number of vision ) give rise to action potentials in spe-
afferent fibers appear to arise from the pon- cific regions of the cerebellum which are or-
tine nuclei, the inferior olivary nucleus, and ganized somatotopically ( 1, 240, 242). The en -
the reticulotegmental nucleus. Both ipsilat - tire body is mapped in two different areas of
eral and contralateral pontine nuclei project the cerebellar cortex: one map lies mainly in
to the dentate nucleus, but the largest num- the anterior lobe and the other lies in the pos-
ber of fibers arise from the opposite side ( 94 ). terior lobe. These two maps are inverted rela -
Olivocerebellar fibers, comprising one of the tive to one another. Tactile stimulation
largest cerebellar afferent systems, pass to all evokes potentials ipsilaterally in the anterior
parts of the cerebellar cortex and to the cere- lobe and simple lobule, and bilaterally in the
bellar nuclei ( 29 ). Afferent projections to the paramedian lobules. The leg area is repre-
dentate nucleus are crossed and arise from sented in the central lobule, the arm in the
cells of the principal inferior olivary nucleus culmen , and the head and face in the simple
( 74 ). The interposed nuclei receive crossed lobule. The somatotopic localization is the re-
fibers from the medial and dorsal accessory verse in the paramedian lobules, with the leg
olivary nuclei, and the fastigial nucleus re- represented caudally and the head repre -
ceives fibers from the dorsomedial cell col- sented rostrally. Responses in this pattern
umn and nucleus Beta , which are caudal sub- were most easily obtained from skin recep-
divisions of the medial accessory olive ( 31, tors or cutaneous nerves. The head area par-
32 ). These projections to the cerebellar nuclei tially overlaps the middle region of the ver-
probablv are collaterals of climbing fibers. mis (i.e., simple lobule, folium and tuber, and
The dentate nucleus and the interposed nu - adjacent areas ) where action potentials were
clei also receive bilateral projections from the recorded following auditory and visual stim -
reticulotegmental nucleus (94 ). The anterior uli ( Fig. 15.20).
interposed nucleus ( i.e., the emboliform nu - The pioneering studies of Adrian and
cleus) receives a projection from the red nu - Snider were based on recording surface po-
cleus which is crossed ( 74 ), and is reciprocal tentials evoked in a population of neurons by
to the major projection from this nucleus. peripheral stimuli. Although two apparently
The fastigial nucleus receives an input continuous body maps were revealed by this
from caudal and dorsal regions of the medial technique, more refined studies using single
and inferior vestibular nuclei and from cells cell recordings have led to a more compli-
of group x, located along the lateral borders cated view of the cerebellar somatotopic lo -
of the inferior vestibular nucleus. These affer- calization . It was shown that inputs from re-
ents are bilateral and fairly symmetric in ori- stricted peripheral sites diverge to influence
gin ( 230 ). The fastigial nucleus also receives several independent patches of granule cells
small inputs from the nucleus prepositus, the that excite a small array of Purkinje neurons
dorsal paramedian reticular nuclei, the retic- ( 297). Thus, even though input from a given
ulotegmental nucleus and the locus coeruleus site activates a small, sharply demarcated
(57, 244, and 245). Although no primary area , adjacent regions may receive afferents
vestibular afferents have been found to termi - from distant body parts, an arrangement re-
nate in the fastigial nucleus, these fibers have ferred to as fractured MiinUotojn/ . The apparent
been shown to end in the small-celled ventro- conflict with earlier studies based on record -
lateral part of the dentate nucleus ( 36, 60). ing of surface potentials can be resolved be-
These findings suggest that practically all cause the peripheral area giving rise to the
information transmitted to the cerebellar cor- largest potential represents only the predomi -
tex also is conveyed to one or more of the nant input to a particular region of the cere-
cerebellar nuclei . bellar cortex ( 104 ).
In addition to receiving sensory informa -
SOMATOTOPIC LOCALIZATION tion directly from the periphery, the cerebel -
lum also receives information from the so-
Afferent systems conveying sensory infor- matic sensory and motor cortices, and this
mation from various kinds of receptors in dif - information is mapped to correspond with
Leg
Sensorimotor
Arm
cortex /
' Audiovisual
Head / / cortex
^
Head
'b
'
// /
/
Arm Leg i
Sensorimotor cortex
A B
Figure 15.20 Somatotopic localization in the cerebellar cortex of a monkey A . Tactile receiving areas of the cere-
bellum mapped by surface potentials recorded in response to movement of hairs on the left side of the body B
Cerebellar cortical areas responding to stimulation of the sensorimotor, auditory and visual cortex in the right hemi-
sphere The leg (red), arm ( blue) and heod ( black slipple) are represented ipsilaterally in the anterior lobe and blldter-
ally in reversed fashion In the paramedian lobules The auditory and visual cortex ( blue stipple) are represented in the
simple lobule, folium, tuber and adjacent cortex.
the peripheral body representation ( 241 ). inputs to the cerebellar cortex are relayed by
Similarly, information from visual and audi- brainstem nuclei, such as the pontine nuclei,
tory cortical regions reaches the audiovisual the inferior olivary nuclei, and a number of
receiving areas of the posterior vermis (118). smaller nuclei located in the medulla and
The entire vermis also receives input from pons. Nuclei in the brainstem that project to
primary and secondary vestibular axons. the cerebellum are referred to as precerebellar
nuclei . The precerebellar nuclei receive affer-
CEREBELLAR CONNECTIONS ents from a variety of sources and differ
greatly with respect to size, cytoarchitecture
Afferent Fibers and cerebellar connections.
The cerebellum receives inputs generated VESTIBULOCEREBELLAR FIBERS

in virtually all kinds of receptors in all parts
of the body. Most afferents enter the cerebel- These fibers enter the cerebellum largely
lum through the inferior and middle cerebel - through the juxtarestiform body and are clas-
lar peduncles, although a small number enter sified as both primary and secondary. The
in association with the superior cerebellar pe- primary afferent fibers originate both in the
duncle. Afferent fibers exceeds efferent fibers semicircular canals, which signal changes in
by an estimated ratio of 40:1 (120). The princi- head position, and in the otoliths, which sig-
pal input and output pathways of the cerebel - nal the orientation of the head with respect to
lum are summarized in Table 15.1. gravity, whereas the secondary afferent fibers
The inferior cerebellar peduncle consists of a arise from the vestibular nuclei .
larger, entirely afferent portion, the restiform Primary vestibulocerebellar fibers arise from
body, and a smaller medial juxtarestiform the vestibular ganglion and project to the ip-
portion that contains both afferent and effer - silateral nodulus, uvula , and flocculus (36).
ent fibers. The juxtarestiform body contains Fibers from all parts of the ganglion project to
primary and secondary vestibulocerebellar parts of the nodulus and uvula , while fibers
fibers and cerebellovestibular fibers originat- from ganglion cells innervating the cristae of
ing from the nodulus, uvula, and the fastigial the semicircular ducts and the maculae of the
nuclei ( Fig. 13.26). Brainstem nuclei project utricle and saccule project to different folia of
fibers directly to the cerebellar nuclei . Quanti- the flocculus ( 60). Primary vestibulocerebel-
tatively , the largest number of cerebellar af - lar fibers end within nearly the entire vermis
ferents terminate in the cerebellar cortex as (159 ). Among the multiple sources of input to
climbing or mossy fibers. Most of the afferent reach the cerebellar cortex, primary vestibu -
15 Cerebellum 607
Table 15.1. Principal Input and Output Pathways ot the Cerebellum
FUNCTIONAL ANATOMIC PRINCIPAL NUCLEUS PRINCIPAL FUNCTION

REGION REGION INPUT DESTINATION
Vest ibu loeerebellum Flocculonodular lobe Vestibular Lateral Medial systems: Axial control
(arch icerebell u m ) labyrinth vestibular axial motor and vestibu -
neurons lar reflexes
Spinocerebellum Vermis Vestibular laby - Fastigial Medial systems: Axial and

( paleocerebellum ) rinth , proximal vestibular nu - proximal
body parts; facial , cleus, reticular motor con -
visual, and formation, and trol ; ongoing
auditory inputs motor cortex execution of
to posterior lobe* movement
only
Spinocerebellum Intermediate part of Spinal afferents Interposed Lateral systems: Distal motor
( paleocerebellum ) hemisphere (distal
body parts ) red nucleus control; ongo-
( magnocellular ing execution
part ) and distal
regions of
motor cortex
Cerebrt K erebel I um Lateral part of Cortical afferents Dentate Integration Initiation ,

( neiKerebellum ) hemisphere areas: red planning, and
nucleus ( parvo - timing
cellular part )
and premotor
cortex ( area b )
lar afferents are the only ones that can do so part of the pyramis and the paramedian lob-
directly from ganglion cells in the periphery ule ( 112, 170, 205, 207). Most of these fibers
without an intervening relay. terminate ipsilaterally in longitudinally
Secondary vestibular fibers originate from arranged zones in what corresponds to
the inferior vestibular nucleus and , to a lesser hindlimb regions. The posterior spinocerebel -
extent, from parts of the medial vestibular lar tract conveys impulses from stretch recep-
nucleus. Although primary and secondary tors via group la and lb muscle afferents,
vestibulocerebellar fibers have similar distrib- exteroceptive impulses from touch and pres-
utions, the number of secondary fibers is sure receptors in the skin, and slow adapting
much greater. Additionally, secondary ves- pressure receptors ( 205).
tibular fibers pass bilaterally to the nodulus, The anterior spinocerebellar tract ascends in
uvula , and the fastigial nuclei (41, 52, 54-56, the brainstem to rostral pontine levels and
160 ). enters the cerebellum in association with the
superior cerebellar peduncle ( Pigs. 11.9 and
SPINOCEREBELLAR TRACTS 13.24 ). Fibers initially located dorsolateral to
the superior cerebellar peduncle arch medi-
The spinocerebellar tracts arise from cell ally over this largely efferent bundle to enter
groups within the spinal cord and pass di- the cerebellum . These fibers pass to essen -
rectly to the cerebellum . Their cells of origin tially the same cortical areas as those of the
receive primary dorsal root afferents. In - posterior spinocerebellar tract . 1 lowever, the
cluded in this group are the posterior, ante- main area of termination is in the anterior
rior , and rostral spinocerebellar tracts, as well lobe with only a few fibers reaching the pyra -
as the cuneocerebellar tract which arises from mis and paramedian lobule ( 112 ). The major-
the accessory cuneate nucleus ( 291 ). ity of the fibers of this tract terminate in the
The posterior spinocerebellar tract enters the cerebellum contralaterally with respect to the
inferior cerebellar peduncle ( 292 ) and projects tract in the spinal cord ( and ipsilateral to the
upon the rostromedial part of the anterior cells of origin ); about 15% of the fibers termi -
lobe ( lobules I to IV; Fig. 15.1 ) and the lateral nate bilaterally ( 112, 170, 205, 237 ). The ante-
rior spinocerebellar tract conveys impulses distribution is localized exquisitely, each por-
from group lb and flexor reflex afferent fibers tion of the olive projecting to a specific cere-
from the hindlimb and lower trunk. bellar area (231 ).
Cuneocerebellar fibers arise from the acces- Anterograde and retrograde axonal trans-
sory cuneate nucleus in the lower medulla, port techniques have demonstrated that the
enter the inferior cerebellar peduncle (292), olivocerebellar projection is more complex
and pass to the posterior part of the anterior than revealed by degeneration studies ( 29).
lobe ( lobule V; Fig. 15.1), the anterior folia of These investigations indicate that cerebellar
the simple lobule, the paramedian lobule, lobules receive afferents from more than one
and the depths of the prepyramidal fissure in region of the inferior olivary complex (31, 42,
the posterior vermis (113, 226, 247). Fibers of 44, 278). It has further been shown that olivo-
this afferent system are ipsilateral. The acces- cerebellar fibers terminate in a pattern of thin
sory cuneate nucleus is regarded as the sagittal strips that alternate with unlabeled
medullary equivalent of the dorsal nucleus of strips which are supplied by fibers from an-
Clarke, and the cuneocerebellar tract is re- other region of the inferior olive (73, 78). Each
garded as the forelimb equivalent of the pos- of these parasagittal zones of terminations
terior spinocerebellar tract. This tract conveys appears to originate from small, well-defined,
impulses from group la and lb muscle affer- rostrocaudally oriented cell columns in the
ents and exteroceptive impulses from cuta- inferior olivary nucleus (14). The inferior
neous afferents ( Fig. 11.9). Receptive fields olive also sends fibers to the cerebellar nuclei
for cutaneous impulses are smaller than those that are crossed and believed to be collaterals
associated with the posterior spinocerebellar of fibers projecting to the cortex (31, 74).
tract ( 205). The inferior olivary nucleus, a highly de-
The rostral spinocerebellar tract , identified in veloped complex in humans ( Fig. 15.18), is
the cat ( 204, 205), is the forelimb functional the major source of climbing fibers that have
equivalent of the anterior spinocerebellar potent excitatory synapses on Purkinje cell
tract, but is uncrossed. This tract arises from dendrites (73, 78, 90, 91, 117, 251 ). The princi-
cells rostral to the dorsal nucleus of Clarke, pal olivary nucleus receives descending
ascends in the anterior part of the spinal cord fibers from the central tegmental tract, a com-
and enters the cerebellum via both the infe- posite bundle originating from multiple
rior and superior cerebellar peduncles. Fibers brainstem nuclei. Descending fibers in this
of this tract are distributed almost exclusively tract passing to the principal part of the infe-
to the anterior lobe of the cerebellum in lob- rior olivary nucleus arise from the red nu-
ules I to V ( Fig. 15.1 ). Fiber terminations are cleus, the central gray substance, and the
predominantly ipsilateral (205, 206). This midbrain tegmentum. Fibers from the senso-
tract is activated monosynaptically by group rimotor cortex pass to the ventral lamella of
lb muscle afferents and polysynaptically by the principal olive via the crus cerebri and the
flexor reflex afferents. pyramid ( 274).
The most important afferents to the infe-
OLIVOCEREBELLAR FIBERS rior olivary complex arise from the spinal
cord. Spino-olivary fibers project to specific
These fibers form the largest component of parts of the medial and dorsal accessory oli-
the inferior cerebellar peduncle. They arise vary nuclei, and spinal pathways belonging
from the contralateral inferior olivary nucleus to the olivary system have been identified
and are distributed to all parts of the cerebel- physiologically by their climbing fiber re-
lar cortex in an orderly pattern ( Figs. 15.21 sponses in the anterior lobe of the cerebellum
and 15.27A ). In humans, fibers from the me- (194). Fibers arising in the spinal cord and as-
dial portion of the principal olive and the ac- cending in the anterior funiculus form the an-
cessory olives go to all portions of the vermis. terior spino-olivary tract that terminates
A much larger component from the lateral upon cells of the medial and dorsal accessory
portion of the principal olivary nucleus is dis- olivary nuclei (25). Fibers ascending in the
tributed to the cerebellar hemisphere. The posterior columns synapse upon the poste-
dorsal part of the olive projects to the superior column nuclei and project contralaterally
rior surface of the cerebellum, while the ven- to the same olivary nuclei (88, 147), and form
tral part projects to its inferior surface (127). a dorsal ( funicular ) spino-olivary pathway .
The intracerebellar nuclei, as well as all parts Additional spino-olivocerebellar pathways
of the cortex, receive olivary fibers, and the have been described , all of which project to
15 Cerebellum 609
Thalamic
nuclei
VLc, VPLo, area x Motor
cortex
area 4
Thalamus
Thalamocortical
fibers
Red
nucleus
1 r
Decussation
Superior
cerebellar Descending division
peduncle \ sup. cerebellar peduncle
r-Retinculotegmental
nucleus
I- Middle
Cerebellar
T — Interior peduncles
Dentate
nucleus nferior olive
Cerebellum
Figure 15.21 Efferent fibers from the dentate nucleus. These fibers emerge as the major constituent of the superior
cerebellar peduncle ( blue) and decussates completely in the caudal portion of the midbrain. Ascending fibers pro-
.
ject to rostral parts of the contralateral red nucleus and to the cell sparse zone of the thalamus (i e , ventral lateral nu-
. .
cleus pars caudalis (VLc), the ventral posterolateral nucleus, pars oralis (VPLo) and the so-called area X) , Fibers from
the dentate nucleus terminate somatotopically in these thalamic nuclei, which in turn project upon the primary motor
cortex (area 4) Fibers forming the descending division of the superior cerebellar nucleus project to reticular nuclei
and the inferior olivary nucleus ( blue), which project back to the cerebellar cortex of the opposite hemisphere
parasagittal zones in the anterior lobe. These crimination . Certain evidence suggests that
parasagittal projection zones display a soma - olivary neurons may convey specific informa -
totopic pattern in lobules IV and V of the ver- tion related to interneuronal activities at
mis ( 208). Spino-olivocerebellar pathways re- spinal and brainstem levels ( 194 ). The spino-
semble the spinocerebellar tracts ( 43). olivary systems may be activated by either
Responses in these systems are evoked by flexor reflex afferents or by the corticospinal
stimuli activating group II and III muscle af - tract through a common set of interneurons,
ferents, cutaneous afferents, and high thresh- which are assumed to influence motor neu -
old joint afferents with wide receptive fields. rons and to be part of the segmental reflex
These impulses, referred to as flexor reflex af - -
arc. Thus, the spino olivocerebellar system
ferents , also have actions upon segmental re- may monitor the activity of interneurons at
flexes and are transmitted by several other spinal levels and transmit such signals to the
ascending tracts. There is difficulty in cerebellum .
interpreting the information transmitted by The inferior olivary nucleus also receives
these pathways because it lacks modality afferent fibers from the contralateral cerebel -
specificity and permits only crude spatial dis- lar nuclei which are topographically orga -
nized ( 263). The dentate nucleus projects to sions, and enter the cerebellum via the infe-
the principal olivary nucleus and the inter- rior cerebellar peduncle. Degeneration and
posed nuclei project to the medial and dorsal autoradiographic studies indicate that projec -
accessory olivary nuclei. Projections from the tions of the lateral reticular nucleus terminate
cerebellar nuclei to the inferior olive appear as mossy fibers in the anterior lobe, in both
reciprocal to olivonudear fibers, except that vermal and intermediate parts, in the para -
no fibers from the fastigial nucleus terminate median lobule, and in lobule VII of the ver -
in the inferior olive. These observations sug- mis (162, 186 ). The projection is bilateral with
gest that the activities of the inferior olivary ipsilateral predominance. Although there is a
nucleus may be modulated bv feedback from topographic projection from the nucleus to
the cerebellar nuclei . the anterior lobe and the paramedian lobule,
the entire cerebellar cortex appears to receive
RETICULOCEREBELLAR FIBERS some fibers < 4s. si , 110).
The ( hirainedian reticular nuclei of the
Three nuclei of the reticular formation pro- medulla ( Fig. 12.13) receives afferent fibers
ject fibers to the cerebellum and can be re- from the spinal cord ( 34), the fastigial nucleus
garded as precerebellar nuclei: (a ) the reticu - ( 18), the cerebral cortex ( 34, 249), and the
lotegmental nucleus, ( b) the lateral reticular vestibular nuclei (164). Projections from these
nucleus of the medulla, and (c) the parame- nuclei are mostly uncrossed, terminate prin -
dian reticular nucleus ( 296 ). cipally in the vermis of the anterior lobe and
The reticulotegniental nucleus ( Figs. 13.28 in the pyramis and uvula ( 40, 244 ), and , less
and 13.33) receives afferents from the cerebral abundantly, in the fastigial nucleus ( 230). The
cortex and the cerebellar nuclei ( 39, 59, 163, dorsal paramedian reticular nucleus appears
229 ). Projections from the frontal and parietal to be connected with a somewhat wider re-
cortex are bilateral, but mainly ipsilateral, gion of the cerebellar cortex than other nuclei
and end in ventral parts of the nucleus (33). A of this group. These nuclei, like others in the
larger and more important group of afferent reticular formation projecting to the cerebel -
fibers arises from the dentate and anterior in - lum, are involved in feedback systems.
terposed nuclei, enter the superior cerebellar
peduncle, cross in its decussation, and de- PONTOCEREBELLAR PROJECTIONS
scend as the crossed descending limb of the
superior cerebellar peduncle ( 37). Cerebellar The pontine nuclei represent the largest
projections from this nucleus pass via the collection of precerebellar nuclei and consti-
middle cerebellar peduncle to vermal re- tute the most important relay in the conduc-
gions, particularly lobules VI and VII , and to tion of impulses from the cerebral cortex to
the flocculus, but all parts of the cortex re- the cerebellum ( 195). Corticopontine fibers
ceive some fibers ( 123). Projections of the arise from all of the four major lobes of the
reticulotegmental nucleus are bilateral and cerebrum, descend in the internal capsule
end as mossy fibers in the granular layer. and crus cerebri, and terminate on the ipsilat -
-
This nucleus participates in a cerebellar retic- eral pontine nuclei. The most massive cortical
ular feedback system, but its efferent fibers projections arise from the sensorimotor cor-
do not project back to the cerebellar nuclei tex and project in a somatotopical fashion
that supply it . onto longitudinally oriented cell columns
The lateral reticular nucleus of the medulla within the pontine nuclei (32, 45). Each part
( Figs. 12.8 and 12.13), consisting of three cyto- of the cerebral cortex projects to several well -
logically distinct subdivisions, receives in - defined areas within the pontine nuclei ( 46,
puts from a variety of sources including the 47, 49). Fibers from the temporal cortex termi -
spinal cord (30, 161 ), the cerebral cortex (50), nate in the caudal pons and those from the
the red nucleus (275), and the fastigial nu - frontal cortex end in the rostral pons. Al-
cleus ( 279 ). Spinal afferents contained in the though projections from the motor and so-
anterolateral funiculus terminate in a specific matosensory cortical areas are somatotopi-
manner upon the small -celled part of the nu - cally organized , they are separated from each
cleus and appear to transmit exteroceptive other.
impulses somatotopically (71 ). All cells of the pontine nuclei project their
Cerebellar projections of the lateral reticu - axons to the cerebellum via the middle cere-
lar nucleus arise from cells in all subdivi- bellar peduncle and most, but not all, of these
15 Cerebellum 611
fibers are crossed . Fibers projecting to the possibly also from the facial muscles. Sec-
cerebellar hemisphere are mainly crossed, ondary trigeminocerebellar fibers from the
while projections to the vermis are bilateral principal sensory and spinal trigeminal nu -
(32). The nodulus appears to be the only part clei (168, 288, 298) enter the cerebellum via
of the cerebellum that does not receive a pon - the inferior cerebellar peduncle and termi-
tine projection. Most of the pontocerebellar nate in the upper culmen and declive ( 170,
fibers terminate as mossy fibers (192, 238). 242, 285, 298).
The pontocerebellar projection are precisely Studies based upon retrograde transport
organized and most cerebellar lobules receive techniques indicate trigeminocerebellar fibers
afferents from two or more different sites arising from the spinal and principal trigemi -
within the pontine nuclei (35, 42, 122 ). This nal nuclei are exclusively ipsilateral and pro-
pattern of termination suggests that impulses ject mainly to the simple lobule and the dor-
from different regions of the pontine nuclei sal part of the paramedian lobule (129, 131,
that receive inputs from various cortical 243). Most of the efferent fibers originate
areas converge onto a particular cerebellar from the nuclei interpolaris and oralis of the
lobule ( 28). spinal trigeminal complex and terminate as
The pontine nuclei also receive afferents mossy fibers in the form of typical parasagit-
from the superior and inferior colliculi (5, tal bands (131 ). According to some studies
150, 196) and from the cerebellar nuclei (18, the motor trigeminal nucleus projects some
273). The dorsolateral pontine nuclei, which fibers to the dentate nucleus (94, 158). A small
receive fibers from the tectum, project to re- number of the cells in the nucleus of the soli-
gions of the cerebellum where visual and au - tary tract and a number of motor cranial
ditory impulses have been recorded . nerve nuclei also project to the cerebellum
(158, 232, 243, 246).
OTHER PRECEREBELLAR AFFERENTS Projections from the rnplie nuclei , which con-
tain serotoninergic neurons, have been traced
A number of other brainstem nuclei pro- to all parts of the cerebellar cortex, except lob-
ject smaller numbers of fibers to the cerebel- ule VI, by retrograde transport techniques
lar cortex. These precerebellar nuclei include ( 252). The most profuse projections are to ver-
the perihypoglossal nuclei, the trigeminal mal lobules VII and X and to crus I and II
sensory nuclei, the nucleus of the solitary (110). According to Chan-Palay (66 ), axons of
tract, the locus coeruleus and the raphe serotoninergic neurons (a ) terminate as
nuclei. mossy fiber rosettes, and ( b) traverse the mo-
The perihypoglossal nuclei ( Fig. 12.13) pro- lecular layer like parallel fibers, but terminate
ject to the vermis and fastigial nucleus ( 264 ), on cortical intemeurons, rather than on Pur-
the flocculus, paraflocculus, and nodulus (4, kinje cells.
157), as well as the fastigial nucleus and the Projections from the locus coeruleus , convey
anterior interposed nucleus (178, 230). The noradrenergic input to the cerebellum via the
nucleus prepositus, the largest of the perihy - middle and superior cerebellar peduncles
poglossal nuclei, also gives rise to ascending (180, 218). In the cerebellar cortex, noradren-
fibers that terminate in the oculomotor nuclei. ergic fibers terminate massively around Pur-
Trigeminocerebellar fibers , both primary and kinje cell somata ( 70). The extent of the distri-
secondary, derive from different subdivisions bution of these fibers in the cerebellum is
of the trigeminal nuclear complex. Although unclear . According to Somana and Walberg
primary trigeminocerebellar fibers have been ( 245), most fibers project to the cerebellar ver-
observed in nonmammalian vertebrates (121, mis, although a few project to the fastigial nu -
166, 167, 288), their areas of termination in the cleus.
cerebellum have not been established .
Trigeminocerebellar fibers from the mesen- Efferent Fibers
cephalic nucleus of N. V, studied in human
fetal material ( 214, 215), enter the cerebellum Cerebellar efferent fibers arise from all of
in association with the superior cerebellar pe- the cerebellar nuclei and from specific re-
duncle and are distributed to the dentate and gions of the cerebellar cortex. Direct projec-
the emboliform nuclei. These fibers are be- tions from the cortex of the vermis and from
lieved to conduct impulses from stretch re- vestibulocerebellum ( regions of the cerebellar
ceptors in the muscles of mastication and cortex receiving vestibular inputs ) pass to the
ipsilateral vestibular nuclear complex and the mediodorsal nucleus serve as relays in a
collectively constitute the cerebellovestibular cerebelloprefrontal connection. Other studies
projection ( 271 ). The largest and most widely with retrograde double-labeling methods in
distributed cerebellar efferent fibers arise the rat revealed that single neurons in the
from the cerebellar nuclei and are organized cerebellar nuclei provide axon collaterals
into two major systems contained in three to thalamic, brainstem , and spinal cord
separate bundles. The major efferent systems levels ( 21 ).
are the superior cerebellar peduncle and the The ventral lateral ( VLc) and the ventral
fastigial efferent projection . posterolateral ( VPLo ) nuclei of the thalamus
project in a topical fashion on the primary
SUPERIOR CEREBELLAR PEDUNCLE motor cortex ( 203, 280-282 ). Thus, impulses
from the dentate nucleus are conveyed via
This is the largest cerebellar efferent bun- contralateral thalamic nuclei to the motor cor-
dle. It is formed by fibers from the dentate, tex ( 203, 267). In this manner, signals from the
emboliform, and globose nuclei ( Figs. 2.26, dentate nucleus can influence activity of
13.26, 13.32, and 15.21 ). These fibers emerge motor neurons in the cerebral cortex. Im-
from the hilus of the dentate nucleus and pulses from the motor cortex are transmitted
pass rostrally into the upper pons where they to spinal levels via the corticospinal tract .
form a compact bundle along the dorsolateral This system , concerned primarily with the co-
wall of the fourth ventricle ( Figs. 2.25 and ordination of somatic motor function , also
2.26 ). At isthmus levels, fibers of the superior provides the explanation for occurrence of ip-
cerebellar peduncle sweep ventromedially silateral asynergic disturbances with unilat-
into the tegmentum and all fibers decussate eral cerebellar lesions.
at levels through the inferior colliculus ( Figs. A relatively small number of cerebellar ef -
13.32 and 14.2 ). Most of these crossed fibers ferent fibers from the ventrocaudal dentate
ascend to enter and surround the contralat- nucleus decussate in the caudal mesen-
eral red nucleus. A relatively small part of the cephalon, pass dorsally, and are distributed
fibers from the dentate nucleus terminate in differentially within the lateral somatic cell
the rostral third of the red nucleus (9, 72 ). The columns of the contralateral oculomotor nu -
bulk of these fibers project to the thalamus clear complex (61 , 66, 183, 193). Most of these
and end in parts of the ventral lateral ( VL) fibers terminate about cells that innervate the
and ventral posterolateral thalamic ( VPL ) nu - superior rectus muscle on the opposite side
clei ( Fig . 15.21 ) ( 53, 66, 132, 146, 190, 193, 216, ( Fig. 14.14 ). The part of the dentate nucleus
225). Fibers from the dentate nucleus termi- from which these fibers arise receives pri -
nate somatotopically in the ventral postero- mary vestibular fibers ( 36, 60 ). Thus, this den -
lateral pars oralis ( VPLo) and the ventral lat- tato-oculomotor projection may constitute a
eral pars caudalis ( VLc ) thalamic nuclei . link in a vestibulo-oculomotor pathway ( 116).
Although somatotopic features of the cerebel- Another small group of fibers in the supe-
lar nuclei are not compelling, the pattern of rior cerebellar peduncle decussate with the
termination of these fibers in thalamic nu - main bundle and descend in the ventrome-
clear subdivisions appears similar to that of dial tegmentum of the brain stem near the
the somatosensory relay nuclei. In this median raphe. These fibers, constituting the
arrangement, the head is represented medi - descending division of the superior cerebellar
ally and caudal parts of the body are lateral; peduncle, project to the reticulotegmental,
the extremities lie centrally and the back lies the paramedian reticular nuclei, and portions
dorsally (15, 16, 256). A small number of of the inferior olivary nucleus ( 39, 59, 183,
fibers from the dentate nucleus project to the 263). Because these nuclei are known to pro-
rostral intralaminar thalamic nucleus, mainly ject to the cerebellum, this component of the
the central lateral ( Cl ) nucleus ( 15, 16, 191, superior cerebellar peduncle is a part of both
224, 256). Furthermore, recent axonal trans- a cerebelloreticular and a cerebello-olivary
port studies indicate that the cerebellar nuclei feedback system ( Fig. 15.21 ).
also project to ventrolateral parts of the Fibers from the interposed nuclei ( i .e., the
mediodorsal thalamic nucleus, where they emboliform and globose nuclei ) project pri -
terminate upon thalamic neurons projecting marily to cells in the caudal two- thirds of the
to the prefrontal cortex ( 293). These findings red nucleus. A smaller number of fibers pass
suggest that neurons in ventrolateral parts of beyond the red nucleus to the same thalamic
15 Cerebellum 613
nuclei as fibers from the dentate nucleus. via the superior cerebellar peduncle to the
Fibers from the interposed nuclei end in an opposite red nucleus. Somatotopically orga-
interdigitate fashion in VPLo and VLc, but do nized rubrospinal fibers cross in the midbrain
not overlap those from the dentate nucleus. and descend to spinal levels. This small sys-
Fibers from the interposed nuclei project so- tem involved two decussations, that of the
matotopically on cells of the red nucleus, and superior cerebellar peduncle and that of the
rostral parts of the interposed nucleus project rubrospinal tract ( Fig. 15.22). Thus, impulses
to hindlimb regions of the red nucleus ( ven- conveyed from the paravermal cortex to the
tral and ventrolateral areas), while caudal spinal cord end on the same side. This system
parts of the nucleus project to forelimb reappears to be primarily concerned with
gions of the red nucleus ( dorsal and dorso- mechanisms that facilitate ipsilateral flexor
medial areas; Fig. 15.22 ) ( 72, 184, 221 ). These muscle tone.
fibers form part of a somatotopic linkage ex- A number of studies indicate that axons
tending from the paravermal cortex to the from cells of the interposed nuclei also pro-
spinal levels. In this pathway, fibers from the ject to the VLc nucleus of the thalamus after
paravermal cortex pass to the interposed nu - giving off collaterals to the red nucleus (8, 13,
clei . Fibers from the interposed nuclei project 89, 261 ) .
Putamen
Tholamus
Globus
Red nucleus pal lidus
Superior
cerebellar peduncle
Anterior lobe Dentate nucleus

( paravermal area )
V
V
Emboliform nucleus
Globose nucleus
Rubrospinal tract
Figure 15.22 Projections from the interposed nuclei of the cerebellum (i.e emboliform and globose nuclei) via the
superior cerebellar peduncle (blue). The interposed nuclei receive afferents from the paravermal cortex (.black ) and
project somatotopically ( blue) upon cells in caudal portions of the contralateral red nucleus Cells In caudal portions
of the red nucleus give rise to the crossed rubrospinal tract (red), which influence flexor motor tone. Thalamic projec -
tions from the interposed nuclei ( blue) terminate in the cell sparse zone of the thalamus (VLc, VPLo, and area X) con -
tralaterally . Thalamic terminations interdigitate with those of the dentate nucleus without overlap Thalamic neurons
receiving input from the interposed nuclei project to the primary motor cortex ( blue)
FASTIGIAL EFFERENT PROJECTIONS A small number of crossed fastigiospinal

fibers descend into the upper cervical spinal
Efferent projections of the fastigial nucleus cord where they contact anterior horn cells
are unique in that (a ) they do not emerge via (102, 185). Physiologic evidence based upon
the superior cerebellar peduncle, ( b ) a large antidromic stimulation of the upper cervical
part of the efferent fibers cross within the spinal cord and direct stimulation of the fasti-
cerebellum, and (c ) they project to nuclei at gial nucleus indicate that axons of fastigial
all levels of the brainstem ( 57). Crossed fibers neurons make monosynaptic contacts with
from the fastigial nucleus emerge from the motoneurons at the C2 C3 level ( 286, 287).
cerebellum via the uncinate fasciculus ( Russell ) ,
-
Small numbers of fastigial fibers ascending
which arches around the superior cerebellar in the dorsolateral region of the brainstem
peduncle ( Figs. 15.23 and 15.24 ). Uncrossed provide collaterals to the superior colliculus
fastigial efferent fibers project to the brain- and the nuclei of the posterior commissure (7,
stem in the juxtarestifonn body ( Figs. 13.7 and 10) and terminate bilaterally in the cell sparse
15.24 ). Crossed efferent fibers contained in zone of the thalamus ( VLc and VPLo ) (10, 18,
the uncinate fasciculus arise from cells in all 58, 153, 257). These terminations do not over-
parts of the fastigial nucleus and outnumber lap those of the dentate and interposed nu -
uncrossed efferents in the juxtarestiform clei . In the superior colliculus, fastigial fibers
body. The largest number of fastigial efferent terminate principally within the intermediate
fibers project to structures in the lower brain- gray layer, which contains neurons giving
stem . Fastigial projections to the vestibular rise to the tectospinal pathway (189 ). The
nuclei are bilateral, symmetric, and terminate cerebellocollicular fibers, together with other
in ventral parts of the lateral and inferior cerebellar efferent fibers terminating in vari-
vestibular nucleus ( 18). Fastigioreticular ous brainstem regions containing premotor,
-
fibers arise predominantly from rostral parts saccade related neurons, indicate that cere-
of the nucleus, are mainly crossed , and pro- bellar output is involved in saccade program-
ject to (a ) medial regions of the nucleus retic- ming neural circuits ( 189, 200).
-
ularis gigantocellularis, ( b ) parts of the cau -
dal pontine reticular formation, (c ) the dorsal CEREBELLOVESTIBULAR PROJECTIONS
paramedian reticular nucleus, and ( d ) por-
tions of the lateral reticular nucleus (57). Certain regions of the cerebellar cortex
Crossed fastigiopontine fibers separate from project to the vestibular nuclei. These projec-
the uncinate fasciculus and pass ventrally to tions are composed of axons of Purkinje cells
terminate in the dorsolateral pontine nuclei. and arise from the cerebellar vermis and the
vestibulocerebellum ( i.e., the flocculonodular
lobule). Thus, the vestibular nuclei receive
cerebellar afferents bilaterally from the fasti -
gial nucleus and ipsilaterally from specific
cortical regions. Direct projections from the
cerebellar vermis terminate in dorsal regions
of the ipsilateral lateral and inferior vestibu -
lar nuclei, are soma totopically organized
(115, 276, 277), and have GABA as neuro-
transmitter. Efferent fibers from the anterior
lobe establish synaptic contacts of the sym-
metric type on sornata and dendrites of cells
of all sizes in the lateral vestibular nucleus
(199). Stimulation of the anterior lobe of the
cerebellum produces a monosynaptic inhibi-
tion of neurons of the lateral vestibular nu -
cleus (134, 138).
The regions of the cerebellum that receive
primary and secondary vestibular fibers con-
Figure 15.23 Darkfield photomicrograph of ( ’H) -labeled
stitute the "vestibulocerebellum." This desig-
amino acids transported by fibers of fhe uncinate fasci- nation includes ventral parts of the uvula in
culus as seen in an autoradiograph addition to the flocculonodular lobule. All
15 Cerebellum 615
Thalamus
'utamen
Globus
pallidus
Superior cerebellar
Uncinate peduncle
fasciculus
Juxtarestiform
Dentate nucleus
Fastigiopontine Vestibular nuclei

fibers
Fastigiospinal fibers Reticular formation
Figure 15.24 Fostigiol efferent projections , Crossed fostigiol efferent fibers contained in the uncinate fasciculus arise
from cells in all parts of the fastigial nucleus (FN) and outnumber uncrossed efferent fibers that emerge in the juxtares-
tiform body. Fastigiovestibular fibers project bilaterally and symmetrically upon ventral portions of the lateral (i.) and
Inferior (/) vestibular nuclei. Fastigioreticular fibers arise predominantly from rostral parts of the fastigial nucleus.
Crossed fastigiopontine fibers separate from the uncinate fasciculus and pass to the dorsolateral pontine nuclei.
Crossed fastigiospinal fibers pass to upper cervical spinal segments and exert excitatory effects upon motoneurons.
Ascending fastigial projections arise from caudal parts of the nucleus, are entirely crossed, and course In dorsolateral
parts of the midbrain tegmentum. These fibers project to parts of the superior colliculus, the nuclei of the posterior
commissure, and to the ventral posterolateral ( VPL ) and ventral lateral ( VL ) thalamic nuclei. DM, dorsomedial nu-
cleus. FN, fastigial nucleus; RN, red nucleus; VL VPL and VPM, ventral lateral, ventral posterolateral, and ventral pos-
. .
teromedial thalamic nuclei, vestibular nuclei: / inferior, L lateral M, medial, and S, superior
Primary fissure
Upper extremity
Anterior lobe
cerebellar
vermis Pyramis
Lower Uvula
extremity
Nodulus
Dorsal V -
Ventral
Lateral vestibular
nucleus
Figure 15.25 Cerebellovestibular projections from the anterior and posterior vermis Purkmje cell axons from the an
tenor vermis project somatotopically upon dorsal regions of the lateral vestibular nucleus and exert inhibitory influ-
ences. Similar direct projections from the pyramis and parts of the uvula which are not somatotopically arranged are
shown by arrows.
parts of the vestibulocerebellum project fibers 272, an 273). This zonation provides an ele-
to the vestibular nuclei (11 ). The flocculus mentary view of the functional organization
projects to the superior and medial vestibular of the cerebellum. In this simplified scheme,
nuclei, while the nodulus and uvula project the cerebellar efferent systems are related to
fibers to the superior, medial, and inferior three longitudinal (sagittal ) zones referred to
vestibular nuclei . All of these cerebello- as vermal, paravermal, and lateral ( Fig.
vestibular projections are ipsilateral ( Fig. 15.28).
15.25). The vermal zone is the midline, unpaired
By its action on the vestibular nuclei , the portion of the cerebellum related to fastigial
vestibulocerebellum plays a critical role in nuclei, and is concerned primarily with
equilibrium and in the control of axial mus- mechanisms that modify extensor muscle
cles that are used to maintain balance. Addi - tone. Direct projections from the anterior and
tionally, the vestibulocerebellum functions to posterior vermis exert inhibitory influences
control eye movement and to coordinate upon the vestibular nuclei which could result
movements of the head with those of the eye in a reduction of extensor muscle tone. The
( 104 ). projections of the fastigial nucleus which re-
ceive strictly ipsilateral afferents from the
FUNCTIONAL ORGANIZATION vermis (77) are bilateral, although crossed
fibers are more numerous (57). These excita-
On the basis of cortical projections to the tory fibers terminate in the vestibular nuclei
cerebellar nuclei and projections from the nu - and in broad regions of the reticular forma -
clei to the cerebellar cortex, the cerebellum tion of the pons and medulla . A small num -
has been divided into three sagittal zones of ber of crossed fastigiospinal fibers descend
cortex and their connecting nuclei ( 22, 77, 80, directly to the upper cervical spinal cord and
85, 109, 111, 115, 143, 144 , 156, 258-260, 270, have excitatory influences upon motoneurons
15 Cerebellum 617
( 286 ) .
Ascending fastigial efferents projecting neural device that compensates for errors in
to thalamic nuclei bilaterally contribute to co - motor behavior by comparing intention with
ordinated somatic motor activity. The vermal performance ( 104 ).
zone of the cerebellum is particularly con - Some of the neocerebellar connections in
cerned with control of posture, muscle tone, humans are especially evident in Figure
locomotion, and equilibrium for the entire 15.27, which shows sections through the
body (64, 65). medulla , pons, and isthmus from an individ -
The paravcrmal zone relates the paravermal ual in whom the left cerebellar hemisphere
cortex with the emboliform and globose nu - failed to develop ( 250 ). There was also a cor-
clei, which have connections predominantly related agenesis of all the afferent and effer-
with the contralateral red nucleus. The inter - ent pathways to and from the left cerebellar
posed nuclei project somatotopically on the hemisphere. The left dentate nucleus was
caudal two-thirds of the red nucleus (8, 72, represented by a minute structure, the right
95). This somatotopically organized system is inferior olive was greatly reduced , and the
concerned with mechanisms that can facili- right red nucleus ( not shown ) and pontine
tate ipsilateral flexor muscle tone via the nuclei were practically absent . All of the cere-
rubrospinal tract ( Fig. 15.22 ). Additionally, bellar peduncles on the left were greatly re-
the interposed nuclei have modest projec - duced in size. These preparations emphasize
tions to the contralateral thalamic nuclei . that in humans the middle cerebellar pedun-
The lateral zone relates the cortex of the cle and the olivocerebellar fibers are practi-
cerebellar hemisphere with the dentate nu - cally all crossed .
cleus which has the most extensive thalamic
projections ( Fig. 15.21 ). These efferent fibers CLINICAL CONSIDERATIONS
project somatotopically on the cell sparse
zone of the thalamus ( VLc and VPLo ). This is The cerebellum is concerned with the co-
the largest cerebellar efferent system and it ordination of somatic motor activity, the reg-
appears to be concerned with the coordina- ulation of muscle tone, and mechanisms that
tion of ipsilateral somatic motor activity. influence and maintain equilibrium. Afferent
Neurons in the cell sparse zone of the thala - cerebellar pathways convey impulses from a
mus project somatotopically upon the pri - variety of different receptors including the
mary motor cortex where they can modify organs of special sense. Among these afferent
the activity of neurons projecting to spinal systems, the input from stretch receptors ( i.e.,
and pontine levels. muscle spindle and Golgi tendon organ ) is es-
Some relay nuclei at all brainstem levels, pecially prominent. These impulses are con -
receiving part of the cerebellar output , project veyed by the spinocerebellar and cuneocere -
fibers back to the cerebellum. The motor cor- bellar tracts. The principal function of stretch
tex , in turn , gives rise to frontopontine fibers, receptors appears to be the unconscious
which convey impulses back to the contralat - neural control of muscle tone. The cerebel -
eral cerebellar hemisphere via the pontine lum , which receives a major afferent input
nuclei and the middle cerebellar peduncle from the stretch receptors, is an integral part
( Fig. 15.26 ). Other areas of the cerebral cortex of the neural mechanism that ( a ) effects grad -
also influence the activity of the cerebellum ual alterations of muscle tone for proper
via corticopontine and pontocerebellar path - maintenance of equilibrium and posture, and
ways. The central tegmental tract conveys im- ( b) assures the smooth and orderly sequence
pulses from the red nucleus and the midbrain of muscular contractions that characterize
tegmentum which reach the contralateral skilled voluntary movement ( 205).
cerebellar hemisphere by way of parts of the Each movement requires the coordinated
inferior olivary nuclear complex. Certain action (synergy ) of a group of muscles. The
fibers of the superior cerebellar peduncle that agonist is the muscle that provides the actual
descend in the brainstem terminate upon movement of the part, while the antagonist is
reticular and olivary nuclei, which project the opposing muscle which must relax to per-
fibers back to the cerebellum ( Fig. 15.21 ). Ef - mit movement. Other muscles must fix, or
ferent fibers from the red nucleus also project stabilize, certain joints in order to produce
directly to the interposed nucleus ( 75). All the desired movement . Such synergistic
these feedback pathways help the cerebellum motor activity requires not only complex reci -
to play its role as a comparator, that is, a procal innervation but coordinated control of
Cerebral cortex
Putamen
Globus
pallidus
Red nucleus
Sup cerebellar
peduncle Corticopontine
fibers
- Dentate
1 nucleus
Central tegmental
tract
Ponto -
cerebellar fibers Pontine nuclei
Olivocerebellar
fibers Inferior olive
Figure 15.26 Principal afferent and efferent cerebellar connections. Cerebellar efferent fibers from the dentate nu-
cleus are shown in blue Corticopontine and pontocerebellar fibers ( black ) represent the most massive cerebellar af -
ferent system. The principle inferior olivary nucleus receives uncrossed descending fibers from the red nucleus and pe-
riaqueductal gray via the central tegmental tract. Cortico-olivary fibers (not shown) to the principal Inferior olivary
nucleus pass via the medullary pyramids Olivocerebellar fibers ( black ) cross, enter the restiform body (largest compo-
nent of the superior cerebellar peduncle), and are distributed to (a) the cerebellar cortex as climbing fibers, and (b)
the cerebellar nuclei, most likely as collaterals of fibers terminating in the cerebellar cortex
muscle tone and movement . The cerebellum turbances; (b) cerebellar disturbances usually
provides this control for the somatic motor occur as a constellation of intimately related
system in an efficient, automatic manner phenomena; (c ) cerebellar disturbances due
without our being aware of it . to nonprogressive pathologic changes show a
There are certain general principles that gradual but definite attenuation with time;
pertain to most of the disturbances resulting and (d ) cerebellar disturbances resulting from
from cerebellar lesions . These principles are: cerebellar lesions probably are the physio-
(a ) cerebellar lesions produce ipsilateral dis- logic expression of intact neural structures
15 Cerebellum 619
Lateral „ Superior
lemniscus cerebellar
peduncle
Central
tegmental Lateral
tract lemniscus
c Medial
lemniscus
Pontine
nuclei
Dentate nucleus
Central Medial
tegmental lemniscus
tract
Corticospinal
Pontine tract
nuclei
Inferior cerebellar
Spinal troct
of N 1 Olivocerebellar
fibers
Inferior olive
Inferior,^" Pyromid
olive
Figure 15.27 Transverse sections through ( A) the medulla, (B). midpons, and (C) upper pons or isthmus from a case
of left cerebellar agenesis These sections clearly demonstrate the crossed nature of olivocerebellar and ponfocere-
bellar fibers (Weigerts myelin stain)
Spinocerebellum
Vermis Fastigial —* To medial

nucleus descending systems
Motor
Intermediate Interposed —*• To lateral execution
hemisphere nuclei descending systems
Dentate To motor and Motor

nucleus premotor cortices planning
Cerebrocerebellum
( Lateral hemisphere )
To vestibular Balance and
nuclei eye movements
A Vestibulocerebellum
Corticopontine inputs
Visual and auditory inputs
Spinal and trigeminal inputs
a Vestibular inputs
B
Figure 15.28 Three major functional compartments of the cerebellum with their major ( A) output and (B) input sys -
tems .
deprived of the controlling and regulating in - ceed it ( pastpointing ). Rapid successive move-
fluences of the cerebellum . Lesions involving ments, such as alternately supinating and
the dentate nuclei or the superior cerebellar pronating the hands and forearms, are poorly
peduncle produce the most severe and en- performed ( dysdiadochokinesis ). The patient is
during disturbances. The distinctive symp- unable to adjust to changes of muscle tension.
toms and signs that result from cerebellar dis- When the forearm is flexed at the elbow and
orders were comprehensively described by held flexed against resistance, a sudden re-
Gordon Holmes in ll)3y ( 51 , 105). lease of resistance causes the forearm to strike
the chest . This is an example of the rebound
NEOCEREBELLAR LESIONS phenomenon . These patients also demonstrate
a decomposition of movement in which phases
Lesions involving the cerebellar hemi- of complex movements are performed as a
spheres and the dentate nucleus affect pri - series of successive single simple move-
marily skilled voluntary and associated ments.
movements ( i .e., movements related to the The tremor seen in association with neo -
corticospinal system ). The muscles become cerebellar lesions occurs primarily during
hypotonic ( flabby ) and tire easily. The deep voluntary and associated movements ( 125,
tendon reflexes tend to be sluggish and often 126 ). This tremor is referred to as intention
have a pendular quality . There are severe dis- tremor because it is not present at rest . It in -
turbances of coordinated movement, referred volves especially the proximal appendicular
to as asynergia , in which the range, direction , musculature, but is transmitted mechanically
amplitude, and force of muscle contractions to distal parts of the extremities. Tremor is
are inappropriate. Cerebellar asynergia can most evident in the upper extremities be-
be demonstrated by many tests. Among these -
cause weight bearing masks the disturbance
are tests of precise movements to a point; dis- in the lower extremities.
tances frequently are improperly gauged Ataxia is an asynergic disturbance associ-
( dysmetria ) and fall short of the mark or ex- ated with neocerebellar lesions which result
15 Cerebellum 621
in a bizarre distortion of voluntary and asso- that arises from cell -rests in the inferior
ciated movements. It involves particularly medullary velum at the base of the nodulus.
the axial muscles, and groups of muscles
around the shoulder and pelvic girdles. This ANTERIOR LOBE OF THE CEREBELLUM
disturbance is evident during walking and is
There is no established paleocerebellar
characterized by muscle contractions which
are highly irregular in force, amplitude, and syndrome in humans, but lesions of the ante-
rior lobe of the cerebellum in experimental
direction, and which occur asynchronously in
different parts of the body. Frequently, there animals produce severe disturbances of pos-
ture and greatly increased extensor muscle
is unsteadiness in standing, especially if the
tone. These animals exhibit many of the fea -
feet are close together . The gait is broad -
tures seen in association with decerebration
based and the patient reels, lurches, and ( e.g.,extreme opisthotonus, tight closure of
stumbles.
the jaw, and hyperactive deep tendon re-
Nystagmus is commonly seen in associa - flexes), but in time regain the ability to walk
tion with cerebellar disease. It is most pro-
and perform voluntary movements ( 27, 103).
nounced when the patient deviates the eyes
Sherrington ( 235), in a classic experiment ,
laterally toward the side of the lesion. This
disturbance consists of an oscillatory pattern
demonstrated that electrical stimulation of
the anterior lobe of the cerebellum could in -
in which the eyes slowly drift in one direction
hibit extensor muscle tone in a decerebrate
and then rapidly move in the opposite direc-
animal . This experiment, confirming the early
tion to correct the drift. Although nystagmus
work of Loewenthal and Horsley ( 174 ),
seen in association with cerebellar disease is
showed that both inhibitory and facilitatory
considered as an expression of asynergic phe-
effects upon muscle tone could be obtained
nomena in the extraocular muscles, many
pathologic processes which affect the cerebel -
by stimulating the anterior lobe of the cere-
bellum depending on the parameters of stim-
lum also involve the underlying brainstem
ulation ( 84 ). Stimulations at low repetitive
and the vestibular nuclei located in the floor
rates ( 2-10 cycles / sec ) cause a slow increase
of the fourth ventricle.
in ipsilateral extensor muscle tone, while
Speech disturbances are common in associa -
rapid stimulation (30-300 cycles / sec ) pro-
-
tion with cerebellar lesions of long standing.
duces a relaxation of muscle tone. Inhibitory
Speech often is slow, monotonous, and some influence obtained by stimulating the ante-
syllables are unnaturally separated . There is a
slurring of speech and some words are ut- rior lobe appears to be mediated by (a ) cere
bellovestibular fibers of cortical origin which
-
tered in an explosive manner.
project to the lateral vestibular nucleus, and
( b) fastigial efferent projections to the reticu -
ARCHICEREBELLAR LESIONS
lar formation. Facilitatory influence obtained
Lesions involving portions of the posterior from stimulating the anterior lobe of the cere-
cerebellar vermis ( i.e., nodulus and uvula), bellum is mediated by projections from the
and probably portions of the flocculus, pro - fastigial nucleus acting on the lateral vestibu -
duce what has been called the arcliicerebellar lar nucleus ( 38, 89, 136, 138).
syndrome. These lesions produce disturbances Other cerebellar mechanisms which can
of locomotion and equilibrium bilaterally. influence muscle tone involve the paravermal
The patient is unsteady in the standing posi - cortex, the interposed nuclei, and the con -
tion and shows considerable swaying of the tralateral red nucleus ( 184 ). All of these struc-
body. When attempts are made to walk, there tures are somatotopically interconnected .
is staggering and a tendency to fall to one Stimulation of the rostral part of the inter-
side or backwards. The gait is jerky , uncoor - posed nuclei in the cat produces flexion in the
dinated , and resembles that of a drunk ipsilateral hindlimb, while stimulation of the
individual. Muscle tone is not significantly caudal part of these nuclei produces flexion
altered and no tremor or asynergic dis- in the ipsilateral forelimb ( 181, 220 ). These re-
turbances are seen in the extremities. This sponses are ipsilateral because fibers of both
syndrome is primarily a truncal a ' axia that the superior cerebellar peduncle and the
frequently occurs in children with tumors in rubrospinal tract are crossed ( Fig. 15.22 ). In -
the posterior cerebellar vermis. This particu - tracellular recordings in the red nucleus
lar syndrome is frequently a consequence of a demonstrate that stimulation of the inter-
midline cerebellar tumor ( medulloblastoma) posed nuclei produces excitatory postsynap-
tic potentials with a monosynaptic latency provide a rapid and clear response to any
(184, 266). The pathway between the inter- "sensory" input.
posed nucleus and the red nucleus is re-
garded as purely excitatory and impulses CEREBELLUM AND LEARNING
conveyed by this system have an important
facilitatory influence upon flexor muscle On the basis of mathematic models they
tone. These impulses are conveyed to spinal independently developed to simulate the op-
levels by the rubrospinal tract . Although the eration of cerebellar circuitry, David Marr
Purkinje cell output from the cerebellar cor - (182 ) and James Albus (3) proposed that the
tex is inhibitory , variations in the activity of cerebellum plays a crucial role in the learning
those cells are responsible for the inhibition, of motor skills. They both suggested that the
or activation , of cells in the interposed nu - function of the climbing fiber input is to mod -
cleus, which directly affects cells of the con - ify, for prolonged periods of time, the re-
tralateral red nucleus. sponse of Purkinje cells to mossy fiber inputs
(107). Electrophysiologic studies by Ito and
INFORMATION PROCESSING AT CEREBELLAR colleagues had already led to the suggestion
LEVEL that the cerebellum consists of an excitatory
loop circuit in which specific information is
The functional organization of the cerebel - processed in the nuclei, and that this process
lar cortex suggests that the cerebellum is regulated by changing Purkinje cell inhibi-
processes information related to the regulation tion (89, 134 ). In accordance with Ito's find -
and control of movement as a computer- ings, Marr and Albus suggested that the
like neural device (89, 212 ). The cerebellum climbing fiber input on specific Purkinje cells
organizes and integrates in a modular fashion could alter the effectiveness of the mossy
the information that flows to it via numerous fibers.
.
neural pathways The cerebellar output par - The idea that cerebellar circuits are modi-
ticipates in the control of motor function by fied by experience and that these changes are
conveying impulses to (a ) brainstem nuclei important in motor learning is supported by
( i.e., lateral vestibular and red nuclei ) that the results of many experimental studies on
project to spinal levels, and ( b ) thalamic nu - the control of eye movement when the visual
clei which can modify the activity of cortical world is experimentally altered , particularly
regions concerned with motor function. experiments dealing with the vestibulo-ocu-
Every part of the cerebellar cortex receives lar reflex ( VOR ) and the optokinetic eye
two different excitatory inputs, that of the movement response (OKR ) (151 ). There is
mossy fibers and that of the climbing fibers. also direct electrophysiologic evidence that
Although these inputs differ in their struc - climbing fiber activity modifies the response
tural characteristics, they appear to convey of Purkinje cells to mossy fiber inputs for
similar "sensory" information to particular long periods of time and this modification is
areas of the cerebellar cortex. The only output responsible for learned changes in the VOR
of the cerebellar cortex is conveyed by Pur- ( 135). Other investigators further suggested
kinje cell axons. This output , entirely in - that the role of the cerebellum in motor adap-
hibitory , is exerted on the cerebellar nuclei tation may be the expression of a more gen-
and the lateral vestibular nucleus. The output eral role in certain forms of Pavlovian condi-
of the cerebellar nuclei is largely excitatory, tioning ( 176). In the rabbit, lesions of the
which implies that both excitatory and in- cerebellum both prevent the acquisition and
hibitory impulses must reach these nuclei . selectively disrupt the retention of a condi-
Excitatory impulses passing to the cerebellar tioned eye blink reflex. All these findings
nuclei, derived from extracerebellar sources, suggest that the cerebellum has functions that
is conveyed via collaterals of both climbing go beyond its contribution to the control of
and mossy fibers ( 154, 173, 178). movement . The role of the cerebellum in
The fact that the cerebellar cortex trans- motor learning is crucial to movement be-
forms all inputs into inhibition , suggests that cause even normal motor behavior requires
there is probably no dynamic storage of infor- constant adaptation as circumstances change
mation . The cerebellum processes its input 255).
( 104, 107, 108,
information rapidly and conveys its output Neuropsychologic experiments in humans
indirectly to specific brainstem nuclei. This have led to the suggestion that the cerebel -
type of organization allows the cerebellum to lum is able to contribute not only to motor
15 Cerebellum 623
skills but also to higher cognitive functions lieved to contribute to various mental and
( 165, 172, 234, 283) . It is suggested that the language manipulations. As is the case for its
cerebellum can function at two different hier- contribution to motor functions, the cerebel -
archic levels. At a lower level, the cerebellum lum could serve as an adaptive mechanism
can supply signals to the frontal motor areas whose signals enable the frontal cortex to ex -
for effecting the manipulation of muscles . At ecute learned procedures optimally . In the
a higher level , the cerebellum can supply sig - absence of such cerebellar signals, the frontal
nals to some prefrontal areas for affecting the cortex would have to perform these proce-
manipulation of symbols ( 172 ). In the same dures less rapidly and fluently ( 172 ) . Al -
manner as cerebellar programs are used in though very attractive and certainly sup-
the primary motor cortex to control the exe- ported by some clinical and experimental
cution of movement, cerebellar programs act- data ( 165, 234, 283), the issue of cerebellar in -
ing in different prefrontal areas ( e.g . , area 8 volvement in higher cognitive functions is
and the inferior frontal convolution ) are be- still a matter of much controversy .
References 13. Appelberg B . Localization of focal nucleus interpositus posterior of

potentials evoked in the red nu - the cat . J Comp Neurol 1979;
1. Adrian F.D. Afferent areas in the -
185:735 756.
cerebellum connected with the
limbs. Brain 1943;66:289 315.-
cleus and ventrolateral nucleus of
the thalamus by electrical stimula -
tion of the cerebellar nuclei. Acta
23. Bloom FE, Hoffer BJ, Siggins C R
Studies on norepinephrine-con -
.
2. Aguado F, Sanchez-Franco F, Physiol Scand 196051:356 370. taining afferents to Purkinje cells
Cacidedo L , Fernandez T, Rodrigo 14 . Apps R. Columnar organization of of rat cerebellum . I . Localization of
I , Martinez - Murillo R. Subcellular the inferior olive projection to the the fibers and their synapses . Brain
localization of insulin - like growth
.
factor I ( IC F-1 ) in Purkinje cells of
posterior lobe of the rat cerebel - -
Res 1971;25:501 521.
'
lum . J Comp Neurol 1990;302: 24 . Boegman RJ , Parent A , I lawkes R .

the adult rat : an immunocyto- 236-254. Zonation in the rat cerebellar cor -
chemica! study. Neurosci Lett
1992;135:171-174.
15. Asanuma C, Thach WT, Jones EG. tex : patches of high acetyl -
Distribution of cerebellar termina - cholinesterase activity in the gran-
3. Albus JS. A theory of cerebellar tions and their relation to other af - ular layer are congruent with
function. Math Biosci 1971; ferent terminations in the ventral Purkinje cell compartments. Brain
10: 25-61. lateral thalamic region of the mon - Res 1988;448:237-251 .
4. Alley KR , Baker R , Simpson JI . Af - key. Brain Res Rev 1983;5:237-265. 25.
ferents to the vestibulocerebellum
and the origin of the visual climb-
16. Asanuma C, Thach WT, Jones EC .
Anatomical evidence for segre-
. Boesten AJP, Voogd J Projections
of the dorsal column nuclei and
the spinal cord on the inferior olive
ing fibers in the rabbit . Brain Res gated focal groupings of efferent in the cat. J Comp Neurol 1975;
1975,98:582-589. cells and their terminal ramifica - 161:215-238.
5. Altman J , Carpenter MB. Fiber pro - tions in the cerebellothalamic path - 26. Braitenberg V, Atwood RP. Mor-
jections of the superior colliculus way of the monkey Brain Res Rev phological observations on the
in the cat . J Comp Neurol 1961; 1983;5:267-297. cerebellar cortex. J Comp Neurol
-
116:157 178. 17. Batini C, Corvisier J , Destombe* J , 1958;109: 1-27.
6. Andersen BB, Korbo L , Pakken - Gioanni H , Everett J . The climbing 27. Bremer F. Contributions a l 'etude
berg B. A quantitative study of the fibers of the cerebellar cortex, their de la physiologie du cervelet . La
human cerebellum with unbiased origin and pathway in cat . Exp fonction inhibitrice du paleo-cere-
stereological techniques. J Comp Brain Res 1976;26:407-422. bellum . Arch Int Physiol Biochim
-
Neurol 1992;326:549 560. 18. Batton RR III, Jayaraman A , Rug- 1922;19:189-226.
7. -
Angaut P. The fastigio tectal pro- giero D, Carpenter MB. Fastigial 28. Broch -Smith T. Brodal P. Organi -
jections: an anatomical experimen -
tal study. Brain Res 1969;13:
efferent projections in the monkey: -
zation of the cortico ponto-cerebel -
'
an autoradiographic study. J Comp lar pathway to the dorsal parafloc-
186-189.
Angaut P. The ascending projec-
-
Neurol 1977;174:281 306. culus. An experimental study with
8. 19. Barmack Nil, Baughman RW , Eck - anterograde and retrograde trans-
tions of the nucleus interpositus
posterior of the cat cerebellum: an
enstein FP, Shojaku H. Secondary -
port of WCA 1 IRP in the cat . Arch
vestibular cholinergic projection to Ital Biol 1990;128:249-271 .
experimental anatomical study the cerebellum of rabbit and rat as 29. Brodal A . Experimented Unter-
using silver impregnation meth - revealed by choline acetyltrans- suchungen liber die olivocerebel -
ods. Brain Res 1970;24:377-394. ferase immunohistochemistry, ret - lare Lokalisation . Z Gesamte Neu -
9. Angaut P, Bowsher D. Cerebello- rograde and orthograde tracers. J rol Psychiatry 1940;169: 1 -153.
rubral connexions in the cat. Na -
ture 1965;208:1002-1003.
-
Comp Neurol 1992;317:250 270.
20. Bell CC, Dow RS. Cerebellar cir -
30. Brodal A . Spinal afferents to the
lateral reticular nucleus of the
10. Angaut P, Bowsher D. Ascending cuitry . Neurosci Res Program Bull medulla oblongata in the cat: an
projections of the medial ( fastigial ) -
1967;5:121 222. experimental study . J Comp Neu -
nucleus: an experimental study in
the cat . Brain Res 1970;24:49-68.
21 . Bentivoglio M , Kuypers 11GJM . Di - rol |94Wrm :25M 2M 5.
vergent axon collaterals from rat 31 . Brodal A. The olivocerebellar pro-
11 . Angaut P. Brodal A . The projection cerebellar nuclei to diencephalon , jection in the cat as studied with the
of the "vestibulocerebellum" onto mesencephalon, medulla oblon - method of retrograde axonal trans-
the vestibular nuclei in the cat . gata and cervical cord . Exp Brain port of horseradish peroxidase. II .
Arch Ital Biol 1967;105:441 479.
12. Angevine |B Jr, Mancall EL,
- .
Res 1982;46:339-356.
22. Bishop C A , McCrea RA, l .ighthall
The projection of the uvula . J Comp
Neurol 1976;166: 417-426.
Yakovlev PI . The human cerebel - JW , Kitai ST. An IIRP and autora - 32. Brodal A . Neurological anatomy in
lum . An atlas of gross topography diographic study of the projection relation to clinical medicine. 3rd
in serial sections. Boston : Little, from the cerebellar cortex to the ed . New York: Oxford University
Brown & Company, 1961. nucleus interpositus anterior and Press, 1981.
33. Bn >dal A , Brodal IV The organiza - 47. Brodal P. The corticopontine pri >- Cerebello-oculomotor fibers in the
tion of the nucleus reticularis jection from the visual cortex in the rhesus monkey j Comp Neurol,
tegmenti pontis in the cat in the cat . II . The projection from areas 18 1964;123:211 230. -
light of experimental anatomical and 19. Brain Res 1972;39:319-335. 62. Carrea RME, Reissig M, Met tier
studies of its cerebral cortical affer - 48 . Brodal P. Demonstration of a so- FA . The climbing fibers of the
ents. Exp Brain Res 1971 ;13:90-1 It ). matotopically organized projection simian and feline cerebellum . |
34. Brodal A , Gogstad AC . Afferent onto the paramedian lobule and Comp Neurol 1947;87:321-365.
connexions of the paramedian the anterior lobe from the lateral 63. Carrea R , Volkind R , Folins JC,
reticular nucleus of the medulla reticular nucleus: an experimental Cosarinsky D, Suarez AM Alfonso .
oblongata in the cat: an experimen - study with the horseradish peroxi - J . Some physiological and statisti-
tal study. Acta Anat ( Basel ) 1957; dase method . Brain Res 1975; cal observations on single unit ac-
30:133 151 95:221-239. tivity of the feline inferior olive. In:
15. Brodal A , .
Iloddevik C l I . The pon -
tocerebellar projection to the uvula
49. Briklal P. Principles of organiza -
tion of the monkey corticopontine
Fields WS, Willis WD, eds. The
cerebellum in health and disease.
in the cat. Exp Brain Res 1978; projection. Brain Res 1978;148: Ch . 7. St . Louis: Warren H. Green .
-
32: 105 116. 214 218 Inc., 1970:201-216.
.36. Brodal A , lloivik B. Site and mode 50. Brodal P, Marsala ) , Brodal A . The 64. Chambers WW , Sprague|M . Func-
of termination of primary ves- cerebral cortical projection to the tional localization in the cerebel -
tibulocerebellar fibres in the cat . lateral reticular nucleus in the cat , lum . I . Organization in longitudi -
Arch Ital Biol 1964;102:1 -21. with special reference to the senso- nal corticonuclear zones and their
37 .
Brodal A Lacerda AM , Destombes rimotor cortical area . Brain Res contribution to the control of pos -
I . Angaut P. The pattern of the pro- -
1967,6:252 274 ture, both extrapvramidal and
tection of the intraccrebellar nuclei 51 . Brooks VB, Thach WT. Cerebellar pyramidal. J Comp Neurol 1955;
onto the nucleus reticularis teg- control of posture and movement . 103:105-130.
menti pontis in the cat : an experi - In : Brooks VB, ed . Handbook of 65. Chambers WW , Sprague JM . Func -
mental anatomical study . Exp physiology. Section I : The nervous tional localization in the cerebel -
Brain Res 1972;16:140-160. system . Vol II : Motor control . Part lum . II . Somatotopic organization
18 Brodal A, Pompeiano O, Walberg 2 . Bethesda , MD: American Physi- in cortex and nuclei . Arch Neurol
F. The vestibular nuclei and their ological Society , 1981:877-946. Psychiatry 1955;74:653 680. -
connections, anatomy and func - 52. Carleton SC , Carpenter MB. Affer - -
66. Chan Palay V. Cerebellar dentate
tional correlations . Springfield , IL: ent and efferent connections of the nucleus: organization , cytology
Charles C. Thomas, 1962 . medial, interior and lateral and transmitters. Berlin : Springer -
39. .
Brodal A Szikla G The termina - vestibular nuclei in the cat and Verlag, 1977.
tion of the brachium conjunctivum monkey. Brain Res 1983;278:29-51. 67. Chan - Palay V , Nilaver G , Palay S,
descendens in the nucleus reticu - 53. Carpenter MB. Ventral tier thala - et al . Chemical heterogeneity in
laris tegmenti pontis: an experi - mic nuclei . In : Williams D, ed . cerebellar Purkinje cells: existence
mental study in the cat Brain Res Modern trends in neurology. Vol. and coexistence of glutamic acid
1972 39*337 351 .
* 4 . London: Butterworths, 1967: -
decarboxylase like and motilin -like
40. Brodal A , Torvik A . Cerebellar 1-20. immunoreactivities. Proc Natl
projection of paramedian reticular 54 . Carpenter MB. Vestibular nuclei: Acad $d USA 1981 78:7787 7791 .
nucleus of medulla oblongata in afferent and efferent projections. -
68. Chan Palay V , Palay * SL . Interrela -
the cat I Neurophysiol I 954;17: In: Pompeiano O, Allum JHJ , eds. tions of basket cell axons and
4*4-445. Vestibulospinal control of posture climbing fibers in the cerebellar
41. Brodal A , Torvik A . Uber den Ur - and movement. Progress in brain cortex of the rat. Z Anat Entwickl -
sprung der sekundaren vestibulo - research. Amsterdam : Elsevier, Gesch 1970;132:191-227.
cerebellaren Fasern bei der Katze. -
1988:76:5 15. -
69. Chan Palay V, Palay SL. Tendril
-
E i ne ex peri men telle anatomisc he.
Studie Arch Psychiatr 1957;195:
55. Carpenter MB. Connectivity pat -
terns of thalamic nuclei implicated
and glomerular collaterals of
climbing fibers in the granular
550-567. in dyskinesia . Stereotact Fund layer of the rat 's cerebellar cortex.
42. Brodal A , Walberg F. The olivo
cerebellar projection in the cat
- -
Neurosurg 1989;58:79 119.
56. Carpenter MB, Bard DS, Ailing FA .
/ Anat Entwickl Gesdi 1971;
133:247-273.
-
studied with the method of retro- Anatomical connections between 70. Chu NS, Bloom FE. The cate-
grade axonal transport ol horse- the fastigial nuclei, the labyrinth -
cholamine containing neurons in
radish peroxidase. IV . The projec - and the vestibular nuclei in the cat . the cat dorsolateral pontine teg-
tion to the anterior lobe ) Comp |Comp Neurol 1959; 111 : 1 -26. mentum : distribution of the cell
Neurol 1977;172:85-108. 57. Carpenter MB. Batton RR III . Con- bodies and some axonal projec -
43. Brodal A , Walberg F, Blackstad T nections of the fastigial nucleus in tions. Brain Res 1974;66: 1 -21 .
Termination of spinal afferents to the cat and monkey . In ; Palay SL, 71. Combs CN . Bulbar regions related
inferior olive in cat . J Neurophvsiol Chan - Palay V, eds. The cerebel - to localized cerebellar afferent im -
1950;13:431 454. -
44 Brodal A , Walberg F, Hod -
—
lum new vistas. Experimental
brain research (Suppl 6 ). Berlin .
pulses. J Neurophvsiol 1956;
-
19:285 300.
devik EG. The olivocerebel - -
Springer Verlag 1982:250-295. 72. Courville ) . Somatotopical organi -
lar projection in the cat studied
with the method of retrograde ax -
.
58. Carpenter MB, Brittin C M , Pines J .
Isolated lesions of the fastigial nu -
zation of the projection from the
nucleus interpositus anterior of the
onal transport of horseradish per - clei in the cat. | Comp Neurol cerebellum to the red nucleus: an
oxidase.
1975;164:449 -470.
Comp Neurol - .
1958;109:65 90
59 . C arpenter MB, Nova HR . Descend -
experimental study in the cat with
silver impregnation methods. Exp
45. Brodal P . The corticopontine pro- ing division of the brachium con - Brain Res 1966;2:191-215.
lection in the cat I Demonstration
of a somatotopically organized
junctivum in the cat: a cerebello- 73. Courville J . Distribution of olivo -
reticular system . | Comp Neurol cerebellar fibers demonstrated by a
projection from the primary senso - 1960;114:295 305. radioautographic tracing method .
rimotor cortex. Exp Brain Res 60. Carpenter MB, Stein BM , Peter P. Brain Res 1975;95:253-263.
1968;5:212 237. - Primary vestibulocerebellar fibers 74. Courville J , Augustine |R , Martel
46. Brodal P . The corticopontine pro - in the monkey: distribution of P. Projections from the inferior
jection from the visual cortex in the fibers arising from distinctive cell olive to the cerebellar nuclei in the
cat. I . The total projection and the groups of the vestibular ganglia . cat demonstrated by retrograde
projection from area 17 Brain Res Am | Anat 1972;135:221-250. transport of horseradish peroxi -
1972;39:297-317. 61 . Carpenter MB, Strominger NL . dase . Brain Res 1977;130:405 419. -
15 Cerebellum 625
.
75. Courville J Brixlal A Rubnxere- inhibitory intemeurones within tific basis of clinical neurology .
bellar connections in the cat : an ex- the cerebellar cortex . Exp Brain Res New York: Churchill Livingstone,
perimental study with silver im - 1966;1 :1-16. 1985
pregnation methods. J Comp 92. Eccles JC, Llinas R , Sasaki K. The 106 Glaum SR , Slater NT, Rossi DJ .
Neurol 1966;126:471-485. excitatory synaptic action of climb- Miller RJ. Role of metabotropic
76. Courville J , Cooper CVV . The cere - ing fibres on the Purkinje cells of glutamate ( AC PD ) receptors at the
bellar nuclei of Manna mulatta: a the cerebellum. J Physiol ( Lond ) -
parallel fiber Purkinje cell synapse.
morphological study. ) Comp Neu - 1966;182:268-296. J Neurophysiol 1992;68:1453-1462.
rol 1970;140:241-254 . 93. Eccles JC , Llinas R, Sasaki K . Paral- 107. Glickstein M The cerebellum and
.
77. Courville J Diakiw N . Cerebellar lel fibre stimulation and responses motor learning. C urr Opin Neuro-
corticonuclear projection in the cat : induced thereby in the Purkinje biol 1992;2:802 806. -
the vermis of the anterior and pos - cells of the cerebellum . Exp Brain 108. Glickstein M , Yen C. The cerebel -
terior lobes. Brain Res 1976; 110: Res 1966; 1 :17-39. lum and motor learning. J Cogn
1-20. 94 . -
Eller T, Chan Palay V . Afferent* to Neurosci 1990;2:69-80.
78. Courville J , Faraco-Cantin F. On the cerebellar lateral nucleus: evi - 109. Gould BB. The organization ol af -
the origin of the climbing fibers of dence from retrograde transport of ferent* to the cerebellar cortex in
the cerebellum : an experimental
study in the cat with an autoradi-
horseradish peroxidase after pres
sure injections through microp
-- the cat : projections from the cere-
bellar nuclei. | Comp Neurol 1979;
ographic tracing metluxl Neuro- ipettes. J Comp Neurol 1976; 166: 184:27-42.
science 1978;3:797-809.
79. De Camilli P, Miller PE, Levitt I \
-
285 301 . 110. Gould BB. Organization of affer -
95. Flumerfelt BA , Otabe S, Courville ent * from the brain stem nuclei to
Walter U, Greengard P. Anatomy J . Distinct projections to the red the cerebellar cortex in the cat . Adv
of cerebellar Purkinje cells in the nucleus from the dentate and inter - Anat Embryol Cell Biol I 980;62
rat determined by a specific im - posed nuclei in the monkev . Brain
munohistochemical marker. Neu
-
roscience 1984;!1:761 817.
-
96
Res 1973;50:408-414.
-
Fonnum F, Storm Mathisen J , Wal -
I
.90
111 . Could BB, Graybiel AM Afferent*
to the cerebellar cortex in the cat
80. Dietrichs F., Walberg F. The cere - berg F. Glutamate decarboxylase evidence for an intrinsic pathway
bellar corticonuclear and nucleo - in inhibitory neurons: a study of leading from the nuclei to the cor -
cortical projections in the cat as the enzyme in Purkinje cell axons tex . Brain Res 1976; 110:601-611 .
studied with anterograde and ret -
rograde transport of horseradish
and boutons in the cat . Brain Res
1970;20:259-275.
112. Grant G . Spinal course and soma -
totopicallv localized termination of
peroxidase. I. The paramedian lob- 97. Fonnum F, Walberg F. An estimate the spinocerebellar tracts: an ex -
ule An .it Embryol (Berl) 1979; of the concentration of •y -aminobu - perimental study in the cat . Acta
158 13 39 tyric and glutamate decarboxylase Physiol Stand !962;56(Suppl 193) :
81 . Dietrichs E, Walberg F. The cere - in the inhibitory Purkinje axon ter- 1-45.
bellar projection from the lateral minals in the cat. Brain Res 113. Grant G. Projection of the external
reticular nucleus as studied with -
1973;54:115 127. cuneate nucleus onto the cerebel -
retrograde transport of horserad - 98. Fox CA, Barnard JW . A quantita - lum in the cat: an experimental
ish peroxidase. Anal Embrvol tive study of the Purkinje cell , den - studv using silver methods. Exp
-
( Berl ) 1979;155:273 290. dritic branchlets and their relation - Neurol 1962;5:179-195.
82. Dow RS The fiber connections of ship to afferent fibres. J Anal 114 . Grav EG. The granule cells, mossy
the posterior parts of the cerebel- -
1957;91:299 313. synapses and Purkinje spine
lum in the rat and cat I Comp 99 Fox CA , Hillman DE, Siegesmund synapses of the cerebellum : light
83.
Neurol 1936;63:527-348.
Dow RA . Efferent connections of
KA, Dutta CR . The primate cere
bellar cortex: a Golgi and electron
- and electron microscopic observa -
tions . | Anat 1961;95:345-356.
the flocculonodular lobe in Manna .
microscope study In : Fox CA , 115. Haines DF. Cerebellar corticonu -
mulatta . | Comp Neurol 1938; 68: Snider RS, eds. The cerebellum , clear and corticovestibular fibers of
-
297 305. progress in brain research . Vol. 25. the anterior lobe vermis in a
84 . Dow RS. Moruzzi G. The physiol - Amsterdam: Elsevier, 1967:174 prosimian primate ( Galago sene -
ogy and pathology of the cerebel - 225. galensis ). J Comp Neurol 1976;
lum . Minneapolis: University of 100. Fox CA , Siegesmund KA , Dutt CR . 170:67-96
Minnesota Press, 1938. The Purkinje cell dendritic branch - 116. I laines DE. A proposed functional
83. -
Eager RP. Efferent cortico nuclear
pathways in the cerebellum of the
lets and their relation with the par -
allel fibers: light and electron mi -
significance of parvicellular re-
gions ol the lateral and medial
cat . | Comp Neurol 196.3; 120: croscopic observations. In : Cohen cerebellar nuclei Brain Behav Evol
-
81 103. MM , Snider RS, eds , Morphologi - -
1977;14:328 340.
86. Eager RP. Cortical association cal and biochemical correlates of 117. Hamori J , Szentagothai I Identifi -
pathways m the cerebellum of the neural activity . Ch. 7. New York: cation under the electron micro-
cat | Comp Neurol 1963;121: Harper & Row, 1964:112-141 . scope of climbing fibers and their
381-393. 101. Fredette BJ , Mugnaini F. The synaptic contacts. Exp Brain Res
87. Eager RP. The mixle of termination -
GABAergic cerebello olivary pro- 1966;1 :65-81.
and temporal course of degenera - jection in the rat . Anat Embryol 118 . Hampson JL , Harrison CR ,
tion of cortical association path - -
( Berl ) 1991;184:225 243. Woolsev CN . Cerebro-cerebellar
ways in the cerebellum of the cat I 102. Fukushima K , Peterson BW , projections and the somatotopic lo -
Comp Neurol 1963;124:243-257. Uchino Y , Coulter JD, Wilson VJ calization of motor function in the
88. Ebbesson SOE . A connection be- Direct fastigiospinal fibers in the cerebellum . Proc Asstx Res Nerv
’
tween the dorsal column nuclei cat . Brain Res 1977;126:538-342. Ment Dis 1952;30:299-316.
and the dorsal accessory olive. 103. Fulton JF. Functional localization 119. I lawkes R , Gravel C . The modular
Brain Res 1968;8:393 397.-
89. Eccles JC, I to M . Szentagothai |.
in the frontal lobes and cerebellum . cerebellum . Prog Neurobiol 1991 ;
Oxford:C larendon Press, 1949 .36:309-327.
The cerebellum as a neuronal ma - 104 Ghez C The cerebellum . In : Kan- 120. Heidary H , Tomasch | Neuron
chine. New York: Springer - Verlag, del FR, Schwartz JH , Jessell TM , numbers and perikaryon areas in
'
1967. eds. Principles of neural science. the human cerebellar nuclei. Acta
90. Eccles JC, Elinas R , Sasaki K . Exci- 3rd ed . Ch . 41 . New York . Elsevier, Anat ( Basel ) 1969;74:290-296.
tation of cerebellar Purkinje cells 1991 :626-646. 121 . Herrick CJ . The brain of the tiger
bv the climbing fibers. Nature 105. Gilman S. The cerebellum: its role salamander. Chicago: University of
1964;203:245 246.- in pt »slure and movement . In: Chicago Press, 1948.
91. Eccles JC, Llinas R , Sasaki K . The Swasch M , Kennard C, eds. Scien - 122 . Hoddevik Gl I I he pontocerebel
lar projection onto the paramedian Deiters neurones. Experientia serotoninergic projections to differ-
lobule in the cat : an experimental 1964;20:515. ent regions of the cat cerebellar
study with the use of horseradish 138. Ito M, Yoshida M. The origin of cortex. J Comp Neurol 1991;
peroxidase as a tracer. Brain Res cerebellar-induced inhibition ot 304:502-515.
1975,05:291-307.
123. I loddevik GH. The projection from
Deiters neurones. I. Monosynaptic
initiation of the inhibitory postsy-
153. Kievit |, Kuypers HGJM. Fastigiil
cerebellar projections to the ven-
.
nucleus reticularis tegmenti pontis naptic potentials. Exp Brain Res trolateral nucleus of the thalamus
onto the cerebellum in the cat : a 1966;2:330-349. and the organization of the de-
study using the methods of antero- 139. Ito M, Yoshida M, Obata K . Mono- .
scending pathways In: Frigyesi
grade degeneration and retrograde synaptic inhibition of the intracere- .
Tl., Rinvik E Yard MD, eds. Corti-
axonal transport of horseradish bellar nuclei induced from the cothalamic projections and sensori -
peroxidase. Anat F.mbryol (Berl ) cerebellar cortex. Experientia 1964; motor activities. New York: Raven
1978;153:227- 242. 20:575-576. Press, 197201- ill
124 llbkfelt T, Fuxe K Cerebellar
monoamine nerve terminals : a new
140. Ito M, Yoshida M, Obata K, Kawai
N, Udo M. Inhibitory control of in-
. .
134. Kitai ST McCrea RA Preston R|,
Bishop GA . F.lectrophysiological
type of afferent liber to the cerebel- tracerebellar nuclei by the Burkinje and horseradish peroxidase stud -
lar cortex . Exp Brain Res 1%9, cell axons. Exp Brain Res 1970; ies of precerebellar afferents to the
9:63-72. -
10:64 80. nucleus interpositus anterior. I.
125. Holmes G. The Croonian Lectures 141. Jakob A . Das Kleinhirn. In: von Climbing fiber system. Brain Res
on the clinical symptoms of cere- Mollendorff W, ed. 1 iandbuch der 1977;122:197-214
bellar disease and their interpreta - mikroskopishen Anatomic des 133. Korneliussen I IK . On the ontoge-
tion. Uncet 1922;1:1177- 1182. Menschen. Vol. IV . Berlin: Julius netic development of the cerebel -
126. Holmes JG. The cerebellum of Springer, 1928:674-916 . lum nuclei, fissures and cortex of
man. Brain 1939;62:l 30. 142. Jansen J . Vertebrate history with the rat with special reference to re-
127. I lolmes C i, Stewart TG. On the con- special reference to factors related gional variations in corticogenesis.
nections of the inferior olive with to cerebellar evolution. In: Llinas J Hirnforsch 1%8;10:379-412.
the cerebellum in man. Brain R, ed. On cerebellar evolution and .
156 Korneliussen I IK . Histogenesis of
1908;31:125- 137. organization from the point of the cerebellar cortex and cortical
128. lacopino AM, Rhoten WB, Chris- view of a morphologist . Chicago: zones. In: Larsell O, jansen j, eds.
takos S. Calcium binding protein American Medical Association, The comparative anatomy and his -
(calbindin-D28k ) gene expression 1969:881-893. tology of the cerebellum: the
in the developing and aging mouse 143. Jansen J, Brodal A . Experimental human cerebellum, cerebellar con-
cerebellum. Mol Brain Res studies on the intrinsic fibers of the nections and cerebellar cortex.
1990;8:283- 290. cerebellum. 11. The corticonuclear Minneapolis: University of Min-
129. Ikeda M Projections from the projection. J Comp Neurol 1940; nesota Press, 1972:164-174.
spinal and the principal sensory 73:267-321. 157. Kotchabhakdi N, Hoddevik GH,
nuclei of the trigeminal nerve to 144 . Jansen J, Brodal A . Experimental Walberg F. Cerebellar afferent pro-
the cerebellar cortex in the cat, as studies on the intrinsic fibers of the jections from the perihypoglossal
studied by retrograde transport of cerebellum. The cortico-nuclear nuclei: an experimental study with
horseradish peroxidase. J Comp projection in the rabbit and in the the method of retrograde transport
Neurol 1979;184:567-585. monkey ( Macaco rhesus ). Norske of horseradish peroxidase. Exp
130. Ikeda M, Houtani T, Uevama T, Vid - Akad Avh Mat -Naturv 1942; Brain Res 1978;31:13-29.
Sugimoto T. Choline acetyltrans- 3:1-50. 158. Kotchabhakdi N, Walberg F. Cere-
ferase immunoreactivity in the cat 145. Jansen J, Brodal A, eds. Aspect of bellar afferent from neurons in
cerebellum. Neuroscience 1991;45: cerebellar anatomy . Oslo: J.G. motor nuclei of cranial nerves
671-690. Tanum, 1954 . demonstrated by retrograde ax -
131. Ikeda M, Matsushita M. Tri- 146. Jansen J, Brodal A. Das Kleinhirn. onal transport of horseradish per-
geminocerebellar projections to the In: Von Mollendorff W, ed . oxidase. Brain Res 1977;137:
posterior lobe in the cat, as studied Handbuch der mikroskopischen 158 163
by anterograde transport of wheat Anatomie des Mensche. Vol. Ill 159. Kotchabhakdi N, Walberg F. Pri-
germ agglutinin-horseradish per - Berlin: Julius Springer, 1958:1-323. mary vestibular afferent projec -
oxidase*. J Comp Neurol 1992; 147. Kalil K . Projections of the cerebel- tions to the cerebellum as demon-
316:221-237. lar and dorsal column nuclei upon strated by retrograde axonal
132. Ilinsky IA, Kultas - llinsky K . Sagit - the inferior olive in the rhesus transport of horseradish peroxi-
tal cytoarchitectonic maps of the monkey: an autoradiographic dase Brain Res PCS; 142 : 142 I 4h
Mihiiai mulutla thalamus with a re- study . J Comp Neurol 1979; 188: 160. Kotchabhakdi N, Walberg F. Cere-
vised nomenclature of the motor - 43-62 . bellar afferent projections from the
related nuclei validated by obser- 148. Kan KSK, Chao LP, Eng LF. Im - vestibular nuclei in the cat: an ex -
vations on their connectivity. J munohistochemical localization of perimental study with the method
Comp Neurol 1987;262:331 364. choline acetyltransferase in rabbit of retrograde transport of horse-
133. Illing RB. A subtype of cerebellar spinal cord and cerebellum . Brain radish peroxidase. Exp Brain Res
Golgi cells may be cholinergic. Res 1978;146:221-229. 1978;31:591-604 .
Brain Res 1990;522:267-274. 149. Kan KSK, Chao LP, Forno LS. Im- 161. Kunzle H. The topographical orga -
134 . Ito M. The cerebellum and neural muno-histochemical localization of nization of spinal afferents to the
control. New' York : Raven Press, choline acetyltransferase in the lateral reticular nucleus of the cat J.
1984. human cerebellum. Brain Res Comp Neurol 1973;149:103-117.
-
135. Ito M. Long term depression . 1980;193:165-171 . 162 . Kunzle H. Autoradiographic trac -
Annu Rev Neurosci 1989;12: 150. Kawamura K . The pontine projec - ing of the cerebellar projections
85-102. tion from the inferior colliculus in from the lateral reticular nucleus in
136. Ito M, Obata K, CVhi R. The origin the cat: an experimental anatomi- tin ' cat I xp Brain Kes PC > 22
of cerebellar -induced inhibition of cal study. Brain Res 1975,05: 253- 2 <>h.
Deiters neurones. II. Temporal cor - 309-322. 163. Kuypers HGJM, Lawrence DG.
relation between the trans-synaptic 151. Kawato M, Gomi H. The cerebel- Cortical projections to the red nu-
activation of Purkinje cells and the lum and VOR /OKR learning mod - cleus and the brain stem in the rhe-
inhibition of Deiters neurones . Exp .
els Trends Neurosci 1992;15: sus monkey Brain Res 1%7;4:
Brain Res 1966;2:350-364. 445-453. 151-188.
137. Ito M, Yoshida M. The cerebellar- 152. Kerr CW, Bishop GA. Topographi- 164. Ladpli R, Brodal A . Experimental
evoked monosynaptic inhibition of cal organization in the origin of studies of commissural and reticu-
15 Cerebellum 627
lar projections from the vestibular tegmentum pontique et leurs voies 196. Mihailoff GA, Kosinski RJ , Border
nuclei in the cat . Brain Res
1968;8:65-96.
de projection chez le chat . Brain BG, Azizi SA A survey of non cor - -
Res 1973;57:119-152. tical afferent projections to the
165. Lalonde R , Bote/ Ml . The cerebel - 181 Mattel L , Pompeiano O. Cerebellar basilar pontine nuclei, a retrograde
lum and learning process in ani - control of flexor motoneurons. tracing study in the rat . J Comp
mals. Brain Res Rev 1990;15:
-
325 332. 182.
-
Arch Ital Biol 1962;100:476 509.
Marr D. A theory of cerebellar cor -
Neurol 1989;282:617-643.
197. Mufson EJ , Higgins GA, Kordower
166. Larsell O. The cerebellum of the tex . J Physiol ( Lond ) 1969; JH . Nerve growth factor receptor
frog. | Comp Neurol 1923;36:
89-122.
-
202:437 470. immunoreactivity in the new
183. Martin GF, King JS, Dorn R . The world monkey (Cr /»i/s apella ) and
167. Larsell O. The cerebellum of myxi - projections of the cerebellar nuclei human cerebellum. J Comp Neurol
noidsand petromy /onts, including of the opossum Diiielphis Marsupi 1991;308:555 575.-
developmental stages in the lam - alts Virginiatta . J Hirnforsch 1974; 198. Mugnaini E. The histology and cy -
—
preys. J Comp Neurol 1947;86:
395 146.
168. larsell O. The development of the
cerebellum in man in relation to its
184 .
185.
15.545-573.
Massion J . The mammalian red nu -
cleus. Physiol Rev 1967;47:383 136.-
Matsushita M , I losoya Y . The loca -
tology of the cerebellar cortex. In :
Larsell O, Jansen J , eds. The com-
parative anatomy and histology of
the cerebellum. The human cere-
comparative anatomy . I Comp tion of spinal projection neurons in bellum , cerebellar connections, and
Neurol 1947;87:85-129.
169. Larsell O. Anatomy of the nervous
the cerebellar nuclei ( cerebel - cerebellar cortex. Minneapolis:
lospinal tract neurons ) of the cat : a University of Minnesota Press,
system . 2d ed . New York: Apple- study with the horseradish peroxi - 1972:201-262.
- -
ton Century C rofts, 1951. dase technique. Brain Res 1978; 199. Mugnaini E , Walberg F An experi -
.
170. Larsell O, Jansen J eds. The com- 142:237-248. mental electron microscopical
parative anatomy and histology of 186. Matsushita M , Iked a M . Projec - study on the nude of termination
the cerebellum : the human cerebel -
lum , cerebellar connections and
tions from the lateral reticular nu - of cerebellar corticovestibular fi -
cleus to the cerebellar nucleus to bres in the cat lateral vestibular nu -
cerebellar cortex . Minneapolis: Uni - the cerebellar cortex and nuclei in cleus ( Deiters' nucleus). Exp Brain
versity of Minnesota Press, 1972 the cat . Exp Brain Res 1976; Re's 1967;4:212-236.
171. Leclerc N, Dore L, Parent A,
llawkes R. The compartmentaliza - 187.
-
24:403 422.
Matsushita M , Iwahori N Struc -
200. Noda II . Cerebellar control of sac -
cadic eye movements: its neural
tion of the monkey and rat cerebel - tural organization of the fastigial mechanisms and pathways. Jpn |
lar cortex: zebrin I and cytochrome nucleus. I. Dendrites and axonal Physiol 1991 ,41:351 368 .
oxidase. Brain Res 1990;506:70-78. pathways. Brain Res 1971;25: 201 . Oertel WH. Neurotransmitters m
172. Leiner HC, Leiner AL, Dow RS. 597-610. the cerebellum. Scientific aspects
Reappraising the cerebellum : What 188. Matsushita M , Ragnarson B, Grant and clinical relevance. Adv Neurol
diK*s the hindbrain contribute to G. Topographic relationship be - 1993;61:33-75.
the forebrain . Behav Neurosci tween sagittal Purkinje cell bands 202. Olson L, Fuxe K . On the projec -
1989;103:998-1008 . revealed by a monoclonal antibody tions from the locus coeruleus no-
173. Llimis R , Walton KD. Cerebellum. to zebrin I and spinocerebellar pro- radrenaline neurons the cerebellar
In : Shepherd GM , ed . The synaptic jections arising from the central innervation . Brain Res 1971;28:
organization of the brain Chap. 7. cervical nucleus in the rat . Exp 165-171.
New York: Oxford University -
Brain Res 1991;84:133 141. 203. Orioli PJ , Strick PL. Cerebellar con -
Press, 1990:214-245.
174 . Loewenthal M , Horsley V . On the
189. -
May PJ , Hartwich Young R , Nel -
son |, Sparks DL, Porter JD. Cere -
nections with the motor cortex and
the arcuate premotor area: an
relations between the cerebellum
and other centre's ( namely cerebral
and spinal ) with special reference
bellotectal pathways in the
macaque: implications for collieu
lar generation of saccades. Neuro
-
-
analysis employing retrograde
transneuronal transport of WC A -
HRP. J Comp Neurol 1989;288:
.
to the action of antagonistic mus- science 1990;36:305-324. 612-626.
cles. Proc R Soc Ser B 1897: 190. Mehler WR, Nauta WJH . Connec- 204 . Oscarsson O. Integrative organiza -
61 :20-25. tions of the basal ganglia of the tion of the rostral spinocerebellar
175. Lorente De No R . Etudes sur le cerebellum. Confin Neurol tract in the cat. Acta Physiol Scand
cerveau posterieur. Trav Lab Rech -
1974;36:205 222. 1964;64:154-166.
-
Biol Univ Madrid 1924;22:51 65. 191. Mehler WR , Verier VG, Nauta 205. Oscarsson O. Functional organiza -
176. McCormick DA , Thompson RF. WJH Efferent projections from the -
tion of the spino and cuneocerebel -
Cerebellum: Essential involvement dentate and interpositus nuclei in lar tracts. Physiol Rev 1965;45:
in the classically conditioned eye - primates. Anat Rec 1958;30: -
495 522.
lid response. SdoiR 1964223: -
430 431. 206. Oscarsson O. Functional signifi -
296*299 192. Mettler FA, Lubin AJ . Termination cance of information channels
177. McCrea RA , Bishop GA, Kitai ST. of the brachium pontis. J Comp from the spinal cord to the cerebel -
Intracellular staining of Purkinje Neurol 1942;77:391-397. lum In: Yahr MD, Purpura DP,
cells and their axons with horse- 193. Miller RA , Strominger NL. An ex - ids. Neurophysiological basis of
radish peroxidase. Brain Res perimental study of the efferent normal and abnormal motor activi -
-
1976;118:132 136. connections of the superior pedun - ties. New York . Raven Press,
178. McCrea RA , Bishop GA , Kitai ST. cle in the rhesus monkey . Brain 1967:93-113.
Electrophysiological and horserad - Res 1977, l »237 25a 207. Oscarsson O. Functional organiza -
ish peroxidase studies of precere- 194. Miller S, Oscarsson O. Termination tion of spinocerebellar paths In :
bellar afferents to the nucleus in - and functional organization of Iggo A, td . Handbook of sensory
terpositus anterior. II . Mossy fiber -
spi no olivocerebellar paths. In : physiology . Vol . 2. Berlin :
system.
-
215 228.
Brain Res 1977;!22: Fields WS, Willis WD, eds. The
cerebellum in health and disease.
-
Springer Verlag, 1973:3.39 - 380.
208. Oscarsson O, Sjdlund B. The cen -
179. Madigan JC Jr, Carpenter MB Ch . 6. St . Louis: W. H . Green , -
tral spino olivocerebellar system in
Cerebellum of the rhesus monkey: 1970:172 -200. the cat . I . Identification of five
atlas of lobules, laminae, and folia ,
in sections. Baltimore: University
.
195. Mihailoff C A. Cerebellar nuclear
projections from the basilar pon -
paths and their terminations in the
cerebellar anterior lobe. F.xp Brain
Park Press, 1971 . tine nuclei and nucleus reticularis Res 1977;28:469-486
180. Maeda T, Pin C, Salvert D, Ligier tegmenti pontis as demonstrated 209. Ottersen OP, Laake JH , Storm -
M. Jouvet M . l .es neurones con - with PHA - L tracing in the rat . J Mathisen J . Demonstration of a re -
tenant des catecholamines du Comp Neurol 1993;330:130 146. - leasable pool of glutamate in cere -
bellar mossy and parallel fibre ter - vestigaciones Cientificas, lnstituto 238. Snider RS. Alterations which occur
minals by means of light and elec - Ramon v Cajal , Madrid , 1972. ) in mossy terminals of the cerebel -
tron microscopic immunocyto
chemistrv' . Arch Ital Biol 1990;128:
- 224. Ranson SW , Ingram WR . The dien-
cephalic course and termination
lum following transection of the
brachium pontis. J Comp Neurol
111 - 125. of the medial lemniscus and -
1936;64:417 435.
-
210. Ottersen OP, Storm Mathisen I. brachium conjunctivum . J Comp 239. Snider RS . Morphology of the cere-
-
Glutamate and GABA containing- Neurol 1932;56:257-275. bellar nuclei in rabbit and cat . |
neurons in the mouse and rat 225. Rinvik E, Grofova I. Cerebellar Comp Neurol 1940;72:399-415.
brain, as demonstrated with a new projections to the nuclei ventralis 240. Snider RS. Recent contributions to
immunocytochemical technique. J lateralis and ventralis anterior thal- the anatomy and physiology of the
Comp Neurol 1984;229:374-392. ami. Anat Embryol ( Berl ) 1974; cerebellum . Arch Neurol Psychia -
211 Ottersen OP, Zhang N , Walberg F. 14605 ill. -
try 1950;64:196 219.
Metabolic compartmentation of
glutamate and glutamine: morpho-
226. Rinvik E, Walberg F. Studies on
the cerebellar projections from the
241 . Snider RS, Eld red E. Cerebro cere
bellar relationships in the monkey.
- -
logical evidence obtained by quan- main and external cuneate nuclei J Neurophvsiol 1952;15:27-40.
titative immunocytochemistry in in the cat by means of retrograde 242. Snider RS, Stowell A . Receiving
46519 534-
rat cerebellum. Neuroscience 1992;
.
212. Palay SL, Chan - Palav V . Cerebellar
cortex: cytology and organization.
axonal transport of horseradish
peroxidase. Brain Res 1975,'95:
371-381.
227. Romer AS. Vertebrate history with
areas of the tactile, auditory, and
visual systems in the cerebellum . J
N eu rophysiol 1944;7:331-357.
243. Somana R , Kotchabhakdi N , Wal-
-
Berlin: Springer Verlag, 1974. special reference to factors related berg F. Cerebellar afferents from
213 Panagopoulos NT, Papadopoulos to cerebellar evolution. In : Elinas the trigeminal sensory nuclei in the
GC, Matsokis \ A . Dopaminergic R , ed . Neurobiologv of cerebellar cat . Exp Brain Res 1980;38:57-64.
innervation and binding in the rat evolution and development . 244 . Somana R , Walberg F. Cerebellar
cerebellum. Neurosci Lett 1991; Chicago: American Medical Asso - afferents from the paramedian
130: 208-212. ciation , 1969:1-18. reticular nucleus studied with ret -
214. Pearson A A . The development and 228. Ross CA , Bredt D, Snyder SH. rograde transport of horseradish
connections of the mesencephalic Messenger molecules in the cere - peroxidase. Anat Embryol ( Berl )
root of the trigeminal nerve in bellum. Trends Neurosci 1990,13: -
1978;154:353 368.
man . I Comp Neurol 1949;90:1 -46. 216-222 245. Somana R , Walberg F. The cerebel -
215. Pearson A A . Further observations 229. Rossi C» F, Brixlal A . Corticofugal lar projection from locus coeruleus
on the mesencephalic root of the fibers to the brain stem reticular as studied with retrograde trans-
trigeminal nerve. J Comp Neurol formation: an experimental study port of horseradish peroxidase in
1949;91 : 147-194. in the cat . J Anat 1956;90:42-62. the cat. Anat Embryol ( Berl )
216. Percheron G . The thalamic terri - 230. Ruggiero D, Batton RR III , Jayara - 1978;155:87-94.
tory of cerebellar afferents and the man A , Carpenter MB. Brainstem 246. Somana R , Walberg F. Cerebellar
lateral region of the thalamus of afferents to the fastigial nucleus in afferents from the nucleus of the
the macaque in stereotaxic coordi - the cat demonstrated by transport -
solitary tract . Neurosci l ett 1979;
—
nates.
375 MX ).
.
llirnforsch 1977; 18:
217. Peters A Palay SL, Webster H

deF. The fine structure of the ner -
of horseradish peroxidase. J Comp
Neurol 1977;172:189-210.
231 . Ruigrok TJ , Osse RJ , Voogd J . Or-
ganization of inferior olivary pro-
11:41-47.
247. Somana R , W'alberg F. A re exami --
nation of the cerebellar projections
from the gracile, main and external
vous system: neurons and their jections to the flocculus and ventral cuneate nuclei in the cat . Brain Res
supporting cells. 3 rd ed . New
York: Oxford University Press,
paraflocculus of the rat cerebellum .
J Comp Neurol 1992;316:129-150.
-
1980;186:33 42.
248. Sotelo C. Cerebellar neuroglia:
1991 232. Saigal RP, Karamanlidis AN , morphological and histochemical
218 Pickel VM , Segal M , Bloom FE . A Voogd I , Michaloud 11, Mangana aspects. In : Fox CA, Snider RS, eds.
radioautographic study of the ef - O. Cerebellar afferents from motor Progress in brain research . Vol . 25:
ferent pathways of the nucleus nuclei of cranial nerves, the nu - The cerebellum . Amsterdam: Else-
locus coeruleus. j Comp Neurol cleus of the solitary tract and nu - vier, 1967:226-250.
1974;155:15-42. clei coeruleus and parabrachialis in -
249. Sousa Pinto A . Cortical projections
219. Plioplys AV , Thibault 1 , 1 lawkes R . sheep, demonstrated with retriv- of the medial geniculate bixiv in
Selective staining of a subset of grade transport of horseradish per- the cat. Adv Anat Embryol Cell
Purkinje cells in the human cere- oxidase. Brain Res 1980;197:20-206. Biol 1973;48:1 -42.
bellum with monoclonal antibody 233. Scheibel ME, Scheibel AB Obser - 250. Strong OS. A case of unilateral
mabQH 3. ) Neurol Sci 1986; vations on the intracortical rela - cerebellar agenesia , j Comp Neurol
70:245-256. tions of the climbing fibers of the 1915;25:361 391.-
220. Pom pcia no O Organ izzazione so- cerebellum: a Golgi study. J Comp 251. Szentagothai J , Rajkovits K . liber
matotopica delle risposte flessorie Neurol 1954;101:733-764 den Ursprung der Kletterfasern
alia stimolazione elettrica del nu - 234. Schmahmann JD. An emerging des Kleinhirn . Z Anat Entwickl -
clei! interposito nel gatto decere- concept. The cerebellar contribu - Gesch 1959;121:130-141.
brato. Arch Sci Bio ( Bologna ) tion to higher function. Arch Neu - 252. Taber- Pierce E , Hoddevik GH .
1959;43: 163-176. rol 1991;48:1178-1187. Walberg F. The cerebellar projec-
221 . Pompeiano O, Brodal A . Experi- 235. Sherrington CS. Decerebrate rigid - tion from the raphe nuclei in the
mental demonstration of a somato- ity , and reflex co-ordination of cat as studied with the method of
topical origin of rubrospinal libers movements. J Physiol ( Lond ) retrograde transport of horserad -
in the cat . | Comp Neurol 1898;22:319-322. ish peroxidase. Anat Embryol
1957;108:225-251. 236. Simon II , Le Moal M , Calas A. Ef - ( Berl ) 1977;152:73 87.-
222 . Puymirat ) , Marchand K , Dussault ferents and afferents of the ventral 253. Takeuchi V , Kimura 11, Sano V . Im -
Jll Immunocytochemical localiza-
. tegmental - A - 10 region studied munohistochemical demonstration
tion of beta thyroid receptor in the after local injections of Till leucine of serotonin -containing fibers in
rat cerebellum. Neurosci Lett and horseradish peroxidase. Brain the cerebellum. Cell Tissue Res
-
1992;135:239 242. Res 1979;175: 1 -23. 1982;226:1-12.
223. Ramon y Cajal S. Histologic du 237 Smith M ( The anatomy of the 254 Thach WT . The behavior of Pur-
Systeme Nerveux de 1' Homme spino-cerebellar fibers in man. II kinje and cerebellar nuclear cells
et des Vertebres . ( Azoulay L, The distribution of the fibers in the during two types of voluntary arm
trans.) Paris: Maloine, 1909, 1911. cerebellum. J Comp Neurol 1961 ; movement in the monkey . In:
( Reprinted , Consejo Superior de In- 117:329-354 Fields WS, Willis WD, eds The
15 Cerebellum 629
cerebellum in health and disease. 269. Vincent SR, Hope BT. Neurons cerebellum. J Comp Neurol 1952;
Ch. 8. St . Louis: Warren H. Green, that sav NO. Trends Neurosci 97567 636
Inc., 1970:217-230. 1992;15:108-113 . 286 Wilson V |, Uchino Y, Maun/ RA,
255. Thach VVT, Goodkin HI’, Keating 270 Voogd |. The morphology’ of the Susswein A , Fukushima K Proper -
JG. The cerebellum and the adap- cerebellum the last 25 years. F.ur I ties and connections of cat fasti -
tive coordination of movement. Morphol 1992;30:81-96. giospinal neurons Exp Brain Res
Annu Rev Neurosci 1992;15: 271. Voogd J, Epema AIL Rubertone 1978;32: 1 - 17.
403-442. I A. Cerebello- vestibular connec - 287. Wilson VJ, Uchino Y, Susswein A .
256. Thach VVT, Jones EG. The cerebel- tions of the anterior vermis. A ret - Fukushima K. Properties of direct
lar dentatothalamic connection: rograde tracer study in different fastigiospinal libers in the cat .
Terminal field, lamellae, rods and
somatotopv. Brain Res 1979;169:
mammals including primates.
Arch Ital Biol 1991,129: 3- 19
Brain Res 1977;126:543- 5 16
288. Woodburnt* RT. A phylogenetic
-
168-172. 272. Voogd I, Feirabend HKP, Schoen consideration of the primary and
257. Thomas DM, Kaufman Rl \ JHR . The cerebellum and precere- secondary centers and connections
Sprague JM, Chambers WW . Ex- bellar nuclei. In: Paxinos C, ed The of the trigeminal complex in a se-
perimental studies of the vermal human nervous system. Ch 14 nes of vertebrates . I Comp Neurol
cerebellar projections in the brain New York: Academic Press, 1990; 1936;65:403- 501.
stem of the cat ( fastigiobulbar 321- 386. 289. Woodward Dl , Moises lit Water .
tract ). | Anat 1956;90:371 -385. 273. Voogd |. The cerebellum of the cat. . .
house BD Yeh Illl Chcun JE Hu -
258 .
Tolbert DL, Bantli H An MRP and Structure and fibre connexions. cerebellar norepinephrine system
autoradiographic study of cerebel - Assen, The Netherlands: Gorcum, inhibition, modulation, and gating
lar corticonuclear -nucleivortical 1964. Prog Brain Res 199|;8S: 33| VH
reciprocity in the monkey. Exp 274 . Walberg I Descending connec - 290 . Woodward DJ, Moises 11C, Water
Brain Res 1979;36 565 571 tions to the inferior olive: an exper - house BD, Yeh 1111, Cheun JE
259. Tolbert DL, Bantli H, Bloedel |R imental study in the cat . J Comp Modulatory actions of norepineph
Anatomical and physiological evi - Neurol 1956;il)4:77-173. rino on neural circuits. Adv Exp
dence for a cerebellar nucleocorti- 275. Walberg F. On the termination of Med Biol 1991;287:193-208 .
cal projection in the cat . Neuro- rubrobulbar fibers: experimental . .
291 Yaginuma II Matsushita M Spin
science 1976;1:205- 217. observations in the cat. I Comp ocerebellar projections from the
260. Tolbert DL, Bantli H, Bloedel JR . Neurol 1958;110:66-73. upper lumbar segments in the cat,
The intracerebellar nucleocortical 276. Walberg E. Cerebellovestibular re- as studied by anterograde trans -
projection in a primate. Exp Brain lations: anatomy. Prog Brain Res port of wheat germ agglutinin -
Res 1977;30:425-434. 1972;37:361-376. horseradish peroxidase. | Comp
261 Tolbert DL, Bantli H, Bloedel |R 277. Walberg F, Jansen J. Cerebellar cor - Neurol 1989;281:298- 319
Multiple branching of cerebellar ticovestibular fibers in the cat . Exp 292. Yamada J, Shirao K, Kitamura T,
efferent projections in cats. Exp Neurol 1961;3:32-52. Silo II. Trajectory of spinocerebel-
Brain Res 1978;31:305- 316 278. Walberg E, Kotchabhakdi H, llod - lar fibers passing through the inte-
262. Tolbert DL, Bantli H, Bloedel JR. devik GIL The olivocerebellar pro- rior and superior cerebellar pedun-
Organization features of the cat jections to the flocculus and cles in the rat spinal cord : a study
and monkey cerebellar nudeocor - paraflocculus in the cat, compared using horseradish peroxidase with
tical projection J Comp Neurol to the rabbit : a study using horse- pedunculotomy. J Comp Neurol
1978:182:39-56. radish peroxidase as a tracer. Brain 1991;304:147-160.
263 Tolbert DL, Massopust LC, Mur - Res 1979;161:389-398 293. Yamamoto T, Yoshida K,
phv MG, Young PA . The anatomi- 279. Walberg F, Pompeiano O. Fasti- .
Yoshikawa 11 Kishimoto Y Oka 11 .
cal organization of the cerebello-
olivary projection in the cat J
giofugal fibers to the lateral reticu-
lar nucleus. An experimental study
-
flu medial dorsal nucleus is one ot
tin* thalamic relays of the cerebel -
C omp Neurol 1976;170:525- 544 in the cat. Exp Neurol 19644; locerebral responses to the frontal
264. Torvik A, Brodal A . The cerebellar 2:40-53. association cortex in the monkey :
projection of the peri-hypoglossal 280. Walker AE. The thalamus of the horseradish peroxidase and fluo-
nuclei ( nuclei intercalatus, nucleus chimpanzee. IV . Thalamic projec- rescent dye double staining study
praepositus hypoglossia and nu- tions to the cerebral cortex . | Anat Brain Res 1992579: 315-320.
cleus of Roller ) in the cat. J Neti - - .
1938;73:37 93 294 . Purkinje JE. Neusle untersuchun-
ropathol Exp Neurol 1954;| 3 :
515-527.
281 Walker AE. Afferent connections.
In: Buev IV, ed. The precentral
—
gen aus der nerven und llirn
Anatomie. In: Sternberg K,
-
265. Triarhou LC, Ghetti B. Serotonin- motor cortex . 2d ed Ch. 4. Urbana: Kromblioltz JV, eds. Bench! uber
immunoreactivity in the cerebel - University' of Illinois, 1949: die versammlung deutsches Na -
lum of two neurological mutant 112-132. turforscher und Art / e in Prag,
mice and the corresponding wild- 282 Walker AE. Internal structure and 1837:177- 180
type genetic stixks. | Chem Neu- afferent -efferent relations of the .
295 Ingram VI, Ogren MP Chatot CL,
roanat 1991;4:42l ^428. thalamus. In: Purpura DP Yahr . Gossels JM, Owens BB. Diversity
.
266. Tsukahara N Toyama K, KOsaka MD, eds. The thalamus. New York: among Purkinje cells in the mon-
K Intracellular recorded responses Columbia University Press, 1966 key cerebellum. Proc Natl Acad Sci
of the red nucleus neurons during 1-12. USA 1985;82:7131-7135.
antidromic and orthodromic acti- 28.3. Wallesch CW, Horn A. Long-term 296. Newman DB, Ginsburg CY Brain -
vation. Experientia 1964:20:632- effect of cerebellar pathology on stem reticular nuclei that project to
637 . cognitive functions. Brain Cogn the cerebellum in rats; a retrograde
267. Uno M, Yoshida M, Hirota I. The 1990;14:19-25. tracer study. Brain Behav Evol
mode of cerebellothalamic relay 284. Wassef M, Sotelo C. Asynchrony in 1992;39:24-68 .
transmission investigated with in- the expression of guanosine 3 ,5 ' - 297. Shambles CM, Gibson JM, Welker
tracellular recordings from cells of phosphate-dependent protein ki- W . Fractured somatography in
the ventrolateral nucleus of cat 's nase by clusters of Purkinje cells granule cell tactile areas of rat cere-
.
thalamus Exp Brain Res 1970; during the perinatal development bellar hemispeheres revealed by
10:121-139. of rat cerebellum. Neuroscience micromapping. Brain Behav Evol
268. Van der Want JJL, Voogd J. Ultra - 1984;13:1217-1241. 1978;15:94-140.
structural identification and local- 285 Whitlivk DG. A neurohistological
. 298. Carpenter MB, Hanna GR . Fiber
ization of climbing fiber terminals and neurophysiological investiga - projections from the spinal trigem -
in the fastigial nucleus of the cat. I tion of the afferent tiber tracts and inal nucleus in the cat . J Comp
Comp Neurol 1987;258:81-90. the receptive areas of the avian -
Neurol 1961;117:117 132.
Section VI
Forebrain
16
Thalamus
REGIONAL ORGANIZATION OF THE nuclei. It neither sends fibers to nor receives
DIENCEPHALON fibers from the cerebral cortex, blit has closer
affinity with the hypothalamus ( 173). The
The thalamus is the gateway to the cere- dorsal thalamus, currently referred to simply
bral cortex and , as such , it has evolved phylo- as the thalamus, is by far the largest thalamic
genetically in close parallel with the cerebral division . It has massive and reciprocal con -
cortex. Thus, although present in all verte- nections with the cerebral cortex and striatum
brate groups, the thalamus is most highly de- and comprises most of the nuclei described in
veloped in mammals and especially so in pri - this chapter. The ventral thalamus includes
mates. Virtually all sensory systems pass the reticular nucleus, ventral lateral genicu -
through the thalamus on their way to the late nucleus, the zona incerta , and the nu -
cerebral cortex and, in turn , each part of the cleus of the fields of Forel . The latter two
thalamus receives projections from the corti- structures are often regrouped in what is
cal area to which it projects (173). Our con - known as the subthalamus or subthalamic re-
scious perception of the world around us is gion, which is described in detail in connec-
critically dependent on the information that tion with the basal ganglia (Chapter 19). The
reaches the cerebral cortex to be analyzed ventral thalamic structures, principally the
there, and the thalamus represents a key-link reticular thalamic nucleus, receive inputs
in this process ( 393). As we shall see, the thal - from the ceret> ral cortex, but do not, them-
amus is much more than a passive relay of in - selves, project to the cortex ( 173).
formation to the cortex. It actively filters the
flow of information to the cortex and thus is
MIDBRAIN - THALAMIC JUNCTION
an important neuronal substrate for many
forms of the attention phenomenon (397). Several nuclear masses of the caudal thala-
The thalamus represents the major portion mus closely surround the posterior and lat-
of the diencephalon, which is a nuclear com - eral surfaces of the midbrain . These struc-
plex located at the rostral end of the brain - tures include the medial and lateral geniculate
stem ( 130, 263) ( Figs. 16.1 , 16.2, and 16.6 ). The nuclei and the pulvinar . External to all of these
smaller and most ventral portion of the dien - is the retrolenticular portion of the internal
cephalon is represented bv the hypothala - capsule ( Figs. 16.3, 16.4, and A.12 in the atlas
mus, which is considered in detail in Chapter of the human brain, section VII ). The pineal
17. The thalamus extends caudorostrally gland lies dorsally between the superior colli -
from the region of the posterior commissure culi, while portions of he hypothalamic
to the region of the interventricular foramen . mammillary bodies can be seen in the in -
It is bounded laterally by the posterior limb terpeduncular fossa ( Fig. 16.3). Projections
of the internal capsule, the tail of the caudate from thalamic nuclei pass laterally into the
nucleus, and the stria terminalis ( Figs. 16.4, internal capsule, through which they are dis-
16.6, and 16.7). The third ventricle separates tributed to various parts of the cerebral cor-
the thalamus into two symmetric halves, ex- tex . The internal capsule also contains corti-
cept in the region of the interthalamic adhe- cofugal fibers projecting to thalamic nuclei.
sion ( massa intermedia ) where the medial Thalamocortical and corticothalamic fibers con-
surfaces of the thalami may be in continuity. stitute a large part of the internal capsule re-
The thalamus can be divided on developmen - ferred to as the thalamic radiations ( Fig. 16.39 ).
tal, comparative, and connectional bases into The pulvinar is a large nuclear mass dorsal
(a ) the epithalamus, ( b) the dorsal thalamus to the medial and lateral geniculate nuclei. Its
or thalamus proper, and (c ) the ventral thala- dorsal surface is covered by a thin plate of
mus. The epithalamus is composed princi- fibers, the stratum zonale ( Figs. 16.3-16.3).
pally of the pineal gland and the habenular Fibers passing laterally from this nucleus
633
634 Section VI Forebrain
Stria medullaris
Anterior tubercle
Stria termmalis
Thalamus V Lamina affixa
Tenia
choroidea
Habenula
Pineal Pulvinar
Superior
Colliculus
Inferior
Cerebellar
peduncles
Facial
colliculus
Striae
medullares^ — Hypoglossal trigone
- Area postrema
— Accessory nerve
Twberculum
Gracilis Obex
'- Posterior median sulcus
Figure 16.1 . Posterior aspect of the brainstem with the cerebellum removed to show the epithalamus and the
pulvinar .
contribute to the retrolenticular portion of the commissure is the stalk of the pineal gland, en-
internal capsule ( Figs. 16.3 and 16.39 ). The in- closing the pineal recess of the third ventricle
nermost portion of the internal capsule, ( Fig. 16.4 ). The superior colliculi are replaced
wedged between the pulvinar and lateral by the pretectal region , considered to be a cen-
geniculate body, forms a triangular area ter for the pupillary light reflex ( see Chapter
known as the zone of Wernicke. This zone, 14). The area lateral to the posterior commis-
composed of a mixture of transverse and lon- sure and ventral to the pretectum contains the
gitudinal fibers ( Fig. 16.3), includes the optic nuclei of the posterior commissure ( Fig. 14.10).
radiations and fibers from the pulvinar and Transverse sections through the habenular
the medial geniculate nucleus. nuclei ( Fig. 16.5) reveal the structural organi -
At more rostral levels, the pulvinar is larger, zation of the caudal thalamus. The habenular
the medial geniculate nucleus is smaller, and nuclei are two small gray masses forming tri-
some fibers of the optic tract can be seen enter- angular eminences on the dorsomedial sur -
ing the lateral geniculate body. Lateral to the faces of the thalami . These nuclei receive fibers
pulvinar is the body of the caudate nucleus, mainly from the septal nuclei and the preoptic
separated from the pulvinar by fibers of the area via the striae medullares ( Figs. 2.29, 16.1,
stria terminalis ( Figs. 16.3-16.5). The cerebral 16.2, and 17.14). Some fibers cross to the oppo-
aqueduct expands into the deeper third ventri- site side in the habenular commissure. Axons
cle and the posterior commissure marks the from the habenular nuclei form a well defined -
midline dorsal boundary between midbrain bundle, the fasciculus retroflexus or habenulo-in-
and diencephalon. Superior to the posterior terpeduncular tract , which passes ventrally and
16 Thalamus 635
Anterior nucleus thalamus

Ant commissure
\ Septum pellucidum Mammillothalamic tract
Fornix
Dorsomedial nucleus
Stria medullaris
Habenular nucleus
Posterior commissure
Superior colliculus
Nucleus N HL
v—-— Med long fasciculus
Decussation N EZ-
Optic nerve
Tuber cinereum
/ Ventricle GZ
Mammillary nucleus
Nucleus N TZI
Sup cerebellar peduncle
- Nucleus gracilis
Medial lemniscus
Pyramid
Fasciculus gracilis
Figure 16.2 . Sagittal section of the brainstem and thalamus through the pillar of fornix and root of the third nerve
(Welgert ' s myelin stain).
caudally to terminate in the interpeduncular third ventricle ( Figs. 2.29 and 16.7). In hu -
nuclei. The third ventricle is enlarged ( Figs. mans, the habenula consists of a smaller me-
16.5 and A .13), and its major portion occurs dial and a larger lateral nucleus ( Figs. 16.5
dorsally, where it is covered by a thin roof ex- and 17.14 ). The medial nucleus consists of
tending between the habenular nuclei and the small, closely packed , deeply staining round
striae medullares. The margins of this attach- cells. In the lateral nucleus, the cells are
ment on each side constitute the tenia thalami. larger, paler, and more loosely arranged.
These nuclei receive the terminals of the stria
EPITHALAMUS medullaris ( Figs. 16.2 and 16.7 ) and give ori -
Habenula gin to the habenulo-interpeduncular tract or
fasciculus retroflexus. Fibers arising from the
The epithalamus comprises the pineal medial habenular nucleus course within the
body, the habenular trigones, the striae core of the habenulo-interpeduncular tract
medullares, and the epithelial roof of the and terminate exclusively in the interpedun-
Caudate nucleus Superior colliculus

Cerebral aqueduct
Internal capsule
Central gray
Zone of Wernicke
Brachium of superior
Pulvmar colliculus
Brachium of Lateral
inferior colliculus geniculate body
Crus cerebri Medial

Red nucleus geniculate body
Mammillary body
Substantia nigra
Medial lemniscus
Figure 16.3. transverse section through the rostral midbrain demonstrating relationship of midbrain and caudal por -
tions of the thalamus (Weigert s myelin stain)
Caudate nucleus
Stria termmalis
Forel 's field H
Pretectal area
Interstitial nuc
( Cajal )
Pulvmar
Post thalamic
zone
Medial and
a * eral geniculate bodies
Optic tract '
Substantia mgra
Medial lemniscus
Crus cerebri
Red nucleus
Fasciculus retroflexus
Mammillary body
Figure 16 4. transverse section of the brainstem at the junction of mesencephalon and diencephalon The posterior
nuclear group, which receives collaterals from the spinothalamic tract, lies medial to the medial geniculate body (or
nucleus) This cell group lies caudal to the ventral posterior thalamic nucleus (Weigert s myelin stain)
16 Thalamus 637
Caudate nucleus
Ventrol posterior nucleus
Pulvinar
VPL Fasciculus retroflexus
Centromedian
nucleus
Forel 's field H
Subthalamic
nucleus
Substantia nigra
tract
- Supramammillary commissure
Crus cerebri
Mammillary body
Red nucleus
Tuber cinereum
Infundibulum Infundibular recess

!
Lateral geniculate body
Figure 16.5 . Transverse section of the diencephalon through levels of the habenula, the fasciculus retroflexus. the
mammillary bodies, and the infundibulum. VPL ventral posterolateral nucleus: VPM, ventral posteromedial nucleus;
Pf. parafascicular nucleus (Weigert ' s myelin stain).
cular nucleus. Fibers originating in the lateral nata, and the lateral preoptic area, as well as
habenular nucleus lie predominantly at the from the ventral tegmental area and the mid -
-
periphery of the habenulo interpeduncular brain raphe nuclei ( 140, 216, 290, 295). Be-
tract and terminate in the raphe nuclei , as cause inputs from limbic and basal ganglia
well as in a large region of the reticular structures have been shown to converge
formation adjoining the median raphe nu - upon single neurons in the lateral habenular
cleus ( 141 ) ( Figs. 16.5 and 17.14 ). The stria nucleus of the rat (98 ), the lateral habenular
nwditllaris is a complex bundle composed of nucleus is considered as a functional interface
fibers arising from (a ) the septal nuclei, ( b) the between limbic and motor systems ( 269 ). In
lateral preoptico-hypothalamic region ( 292), primates, however, the pallidohabenular pro-
and ( c) the anterior thalamic nuclei . Some jection is much less prominent than in
fibers of the stria medullaris cross to the op- nonprimates, and it arises from pallidal neu -
posite side in the habenular commissure. rons distinct from those projecting to other
Both the hippocampal formation and the thalamic nuclei ( 322, 324, 326 ). The lateral
amygdaloid nuclear complex project pro- habenular nucleus in the rat has also been
fusely to the septal nuclei, which, in turn , pro- shown to project to the substantia nigra pars
ject to the medial habenular nucleus. Thus, in- compacta ( 141 ) and to receive, in turn , a
puts from structures belonging to the limbic dopaminergic input from neurons of the
system appear to converge onto the medial ventral tegmental area ( 28, 343). The latter
habenular nucleus, whereas inputs to the lat - projection is known as the mesohabenular
eral habenular nucleus are more diversified. dopaminergic pathway (28).
The lateral habenular nucleus receives af - The medial habenular nucleus contains
ferents from the internal segment of the cholinergic neurons ( i.e., group Ch 7 of
globus pallidus ( or the entopeduncular nu - Mesulam et al . ( 260 ) ) that receive afferents
cleus, its homologue in nonprimates), the lat- from posterior parts of the septal nuclei and
eral hypothalamus, the substantia innomi- the midbrain raphe nuclei. Serotoninergic
projections from the midbrain raphe nuclei The pineal gland synthesizes melatonin
and adrenergic innervation from the supe - from serotonin by the action of two enzymes
rior cervical ganglion reach the medial habe - sensitive to variations of diurnal light,
nular nucleus ( 28, 29, 217). Although the N-acetyltransferase and hydroxyindole-O-
habenular nuclei are adjacent to each other, methyltransferase (15, 199). Daily fluctua-
they do not appear to have interconnections. tions in melatonin synthesis are rhythmic and
As a whole, the habenula may be viewed as a in direct response to the daily cycle of photic
site of convergence of limbic forebrain path- input. Light entrains the circadian rhythm to
ways that convey impulses to rostral por - the environmental light cycle (199, 276) and
tions of the midbrain . also acts by an unidentified pathway to
rapidly block the transmission of neural sig-
Pineal Gland nals to the pineal gland ( 200). N-acetyltrans-
ferase activity is elevated during the night,
The pineal gland , or epiphysis , is a small, but exposure to light turns off enzyme activ-
cone-shaped body attached to the roof of the ity (198). Exposure of a rat to constant light
third ventricle in the region of the posterior for 30 days results in a reduction of hydrox-
commissure ( Figs. 16.1 and 16.4 ). It appears yindole-O-methyltransferase and the disap-
as a rudimentary gland consisting of a net- pearance of the rhythm in N-acetyltransferase
work of richly vascular connective tissue con- activity. If animals are blinded , the suppres-
taining glial cells and pinealocytes or epiphysial sive effects of light on hydroxyindole-O-
cells . Pinealocytes in monkeys contain sero- methyltransferase are abolished , but the
tonin and cholecystokinin (CCK ). Mam- rhythm of N-acetyltransferase activity per-
malian pinealocytes are phylogenetically re- sists (15, 199, 273). Bilateral lesions of the
lated to the neurosensory photoreceptor suprachiasmatic nucleus of the hypothala-
elements that become predominantly secre- mus ( Fig. 17.1 ), which receives the retinohy-
tory cells, but they remain indirectly photo- pothalamic tract, abolish the rhythm in pineal
sensitive (9). The mammalian pineal gland is N-acetyltransferase activity, and result in low
regarded as an indirectly photosensitive neu - levels of hydroxyindole-O-methyltransferase
roendocrine organ derived from embryonic activity (198). Such lesions abolish the circa-
neuroepithelium . The pinealocyte has one or dian rhythms of spontaneous locomotor ac-
more processes of variable length which from tivity and of both feeding and drinking ( 286,
ultrastructural studies appear adapted for se- 436). In female rats, the normal estrous cycle
cretory function (248). The club-shaped end - is abolished by lesions of the suprachiasmatic
ings of these processes terminate close to the nuclei ( 286). These studies indicate that pho-
perivascular space surrounding capillaries toregulation of pineal N-acetyltransferase
that have fenestrations. Pinealocytes receive a and hydroxyindole-O-methyltransferase is
direct innervation from sympathetic neurons via the retinohypothalamic tract and suggest
which form recognizable synapses (395). that the suprachiasmatic nuclei are the en-
The best known pineal secretions are the dogenous sources of signals which generate
biogenic amines serotonin, norepinephrine the circadian rhythms in pineal N-acetyl-
and melatonin, but the gland also contains transferase activity and tonically elevate
significant concentrations of identified hypo- hydroxyindole-O-methyltransferase activity
thalamic peptides such as thyrotropin releas- (198). The retinohypothalamic projection al-
ing hormone (TRH ), luteinizing hormone- ters pineal function by directly interacting
releasing hormone ( LHRH ), and somatostatin with structures in the suprachiasmatic nu-
( 248). Serotonin synthesis from tryptophan cleus. Environmental light can be regarded as
involves two enzymes, tryptophan hydroxy- having an entraining function and a trans-
lase and aromatic amino acid decarboxylase, mission function. The effect of light in en-
both of which are found in pinealocytes (197). training the endogenous oscillator to the light
Only the raphe nuclei of the brainstem have cycle is slow, but the effect of light on signal
higher levels of tryptophan hydroxylase. transmission is rapid and probably accounts
Serotonin is synthesized in pinealocytes and for the rapid "turn off " of N-acetyltransferase
released into the extracellular space. Norepi- by light and the blocking of circadian rhythm
nephrine is synthesized in sympathetic neu - by constant light.
rons which terminate on pineal parenchymal Although a single neural pathway from
cells ( 355). the suprachiasmatic nucleus regulates both
16 Thalamus 639
enzymes involved in the formation of mela - amus from the hypothalamus The dorsal.
tonin by the pineal gland , details concerning surface of the thalamus is covered by the stra -
these connections are not known. Indirect ev- tum zonale. At the junction of the dorsal and
idence suggests that the pathway from the medial thalamic surfaces, fibers of the striae
suprachiasmatic nucleus to the pineal in - medullares are cut transversely and appear
volves relays to the tuberal region of the hy- as small bundles of myelinated fibers.
pothalamus, the medial forebrain bundle, The thalamus is commonly divided by the
and spinal pathways that reach the interme- fibers of the internal medullary lamina into
diolateral cell column and cells of the supe- three major nuclear masses that correspond
rior cervical ganglion ( 201, 276, 278). Thus, to the anterior, medial, and lateral nuclear
the pineal gland appears to be a neuroen- groups ( Fig. 2.29 and Table 16.1 ) . The anterior
docrine transducer that converts neural sig- nuclear group of the thalamus forms a rostro-
nals into an endocrine output, melatonin . medial swelling known as the anterior tuber -
Pineal secretions that alter hypothalamic cle and is separated from other thalamic nu -
functions do so after they enter the general clei by a myelinated capsule ( Figs. 16.1 , 16.2,
circulation or the cerebrospinal fluid (86, and 16.8). At slightly more caudal levels, the
248 ). Daily fluctuations in pineal serotonin internal medullary lamina becomes more
and melatonin are rhythmic in response to prominent and contains several cellular ag-
the cycle of photic input. These rhythmic gregates, collectively referred to as the in -
changes in pineal activity suggest that this tralaminar nuclear group. The lateral nuclear
gland functions as a biologic clock delivering mass is further divided into ventral and lat -
signals that regulate both physiologic and be- eral (dorsal ) nuclear groups ( Figs. 16.6, 16.1.3,
havioral processes. Fluctuations, called circa - and Table 16.1 ).
dian rhythms , have a period of exactly 24 The ventral nuclear group, extending
hours in the presence of environmental cues, nearly the entire length of the thalamus, is di -
while in the absence of such cues they only visible into three separate nuclei: (a ) a caudal,
approximate the 24- hour cycle ( 26 ). ventral posterior nucleus ( VP ); ( b ) an intermedi-
Parenchymatous pinealomas are associate, ventral lateral nucleus ; and ( c) a rostral,
ated with depression of gonadal function and ventral anterior nucleus . The ventral posterior
delayed pubescence, while lesions which de- nucleus is subdivided into a ventral postero-
stroyed the pineal frequently are associated lateral nucleus, located laterally, and a ven -
with precocious puberty ( 366). These obser- tral posteromedial nucleus, located medially
vations are consistent with experimental ( Figs. 16.6, 16.11 , 16.1.3, and Table 16.1 ). These
studies indicating that the pineal gland exerts are the ventral tier thalamic nuclei. Caudal to
an inhibitory influence on the gonads and the the VP is the posterior nuclear group, which
reproductive system (86). After the age of 16, includes (a ) the posterior nucleus, ( b ) the lim -
calcareous bodies, consisting of calcium and itans nucleus, and ( c ) the suprageniculate nu -
magnesium phosphates and carbonates, fre- cleus (Table 16.1 ).
quently are present in the pineal gland . These The lateral nuclear group of the thalamus,
calcareous bodies form large conglomera - located dorsal to the ventral nuclear group
tions that often are visible in skull radiogra- discussed earlier, also is divided into three
phy. Identification and measurements of the separate nuclei: (a ) a greatly expanded caudal
position of the pineal gland in skull films can part , the pulvinar; (b ) an intermediate part,
provide useful information , especially in the the lateral posterior nucleus ; and (c) a more ros-
-
diagnosis of space occupying intracranial le- tral part, the lateral dorsal nucleus. ( Figs. 16.12,
sions. 16.13, and Table 16.1 ). These are the dorsal
tier thalamic nuclei.
TOPOGRAPHICAL ORGANIZATION OF The medial nuclear group of the thalamus,
THE THALAMUS located medial to the internal medullary lam -
ina , contains the mediodorsal ( or dorsomedial )
The narrow third ventricle, extending nucleus , a nuclear mass intimately related to
from the region immediately ventral to the the cortex of the frontal lobe ( Fig. 16.6 ).
striae medullares to the optic chiasm , com - Wedged between the dorsomedial nucleus
pletely separates the thalami. A shallow and the ventral nuclei caudally is the centro-
groove on the ventricular surface, the hypo- median nucleus , the largest component of the
thalamic sulcus ( Fig. 16.6), separates the thal - intralaminar nuclear group ( Figs. 16.5, 16.6,
Nucleus
Stratum zonale Nucleus VPM
VPL
Caudate
nucleus Reticular
Putamen
Globus pallidus
\ External
Mammillothalamic tract / Extreme
/ Zona incerta
Fornix /
Thalamic fasciculus
/
Optic tract Subthalamic nucleus
Optic nerve, chiasm

Forel ' s field H
Dorsal supraoptic commissure
Figuie 16.6. Transverse section through the diencephalon and basal ganglia at the level of the optic chiasm Hs indi-
cates the hypothalamic sulcus in the wall of the third ventricle, whereds VPM dnd VPL refer to the ventral posterome-
dial and ventral posterolateral nuclei of the thalamus (Weigert s myelin stain)
16.11-16.13, and Table 16.1 ). The internal the reticular nucleus becomes continuous
medullary lamina partially splits to surround with the zona incerta ( Fig. 16.7), and both
this nucleus. The two halves of the mediodor- structures are believed by some to be part of
sal nucleus are separated by more or less dis- the ventral thalamus ( 173). The medial and
tinct cell clusters which lie in the periventric- lateral geniculate nuclei lie in the caudal por-
ular pray matter of the dorsal half of the tion of the thalamus in a region that is some-
ventricular wall and in the interthalamic ad - times referred to as the melathalamus .
hesion . These nuclei are part of the midline
nuclear group (Table 16.1 ). NUCLEAR ORGANIZATION OF THE
Along the lateral border of the thalamus, THALAMUS
near the internal capsule, is a narrow band of
myelinated fibers, the external medullary lam - The thalamic nuclei, many of which are
ina of the thalamus. Cells located external to microscopic subdivisions, are particularly
these fibers form a thin outer envelope, the difficult to visualize in three dimensions ( Fig.
reticular nucleus of the thalamus ( Figs. 16.6, 16.13). The nomenclature of the thalamus is
16.10, 16.11, 16.13, and Table 16.1 ) . Ventrally, complex, and in some instances the fiber con -
t 16 Thalamus 641
Table 16.1. Classification of Thalamic Nuclei
A . ANTERIOR NUCLEAR GROUP F. VENTRAL NUCLEAR GROUP
Antcrovontivil nucleus ( AV ) R Ventral .interior nucleus ( VA )

.
Antcnxiors il nucleus ( AD ) R parvicellular part ( VApe ) K.
AntcromcJi .il nucleus ( AM ) R si / H
magmxellular part ( VAmc ) K.
B. MEDIAL NUCLEAR ( IROUP SC
Ventral lateral nucleus ( VL )
Dorsomedial nucleus ( DM ) oral part ( VLo ) R
parvicellular part 11 )Mp< i A caudal part ( V i c) K
magmxellular part ( DMme ) SC medial part ( VI m ) R
.
paralaminar part ( DM pi )
Ventral posterior nucleus ( VP ) R
C. MIDLINE NUCLEAR GROUT ventral posterolateral
oral part ( VI ’ LoP ) R
Paratenial nucleus ( pt ) A . SC caudal part ( VPLc ) R
Paraventricular nucleus ( pv ) A . SC ventral posteromedial ( VPM ) R

parvicellular part ( VPMpc ) R
Reunions nucleus ( Re ) A SC. ventral posterior interior ( V PI ) R
Khomhoidal nucleus ( Rh ) A SC.
Median central nucleus ( Me ) A , SC
C , . POSTERIOR NUCLEAR CiROUP
D INTRALAMIN AR NUCLEAR CROUP
Posterior nucleus ( PO )
Centromedian nucleus ( CM ) SC . DC Suprageniculate nucleus ( SCi )
Parafascicular nucleus ( Pf ) SC DC . Limitans nucleus ( LI )
Subparatascicular nucleus ( sPf ) SC

Paracentral nucleus ( Pc ) SC , DC II GENICULATE NUCLEAR GROUP
Central lateral nucleus ( Cl ) SC . DC
Central median nucleus (cm ) SC , F Medial geniculate nucleus ( MGN ) R
parvicellular part ( MGpc ) R
E LATERAL NUCLEAR GROUP

magnocellular part .
( M ( me ) R
dorsal part R
Lateral dorsal nucleus ( LD ) A
Literal posterior nucleus ( LIMA
Lateral geniculate nucleus ( LGN ) R
dorsal part R
Pulvinar ( IMA
ventral part SC
medial part
lateral part
interior part I RETICULAR NUCLEUS | ( RN )
nections and the significance of the smaller jecting to the cortex, receive their input from
thalamic nuclei are unknown . Depending other thalamic nuclei. Since there appears to
upon their connections, most of the major be no foundation for this assertion , he pro-
( principal ) thalamic nuclei can be classified posed that every thalamic nucleus be consid -
either as specific relay nuclei ( R ) or as associ - ered as a relay nucleus (173). This objection is
ation nuclei ( /) ). The specific relay nuclei pro- certainly valid, but the terms association and
ject to, and receive fibers from, well-defined specific nuclei are useful as they allow us to
cortical areas related to specific functions. distinguish between (a ) thalamic nuclei that
The association nuclei of the thalamus do not receive a unimodal and highly specific input
receive prominent inputs from single specific and project to cortical areas that process the
ascending systems, but project to association same type of information , and ( b ) thalamic
areas of the cortex. Other thalamic nuclei nuclei that receive multimodal inputs and
have predominantly, or exclusively, subcorti - project to cortical regions involved in the
cal (SC) connections. Physiologic and ana - complex computation of several types of in -
tomic studies suggest that certain thalamic formation ( association cortices ).
nuclei may have diffuse cortical ( D C ) connec - The classification of thalamic nuclei used
tions. in this chapter is based upon functional and
Jones (173) has questioned the validity and morphologic data drawn from many sources,
usefulness of subdividing the thalamic nuclei but especially from the works of Le Cros
into relay nuclei and association nuclei. He Clark ( 214 ), Walker ( 443, 446, 444 ), Olszewski
aptly pointed out that this subdivision is ( 314 ), Russell ( 381 ), Van Buren and Borke
based , at least in part , upon the erroneous as- ( 435), as well as from more recent investiga -
sumption that association nuclei , though pro- tions ( 173, 304 ). This classification is pre-
Caudate nucleus Corpus callosum

( head )
- Septum pellucidum
Putamen
Internal capsule
Columns Stria terminalis

of fornix S terminal vein
T Stria medullaris
Thalamus "' - Pineal
Inferior horn /
lateral ventricle Superior colliculus
Fimbria of fornix Inferior colliculus

Figure 16.7 . Brain dissection showing gross relationships of the thalamus, internal capsule, basal ganglia, and the
ventricular system
sented in Table 16.1, which regroups the rocally connected . The anteroventral and
major thalamic nuclei into distinct functional anteromedial nuclei are particularly well -
entities, indicates in parentheses the abbrevi- developed in apes and humans (10). Cells
ations most frequently used to designate composing the anterior group nuclei in hu -
these nuclear subdivisions, and identifies by mans are of medium size (average cell vol -
letters in italics specific relay nuclei ( R ), asso- ume 3000 gm1), they have little chromophilic
ciation nuclei ( 4 ), and nuclei with subcortical substance, moderate amounts of yellow pig-
( SC) or diffuse cortical ( DC ) projections. ment , and are surrounded by a capsule of
myelinated fibers.
Anterior Nuclear Group Approximately 25-30% of human anterior
nuclei neurons are interneurons (10). The an -
The anterior nuclear group lies beneath terior nuclei receive both direct and indirect
the dorsal surface of the most rostral part of projections from the hippocampal formation,
the thalamus, where it forms a distinct essentially from the pre- and parasubiculum.
swelling, the anterior tubercle ( Figs. 2.26, The direct hippocampal projection is formed
16.1 , 16.2, 16.8, 16.10, 16.13, A .16, and A .17). It by fibers that leave the fornix as they course
consists of three nuclei : ( a ) the anteroventral through the thalamus, whereas the indirect
nucleus ( AV ), ( b ) the anterodorsal nucleus ( AD), projection is mediated via the hypothalamic
and (c) the anteromedial nucleus ( AM ). These mammillary bodies and the mammillothala -
nuclei can be identified easily in most mam - mic tract ( 222, 352) ( Fig. 16.13B ). Fibers from
mals and their names date back to Nissl ( 302). the medial mammillary nucleus project to the
Their relative development in the different ipsilateral anteroventral and anteromedial
species varies with the development of the nuclei, while the lateral mammillary nucleus
limbic cortical regions to which they are recip - projects bilaterally to the anterodorsal nu -
16 Thalamus 643
Ventral lateral nucleus

Dorsomedial nucleus Anterior nuclear group
Lateral dorsal nucleus Ventral anterior nucleus
Column of Anterior Putamen

Globus pallidus
fornix commissure
Caudate nucleus
Figure 16.8. Asymmetric transverse section through rostral portions of the thalamus and basal ganglia The right side
reveals the most rostral level (Weigert ' s myelin stain)
cleus, but not to other subdivisions of the nu - tions are via the cingulum to the entorhinal
clear group ( 91, 439 ). These observations cortex ( Fig. 18.16 ) ( 357, 358 ). The anterior nu -
were confirmed by fluorescent retrograde clei also receive prominent projections from
-
double labeling techniques, which also indi - various brainstem structures, including the
cate that cells of the lateral mammillary nu - serotoninergic dorsal raphe nucleus and the
cleus project fibers to both the thalamus and cholinergic pedunculopontine and laterodor-
the midbrain tegmentum ( 437). sal tegmental nuclei . These brainstem nuclei
The cortical projections of the anterior nu - innervate several other thalamic nuclei and
clei are to the cingulate gyrus (areas 23, 24, their organization is discussed later in the
and 32) via the anterior limb of the internal section dealing with the chemical anatomy of
capsule ( Figs. 16.14 and 20.10). The an- the thalamus.
terodorsal nucleus sends fibers to the poste- Because of their connections with various
rior cingulate gyrus, including the retrosple - cortical and subcortical limbic areas, the ante-
nial area , while the anteroventral nucleus rior nuclei ( together with the mediodorsal
projects to the middle and posterior cingulate nucleus) are often considered as limbic thala -
cortex (301 ). The anteromedial nucleus pro - mic nuclei (10, 442 ). The functions of the ante-
jects largely to the anterior cingulate cortex, rior nuclei, however, are not known with any
but its diffuse projections extend into the en - degree of certainty. Stimulation and lesion
tire limbic cortex and the orbitofrontal region. experiments in laboratory animals suggest
Although there is considerable overlap, the that the anterior nuclei modulate states of
cingulate cortex receives most of its input alertness and attack, and are also involved in
from the anteroventral and anteromedial nu - memory and learning (10 ). Little is known
clei ( 299). These cortical areas were consid - functionally about the anterior nuclei in hu -
ered to project back to the anterior thalamic mans. Analysis of diencephalic lesions and
nuclei (88, 264 ), but the bulk of the projec - behavioral deficits suggests that the mammil -
lothalamie tract and the anterior nuclei may rostrally and dorsomedially and consisting of
be critical for encoding memory and for sus- fairly large, polygonal, deeply staining cells,
tained attention . Whether the anterior nuclei ( b ) a larger dorsolateral and caudal parvicel-
have a more central role in mnemonic and at- lular portion ( MDpc ) made up of small, pale-
tentional processes than the mediodorsal nu - staining cells that tend to occur in clusters,
cleus is still a matter of controversy ( 10 ). In - and (c) a paralaminar portion ( MDpl , pars
terestingly, the nuclei of the anterior group multiformis ) characterized by very large cells
are believed to undergo marked cell degener- occupying a narrow band adjacent to the in-
ation in cases of Alzheimer's disease, which is ternal medullary lamina ( 10, 69, 173, 211, 227,
characterized by severe memory losses (30). 309, 314, 394 ). The medial magnocellular divi-
sion of the mediodorsal nucleus receives
Medial Nuclear Group fibers from the amygdaloid complex, basal
forebrain, temporal neocortex, and the caudal
Although some authors include paratae- orbitofrontal cortex ( Fig. 16.13) ( 5, 293, 330,
nial and reunions nuclei as members of the 331 , 365, 450 ) . The medial subdivision of the
medial nuclear group ( 173), the mediodorsal mediodorsal nucleus also receives projections
nucleus ( MD ), or dorsomedial nucleus ( DM ), from the piriform cortex, olfactory tubercle,
is by far the most prominent component of as well as direct projections from the olfac -
this group. The mediodorsal nucleus occu - tory bulb ( 173, 203, 227, 353). The caudal or -
pies most of the area between the internal bitofrontal cortex also has connections with
medullary lamina and the periventricular the medial division of the dorsomedial nu -
gray matter ( Figs. 16.2, 16.6, 16.11-16.13A , cleus ( 294 ). Most of these fibers constitute
and A . 16 ). It is the second largest complex in components of the ansa fieduncitlaris, which
the human thalamus; only the pulvinar has consists of the inferior thalamic peduncle
more neurons ( 10 ). Three cytologically dis- ( Fig. 16.9 ), plus fibers interconnecting the
tinct regions of the nucleus are recognized : amygdaloid complex and the preopticohypo-
( a ) a magnocellular portion ( MDmc ), located thalamic region ( 295).
Dorsomedial nucleus
Fornix
Internal capsule
Putamen
Globus pal I idus
Anterior commissure
Mammillothalamic Inferior thalamic peduncle

tract
Fornix
Figure 16.9. Transverse section through the diencephalon and basal ganglia demonstrating fibers of the inferior thal-
amic peduncle This peduncle consists of fibers from the amygdaloid complex, temporal neocortex, and possibly the
substantia mnominata which project to the dorsomedial nucleus of the thalamus. The inferior thalamic peduncle plus
amygdaloid projections to the hypothalamus and preoptic regions constitute the ansa peduncularis (Weigert ' s
myelin stain)
16 Thalamus 645
The amygdaloid afferent projection to the however, indicate that the relationship be-
mediodorsal nucleus, which is not recipro- tween the mediodorsal nucleus and the pre-
cated ( 256 ), is topographically organized . The frontal cortex is not an exclusive one, because
medial basal amygdaloid nucleus makes the the mediodorsal nucleus projects to other
greatest contribution and projects to dorsal areas of the premotor , limbic, and association
portions of MDmc, while the more lateral cortex as well (101 , 110 ). There are reciprocal
amygdaloid nuclei supply the anteroventral connections between the mediodorsal nu -
and central regions of MDmc (5 ). Further- cleus and the granular frontal cortex ( i.e., pre-
more, the medial portion of the mediodorsal frontal cortex ). Particularly profuse reciprocal
nucleus projects to the nucleus basalis of connections exist between area 8 ( i.e., frontal
Meynert in the basal forebrain ( 176 ). One of eye field ) and the paralaminar part of the
the major sources of basal forebrain afferents mediodorsal nucleus ( 7, 211 , 342 ).
to the mediodorsal nucleus is the ventral pal - The results of several behavioral analyses
lidum , which refers to that portion of the pal- are in keeping with those of the tract -tracing
lidum that plunges beneath the anterior com- studies mentioned earlier. Both sets of data
missure within the area of the substantia suggest that the mediodorsal nucleus medi -
innominata ( 120, 460 ). The ventral pallidum ates principally limbic and cognitive
appears to project to large portions of the processes. Lesions within the mediodorsal
mediodorsal nucleus, and this projection is nucleus are reported to decrease the emo-
believed to plav a crucial role in the transfer tional responsiveness of nonhuman primates,
of information from the ventral striatopallidal so that they are placid and do not withdraw
system to the cerebral cortex ( 120, 460 ). The from the human experimenter (104 ). Such le-
ventral striatopallidal system is considered as sions also produce problems in executing
the portion of the basal ganglia more specifi- delayed response tasks, implicating the
cally concerned with limbic types of informa - mediodorsal nucleus with learning and mem -
tion ( 460 ). Recent anatomic investigations, ory ( 4 ). In both human and nonhuman pri -
however, revealed that the ventral pallidal mates, lesions in the mediodorsal nucleus
input to the mediodorsal nucleus is much less result in transient losses of memory, particu -
prominent in primates that it is in rodents larly anterograde amnesia ( 405, 461 ). Hu -
( 121 ). The paralaminar part of the mediodor - mans with lesions confined to the left portion
sal nucleus receives a substantial projection of the mediodorsal nucleus, as confirmed by
from the pars reticulata of the substantia axial tomography scanning, showed a defi -
nigra ( 52, 53, 156 ), and thus can be considered ciency in learning verbal, rather than nonver-
as an additional locus of interaction between bal material ( 405). The verbal nature of the
the mediodorsal nucleus and the basal gan - deficit with a left-sided lesion is of particular
glia . interest in view of Ojeman's demonstration of
The large parvicellular portion of the functional asymmetry in the human thalamus
mediodorsal nucleus is connected by a mas- ( 310 ). In studies involving intrathalamic elec -
sive projection with practically the entire trical stimulation , Ojeman has found that the
frontal cortex rostral to areas 6 and 32 ( Figs. left thalamus is specialized for verbal skills
16.13 and 16.14 ). After extensive prefrontal and the right thalamus for nonverbal skills. It
cortical lesions ( i.e., prefrontal lobotomy ), or is unlikely, however, that this functional
lesions interrupting fibers to this region ( i.e., asymmetry is entirely attributable to the
prefrontal leucotomy ), nearly all small cells of mediodorsal thalamus ( 173).
the mediodorsal nucleus degenerate (88, 241,
264, 394, 444 ). Axoplasmic transport studies Midline Nuclear Group
indicate that cells of the mediodorsal nucleus
project to all parts of the prefrontal cortex The midline nuclei are less distinct cell
( i.e., rostral to the premotor area (area 6) ) in - clusters which lie in the periventricular gray
cluding the cortex on the medial aspect of the matter of the dorsal half of the ventricular
hemisphere and the orbitofrontal cortex ( 427). wall and in the interthalamic adhesion ( Figs.
More specifically, the parvicellular and par- 16.10 and 16.11 ). These nuclei are small and
alamellar parts of the mediodorsal nucleus difficult to delimit in humans, and some are
project to the anterior and posterior dorsolat- included in other thalamic groups ( 173). In
eral prefrontal cortex, respectively, while the nonprimate species, however, these nuclei,
magnocellular part projects to the orbital and together with some of the intralaminar nu -
ventral surface (101 , 110 ). Recent studies . clei, form a significant portion of the thala -
Caudate nucleus
Anterior nucleus
Paraventricular nucleus ^
Reticular nucleus
Dorsomedial nucleus
( DM ) — Ventral lateral nucleus
( VLC )
Midline nucleus '
Paracentral nucleus
Nucleus reumens
( VLO)
Mommillothalamic Subthalamic nucleus
tract
Fornix Nuclei of Forel 's field
Ventromedial nucleus Lateral hypothalamic nucleus

( hypothalamus )
Tuberal nuclei
Figure 16.10. Transverse Nissl- stained section through the diencephalon at the level ot the tuber cmereum showing
nuclei of the thalamus and hypothalamus -
Central lateral
nucleus Caudate nucleus
Paraventricular nucleus
Dorsomedial nucleus Ventral lateral nucleus
¥9. : \
'
( DM ) ( VLC )
Habenular nucleus Reticular nucleus
Midiine nucleus
'
Centromedian nucleus
( CM )
Red nucleus -
Posterior _ Ventral posterolateral
hypothalamic nucleus ( VPL )
nucleus
nucleus ( VPM )
Mammillary
nuclei Subthalamic nucleus
lateral / Parafascicular nucleus
medial Substantia nigra
Figure 16.11. Transverse Nissl-stained section through the diencephalon at the level of the habenular nuclei and the
mammillary bodies showing the nuclei of the thalamus and hypothalamus .
16 Thalamus 647
mus that is sometimes referred to as the paleo - project to the anterior cingulate cortex ( 441 ).
thalamus. Fine myelinated and unmyelinated fibers
The most distinct midline cell groups in - coursing in the periventricular gray matter
clude the paratenial nucleus ( pt ), near the stria are thought to relate these nuclei to the hypo-
medullaris, and the paraventricular nucleus thalamus.
( pv ), in the dorsal ventricular wall ( Fig.
16.10). In an attempt to homologize these ill -
Intralaminar Nuclear Group
defined nuclei with the more developed nu -
clei of nonprimates, some authorities recog- The intralaminar nuclei ( Figs. 16.5, 16.6,
nize several cell groups in this periventricular and 16.10-16.13) are cell groups within the in -
gray matter: (a ) the nucleus reunions ( Re), ( b ) ternal medullary lamina , which separates the
the rhomboidal nucleus ( Rh ), and ( c) the median medial from the lateral thalamic mass. Cells
central nucleus ( Me ). The reuniens, rhom - vary in size in the different nuclei, are
boidal, and median central nuclei all bear fusiform and dark staining, and resemble
close relationships with the interthalamic ad - those of the midline nuclei. They are usually
hesion ( massa intermedia ), when present . regrouped into a rostral division comprising
The latter structure is reported to be absent in the paracentral, central lateral, and central
about 30% of human brains ( 274 ) . Most mid - medial nuclei, and a caudal division com -
line nuclei are composed of small , fusiform, posed essentially of the centromedian and
rather darkly staining cells ( 246 ), and are be- para fascicular nuclei.
lieved to be concerned principally with vis-
ceral activities. Efferent fibers from the para- ROSTRAL INTRALAMINAR NUCLEI
ventricular nucleus, the central nuclear
complex, and the nucleus reuniens, project to The rostral division of the intralaminar nu -
the amygdaloid nuclear complex ( 256 ), as clei comprises (a ) the paracentral nucleus ( Pc),
well as to ventral parts of the striatum ( 22 ). ( b) the central lateral nucleus (Cl ), and (c) the
Some of the midline thalamic nuclei may also central medial nucleus (Cnm ). These nuclei are
Anterior nuclear
group
Lateral dorsal
nucleus
Mediodorsal
nucleus
Anterior Habenula
commissure
— Centromedian
nucleus
Ventral anterior Superior
nucleus colliculus
Mammillothalamic
Optic chiasm Fornix Mammillary body Red nucleus Inferior colliculus

Figure 16.12. Saggitol section through medial parts of the thalamus showing the anterior tubercle (anterior nuclear
group), the mammillothalamic tract, and the fornix . The relationship of the anterior thalamic nuclei to the lateral dor -
sal nucleus may also be appreciated The centromedian nucleus, the largest of the intralaminar thalamic nuclei, lies
ventral to the mediodorsal nucleus (Wiegert ' s myelin stain)
.ill associated vvitli the internal medullary the centromedian nucleus and ventral to the
lamina of the thalamus. The paracentral nu - caudal part of the dorsomedial nucleus ( Figs.
cleus lies in the internal medullary lamina ad - 16.5, 16.11 , and 16.15). The most distinguish-
jacent to the rostral part of the dorsomedial ing feature of the parafascicular nucleus is
nucleus. Cells are large, dark, multipolar, and that its more deeply stained cells surround
grouped into clusters. Caudally , the paracen - the dorsomedial part of the fasciculus
tral nucleus appears to fuse with the central retroflexus ( 446 ). The two major components
lateral nucleus, which borders laterally the of the posterior division of the intralaminar
dorsomedial nucleus ( Figs. 16.10, 16.11 , and nuclei are often considered as a single entity,
16.15). The central lateral nucleus is broader referred to as the centromedian- parafascicu-
than the paracentral nucleus and composed lar (CM - Pf ) nuclear complex.
of similar cells. The central medial nucleus The subparafascicular nucleus is an ill -de-
lies adjacent to the medial part of the para - fined structure that lies between the CM - Pf
central nucleus ( 173, 314, 429). complex and the midbrain tegmentum ( 11 ).
It is partly intercalated within the fiber cap-
CAUDAL INTRALAMINAR NUCLEI sule surrounding the CM - Pf complex, and it
impinges upon this complex at various
The caudal division of the intralaminar points along its rostrocaudal extent . The sub-
nuclei comprises ( a ) the centromedian nucleus; parafascicular nucleus can be divided into
( CM ), ( b ) the innafascicular nucleus ( Pf ), and parvicellular and magnocellular parts occu -
( c ) the subfnirafiisciculnr nucleus ( sPf ). pying, respectively, the lateral and medial
The centromedian nucleus was first identi - sector of the nucleus. Laterally, neurons of
fied in the human thalamus in 1865 by the the parvicellular portion are interspersed
French anatomist Jules Bernard Luys who among fibers of the medial lemniscus and ex-
named it the "centre median" ( or centrum tend between the CM - Pf complex dorsally
medianum ). The term centre median is still and the zona incerta ventrally. Medially,
widely used ( 173), but is currently being re- neurons of the magno-cellular portion of the
placed , at least in the American nomencla - subparafascicular nucleus merge impercepti-
ture, by the name centromedian nucleus. The bly with those of the parafascicular nucleus
centromedian nucleus is the largest and most at various points along the rostrocaudal ex-
easily defined of the intralaminar thalamic tension of the subparafascicular nucleus
nuclei ( Figs. 16.5, 16.6, and 16.13). It is located ( 16.16 ).
in the caudal third of the thalamus between
the dorsomedial nucleus and the ventral pos-
CONNECTIONS AND FUNCTIONAL
terior nucleus ( Figs. 16.5, 16.6, 16.11, and
ORGANIZATION
16.12 ). The centromedian nucleus is almost
completely surrounded by fibers of the inter- The intralaminar nuclei receive a topo-
nal medullary lamina , except along its medial graphically organized input from the cerebral
border, where it merges bv interdigitations cortex. This projection originates principally
with the parafascicular nucleus ( Figs. 16.5, from smaller pyramidal cells of layer V, some
16.11, and 16.15). It is composed of small, of which send a collateral to the striatum
loosely arranged , ovoid or round cells con - ( 380) . Overall, the prefrontal granular cortex
taining a considerable amount of yellow pig- and the limbic cortex on the medial surface of
ment ( lipofuscin ). Cells in the lateral portion the hemisphere project to the paracentral and
of the nucleus are small, while those in more central medial nuclei, the premotor cortex
medial regions bordering the dorsomedial ( area 6 ) to the central lateral and parafascicu -
nucleus are larger and more densely lar nuclei, and the motor cortex ( area 4 ) to the
arranged. There has been considerable con- centromedian nucleus and / or adjacent cen -
troversy concerning precise delimitation of tral lateral nucleus. The somatic sensory and
the centromedian nucleus, particularly with anterior parietal areas project to the posterior
respect to the border separating it from the part of the central lateral nucleus. Few fillers
parafascicular nucleus. According to Mehler reach the intralaminar nuclei from more pos-
( 253 ), only the ventrolateral small -celled re- teriorly and laterally situated areas of the cor-
gion should be identified as the centromedian tex such as the visual and temporal areas (7,
nucleus. 173, 209, 210, 253, 339, 341 ).
The parafascicular nucleus lies medial to The intralaminar nuclei also receive affer-
16 Thalamus 649
Ventral anterior nucleus ( VAmc )

Anterior nuclear group
r— Lateral dorsal nucleus
- Dorsomedial nucleus
'
Pulvinar
Superior colliculus
Inferior colliculus
Superior cerebellar peduncle

Red nucleus
Mammillary body
Mammillothalamic tract
Figure 16.13. Major thalamic nuclei An oblique dorsolateral view of the thalamus and its major subdivisions is shown
in A A transverse section of the thalamus at level of arrows, shown on fhe right in A indicates (a) the relationships be-
tween VPM and VPL. and (b) the location of CM with respect to the internal medullary lamina of the thalamus. In B
the principal afferent and efferent projections of particular thalamic subdivisions are indicated While most cortical
.
.
areas project fibers back to the thalamic nuclei from which fibers are received, not all of these are shown. CM cen-
.
toromedian nucleus DM. dorsomedial (or mediodorsal) nucleus; LD. lateral dorsal nucleus; LP. lateral posterior nu-
.
cleus, VA, ventral anterior nucleus; VLc ventral lateral nucleus pars caudalis; VLo, ventral lateral nucleus pars oralis;
VPL ventral posterolateral nucleus; VPM. vental posteromedial nucleus.
ents from subcortical structures, including cleus, deep layer of the superior colliculus,
the basal ganglia , the cerebellum, the spinal pretectum, substantia nigra, and dorsal raphe
cord , and various parts of the brainstem retic- nucleus (173, 380). The fibers from most of
ular formation. The centromedian nucleus re- these sites appear to arborize rather diffusely
ceives a heavy projection from the internal throughout the intralaminar nuclei.
( medial ) segment of the globus pallidus, and The intralaminar nuclei project heavily
this input is largely made up of collaterals of and in a highly ordered fashion upon the
pallidal fibers terminating in the ventral lat- striatum , and more lightly and diffusely
eral thalamic nucleus (196, 212, 216, 295, 325) upon widespread areas of the cerebral cortex.
( Figs. 16.13, 19.36, and 19.38) . The central lat - Earlier studies have identified the striatum as
eral nucleus and the adjoining part of the the primary target of the CM - Pf complex ( 78,
parafascicular nucleus are major targets of 87, 178, 202, 240, 253, 261, 291, 296, 349, 363,
the deep cerebellar nuclei (13, 49, 138, 254, 388). These thalamostriatal fibers follow a
258, 406, 424 ). Most of the intralaminar nuclei wide curved path through the ventral ante-
also receive fibers from the spinal cord and rior and rostral reticular nuclei of the thala -
the caudal nucleus of the trigeminal nerve, mus, but do not appear to establish terminal
and some of these appear to be branches of connections within the ventral anterior nu -
fibers terminating in the ventral posterior nu - cleus ( 253). Some of these fibers, however,
cleus ( 99, 257). Other afferents arise in the may terminate in portions of the thalamic
reticular formation of the medulla oblongata reticular nucleus (169 ).
and pons, parabrachial nucleus of the pons, More recent studies in primates have
nucleus cuneiformis of the midbrain reticular shown that the thalamostriatal projection is
formation , pedunculopontine tegmental nu - topographically organized and complemen-
tary . The centromedian nucleus projects tex ( 222, 223, 296). Retrograde transport of
specifically to the region of the putamen re- the enzyme horseradish peroxidase ( HRP)
ceiving input from sensorimotor cortices, suggested that thalamostriatal fibers gave rise
while the parafascicular nucleus sends fibers to collateral systems that project to broad cor-
to large sectors of the caudate nucleus inner- tical regions. Electrophysiologic studies,
vated by association cortices (242, 243, 327, however, have shown that neurons in the ros-
382, 383). Additionally, the parafascicular nu - tral intralaminar nuclei do not have such bi-
cleus projects more discretely to the nucleus furcating axons and conduction velocities of
accumbens and the olfactory tubercle, which fibers projecting to cortex and striatum are
represent the limbic portion of the striatum . different ( 412). Likewise, retrograde double-
Therefore, the projections from the centrome- labeling methods reveal that neurons in the
dian and parafascicular nuclei cover the en- caudal intralaminar nuclei projecting to cor -
tire striatum, with those from the centrome- tex are distinct from those projecting to stria -
dian arborizing in the "sensorimotor" striatal tum (382). At CM - Pf levels, neurons project -
territory and the ones from the parafascicular ing to the cortex are mostly confined to the
nucleus terminating in the "associative-lim- lateral aspect of the CM, while those project -
bic" striatal territory ( 382). Furthermore, the ing to the striatum are more numerous and
CM - Pf complex sends fibers to other compo- centrally located in CM ( Fig. 16.16 ).
nents of the basal ganglia , namely the sub- This intralaminocortical projection is prin -
thalamic nucleus, globus pallidus, and sub- cipally concentrated in frontal, medial, and
stantia nigra , where they also terminate in a dorsolateral cortex, although cells can be ret -
complementary fashion . The subparafascicu - rogradely labeled from virtually every corti -
lar nucleus gives rise to both ascending and cal area , including that of the piriform lobe
descending projections, the former terminat - and occipital pole ( 173). Although projecting
ing in various limbic forebrain areas, includ - rather widely upon the cerebral cortex, each
ing the substantia innominata , the amygdala , intralaminar nucleus appears to have a par -
and the hypothalamus, and the latter arboriz- ticular region upon which most of its cortical
ing in different brainstem structures, particu - projection is focused ( 242, 243). Thus, the
larly the inferior olivary nucleus ( Fig. 16.16 ). - -
intralaminar nudeus to cortex projection can -
Thus, each component of caudal intralaminar not be regarded as totally diffuse or non-
nuclei appears to be involved in different, but specific (173, 412 ). The topography of the
complementary, aspects of the basal ganglia intralaminocortical projection conforms to
function . the pattern of "nonspecific" thalamocortical
Neurons of the anterior intralaminar nu - connections demonstrated earlier following
clei, as well as neurons scattered on each side electrical stimulation of the intralaminar or
of the internal medullary lamina within the midline nuclei (71, 72, 164, 285, 408). These
territories of the medial, lateral, and ventral connections were thought to be part of a dif -
nuclear groups, also participate in the thala - fuse cortical activating system that mediates
mostriatal projections ( 327, 380, 382 ). The in - the cortical recruiting response via axons termi -
tralamino-striatal projections terminate in a nating in layer I of the cerebral cortex ( 234 ).
highly patchy manner . Thalamofugal fibers The recruiting response is a surface negative
arborize profusely in the matrix compartment response evoked by repetitive low frequency
of the striatum, and much less in the strio- stimulation of the midline, intralaminar, and
some or patch compartment (383). The thala- ventral anterior thalamic nuclei that waxes
mostriatal fibers terminate principally on the and wanes and can be recorded over broad
dendritic shafts of the medium spiny projec- areas of the cerebral cortex . The question of
tion neurons located in the extrastriosomal the laminar site of termination of the in -
matrix of the striatum (383). tralaminocortical fibers is still unresolved .
The intralaminar nuclei of the thalamus Some data obtained from cats suggest that
were long regarded as having no cortical pro- these fibers terminate exclusively in layer 1
jections. This conclusion is based on the ab- (170), while other findings in rats point to
sence of retrograde cell changes in these layer VI as their main target ( 139 ).
nuclei following virtually complete decortica - The intralaminar thalamic nuclei show a
tion ( 62, 348, 394, 445, 446) and the absence of striking development in human and nonhu -
degeneration traceable from lesions in the man primates, in relation to thalamic relay
centromedian nucleus to any part of the cor- nuclei, suggesting that they constitute a com -
16 Thalamus 651
-
plex intrathalamic regulating mechanism LATERAL POSTERIOR NUCLEUS
concerned with diverse functions. The in -
This nucleus lies caudal, lateral, and ven-
tralaminar thalamic nuclei have been consid -
ered to serve as the thalamic pacemaker, con - tral to the lateral dorsal nucleus ( Figs. 16.13
and 16.22 ), and is composed of medium -sized
trolling in a state-dependent manner the
electrocortical activities. For example, in re- cells evenly distributed . This irregularly
laying activity from the midbrain reticular shaped nucleus lies dorsal to the ventral pos-
terolateral nucleus and adjacent to the lateral
formation to the cerebral cortex, the rostral
intralaminar nuclei play an important role in medullary lamina . Caudally, the nucleus
processes that characterize wakefulness and merges with the oral and medial parts of the
pulvinar, from which it is not easily distin -
desynchronized sleep. The posterior in
tralaminar nuclei ( i.e., the large CM-Pf com -
- guished (314 ). Unlike the lateral dorsal nu -
cleus, it has no myelin capsule. The input to
plex ) appear more closely related to motor
functions in that they receive inputs from the this thalamic nucleus is similar to that of the
motor and premotor cortex and from the pulvinar, and both structures are often con -
sidered as a single functional entity ( 173). In
globus pallidus, and , in turn , project to
the striatum . The intralaminar nuclei are be- the cat, the lateral posterior nucleus receives
lieved to also be involved in the processing of inputs from the superficial layers of the supe-
rior colliculus, the pretectal region, and from
diffuse sensory inputs, particularly those per-
the superior and inferior parietal lobules ( 112,
taining to pain .
187, 342, 373, 434 ). Some of these thalamic
neurons appear to have reciprocal cortical
Lateral Nuclear Group connections. Retrograde transport studies in -
The lateral nuclear group begins as an dicate that the lateral posterior nucleus pro-
jects to areas 5 and 7, as well as to various
oblique narrow strip on the dorsomedial sur-
face of the thalamus caudal to the anterior cortical regions involved in the processing of
visual information ( 173, 334 ).
nuclear group. This group consists of three
nuclear masses arranged in rostrocaudal se-
quence: ( a ) the lateral dorsal nucleus ( LD ), ( b) PULVINAR
the lateral posterior nucleus ( LP), and ( c) the
pulvinar ( P) ( Figs. 16.12 and 16.13). This large nuclear mass, forming the most
caudal portion of the thalamus, overhangs
LATERAL DORSAL NUCLEUS the geniculate bodies and the dorsolateral
surface of the midbrain ( Figs. 16.3-16.5 and
This nucleus, which lies on the dorsal sur- 16.13). Because the pulvinar exhibits consid -
face of the thalamus, extends along the upper erable cytologic uniformity, it is subdivided
margin of the internal medullary lamina and on a topographic basis into four parts: (a ) a
is surrounded by a myelin fiber capsule, simi - pars oralis, located between the ventral pos-
lar to that of the anterior nuclear group ( Fig. terolateral and centromedian nuclei, ( b) a
16.12). The nucleus achieves its largest size pars inferior, located ventrally between the
dorsal to the paracentral and central lateral medial and lateral geniculate bodies, (c) a
nuclei ( Figs. 16.8, 16.13, and 16.15) and some- pars medialis forming the medial half of the
times is considered as a posterior extension of pulvinar, and (d ) a pars lateralis extending
the anterior nuclear group ( 173, 232, 449 ). along the external medullary lamina which is
While many authors believe that this nucleus traversed by fibers ( 314 ). The basic element of
sends fibers to the posterior parietal cortex the pulvinar is a lightly stained , medium -
( Fig. 16.13), recent data indicate that the lat- sized , multipolar cell, whose density and pat -
eral dorsal nucleus projects mainly to poste- tern of arrangement varies in the different
rior parts of the cingulate gyrus. It also sends subdivisions. Cells in the oral division of the
fibers to the supralimbic cortex of the parietal pulvinar are small , light -staining, and loosely
lobe ( 173, 233, 297, 299, 438). Although af - arranged . The pars inferior, separated from
ferent fibers to this nucleus are poorly under- the main body of the pulvinar by fibers of the
stood , it is believed that the lateral dorsal brachium of the superior colliculus, is com -
nucleus receives inputs that are similar to posed of large dark-staining cells scattered
those terminating in the anterior thalamic among medium -sized elements. The lateral
nuclei (173). pulvinar is traversed by oblique fiber bundles
extending from the external medullary lam - medial and lateral geniculate bodies together
ina and among which small cells are scat - constitute the geniculate nuclear group or
tered . The medial nucleus contains evenly metathalamus, these well-defined nuclear
distributed medium -sized cells and very few masses may be considered as a caudal contin -
fibers. uation of the ventral nuclear group ( Figs.
The nuclei of the pulvinar do not receive 16.3, 16.4, and 16.13). The ventral and genicu -
inputs from long ascending sensory path - late nuclear groups constitute the largest di -
ways, but the inferior division receives a pro- vision of the thalamus concerned with relay-
jection from the superficial layers of the supe- ing impulses from other portions of the
rior colliculus ( 19, 128, 330 ). Topographically, neuraxis to specific parts of the cerebral cor-
this projection represents the contralateral vi - tex . Caudal parts of this complex are con -
sual field , with the lower visual field lying cerned with relaying impulses of specific sen-
dorsomedially and the upper field ventrolat- sory systems to cortical regions, while more
erally . Both the inferior pulvinar and the ad - rostral nuclei ( ventral anterior and ventral
jacent portion of the lateral pulvinar have reci - lateral nuclei ) relay impulses from the basal
procal connections with occipital cortex, ganglia and cerebellum.
including striate cortex ( 173, 307, 434 ). The in -
ferior pulvinar and the adjacent lateral pul - VENTRAL ANTERIOR NUCLEUS
vinar each contain a representation of the
contralateral visual hemifield and project This thalamic nucleus occupies the ex-
retinotopically on (a ) cortical areas 18 and 19, treme rostral part of the ventral nuclear
where fibers end in layers IV , III and I ( 20 ), group and is bounded anteriorly and ventro-
and ( b ) the striate cortex (area 17), where laterally bv the thalamic reticular nucleus
fibers terminate upon the supragranular lay- ( Fig. 16.13) . Rostrally the ventral anterior nu -
ers ( 367 ). In contrast, the dorsal lateral genic- cleus occupies the entire thalamic region lat -
ulate nucleus projects retinotopically largely eral to the anterior nuclear group ( Fig. 16.8),
upon the striate cortex ( area 17) , where fibers but caudally it becomes restricted to a more
end upon cells in layer IV . These findings in - medial region . The mainmillothalamic tract
dicate three visuotopically organized inputs passes through the ventral anterior nucleus
—
from the thalamus the lateral geniculate nu - but does not form its medial border. The nu -
cleus, inferior pulvinar, and adjacent lateral cleus is composed of large and medium -sized
—
pulvinar to the primary visual cortex that multipolar cells arranged in clusters. The
terminates upon different layers. Projections clustering of cells is particularly evident in
from the inferior pulvinar to cortical areas 17, rostrolateral parts of the nucleus where thick
18, and 19 constitute the final link in an extra - myelinated fiber bundles course longitudi-
geniculate visual pathway. nally within the nucleus.
The lateral nucleus of the pulvinar (other Parts of the nucleus adjacent to the mam-
than that portion adjacent to the inferior pul - millothalamic tract and along the ventral bor-
vinar ) projects to the temporal cortex and re- der of the nucleus are composed of large,
ceives reciprocal projections from the same dark, densely arranged cells. This subdivi-
region ( 398, 399, 432 ). The medial pulvinar sion , called the magnocellular part ( VArnc)
appears to project to the superior temporal ( 314 ), extends further caudal than the princi-
gyrus and to the inferior parietal lobule (126). pal part of the ventral anterior nucleus
( VApc). Thus, there are two distinctive cyto-
Ventral Nuclear Group logic subdivisions of the ventral anterior nu -
cleus. Each of these subdivisions receives
The ventral nuclear group of the thalamus fibers from different sources without overlap.
is composed of three nuclei: (a ) the ventral an - The principal part of the nucleus is inner-
terior nucleus ( VA ) , ( b) the ventral lateral nu - vated by fibers from the internal segment of
cleus ( VL ), and ( c) the ventral posterior nucleus the globus pallidus, while the magno-
( VP). The ventral anterior nucleus is the most cellular part receives input from the substan -
rostral and the smallest nucleus of this group. tia nigra ( 159 ) .
The ventral posterior nucleus, the largest and Afferent fibers from the medial segment of
most posterior nucleus of the group, is fur- the globus pallidus ( Figs. 19.36 and 19.38)
ther subdivided into the ventral posterolat - reach the nucleus via the lenticular fasciculus
eral and ventral posteromedial nuclei ( Figs. and ansa lenticularis ( 131, 196, 216, 295, 318,
16.11 , 16.13, 16.15, and 16.21 ). Although the 324, 361 , 387). These fibers enter the thalamic
16 Thalamus 653
Central sulcus
Lateral sulcus
Lateral surface
Central sulcus
Parieto -
occipital
sulcus
Calcarine sulcus
Medial s u r f a c e
Figure 16.14 . Left cerebral hemisphere showing the cortical projection areas of thalamic nuclei The color code is the
same as in Figure 16.13. The diffuse projection of the ventral anterior nucleus (VApc) to the frontal lobe appears to
largely overlap the projection of the dorsomedial nucleus (DM) Information concerning the cortical projection areas
of some thalamic nuclei is incomplete
fasciculus, turn dorsolaterally, and are dis- ( VLo ). In nonhuman primates, most pallidal
tributed in a rostrolateral direction within the fibers that arborize in the ventral nuclear
ventral anterior nucleus. Pallidothalamic group were shown to be collaterals of those
fibers projecting to the rostral ventral tier that project to the centromedian nucleus and
thalamic nuclei ( i.e., VApc and VLo) appear the brainstem pedunculopontine tegmental
organized in a specific manner (50, 212). Ros- nucleus ( 324 ). Furthermore, up to 20% of the
tral parts of the medial pallidal segment pro- pallidothalamic fibers cross the midline at the
ject most profusely to VApc. More caudal level of the central medial nucleus and ar-
parts of the medial pallidal segment project borize within the contralateral ventral ante-
fibers to parts of the ventral lateral nucleus rior nucleus according to a pattern similar to
t v» / , tn
m:
&
i ..
i •.
^ 4-
>< \
& .:
v
,.Av
Figure 16.15. Transverse section of the thalamus through the ventrobasal complex and the intralaminar nuclei in a
monkey CL central lateral nucleus. CM. centromedian nucleus: LD. lateral dorsal nucleus; MD. mediodorsal nucleus.
PF. parafascicular nucleus; pv . ventral paralaminar part of dorsomedial nucleus; VPI. ventral posterior inferior nucleus.
VPL ventral posterolateral nucleus: VPM. ventral posteromedial nucleus; VPMpc, parvlcellular part of VPM Arrows on
superior border of the internal medullary lamina define limits of pv . Numbers refer to animal and sequential section
(cresyl violet. x 22).
one observed ipsilaterally ( Fig. 16.17 ) ( 131, about groups of cells in the niagnocellular
158, 289, 324 ). Despite the fact that most of part of the ventral anterior nucleus.
them originate from the same neurons in the Cortical area 6 projects primarily to the
internal globus pallidus, pallidothalamic principal part , while fibers from area 8 termi-
fibers display significantly different patterns nate in the magnocellular part of the ventral
of arborization within the different thalamic anterior nucleus ( 210, 211 ). Fibers from the
territories. Pallidal fibers in the ventral ante- primary motor area do not reach any part of
rior nucleus form several characteristic the nucleus ( 209 ).
-
glomerulus like terminal fields, while those Information concerning the efferent pro-
in the centromedian course in a more linear jections of the ventral anterior nucleus is in -
fashion giving off only a few thin collaterals complete and conflicting ( 16, 47, 87, 317, 348,
throughout the nucleus ( 131 ) ( Fig. 16.18). 446, 457). Efferent fibers from this nucleus are
Pallidal fibers reaching the habenula form a distributed to widespread areas of the frontal
dense field composed of numerous thin and cortex (195). Rostrally projecting cells in the
closely packed terminals, while those reach - magnocellular part of the ventral anterior nu -
ing the brainstem pedunculopontine tegmen - cleus have been described as terminating in
tal nucleus remain poorly branched (131 ). localized regions of the caudal and medial or-
The niagnocellular part of the ventral ante- bital cortex ( 47, 387).
rior nucleus receives a significant fiber projec- Results from pioneering electrophysio-
tion from the substantia nigra ( 3, 50, 52, 54, logic studies ( 165, 166, 407) indicate that the
60, 84, 156, 157). Nigrothalamic fibers arise ventral anterior nucleus may be functionally
from the pars reticularis, pass medially and related to the intralaminar nuclei of the thala -
rostrally through Forel 's field H, and follow a mus in that recruiting responses in wide-
course parallel to that of the mammillothala- spread cortical areas can be evoked by re-
mic tract ( Figs. 16.2 and 16.9) (50, 53). Ni - peated low frequency stimulation of the
grothalamic fibers form a dense terminal felt nucleus. Other authors demonstrated that the
16 Thalamus 655
MOTOR & PREMOTOR FRONTAL EYE FIELDS, PREFRONTAL,

CORTICES PREMOTOR & CINGULATE CORTICES
ASSOCIATIVE -LIMBIC
L < L
SENSORIMOTOR
STRIATUM I
t i
STRIATUM
GPe (caudal 2/3) GPe (rostral 1/3)

GPi (lateral) GPi (medial)
STN (caudolateral) GPv
SNr STN (rostromedial)
THALAMUS SNr, SNc, VTA
SI
HYPOTHALAMUS
THALAMUS
ZONA INCERTA
FOREL'S FIELDS
PVG
AMYGDALA
HYPOTHALAMUS
SI
BRAINSTEM
LIMBIC
STRIATUM
Figure 16.16. Output organization ot the centromedian-parafascicular-subparafascicular (CM-Pf -sPf) complex in pri-
mates The major efferent projections are indicated by uninterrupted lines, whereas broken lines represent less promi-
nent projections, Cross-hatched regions in the CM-Pf -sPf complex indicate areas of overlap of cells bearing efferent
characteristics of CM. Pf. or sPf .
ventral anterior nucleus is essential for the re- VENTRAL LATERAL NUCLEUS
cruiting response and that lesions in this nu -
cleus block the responses elicited by the stim- This nucleus, caudal to the ventral anterior
ulation of the intralaminar thalamic nuclei nucleus, is composed of small and large neu -
(400). The ventral anterior nucleus appears to rons that show considerable differences in
be the preeminent site among thalamic nuclei various parts of the nucleus ( Figs. 16.10 and
for production of the recruiting response. 16.11 ). It has been subdivided into three main
I CORTEX | CORTEX
Figure 16.17 . Crossed and uncrossed pallidothalamic fibers The number of contralaterol fibers amounts to approxi-
mately 20% of the ipsilateral fibers These fibers arise from the internal segment of the globus pallidus (GP/ ) and termi-
nate within specific regions of the ventral anterior ( VA) and ventral lateral ( W.) thalamic nuclei. In turn VA /VL neurons
project to the cerebral cortex. Also shown is a decussating fiber from one neuron in the reticular thalamic nucleus
( /?N) The location of the external segment of the globus pallidus (GPe) is indicated
parts ( 314 ): (a ) pars oralis ( VLo), ( b) pars cau- nal pallidal segment project to the ventral lat -
dalis ( VLc ), and (c) pars medialis ( VLm ). The eral nucleus of the thalamus via the thalamic
pars oralis is the largest subdivision and fasciculus. The major pallidal projection is to
consists of numerous deep-staining cells VLo and the lateral part of VLm ( 50, 159, 196,
arranged in clusters. The pars caudalis is 212, 295). Pallidofugal fibers also project ros-
composed of a smaller number of scattered trallv to ventral anterior nucleus ( VApc) and
large cells. The pars medialis begins ventral give off collateral fibers to the centromedian
to the ventral anterior nucleus and extends nucleus (CM ) ( Figs. 19.37 and 19.38). These
caudally toward the subthalamic region . A pallidal projections are topographically orga -
crescent-shaped thalamic area in nonhuman nized (50, 52, 53, 196, 212, 431 ).
primates caudal to VAmc and medial to VLo, Efferent fibers, originating in the deep
designated as "area x" (314), appears, on the cerebellar nuclei and ascending beyond the
basis of connectivity, to be an integral part of contralateral red nucleus, enter the thalamic
the ventral lateral nuclear complex ( 47, 254, fasciculus and project to nuclei composing
337, 338). Nuclear subdivisions designated as the "cell-sparse" zone of the ventral lateral
VLc, "area x," and the oral part of the ventral thalamus ( VLc, VPLo, and area x ) ( 50, 56, 138,
posterolateral nucleus ( VLI’o ) have been re- 191, 254, 265, 406 ). Single-unit recordings
ferred to as the "cell-sparse" zone, and cyto- have not revealed a sharp somatotopic orga-
logically are distinct from VLo, VPLc, and nization within the deep cerebellar nuclei,
VPM . A recent investigation indicates that but thalamic nuclei receiving these efferents
the various subdivisions of the ventral lateral have a somatotopic representation similar to
nucleus disclosed in monkeys are largely that of thalamic somatosensory relay nuclei.
valid for the ventral lateral thalamic mass in Different parts of the body are systematically
humans (145). represented with rostral body regions medial
Pallidofugal fibers arising from the inter- and caudal parts of the body lateral. The ex -
16 Thalamus 657
able number of fibers from the precentral cor-

tex ( 214, 224, 230, 262, 440 ). Studies in mon -
keys demonstrate that area 4 projects to VLo,
VLc, and VPLo, as well as to the centrome-
dian, the paracentral nucleus, and the central
lateral nucleus ( 14 , 114, 204, 334, 340, 341 ,
368). The projection from area 4 to VLc is not
as impressive as that from area 6, which also
projects to "area x" ( 210 ). A systematic analy -
sis indicates that the "cell-sparse" zone of the
ventral lateral thalamic region, consisting of
VPLo and VLc, projects topographically upon
area 4. Medial parts of the zone send fibers to
the face area , lateral parts send fibers to the
leg area , and fibers from intermediate por -
tions of the zone pass to cortical regions rep-
resenting the arm and trunk ( 143, 418, 443,
447) ( Fig. 16.14 ). Thus, the thalamic termina -
tion zones for the dentate, interposed, and
fastigial nuclei are nearly identical and relay
impulses to the primary motor area . The cor -
tical projection zone for the VLo, which re-
ceives input from the internal pallidal seg-
ment , appears different in that VLo projects
to the supplementary motor area and the lat -
eral premotor area ( 167, 384 ). The distinctive
cytoarchitectural subdivisions of the ventral
lateral thalamic region project to separate cor-
tical areas concerned with different aspects of
motor function .
VENTRAL POSTERIOR NUCLEUS

The ventral posterior nucleus ( VP), whose
M cells are among the largest in the thalamus, is
composed of two major divisions, the ventral
Figure 16 18 . Darkfield photomicrographs comparing
two forms of terminal arborizations of pallidothalamic
posteromedial nucleus ( VPL ) and the ventral
fibers that were anterogradely labeled with the lectin posterolateral nucleus ( VPM ), and a smaller in -
Phaseolus vu/gans-leucoagglutinin (PHA -L) in the squirrel termediate division , the ventral posterior infe-
monkey A and B. Terminal arborizations in the form of rior nucleus ( VPI ) ( Figs. 16.6, 16.11, 16.13, and
glomeruli in the ventral lateral thalamic nucleus. C. Nu- 16.15). The VP is the largest primary somatic
merous thin fibers forming a dense and relatively homo-
geneous terminal field in the centromedian nucleus The sensory relay nucleus of the thalamus and is
arrow indicates the habenulo-interpeduncular tract. referred to as the ventrobasal complex.
Scale bar 200|im ( A) and 360 urn (B. C)
VENTRAL POSTEROLATERAL NUCLEUS
tremities are represented ventrally. Although This nucleus has been subdivided into a
dentatothalamic and interpositothalamic fi- pars oralis ( VPLo ), characterized by very
bers appear to end in the same region, ter- large, sparsely distributed cells, and a pars
minations are in an interdigitating pattern caudalis ( VPLc), containing large, evenly dis-
without overlap. Fastigiothalamic fibers are persed cells and a high density of small cells.
bilateral with fibers crossing the region of the Both divisions of the nucleus contain
posterior commissure and / or the internal medium-sized fiber bundles radiating in an
medullary lamina of the thalamus ( 158). oblique dorsal direction .
The ventral lateral nucleus of the thalamus As described earlier, VPLo constitute a
has long been known to receive a consider- distinctive part of the "cell -sparse" zone of
the ventral thalamic region, which receives lamellae related to neighboring body parts
inputs from the contralateral deep cerebellar ( 173, 187). Lamellae representing large divi-
nuclei and projects to the primary motor sions of the body contain labeled axons aris-
cortex. ing from cell groups in the dorsal column nu -
Thalamic inputs to VPLc convey somes- clei that are in register with retrogradely
thetic impulses from the spinal cord and so- thalamic neurons projecting to corresponding
matosensory relay nuclei in the medulla via regions of the somesthetic cortex. Representa -
( a ) the medial lemniscus, and ( b) the tion of the body in VP is continuous, but dis-
spinothalamic tracts ( 24, 35-37, 220, 251 , 257, torted in a fashion that reflects the greater in -
3h4, 446, 452 ). Fibers of the medial lemniscus nervation density of receptors in peripheral
course through the brainstem, without sup- parts of the extremities and in the oral region.
plying collateral or terminal fibers to the The distribution of individual, medial lemnis-
reticular formation, and terminate exclu - cus axons in the VPLc suggests that all axons
sively in VPLc ( Fig. 18.13) ( 32, 191, 431 , 452 ). have terminal ramifications at one level, are
Fibers arising from the nucleus gracilis termi - focal, and none are sufficiently long to oc-
nate lateral to those of the nucleus cuneatus cupy more than one-half of the anteroposte-
( 191 , 220, 431 , 440, 452 ). Terminals of the me- rior extent of the nucleus. Terminal ramifica -
dial lemniscus establish predominantly axo- tions are compressed into narrow sagittal
dendritic contacts throughout VPLc. slabs 200-300 p.m wide. Axonal ramifications
Results from single- unit recording studies end in either an anterodorsal shell or in the
in VP in a large number of species ( 287, 288, central core of VPLc. Cells in the anterodorsal
377, 378, 345, 340 ) have revealed somatotopic shell respond to stimulation of deep tissue
features in which the contralateral limbs, and largely terminate in cortical areas 3b and
trunk, and tail are represented in VPLc, and 1 (80, 171 , 173, 174, 177, 185, 188 ).
the head , face, and intraoral structures in The spinothalamic tracts form a far less
VPM ( Fig . 10.19 ). Each large body part is rep- discrete ascending sensory pathway than the
resented by a curved lamella with adjacent medial lemniscus. The spinothalamic tract,
Deep
structures
Cutaneous
Figure 16.19 . Ventrobasal complex in the monkey indicating the cutaneous somatotopic representation ot the body
surface on the left Neurons responsive to stimulation of deep receptors lie in a dorsal shell. Areas representing the
head. face, and tongue lie in the ventral posteromedial nucleus ( VPM) The body is represented in the ventral pos-
.
terolateral nucleus pars caudalis ( VPLc ) with the trunk dorsal and the extermities ventral Nuclear subdivisions of the
thalamus are shown on the right . CM, centromedian nucleus. CN, caudate nucleus, 1C. internal capsule. LD. lat-
erodorsal nucleus. MD. mediodorsal nucleus; VLc. ventral lateral nucleus, pars caudalis; VPI, ventral posteroinferior nu-
cleus.
16 Thalamus 659
and fiber systems ascending with it, con- Secondary gustatory fibers arising from
tributes a large number of projections and the nucleus solitarius ascend ipsilaterally in
collaterals to the brainstem reticular forma - the central tegmental tract to terminate in
tion at all levels. VPMpc ( 18) ( Figs. 16.21 ). The VPMpe also re-
Physiologic studies indicate the precise ceives indirect ipsilateral gustatory fibers via
and orderly fashion in which the contralat- a relay in the parabrachial nuclei of the brain -
eral body is represented in VPLc and the stem ( 304, 305 ).
spinothalamic tracts. There is a complete,
though distorted, image of the body and vol - VENTRAL POSTERIOR INFERIOR NUCLEUS
ume representation of a given part of the
body is related to its effectiveness as a tactile This smallest subdivision of the ventral
organ ( i.e., to its innervation density ). Cervi - posterior nucleus lies ventrally between VPL
and VPM ( Fig. 16.15). The ventral border of
cal spinal cord segments are represented
most medially and sacral segments most lat- the nucleus is adjacent to the reticular nu -
erally. The thoracic and lumbar regions are cleus and the thalamic fasciculus. Cells of the
represented only dorsally, while the regions nucleus are medium-sized and light-staining.
concerned with the distal parts of the limbs Inputs to VPI are not fully understood , but
extend ventrally. Each neuron of this com - cells in this nucleus appear to provide the
plex is related to a restricted , specific, and un - major projection to somatic sensory area II (S-
changing receptive field on the contralateral II ). It has been suggested that a population of
side of the body . The neurons are regarded as sensory neurons of VP with projections to S- ll
place specific, modality specific, and con- become progressively segregated in VPI .
cerned almost exclusively with the percep-
tion of tactile sense and position sense ( kines- CORTICAL CONNECTIONS OF THE VENTRAL
thesia ). Only a few cells of VP appear to be POSTERIOR NUCLEUS
activated by noxious stimuli .
The ventral posterior nucleus has a precise
topical projection to the cortex of the postcen -
VENTRAL POSTEROMEDIAL NUCLEUS
tral gyrus ( 204, 224, 226, 446 ) ( Figs. 16.13 and
This crescent-shaped nucleus with a rela - 16.14 ). Portions of the gyrus high on the lat-
tively light-staining neuropil lies medial to eral convexity receive fibers from VPLc,
VPL and lateral to the curved boundary of while inferior portions of the gyrus near the
the centromedian nucleus ( Figs. 16.5, 16.6, lateral sulcus are supplied by fibers from
16.11, 16.13, and 16.15). The ventral postero- VPM ( 118, 180, 182-184 ). This thalamocortical
medial nucleus ( VPM ) consists of two distinct projection forms a large part of the superior
parts: (a ) a principal part composed of both thalamic radiation . Neurons in the large cen-
small and large cells, designated simply as tral core of VPLc, responsive to cutaneous
- -
VPM, and ( b) a small celled , light staining stimuli , project to cortical area 3b on the pos-
part , which occupies the medial apex of this terior surface of the central sulcus and to area
-
arcuate shaped nucleus, referred to as the 1 on the lip of the sulcus. Cells in the thinner
pars parvicellularis ( VPMpc ). The principal peripheral shell of VPLc, responsive to stimu -
part of VPM receives somatic afferent fibers lations of deep tissues, project to cortical area
from receptors in the head , face, and intraoral 3a in the depths of the central sulcus and to
structures, while VPMpc is concerned with area 2, which forms the posterior part of the
taste ( Fig. 16.21). Ascending secondary postcentral gyrus ( Fig. 16.20). Collectively,
trigeminal fibers terminating in VPM include VPLc and VPM project somatotopically upon
(a ) crossed fibers from the spinal and princi- the primary somesthetic cortex with a modal -
pal sensory trigeminal nuclei, which ascend ity segregation. Cells of VPMc that receive as-
in association with the medial lemniscus ( 51 ), cending gustatory fibers project upon the
and ( b) uncrossed fibers of the dorsal trigemi - parietal operculum, area 43. Study of the pro-
nal tract ( 43, 48, 430), originating from the cessing of somatosensory information in the
dorsal part of the principal sensory nucleus brain has led to the important concept of par
of the trigeminal nerve. Tactile impulses allcl processing ( 79 ), whereby each of the path -
from the face and intraoral structures are ways that composed the complex somatosen -
transmitted bilaterally to parts of the VPM sory neural system analyses and treats
( 23, 288, 377). somewhat different aspects of the somes-
Central
sulcus
Postcentral gyrus
5
VLc LP
Deep Medial
r lemniscus
VPI
Spinothalamic
Deep VPLC Cutaneous tracts
cerebellar
nuclei
Figure 16.20. Saggital plane showing projections of thalamic subdivisions to the sensorimotor cortex Neurons in the
ventral posterolateral pars caudalis ( VPLc ) and ventral posteromedial ( VPM) nuclei form a central core ( blue) consist -
ing of two parts responsive to cutaneous stimuli and an outer shell ( white) composed of neurons responsive to deep
stimuli. Inputs to VPLc are via the medial lemniscus and the spinothalamic projections. Cells in the outer shell project to
cortical area 3a (muscle spindles) and to area 2 (deep receptors) Cells in the central core project to areas 3b and 1
(cutaneous) These projections are somatotopic . Inputs to the ventral posterolateral nucleus, pars oralis ( VPLo) and .
the ventral lateral nucleus pars caudalis ( VLc ) ( red) are from the contralateral cerebellar nuclei. Cerebellar input to
these thalamic nuclei is considered to be somatotopically organized in nearly the same way as in VPLc and VPM.
VPLo and VLc project somatotopically on the primary motor area (area 4)
Figure 16.21. Autoradiograph demonstrating transport of isotope from the rostrolateral nucleus of the solitary fascicu-
. .
lus to the ipsilateral ventral posteromedial nucleus (pars parvicellularis) CM centromedian nucleus VPM somatic .
.
part of the ventral posteromedial nucleus, Zl zona incerta.
660
16 Thalamus 661
thetic scene. Parallel processing seems to be a

feature of all sensory systems (79, 173).
Posterior Nuclear Group

Caudal to the VPL there is a transitional
diencephalic zone with a complex and varied
cellular morphology that has been referred to
as the posterior thalamic nuclear group ( 379).
The posterior nuclear group (zone) lies cau -
dal to VPLc, medial to the rostral part of the
pulvinar, and dorsal to the medial geniculate
body ( Fig. 16.4). This nuclear complex con-
sists of ( a ) the supra-geniculate nucleus , ( b) the
nucleus limHans , and (c) an ill -defined region
of heterogeneous cell types that extends ros-
trally toward the caudal pole of VPLc, re-
ferred to as the posterior nucleus ( 44, 173). The
suprageniculate nucleus is a pyramid -shaped
cell mass that extends dorsomedially from
the dorsal part of the principal division of the
medial geniculate body ( Fig. 16.22 ). The nu -
cleus limitans is a narrow band of oval or
spindle-shaped cells that separates the pre-
tectum and medial nucleus of the pulvinar
(314). These cells merge laterally with those
of the suprageniculate nucleus. The posterior Figure 16.22. Two levels of the caudal thalamus in the
nucleus, composed of small- and medium- cat showing relationships of the nuclei of the posterior
thalamic complex to other thalamic nuclei. Two divisions
sized cells which lie rostral to the supragenic- of the posterior thalamic nuclei are recognized, a me-
ulate nucleus, extends rostrally toward VPLc dial (POm) and a lateral (PO, ) In B. the posterior thalamic
and becomes continuous with VPL The dor- nuclei lie medial and dorsal to the magnocellular part of
sal part of the posterior nucleus is difficult to the medial geniculate nucleus (MGf„); the medial nu-
distinguish from overlying regions of the pul - .
cleus F>Om appears continuous with the suprageniculate
nucleus (SG). In A, PO„, and PO, lie dorsal and lateral to
vinar and the small-celled part of the supra - the ventral posterior medial nucleus (VPM) and immedi-
geniculate nucleus. The magnocellular part of ately caudal to the ventral posterolateral nucleus ( VPL).
the medial geniculate nucleus lies ventral to CC, crus cerebri; CM. centromedian nucleus. DM, dorso-
the rostral part of the suprageniculate nu - . . .
medial (mediodorsal) nucleus Hb. habenula LG lateral
cleus and ventral to the posterior nucleus .
geniculate body; LP lateral posterior nucleus; MGp. me-
dial geniculate nucleus, patvicellular part. NR. red nu-
( Fig. 16.22).
cleus. OF. optic tract. Pf. pretectum. Put. pulvinar; RN.
Functionally, the posterior nucleus is of reticular nucleus of thalamus; SN. substantia nigra; Zl .
particular interest because it receives zone incerta
spinothalamic medial lemniscal fibers and
appears involved, at least in part, in the noci-
ception (13, 30, 32, 33, 35, 37, 173, 193, 194, from the insular cortex and , in turn , projects
252, 253, 255, 257, 359 ). The medial part of the to the insular cortex (173, 175, 372 ).
posterior nucleus may also receive projec- Recent studies make it clear that the poste-
tions from the primary (S-l ) somatosensory rior nuclei cannot be thought of as a single
cortex (136, 180, 181 ). Studies in cats and functional entity. The only common denomi-
monkeys indicate that cells in the medial di- nators are their intimate topographic relation -
vision of the posterior nucleus project to the ship with other thalamic nuclei and their pro-
retroinsular cortex, and cells in the lateral di- jections to cortical fields in and around the
vision of this nucleus project to postauditory insula. These nuclei are clearly multimodal as
cortex ( 44 ). Neither of these cortical projec- they integrate information of the visual, audi-
tions overlap recognized somatosensory or tory, and somesthetic types. There is a slight
auditory areas. The suprageniculate-limitans preponderance of visual influences in the
nuclear complex receives inputs from the suprageniculate-limitans complex, while the
deep layers of the superior colliculus and posterior nucleus appears to be more under
auditory influence. None of the posterior nu - (127, 280, 311 ). The three main divisions of
clei, however, appear to have the specificity the MGN are referred to as medial, dorsal,
of organization of a typical thalamic relay and ventral ( 280, 311 ) ( Fig. 16.23). These sub-
nucleus. divisions of the medial geniculate nucleus,
not easily distinguished in ordinary histo-
Geniculate Nuclear Group logic preparations, become apparent in Golgi
MEDIAL GENICULATE NUCLEUS preparations ( 280-282 ).
The ventral nucleus extends throughout
The medial geniculate nucleus ( MGN ) lies most of the rostrocaudal length of the MGN
on the caudal ventral aspect of the thalamus, and is bounded medially by the brachium of
medial to the lateral geniculate nucleus the inferior colliculus. Unlike all other major
( LGN ) and dorsal to the crus cerebri ( Figs. subdivisions of the MGN , the ventral nucleus
16.3, 16.4, and 16.13). This large nuclear mass has a distinct laminar organization. Cells of
is the thalamic auditory relay nucleus, receiv - the ventral division are fairly constant in size
ing fibers from the inferior colliculus via its and shape and have tufted dendrites. The
brachium and giving rise to the auditory ra - lamination, produced by the dendritic pat -
diation ( Fig. 13.13). Unlike auditory relay nu- tern of tufted cells and fibers of the brachium
clei at lower brainstem levels, there are no of the inferior colliculus, is in the form of spi-
commissural connections between the medial rals or curved vertical sheets ( Fig. 16.23). Af -
geniculate nuclei. The medial geniculate nu - ferent fibers from the inferior colliculus enter
cleus consists of several subdivisions with particular laminae and remain continuously
distinctive cytoarchitecture and connections associated with the same layers. The lamina -
Medial Geniculate
VENTRAL
NUCLEUS
Figure 16.23 . Transverse reconstructions of the fibrodendritic laminations in the ventral nucleus of the medial genicu-
late body In the cat based on Golgi preparations. A. Transverse section of midbrain through the superior colliculus
(SO and medial geniculate body (MGS) or nucleus; M and D Indicate the magnocellular and dorsal nuclei of the
MGB The laminated ventral nucleus of MGB is shown in A B and C The lamination in the ventral nucleus, produced
.
by the arrangement of dendrites of geniculate neurons and fibers in the brachium of the inferior colliculus (8/Q oc -
curs in spirals and vertical sheets (B C) CC. crus cerebri. CSC. commissure of the superior colliculus ML medial lemnis-
.
cus. SN. substantia nigra; III oculomotor nucleus
16 Thalamus 663
tion in the ventral division of the MGN is portions of MGN (i.e., the dorsal and medial
analogous to that in the lateral geniculate nu- divisions) send fibers ipsilaterally to at least
cleus, except the cellular laminae are not sep- five cytoarchitectonically distinct areas which
arated by bands of myelinated fibers. The form a cortical belt surrounding the primary
laminar organization of the ventral division auditory area (311, 356, 453). There is very lit-
of the MGN resembles that of the ventrolat- tle overlap in the cortical projections of these
eral division of the central nucleus of the infe- MGN subdivisions. One exception to the
rior colliculus from which it receives its major foregoing concerns the caudal magnocellular
input (55, 205, 274, 280, 311, 375). Physiologic part of the medial division which projects to
mapping of the ventral division of the MGN most, if not all, of the cortical target areas of
reveals that the cellular laminae are related to MGN. Thus, the cortical projection of the
the tonotopic organization in which high fre- magnocellular MGN overlaps terminations of
quencies are represented medially and low the ventral laminated part of the MGN in the
frequencies laterally (6, 93, 115). Neurons in primary auditory area and the terminations
the ventral division of the MGN give rise to of all nuclei in other subdivisions projecting
the auditory radiation which terminates to the secondary auditory cortex. However,
in the primary auditory cortex ( Figs. 13.13, there is a difference in the cortical termina-
20.29, and 20.30) where there is a spatial rep- tions of these fibers in that fibers from the
resentation of tonal frequencies (55, 298, 312, magnocellular division terminate mainly in
356, 453). The primary auditory cortex gives layer 1 of the cortex, while all other parts of
rise to reciprocal corticothalamic fibers that the MGN send fibers primarily to cortical
terminate in the ventral division of the MGB layer IV and / or 111 (173).
(75, 85, 312). Both geniculocortical and cor- Although ascending pathways in the audi -
ticogeniculate fibers are ipsilateral. tory system are paralleled by descending
In humans, the MGN projects principally fiber linkages which can facilitate or inhibit
to the superior temporal convolution ( trans- transmission of impulses at numerous relay
verse gyrus of Heschl ) via the geniculo-tem- nuclei, or in the hair cells of the cochlea, the
poral or auditory radiations ( Figs. 13.13, MGN does not participate in this descending
16.13, and 16.39). This cortical projection area system. Cortical projections from the primary
(area 41 ) has a tonotopic localization in which and secondary auditory areas are back to the
high tones are appreciated in medial regions subdivisions of the MGB from which they re -
and low tones are represented laterally and ceive afferents (55, 312).
anteriorly ( Fig. 20.10) (160, 259).
The dorsal division of the MGN contains LATERAL GENICULATE NUCLEUS
several nuclei, among which are the supra -
geniculate and the dorsal nuclei (311). The In most species, the lateral geniculate nu-
dorsal nucleus, prominent at caudal levels of cleus is a nuclear complex rather than a single
the MGN ( Fig. 16.23), receives projections nucleus, since two or more components can
from a broad lateral tegmental area that ex- be recognized (173). One of these, the dorsal
tends from the deep layers of the superior lateral geniculate nucleus ( LGNd ), projects to
colliculus to the area adjacent to the lateral the cortex and is the major relay nucleus for
lemniscus ( 205, 311). The suprageniculate nu- the visual system. The other component, the
cleus ( Fig. 16.22) appears to receive projec- ventral lateral geniculate nucleus ( LGNv), is
tions from deep layers of the superior collicu- developmentally a part of the ventral thala-
lus and the dorsal midbrain tegmentum (44, mus and does not project to the cortex. In pri-
311). This nucleus was considered earlier as mates, probably because of the descent and
part of the posterior nuclear group. rotation of the dorsal lateral geniculate nu -
The medial division, containing the largest cleus during development (219), the ventral
cells in the MGN and lying dorsomedial to lateral geniculate nucleus lies above the dor-
the ventral division, is known as the magno- sal nucleus. In this position, it is often re -
cellular part ( Figs. 16.22 and 16.23). Rostrally, ferred to as the pregeniculate nucleus (173).
the magnocellular part of the MGN borders This component is not considered further
the suprageniculate nucleus and the posterior here.
thalamic nucleus. This division of the MGN The (dorsal ) lateral geniculate nucleus
receives inputs from the inferior colliculus, ( LGN ), the thalamic relay nucleus for the vi-
lateral tegmentum, and spinal cord (31, 55, sual system, lies rostral and lateral to the me-
185, 253, 274, 275, 282, 311 ). All nonlaminated dial geniculate nucleus ( MGN ), lateral to the
ers 1 , 4 and 6, while uncrossed fibers termi-

nate in layers 2, 3 and 3 (106, 107, 117, 137,
142, 168, 190, 215, 250, 266, 425, 426).
—
A
The monocular crescent of the visual field
? is subserved bv receptor elements in the most
' medial part of the nasal retina ( Fig. 16.27).
3 V
'•
. -
:
-
. I : '
., .2 . ,> Ganglion cells in this part of the retina project
crossed fibers to the biiaminar segment of op-
posite LGN, located laterally where parts of
layers 4 and 6 fuse (142, 189 ) ( Fig. 16.25). The
optic disc, located in the nasal half of the
retina and representing optic nerve fibers, has
figure 16 24 Cellular lamination of the lateral genicu- no photoreceptors and is responsible for the
late nucleus with laminae numbered from the hilus . The blind spot detectable on perimetry. The optic
magnocellular laminae (1 and 2) constitute the ventral
disc, represented in the contralateral LGN by
subdivision. Parvicellular laminae 3 through 6 are re-
ferred to as the dorsal subdivision Crossed fibers of fhe cellular discontinuities in layers 4 and 6, is a
.
opfic tract terminate in laminae ) 4, and 6; uncrossed constant feature ( 142) ( Fig. 16.25).
optic fibers terminate on other laminae Nissl preparations through the human lat -
eral geniculate nucleus reveal a linear cellular
organization in which the long axis of the
cells tend to run perpendicular to the lami-
crus cerebri, and ventral to the pulvinar ( Figs. nae. This linear cellular orientation corre-
2.26, 16.3, 16.4, 16.13, and 16.24 ). This lami - sponds to the orientation of small blood ves-
nated cellular structure has a horseshoe- sels running through the nucleus from its
shaped configuration in transverse sections,
with the hilus directed ventromedially.
ventral surface ( 142 ). Perikarya of the parvi
cellular layers are oriented perpendicular to
-
Crossed and uncrossed fibers of the optic laminae so that the long axis of the cells par-
tract enter via the hilus and are distributed in allel "lines of projection" which indicate
a precise pattern. In human and nonhuman isorepresentation of points in the visual field
primates, the LGN consists of six cellular lay - ( 27, 189 ) ( Fig. 16.26).
ers or laminae arranged in two major subdi - The topographic representation of the reti -
visions ( 142, 221, 225). The six concentric cell nal surface within the LGN is highly orga -
layers, separated by intervening fiber bands, nized and precise. The contralateral half of
customarily are numbered from 1 to 6, begin - the binocular visual field is represented in
ning from the hilar region ( Fig. 16.24 ). Subdi- each of the six layers of the LGN , even
visions of the LGN are magnocellular ( layers though crossed and uncrossed fibers end in
1 and 2 ) and parvicellular (layers 3 to 6) ( 246 ). different layers. The projection loci in the six
Both divisions of LGN receive afferents from layers lie in perfect register so that any small
the ganglion cells of the retina ( 384 ). area in the contralateral binocular visual field
The parvicellular layers of LGN , consisting can be shown to correspond to a dorsoventral
of layers 3, 4, 5, and 6 in ventro-dorsal se- column of cells extending radially through all
quence, are easily distinguished in caudal six layers parallel to the "lines of projection ,"
parts of the nucleus ( Fig. 16.25). As these lay- which indicate identical points in the visual
ers are traced laterally they fuse in pairs: field ( Fig. 16.27) ( 189 ). The LGN consists of
layer 4 with layer 6, and layer 3 with layer 5 six sheets of cells bent in a horseshoe configu -
( 142 ) . In rostral parts of LGN , the individual ration, but in exact registration, so that
layers are more difficult to identify because columns of cells in the "lines of projection"
layer 3 does not extend as far rostrally as receive inputs from corresponding points in
layer 5, and layers 4 and 6 fuse medially as the retina of each eye related to the contralat -
well as laterally. The projection from the eral binocular visual field . Binocular fusion
retina onto LGN is precise, and crossed and does not occur in the LGN because retino-
uncrossed fibers in the optic tract end upon geniculate fibers end on different layers. Fol -
separate layers. Anterograde and retrograde lowing section of the optic nerve, anterograde
degeneration studies, as well as more recent degeneration or transneuronal degeneration
autoradiographic studies have revealed that (after long survival ) occurs in three layers of
crossed fibers of the optic tract end upon lay- the LGN on each side. The layers in which
16 Thalamus 665
ft
/> '
v- '
’minis
**
'
1m m '
Figure 16.25. Sections through the human lateral geniculate nucleus The blind spot is represented by discontinuities
In layers 6 (A. arrow ) and 4 (B arrow ) Ldyers 4 dnd 6 fuse laterally ( right ) in both A and B producing the bilaminar
segment ventrally . The bilaminar segment receive an input from the most medial contralateral nasal retina that sub-
serves the monocular visual field (i.e.. the monocular crescent).
degeneration of fibers or cells occur differs in sual field ( monocular crescent ) related to re-
accordance with the disposition of crossed ceptor elements in the most medial nasal
( layers 1, 4, and 6 ) and uncrossed ( layers 2, 3, retina , is represented by crossed fibers termi -
and 5) retinal fibers (107, 117, 142, 250, 347). nating in the only bilaminar segment ( Figs.
Small lesions of the retina produce transneu - 16.25 and 16.27) ( 142, 184 ).
ronal degeneration in localized clusters of The "lines of projection" in the LGN also
cells in three different layers on each side can be demonstrated by the study of retro-
aligned according to the "lines of projection" grade cell degeneration in the LGN following
(96, 225, 347). The contralateral monocular vi- small lesions in the striate cortex (95, 119, 142,
A
-n ’ >•
$
--
. •
„ V /
Figure 16.26 . Lateral geniculate nucleus of a baboon that sustained several lesions in the striate cortex Retrograde
degeneration In a large V -shaped sector of the lateral geniculate nucleus demonstrate the lines of projection Lines
of projection represent points of isorepresentation in the visual field
-
189, 376). Since one half of the visual field is the superior retinal quadrants of both eyes
represented topographically in the striate cor- project to the medial half of LGN while the
tex of each hemisphere, the zone of retro- inferior retinal quadrants send fibers to the
grade cell degeneration in the LGN is lateral half of the nucleus. The retinal projec-
bounded on each side by lines of projections. tion from the macula is represented in a
Cortical projection zones in geniculate seg- wedge-shaped sector in the caudal part of
ments involve cells of LGN in all layers, and LGN on both sides. The macular representa -
neurons in the LGN with identical receptive tion account for about 12% of the total vol -
fields form a column of cells extending ume of LGN . The vertical meridian of the vi-
through all laminae. Cells in each of these sual field , corresponding to the line
columns in LGN project to the same region of separating temporal and nasal parts of the
the striate cortex. retina , is represented along the caudal mar-
In the LGN , the horizontal meridian of the gin of the nucleus from its medial to lateral
visual field corresponds to an oblique borders (41, 142, 149, 150, 189, 213, 225, 247,
dorsoventral plane that divides the nucleus 347) ( Figs. 16.28 and 16.29 ).
into medial and lateral segments. Fibers from Retinofugal fibers entering various lami-
16 Thalamus 667
Fixation point
to
9 8
77
6
5
Binocular field v
N
* u>
Monocular Monocular ^3
visual field visual field
to
ft
Retina
i
r°
Temporal
L
Retina
«
Nasal
Uncrossed Crossed
optic fibers optic fibers
Lateral geniculate
nucleus
Figure 16.27. Representation of the visual field in the retinae and in the layers of the lateral geniculate nucleus Por-
tions of the binocular visual field are shown in red ( left ) and blue ( right ), while the monocular visual fields are white
Light from numbered sectors of both the binocular and monocular visual fields falls upon corresponding numbered
sectors of the retinae Crossed and uncrossed retinofugal fibers project upon columns of cells in different laminae of
the lateral geniculate nucleus which are in exact registration, represented here by corresponding numbers. A repre-
. . .
sents laminae receiving uncrossed fibers (i.e. laminae 2 3 and 5) B represents laminae receiving crossed fibers (i.e . ,
laminae 1, 4, and 6). Light from the right monocular visual field (sectors 1 and 2) falls upon retinal receptors of the cor -
responding number in the most medial ipsilateral nasal retina. Crossed retinofugal fibers project to cell columns of the
.
left lateral geniculate nucleus (1 2) Cell columns 1 and 2 are best developed in laminae 4 and 6 which fuse to form
the bilaminar segment .
Right
SNQ
Retina J
INQ
///
/
Optic nerves
/
/
Optic chiasm
Optic tracts
Lateral geniculate bodies
Figure 16.28. Retinal ganglion cell projections through the optic nerves, optic chiasm, and optic tracts to termina-
tions within the lateral geniculate nuclei. Superior peripheral quadrants of the retina on both sides (SNQ, superior nasal
quadrant, and STQ. superior temporal quadrant), shown in red. project to the medial part (SO) of the left lateral
geniculate nucleus (red) Inferior peripheral quadrants of the retina (INQ. inferior nasal quadrant, and ITQ. inferior tem-
poral quadrant), shown In blue, project to the lateral part ( IQ) of the left lateral geniculate nucleus ( blue). Superior
central regions of the retina on nasal and temporal sides ( black ) on the opposite side project to the region of the right
lateral geniculate nucleus indicated by SC. Inferior central regions of the retina ( white) project In the same fashion to
the region of the right lateral geniculate body indicated by 1C The macular projection to the lateral geniculate is in
the caudal region of the nucleus. Numbers in the left lateral geniculate body indicate two of the six laminae.
16 Thalamus 669
Vertical Left lateral

Right visual hemifield meridian —y geniculate body
Lateral
+ 80° + 401+ 60°
20i
+ 60° + 8° /
I
l ' I \
Upper binocular + 40 °
/
r
visual hemifield — V
/
+ 20° l Caudal
Central 5 °
i
t i
'
11 8*
I i
of vision - o°. <
i
'•V
20' 40' 60 I /
I I I I
Lower binocular - 20° * 1
visual hemifield — I
±-h-+
I I
- 40° Horizontal -8 \ \
°
l ///
I / A - 20° \\
- 60°
- 80°
meridian
Monocular crescent
- 40°
- 60°
^ [I / A
Medial
A visual field B
Figure 16.29 . Right visual hemifield of the monkey ( A) and its projection onto the dorsal surface of the unfolded left
lateral geniculate body ( t GB) or nucleus (B) The vertical meridian is represented by the heavy black line on the left in
both A and B visual field zones of increasing eccentricity are represented serially in degrees by bashed lines. In the
.
left lateral geniculate nucleus, visual field zones ( dashed lines) are represented serially among the caudorostral axis of
the nucleus in degrees. The horizontal meridian of the hemifield at zero degrees is represented by a curved line in the
caudorostral axis of the LGB (B) Thin lines above and below the horizontal meridian indicate positive or negative ele-
vations in degrees Upper ( blue) and lower ( red) portions of the binocular visual hemifield indicated in A are repre-
sented by the same colors in B The central 5° of vision, a generous estimate of the angle subtended by the fovea
centralis, are shown in black and white at the intersection of the vertical and horizontal meridians The monocular .
crescent ( white) in A is represented along the rostral border of the LGB
nae of LGN establish synaptic contact with nal ending. These "triads" are found
dendrites of geniculate neurons which are throughout the LGN , as well as in character-
distributed within their particular lamina ( 45, istic glial encapsulated synaptic complexes
61, 116, 422 ). Cells in LGN exhibit both con- known as glomeruli. This triadic synaptic
vergence and divergence: retinal afferent arrangement serves as a mechanism for pha -
fibers may synapse with several neurons in sic inhibition of geniculate relay neurons. In
LGN ( divergence), and each neuron of the this action it is assumed that the retinal axon
LGN may receive inputs from several excites both the geniculate relay neuron and
retinofugal fibers (convergence). the interneuron. The discharge of the in-
Laminae of LGN also contain substantial terneuron, in turn, inhibits the same relay
numbers of Golgi type II neurons that play an neuron excited by the retina afferent.
important role in processing visual informa - Glomeruli in the LGN constitute a synap-
tion ( 116, 124, 214, 331, 332, 422 ). Electron mi- tic complex of interlocking nerve processes of
croscopic observations reveal a synaptic various origins, are arranged in a specific
arrangement in which retinal axon terminals manner, and separated from the environment
establish synaptic contact with both relay by a capsule of glial processes ( Fig. 16.30)
neurons and Golgi type II cells (124, 331 ). ( 421 ). The axon terminals of retinal afferents
This pattern of synaptic articulation, termed occupy the central position in these
triadic synaptic arrangement , is a fundamental glomeruli . Unlike the cerebellar glomeruli,
ultrastructural feature of LGN as well as of which contain only one mossy fiber rosette,
other thalamic sensory nuclei. This synaptic several club-shaped retinal afferents may
arrangement consists of a retinal axon termi- occur in a LGN glomerulus. Other contribu -
nating upon dendrites of both a LGN relay tions to the glomeruli arise from Golgi type II
neuron and a Golgi type II interneuron . The cells and corticofugal fibers ( Fig. 16.30).
Golgi type II neuron is presynaptic to the Glomeruli often are located at the bifurcation
same relay neuron that received a direct reti- of stem dendrites of a LGN neuron . Axons of
Striate cortex
Axonal collateral
Corticofugal fiber
Lateral geniculate
relay neuron
- Golgi type II cell
Oendrite
Lateral geniculate
glomerulus
Primary retinal afferent
Figure 16.30. Neuronal arrangements in a glomerulus of the lateral geniculate nucleus A primary retinal afferent is in-
dicated in red. while the lateral geniculate nucleus relay neuron Is in blue A corticofugal fiber and a Golgi type II cell
.
are shown in black The glomerulus contains a terminal of a primary retinal afferent, several club-shaped terminals of
a relay neuron of the lateral geniculate nucleus, and contributions from both Golgi type II neurons and corticofugal
fibers This synaptic complex is enclosed in a capsule of glial processes, indicated by the dashed hne.
Golgi type II cells enter the glomeruli and es- contributed by terminals of the retinofugal
tablish synapses with relay cell ( LGN neuron ) fibers. The most remarkable feature of these
dendrites. These cells exert a GABAergic in- glomeruli is the frequent occurrence of
hibitory influence upon these dendrites. The axoaxonic synapses. Some glomeruli of the
LGN glomerular complex contains (a ) axo- LGN contain the triadic synaptic arrange-
dendritic synapses on stem, secondary , and ment previously described . In the triadic
peripheral dendrites, and ( b) axoaxonic arrangement, the participating neural ele-
synapses in which the presynaptic portion is ments remain the same, but the receptive sur-
16 Thalamus 671
faces on geniculate relay neurons or Golgi caudal levels, the reticular nucleus is continu-
type II cell may be either the soma or a den - ous with the perigeniculate nucleus that sur-
drite ( 124 ). Among the participating ele- rounds the lateral geniculate nucleus. Mor-
ments, terminals from corticogeniculate phologically and physiologically the two
fibers and those from fibers originating in the structures are alike and may be part of a sin -
reticular thalamic nucleus are functionally gle entity ( 173).
important. Neurons of the reticular nucleus belong to
The complex synaptic arrangements several single classes, but the majority of
within LGN glomeruli are effective in the them are large, fusiform, or triangular, with
versatile processing of visual information long dendrites mainly disposed parallel to
( 393). The LGN is not a simple cortical relay the surface of the underlying thalamus and at
nucleus, but a structure in which important right angles to the fibers entering and leaving
transformations of visual information occur the thalamus ( 169, 173, 235, 360, 386, 404 ).
through physiologic processes involving in - The axons of reticular neurons penetrate
hibition from a variety of sources that change deeply into the thalamus where they ramify
the pattern and strength of neuronal re- over wide areas ( 386, 459 ). The axons of retic-
sponses. It is worth noting that the cortico- ular neurons arborize at least twice in the
geniculate fibers outnumber the geniculocor- thalamus. They usually give off several col -
tical fibers by a factor of 2 ( 393). Thus, laterals that branch profusely within a proxi-
corticogeniculate fibers are likely to play an mal thalamic nucleus and then continue its
important role in the complex internal pro- course toward more remote thalamic nuclei
cessing of visual information that occur at where they arborize again ( Fig. 16.31 ). In be-
LGN level. tween these two, or more, terminal fields, the
The lateral geniculate nucleus is the main axons of reticular neurons remain relatively
end station of the optic tract and, in turn, the poorly branched. Terminal of reticular nu -
nucleus projects massively to the visual (cal- cleus, axons in the thalamus contain flattened
carine) cortex via the geniculocalcarine tract or pleomorphic synaptic vesicles and make
or visual radiations ( Fig. 16.42 ). Cells of LGN symmetric synapses, primarily on dendrites
project retinotopically, primarily upon the of relay neurons. There appear to be no in-
striate cortex (area 17), but also upon the terneurons in the reticular nucleus. The in-
parastriate (area 18) and peristriate (area 19) tranuclear communication is ensured by local
cortex (82, 97, 102, 109, 148, 3( H), 433, 451, axon collaterals of reticular neurons.
454 ). The striate cortex has reciprocal connec- Inputs to the reticular nucleus are derived
tions with the LGN and also projects to the from the principal thalamic nuclei and from
superior colliculus and the pretectum (102, the cerebral cortex ( 46, 169 ). Fibers emanating
147, 236). from a nucleus of the thalamus and destined
for a specific cortical area give collateral
Reticular Nucleus branches that terminate in a particular part of
the reticular nucleus. Corticothalamic fibers
The thalamic reticular nucleus is a thin passing toward a particular nucleus of the
neuronal shell which surrounds the lateral, thalamus give collaterals to the same portions
superior, and anteroinferior aspects of the of the reticular nucleus as the target nucleus
thalamus ( Figs. 16.6, 16.10, 16.11 , and 16.13). to the thalamus. Cells in restricted sectors of
This thalamic nuclear envelope is a derivative the reticular nucleus project back to the thala -
of the ventral thalamus that has migrated mic nucleus from which it receives an input .
dorsally and lies between the external The consequence of this pattern of organiza -
medullary lamina of the thalamus and the in- tion is that a particular sector of the reticular
ternal capsule ( 70, 207 ). Morphologically, the nucleus can be dominated by a particular
reticular nucleus is closely related to the zona sensory (or other ) system (173). Both the in-
incerta and the ventral lateral geniculate nu - tralaminar and relay nuclei of the thalamus
cleus. The anterior part of the nucleus com - project to the reticular thalamic nucleus and
pletely surrounds the rostral pole of the thal - both receive fibers from it. The only thalamic
amus. It becomes thinner more posteriorly as nuclei that appear to be devoid of input from
it curves around the lateral and ventral as- the reticular nucleus are those of the anterior
pects of the thalamus. Still more caudally, the nuclear group ( 414).
reticular nucleus is displaced laterally by the The reticular nucleus probably also re-
dorsal lateral geniculate nucleus. At these ceives collaterals from the pallidothalamic
A P
RN
VPI
150 pm
Figure 16.31 . Camera luoda drawing of a neuron of the rat reticular ttialamic nucleus (.RN) that has been intracellu-
larly labeled with biocytm The drawing shows both the dendritic and the profuse axonal arborization, as seen on a
horizontal section The axons of this particular neuron traverse the ventral posterolateral nucleus ( VPL) and aborize
profusely within the ventral posteromedial nucleus (VPM )
and thalamostriatal fibers ( 173). Furthermore, Recent tract - tracing studies revealed that
it is innervated bv cholinergic fibers originat - the reticular nucleus receives sparse fibers
ing in the pedunculopontine and laterodorsal from the substantia nigra pars reticulata (319)
tegmental nuclei of the brainstem (groups Ch and from the external ( lateral ) pallidal seg -
5 and Ch 6 ) ( 122, 320), as well as in the basal ment ( 132 ). These projections indicate that the
forebrain (group Ch 4 ) ( 122, 328, 415). In turn , two main output nuclei of the basal ganglia
as predicted by the Scheibels on the basis of have a dual entry into the thalamus: (a ) a
Golgi studies ( 386 ), the reticular nucleus major direct input, whereby pallidal and ni-
sends some descending fibers that arborize gral neurons can affect specific groups of
principally in the midbrain reticular forma - thalamocortical neurons in the ventral lateral
tion , the superior colliculus, and the peri - and ventral anterior nuclei, and ( b) a minor
aqueductal gray (329, 371 ). The chemospecific indirect input via the reticular nucleus,
inputs from the brainstem tegmentum are be- whereby pallidal and nigral neurons can in -
lieved to play an important role in the en- fluence diffusely vast collections of thalamo -
trainment of reticular neuron activity in ac- cortical neurons. Other studies showed that
-
cordance with various state dependent brain
conditions ( 410 ).
axons of some reticular neurons traverse the
midline to innervate the contralateral nuclei
16 Thalamus 673
of the thalamus (131, 321, 362, 369) ( Fig. species, with emphasis on data relevant to
16.17). An important role is attributed to this human and nonhuman primates.
projection in the bilateral functioning of the
thalamus in rodents ( 362). In primates, how - Acetylcholine
ever, fibers from the reticular nucleus that
crossed the midline are very sparse by com - Histochemical techniques allowing the vi-
parison with those that arborize ipsilaterally sualization of acetylcholinesterase ( AChE ),
(131 ). Thus, this small contralateral projection the enzyme that catabolyzes acetylcholine
is unlikely to play a major role in the func - ( ACh ), as well as various nonspecific
tional organization of the thalamus in pri - cholinesterases, has been the first approach to
mates. A particularly interesting feature of be used for the study of the chemoarchitec-
the morphologic organization of the reticular ture of the thalamus ( 313, 396 ). A moderate to
thalamus is the occurrence of multiple den- strong AChE staining was found in the in -
drodendritic synapses (73). Such dendroden - tralaminar nuclei, the anterior nuclei, the lat -
dritic contacts are believed to be responsible eral and medial geniculate nuclei, and the
for the synchronization of thalamic spindling, reticular nucleus, and part of the midline nu -
that is, the synchronization of low-frequency clei (313, 323, 382, 396 ) ( Fig. 16.32 ). Since this
( 7-14 Hz ) rhythmic hyperpolarizations that AChE staining disappeared after destruction
underlie the highly characteristic repetitive of parts of the midbrain reticular formation,
spike bursts ( "spindles" ) that reticular neu - Shute and Lewis ( 396 ) concluded that the
rons display during anesthesia or slow-wave thalamic cholinergic innervation was part of
sleep ( 73). the ascending reticular cholinergic system,
The reticular nucleus is an important func- particularly its dorsal tegmental portion,
tional interface between the thalamus and the which arises in the nucleus cuneiformis and
cerebral cortex. This nucleus is ideally situ - extends up through the tectum to the thala -
ated so as to sample neural activity passing mus and possibly beyond. The thalamic
the cerebral cortex and nuclei of the thala- AChE staining was largely confined to the
mus, but it has no projection to the cerebral neuropil and , since the presence of AChE
cortex ( 46, 169, 173, 386 ). Cortical projections does not necessary imply cholinergic trans-
to portions of the reticular nucleus arise from mission , the significance of these regional
the entire cerebral cortex and are topographi- thalamic concentrations in AChE remained
cally organized. Since the major projections unclear. The pattern of thalamic AChE distri -
of the thalamic reticular nucleus are to spe- bution, however, appears to follow quite
cific and nonspecific thalamic nuclei, it proba - well that of the distribution of cholinergic
bly serves to integrate and "gate" activities of receptors of both muscarinic and nicotinic
thalamic neurons ( 74, 90, 173, 354, 390, 411 ). types ( 2, 155, 172 ). Thus, the presence of
AChE at thalamic levels may be indicative
CHEMICAL ANATOMY OF THE of cholinoceptive rather than cholinergic
THALAMUS neurons.
Studies combining immunohistochemistry
The subdivision of the thalamus presented for choline acetyltransferase (CHAT), the en -
earlier is largely based on cytoarchitectural zyme that synthesizes ACh , with retrograde
and hodologic criteria . The recent develop- tracer methods confirmed , at least in part ,
ment of ever more powerful methods for the Shute's and Lewis's insights, by demonstrat-
localization of various molecules involved in ing that the thalamic cholinergic innervation
neuronal communication has yielded a large derive largely from brainstem mesopontine
amount of new findings on the chemospecific reticular nuclei, principally the pedunculo-
neuronal systems related to the thalamus. Al- pontine ( group Ch 5) and laterodorsal
though our knowledge of the chemoarchitec - tegmental (group Ch 6 ) nuclei ( 122, 161, 320,
ture of the thalamus is still limited , the chem- 403, 415, 455). The para bigeminal nucleus
ical anatomy approach has already provided (group Ch 8) also provides thalamic inputs,
new insights on the functional organization particularly to the pulvinar regions ( 462).
of the thalamus ( 143, 144, 172, 237). The fol - Furthermore, neurons of the nucleus basalis
lowing section provides a brief review of of Meynert (group Ch 4 ) in the basal fore-
some of the new findings on the distribution brain contribute to the cholinergic innerva -
of different transmitters and / or transmitter- tion of certain thalamic nuclei, particularly
related molecules in the thalamus of various the reticular and mediodorsal nuclei ( 122,
Figure 16.32. Transverse sections at rostral ( A C E) and middle (B 0 F) thirds of the centromedian(CM)-parafascicu-
lar (Pf) complex of the squirrel monkey Sections show Nissl cell staining (A B) acetylcholinesterase (AChE) hlstochem-
ical staining (C D) and calbindin D -28k immunostaimng (E. F) Asterisk (B) indicates the habenulo-interpeduncular
troct and sPt mdentifves the location of the subparafascicular nucleus ( A B)
328, 415). The ascending cholinergic projec- tral ), the reticular nucleus, midline nuclei
tion from the brainstem appears divergent in ( paraventricular and reuniens nuclei ), some
-
that single ChAT positive axons provide col - nuclei associated with the limbic system ( an -
laterals to several thalamic nuclei ( 34 ). terodorsal nucleus and medially situated
-
The distribution of ChAT immunoreactive patches in the mediodorsal nucleus), and the
fibers has been studied in detail in rodents lateral geniculate nucleus displayed the high-
( 228) and in humans ( 133). These studies re- est density of ChAT-positive axon terminals.
vealed that the only group of cholinergic The remaining sensory relay nuclei and the
( ACh producing ) neurons in the mammalian nuclei interconnected with the motor and as-
thalamus is found in the medial habenular sociation cortex are less densely innervated .
nucleus. In humans, some intralaminar nuclei Since cholinergic neurons of the basal fore-
(central medial, central lateral, and paracen - brain display immunoreactivity for the nerve
16 Thalamus 675
growth factor receptor ( NGFr ) while those in lar nucleus are strongly GABA- positive in all
the brainstem do not, it was possible to spec- species ( Fig. 16.35). GABA-immunoreactive
ify the contribution of these two sources to neurons in the thalamus, other than the retic-
the cholinergic innervation of the human ular nucleus, appear more numerous in pri -
thalamus. This indirect approach revealed mates than in nonprimates. Most of these
that the anterior intralaminar nuclei, the retic- GABAergic neurons in monkeys are small
ular nucleus, and medially situated patches and are regarded as interneurons. In nonhu -
in the mediodorsal nucleus receive a projec - man primates, GABAergic neurons occur in
tion from the nucleus basalis. The other thala - virtually all thalamic nuclei ( Figs. 16.33 and
mic nuclei contain only scarce NGFr- positive 16.34 ). In the anterior nuclear group, GABA-
axons ( 133). These observations suggest that immunoreactive cell bodies abound particu -
thalamic nuclei affiliated with limbic struc - larly in the anterodorsal nucleus. In the ante-
tures and with the ascending reticular acti- rior group, GABA- positive neurons tend to
vating system are under particularly intense cluster rostrally while they are more uni -
cholinergic influence. formly distributed caudally . In the intralami-
The thalamic cholinergic innervation was
also investigated at the ultrastructural level
-
nar nuclei, GABA immunoreactive cells pre-
vail in dorsal parts of the central lateral and
( 123, 162, 391 ). These studies have demon - paracentral nuclei, as well as in the entire
strated the presence of cholinergic synapses parafascicular nucleus. In the mediodorsal
of the asymmetric type onto dendrites of both nucleus, GABA- positive neurons are more
relay projection neurons and interneurons in heterogeneously distributed in the lateral
the mediodorsal nucleus ( 391 ). This finding parvicellular part than in the medial magno-
indicates that cholinergic input to thalamic cellular part . GABA-immunoreactive neu -
nuclei influence relay cell activity both di- rons are uniformly distributed in the nuclei of
rectly and indirectly vial local circuit neu - the posterior group, except in the pulvinar
rons. In the reticular nucleus, cholinergic where they abound in the pars inferior and
synapses were found on the dendrites of in- oralis of this nucleus. In the lateral geniculate
trinsic neurons but not on cortical and thala - nucleus, GABAergic cell bodies occur in all
mic fibers passing through the reticular nu - laminae but are more abundant in the mag-
cleus ( 123). The occurrence of cholinergic nocellular laminae ( Figs. 16.33 and 16.34).
synapses on identified intralaminostriatal In addition to GABAergic cell bodies, nu -
neurons has been documented (162 ). merous GABA-immunoreactive axon termi-
These findings indicate that thalamic nu - nals occur in the various thalamic nuclei
clei are under a strong cholinergic influence ( Figs. 16.33 and 16.34 ) . A significant propor-
originating principally in the brainstem retic - tion of these axon terminals derive from the
ular formation and less abundantly in the neurons of the reticular nucleus, but ex-
basal forebrain . This chemospecific projection trathalamic sources also exist . The major pro-
could directly modulate the neural activity of jections of the internal pallidal segment to
thalamic neurons according to various state- VApc and VLo and the projection from the
dependent activities ( 410 ). pars reticulata of the substantia nigra to
VAmc and MDpl are GABAergic ( 57). These
Gamma- Aminobutyric Acid projections are considered to play a major
role in aspects of motor function . Further-
The presence of y-aminobutyric acid more, in addition to GABAergic axon termi -
(GABA )- producing neurons in the thalamus nals of intrinsic origin (65), the reticular
has been documented in various species with nucleus contains numerous GABAergic ter-
antibodies directed either against the synthe- minals that arise from caudal parts of the
sizing enzvme, glutamate acid decarboxylase
'
basal forebrain (12 ).
(GAD ), or GABA itself ( 129, 308, 370, 402 ), as
well as with in situ hybridization methods Neuroactive Peptides
that reveal the expression of the gene coding
for GAD ( 21 ). Furthermore, both GABAA and Immunohistochemical studies have re-
GABAB receptor types occur at thalamic lev - vealed the presence of numerous neuroactive
els, some of these receptors being localized peptides belonging to several distinct fami -
directly on thalamocortical projection neu - lies in the thalamus. Among those are ( a ) the
-
rons (63, 208). Virtually all cells in the reticu brain -gut peptides substance P (SP), chole -
LD AD PT
/ ••
••
RN /
. . * • \CSL
• • ••
•• VLO
VLC
*
*
"
:
'
:
*
. •:
"
•• ' CN
I•
• . MD
•
•.
i
•
.• / CeL •
\ . ••
• * • VPL .’ M •
•• -H
fi *
.. • •
• VPM
• •* .•
•••m
•••• • Zl
B
Figure 16.33. Transverse sections through rostral (A), midale (B). and caudal (C) portions of the thalamus in the squir
rel monkey illustrating the distribution and relative density of GABA -immunoreactive cell bodies (large dots) and axon
terminals ( fine dots), as visualized with an antibody raised directly against GABA AD anterodorsal nucleus; AM an- . .
. . . .
teromedial nucleus AV anteroventral nucleus CeL centrolateral nucleus CeM, centromedial nucleus; CM centro- .
. .
medlan nucleus, CN central nucleus CSL central superior lateral nucleus; dLGN dorsal lateral geniculate nucleus .
.
(layers 1 to 6); ILe external intercalated layer of dlGN; ILL internal intercalated layer of dLGN, LD laterodorsal nucleus . .
.
LP lateroposterior nucleus; MD. mediodorsa! nucleus; MT, mammillothalamic tract; Pf. parafascicular nucleus; PULo.
. . . .
pulvinar oral part; PT parataenial nucleus Pv. paraventricular nucleus, RE nucleus reuniens; RN reticular nucleus; SM . .
stria medullaris; VLc, ventral lateral nucleus, caudal part; VA ventral anterior nucleus; VLo ventral lateral nucleus, oral .
. .
part . vLGN ventral lateral geniculate nucleus; VPt ventral posteroinferior nucleus. VPL ventral posterolateral nucleus,
.
VPM. ventral posteromedial nucleus; Zl zona incerta
• AV
Figure 16.34. Features of the GABA -immunoreactive neuronal profiles disclosed in some rostral and lateral thalamic
nuclei and in the zona incerta of the squirrel monkey . A. Some GABA -positive cells in the reticular nucleus ( /7) border -
ing the internal capsule (/C) and in the adjoining ventral anterior (VA) nucleus. Note that the immunoreactive cells in
the reticular nucleus are larger than those in the ventral anterior nucleus B. Some GABA -immunoreactive neuronal el-
.
ements in the anterodorsal (AD) and anteroventral (AV) nuclei. The GABA -positive puncta Indicative of GABAergic
axon terminals, are particularly numerous In the anterodorsal nucleus C. Distribution of GABA - immunoreactive profiles
in the habenula Note the absence of GABA -positive cell bodies in the medial habenular nucleus (MH) and the nu-
merous GABA -immunoreactive terminals with a few cell bodies in the lateral habenular nucleus ((.H) D. Some of the
numerous small GABA -positive neurons and one of the few larger positive cells present in the anteroventral nucleus. E
Numerous small GABA -immunoreactive cell bodies and axon terminals in the zona incerta. Scale bars 25 (im.
SP ( 419), CCK (1 ), and CGRP ( 458). Many of

the fibers and axon terminals containing neu -
roactive peptides in the thalamus are of ex -
trinsic origin . Several neurons of the brain -
stem tegmentum that project massively to the
thalamus contains SP, CGRP, CCK , and , less
abundantly, NPY, DYN , and ENK ( 218).
These peptides are either coexpressed with
ChAT in cholinergic neurons of pedunculo-
pontine and lateral tegmental nuclei, or are
present in various combinations in non
cholinergic neurons of the same nuclei and in
-
the locus coeruleus, periaqueductal gray,
parabrachial, and paragigantocellularis nu -
clei ( 218). Other peptides, such as SP and
ENK , occur in spinothalamic fibers together
with glutamate and / or aspartate as the major
small molecule transmitter (17 ). In humans,
SP- and ENK-immunoreactive fibers were
seen to enter the thalamus anteromedially
from the hypothalamus, and posterolaterally
from the midbrain tegmentum ( 143). These
fibers arborize principally in the nuclei of the
posterior group and in the intralaminar nu
clei, except the centromedian nucleus. All
-
these structures have been implicated in pain
phenomena . No SP- and ENK -immunoreac-
Figure 16.35. Darkfield autoradiograph showing neu- tive cell bodies were disclosed in the human
rons of the rat reticular nucleus that express glutamic thalamus.
acid decarboxylase (GAD), the enzyme that synthesizes
GABA, as revealed by in situ hybridization technique The
In nonhuman primates, SOM , NPY, SP,
results were obtained with a cDNA probe that encodes and ENK of extrinsic origin innervate the
the 67k form of the enzyme , dorsal and ventral thalami and the epithala -
mus ( 270 ). They reach the thalamus via a ros-
tral and a caudal route. Fibers that follow the
rostral route course along the classic periven-
cystokinin (CCK ), neurotensin ( NT), vasoac- tricular system that links the hypothalamus
tive intestinal peptide ( VIP), and neuropep- with the epithalamus, while those in the cau -
tide Y ( NPY); ( b) the opiate peptide leu - dal route ascend within the lateral midbrain
and met -enkephalins ( ENK ) and dynorphin tegmentum. Some NPY- and SOM-positive
( DYN ); (c) the hypophysiotropic peptides so- fibers were also seen to enter the thalamus in
matostatin (SOM ) and corticotropin-releasing association with the ansa peduncularis,
factor (CRF); (d ) angiotensin; (e) calcitonin whereas SP- positive fibers appeared to as-
gene-related peptide; and ( f ) the calcium cend from the substantia nigra . The four
binding proteins calbindin D-28k (CaBP), par - types of fibers arborize densely within the in -
valbumin ( PV ), and calretinin (CR ). Largely tralaminar nuclei and in the reticular nucleus
because of species variations and / or differ- (270). Another immunohistochemical study
ences in the methodologic approach used , it is has revealed the presence of cell bodies im-
not possible at present to provide a general munoreactive for neurotensin ( NT) in the
picture of the distribution of all these peptides midline and mediodorsal nuclei, and less
for the mammalian thalamus. Only the most prominently in the intralaminar nuclei of
salient features are discussed here. monkeys ( 245 ). Neurotensin-immunoreactive
Relatively few thalamic cell bodies were fibers arborize profusely in the midline nu -
found to contain neuroactive peptides in the clei, particularly in the nucleus rhomboidalis.
thalamus of primates. In nonprimate species, Some NT- positive fibers were also encoun -
however, neurons of the CM - Pf complex pro- tered in the inferior thalamic peduncle ( 245).
jecting to the striatum were found to contain The two calcium binding proteins cal-
16 Thalamus 679
bindin D-28 k (CaBP) and parvalbumin ( PV ) cleus to anterior cingulate cortex is gluta -
are distributed in the primate thalamus ac - matergic and that its excitatory action is me-
cording to a strikingly complementary pat - -
diated by AMPA (a methyl propionic acid )
tern , and this has been used for providing a type receptor (100 ). The same investigations
new parcellation of the thalamus (144 ). For revealed that the response of cingulate cortex
example, in the posterior intralaminar nuclei, neurons to thalamic stimulation is regulated
PV labels intensely the CM - Pf complex, by GABA acting at both GABAA and GABAB
whereas this complex is virtually devoid of receptors.
CaBP immunoreactivity ( 144 ) ( Fig. 16.32). Glutamate immunoreactivity is also pre-
The subparafascicular nucleus, however, is sent in the axon terminals of various other
intensely stained for CaBP. In the reticular thalamic afferent systems, including ( a )
nucleus of cats and monkeys, GABAergic the medial lemniscal fibers terminating in
neurons coexpress somatostatin (SOM ), but the VP nucleus ( 66, 385), ( b ) the cervico-
such is not the case in the reticular nucleus of thalamic fibers (40 ), ( c) the retinogeniculate
rats, whose neurons appear to coexpress VIP fibers ( 271 ), and (d ) the trigeminothalamic
( 113, 306 ). The GABAergic neurons of the fibers ( 244 ).
reticular nucleus in most species display PV
but not CaBP immunoreactivity ( 59, 267). The Monoamines
comparative study of the immunoreactivity
for each of these two calcium binding pro- The thalamus receives a profuse mono-
teins and for GABA has led to a new func - aminergic innervation that derives princi-
tional parcellation of the reticular nucleus in pally from the noradrenergic neurons of the
rodents ( 268). locus coeruleus and from the serotoninergic
neurons of the dorsal raphe nucleus. A
Excitatory Amino Acids smaller contribution from the noradrenergic
neurons of the subcoeruleus region and from
Pharmacologic and electrophysiologic stud- the serotoninergic neurons of the median and
ies have revealed that excitatory amino acids pontine raphe nuclei has also been noted . Ex-
( EAA ) play a crucial role in the functional or- cept for a projection originating in the ventral
ganization of the thalamus ( 393). In keeping tegmental area and terminating in the habe-
with such a view , recent immunohistochemi - nula ( the so-called mesohabenular dopamin -
cal studies have shown that most principal ergic pathway ), the midbrain dopaminergic
afferent and efferent connections of the thala - neurons do not contribute significantly to the
mus use glutamate and / or aspartate as a innervation of the thalamus ( 28).
neurotransmitter. Glutamate and / or aspar - The noradrenergic innervation of the thal -
tate was shown to mediate the excitatory ef - amus has been studied in detail in rodents
fect of corticofugal fibers upon neurons of the with antibodies raised against the enzyme
reticular nucleus, as well as those of most --
dopamine p hydroxylase ( DBH ) that trans-
dorsal thalamic nuclei (66, 67, 105). Com - forms dopamine into noradrenaline ( 146,
bined retrograde transport techniques and 420 ). The noradrenergic fibers terminating in
immunohistochemical methods clearly reveal the thalamus form part of the large dorsal
that corticothalamic neurons in lamina VI are catecholamine bundle that courses in the dor-
positive for these EAA . Approximately 90% somedial part of the midbrain tegmentum .
of corticothalamic neurons are immunoreac- The fibers ascend beneath the thalamus in
tive for either glutamate or aspartate, and close association with the superior cerebellar
about 25% of these neurons are positive for peduncle. The fibers enter the thalamus
both (105). The excitatory action of the cor - through the zona incerta and the reticular nu -
ticothalamic fibers is mediated via both cleus. The noradrenergic innervation of the
N- methyl - D-aspartate ( NMDA ) and non - anteroventral nucleus is dense, whereas that
NMDA receptors ( 81 , 238, 385 ) . There is also of the other anterior nuclei , as well as that of
ample evidence to support the fact that the ventral and dorsal lateral geniculate nu -
thalamocortical neurons also use glutamate clei and the intralaminar nuclei, is moderate.
and / or aspartate as neurotransmitter (100, Only a few noradrenergic fibers are scattered
237, 271, 393). For example, anatomic and within the other nuclei of the thalamus. In the
physiologic studies in the rat suggest that the epithalamus, concentrations of fibers, enter-
thalamic projection from the mediodorsal nu - ing from behind , appear in the paraventricu-
lar and medial habenular nuclei. The main contains immunoreactive fibers and isolated
bundle of noradrenergic fibers that give rise varicosities that are distributed according to a
to the thalamic innervation continues ros - mediolateral gradient. The habenula and the
trally into the septum , medial cortical areas, ventral anterior nucleus are among the most
and hippocampal formation (146, 420). weakly innervated nuclei. In the latter nu -
Electron microscopic studies of the cate- cleus, as well as in more densely innervated
cholaminergic (and serotoninergic) terminals nuclei, thin varicose fibers form numerous
in the ventral posterior nucleus in monkeys pericellular contacts on cell bodies and proxi -
revealed that only 7-10% of the immunoreac- mal dendrites of thalamic neurons. The sero-
tive terminals form conventional synaptic toninergic innervation of the lateral nuclear
contacts in this region of the thalamus ( 231 ). group, as well as that of the medial and lat -
The dendritic shaft and somata of relay neu - eral geniculate nuclei, ranges from very weak
rons appear to be the major target of these to dense. The mediodorsal nucleus displays a
synaptic contacts that were mostly of the highly heterogeneous serotoninergic innerva -
asymmetric type. The vast majority of the im - tion that varies from weak in its central por -
munoreactive terminals made intimate mem - tion to moderate or dense in its medial and
brane associations with relay cell dendrites lateral borders. A moderate serotoninergic in -
and somata or presynaptic dendrites of in - nervation is observed in the anterior nuclear
terneurons, but no obvious membrane spe- group. The surprisingly dense and heteroge-
cializations could be found . These findings neous serotoninergic innervation of the thala -
suggest that the modulation of thalamocorti - mus noted here, suggests that this neuro-
cal relay function by brainstem monoaminer - transmitter is involved in several specific
gic pathways in the somatosensory thalamus functions of the primate thalamus ( 217).
may occur by release of transmitter at atypi- The presence of numerous serotoninergic
cal contact sites ( 231 ). receptors heterogeneously distributed in the
The serotoninergic innervation of the thal - thalamus of rats and primates strongly sup-
amus in monkeys has been studied in detail ports the hypothesis of a specific role of sero -
with antibodies raised directly against serotonin in thalamic functions. The serotoniner-
tonin ( 217) ( Figs. 16.36 and 16.37). As in the gic receptors in theCNS are divided into four
rat, the serotoninergic innervation of the thal- „ - - „
subtypes: 5- HT 5 HT2, 5 HT and 5 HT4 -
amus derives from extrinsic fibers arising (108). In most species, the serotoninergic re-
mostly from the midbrain raphe nuclei and ceptors disclosed at thalamic levels are
forming the transtegmental system (326). ,
mainly of the 5- HT subtype. Different sub-
Most of the fibers destined to the thalamus - ,
classes of 5 HT receptors have been de-
collect into a major bundle that sweeps , ,„ ,
scribed and termed 5- HT A, 5- HT , 5- HT c , 5-
dorsoventrally within the midbrain tegmen - HTID and 5-HT , E (108). The distribution of
(
tum and courses beneath the thalamus along the 5- HTK receptor subclass at thalamic lev -
its entire caudorostral extent. Several fiber els has been described in detail in several
fascicles break off from this main bundle at species, and the presence of 5-HT H and 5, -
different levels and ascend dorsally to inner- HTip, receptor subclasses has also been re-
vate the various thalamic nuclei. Overall, the ported in the thalamus ( 217). In nonhuman
-
5 HT innervation of the primate thalamus is primates, high levels of 5- HT , binding sites
more massive than would have been ex- are observed in most of the midline nuclei as
pected based on earlier studies in nonprimate well as in the parafascicular nucleus, whereas
species. Marked differences in the regional moderate levels are noted in the central me-
density of innervation can be noted both be- dial and anteroventral nuclei and in the ven -
tween the various nuclei and within single tral lateral geniculate nucleus. The remaining
nuclei. thalamic nuclei display low binding levels. In
The most densely innervated nuclei are humans, a similar distribution of 5- HT re- ,
those delineating the principal subdivisions ceptors, mainly 5-HTIA subclass, is observed
of the thalamic mass, that is the midline, ros- (333).
tral intralaminar, limitans, and reticular nu - The involvement of serotonin in pain
clei, where very dense fields of isolated ax- modulation is one of the most well -docu-
onal varicosities occur . In contrast to the mented roles of this indolamine at thalamic
rostral intralaminar nuclei, which are rather levels. Several studies in the rat have demon-
uniformly innervated , the CM-Pf complex strated that stimulation of the dorsal raphe
16 Thalamus 681
Figure 16.36. Camera lucida drawings of transverse sections through rostral (A), middle (B). and caudal (C) portions
of the thalamus in the squirrel monkey illustrating the distribution and relative density of serotonin-munoreactive fibers
(fines) and axon terminals ( dots), as visualized with an antibody raised directly against' serotonin AD. anterodorsal nu-
cleus. AV. anteroventral nucleus, C. central nucleus: CelW, centromedial nucleus; CM. centromedidn nucleus; CS .
. . .
central superior lateral nucleus: dLG dorsal lateral geniculate nucleus; H Forel' s field HI habenulo-lnterpeduncular
. .
tract; LD. lateral dorsal nucleus; LP. lateral posterior nucleus. MD mediodorsal nucleus Ml mammillothalamic tract;
. .
Pc paracentral nucleus. Pf parafascicular nucleus; RN. reticular nucleus; RE. nucleus reuniens; SM. stria medullaris;
VA ventral anterior nucleus. VL ventral lateral nucleus. vLG. ventral lateral geniculate nucleus. VPI. ventral posteroin-
ferloi nucleus. VPL ventral posterolateral nucleus: VPM. ventral posteromedial nucleus, 21 zona incerta
longed neuronal excitation associated with

the occurrence of single spike activity ( 239).
This excitation was specifically blocked by 5-
,
HT2 and 5-HT c antagonists, and appeared to
be mediated through a decrease in potassium
current . The same study showed that nor-
adrenaline produces a similar excitation and
that both noradrenaline and serotonin con-
verge onto the same potassium conductance.
In contrast, application of acetylcholine on
the same neurons results in a brief period of
inhibition (239 ). These results indicate that
serotonin exerts a specific excitation on thala -
mic neurons and that this neurotransmitter is
also involved in complex interactions with
other neurotransmitters, particularly nor-
adrenaline and acetylcholine, that are used
by well-characterized brainstem ascending
systems.
THALAMIC RADIATIONS AND

INTERNAL CAPSULE
Fibers that reciprocally connect the thala -
mus and the cortex constitute the thalamic ra-
diations. Thalamocortical and corticothalamic
figure 16.37. Darkfield photomontages showing the dis-
fibers form a continuous fan that emerges
tribution of serotonin-immunoreactive fibers and axon
terminals in lateral (dtG) and medial (MG) geniculate nu- along the whole lateral extent of the caudate
clei ( A), and in different rostral thalamic nucleis, including nucleus. Fiber bundles radiating forward ,
the reticular (/7), ventral anterior ( VA). anteromedial backward , upward , and downward form
( AM ), and central nuclei (B) Scale bar 500 jim
large portions of various parts of the internal
capsule ( Figs. 2.12, 2.14, 16.38, and 16.39).
Though the radiations connect with practi-
nucleus attenuates the increase in the firing cally all parts of the cortex, the richness of
rate of the parafascicular neurons induced by connections varies in different cortical areas.
noxious stimuli . In serotonin-depleted rats, Most abundant are the projections to the
both the stimulation of the dorsal raphe nu- frontal granular cortex, the precentral and
cleus and noxious stimuli elicited an in- postcentral gyri, the calcarine area, and the
crease in the firing rate of the parafascicular gyrus of Heschl. The posterior parietal region
neurons. The fact that this effect was not ad - and adjacent portions of the temporal lobe
ditive indicates that the serotoninergic projec- also have rich thalamic connections, but rela -
tion to the parafascicular nucleus has a tonic tively scanty radiations go to other cortical
inhibitory influence on the response to nox - areas ( 448).
ious stimuli (8). Likewise, iontophoretic ap- The thalamic radiations are grouped into
plication of serotonin upon neurons of the four subradiations designated as the thalamic
parafascicular nucleus reduced their re- peduncles ( Fig. 16.39). The anterior or frontal
sponse to noxious stimuli ( 64). peduncle connects the frontal lobe with the
Interesting information has been obtained medial and anterior thalamic nuclei. The su -
on the possible role of serotonin at thalamic perior or centroparietaI peduncle connects the
levels by in vitro experiments. For instance, it Rolandic area and adjacent portions of the
has been shown that serotonin reduces the frontal and parietal lobes with the ventral tier
ability to generate burst firing in lateral genic- thalamic nuclei. Fibers, carrying general sen-
ulate neurons ( 316 ). A similar effect was ob- sory impulses from the body and head , form
served in the reticular and suprageniculate part of this radiation and terminate in the
nuclei ( 239 ). Furthermore, local serotonin ap- postcentral gyrus ( Figs. 16.13, 16.14, and
plications resulted in a pronounced and pro- 16.39 ). The posterior or occipital peduncle con -
16 Thalamus 683
Lateral ventricle
Septum pellucidum Caudate nucleus
Internal capsule ^ / Globus palhdus

( anterior limb )
Putamen
^
Column of fornix Thalamus
anterior nuclear group
Internal capsule
( posterior iimb )
—.— . *Wi
ventral nuclear group
reticular nucleus
dorsomedial nucleus
Pulvmar
Pulvinar
Caudate nucleus —
^ Lateral ventricle
Fimbria
Hippocampal formation Stria medullaris
Figure 16.38. Horizontal section through thalamus, internal capsule, and basal ganglia (Weigert ' s myelin stain)
nects the occipital and posterior parietal con- earlier. The rest is composed mainly of corti-
volutions with the caudal portions of the thal- cal efferent fiber systems ( i.e., corticofugal
amus. It includes the optic radiations from fibers ), which descend to the brainstem and
the lateral geniculate nucleus and claustro- to the spinal cord . These include the corti -
cortical projections to the calcarine cortex cospinal, corticobulbar, corticoreticular, and
(striate area ) . The inferior or temporal peduncle corticopontine tracts ( Fig. 16.39 ).
is small and includes the connections of the The internal capsule, as seen in a horizon -
thalamus with the temporal lobe and the in- tal section, is composed of a shorter anterior
sula . Included in this peduncle are the audi - and a longer posterior limb , which meet at an
tory radiations from the medial geniculate obtuse angle. The junctional zone is known as
nucleus to the transverse temporal gyrus of the genu ( Figs. 2.13, 2.14, 16.38, 16.39, and
Heschl ( Fig. 16.39). 16.42). The anterior limb lies between the
The cerebral hemispheres are connected lentiform and caudate nuclei. The posterior
with the thalamus, brainstem, and spinal limb of the internal capsule Uenticulothalamic
cord by an extensive projection system. These portion ) lies between the lentiform nucleus
fibers arise from the whole extent of the cor- and the thalamus. A retrolenticular part of the
tex, enter the white substance of the hemi - internal capsule extends caudally for a short
sphere, and appear as a radiating mass of distance behind the lentiform nucleus. In this
fibers, the corona radiata , which converges to- caudal region , a number of fibers passing be-
ward the thalamus ( Fig. 2.12 ). On reaching neath the lentiform nucleus to reach the tem -
the latter, they form a broad , compact fiber poral lobe collectively form the sublenticular
band , the internal capsule , flanked medially by portion of the internal capsule.
the thalamus and caudate nucleus and later- The anterior limb of the internal capsule
ally by the lentiform nucleus ( Figs. 2.14, contains the anterior thalamic radiation or
16.38, and 16.39). Thus, the internal capsule is peduncle, and the prefrontal corticopontine
composed of all the fibers, afferent and effer- tract . The genu contains corticobulbar and
ent, which go to, or come from, the cerebral corticoreticular fibers.
cortex. A large part of the capsule is com- The posterior limb of the internal capsule
posed of the thalamic radiations described contains (a ) corticospinal fibers, ( b ) fronto -
Anterior limb
Frontopontine fibers
Anterior thalamic radiation

/ Head
caudate Posterior limb
Genu nucleus.
orticopontine fibers
Corticobulbar
fibers
.Superior thalamic radiation
.Corticofugal fibers
Corticospinal fibers
Thalamus
Pulvinar L' Auditory radiation
Geniculate body
-
*
Medial
Lateral -
Optic radiation
Corticofugal Thalamocortical
fibers fibers
Figure 16.39. Right internol capsule as seen in a horizontal section similar to that shown in Figure 16.38 Corticospinal
fibers in humans occupy the caudal third of the posterior limb of the internal capsule
pontine fibers, (c) the superior thalamic radia- -

the medial three fifths of the crus cerebri ap -
tion , and (d ) relatively smaller numbers of pears unreasonable on the basis of the num -
corticotectal, corticorubral , and corticoreticu- ber of fibers in this structure. Corticospinal
lar fibers. Corticospinal fibers in humans fibers in humans account for only 1 million of
have classically been considered to lie in the the 20 million fibers in this massive bundle -
posterior limb of the internal capsule rela- (428). The somatotopic arrangement of corti -
tively close to the genu (68). Results from cospinal fibers in the crus cerebri is much less
electrical stimulation and neuropathologic precise than commonly depicted. Fibers of
analyses suggest that corticospinal fibers are the superior thalamic radiation, located cau -
largely confined to a compact region in the dal to the corticospinal fibers, project signals
posterior half of the posterior limb of the in - concerned with general somatic sense to the
ternal capsule ( 25, 83, 103, 125, 401 ). Fibers of postcentral gyrus.
the corticospinal tract are somatotopically The rctrolcnticidar portion of the posterior
arranged in this part of the internal capsule, limb contains the posterior thalamic radia-
with those destined for cervical, thoracic, tions, including the optic radiations, parietal
lumbar, and sacral spinal cord segments and occipital corticopontine fibers, and fibers
arranged in a rostrocaudal sequence. The from the occipital cortex to the superior colli -
classic view that corticospinal fibers occupy culi and pretectal region ( Figs. 16.3 and
16 Thalamus 685
16.42). The sublenticular portion , difficult to with paracentral and peripheral vision . In the
separate from the retrolenticular, contains the macular region, the inner layers of the retina
inferior thalamic peduncle ( Fig. 16.9), the audi- are pushed apart, forming a small central pit,
tory radiations ( Figs. 2.11 and 16.39), and cor- the fovea centralis , which constitutes the point
ticopontine fibers from the temporal and the of sharpest vision and most acute color dis-
parieto-occipital areas. crimination. Here the retina is composed en -
Thalamocortical and corticofugal fibers with- tirely of closely packed slender cones (76, 94,
in the internal capsule occupy a compara- 423).
tively small, compact area ( Fig. 16.39). Le- The rods and cones are composed of an
sions in this area produce more widespread outer segment, a narrow neck, an inner seg-
disability than lesions of comparable size in ment, a cell body, and a synaptic base ( Fig.
any other region of the nervous system. 16.40). Photopigments are present in the
Thrombosis or hemorrhage of the anterior outer segments, where the photochemical re -
choroidal, striate, or capsular branches of the actions to light take place that give rise to the
middle cerebral arteries ( Fig. 4.14) are re- generator potential. The outer segment is
sponsible for most lesions in the internal cap- composed of a series of laminated discs de -
sule. Vascular lesions in the posterior limb of rived from the infolding of the plasma mem-
the internal capsule may result in contralat- brane. The photopigments, bound to the
eral hemianesthesia due to injury of thalamo- membranes of the discs, are constantly re -
cortical fibers en route to the sensory cortex. If newed . Rhodopsin is the photopigment of the
the genu of the internal capsule is included in rods in primates, and three pigments with
the injury, corticobulbar fibers may be de- maximum absorptions for blue, green, and
stroyed . Lesions in the posterior region of the red are present in the cones (443). The synap-
posterior limb may include the optic and au- tic base of the cone is called a pedicle, while
ditory radiations. In such instances, there that of the rod is referred to as a spherule.
may be a contralateral triad consisting of Each cone pedicle has several invaginations
hemianesthesia, hemianopsia, and hemihypa - which contain terminals of horizontal, midget
cusis ( Figs. 2.11, 16.39, and 16.42). More ex- bipolar, and flat bipolar cells in a specific
tensive vascular lesions may include the thal- arrangement. Rod spherules have a single in -
amus or corpus striatum, so that affective vagination containing multiple processes of
changes and symptoms due to injury of the horizontal and rod bipolar cells ( Fig. 16.40)
basal ganglia may be added to those charac- (303). Each midget ganglion cell makes sev-
teristic to the internal capsule. eral synaptic contacts with a single midget
bipolar cell. Diffuse ganglion cells establish
synaptic contacts with all types of bipolar
VISUAL PATHWAYS cells (77). Horizontal cells and amacrine cells
Retina constitute retinal interneurons. It is difficult
to determine whether processes of horizontal
The rods and cones of the retina are visual cells are axons or dendrites, and it is possible
receptors that react specifically to physical that each process may be capable of both re -
light. The cones, numbering some 7 million in ceiving and transmitting signals. Amacrine
the human eye, have a higher threshold of ex- cells in the inner plexiform layer have no
citability and are stimulated by light of rela- axon, but make synaptic contacts with all
tively high intensity. They are responsible for types of bipolar cells, other amacrine cells,
sharp visual definition and for color discrimi- and the dendrites and somata of ganglion
nation in adequate illumination. The rods, cells. The axons of ganglion cells, at first un-
whose number is estimated at more than 100 myelinated, are arranged in fine radiating
million, react to low intensities of illumina- bundles which run parallel to the retinal sur-
tion and subserve twilight and night vision. face and converge at the optic disc to form
Close to the posterior pole of the eye, the the optic nerve. On emerging from the eye -
retina shows a small, circular, yellowish area , ball the fibers immediately acquire a myelin
the macula lutea. The macula represents the sheath, and there is a consequent increase in
retinal area for central vision, and the eyes the size of the optic nerve.
are fixed in such a manner that the retinal In the retina, the transformation from opti-
image of any object is always focused on the cal to neural image involves three stages: (a )
macula . The rest of the retina is concerned phototransduction by a layer of receptor neu-
Pigment
epithelium
External limiting
membrane
Spherule Pedicle
Plexiform layers
Ganglion cell layer
Figure 16.40. Ultrastructural organization of the retina Rods ( blue) and cones (red) are composed of an outer seg-
ment (OS), an Inner segment ( IS), a cell body, and a synaptic base. Photopigments are present in the outer segments,
which are composed of laminated discs . The synaptic base of the rod Is called a spherule, while the synaptic base of
.
the cone is called a pedicle In the plexiform layers RB indicate rod bipolar cells. MB a midget bipolar cell, and FB a
.
flat bipolar cell. AM indicates an omacrine cell. Ganglion cells (MG midget ganglion cell; DG. diffuse ganglion cell)
and retinal afferents are In yellow
rons; ( b ) transmission of their signals by cells that convey signals from the inner
chemical synapses to a layer of "bipolar" svnaptic layer back to the outer one (94, 416,
cells; and (c) transmission of these signals, 423).
also by chemical synapses, to the ganglion Retinal ganglion cells are of different sizes,
cells, which are the output elements of the project to different sites and form at least
retina ( 416, 423). At both synaptic stages ( i .e., three functional classes (38, 42, 92, 173, 192,
receptors to bipolar cells and bipolar to gan- 416, 417). Distinct classes of ganglion cells are
glion cells) the horizontal and amacrine cells referred to as X, Y, and W cells. The X class
serve to modify the transmission across the cells have slower conduction velocities than
synaptic layers. There are also interplexiform Y cells, exhibit sustained or tonic responses,
16 Thalamus 687
and project to the dorsal lateral geniculate Optic Tract

nucleus and the pretectum. The Y cells have
rapidly conducting axons, exhibit transient or On each side, the optic tract partially encir -
phasic responses, and project to both the dor- cles the hypothalamus and the rostral por-
sal lateral geniculate nucleus and the superior tions of the crus cerebri . Most of its fibers ter-
colliculus. The W ganglion cells have either minate in the lateral geniculate nucleus,
tonic or phasic responses, very slow axonal though small portions continue as the
conduction velocities, and project to the supe- brachium of the superior colliculus to the su -
rior colliculus and the pretectum . It has been perior colliculi and pretectal area ( Fig. 16.41 ).
suggested that (a ) the largest ganglion cells The lateral geniculate nucleus gives rise to
correspond to the Y cells, (b) the medium- the geniculocalcarine tract, which forms the
sized cells with narrow dendritic arboriza- last relay of the visual pathway. The pretectal
tions correspond to the X cells, and (c) the area is concerned with light reflex, and the
smallest ganglion cells with the widest den - superior colliculi with reflex movement of the
dritic arborizations correspond to the W cells. eyes and head and tracking of visual stimuli.
Because the central projections of these Retinohypothalamic fibers terminate bilater -
classes of retinal ganglion cells differ, it is ally in the suprachiasmatic nucleus of the hy-
presumed that their functional roles also dif - pothalamus ( 272, 277, 344, 425). This direct
fer. Both X and Y cells possess properties that retinal projection is functionally relevant to
contribute to the highly discriminative as- neuroendocrine regulation ( 249).
pects of vision. The smaller receptive field of
the X cells permit resolving higher spatial fre- Geniculocalcarine Tract
quencies than Y cells, but Y cells are more
sensitive to moving stimuli. The X cells tend This tract arises from cells of the dorsal lat-
to be concentrated near the central retina, eral geniculate nucleus, passes through the
whereas Y cells occur in all parts of the retina. retrolenticular portion of the internal capsule,
The Y cells are much less numerous than ei- and forms the optic radiations. Its fibers ter-
ther X or W cells. Since W cells do not project minate on both sides of the calcarine sulcus in
to the dorsal lateral geniculate nucleus, it is the striate cortex (area 17) ( Figs. 2.6, 16.14,
presumed that X-type ganglion cells must be 16.41, and 16.42). All fibers of the optic radia -
concerned with central vision (92). tion do not reach the cortex by the shortest
route ( Figs. 16.41 and 16.42). The most dorsal
Optic Nerves fibers pass almost directly backward to the
striate area. More ventral fibers first turn for-
These nerves enter the cranial cavity ward and downward into the temporal lobe,
through the optic foramina and unite to form and spread out over the rostral part of the in-
the optic chiasm, beyond which they are con- ferior horn of the lateral ventricle, and then
tinued as the optic tracts. Within the chiasm a loop backward. These fibers pass close to the
partial decussation occurs, the fibers from the outer wall of the lateral ventricle (external
nasal halves of the retina crossing to the oppo- sagittal stratum ) to reach the occipital cortex
site side, and those from the temporal halves of ( Fig. 2.22). The most ventral fibers make the
the retina remaining uncrossed (Fig. 16.41). In longest loop ( Figs. 16.41 and 16.42). These
binocular vision, each visual field, right and fibers, which are referred to as the temporal or
left, is projected upon portions of both retinae. Meyer' s bop of the geniculocalcarine tract, ter-
Thus, the images of objects in the right field of minate in the visual cortex below the cal-
vision ( red in Fig. 16.41) are projected on the carine sulcus. Lesions in the temporal lobe in-
right nasal and the left temporal half of the volving Meyer's loop causes a defect in the
retina. The right monocular crescent of the vi- upper visual field on the side opposite to the
sual field projects upon retinal receptors only lesions. Lesions in the parietal lobe, on
in the most medial part of the right nasal retina the other hand , involving the more direct
(Fig. 16.27). In the chiasm, the fibers from these geniculocalcarine fibers that terminate above
two retinal portions are combined to form the the calcarine sulcus, may produce a defect in
left optic tract. By this arrangement, the whole the lower visual field on the side opposite
right field of vision is projected upon the left to the lesions.
hemisphere, and the left visual field upon the The retinal areas have a precise point- to-
right hemisphere (94, 249). point relationship with the lateral geniculate
Visual fields
Upper quadrant
.1L .
Macular area
Lower quadrant
\ i
* i
\ / Nasal
\ / retinae
\ I. .
. .
i:
\ if Optic tract
Temporal retina I
j \ iitt
Oculomotor
Optic nerve tl Nerve
Nuclei
Optic chiasm
a
Ventricle Geniculate bodies

Lateral
Medial
Superior colliculus
[ i
r
Optic radiations
Calcarine sulcus
Visual cortex
Left occipital cortex
( area 17 )
Figure 16.41 . Visual pathways viewed from the ventral surface of the brain Light from the upper halt of the visual
field falls on the inferior half of the retina. Light from the temporal half of the visual field falls on the nasal half of the
retina, while light from the nasal half of the visual field falls on the temporal half of the retina. The visual pathways from
the retina to the striate cortex are shown. The plane of the visual fields has been rotated 90° toward the reader . The in-
sert shows the projection of the quadrants of the visual field upon the left calcarine (striate) cortex The macular area
of the retina is represented nearest the occipital pole. Fibers mediating the pupillary light reflex leave the optic tract
and project to the pretectal region; other fibers relay Impulses indirectly to the visceral nuclei of the oculomotor com-
plex.
nucleus, each portion of the retina projecting dal part of the lateral geniculate nucleus on
on specific and topographically limited por- both sides of the plane representing the hori-
tions of the layers of the lateral geniculate nu - zontal meridian ( 247). The peripheral field ,
cleus ( Figs. 16.27, 16.28, and 16.29 ). The fibers including the monocular crescent, is repre-
from the upper retinal quadrants ( represent - sented rostrally in the lateral geniculate nu-
ing the lower visual field ) terminate in the cleus and is continuous across the horizontal
medial half , while those from the lower quad - meridian ( Fig. 16.29 ). A similar point -to-point
rants terminate in the lateral half of the lateral relation exists between the lateral geniculate
geniculate nucleus. The macula is repre- nucleus and the striate cortex. The medial
sented by a wedge-shaped sector in the cau - half of the lateral geniculate nucleus, repre -
16 Thalamus 689
Somatosensory Posterior limb 1 Internal

radiation Anterior limbi capsule
Frontopontine
fibers
Uncinate
fasciculus
radiation
Anterior commissure
Auditory radiation
Lentiform nucleus (removed)
Figure 16.42. Brain dissection showing the corona radiata The lentiform nucleus has been removed and its position
marked by an asterisk . The visual, auditory, and somatosensory radiations are identified
senting the upper retinal quadrants ( lower vi - general types of receptive fields have been
sual fields), projects to the superior lip of the described: (a ) those with an "on" center and
calcarine sulcus. These fibers form the supe- an "off " surround , and ( b) those with an "off "
rior portion of the optic radiation ( Fig. 16.41 ). center and an "on" surround . If a light stimu -
The lateral half of the lateral geniculate nu - lus illuminates an "on" center, or an "on"
cleus, representing the lower retinal quad - surround the ganglion cell will fire vigor-
rants ( upper visual field ), projects to the infe- ously. If the light stimulus strikes an "off"
rior lip of the calcarine sulcus. These fibers center, or an "off " surround, the ganglion cell
form the inferior portion of the optic radia - is inhibited until the light is turned off . When
tion . The macular fibers, which constitute the the light is withdrawn , the ganglion cell will
intermediate part of the optic radiation, ter- fire ( Fig 20.22 ). If the light stimulus illumi-
minate in the caudal third of the calcarine nates both "on" and "off" zones, mutual inhi-
cortex. Those from the paracentral and pe- bition cancels the stimulus. Retinal connec-
ripheral retinal areas end in respectively tions account for the concentric circular
more rostral portions. receptive fields at the ganglion cell level ( 76,
Experimental studies with stationary spots 77). Impulses from the central zone are said
of light have revealed important information to be mediated by direct connections between
regarding the organization of the receptive receptor cells, bipolar cells and ganglion cells,
fields of retinal ganglion cells and collicular w'hile the antagonistic surround zone has in-
neurons (151, 154, 206 ). In the retina, the re- terposed connections with amacrine cells ( i.e.,
ceptive field is related to those receptors, rods between bipolar and ganglion cells).
and cones, and other retinal neurons which The receptive fields of neurons in the lat-
influence the excitability of a single ganglion eral geniculate nucleus appear similar with
cell (163). The retina is a composite of as stationary spots of light (151, 154, 249), but
many receptive fields as there are ganglion lateral geniculate neurons show a greater
cells. Each receptive field is organized into suppression of the receptive field periphery
two zones: (a ) a small circular central zone, (163). Cells in the different laminae of the lat -
and ( b ) a surrounding concentric zone re - eral geniculate nucleus are driven from re-
ferred to as the periphery, or surround . These ceptive fields in one eye, either ipsilaterally
two zones are functionally antagonistic. Two or contralaterally. No cells in the lateral
geniculate nucleus are influenced binocu- that homonymous defects are caused by le -
larly. An important transformation of the re- sions on one side anywhere behind the
ceptive field properties occur between the lat- chiasm ( i.e., optic tract, lateral geniculate nu -
eral geniculate nucleus and cells in the striate cleus, optic radiations, and visual cortex ).
cortex. Cells in the striate cortex respond to Complete destruction of any of these struc-
"slits" of light, or moving visual patterns ori- tures results in a loss of the whole opposite
ented in specific directions ( Fig. 20.23) field of vision ( homonymous hemianopsia ) ( Fig.
(152-154). The transformation that occurs in 16.43C). Partial injury may produce quadran-
the striate cortex is based upon columns of tic homonymous defects. Lesions of the tempo -
cortical cells of different functional types that ral lobe, destroying the looping fibers in the
encode a wide variety of variables in vertical lower portion of the optic radiations, are
and horizontal systems (173, 249). likely to produce homonymous quadrantic
defects in the upper visual field . Injury to the
Clinical Notes parietal lobe may involve the most superiorly
placed fibers of the radiations and cause simi -
Injury to any part of the optic pathway lar defects in the lower field of vision.
produces visual defects whose nature de- Lesions of the chiasm may cause several
pends on the location and extent of the injury. kinds of heteronymous defects. Most com-
During examination, each eye is covered in monly, crossing fibers from the nasal portions
turn as the retinal quadrants of the opposite of the retina are involved, with consequent
eye are tested . Visual defects are said to be loss of the two temporal fields of vision
homonymous when restricted to a single visual ( bitemporal hemianopsia ) ( Fig. 16.43D ). Visual
field, right or left, and heteronymous when defects of this type result from pituitary ade-
parts of both fields are involved. It is evident nomas that expand out of the sella turcica.
Left Right
Visual Fields
I T 1 N | M 1 T |
_Nasal
retina Total blindness of
Temporal A right eye
D
retina
Optic N .
Optic
B
C
B
O
Right nasal
hemianopsia
tract
Oij
'
A
•© Left homonymous
hemianopsia
Visual
Bitemporal heterony -
9
Optic cortex mous hemianopsia
radiation
Figure 16.43. Common lesions within the visual pathway On the left. A through D indicate lesions , Corresponding vi-
sual field defects are shown on the right ,
16 Thalamus 691
Rarely, both lateral angles of the chiasm may cortex lie in the ventral tier of the lateral nu -
be compressed. In such cases, the nondecus- clear group. The so-called specific sensory
sating fibers from the temporal retinae are af - relay nuclei include the medial and lateral
fected , which results in loss of the nasal vi- geniculate nuclei and the major divisions of
sual fields ( binasal hemianopsia ). Injury of one the ventral posterior nucleus, known as the
optic nerve naturally produces blindness in ventrobasal complex. The medial geniculate
the corresponding eye with loss of the pupil- nucleus receives fibers from the inferior col -
lary light reflex ( Fig. 16.43A ). The pupil will , liculus. The laminated , tonotopically orga -
however, contract consensually to light enter- nized parvicellular part of the nucleus pro-
ing the other eye, since the pretectal reflex jects fibers via the geniculotemporal radiation
center is related to both Edinger- Westphal to the transverse temporal gyrus of 1 leschl,
nuclei . The pupillary light reflex will not be the primary auditory area ( Figs. 13.13 and
affected by lesions of the visual pathway 16.13). The lateral geniculate nucleus, receiv -
above the brachium of the superior colliculus ing both crossed and uncrossed fibers of the
( Fig. 16.41 ) . optic tract , gives rise to the geniculocalcarine
fibers, which project in a specific way to the
FUNCTIONAL CONSIDERATIONS cortex surrounding the calcarine sulcus. This
cortex represents the primary visual area ( Fig.
All sensory impulses, with the sole excep- 16.41 ).
tion of the olfactory ones, terminate in the The divisions of the ventral posterior nu -
gray masses of the thalamus, from which cleus ( VPLc, VPM , and VPMpc ) project to the
they are projected to specific cortical areas by cortex of the postcentral gyrus. In the post -
the thalamocortical radiations. Some fibers central gyrus, all parts of the body are repre-
from the olfactory tubercle, piriform and en- sented in a definite sequence ( 336). This corti-
torhinal cortex, and basolateral amygdaloid cal region is referred to as the primary
nuclei project to the mediodorsal nucleus, but somestlwtic area (somatic sensory area I ). The
this nucleus does not relay impulses to the sensory representation of the body in the pri-
primary olfactory cortex ( 203, 227, 353). mary somesthetic area (S- I ) is duplicated in a
While portions of the thalamus serve as pri - different sequence in the second somatic area
mary relay nuclei in various sensory path- (S-II ), which lies buried along the superior
ways in which impulses are projected to bank of the lateral sulcus (335, 456 ). Somatic
specific regions of the cerebral cortex, the sensory area II receives fibers ipsilaterally
structure and organization of the thalamus from VPI and bilaterally from S- I ( 44, 89, 181,
indicate that its function is more complex and 182, 184, 186 ), and responds mainly to cuta-
elaborate than that of a simple relay station . neous stimuli ( 374 ).
The thalamus is obviously one of the chief Signals from peripheral receptors do not
sensory integrating mechanisms of the neu - pass through the thalamus without modifica -
raxis, but its functions are not limited to this. tion. Many of the impulses are modified and
There is abundant evidence that specific parts integrated at the thalamic level before being
of the thalamus play a dominant* role in the projected to specific cortical areas. The thala -
maintenance and regulation of the state of mocortical projection, which represents one
consciousness, alertness, and attention, but of the most massive fiber collections of the
also with the emotional correlates that accom - entire neuraxis, is likely to play a very active
pany most sensory experiences. Other data role in the modulation of the information it
suggest that some thalamic nuclei serve as in - receives from the thalamus. It is through this
tegrative centers for motor and limbic func- cortico- thalamo-cortical loop that the cerebral
tions, since their principal afferent projections cortex can direct its attention to certain sen -
are from the cerebellum and the basal gan- sory experiences and amplify specific sensory
glia, on one hand , and from various limbic messages at the expense of others. In certain
structures on the other. lesions of the thalamus or of the thalamocor -
tical connections, after a brief initial stage of
Thalamic Relay Functions complete contralateral anesthesia, pain, crude
THALAMUS AS A SPECIFIC SENSORY RELAY touch , and some thermal sense return . How-
ever, tactile localization , two-point discrimi-
Thalamic nuclei involved in the relay of nation, and the sense of position and move-
specific sensory information to the cerebral ment remain severely impaired (134, 135).
The sensations recovered are poorly localized medial geniculate nucleus project to the pri-
and are accompanied by a great increase in mary auditory cortex, while those in other cy-
"feeling tone," most commonly of an un - tologic subdivisions of the medial geniculate
pleasant character. This condition is referred nucleus project to a belt of secondary audi-
to as the "thalamic syndrome" ( Dejerine- tory cortex surrounding the primary auditory
Roussy syndrome). Though the threshold of area.
excitability is raised on the affected side, tac- The "affective" side of sensation is con-
tile and thermal stimuli, previously not un- cerned with pain, agreeableness, and dis-
pleasant, evoke disagreeable sensations agreeableness. Pain is a subjective sensation
(dysesthesias). that often is difficult to describe and almost
There are two aspects to sensation: the dis - impossible to measure. The localization of
criminative and the affective. In the former, different types of pain is often inexact and
stimuli are compared with respect to inten- clinical judgment of its intensity must take
sity, locality, and relative position in space into account the personality of the patient.
and time. These impulses are integrated into Temperature and many tactile sensations
perceptions of form, size, and texture; move- likewise have a marked affective tone. This is
ments are judged as to direction, amplitude, especially true for visceral sensations, in
and sequence. These aspects of somatic sen
sation are related to VPLc and VPM and their
- which the discriminative element is practi
cally absent. This affective quality , which
-
restricted cortical projection areas. There is a forms the basis of general bodily well-being
complete, though distorted , representation of or malaise, and of the more intense emotional
the body in VPLc and VPM , and VP neurons states, is believed to be "appreciated" at the
are modality specific, being concerned thalamic rather than the cortical level, though
mainly with tactile and position sense, and
responding to either superficial mechanical
it may be profoundly modified and con
trolled by the latter.
-
stimulation of the skin , mechanical distortion
of deep tissues, or joint rotation, but not more THALAMUS AS A LIMBIC -MOTOR RELAY
than one of these (58, 111 ). Some impulses
arising from primary endings in muscle spin - The so-called cortical relay nuclei of the
dles ( group la fibers), conveyed to the outer thalamus (or specific thalamic relay nuclei )
shell of the ventrobasal complex, are relayed receive impulses from specific subcortical
to the depths of the central sulcus ( area 3a ) structures and project to well-defined cortical
(179, 315, 431 ). These responses from muscle regions. These nuclei include (a ) the anterior
spindles reach the thalamus via the posterior nuclei, ( b) the ventral posterolateral nucleus,
column nuclei and VPLc. pars oralis ( VPLo), and the ventral lateral nu -
The visual and auditory thalamic nuclei cleus, pars caudalis ( VLc), and (c ) the ventral
are organized in a very specific manner in lateral nucleus, pars oralis ( VLo) and the ven -
-
which point for- point relationships exist be- tral anterior nucleus, pars parvicellularis
tween the receptor organ, thalamic nuclei, ( VApc ). The anterior nuclei of the thalamus
and the thalamocortical projections. Columns receive the largest efferent fiber bundle from
of cells in all layers of the lateral geniculate
nucleus receive inputs from corresponding — —
the hypothalamus the mammillothalamic
tract and direct projections from the hip-
points in the retina and , in turn , project to the pocampal formation via the fornix ( Figs. 16.2,
striate cortex in a retinotopic fashion . No 16.8, and 17.14 ). These nuclei, in turn , project
binocular fusion occurs in the lateral genicu - to the cingulate gyrus, a cortical area demon-
late nucleus. This visual input to the cortex is strated to produce a variety of visceral and
transformed in a manner that gives individ- limbic functions.
ual cortical neurons properties different from The contralateral deep cerebellar nuclei
the lateral geniculate neurons, but better project most of their ascending fibers to nu -
suited to detect shapes and patterns, and to clei of the "cell-sparse" thalamic region
provide binocular vision ( Figs. 20.22 and ( VPLo, VLc, and "area x"), which in turn pro-
20.23). The auditory thalamic relay nuclei are jects somatotopically on the primary motor
organized in a similar specific manner. The ( M - l , area 4 ). Furthermore, the "cell -sparse"
cellular laminae in the medial geniculate nu - zone in the ventral lateral thalamic region re-
cleus, evident only in Golgi preparation, ceives projection from the two major output
forms the basis for the tonotopic organiza - structures of the basal ganglia, namely the in-
tion . Neurons in the ventral division of the ternal pallidal segment and the substantia
16 Thalamus 693
nigra pars reticulata . The termination fields between relay and burst modes at any time,
of cerebellar, pallidal, and nigral projection to the relay mode appears to be the state of most
the thalamus do not overlap. Pallidal fibers thalamic neurons in the awake, alert animal,
terminate in VLo and VApc that in turn pro- whereas the burst mode dominates during
ject to the supplementary motor area ( M -1 I ), less alert periods, including drowsiness and
whereas nigral fibers arborize in VAmc quiet or non-REM sleep ( 413). During such
and MDpl that project to the prefrontal cor
tex. The pallidal and nigral fibers exert a
- inattentive periods, the electroencephalogram
( EEG ) in all animals, including humans, be-
GABAergic inhibitory action on thalamic comes highly synchronized and fast. Rhyth-
relay neurons, while the effect of cerebellar mic, spike-like electrical phenomena known
fibers is a glutamatergic excitation . Each of as spindles can be seen . These spindles have a
three neuronal systems (cerebellar, pallidal, frequency of 7-14 Hz.
and nigral ) form parallel segregated channels This dominant feature of the synchronized
that are concerned with unique and different EEG is generated in the thalamus ( 413). Elec-
aspects of motor function . trophysiologic studies of thalamic neurons
Low frequency electrical stimulation of in - have shown that all neurons of the reticular
dividual specific sensory relay nuclei, and nucleus can spontaneously generate rhythmic
certain cortical relay nuclei ( i.e., the ventral discharges at a rate of approximately 10 Hz.
lateral nucleus), evokes a primary surface po- The low-threshold spike appears to be the
tential followed by an augmenting sequence underlying cause of this endogenous burst-
which is limited to the cortical projection ing behavior, and the oscillations can be gen -
area. This response is called the augmenting erated within individual reticular nucleus
response. Characteristically, the augmenting neurons. Dendrodendritic synapses between
responses ( a ) have a short latency, ( b ) are reticular nucleus neurons could serve to syn-
dysphasic and increase in magnitude during chronize the entire reticular nucleus region
the initial four or five stimuli of a repetitive and , hence, influence in a highly coordinated
train, and (c) are localized to the primary cor- fashion the neuronal activity of virtually all
tical projection area of the specific thalamic thalamic nuclei ( 73). Neurons of the reticular
nucleus stimulated ( 71 ). nucleus can generate such synchronized os-
cillatory activity in the absence of external in -
Thalamic Gating Functions puts, whereas neurons of thalamic nuclei de-
prived of their reticular nucleus input fail to
Thalamic relay cells exhibit two response display spindling activity ( 74, 411, 413).
modes: a relay mode and a nonrelay burst These findings suggest that the reticular nu -
mode (393). If a cell is at rest or slightly depo- cleus acts as a kind of pacemaker for thalamic
larized , it is in a relay mode. In such a condi - relay cells. Since it can induce synchronized
tion , a suprathreshold excitatory postsynaptic bursts in thalamic neurons, the reticular nu -
potential ( EPSP) will induce a train of action cleus can markedly affect the gating functions
potentials. The frequency of action potentials of the thalamic neurons. Hence, the reticular
monotonically rises with increasing EPSP nucleus appears capable of modulating thala -
amplitude. Under these conditions, transmis- mic neural activity, particularly in relation to
sion through the thalamic relay neuron to the the passage of afferent volleys through the
cortex will lead to a pattern of input to the thalamus. It also appears involved in the
cortex that faithfully reflects the pattern of modulation of thalamic activity during
retinal or lemniscal input to the thalamus. sleep and arousal, and this may reflect its
However, once a thalamic neuron becomes own underlying control by brainstem cholin -
hyperpolarized sufficiently long to deinacti - ergic, noradrenergic, and serotoninergic af -
vate a low threshold spike, it enters the burst ferents.
mode. In such a state, a suprathreshold EPSP
will trigger a low-threshold spike, and many Thalamic Association Functions
such spikes may ensue as the cell bursts
rhythmically. Until this bursting cycle is bro- -
The so called association nuclei of the thal -
ken, the neuron no longer relays sensory amus are those nuclei that are not governed
input to the cortex because its firing pattern by a single sensory modality and project
bears no resemblance to the pattern of its reti - largely to association areas of the cerebral
nal or lemniscal inputs (393). cortex in the frontal and parietal lobes and , to
Although thalamic neurons may switch a lesser extent, in the occipital and temporal
lobes. The principal association nuclei in - clei and part of the ventral anterior nucleus.
clude the mediodorsal nucleus ( MD), the lat - Repetitive stimulation of these thalamic nu -
eral dorsal nucleus ( LD), the lateral posterior clei alters spontaneous electrocortical activity
nucleus ( LP), and the pulvinar ( P ) ( Pip. 16.12 ). over large areas and , under certain condi -
The mediodorsal nucleus, the most promi- tions, resets the frequency of brain waves by
nent gray mass of the medial thalamus, is eliciting responses that are time-locked to the
highly developed in primates, especially hu - thalamic stimulus ( 71, 72, 283). The most
mans ( Fig. 16.13). This nucleus is character- characteristic effect of stimulating the non-
ized by its massive and reciprocal connec - specific thalamic nuclei is the recruiting re-
tions with the granular frontal cortex. Large sponse. When the frequency of stimulation is
bilateral injuries to the frontal lobes cause de- in the range of 6 to 12 cycles per second, pre-
fects in complex associations, as well as dominantly surface negative cortical re-
changes in behavior, expressed by loss of ac - sponses rapidly increase to a maximum ( by
quired inhibitions and excessive, and some- the fourth to sixth stimulus of the train ) and
times inappropriate, emotional responses. then decrease over a broad area. Continued
These alterations in emotional behavior are stimulation causes the evoked responses to
produced when the pathways between the wax and wane. Stimulation of one of the non -
dorsomedial nucleus and the frontal cortex specific thalamic nuclei causes all others to be
are severed ( e.g., in frontal lobotomy ). activated in a mass excitation ( 407). Although
The lateral dorsal nucleus projects upon stimulating the nonspecific thalamic nuclei
portions of the limbic and precuneal cortex. produces changes in electrocortical activity
The larger lateral posterior nucleus has exten - over broad areas, these effects are not indis-
sive connections with the association cortex criminate or equal in all cortical areas. Re-
of the superior and inferior parietal lobules, sponsive cortical zones appear to be rela -
concerned with cognitive and symbolic func - tively specific in the frontal, cingulate, orbital ,
tions. The pulvinar develops as a huge nu - parietal and occipital association areas. This
clear mass concerned with the integration of diffuse thalamic projection system appears
general and special somatic senses, particu - capable of exerting a massive influence
larly vision and audition. The inferior and mainly upon large regions of associate cortex,
parts of the adjacent lateral pulvinar are in - but the most profound effects are upon the
volved in extrageniculate projections to the frontal association cortex ( 409).
secondary visual area . The original observation of Moruzzi and
Magoun ( 285) that cortical recruiting re-
Thalamic State - Dependent Functions sponses induced by low frequency stimula -
tion of the nonspecific thalamic nuclei could
Stimulation of the ascending reticular acti- be reduced , or blocked , by stimulation of the
vating system and various kinds of sensory bulbar reticular formation provides evidence
stimuli result in a generalized desynchroniza - that the nonspecific nuclei of the thalamus
tion and activation of the electroencephalo- are within the sphere of influence of the as-
gram , and behavioral arousal. The EEC cending reticular formation. The cholinergic,
arousal response, which produces dramatic noradrenergic, and serotoninergic systems
effects upon cortical activity, is mediated, in represent some of the brainstem ascending
large part, by the intralaminar thalamic nu - neuronal systems that can modulate neurons
clei . Physiologic studies presumed that im - of the nonspecific thalamic nuclei and hence
pulses producing these changes in cortical ac- exert a profound influence upon the electro-
tivity reached the cortex via a diffuse, cortical activity according to various state -
nonspecific thalamic projection system (164, dependent conditions. Some of these long
166, 284, 285, 407 ). The more rostral intralam - ascending chemospecific systems ( i.e., nora -
inar thalamic nuclei (CL and PCN ), which drenergic and serotoninergic systems) also
receive fibers from the midbrain reticular for- have straight access to the cerebral cortex,
mation , project directly to widespread corti- where they can directly modulate the activity
cal regions. of vast cortical neuronal assemblies.
Stimulation of the so-called nonspecific The largest component of the intralaminar
thalamic nuclei, produces widespread and nuclei, the centromedian - parafascicular (CM -
pronounced effects on the electrocortical ac- Pf ) nuclear complex receives its input mainly
tivity . The nonspecific , or diffuse , thalamic nu- from forebrain derivatives. The precentral
clei include the intralaminar and midline nu- and premotor cortex project profusely upon
16 Thalamus 695
these nuclei ( 7, 209, 210). The centromedian bellar nuclei , the internal pallidal segment,
nucleus (CM ) also receives collaterals of pal - and the pars reticulata of the substantia nigra
lidofugal fibers arising in the internal pallidal concerned with different aspects of motor
segment. The principal projection of the CM - function . Massive cortical projections bring
Pf complex is to the striatum, with cells in Pf thalamic nuclei under the influence of sen-
projecting to the caudate nucleus (associative sory , motor, and association areas of the cor-
striatal territory ) and those in CM projecting tical mantle. Most of the sensory and motor
to the putamen (sensorimotor striatal terri - systems converge on thalamic nuclei in a
tory ) . These connections suggest that the CM - very specific manner without overlap. The
Pf complex plays an important role in motor thalamus integrates these systems and dis-
integration . tributes projections to specific areas of the
The thalamus is played upon by two great cerebral cortex . The thalamus is a neural cen -
streams of afferent fibers, one peripheral and ter where highly complex neural integration
one central . Signals are generated in receptors occurs, involving sensory , motor, limbic, and
in all parts of the body and convey informa - state-dependent neuronal systems. The result
tion concerning changes in the external envi - of such high- level integration will markedly
ronment . Additionally, the thalamus receives influence the activity of the entire brain .
significant subcortical inputs from the cere-
References Paxinos G, ed . The human nervous ( Miiaicii mulatta ). | Comp Neurol

system . Ch. 18. New York: Acade- 1975;!60*339 362
1. Adams CE, Fisher RS. Sources of mic Press, 1990:469-481. 20. Benevento LA , Rezak M . The corti -
neostriatal cholecystokinin in the 11 . Aronson LR, Papez JW . The thala - cal projections of the inferior pulv -
cat . J Comp Neurol 1990;292: mic nuclei of Pithecus ( Macacus ) inar and adjacent lateral pulvinar
-
563 574. Rhesus. II . Dorsal thalamus. Arch in the rhesus monkey ( Macaco mu
2. Adem A, Jossan SS, d ' Argy R, Neurol Psychiatr 1934;32:27-44. hit hi ): an autoradiographic study .
Brandt I , YVinblad B, Nordberg A . 12. Asanuma C, Porter LL . Light and Brain Res 1976;108:1-24
Distribution of nicotinic receptors electron microscopic evidence for a 21. Benson DL, Isackson PJ, Hendry
in human thalamus as visualized GABAergic projection from the SH, Jones F.G . Differential gene
by ( 3H| nicotine and |’H| acetyl - caudal basal forebrain to the thala - expression for glutamic acid decar -
choline receptor autoradiography . mic reticular nucleus in rats. J boxylase and type II calcium -
J Neural Transm 1988;73:77-83. Comp Neurol 1990;302:159-172. calmodulin -dependent protein ki -
3. Afifi A , Kaelber YVYV. Efferent con - 13. Asanuma C, Thach YVT, Jones EG. nase in basal ganglia , thalamus,
nections of the substantia nigra in Anatomical evidence for segre - and hypothalamus of the monkey .
the cat . Exp Neurol 1965;11: gated focal groupings of efferent J Neurosci 1991; 11 :1540-1564 .
474-482. cells and their terminal ramifica - 22. Berense HYV, Groenewegen HJ .
4 . Aggleton JP, Miskin M . Memory tions in the cerebellothalamic path - Organization of the thalamostri -
impairments following restricted way of the monkey . Brain Res Rev atal projection in the rat , with spe -
medial thalamic lesions in mon -
key . Exp Brain Res 1983;52:
-
1983;5:219 235. cial emphasis on the ventral stria -
14. Auer J . Terminal degeneration in tum . J Comp Neurol 1990;299; 1
199-209. the diencephalon after ablation of 87- 22 s
5. Aggleton JP, Miskin M. Projections frontal cortex in the cat . J Anat 23. Berry CM , Anderson FD, Brooks
of the amygdala to the thalamus in 1956;90:30-41. DC. Ascending pathways of the
the cynomolgus monkev. J Comp 15 Axelrod J , Wurtman RJ , Snyder trigeminal nerve in cat . J Neun >-
Neurol 1984;222:56-68. SH. Control of hydroxyindole-o- physiol 1956;19: 144-153.
6. Aitkin LM, YVebster YVR . Medial methyl transferase activity in the 24 Berry CM , Karl RS, Hinsey JC .
geniculate body of the cat: organi - rat pineal gland by environmental Course of spinothalamic and me -
zation and responses to tonal stim - lighting. J Biol C' hem 1965;240: dial lemniscal pathways in the cat
uli of neurons in the ventral divi - 949-955. and rhesus monkey . J Neurophys-
sion. J Neurophvsiol 1972;35: 16. Bard P, Rioch DM . A study of 4 iol 1950;13:149-156.
365-380. cats deprived of neocortex and ad - 25. Bertrand GL, Blundell J , Musella R .
-
7. Akert K, Hartmann von Monakow ditional portions of the forebrain . Electrical exploration of the in -
K . Relationships of precentral , pre- Bull Johns Hopkins Hosp 1937; ternal capsule and neighboring
motor and prefrontal cortex to the 60:73-147. structures during stereotaxic pro-
mediodorsal and intralaminar nu - 17. Battaglia G , Colacitti C, Ben - cedures. J Neurosurg 1%5;22:
clei of the monkey thalamus. Acta tivoglio M . The relationship of cal - 333-343.
Neurobiol Exp ( YVarsz ) 1980;40: bindin -containing neurons with 26. Binkley S. A timekeeping enyme in
7-25. substance P, leu -enkephalin and the pineal gland . Science
8. Andersen E, Dafny N . Microion - cholecystokinin fibres: an immuno- 1979;240:66-71.
tophoretically applied 5- HT re - histochemical study in the rat thal - 27. Bishop PO, Kozak YV, Levick YVR ,
duces responses to noxious stimu - amus. J Chem Neuroanat 1992; Vakkur GJ . The determination of
lation in the thalamus. Brain Res
1982;241 :176-178.
-
5:453 464.
18. Beckstead RM , Morse JR , Norgren
the projection of the visual field on
to the lateral geniculate nucleus in
9. Ariens Kappers J . The pineal R. The nucleus of the solitary tract the cat. J Physiol ( Lond ) 1962;163:
organ: an introduction . In : YVol -
stenholme GEYV , Knight J , eds. The
in the monkey: projections to the
thalamus and brain stem nuclei . J
-
503 539.
28. Bjdrklund A , Lindvall O. Dopa -
pineal gland . Edinburgh: Churchill Comp Neurol 1980;190:259-282. mine-containing systems in the
-
Livingston , 1971:1 23. 19. Benevento LA , Fallon JIL The as- CNS. In : Bjdrklund A, Hokfelt T,
10. Armstrong E. Limbic thalamus: an - cending projections of the superior eds. Handbook of chemical neu -
terior and mediodorsal nuclei. In: colliculus in the rhesus monkey roanatomy . Vol . 2. Part 1: Classical
transmitters in the CNS. Ch. 3. tion cells in the cat and monkey . 60. Cole M , Nauta WJH , Mehler WR .
Amsterdam : Elsevier, 1984:55-122. Brain Res 1979;161:515-521 . The ascending efferent projections
29. Bjorklund A, Owman C, West KA . 44 Burton H, Jones EG . The posterior of the substantia nigra . Trans Am
Peripheral sympathetic innerva - thalamic region and its cortical Neurol Assoc 1964;89:74-78.
tion and serotonin cells in the projection in new world and old 61. Colonnier ML, Guillery RW ,.
habenular region of the rat brain. Z world monkeys. J Comp Neurol Synaptic organization in the lateral
Zellforsch Mikrosk Anat 1972;127: 1976;168:249-302. geniculate nucleus of the monkey.
-
570 579. 45. Campos-Ortega JA, Glees P, Z Zellforsch Mikrosk Anat 1964;
30. Boivie J . Terminations of the cervi - Neuhoff V . Ultrastructural analysis -
62:333 355.
cothalamic tract in the cat: an ex - of individual layers in the lateral 62. Combs CM . Fiber and cell degen -
perimental study with silver im - geniculate body of the monkey . Z eration in the albino rat brain after
pregnation methods. Brain Res Zellforsch Mikrosck Anat 1968;87: hemidecortication. J Comp Neurol
-
1970;19:333 360. 82-100. 1949;90:373-402.
31 . Boivie J . The terminations of the 46. Carman JB, Cowan WM , Powell 63. Crunelli V, Leresche N . A role for
spinothalamic tract in the cat: an TPS. Cortical connections of the GABAB receptors in excitation and
experimental study with silver im - thalamic reticular nucleus. J Anat inhibition of thalamocortical cells.
pregnation methods. Exp Brain 1964 ;98:587-598. Trends Neurosci 1991;14:16-21 .
Res 1971;12:331-353. 47. Carmel PW . Efferent projections of 64 . Dafny N , Reves- Vazquez C, Qiao
32. Boivie J . Anatomical observations the ventral anterior nucleus of the JT. Modification of nociceptively
on the dorsal column nuclei, their thalamus in the monkey. Am J identified neurons in thalamic
thalamic projection and the cy - Anat 1970;128:159 184.- parafascicularis by chemical stimu -
toarchitecture of some somatosen - 48. Carpenter MB. The dorsal trigemi - lation of the dorsal raphe with glu -
sory thalamic nuclei in the mon - nal tract in the rhesus monkey. J tamate, morphine, serotonin and
key . ) Comp Neurol I 978;178:
-
17 18.
-
Anat 1957;91:82 90.
49. Carpenter MB. Ventral tier thala -
focal dorsal raphe electrical stimu -
lation . Brain Res Bull 1990;24:
33. Boivie J . An anatomical reinvesti- mic nuclei . In: Williams D, ed . 717-723.
gation of the termination of the Modern trends in neurology . Vol . 65. De Biasi S, Frassoni C, Spreafico R
spinothalamic tract in the monkey' . 4 . London: Butterworths, 1967:1-20. GABA immunoreactivity in the
-
J Comp Neurol 1979;186:343 370. 50. Carpenter MB . Anatomy of the thalamic reticular nucleus of the
34 . Bolton RF, Cornwall J , Phillipson corpus striatum and brainstem in - rat . A light and electron micro -
OT. Collateral axons of cholinergic tegrating systems. In : Brooks VB, scopical study. Brain Res 1986;
pontine neurones projecting to ed . Handbook of physiology. Sec. 399:143-147.
midline, mediodorsal and parafas - 1. The nervous system. Vol . II . 66. De Biasi S, Rustioni A . Ultrastruc -
cicular thalamic nuclei in the rat . I Motor control. Ch . 19. Washington , tural immunocytochemical local -
Chem Neuroanat 1993;6:101-114. DC . American Physiological Soci - ization of excitatory amino acids in
35. Bowsher D. Termination of the ety , 1981 :947-995. the somatosensory system. J His -
central pain pathway: the con - 51. Carpenter MB, Hanna GR. Fiber tochem Cytochem 1990;38:1745 -
scious appreciation of pain. Brain projections from the spinal trigem - 1754
-
1957;80:606 622. inal nucleus in the cat. J Comp 67. De Curtis M , Spreafico R , Avanzini
36 Bowsher D. Projections of the
. Neurol 1961;117:117-132. G. Excitatory amino acids mediate
gracile and cuneate nuclei in 52. Carpenter MB, Nakano K, Kim R responses elicited in vitro by stim -
Macaco mulatto: an experimental Nigrothalamic projections in the ulation of cortical afferents to retic-
degeneration study. J Comp Neu- monkey demonstrated by autora - ularis thalami neurons of the rat .
-
rol 1958;110:135 155. diographic techniques. J Comp Neuroscience 1989;33:275-283.
37. Bowsher D. The termination of sec - Neurol 1976;165:401 416. - 68. Dejerine J. Anatomie des centres
ondary somatosensory neurons 53. Carpenter MB, Peter P. Nigrostri - nerveux. Vol. 2. Paris: J . Rueff ,
within the thalamus of Macaco mu
latto: an experimental degeneration
- atal and nigrothalamic fibers in the
rhesus monkey. J Comp Neurol
1901.
69. Dekaban A. Human thalamus. An
study . J Comp Neurol 1961;17: 1972;144:93-116. anatomical, developmental and
213-227. 54. Carpenter MB, Strominger NL. Ef - pathological study . I. Division of
38. Boycott BB, Wassle H. The mor - ferent fibers of the subthalamic nu - the human adult thalamus into nu -
phological types of ganglion cells cleus in the monkey: a comparison clei by use of the cvto- myelo-archi -
of the domestic cat's retina . ) Phys - of the efferent projections of the tectonic method . J Comp Neurol
iol ( Fond ) 1974;240:397-419. subthalamic nucleus, substantia 1953;99:639-683.
39. Braak H, Braak F.. Alzheimer's dis- nigra and globus pallidus. Am J 70. Dekaban A . Human thalamus. An
ease affects limbic nuclei of the Anat 1967;121:41-72. anatomical developmental and
thalamus. Acta Neuropathol ( Berl ) 55. Casseday JH, Diamond IT, Halting pathological study. II. Develop-
-
1991;81:261 268. JK . Auditory pathways to the cor- ment of the human thalamic nu -
40. Broman J , Ottersen OP. Cervi - tex in Tupaia $lfc. J Comp Neurol clei. J Comp Neurol 1954;100:
cothalamic tract terminals are en-
riched in glutamate-like immuno-
-
1976;166:303 340. 63-97.
56. Chan - Palav V. Cerebellar dentate 71. Dempsey EW, Morison RS. The
reactivity: an electron microscopic nucleus: organization , cytology production of rhythmically recur -
-
double labeling study in the cat. J and transmitters. Berlin : Springer- rent cortical potentials after local -
Neurosci 1992;12:204-221 . Verlag 1977. ized thalamic stimulation. Am J
41 . Brouwer B, Zeeman WPC. The 57. Chevalier G, Deniau M . Disinhibi - Physiol 1942;135:293-300.
projection of the retina in the pri - tion as a basic process in the 72. Dempsey EW, Morison RS. The
mary optic neuron in monkeys. expression of striatal functions. electrical activity of a thalamocorti -
Brain 1926;49:1-35. Trends Neurosci 1990;13:277-280. cal relay system . Am J Physiol
42. Bunt All , Hendrickson AE, Lund 58. Clark FJ , Burgess PR . Slowly -
1943;138:283 298.
JS, Lund RD, Fuchs AF. Monkey adapting receptors in cat knee 73. Deschenes M , Madariaga - Domich
retinal ganglion cells: morphomet - joint: can they signal angle ? J Neu - A , Steriade M . Dendriniendritic
ric analysis and tracing of axonal rophysiol 1975;38:1448-1463. synapses in the cat reticularis thal -
projections with a consideration of 59. Clemence AE , Mitrofanis|. Cvtoar - ami nucleus: a structural basis for
the peroxidase technique. J Comp chitectonic heterogeneities in the thalamic spindle synchronization.
Neurol 1975;164:265-286. thalamic reticular nucleus of cats -
Brain Res 1985;334:165 168.
43. Burton H , Craig AD Jr. Distribu - and ferrets. J Comp Neurol 1992; 74. Deschenes M , Roy JP, Steriade M .
tion of trigeminothalamic projec - 322:167-180. Nature of 7 14 Hz rhythmic hyper -
16 Thalamus 697
polarizations in thalamic relay rel monkey. In: Frigyesi TL, Yahr R , eds. Cellular thalamic mecha -
neurons. Neurosci Abstr 1983; MD, eds. Corticothalamic projec- nism *. Amsterdam: Elsevier, 1988:
9:678. tions and sensorimotor activities. 311-320.
75. Diamond IT, Jones EG, Powell New York: Raven Press, 1972: 106. Glees P. Experimental neurology.
TPS. The projection of the auditory
cortex upon the diencephalon and
—
161 195.
91. Fry' WJ , Krumins R , Fry FJ , Thomas
London: Oxford University Press,
1961.
brain stem in the cat. Brain Res G, Borbely S, Ades II . Origins and 107. Glees P, Le Gras Clark WE. The
1969;15:305-340. distribution of some efferent path - termination of optic fibers in the
76. Dowling JE. The retina: an ap- ways from the mammillary nuclei lateral geniculate body of the mon -
proachable part of the brain . Cam - of the cat . J Comp Neurol 196.3; -
key . J Anal 1941;75:295 310.
bridge: Harvard University Press , 120:195-258. 108. Glennon RA . Serotonin receptors:
1987. 92. Fukuda Y , Stone J . Retinal distribu - clinical implications. Neurosci
77. Dowling JE, Boycott BB. Organiza - tion and central projections of Y, X Biobehav Rev 1990;14:35-47.
tion of the primate retina : electron and W cells of the cat's retina. J 109. Glickstein M, King RA , Miller J ,
microscopy. Proc R Soc Lond ( Biol ) Neurophysiol 1974;37:749-772. Berkley M . Cortical projection
1966;166:80-111 . 93. Galambos R , Rose JE. Microelec - from the dorsal lateral geniculate
-
78. Droogieever Fortuyn J , Stefens R . trixle studies on medial geniculate nucleus of cats. J Comp Neurol
On the anatomical relations of the body of the cat . III . Response to 1967;130:55-76.
intralaminar and midline cells of pure tone. J Neurophvsiol 1952; 110. Goldman - Rakic I *S, Porrino LJ . The
the thalamus. Electroencephalogr 15:381-400. primate mediodorsal ( MD) nucleus
Clin Neurophysiol 1951;3:393 400.
79. Dykes RW. Parallel processing of
- 94. Garey LJ . Visual system. In: Paxi -
nos G , ed . The human nervous sys -
and its projection to the frontal
lobe. J Comp Neurol 1985;242:
somatosensory information: a the- tem. Ch. 28. New York: Academic 535-560.
ory. Brain Res Rev 1983;6:47-115. Press, 1990:945-977. 111 . Goodwin ( iM, McCloskey Dl ,
80. Dy kes RW , Herron P, Lin CS. Ven - 95. Garey LJ , Powell TPS. The projec- Matthews PBC. Proprioceptive il -
troposterior thalamic regions priv tion of the lateral geniculate nu - lusions induced by muscle vibra -
jecting to cytoarchitectonic areas 3a cleus upon the cortex in the cat . tion : contribution by muscle spin -
and 3b in the cat. J Neurophysiol Proc R Soc B 1%7;169:107 126.- dles to perception ? Science 1972;
1986;56:1521-1541 96. Garey LJ, Powell TPS. The projec- 175:1382-1384.
81 . Eaton SA , Salt TE. Membrane and tion of the retina in the cat . J Anat 112. Graybiel AM , Berson DM . Misto -
action potential responses evoked 1968;102:189-222. chemical identification and affer -
by excitatory amino acids acting at 97. Garey LJ , Powell TPS. An experi - ent connections of subdivisions in
- --
N methy1 D asparta te receptors
- - - -
and non N methyl D aspartate re-
mental study of the termination of
the lateral geniculo-cortical path -
the lateralis posterior - pul vinar
complex and related thalamic nu -
ceptors in the rat thalamus in vivo. way in the cat and monkey. Proc R clei in the cat. Neuroscience 1980;
Neuroscience 1991 ;44:277-286. Soc Lond ( Biol ) 1971;179:41 63.- 5:1175-1238.
82. Edwards SB, Rosenquist AC, 98. Garland JC, Mogenson GJ . An elec - 113. Graybiel AM , Elde RP. Somato -
Palmer LA. An autoradiographic trophysiological study of conver- statin-like immunoreactivity char -
study of ventral lateral geniculate gence of entopeduncular and lat - acterizes neurons of the nucleus
projections in the cat . Brain Res eral preoptic inputs on lateral reticularis thalami in the cat and
1974;72:282-287. habenular neurons projecting to monkey . ) Neurosci 1983;3:
83. Englander RN , Netskv MG, Adel - the midbrain . Brain Res 1983;263: -
1308 1321.
man LS. Location of human pyra - 33-41. 114 . Grofova I , Rinvik E. Cortical and
midal tract in the internal capsule: 99. .
Giesler GJ Jr Spiel HR , Willis WD. pallidal projections to the nucleus
anatomical evidence. Neurology Organization of spinothalamic ventralis lateralis thalami: electron
-
1975;25:823 826. tract axons within the rat spinal microscopically studies in the cat .
84. Faull RLM , Carman JB. Ascending cord . J Comp Neurol 1981:195: Anat F.mbrvol ( Berl ) 1974;146:
projections of the substantia nigra
in the rat . J Comp Neurol 1968; 100.
243-252.
Gigg J , Tan AM, Finch DM . Gluta -
-
113 132.
115. Gross NB, Lifschitz WS, Anderson
132:73-92. matergic excitatory responses of DJ . The tonotopic organization of
85. Forbes BF, Moskowitz N . Projec- anterior cingulate neurons to stim - the auditory thalamus of the squir-
tions of auditory responsive cortex ulation of the mediodorsal thala - rel monkey ( Saimiri sent reus ). Brain
in the squirrel monkey. Brain Res mus and their regulation by -
Res 1974;65:323 332.
1974;67:239-254 . GABA: an in vivo iontophoretic 116. Guillery RW . A study of Golgi
86. Fraschini F, Collu R , Martini L. study . Cereb Cortex 1992;2: preparations from the dorsal lat -
Mechanisms of inhibitory action of 477-484. eral geniculate nucleus of the adult
pineal principles on gonadotropin 101. .
Giguere M Goldman - Rakic I *S. cat . J Comp Neurol 1966;128:21-50.
secretion . In : Wolstenholme GEW , Mediodorsal nucleus: areal, lami - 117. Guillery RW . The laminar distribu -
Knight J , eds. The pineal gland . nar, and tangential distribution of tion of retinal fibres in the dorsal
Edinburgh: Churchill Livingstone, afferent* and efferents in the fron- lateral geniculate nucleus of the
1971:259-272. tal lobe of rhesus monkeys. J Comp cat : a new interpretation . J Comp
87. Freeman W, Watts JW . Retrograde
degeneration of the thalamus fol - 102.
Neurol 1988;277:195-213.
Gilbert CD, Kelly JP. The projec -
-
Neurol 1970;138:339 369.
118. Guillery RW , Adrian HO, Woolsey
lowing prefrontal lobotomy . J tion of cells in different layers of CN , Ri »se JE . Activation of somoto-
Comp Neurol 1947;86:65-93. the cat’s visual cortex. J Comp sensory areas I and II of the cat's
88. Freeman W , Watts JW . The thala - Neurol 1975;163:81-106. cerebral cortex by focal stimulation
mic projection to the frontal lobe. 103. Gillingham FJ . Small localized sur - of the basoventral complex. In :
Proc Assoc Res Nerv Ment Dis gical lesions of the internal capsule Purpura DP, Yahr MD, eds. The
1948;27:200-209. in the treatment of dyskinesia . thalamus. New York: Columbia
89. Friedman DP, Jones EG, Burton H . Confin Neurol 1962;22:385-392. l Diversity Press, 1966:197 204
Representation pattern in the sec- 104. Girgis M . The role of the thalamus 119. Guillery RW , Stelzner D). The dif -
ond somatic sensory area of the in the regulation of aggressive be- ferential effects of unilateral lid
monkev cerebral cortex. J Comp havior. lilt J Neurol 1971;8:327-351 . closure upon the monocular and
Neurol 1980;192:21-41. 105. Giuffrida R , Rust ion i A . Glutamate binocular segments of the dorsal
90. Frigyesi TL, Schwartz R . Cortical and aspartate immunoreactivity in lateral geniculate nucleus in the
control of thalamic sensorimotor corticothalamic neurons of rats. In : cat . j Comp Neurol I 970;139:
relay activities in the cat and squir - Macchi G, Bentivoglio M , Spreafico 413-422.
120. Haber SN , Groenewegen HJ , 135. Head H , Holmes G . Sensory dis - asm: details of visual fiber organi -
Grove HA , Nauta WJH . Efferent turbances from cerebral lesions. zation studied bv silver impregna -
connections of the ventral pal -
lidum : evidence of a dual striato -
-
Brain 1911;34:102 254.
136. Heath CJ, Jones EG . An experi -
tion techniques. Arch Ophthalmol
1963;70:69-85.
pallidofugal pathway. J Comp mental study of ascending connec - 151. Hubei DH , Wiesel TN . Integrative
Neurol 1985;235:322 335.
-
-
121. Haber SN, Lynd Balta E, Mitchell
tions from the posterior group of
thalamic nuclei in the cat . J Comp
action in the cat's lateral geniculate
body . J Physiol ( Lond ) 1961; 155:
SJ . The organization of the de- Neurol 1971;141:397-426. -
385 398.
scending ventral pallidal projec - 137. Hendrickson AM, Wilson ME, 152. Hubei DH, Wiesel TN . Receptive
tions in the monkey ) Comp Neu - Toyne MJ . The distribution of optic fields, binocular interaction and
-
rol 1993;329:111 128. nerve fibers in Macaco mulatto. functional architecture in the cat 's
122. Hallanger AE, Levey Al , Lee HJ , -
Brain Res 1970;23:425 427. visual cortex. J Phvsiol ( Lond )
Rye nil, Wainer Bl 1. The origins of 138. Hendry SH, Jones EG, Graham J . -
1962;160:106 154.
cholinergic and other subcortical Thalamic relay nuclei for cerebellar 153. Hubei DH, Wiesel TN. Shape and
afferents to the thalamus in the rat . and certain related fiber systems in arrangement of columns in cat's
J Comp Neurol 1987;262:105-124 . the cat. J Comp Neurol 1979;185: striate cortex. J Phvsiol ( Lond )
123. Hallanger AF., Wainer BH. Ultra - 679-713. 1963;165:559-568.
structure of ChAT-immunoreac- 139 . Herkenham M. Laminar organiza- 154. I lubel Dl 1, Wiesel TN. Brain mech -
tive synaptic terminals in the thala - tion of thalamic projections to rat anisms of vision. Sci Amer 1979;
mic reticular nucleus of the rat . J neocortex. Science 1980;207:532 - -
241 :150 162.
Comp Neurol 1988;278:486 497. - 534. 155. 1 lunt SP, Schmidt J . Some observa -
124. Hamori J , Pasik T, Pasik P, Szen - 140. Herkenham M , Nauta WJH . Affer- tions on the binding patterns of u -
tagothai J . Triadic synaptic ar - ent connections of the habenular bungarotoxine in the central ner -
rangements and their possible sig- nuclei in the rat : a horseradish per - vous system of the rat . Brain Res
nificance in the lateral geniculate oxidase study, with a note on the 1978;157:213-232.
nucleus of the monkev Brain Res - -
fiber of passage problem . J Comp 156. Illinsky IA, Jouandet M , Goldman -
1974;80:379-393. Neurol 1977;173:123-145. Rakic PS. Organization of the ni -
125. Hanaway J , Young RR . Localiza - 141. Herkenham M , Nauta WJH. Effer- grothalamocortical system in rhe-
tion of the pyramidal tract in the ent connections of the habenular sus monkey. J Comp Neurol
internal capsule of man. J Neurol nuclei in the rat . J Comp Neurol -
1985;36:315 330.
Sci 1977;34:63-70.
126. Hardy SG, Lynch JC. The spatial
-
1979;187: 19 48
142. Hickey TL, Guillory RW . Variabil -
157. Uinskv I A, Kultas- llinskv K . Sagit -
tal cytoarchitectonic maps of the
distribution of pulvinar neurons ity of laminar patterns in the Macaca mulatto thalamus with a re -
that project to two subregions of human lateral geniculate nucleus. J vised nomenclature of the motor -
the inferior parietal lobule in the Comp Neurol 1979;183:221 246.- related nuclei validated by obser -
macaque. Cereb Cortex 1992;2: 143. Hirai T, Jones EG . Distribution of vations on their connectivity. J
-
217 230. -
tachykinin and enkephalin im - - -
Comp Neurol 1987;262:331 364.
127. Harrison JM , Howe ME. Anatomy munoreactive fibers in the human 158. Ilinsky I A , Kultas-llinsky K ,
of the afferent auditory nervous thalamus. Brain Res Rev 1989; Rosina A , Haddy M . Quantitative
system in mammals in: Keidel, 14:35-52 evaluation of crossed and un -
WO, Neff WD, eds. Handbook of 144 Hirai T, Jones EG. A new parcella- crossed projections from basal gan-
sensory physiology . Vol. III. Berlin : tion of the human thalamus on the glia and cerebellum to the cat thal -
-.
Springer Verlag, 1974:283-336.
128. Harting JK Hall WC, Diamond IT,
basis of histochemical staining .
Brain Res Rev 1989;14 : 1 -34
amus.
207-227.
Neuroscience 1987;21 :
Martin GF. Anterograde degenera - 145. Hirai T, Jones EG. Comparative 159. Ilinsky I A, Tourtellotte WG, Kul -
tion study of the superior collicu - anatomical study of ventrolateral -
tas llinsky K . Anatomical distinc-
lus in Tu/ ktta glis: evidence for a thalamic mass in humans and tions between the two basal gan-
subdivision between superficial monkeys. Stereotact Fund Neuro- glia afferent territories in the
and deep lavers. J Comp Neurol
1973;148:361-386.
-.
Mirg 1993;60:6 16
146. Hokfelt T, Johansson O, Goldstein
primate motor thalamus. Stereo-
tact Funct Neurosurg 1993;60:
129. Houser CR, Vaughn JE, Barber RP, M . Central catecholamine neurons 62-69.
Roberts E. GABA neurons are the as revealed by immunohistochem- 160. Imig TJ , Ruggero MA , Kitzes LM ,
major cell type of the nucleus retic - istry with special reference to Javel E, Brugge JF . Organization of
ularis thalami . Brain Res 1980;200: adrenaline neurons. In: Bjdrklund auditory cortex in the owl monkey
.341-354. A, Hokfelt T, eds. Handbook of ( Actus trivirgatus ). J Comp Neurol
130. Haymaker W . Bing’s local diagno- chemical neuroanatomy. Vol. 2. 1977;171 :111-128.
sis in neurological diseases. St. Part 1 : Classical transmitters in the 161 . Isaacson LG , Tanaka D Jr. Cholin -
Louis: C. V . Mosbv Company , CNS. Ch. 5. Amsterdam : Elsevier, -
ergic and non cholinergic projec -
-
1956:57-62 and 105 112. 1984:157-276. tions from the canine pontomesen -
1.31. Hazrati L- N , Parent A . Contralat - 147. Hollander H . Projections from the cephalic tegmentum (Ch5 area ) to
eral pallidothalamic and palli- striate cortex to the diencephalon the caudal intralaminar thalamic
dotegmental projections in pri - in the squirrel monkey ( Saintin sci - nuclei. Exp Brain Res 1986;62:
mates: an anterograde and ureus): a light microscopic radioau - 179-188.
retrograde labeling study . Brain tographic study following intracor - 162. Isaacson LC« , Tanaka D Jr. Cholin -
-
Res 1991;567:212 223. tical injection of |’H| leucine. J ergic innervation of canine thal -
132 Hazrati L- N , Parent A . Projection Comp Neurol 1974;155:424-440. amostriatal projection neurons:
from the external pallidum to the 148. Hollander H , Vanegas H . The pro- an ultrastructural study combining
choline acetyltransferase immuno-
reticular thalamic nucleus in the
squirrel monkey. Brain Res 1991;
-
550:142 146.
jection from the lateral geniculate
nucleus onto the visual cortex in
the cat : a quantitative study with
.
cytochemistry and WC A - HRP ret -
rograde labeling . J Comp Neurol
133. Heckers S, Geula C, Mesulam M - horseradish peroxidase. J Comp -
1988;277:529 540.
M . Cholinergic innervation of the Neurol 1977,173:519-636. 163. Jacobs GIL Receptive fields in vi -
human thalamus: dual origin and 149. Hoyt WF, Luis O. Visual fiber sual systems. Brain Res 1969;14:
differential nuclear distribution. I anatomy in the infrageniculate 553- 573.
Comp Neurol 1992;325:68-82. pathway of the primate. Arch 164. Jasper HH. Diffuse projection sys -
1 M Head 11. Studies in neurology . Lon - Ophthalmol 1962;68:94-106. tems: the integrative action of the
don Oxford University Press, 1920. 150. Hoyt WF, Luis O. The primate chi - thalamic reticular system . Elec -
16 Thalamus 699
troencephalogr Clin Neurophysiol

-
1949;1:405 420. cal connexions. Brain l %9,-92:
.
rhesus monkey . I . Ipsilater il corti- boodiri AA , Wheler GUT. Indole
metabolism in the mammalian
165. Jasper HH . Functional properties 477-502. pineal gland . In : Reiter RJ , ed . The
of the thalamic reticular system . In: 182. Jones EG, Powell TPS. Connexions pineal gland . Ch . 8. Boca Raton ,
Delafresnaye JF, ed . Brain mecha - of the somatic cortex of the rhesus FL: CRC Press, 1981 :199-227.
nisms and consciousness (sympo - monkey . II . Contralateral cortical 198. Klein DC, Moore RY. Pineal N -
sium ) . Oxford : Blackwell Scientific connexions. Brain 1969;92:717-730. acetyltransferase and hydroxyin -
-
Publications, 1954:374 395. 183. Jones EG, Powell TPS. The cortical dole-o-methyltransferase: control
166. Jasper HH, Ajmone- Marsan C, projections of the ventroposterior by the retinohypothalamic tract
Stoll J . Corticofugal projections to nucleus of the thalamus in the cat. and the suprachiasmatic nucleus.
the brain stem . AMA Arch Neurol Brain Res 1969;13:298-318. Brain Res 1979;174:245-262.
Psychiatry 1932;67:155-171. 184 . Jones EG, Powell TPS. Connexions 199. Klein DC, Weller JL. Indole metab-
167. Jinnai K, Nambu A , Tanibuchi I, of the somatic sensory cortex of the olism in the pineal gland : a circa -
-
Yoshida S. Cerebello and pallido- rhesus monkey . III . Thalamic con- dian rhythm in N acetyltrans- -
thalamic pathways to areas 6 and 4 nexions. Brain 1970;93:37-56. ferase. Science 1970;169:1093-1095.
in the monkey. Stereotact Funct 185. Jones EG, Powell TPS. An analysis 200. Klein DC , Weller JL. A rapid light -
Neurosurg 1993;60:70-79. of the posterior group of thalamic induced decrease in pineal sero-
168. Jones AE. The lateral geniculate nuclei on the basis its afferent con - -
tonin N acetyltransferase activity .
.
nucleus of Atetes ater J Comp Neu - nections. J Comp Neurol 1971; -
Science 1972;177:532 533.
-
rol 1964;123:205 210. -
143:185 216. 201. Klein DC, Weller JL, Moore RY.
169. Jones EG. Some aspects of the or - 186. Jones EG, Powell TPS. Anatomical Melatonin metabolism: neurol reg-
ganization of the thalamic reticular organization of the somatosensory ulation of pineal serotonin N -
complex . J Comp Neurol 1975; cortex . In : Iggo A , ed . Flandbook of acetyltransferase. Proc Natl Acad
-
162:285 308. sensory physiology. Vol . 2. Berlin : Sci USA 1971;68:3107-3110.
170. Jones EG. Possible determinants of
the degree of retrograde neuronal 187.
-
Springer Verlag, 1973379 620«
Jones EG, Wise SP, Coulter JD. Dif -
202. Kocsis JD, Sugimori M , Kitai ST.
Convergence of excitatory synaptic
labeling with horseradish peroxi - ferential thalamic relationships of inputs to caudate spiny neurons .
171.
-
dase. Brain Res 1975;85:249 253.
Jones EG . Distribution patterns of
-
sensory motor and parietal cortical
fields in monkeys. J Comp Neurol
Brain Res 1977;124:403-413.
203 Krettek JE, Price JL. A direct input
individual medial lemniscus axons 1979;183:833-881 . from the amygdala to the thalamus
in the ventrobasal complex of the 188. Kaas JH . How the somatosensory and the cerebral cortex. Brain Res
monkey thalamus. J Comp Neurol thalamus is subdivided and inter - 1974;67:169-174 .
1963 15:1 1 » ' connected with areas of the so-
172. ^
Jones EG. The thalamus. In : Emson
PC, ed . Chemical neuroanatomy.
matosensory cortex in monkeys
204 . Kruger L, Porter P . A behavioral
study of the functions of the
Rolandic cortex in the monkev. J
In: Bentivoglio M, Spreafico R, eds.
New York: Raven Press 1983: . Cerebellar thalamic mechanisms. Comp Neurol 1958;109:439 469. -
257-293. Amsterdam: F.xcerpta Medica, 1988: 205. Kudo M , Niimi K. Ascending pro-
173. Jones EG. The thalamus. New -
143 150. jections of the inferior colliculus on
York: Plenum , 1985. 189. Kaas JH , Guillery RW , Allman JM. the medial geniculate body in the
174 Jones EG, Burton H . Cytoarchitec- Some principles of organization in cat studied by anterograde and ret -
ture and somatic sensory connec- the dorsal lateral geniculate nu - rograde tracing techniques. Brain
tivity of thalamic nuclei other than cleus. Brain Behav Evol 1972;6: -
Res 1978;155: 113 117.
the ventrobasal complex in the cat . 253-299. 206 . Kuftler SW . Discharge patterns
175.
It omp Neurol 1974;154:395 432
Jones EG, Burton H. Areal differ
- -
190. Kaas JH, Huerta MF, Weber JT,
Harting JK. Patterns of retinal ter -
and functional organization of
mammalian retina . J Neurophysiol
ence in the laminar distribution of minations and laminar organiza - 1953;16:37-68.
thalamic afferents in cortical fields tion of the lateral geniculate nu - 207. Kuhlenbeck H . The derivatives of
of the insular, parietal and tempo - cleus of primates. J Comp Neurol the thalamus ventralis in the
ral regions of primates. J Comp 1977;182:517-554 . human brain and their relation to
Neurol 1976;168:197-247. 191 . Kalil K . Projections of the cerebellar -
the so called subthalamus. Milit
176. Jones EG, Burton H , Saper CB, and dorsal column nuclei upon the -
Surg 1948;102:433 447,
Swanson LW . Midbrain , dien - thalamus of the rhesus monkey. J 208 . Kultas- llinskv K, Hughes B, Foga -
cephalic and cortical relationships Comp Neurol 1981;195:25-50. rty JD, Ilinsky IA. GABA and ben -
of the basal nucleus of Meynert 192. Kelly JP, Gilbert CD. The projection zodiazepine receptors in the cat
and associated structures in pri - of different morphological types of motor thalamus after lesioning of
mates. J Comp Neurol 1976;167: ganglion cells in the cat 's retina . J nigro- and pallidothalamic path -
385-420. Comp Neurol 1975;163:65 80. - ways. Brain Res 1990;511 :197-208.
177. Jones EG, Friedman DP. Projection 193. Kerr FWL. Neuroanatomical sub - 209. Kunzle H . Thalamic projections
pattern of functional components strates of nociception in the spinal from the precentral motor cortex in
of thalamic ventrobasal complex cord . Pain 1975;1:325-356. Macaca fascicularis . Brain Res
on monkev somatosensory cortex. 194 . Kerr FWL, Lippan HH . The pri - 1976;105:253-267.
J Neurophysiol 1982;48:521-544 . mate spinothalamic tract as 210. Kunzle H . An autoradiographic
178. Jones EG, Leavitt RY . Retrograde demonstrated by anterolateral cor - analysis of the efferent connections
axonal transport and the demon - dotomy and commissural myelot - from premotor and adjacent pre-
-
stration of non specific projections omy. Adv Neurol 1974;4:147 156. - frontal regions (areas 6 and 9 ) in
to the cerebral cortex and striatum 195. Kievit J , Kuvpers HGJM Organiza - Macaca fascicularis. Brain Behav
from thalamic intralaminar nuclei -
tion of the thalamo cortical con - -
Evol 1978; 15:185 234 .
in the cat , rat and monkev. J Comp nexions to the frontal lobe in the 211 . Kunzle H , Akert K . Efferent con -
Neurol 1974;154:349-378 rhesus monkev . Exp Brain Re** nections of cortical Area 8 ( frontal
179. Jones EG , Porter R . What is area 1977;29:299-322. eye field ) in Macaca fascicularis: a
180.
-
3a ? Brain Res Rev 1980;2:1 43.
Jones EG, Powell TPS. Projections
1 %. Kim R , Nakano K , Jayaraman A ,
Carpenter MB. Projections of the
reinvestigation using the autoradi
ographic technique. J Comp Neu -
-
of the somatic sensory cortex upon globus pallidus and adjacent struc- rol 1977;173: 147-167.
the thalamus in the cat. Brain Res tures: an autoradiographic study 212. Kuo J -5, Carpenter MB Organiza-
1968; 10:369-391 . in the monkey . J Comp Neurol tion of pallidothalamic projections
181 Jones EG , Powell TPS. Connexions 1976;169:263-289. in the rhesus monkey J Comp
of the somatic sensory cortex of the 197. Klein DC, Auerbach DA , Nam - Neurol 1973;151:201-236.
213. Kupter C. The projection of the versity of Illinois Press, 1949:133- son AA , Madl ) E, Beil/ AJ . Local -
macula in the lateral geniculate nu -
cleus of man . Am J Ophthalmol
148.
231 . Liu X - B, Jones EG. The fine struc-
ization of glutamate in trigemi
nothalamic projection neurons: a
-
1962;54:597-609. ture of serotonin and tyrosine hy - combined retrograde transport-im -
214 Laemle LK . Cell populations of the droxylase immunoreactive termi- munohistochemical study. Soma -
lateral geniculate nucleus of the cat
as determined with horseradish
nals in the ventral posterior tha -
lamic nucleus of cat and monkey .
tosens Res 1987;4:177 190. -
245. Makino S, Okamura II , Mori moto
peroxidase. Brain Res 1975;100: Exp Brain Res 1991 ;85:507-518. N , Abe J , Yanaihara N , Ibata Y.
-
650 656. 232. Locke S, Angevine JB |r, Yakovlev Distribution of neurotensin-like
215. I aemle LK , Noback CR. The visual PL Limbic nuclei of thalamus and immunoreactivitv in the dien -
pathways of the lorisid lemurs connections of limbic cortex . I . cephalon of the Japanese monkey
( Nycticebus concang and Galago Tha la mo-cortical projections of the ( Macaco fuscata ). | Comp Neurol
crassicauJatua ). J Comp Neurol lateral dorsal nucleus in man . Arch -
1987;260:552 563.
1970;138.49-62. Neurol 1961;4:355-364. 246. Malone EF. Uber die Kerne des men-
216. Girsen KD, McBride RL. The orga - 233. Locke S, Angevine IB |r, Yakovlev schlichen Diencephalon : Abhand -
nization of feline entopeduncular PI. Limbic nuclei of thalamus and lungen der konighl preuss. Akademie
nucleus projections: anatomical connections of limbic cortex . VI . der Wissenschaften I 910;92.
studies. J Comp Neurol 1979; -
Tha la mo cortical projection of lat - 247. Malpeli JG , Baker FH. The repre-
-
184:293 308. eral dorsal nucleus in cat and mon - sentation of the visual field in the
217. Lavoie B, Parent A. Serotoninergic -
key . Arch Neurol 1964 ;11 : 1 12. lateral geniculate nucleus of the
innervation ol the thalamus in the 234. Lorente de No R. The structure of .
Macaco mulatto | Comp Neurol
primate: an immunohistochemical the cerebral cortex . In: Fulton JF, 1975;161:569-594
study . J Comp Neurol 1991; ed . Physiology of the nervous sys - 248. Martin JB, Reichlin S, Brown
-
312:1 18. tem . 3rd ed Newr York: Oxford GM . Clinical neuroendocrinology.
218. Lechner J , Leah JD, Zimmermann University Press, 1949:288-330. Philadelphia: F A. Davis Com -
M. Brainstem peptidergic neurons 235. Lubke J . Morphology of neurons in .
pany 1977:229-246.
projecting to the medial and lateral the thalamic reticular nucleus 249. Mason C, Kandel HR . Central vi -
thalamus and zona incerta in the (TRN ) of mammals as revealed by sual pathways. In Kandel HR .
rat . Brain Res 1993;603:47 56.
219. I ** Gros Clark WrE . The structure
- intracellular injections into fixed
brain slices. J Comp Neurol 1993,
Schwartz JH, Jessell TM , eds. Prin -
ciples of neural science. Ch . 29.
and connections of the thalamus. 329:458-471 . -
New York: Elsevier , 1991:420 439.
Brain 1932;55: 406-470. 236. Lund JS, Lund RD, Hendrickson 250. Matthews MR , Cowan VVM , Pow -
220. Le Gros Clark WE . The termina - AE, Bunt AH , Fuchs AF. The origin ell TI*S. Transneuronal cell degen -
tion of ascending tracts in the thal - of efferent pathways from the pri - eration in the lateral geniculate nu -
amus of the macaque monkev. J
—
Anat 1936;71:1 40.
221. Le Gros Clark WE. The laminar or -
ganization and cell content of the
mary visual cortex , area 17 of the
macaque monkey as shown by ret -
ri »grade transport of horseradish
peroxidase. J Comp Neurol 1975;
cleus of the macaque monkev . J
Anat 1960;94:145-169.
251. Matzke HA . The course of fibers
arising from the nucleus gracilis
lateral geniculate Kniv in the mon - 164:287-303. and cuneatus of the cat . J Comp
key . J Anat 1941;75:419-433. 237. McCormick DA . Neurotransmitter -
Neurol 1951;94:439 452.
222 . Le Gros Clark WE. Boggon Rll . On actions in the thalamus and cere - 252. Mehler WR . The anatomy of the
the connections of the anterior nu - bral cortex and their role in neuro - -
so called " pain tract" in man : an
cleus of the thalamus. J Anat modulation of thalamocortical ac - analysis of the course and distribu -
-
1933;67:215 226. tivity . Prog Neurobiol 1992;39: tion of the ascending fibers of the
.
223. Le Gros Clark WE Boggon RH . On 337-388. fasciculus anterolateralis. In :
the connections of the medial cell 238. McCormick DA, von Krosigk M . French JD, Porter RW, eds. Basic-
group of the thalamus. Brain 1933; Corticothalamic activation modu - research in paraplegia . Springfield ,
56:83-98. lates thalamic firing through gluta - IL: Charles C. Thomas, 1962:26 55.-
224. Le Gros Clark WE Boggon RH. mate "metabotropic" receptors. 253. Mehler WR . Further notes on the
The thalamic connections of the Proc Natl Acad Sci USA 1992;89: center median nucleus of Luys. In:
parietal and frontal lobes of the 2774-2778. Purpura DP, Yahr MD, eds. The
brain in the monkev . Philos Trans 239. McCormick DA, Wang Z. Sero- thalamus. New York: Columbia
R Soc Lond ( Biol ) 1935;224: tonin and noradrenaline excite Unversity Press, 1966:109-127.
313-359. GABAergic neurones of the guinea 254. Mehler WR . Idea of a new
225. Le Gros Clark WE, Penman GG . pig and the cat nucleus reticularis anatomy of the thalamus. J Psvchi-
The projection of the retina in the
lateral geniculate bodv . Proc R Soc
thalami nucleus. J Physiol ( Lond )
-
1991;442:235 255.
-
atr Res 1971;8:203 217.
255. Mehler WR . Central pain and the
B 1934; 114: 291-313. 240. McLardy T. Projection of the cen- spinothalamic tract . Adv Neurol
226. Le Gros Clark WE , Pow ell TPS. On tromedian nucleus of the human 1974;4:127-146.
the thalamocortical connexions of thalamus. Brain 1968;71:290 303 - . 256. Mehler WR. Subcortical afferent
the general sensory cortex of 241. McLardy T. The thalamic projec - connections of the amygdala in the
monkey . J Comp Neurol 1980;
Macaca . Proc R Soc Lond ( Biol ) tion to frontal cortex in man . J
1953;141 :467-487. Neurol Neurosurg Psychiatry -
190:733 762.
227. Leonard CM . The connections ot 1950;13:198-202. 257. Mehler WB, Feferman ME. Nauta
the dorsomedial nuclei . Brain 242. Macchi G, Bentivoglio M. The thal - WJH. Ascending axon degenera -
Behav Evol 1972;6:524 541 .- amic intralaminar nuclei and the tion following anterolateral cor-
228. Levey Al , Hallanger AE, Wainer cerebral cortex . In: Jones EG , Peters dotomy : an experimental study in
. -
BH . Choline acetyltransferase im - A , eds. Cerebral cortex. Vol. 5. .
the monkey Brain 1960;83:718 750.
munoreactivity in the rat thala - New York: Plenum Press, 1986: 258. Mehler WR , Vernier VG Nauta
mus. J Comp Neurol 1987;257: 355 401 . WJII . Efferent projections from the
317-332. 243 Macchi G , Bentivoglio M , Molinari dentate and interpositus nuclei in
229. Levin PM . The efferent fibers of the M , Minciacchi D. The thalamo-cau - primates. Anat Rec 1958,130:
frontal lobe of the monkey ( Macaca -
date versus thala mo cortical pro- 430-431.
mulatto ). J Comp Neurol 1936;63: jections as studied in the cat with 259. Mer /enich MM , Brugge JF. Repre -
369-419. fluorescent retrograde double la - sentation of the cochlear partition
230. Levin PM. Efferent fibers. In : Buev beling . Exp Brain Res 1984;54: on the superior temporal plane of
PC, I’d . The precentral motor cor- 225-239. the Macaque monkey. Brain Res
tex . 2d ed . Ch . 5. Urbana : Uni - 244 . Magnusson KR, Clements |R , Lar - 1973;50:275-296.
16 Thalamus 701
2M ) Mesulam MM , Mufson EJ , Levey ways and the central neural con - anatomical analysis of the non spe - -
AI , VV,liner BH . Atlas of choliner - trol of a circadian rhythm in pineal cific thalamic projection system . In :
gic neurons in the forebrain and
upper brainstem of the macaque
-
serotonin N acetyltransferase ac
-
tivity Brain Rea 1974;71:17 33 .
- Delafresnaye JF, ed. Brain mecha -
nisms and consciousness ( sympo-
based on monoclonal choline 277. Moore KY , Lenn N ) . A retinohvpo - sium ) . Oxford . Blackwell Scientific
acetvltransferase immunohisto - thalamic projection in the rat . j Publications, 1954:81-98.
chemistry and acetylcholinesterase Comp Neurol 1472;146: 1 - 14 , 297. Niimi K , Inoshita H. Cortical pro -
histochemistry. Neuroscience 1984; 278. Moore RY, Rapport RL. Pineal and jections of the lateral thalamic nu -
12:669-686. gonadal function in the rat follow - clei in the cat . Proc Jpn Acad
261. Mettler FA . The non - pvramidal ing cervical sympathectomy. Neu- 1971 ;47:664-669.
motor projections from the frontal roendocri nology 1470,7:361-374 . 298. Niimi K , Matsuoka II . Thalamo-
cerebral cortex . Proc Assoc Res
Nerv Ment Dis 1947;26: 162-199.
274. Morel F. La massa intermedia ou cortical organization of the audi -
commisure grise. Acta Anal ( Basel ) tory system in the cat studied by
262. Mettler FA . Extracortical connec- - .
1947;4:203 207 retrograde axonal transport of
tions of the primate frontal cere- 280. Morest DK . The neuronal architec- horseradish peroxidase. Adv Anat
bral cortex. I Tha la mo-cortical ture of the medial geniculate body Embryol Cell Biol 1979;57:1-56.
connections. | Comp Neurol -
of the cat . J Anat 1964;98:611 638. 299. Niimi K , Niimi M , Okada Y . Thala -
1947;86:95-117. 281 . Morest DK . The laminar structure mic afferents to the limbic cortex in
263. Mettler FA. Neuroanatomv. St . of the medial geniculate body of the cat studied with the method of
the cat. J Anat 1465;44:143-154.
'
Louis: C.V . Mosbv , 1948 retrograde axonal transport of
264 . Meyer A, Beck E, McLardy T. Pre- 282. Morest DK . The lateral tegmental horseradish peroxidase. Brain Res
frontal leucotomy: a neuroanatom - system of the midbrain and the 1978;145:225- 238.
ical report. Brain 1947;70:18-49. medial geniculate body: study 300. Niimi K , Sprague JM . Thalamo -
265. Miller RA , Strominger NL. An ex - with Golgi and Nauta methods in cortical organization of the visual
perimental study of the efferent the cat. J Anat 1465;44:611-634. system in the cat . J Comp Neurol
connections of the superior pedun - 283. Morison RS, Dempsey EW. A 1970;138:219-250.
cle in the rhesus monkev . Brain study of thalamocortical relations. 301 . Niimi M . Cortical projections of
Res 1977;133:237-250. -
Am j Physiol 1442;135:281 292. the anterior thalamic nuclei in the
266. Minkowski M . Uber den Verlauf , 284 . Moru / zi G. Active processes in the cat . Exp Brain Res 1978;31:403-416.
die Endigung und die zentrale brain stem during sleep. Harvey 302. Nissl F. Die Kerne des Thalamus
Representation von gekreutzten Lect Ser 1963;58:233-247. beim Ka ninehen. Neurol Zentralbl
and ungekreutzten . Sehnerven - 285. Moru / zi G, Magoun IIW . Brain 1889;8:549-550.
tastern bei einigen beim menschen. stem reticular formation and acti - 303 Noback CR , Laemle LK . Structural
Schweiz Arch Neurol Psychiatr vation of the EF.G. F.lectroen- and functional aspects of the visual
1920;6:201-252. cephalogr Clin Neurophvsiol 1444; pathways of primates. In : Noback
267. Mitrofanis |. Calbindin immunore-
activity in a subset of cat thalamic 286.
-
1:455 479.
Mosko SS, Moore RY. Neonatal
CR, Montagna VV, eds. Advances
in primatology . Vol . 1 : The primate
reticular neurons. J Neurocvtol suprachiasmatic nucleus lesions: brain. Ch . 3. New York: Appleton -
1992;21 :495-505. effects on the development of cir - -
Centurv Crofts, 1970:55-81.
268. Mitrofanis J , Guillery RW. New cadian rhythms in the rat . Brain 304. Norgren R , Leonard CM. Ascend -
views of the thalamic reticular nu - Res 1979;164:17-38. ing central gustatory pathways. J
cleus in the adult and the develop- 287. Mountcastle VB, Henneman E. Pat - Comp Neurol 1973;150:217-238.
ing brain . Trends Neurosci 1993; tern of tactile representation in 305. Norgren R , Pfaffman C. The pon -
16:240-245. thalamus of cat . J Neurophvsiol tine taste area in the rat . Brain Res
269. Mogenson GJ , Jones DL, Yim CY . -
1944;12:85 100. 1975;91:99-117.
From motivation to action: func - 288. Mountcastle VB, I lenneman F.. The .306. Oertel VVII, Graybiel AM , Mug-
tional interface between the limbic representation of tactile sensibility naini E, Elde RP, Schmechel DE,
svstem and the motor system. Prog in the thalamus of the monkey . I Kopin I ) . Coexistence of glutamic
Neurobiol 1980; 14:69-97. Comp Neurol 1952;97: 404-440 . acid decarboxylase- and somato -
270. Molinari M , I lendrv SH , Jones EG. 289. Nakano K , Kohno M , Kawahira J , statin - like immunoreactivity in
Distributions of certain neuropep - Tokushige A . Entopeduncular nu - neurons of the feline nucleus retic-
tides in the primate thalamus. cleus projections to the contralat - ularis thalami. J Neurosci 1983;3:
Brain Res 1987;426:270-284. eral thalamic nuclei. Brain Res 1322-1332.
271. Montero VM. Quantitative im - 1983;262:283-287. 307. Ogren MP, Hendrickson AE. Path -
munogold analysis reveals high 240. Nauta HVVJ . Evidence of a pallido - ways between striate cortex and
glutamate levels in synaptic termi - habenular pathway in the cat . ) subcortical regions in Mactioi mu -
-
nals of retino geniculate, cortico- Comp Neurol 1974;156:19-28. latto and Snimiri sciiireus : evidence
-
geniculate, and genicuIo corticaI 291. Nauta HJW, Pritz MB, Lasek RJ . for a reciprocal pulvinar connec -
axons in the cat. Vis Neurosci Afferents to the rat caudoputamen tion . Exp Neurol 1976;53:780-800.
1990;4:437-443. studied with horseradish peroxi- 308. Ohara IT, Lieberman AR , Hunt
272. Moore BW . Brain-specific proteins. dase: an evaluation of a retrograde SP, VVu J - Y . Neural elements con -
In: Schneider DJ , ed . Proteins of neuroanatomical research method . taining glutamic add decarboxy -
the nervous svstem. New York: Brain Res 1974;67:219-238. lase ( GAD ) in the dorsal lateral
.
Raven Press 1973: 1-12. 292. Nauta VVJH. Hippocampal projec- geniculate nucleus of the rat: im -
273. Moore RY. The innervation of the tions and related neural pathways munohistochemical studies by
mammalian pineal gland . In : Re- to the midbrain in the cat . Brain light and electron microscopy.
iter RJ , ed . The pineal and repro- 1958;81 :314-340. Neuroscience 1983;8:189-212.
duction . Basel: S. Karger, 1978: 293. Nauta VVJH. Fibre degeneration 309. Ohye C. Thalamus. In : Paxinos G ,
29.
I following lesions of the amyg- ed . The human nervous system.
274. Moore RY, Goldberg |M . Ascend - daloid complex in the monkev . J Ch . 17. New York: Academic Press,
ing projections of the inferior col - -
Anat 1961;95:151 531. 1990:439-464.
liculus in the cat . J Comp Neurol 294. Nauta VVJH . Neural associations of 310. Ojeman G. Interrelationship in the
1963;121:109-136. the amygdaloid complex in the localization of language, memory
275. Moore RY , Goldberg |M . Projec - monkey. Brain 1962;85:505-520. and motor mechanisms in human
tions of the inferior colliculus in 295. Nauta VVJH , Mehler WR . Projec- cortex and thalamus. In : Thomp-
the monkev. Exp Neurol 1966; tions of the lentiform nucleus in son R , ed . New perspectives in
14:429-438. the monkey. Brain Res 19*16; 1 :3-42. cerebral localization. New York :
276. Moore RY, Klein DC. Visual path - 296. Nauta VVJH, Whitlock DG . An Raven Press, 1981 :157 175.
311. Oliver DL, Hall WC. The medial beling method . Brain Res 1983; the monkey ( Macaca mulatto ). Anat
geniculate body of the tree shrew' , 278:11 -27. Ree 1%4;148:322.
Tupaia # lis . 1. Cytoarchitecture and 326. Parent A, Descarries L , Beaudet A . 340. Petras JM . Fiber degeneration in
midbrain connections. J Comp Organization of ascending sero- the basal ganglia and diencephalon
Neurol 1978;182:423-458. tonin systems in the adult rat following lesions in the precentral
312. Oliver DL, Hall WC. The medial brain. A radioautographic study and postcentral cortex of the mon-
geniculate body of the tree shrew , after intraventricular administra - key ( Macaca mulatto ): with addi -
Tufhiia glis . II . Connections with the -
tion of |'H| 5 hydroxytryptamine. tional observations in the chim-
neocortex. J Comp Neurol 1978;
-
182:459 494 .
Neuroscience 1981;6:115 138. -
327. Parent A , Mackey A, De Belle-
panzee. In : Proceedings of the
VI International Congress on
313. Olivier A, Parent A, Poirier I.J . feuille L. The subcortical afferents Anatomy , Wiesbaden , 1%6.
Identification of the thalamic nu - to caudate nucleus and putamen in 341. Petras ) M. Some efferent connec-
clei on the basis of their cholin - primate: a fluorescence retrograde tions of the motor and somatosen -
esterase content in the monkey J -
double labeling study . Neuro - sory cortex of simian primates and
Anat 1970;106:37 50. - science 1983;10:1137-1150. Felid , Canid and Procvonid carni -
314 Olszewski J . The thalamus of the 328. Parent A, Pare D, Smith Y, Steriade vores. Ann NY Acad Sci 1969;
Macaca mulatto. Basel : S. Karger, M . Basal forebrain cholinergic and 167:469-505.
1952. -
non cholinergic projections to the 342. Petras JM . Connections of the pari -
315. Oscarsson O, Rosen 1. Short - la - thalamus and brainstem in cats etal lobe. I Psychiatr Res 1971;
tencv projections to the cat 's cere- and monkeys. J Comp Neurol 8:189-201.
bral cortex from skin and muscle -
1988;277:281 301 343. Phillipson OT, Griffith AC . The
afferents in the contralateral fore - 329. Parent A , Steriade M . Midbrain neurones of origin for the meso-
limb . J Phvsiol ( Lond ) 1966;182: tegmental projections of nucleus habenular dopamine pathway.
-
164 184. reticularis thalami of cat and mon - Brain Res 1980;197:213-218.
-
316. Pape H C, McCormick DA . Nor - key: a retrograde transport and an- 344 . Pierson RJ , Carpenter MB.
adrenaline and serotonin selec- tidromic invasion study . J Comp Anatomical analysis of pupillary
tively modulate thalamic burst Neurol 1984;229:548-558. reflex pathways in the rhesus mon -
firing by enhancing a hyperpolari - 330. Partlow GD, Colonnier M, Szabo J . key. J Comp Neurol 1974;158:
zation -activated cation current . Thalamic projections of the supe- -
121 143.
Nature 1989;340:715 718.-
317. Papez JW . Thalamic connections in
rior colliculus in the rhesus mon -
key , Macaca mulatto. a light and
345. Poggio GF, Mountcastle VB. A
study of the functional contribu -
a hemidecorticate dog. J Comp electron microscopic study. J tions of the lemnisca! and
Neurol 1938;69:103 119 - Comp Neurol 1977;171:285 318. - spinothalamic systems to somatic
318. Papez JW . A summary of fiber con - 331. Pasik P, Pasik T, Hamori J . sensibility. Bull Johns Hopkins
nections of the basal ganglia with Synapses between mtemeurons in Hosp 1960;106:266-316.
each other and w ith other portions the lateral geniculate nucleus of .346. Poggio GF, Mountcastle VB. The
of the brain. Proc Assoc Res Nerv
Ment Dis 1942;21:21-68.
monkeys. Exp Brain Res 1976;
-
25: 1 13.
functional properties of ven
trobasal thalamic neurons studied
-
319. Pare D, Hazrati L- N , Parent A, Ste- 332. Pasik P, Pasik T, Hamori J , Szen - in unanesthetized monkeys. J Neu -
riade M . Substantia nigra pars
reticulata projects to the reticular
tagothai J . Golgi type II interneu -
rons in the neuronal circuit of the
rophysiol 1963;26:775 806 - .
.347. Polyak SL. The vertebrate visual
thalamic nucleus of the cat: a mor - monkey lateral geniculate nucleus system . Chicago: Unversity of
phological and electrophvsiologi - Exp Brain Res 1973;17:18-34 . Chicago Press, 1957:1390
cal study Brain Res i 990;535: 333. Pazos A , Probst A, Palacios JM . .348. Powell TPS. Residual neurons in
139-146. Serotonin receptors in the human the human thalamus following
320. Pare D, Smith Y, Parent A , Steriade brain. III . Autoradiographic map- hemidecortication. Brain 1952;75:
M . Projections of brainstem core ping of serotonin- 1 receptors. Neu - 571-584.
cholinergic and non -cholinergic -
roscience 1987;21:97 122. 349. Powell TI *S, Cowan WM . A study
neurons of cat to intralaminar and 334. Pearson RC, Brod a I P, Powell TPS. of thalamo-striate relations in the
reticular thalamic nuclei . Neuri > - The projection of the thalamus monkey. Brain 1956;79:364-390.
science 1988;25:69-86. upon the parietal lobe in the mon - 350. Powell TPS, Cowan WM , Raisman
321 . Pare D, Steriade M . The reticular key. Brain Res 1978;144:143-148. G. Olfactory relationship of the di-
thalamic nucleus projects to the 335. Penfield W , Boldrey E. Somatic encephalon . Nature 1963;199:
contralateral dorsal thalamus in motor and sensory representation 710-712.
macaque monkey . Neurosci Lett in the cerebral cortex of man as 351. Powell TPS, Cowan WM , Raisman
1993;154:96-100. studied by electrical stimulation . G . The central olfactory connex -
322. Parent A . Identification of the pal -
lidal and peripallidal cells project -
-
Brain 1937;60:389 443.
336. Penfield W, Rasmussen T. The
ions. ) Anat 1965;99:791-813.
352 . Powell TI*S, Guillerv RW , Cowan
ing to the habenula in monkey. cerebral cortex of man : a clinical WM . A quantitative study of the
Neurosci Lett 1979;15:159-164 . study of localization of function. fornix - mammillothalamic system .
323. Parent A , Butcher LL. Organiza - New York: MacMillan Company , -
J Anat 1957;91:419 432.
tion and morphologies of acetyl - 1950. 353. Price JL. Olfactory system . In: Paxi -
-
choiinesterase containing neurons 337. Percheron G. The thalamic terri - nos G , ed . The human nervous sys-
in the thalamus and hypothalamus tory of cerebellar afferents and the tem Ch. 29. New York : Academic
of the rat . J Comp Neurol 1976; lateral region of the thalamus of -
Press, 1990:979 999.
170:205-226. the macaque in stereotaxic ventric - 354. Purpura DP. Intracellular studies
324 . Parent A , De Bellefeuille L . Organi - ular coordinates. J Hirnforsch of synaptic organization in the
zation of efferent projections from 1977;18:375-400. mammalian brain . In: Pappas GD,
the internal segment of globus pal - 338. Percheron G, Francois C, Talbi B. Purpura DP, eds. Structure and
lidus in primate as revealed by Meder JF, Fenelon G, Yelnik J . The function of synapses. New York:
fluorescence retrograde labeling
method . Brain Res 1982;245:
primate motor thalamus analysed
with reference to subcortical affer -
-
Raven Press, 1972:257 302.
355. Quay WB. Pineal chemistry in the
201-214. ent territories. Stereotact Funct cellular and physiological mecha -
325. Parent A , De Bellefeuille L . The Neurosurg 1993;60:32-41. nisms. Springfield , IL: Charles C .
pallidointralaminar and pallidon - 339. Petras JM . Some fiber connections I homMt 1974 .
igral projections in primate as of the precentral cortex (areas 4 356. Raczkowski D, Diamond IT, Winer
studied by retrograde double-la - and 6) with the diencephalon in J Jr. Organization of thalamocorti -
16 Thalamus 703
cal auditory system in the cat stud - matter and the reticular nucleus of cleus of the cat . Brain Res 1975;
ied with horseradish peroxidase. the thalamus. Anat Embrvol 1990; -
85:313 316.
Brain Res 1976;101:345 354.-
357. Raisman G. Neural connexions of 372.
-
181:577 584.
Roberts TS, Akert K Insular and
385. Salt TE. Electrophysiological stud -
ies of excitatory amino acid neuro-
hypothalamus. Br Med Bull 1966; opercular cortex and its thalamic transmission in the ventrobasal
22:197-210. projection in Manna mulatto. thalamus. In : Macchi G, Ben -
358. Raisman G, Cowan YVM , Powell Schweiz Arch Neurol Neurochir tivoglio M , Spreafico R , eds. Cellu -
TPS. The extrinsic afferent , com-
misural and association fibres of 373.
.-
Psychiat 1963 92:1 43. -
Robertson RT, Rinvik F.. The corti -
lar thalamic mechanisms. Amster -
dam: Elsevier, 1988:297-310.
the hippocampus. Brain I 965;88: cothalamic projections from pari - 386. Scheibel ME, Scheibel AB. The orga -
963-996 , etal regions of the cerebral cortex: nization of the nucleus reticularis
359. Ralston HJ 3d , Ralston DD. The experimental degeneration stud - thalami: a Golgi study . Brain Res
primate dorsal spinothalamic tract: ies in the cat . Brain Res 1973; 1966;1 :43-62.
evidence for a specific termination 51:61-79. 387. Scheibel ME , Scheibel AB. The or -
in the posterior nuclei ( Po/ SG ) of 374. Robinson CJ , Burton 11. The orga - ganization of the ventral anterior
the thalamus. Pain 1992;48: 107 - nization of somatosensory recep - nucleus of the thalamus: a Golgi
118. tive fields in cortical area 7b, study. Brain Res 1966;1:250-268.
360. Ramon y Cajal S. Histologie du retroinsular, postauditory and 388. Scheibel ME, Scheibel AB. Struc-
Systeme Nerveux de I ' Homme et granular of M. fascicular!s. J Comp tural organization of nonspecific
des Vertebres. ( Azoulay L, trans.), Neurol 1980;192:69-92. thalamic nuclei and their projec-
Paris: Maloine, 1909, 1911 . 375. Rockel AJ , Jones EG. The neuronal tion toward cortex. Brain Res
( Reprinted , Consejo Superior de organization of the inferior collicu - 1967;6:60-94.
Investigaciones Cientificas, Insti- lus of the adult cat . I . The central 389. Schell GR, Strick PL. The origin of
tuto Ramon y Cajal , Madrid , 1972.) nucleus. J Comp Neurol 1973; thalamic input to the arcuate, pre-
361 . Ranson SW, Ranson SVV Jr . Effer- -
147:11 60. motor and supplementary areas. J
ent fibers of the corpus striatum. 376. Rose JE, Malis LI . Geniculostriate Neurosci 1984;4:539-560.
Proe Assoc Res Nerv Ment Dis connections in the rabbit . II . Cy - 390. Schlag |, Waszak M . Characteris -
1942;21 :69-76. toarchitectonic structure of the stri - tics of unit responses in nucleus
362. Raos V , Bentivoglio M. Crosstalk ate region and of the dorsal lateral reticularis thalami . Brain Res 1970;
between the two sides of the thala - geniculate body: organization of 21:286 288.
mus through the reticular nucleus: -
the geniculo striate projections. | .391 . Schwartz ML , Mrzljak L. Choliner -
a retrograde and anterograde trac - Comp Neurol N65; 125: 121 140 gic innervation of the mediodorsal
ing study in the rat . J Comp Neurol 377. Rose JE, Mountcastle VB. The thal- thalamic nucleus in the monkey :
1993;332:145-154. amic tactile region in rabbit and cat . ultrastructural evidence support -
363. Rasminsky M , Mauro AJ , Albe- J Comp Neurol 1952;97:441-490. ive of functional diversity. J Comp
Fessard D. Projections of medial 378. Rose JE, Mountcastle VB. Touch Neurol 1993;327:48-62.
thalamic nuclei to putamen and and kinesthesis. In : Fields J , ed . -
.392. Scollo Lavizzari G, Akert K . Corti -
cerebral frontal cortex in the cat . Handbook of physiology. Section I , cal area 8 and its thalamic projec -
Brain Res 1973;61 :69-77 Vol. I: Neurophysiology . Ch. 17. .
tion in Macaca mulatto J Comp
364. Rasmussen AT, Peyton WT. The Washington , DC: American Physi - Neurol 1963;121:259-267.
course and termination of the me- ological Society, 1959:387-429. 393. Sherman SM , Koch C. Thalamus.
dial lemniscus in man . j Comp 379. Rose JE, Woolsey CN. Cortical con - In G . M Shepherd , ed . The synaptic
Neurol 1948;88:411 -424. nections and functional organiza - organization of the brain . Ch. 8.
365. Ray JP, Price JL. The organization tion of the thalamic auditory sys- New York: Oxford University
of the thalamocortical connections tem of the cat. In : Harlow HF, Press, 1990: 246-278.
of the mediodorsal thalamic nu - Woolsey CN , eds. Biological and 394 . Sheps JG . The nuclear configura -
cleus in the rat , related to the ven- biochemical bases of behavior. tion and cortical connections of the
-
tral forebrain prefrontal cortex Madison: University of Wisconsin human thalamus. J Comp Neurol
topography. J Comp Neurol
1992;323:167-197. .380.
Preas, 1958:127 150 - .
Royce GJ . Recent research on the
1945;83:1-56.
395. Sheridan MN , Sladek JR Jr . Ilisto-
.366. Relkin R . The pineal . Montreal: centromedian and parafascicular fluorescence and ultrastructural
Eden Press, 1976. nuclei . In: Carpenter MB, Jayara - analysis of hamster and monkey
367. Rezak M, Benevento LA . A com - man A , eds. The basal ganglia . 11: pineal. Cell Tissue Res 1975;164 :
parison of the organization of the
projections of the dorsal lateral concepts. New York: Plenum
—
Structure and function current 145-152.
.3% Shute CCD, Lewis PR . The ascend -
geniculate nucleus, the inferior Press, 1987:293 319. - ing cholinergic reticular system:
pulvinar and adjacent lateral pulv- 381. Russell GV. A schematic presenta - neocortical, olfactory and subcorti -
inar to primary visual cortex ( area tion of thalamic morphology and cal projections. Brain 1967;90:
17) in the macaque monkey. Brain connections. Tex Rep Biol Med -
497 520.
Res 1979;167:19 -40. -
1955;13:989 992. 397. Singer W . Control of thalamic
368. Rinvik F.. The corticothalamic pro- 382. Sadikot AF, Parent A, Francois C. transmission by corticofugal and
jection from the pericruciate and Efferent connections of the centro- ascending reticular pathways in
coronal gyri in the cat: an experi - median and parafascicular thala - the visual system . Physiol Rev
mental study with silver- impreg- mic nuclei in primates. A PHA L - 1977;57: 386-420.
nation methods. Brain Res 1968; study of subcortical projections. J 398. Simpson DA . The projection of the
10:79-119. Comp Neurol 1992;315:137 - 159. pulvinar to the temporal lobe. |
369. Rinvik E. Thalamic commissural 383. Sadikot AF, Parent A, Smith Y, Anat 1952;86:20 28.-
connections in the cat . Neurosci Bolam JP. Efferent connections of 399. Siqueira EB. The cortical connec-
Lett 1984;44:311-316. the centromedian and parafascicu - tions of the nucleus pulvinaris of
370. Rinvik E, Ottersen OP, Storm- lar thalamic nuclei in the squirrel the dorsal thalamus in the rhesus
Mathisen J . Gamma aminobu - - monkey: a light and electron mi - monkey. J Hirnforsch 1971;10:
-
tyrate like immunoreactivity in the
thalamus of the cat . Neuroscience
croscopic study of the thalamostri
atal projection in relation to striatal
- -
487 498.
400. Skinner JE , Lindslev DB. Electro -
1987;21 :781-805. heterogeneity J Comp Neurol physiological and behavioral ef -
371 . Rinvik E, YViberg M . Demonstra -
tion of a reciprocal connection be- 384 .
^
1992;320:228 242.
Sanides D. The retinal projection to
fects of blockage on the nonspecific
thalamocortical system . Brain Res
tween the periaqueductal gray the ventral lateral geniculate nu - 1967;6:95-117.
.
401. Smith MC Stereotaxic operations 416. Sterling P. Retina . In: Shepherd from the main trigeminal sensory
—
for Parkinson's disease anatomi -
cal observations. In: Williams D,
GM, ed The synaptic organization
of the brain. Ch. 6. New York: Ox-
nucleus: an experimental study in
the cat . Am J Anat 1957;100:1-15.
ed. Modern trends in neurology. ford University Press, 1990: 431. Tracey DJ, Asanuma C, Jones EG,
Vol. 4. London: Butterworths, 170-213. Porter R. Thalamic relay to motor
1967:21-52. 417. Stone J, Fukuda Y. Properties of cat cortex: afferent pathways from
402. Smith Y, Parent A , Seguela P, retinal ganglion cells: a compari- brain stem, cerebellum, and spinal
.
Descarries L Distribution of son of VV cells with X and Y cells J . cord in monkevs. J Neurophvsiol
GABA -immunoreactive neurons in Neurophvsiol 1974;37:722-748. 1980;44:532-553.
the basal ganglia of the squirrel 418. Strick PL. Anatomical analysis of 432. Trojanowski JJ, Jacobson S. A com-
monkey ( Saiiniri Sciiimis ). J Comp ventrolateral thalamic input to pri- bined horseradish peroxidase-au-
Neurol 1987;259:50-65 . mate motor cortex. J Neurophvsiol toradiographic investigation of
403. Sofroniew MV, Priestley JV, Con - 1976;39:1020-1031. reciprocal connections between su-
sola / ione A , Hckenstein F, Cuello 419. Sugimoto T, Takada M, Kaneko T, perior temporal gyrus and pulv -
AC. Cholinergic projections from
the midbrain and pons to the thala-
-
Mi/ uno N. Substance P positive
lhalamocaudate neurons in the
inar in squirrel monkev . Brain Res
1975;85:347-353.
mus in the rat, identified by com-
bined retrograde tracing and
-
center median parafascicular com- 433. Tusa RJ, Rosenquist AC, Palmer
plex in the cat . Brain Res 1984; LA . Retinotopic organization of
choline acetvltransferase immuno- 323:181- 184. areas 18 and 19 in the cat. J Comp
.
histochemistry Brain Res 1985; 420. Swanson LW, Hartman BK. The Neurol 1979;185:657-678.
329:213-223. central adrenergic system: an im- 434 . Updvke BV. A reevaluation of the
404. Spreafico R, Battaglia C», Frassoni munofluorescence study of the lo- functional organization and cy-
C. The reticular thalamic nucleus cation of cell bodies and their effer- toarchitecture of the feline lateral
( RTN ) of the rat: cytoarchitectural, ent connections in the rat utilizing posterior complex, with observa -
Golgi, immunocytochemical, and dopamine-beta-hydroxylase as a tions on adjoining cell groups. J
horseradish peroxidase study |
Comp Neurol 1991;304:478 490. -
. marker. J Comp Neurol 1975;
16.3:467-506.
-
Comp Neurol 1983;219:143 181.
435. Van Buren JM, Borke RC. Varia -
405 Squire LR . Mechanisms of mem- 421. S/entagothai J Glomerular tions and connections of the
ory . Science 1986;232:1612- 1619. synapses, complex synaptic human thalamus. New York:
406. Stanton GB. Topographical organi- arrangements, and their opera- Springer- Verlag, 1972.
zation of ascending cerebellar pro- tional significance. In: Schmitt FO, 4,36. Van den Pol AN, Powley T. A fine-
jections from the dentate and inter - ed. The neurosciences. Second grained anatomical analysis of the
posed nuclei in Macaca nut hi tt a: an study program. Ch. 40. New York: role of the rat suprachiasmatic nu-
anterograde degeneration study. | Rockefeller University Press, 1970: cleus in circadian rhythms of feed-
Comp Neurol 1980;190:699-731. 427-443. ing and drinking. Brain Res
407. Star / 1 TE, Magoun HW . Organiza - 422. Szentagothai J. Neuronal and 1979;160:307-326.
tion of the diffuse thalamic projec - synaptic architecture of the lateral 437. Van der Koov D, Kuypers HGJM,
tion system. J Neurophvsiol geniculate nucleus. In: Jung R, ed. Catsman-Berrevoets CE. Single
1951;14:133-146 Handbook of sensory physiology. mamillary body cells with diver-
408. Starzl TE, Taylor CW, Magoun Vol 7: Central processing of visual gent axon collaterals: demonstra -
HW . Ascending conduction in information. Part B: Morphology tion by a simple fluorescent retro-
reticular activating system, with and function of visual centers in grade double labeling technique in
special reference to the dien- the brain. Berlin: Springer- V erlag,
' the rat. Brain Res 1978;158:189-196.
cephalon. J Neurophvsiol 1951; 1973:141-176 . 438. Van Groen T, Wyss JM. Projections
14:461-477. 423. Tessier -l avigne M. Phototransduc- from the laterodorsal nucleus of
409. Star /I TE, Whitlock DG. Diffuse tion and information processing in the thalamus to the limbic and vi-
thalamic projection system in mon- the retina. In: Kandel ER, Schwartz sual cortices in the rat. J Comp
key . J Neurophvsiol 1952,15: JH, Jesseil TM, eds. Principles of Neurol 1992;324:427-448.
449-468. neural science. Ch. 28. New York: 439. Veazey RB, Amaral DG, Cowan
410. Steriade M, Biesold D. Brain Elsevier, I99I:4(KM17. WM. The morphology and connec -
cholinergic systems. Oxford: Ox - 424. Thach WT, Jones EG. The cerebel- tions of the posterior hypothala -
ford University Press, 1990. lar dentatothalamic connection: mus in the cvnomolgus monkey
411. Steriade M, Deschene M. The thal - terminal field, lamellae, rods and ( Macaca fascicularis ). II. Efferents
amus as a neuronal oscillator. somatotopy. Brain Res 1979;169: .
connections J Comp Neurol 1982,
Brain Res 1984;320:1 -63. 168-172. 207:135-156.
412. Steriade M, Glenn LL. Neocortical 425 Tigges J, O'Stecn WK . Termina- 440. Verhaart WJC, Kennard MA . Cor-
and caudate projections of in- tions of retinofugal fibers in squir - ticofugal degeneration following
tralaminar thalamic neurons and rel monkey: a re-investigation thermocoagulation of areas 4, 6
their synaptic excitation from mid- using autoradiographic methods. and 4S in Macaca mulatta. J Anat
brain reticular core. J Neurophvs- Brain Res 1974;79:489-495 . 1940 74:239 254
iol 1982;48:352-371. 426 . Tigges M, Tigges J . The retinofugal ^
441. Vogt BA , Rosene DL, Pandya DN.
413. Steriade M, Elinas RR. The func - fibers and their terminal nuclei in Thalamic and cortical afferents dif -
tional states of the thalamus and Glingo crastiaiudatus (primates). I ferentiate anterior from posterior
the associated neuronal interplay. Comp Neurol 1970;138:87-102. cingulate cortex in the monkev .
Physiol Rev 1988;68:649-742. 427. Tobias TJ. Afferents to prefrontal Science 1979;204:205-207.
414. Steriade M, Parent A , I lada |. Thal - cortex from the thalamic medio- 442. Vogt LJ, Vogt BA, Sikes RW . Lim-
amic projections of nucleus reticu- dorsal nucleus in the rhesus mon- bic thalamus in rabbit : architec -
laris thaiami of cat : a study by key. Brain Res 1975;83:191-212. ture, projections to cingulate cortex
using retrograde transport of MRP 428. Tomasch |. The numerical capacity and distribution of muscarinic
and fluorescent tracers. I Comp
Neurol 1984;229:531-547.
-
of the human cortico-ponto cere-
bellar system. Brain Res 1969;
acetylcholine, GABAA, and opioid
receptors. I Comp Neurol 1992;
415. Steriade M, Parent A, Pare D, 13:476-484. 319:205-217.
Smith Y . Cholinergic and non- 429. Ioncrav JE, Krieg WJS. The nuclei 443. Wald G. Molecular basis of visual
cholinergic neurons of cat basal of the human thalamus: a compar - excitation. Science 1968;162:
forebrain project to reticular and ative approach. J Comp Neurol 230- 239.
mediodorsal thalamic nuclei. Brain 1946;85:421-459. 444. Walker AF. An experimental study
Res 1987;408:372-376. 430. Torvik A . The ascending fibers of the thalamocortical projection of
16 Thalamus 705
the macaque monkey. J Comp 432. Willis WD jr. Nociception neurons 457. Yakovlev PI, LockeS, Angevine|B
Neurol 1936;64:1 39. - in the primate ventral posterior lat - ) r. The limbus of the cerebral hemi -
443. Walker AE. The thalamus of the eral ( VPL ) neucleus. In . Bentivo - sphere, limbic nuclei of the thala -
chimpanzee. IV. Thalamic projec- glio M , Spreafico R , eds. Cerebel - mus and the cingulum bundle. In :
tions to the cerebral cortex . J Anat lar thalamic mechanisms. Amster - Purpura DP, Yahr MD, eds. The
-
1938;73:37 93. dam: Excerpta Medica , 1988:77-92. thalamus. New York: Columbia
446. Walker AE. The primate thalamus. 433. Winer JA, Diamond IT, l Diversity Press, 1466:77
Chicago: University of Chicago Kac / kowski D. Subdivisions of the 458. Yasui Y, Saper CB, Cechetto DF.
Press, 1938. auditory cortex in the cat : the ret - Calcitonin gene- related peptide
447 Walker AE . Afferent connections rograde transport of horseradish (CGRP ) immunoreactive projec-
In: Buev IXT, ed . The precentral peroxidase to the medial genicu - tions from the thalamus to the
motor cortex . 2d ed . Ch . 4 Urbana : late body and posterior thalamic striatum and amygdala in the rat . J
l m \ vrsit \ t *| Illinois 1949: nuclei. J Comp Neurol 1977; Comp Neurol 1991;308:293-310.
112-132. 176:387-418. -
459. Yen C T, Jones EG . Intracellular
448 Walker AE . Normal and pathologi- 434 . Wong- Riley MTT . Projections from staining of physiologically identi -
cal physiology of the thalamus. In : the dorsal lateral geniculate nu - fied neurons and axons in the MV -
.
Schaltenbrand G , Bailey P eds. In - cleus to prestriate cortex in the matosensorv thalamus of the cat .
troduction to stereotaxis with an squirrel monkey as demonstrated Brain Res 1983;280:148-154.
atlas of the human brain . Vol . I . by retrograde transport of horse - 460 Zahm DS, Zaborszky L , Alheid GE,
Stuttgart : Georg Thieme Verlag, radish peroxidase. Brain Res 1976; Meimer L. The ventral striatopalli -
449
-
1959:291 330.
Walker AE. Internal structure and
-
109:595 600.
433. Woolf NJ , Butcher LL. Cholinergic
dothalamic projection : II . The ven -
tral pallidothalamic link . J Comp
-
afferent efferent relations of the systems in the rat brain : III . Projec - -
Neurol 1987;255:592 605.
thalamus. In: Purpura DP, Yahr
MD, eds. The thalamus . New York :
tions from the pontomesencephalic
tegmentum to the thalamus, tec -
-
461 . Zola Morgan S, Squire LR . Amne
sia in monkeys after lesions of the
-
Columbia University Press, 1968: tum , basal ganglia , and basal fore- mediodorsal nucleus of the thala -
1 -12.
430. .
Whitlock DC, Nauta WJH. Subcor
tical projections from the temporal
-
brain . Brain Res Bull 1986; 16:
-
603 637.
436. Woolsey CN. Organization of so-
mus. Ann Neurol 1985;17:558 564 .
462. Diamond IT, Fitzpatrick D, Conley
M . A projection from the para -
neocortex in the Macaco mulatto. J matic sensory and motor areas of bigerminal nucleus ( Pbg ) to the
-
Comp Neurol 1956;106:183 212. the cerebral cortex . In : Marlow ME , pilvinar nucleus in Galago. J Comp
431 . .
Wilson ME Cragg BG. Projection Woolsey CN, eds. Biological and Neurol 1992;316:375-382.
from the lateral geniculate nucleus biochemical bases of behavior.
in the cat and monkev. j Anat Madison: University of Wisconsin ,
1967;101:677-692. -
1958:63 81.
17
Hypothalamus
At the end of the 19th Century, the French brain for the control of the regulation of hor-
physiologist Claude Bernard drew attention mone release from the pituitary gland or hy -
to the importance of maintaining a constant pophysis. The involvement of the hypothala -
internal environment ( “ milieu interne") for mus in the control of neuroendocrine,
the survival of the organism (8). This notion autonomic, and motivational output systems
was further emphasized by Walter Cannon, has been documented by experimental stud -
who first coined the term homeostasis to refer ies undertaken principally in rodents. By
to the condition that results from various comparison, little is known of the anatomic
mechanisms acting to limit the variability of and functional organization of these hypo-
the body's internal states ( 22). The internal thalamic control systems in primates, particu -
environment of the body is maintained con- larly humans. Nevertheless, the fact that the
stant through the interplay of three major structural organization of the hypothalamus
classes of mechanisms: neuroendocrine, auto- in rodents differs only slightly from that in
nomic, and motivational. The hypothalamus, primates allows interesting interspecies com -
together with a group of highly heteroge- parisons that can shed light on the functional
neous structures referred to as the limbic sys- organization of the hypothalamus in humans.
tem , are key neuronal elements involved in The hypothalamus represents the most
maintaining homeostasis. The hypothalamus ventral portion of the diencephalon. The thal -
and closely related structures in the limbic amus lies dorsal to the hypothalamus, and
system receive information directly from the the subthalamic region is lateral and caudal
internal environment and act directly on the ( Figs. 2.29 and 16.6 ). The hypothalamus is lo-
internal environment . Other brain structures cated in the walls of the third ventricle below
affect the internal environment indirectly the hypothalamic sulci and is continuous
through action on the external environment, across the floor of this ventricle ( Figs. 2.29
and both the direct and indirect ways of regu - and 17.1 ). On the ventral surface of the brain,
lating the internal environment function the infundibulum , to which the hypophysis is
largely in parallel (81, 161 ). In this chapter, attached , emerges posterior to the optic chi-
we examine the anatomic organization of the asm ( Figs. 2.9, 2.10, and 17.1 ). A slightly
hypothalamus and its role in controlling the bulging region posterior to the infundibulum
neuroendocrine and autonomic functions. is the tuber cinereum ( Figs. 2.10, 17.12, and
Structures of the limbic system and their roles 17.13). The mammillary bodies lie posteriorly
in organizing motivational and emotional be- near the interpeduncular fossa ( Figs. 2.9 and
haviors are examined in Chapter 18. 2.28).
More than half a century ago, the English Externally, the hypothalamus is bounded
anatomist Wilfrid Le Gros Clark noted that rostrally by the optic chiasm, laterally by the
the hypothalamus accounts for only about 4 g optic tracts, and posteriorly by the mammil -
-
of the total 1200 1400 g of adult human brain lary bodies. This region is roughly diamond -
weight, or less than 1 % of the total volume of shaped , and its surface is irregular because of
the human brain (83). Despite its small size, several small eminences. The zone forming
the hypothalamus is known to contain the in- the floor of the third ventricle is called the me-
tegrative neural systems critical for basic life dian eminence of the tuber cinereum. The por-
support, including activities such as fluid and tion rostral to the infundibular stem is the an -
electrolytic balance, food ingestion and en- terior median eminence . The portion posterior
ergy metabolism , thermoregulation, repro - to the infundibular stem forms the posterior
duction, and emotional responses (161 ). The median eminence , which is better developed in
hypothalamus is also the key structure of the humans ( Fig. 2.9). Paired lateral eminences
706
17 Hypothalamus 707
Paraventric
Posterior
Preoptic area nucleus
Ventromedial
Anterior nucleu nucleus
Mammillary body
nucli Arcuote nucleus V
Optic chiasm Infundibulum
Hypophysis
Figure 17.1. Major hypothalamic nuclei Nuclei In the supraoptic region are in blue Nuclei of the middle or tuberal
region of the hypothalamus are yellow Nuclei of the caudal or mammillary region are shades of red. The preoptlc
area ( gray ) lies rostral to the supraoptic region.
.
form well-defined landmarks. The ventral HYPOTHALAMIC NUCLEI

protrusion of the hypothalamus and the third
ventricular recess form the infundibulum. The cytoarchitectural organization of the
The most distal portion of the infundibular human hypothalamus is largely similar to
process is the neurohypophysis. Tissue join - that found in other primate and nonprimate
ing the infundibular process to the median species. It was described in detail by Le Gros
eminence is called the infundibular stem . The Clark (82 ), Rioch, et al. (155), Brockhaus ( 14 ),
median eminence represents the final point of and , more recently, by Nauta and Haymaker
convergence of pathways from the central (118), and Saper (161 ). The nomenclature
nervous system upon the peripheral en- used in this chapter is largely based on the re-
docrine system. The median eminence is the sults of the two latter studies. The nuclear
anatomic site of the interface between brain masses in the adult human hypothalamus are
and the anterior pituitary. Primary capillaries not as distinct as their counterparts in other
of the hypophysial portal vessels vascularize mammalian species. Nevertheless, as in other
the median eminence. Ependymal cells lining species, the human hypothalamus is usually
the floor of the third ventricle have processes divided in Nissl-stained material into three
that traverse the width of the median emi - rostrocaudal regions and three mediolateral
nence and terminate near the portal perivas- zones or areas.
cular space. These cells, called tanycytes, pro- Rostrocaudally, the most anterior region of
vide a structural and functional link between the hypothalamus is bordered rostrally by the
the cerebrospinal fluid (CSF) and the perivas- lamina terminalis and caudally by the poste-
cular space of the pituitary portal vessels. rior edge of the optic chiasm . This region can
.AMMS
A Ml ventricle
•f
/— Paraventricular nucleus
Mi Lateral preoptic area
Medial preoptic area

Suprachiasmatic nucleus
Supraoptic nucleus
Optic chiasm
III ventricle
Posterior hypothalamic nucleus
Fornix
Lateral hypothalamic nucleus
Ventromedial hypothalamic nucleu

Tuberal nuclei
Lateral hypothalamic area

c
III ventricle
Posterior hypothalamic nucleus
Crus cerebri Fasciculus mammillary

princeps
Lateral mammillary
nucleus
Medial mammillary nucleus
Intermediate mammillary
nucleus
Figure 17.2. Transverse sections through portions of the human hypothalamus A, supraoptic region. B infundibular
region C. mammillary region
17 Hypothalamus 709
be further subdivided into a preoptic region lo- region is characterized by the presence of the
cated between the lamina terminalis and the mammillary bodies and is referred to as
optic chiasm , and a supraoptic region lying the mammillary region . A small portion of
above the optic chiasm ( Figs. 17.2 and 17.3). the third ventricle, the mammillary recess, is
The middle hypothalamic region gives rise often trapped ventrallv between the mammil -
medially to the pituitary stalk and is often re- lary bodies and the midline. Caudally, the
ferred to as the infundibular or tuberal region. hypothalamus merges imperceptibly into
The lateral surface of the tuberal region often the central gray matter and tegmentum of the
displays several small protuberances, repre- midbrain.
senting the external protrusions of the lateral Mediolaterally, the hypothalamus can be
tuberal nuclei . The posterior hypothalamic subdivided into (a ) a thin and relatively un-
Posterior hypothalamic nucleus Paraventricular nucleus

Anterior commissure
A
Nucleus of diagonal band
Preoptic area
Dorsomedial
hypothalamic nucleus
Medial
mammillary nucleus ~~ Anterior
Supraoptic nucleus
~ Optic nerve
Ventromedial
B
Anterior commissure
Lateral hypothalamic area 4? M
-W
Preoptic area
Mammillary nuclei
v'
, *
W' •
* / —
Fornix
Lateral — Supraoptic nucleus
Intermediate Optic nerve
—
y. / — Anterior commissure
Lateral hypothalamic area v. — Preoptic area

: -2»< •

Lateral mammillary nucleus __ •v
- Supraoptic nucleus
>
Optic nerve
Lateral tuberal nuclei
Figure 17.3. Sagittal sections through portions of the human hypothalamus A near ventricular surface. B through
the anterior column of the fornix; C near lateral border of hypothalamus
differentiated periventricular area , ( b ) a largewhich are found the large cells of the lateral
medial hypothalamic area, which contains hypothalamic nucleus ( Figs. 17.2 and 17.3).
most well -defined hypothalamic nuclear The tuberal nuclei are particularly well-de-
masses, and (c ) a large lateral hypothalamic veloped in humans, but similar nuclei also
area , which contains large neurons scattered exist in a much less developed state in non -
among numerous ascending and descending primates. In rodents, the tuberal nuclei con -
fibers. The anterior columns of the fornix can tain several neuroactive peptides, small-mol-
be used as a landmark to separate the medial ecule transmitters such as GABA , as well as
and lateral hypothalamic areas on sagittal acetylcholinesterase, and they are known to
sections ( Figs. 17.2 and 17.3). The boundary project to the cerebral cortex ( 130, 131, 133,
between the periventricular and medial hy- 161 ). The most prominent of these nuclei, the
pothalamic areas is much more discrete, and tuberomammillary nucleus, is enriched with
neurons in these two zones appear to con- histamine and projects widely to the cere-
tribute in the formation of certain hypothala- bral cortex. In humans, there are acetyl -
mic nuclei . cholinesterase-positive neurons in locations
similar to those of the hypothalamocortical
Lateral Hypothalamic Area groups in the rat, and the fact that the cere-
bral cortex is so greatly enlarged in humans
This area is bounded medially by the compared to rodents may explain the promi-
mammillothalamic tract and the anterior col- nence of the tuberal nuclei in the former
umn of the fornix. The medial edge of the in- group. Interestingly, the tuberal nuclei in hu -
ternal capsule and the subthalamic region mans undergo neurofibrillary degeneration ,
form its lateral boundary ( Figs. 17.2 and 17.3). as is the case for the basal nucleus of Meynert
Rostrally, this area is continuous with the lat- which projects widely to the cerebral cortex
eral preoptic nucleus, while caudally it (160, 162 ). Also of interest is the demonstra -
merges with the ventral tegmental area of the tion of a well-organized network of hista -
midbrain . Rostral and caudal portions of this mine-immunoreactive fibers that covers the
area are narrow , but the tuberal region is ex- frontal temporal cortex in humans (129 ). This
panded . The pattern of organization of the prominent fiber system appears to originate
lateral hypothalamic area is similar through- in the hypothalamus, where numerous hista -
-
out the three principal hypothalamic regions. mine immunoreactive nerve cells occur .
It is composed of a relatively small number of
large, darkly-staining, multipolar cells scat- Medial and Periventricular
tered among numerous nonmyelinated or
Hypothalamic Areas
weakly myelinated fibers. The neurons pre-
sent in the lateral hypothalamic area form the The medial hypothalamic area lies medial
lateral hypothalamic nucleus . Most of the fibers to the fibers of the fornix and the mammil -
that course within the lateral hypothalamic lothalamic tract, whereas the periventricular
area are part of the so-called medial forebrain area borders the ependymal lining of the
bundle. This bundle can be followed as far third ventricle. The medial hypothalamic area
rostrally as the lateral preoptic nucleus , which is the most differentiated zone of the hypo-
is regarded by some authors as the interstitial thalamus. Its nuclear composition is de-
nucleus of the median forebrain bundle (80 ) scribed according to the pattern it displays
( Figs. 17.2 and 17.3). in the anterior, tuberal, and mammillary
The lateral hypothalamic area also con - regions.
tains some well-delineated groups of cells,
the largest of which is the tuberomammillary
nucleus . This nucleus is particularly well-de- Anterior Region
veloped in the tuberal region , but it extends PREOPTIC REGION
caudolaterally and caudoventrally to the
mammillary body ( 118). The lateral tuberal nu - The preoptic region has long been re-
clei ( nuclei tuberales) consists of two or three garded as a forebrain derivative and, as such ,
sharply delimited cell groups that often pro- has often been treated as a distinct entity (83).
duce small visible eminences on the basal Detailed developmental studies, however,
surface of the hypothalamus ( Fig. 16.10). show that the preoptic area arises from a ros-
They consist of small , pale, multipolar cells tral hypothalamic anlage (75, 80 ). Thus, the
surrounded by a delicate fiber capsule about preoptic region is currently believed to be
17 Hypothalamus 711
structurally and functionally a part of the hy- sexually dimorphic part of the medial preop-
pothalamus (7). tic nucleus in rodents.
The preoptic region constitutes the peri- The vascular organ of the lamina termi-
ventricular gray matter of the most rostral nalis (organum vasculosum laminae termi -
part of the third ventricle ( Figs. 17.1-17.3). nalis (OVLT)) is a vascular midline circum -
The periventricular area at this level contains ventricular organ located in the rostral wall
the preoptic periventricular nucleus , which sur- of the third ventricle superior to the optic chi-
rounds the walls of the third ventricle in the asm ( Fig. 1.17). The subfornical organ (SFO)
region of the preoptic recess. The diffusely is another highly vascularized circumventric-
arranged small cells of this nucleus are ular organ that develops from the dorsal ex -
poorly differentiated from the ependymal lin- tremity of the lamina terminalis and lies at
ing. The medial preoptic nucleus , composed of the confluence of the two interventricular
predominantly small cells, lies lateral to the foramina and ventral to the junction of the
preoptic periventricular nucleus and extends two fornix columns in the adult (52, 96).
ventrally to the optic chiasm ( Fig. 17.3). It is These two circumventricular organs are
part of the medial area of the preopticohypo- made up of neural, glial, and ependymal ele-
thalamic complex. The lateral area contains ments, combined with leptomeningeal and
the lateral preoptic nucleus, which is com- vascular tissue of mesodermal origin. The
posed of diffusely dispersed medium-sized blood -brain barrier is absent at these levels
cells. due to fenestrations in the capillary endothe-
The preoptic region plays a role in regulat- lium (96). The SFO and the OVLT are recipro-
ing the release of gonadotropic hormones cally connected with a wide variety of
from the anterior lobe of the hypophysis. In structure, principally the hypothalamus,
the human female, pituitary gonadotropins brainstem , and subcortical and cortical areas
are released in a cyclic manner, and the dura- of the limbic system . They receive a particu -
tion of the cycle determines the length of the larly dense serotoninergic innervation from
menstrual cycle. In the male, the go- the dorsal raphe nucleus ( Fig. 17.5A ). The
nadotropins are released tonically without SFO and OVLT are believed to be involved in
regularly occurring fluctuations. It is, there- the control of body fluid balance and are sites
fore, not surprising that there are differences at which the circulating octapeptide an -
in the functional organization of the preoptic giotensin II binds to receptors and initiates
region in the male and female of the species. water drinking and vasopressin secretion (96,
A morphologic expression of this difference 136). In the rat, intravenous injection of an -
was observed in the preoptic area of the rat, giotensin II induces the expression of the
where a nucleus of densely stained cells was - -
proto oncogene c fos in the OVLT (95). Bind -
larger in the male (49, 50). This nucleus repre- ing sites in the SFO of rats for other circulat-
sents a specialized portion of the medial pre- ing hormones, such as somatostatin, atrial na -
optic nucleus that is termed the "sexually di- triuretic peptide, or calcitonin, have also been
morphic nucleus of the preoptic area" ( Fig. demonstrated , suggesting that angiotensin II
17.22). The full ontogenetic development of may not be the only blood -borne agent acting
this nucleus, as well as the male pattern of at this site. In addition to being a receptor
tonic gonadotropic release, depends upon the zone, morphologic evidence suggests that
presence of testosterone in the circulation hormones such as luteinizing hormone-re-
during the first week of life. If the testes are leasing hormone ( LHRH ), somatostatin, or
removed from the newborn rat, the genetic angiotensin II of central origin are released by
male fails to develop the sexually dimorphic neurosecretion into the blood stream by the
nucleus of the preoptic region and has a fe- SFO (96). Furthermore, the OVLT is believed
male pattern of gonadotropin release at pu - to be involved in the production of the pyro-
berty. Conversely, a newborn female given - -
genic cytokin interleukin 1 (IL 1 ), which acts
exogenous testosterone will, as an adult, on the central nervous system to produce the
show the male pattern of gonadotropin re- fever response in the presence of circulating
lease. A sexually dimorphic nucleus, which pyrogens (111).
was identified in the human preoptic area
(68, 177), contains approximately twice as
SUPRAOPTIC REGION
many neurons in men as in women. Further
evidence is required, however, to determine This region contains two of the most strik-
whether this nucleus is homologous to the ing and sharply defined hypothalamic nuclei .
the paraventricular nucleus and the supraoptic docrine transducers that convert neural infor-
nucleus . Cells of the paraventricular nucleus mation into hormonal information (154 ).
form a vertical plate of densely packed cells lmmunocytochemically large cells in both
immediately beneath the ependyma of the nuclei contain either oxytocin or vasopressin
third ventricle, the dorsal part of which ex- (antidiuretic hormone), each being associated
tends laterally toward the fornix ( Figs. with a distinctive neurophvsin . Although
17.1-17.4 ). The paraventricular nucleus con- they contain several neuroactive peptides (16,
sists of several distinct cell groups, among 70 ), it is generally accepted that one large cell
which are a medial predominantly parvicel - produces only one hormone, either oxytocin
lular group and a prominent lateral magno- or vasopressin (190). Oxytocin and vaso-
cellular group (161 ). The supraoptic nucleus pressin contain nine amino acid residues (37).
caps the optic chiasm and straddles the optic As with most peptide hormones, both oxy-
tract laterally ( Figs. 17.1-17.4 ). This nucleus is tocin and vasopressin are cleaved from a
composed mainly of uniformly large cells. larger prohormone. The prohormone for oxy -
Large cells in both the paraventricular and tocin and vasopressin are synthesized in the
supraoptic nucleus appear similar with pe- cell bodies of the magnocellular neurons, and
ripherally distributed Nissl substance and cleaved within the vesicles during their trans -
colloidal cytoplasmic inclusions, regarded as port down the axons. The peptide neuro-
neurosecretory products. These cells are con- physin is a cleavage product of both oxytocin
sidered as magnocellular neurosecretory ele- and vasopressin . However, the neurophysin
ments. The concept of neurosecretion was deformed in neurons that secrete oxytocin dif -
veloped in the first half of this century by fers slightly from that produced in neurons
Ernst and Berta Scharrer ( 167). This concept that release vasopressin ( 170, 171 ). Each neu -
implies that certain neurons function in two rophysin is released along with its hormone
ways: (a ) as nerve cells that receive and trans- at the terminals of the magnocellular
mit electrical information, and ( b ) as en - supraoptico-hypophysial tract in the neural
docrine cells that release their secretory prod - lobe of the hypophysis ( posterior lobe of the
ucts into the blood stream. The magnocellular pituitary gland ) (17). A small projection from
elements of the paraventricular and supraop- the magnocellular neurons reaches the exter-
tic nuclei are perfect examples of neuroen - nal zone of the median eminence, whereas
wrm
Anterior commissure Paraventricular nucleus
iSi
- v
m mm M
I / 3
• . %I wSiP
#
Optic tract
m - Supraoptic nucleus
III ventricle
Figure 17.4. Human hypothalamus at the level of the anterior commissure demonstrating the paraventricular and
supraoptic nuclei (Nissl stain)
17 Hypothalamus 713
either neurons containing oxytocin or vaso- marked regulatory effect on circadian rhyth -
pressin project as far down as the spinal cord micity ( 107). This complex circadian timing
( 20 ) . system is believed to coordinate the activities
Neurons in the parvicellular portion of the of a series of homeostatic mechanisms with
paraventricular nucleus contain a multitude the control of behavioral state in a temporal
of neuroactive peptides such as enkephalin, pattern that facilitate adaptive behavior, in -
neurotensin, cholecystokinin, somatostatin, cluding reproduction ( 104). Thus, this system
vasoactive intestinal polypeptide. Each of appears to provide the appropriate physio-
these peptides occurs alone or in various logic and behavioral background to facilitate
combinations in single parvicellular neurons adaptation and survival.
(81 ). The parvicellular neurons in the par-
aventricular nucleus give rise to descending Tuberal Region
axons projecting to the brainstem and all lev-
els of the spinal cord ( 181 ). These projections In this region, the hypothalamus reaches
are involved in the mediation of the hypo- its widest extent. The fornix separates the me-
thalamic influence upon lower autonomic dial and the lateral hypothalamic areas ( Figs.
nerve centers (161 ). 17.2 and 17.12). The medial portion forms the
The less differentiated central gray in the central gray substance of the ventricular wall,
supraoptic region constitutes an anterior hypo- in which there may be distinguished a ven -
thalamic nucleus. This nucleus merges imper - tromedial and a dorsomedial nucleus.
ceptibly with the preoptic area ( Figs. 17.1 and The ventromedial nucleus , the largest cell
17.3). group in the tuberal region, has a round or
The suprachiasmatic nucleus forms a group oval shape and is surrounded by a cell-poor
of small round cells immediately dorsal to the zone that helps to delineate its boundaries
optic chiasm and close to the ventral part of ( Figs. 17.1-17.3). Neurons of the ventrome-
the third ventricle ( Figs. 17.1 and 17.2). These dial nucleus typically have dendrites that ex -
small nuclei receive direct bilateral projec- tend beyond the borders of the nucleus (102 ).
tions irom the retina ( Fig. 17.8) ( 103, 105, 137, The cell-free capsular zone around the nu -
139), as well as indirect retinal input via the cleus is formed by a dense ring of axons and
geniculohypothalamic pathway ( 24, 108, 180). terminals ( Fig. 17.9 ). The dorsomedial nucleus
The direct retinal input appears to exert a is a less distinct aggregation of cells that bor-
glutamate-mediated excitatory effect on the ders the third ventricle ( Fig. 17.3).
suprachiasmatic nucleus, whereas the indi- The areua / e nucleus ( infundibular nucleus)
rect pathway exerts a GABA - mediated inis located in the most ventral part of the third
hibitory effect (106). Neurons of the indirect ventricle near the entrance to the infundibu -
geniculohypothalamic projection, which lar recess, and extends into the median emi -
arises mainly from the so-called intergenicu- nence ( Fig. 17.1 ). The small cells of this nu -
late leaflet of the lateral geniculate complex, cleus are in close contact with the ependyma
also express neuropeptide Y (106). lining the ventricle. In frontal sections, the
The well-defined role of the suprachias- nucleus has an arcuate shape ( 118). The effer-
matic nucleus is that of biologic clock . Retino- ent projections of the arcuate nucleus have
hypothalamic projections to the suprachias- been traced to the external layer of the me-
matic nucleus provide the anatomic link dian eminence. This projection is of great im -
between a cyclical environment and the inter- portance to adenohypophysial function . It is
nal clock (104 ). Neurons in the suprachias- composed of axons of neurons producing
matic nucleus use GABA as small- molecule various neuropeptides that are released into
transmitter (106), and also express one or the hypophysial portal system where they act
more specific neuroactive peptides or hor- as inhibiting or releasing factor for the differ-
mones such as vasopressin , somatostatin, va - ent hormones produced in the anterior lobe
soactive intestinal peptide, neurotensin, thy- of the hypophysis. Additionally, neurons of
rotropin hormone, and angiotensin II ( 161, the arcuate nucleus are immunoreactive for
189 ). The cellular levels of some of these pep- the adrenocorticotrophic hormone ( ACTH ),
tides are regulated by photic stimulation -
(3 lipotrophic hormone ( p- LPH ), and (3-en-
while others are not (123). The suprachias- dorphin ( p- END). Chemical substances from
matic nucleus also receive a dense serotonin - the arcuate nucleus play a major role in the
ergic projection from the midbrain raphe nu - regulation of hormonal output from the ante-
clei (132 ) ( Fig. 17.5B ) . This projection exerts a rior pituitary.
X
< N s
V \ ~i. .
OVLT
ivr«5
V i.
- (Attf
•y : A ";
+
fejfr
~
v
Jg
t§n*ri/£
’
A
T
•sr^S?
.''W
- ^v*
•- .
*«
Figure 17.5. Radioautographs showing the dense serotoninergic innervation of ( A) the organum vasculosum lami-
nae terminalis (OVLT), and (B) the suprachiasmatic nucleus (SCH) in the rat. os seen on parasagittal sections. The
serotoninergic fibers and axon terminals are darkly labeled because they have taken up a large amount of (3H) sero-
.
tonin that was injected intraventricularly OC. optic chiasm. SIR striatum. V. third ventricle.
17 Hypothalamus 715
Mammillary Region
This region consists of the mammillary
bodies and the dorsally located cells of the % *
posterior hypothalamic nucleus ( Figs.

17.1-17.3 and 17.12 ). In humans, the mammil-
lary body consists almost entirely of the
large, spherical medial mammillary nucleus ,
v •
«\ -
composed of relatively small cells invested by
a capsule of myelinated fibers. Lateral to this
is the small intermediate ( intercalated ) mammil -
y--
: #» *
-
lary nucleus composed of smaller cells ( Fig.
17.2 ). Even further lateral is a well -defined
•
group of large cells, the lateral mammillary nu - A •
cleus.
The posterior hypothalamic nucleus lies dor-
sal to the mammillary body and caudal to *
portions of the ventromedial nucleus ( Figs.
17.1-17.3). This nucleus consists of a matrix of
small cells in which large round or oval cells
are scattered . The large cells are especially
numerous in humans and extend caudally
over the mammillary body to become contin-
uous with the periaqueductal gray.
General descriptions may suggest that all
hypothalamic nuclei are sharply circum-
scribed , but the cellular matrix of the hypo-
r %i
thalamus is broadly continuous with the sur- B % % *
rounding gray matter. Tissue continuities *
with surrounding gray matter contain the Figure 17.6. Neurons of the paraventricular nucleus In
the rat that express the early proto-oncogene c-fos fol-
major afferent and efferent hypothalamic lowing a pharmacologic treatment that leads to a pro-
pathways. Rostrally and laterally, the hypo- fuse release of serotonin. The animal was injected In-
thalamus is continuous with the basal olfactory traperitoneally with the serotonin releasing agent
region , a large gray mass beneath the rostral fenfluramine (15 mg/kg) and sacrificed 1 hour following
the injection. V . third ventricle.
part of the lentiform nucleus and the head of
the caudate nucleus ( Figs. 18.6 and A .24 in
the atlas of the human brain, section VII ).
Near the median plane, this region extends
dorsally, rostral to the anterior commissure, preoptic region caudally. The septal region
where it becomes the septal region ( Figs. 18.10 contains (a ) the medial septal nucleus , com-
and A .23). Beneath the lentiform nucleus, the posed of fairly large cholinergic neurons
gray mass extends toward the amygdaloid (group Chi of Mesulam, et al . (100)) that pro-
complex. This region contains cell islands and ject to the hippocampal formation, ( b ) the lat -
groups referred to as the substantia innomi- eral septal nucleus , which consists of smaller
nata ( Fig. A .22). The substantia innominata noncholinergic neurons, and (c) the nucleus
contains clusters of large cholinergic neurons, accumbens septi ( Fig. A .24), which leans
which includes the basal nucleus of Meynert against the base of the septum and is situated
(group Ch 4 of Mesulam , et al. (100)). These medially at the junction of caudate nucleus
large cholinergic neurons have widespread and putamen .
projections to the cortex and the amygdala .
Neurons in the basal nucleus constitute the HYPOTHALAMIC CONNECTIONS
major source of cholinergic innervation of
the entire cerebral cortex . The base of the The hypothalamus has extensive and com-
septal region ( i .e., the part ventral to the an- plex fiber connections. Some fibers are orga -
terior commissure) is continuous with the nized into definite and conspicuous bundles,
substantia innominata laterally and with the while others are diffuse and difficult to trace.
Afferent Connections short and long fibers that course both ros-
trally and caudally. This tract is well -devel-
The major afferent connections of the hy- oped in nonmammalian vertebrates, but is
pothalamus are (a ) the medial forebrain bun - relatively small in humans. In most species,
dle, ( b ) the hippocampo-hypothalamic fibers, the ascending dopaminergic, serotoninergic,
(c ) the amygdalo-hypothalamic fibers, ( d )
and noradrenergic fibers systems all course in
brainstem afferents, (e) the retino-hypothala- the medial forebrain bundle.
mic fibers, ( f ) the cortico-hypothalamic fibers,
and ( g ) forebrain afferents, including olfac-
HIPPOCAMPO-HYPOTHALAMIC FIBERS
tory inputs.
The projection from the hippocampal for-
MEDIAL FOREBRAIN BUNDLE mation to the hypothalamus in monkeys
arises somewhat more widely than in rats in -
This bundle is a complex group of fibers cluding cells in the CA 1 field as well as the
arising from the basal olfactory regions, the subiculum (99, 149, 151, 161, 178, 179). These
septal nuclei, the periamygdaloid region, and fibers form the fornix, which is one of the
the subiculum that pass to, and through , the most prominent and heavily myelinated fiber
lateral preoptic and hypothalamic regions bundles in the human hypothalamus ( Figs.
( Figs. 17.14 and 17.15). At levels rostral to the 17.7, 17.12, 17.15, and 18.10). The develop-
anterior commissure, the bundle is formed ment of the temporal lobe in the primate
mainly of fibers from the septal region, and in brain carries the hippocampal formation,
its parasagittal course receives contributions which is located medially in the embryonic
from the substantia innominata and amyg- brain, far from its site of origin near the lam-
daloid complex . In humans, the bundle con - ina terminalis. As a result, the fimbria of the
sists of a loose association of pathways, of fornix is left behind as a long, arching re-
variable degree of myelination, composed of minder of the migration of the hippocampal
Figure 17.7. Paraventricular nuclei in the mouse hypothalamus immunostained with an antiserum to bovine neuro-
physin I demonstrating cells and their processes
17 Hypothalamus 717
formation during development (161 ). In the via the mammillary peduncle and the dorsal lon -
septal region, just dorsal to the anterior com- gitudinal fasciculus. The mammillary peduncle
missure, fibers of the fornix divide into two arises from the dorsal and ventral tegmental
distinct bundles: (a ) a compact fornix column, nuclei in the midbrain and projects mainly to
or postcommissural fornix, which arches cau- the lateral mammillary nucleus (29) ( Fig.
dal to the anterior commissure, and (b) a 17.14 ). It passes rostrally through the rootlets
more diffuse precommissural fornix (32, 145). of the third nerve and courses lateral to the
The precommissural fibers of the fornix are interpeduncular nucleus. A few fibers ascend
distributed to the septal nuclei, the lateral in the medial forebrain bundle beyond the
preoptic region, the nucleus of the diagonal level of the mammillary bodies. The mammil-
band , and the dorsal hypothalamic area (114, lary peduncle is not very well differentiated
161 ). The postcommissural fibers of the fornix in humans. It corresponds to a rather discrete
project principally to the medial mammillary myelinated bundle that lies medial to the
nucleus. However, many of the fibers that cerebral peduncle and caudal to the mammil-
form the columns of the fornix lose their lary body . Its fibers appear to enter the cap-
myelination as they course within the hypo- sule of the mammillary bodies, although it is
thalamus and several of them peel off the not possible to trace them caudally to their
fornix to innervate several medial hypothala- origin (161 ). The dorsal longitudinal fasciculus
mic nuclei ( Fig. 17.9), the lateral hypothala- (of Schutz ) is the main fiber system that runs
mic area, as well as the anterior thalamic nu- longitudinally through the periventricular
clei (161 ). and periaqueductal gray matter, connecting
the hypothalamus with structures in the mid -
AMYGDALO-HYPOTHALAMIC FIBERS brain and pontine tegmentum. Fibers in this
bundle spread out over caudal and dorsal re-
The projections from the amygdaloid nu- gions of the hypothalamus where they be-
clear complex to the hypothalamus follows come part of a periventricular system (118).
two distinctive pathways: (a ) a long, looping Like the medial forebrain bundle, the dorsal
fiber system through the stria terminalis longitudinal fasciculus is composed largely of
( Figs. 16.6 and 16.7), and (b) a short, direct unmyelinated or poorly myelinated fibers.
fiber system beneath the lentiform nucleus, Since fibers of the dorsal longitudinal fascicu-
which is a component of the ansa peduncu- lus conduct impulses both rostrally and cau-
laris termed the ventral amygdalofugal path- dally, this fiber tract may be regarded as a
way (47, 146, 161 ). The stria terminalis arises reciprocally organized association system be-
principally from the corticomedial group of tween the hypothalamus and the midbrain
the amygdaloid nuclei ( Fig. 18.19) and dis- central gray ( Fig. 17.16).
tributes terminals in the medial preoptic area, Brainstem afferents to the hypothalamus
medial parts of the anterior hypothalamic also arise from neurons in the raphe nuclei of
area, and in the ventromedial and arcuate nu- the midbrain, the locus coeruleus, and from
clei (36, 56, 63, 114, 116, 118, 161 ). This path- the lateral parabrachial nucleus in the pons
way has been implicated in the olfactory in- (5, 93, 132). Serotoninergic fibers arising
fluence on reproductive behavior (84). The mainly from the median raphe nucleus (supe-
ventral amygdalofugal pathway arises from the rior central nucleus), ascend in the medial
basolateral amygdaloid nuclei and the piri- forebrain bundle to, and through, the lateral
form cortex and spread medially and ros- hypothalamus. Terminals of these fibers are
trally under the lentiform nucleus to reach distributed preferentially to the preoptic re-
the lateral hypothalamic nucleus and the me- gion, the lateral hypothalamic area , the par-
dial forebrain bundle region ( Fig. 17.17) ( 28, aventricular nucleus, and the suprachias-
56, 147, 161, 188). The amygdalofugal fibers matic nucleus ( Fig. 17.5B ). Noradrenergic
that reach the lateral hypothalamic area have fibers originating in the locus coeruleus as-
been implicated in the amygdaloid influence cend in the dorsal tegmental bundle, which
on the autonomic nervous system (169). distributes terminals in the dorsomedial,
supraoptic, and paraventricular hypothala-
BRAINSTEM AFFERENTS mic nuclei (130). The brainstem monoaminer-
gic afferents are known to exert a profound
Fibers from the brainstem reticular forma- modulatory effect on the activity of various
tion ascend to the hypothalamus principally subsets of hypothalamic neurons. For exam-
pie, a pharmacologic increase in the release of RETINOHYPOTHALAMIC FIBERS

serotonin can readily induce the expression
of the immediate gene c- fos ( Fig. 17.6). The These fibers arise from the ganglion cells
early and transient expression of this proto- of the retina and project bilaterally to the
oncogene can be used to study the topogra- suprachiasmatic nuclei via the optic nerve
phy and time course of the metabolic activa- and chiasm (156) ( Fig. 17.8). The retinal axons
terminate principally on dendrites of the
tion in different groups of neurons. A simi - suprachiasmatic nucleus cells (61, 65, 105).
lar expression of c - fos can be induced in
The suprachiasmatic nuclei also receive in-
-
oxytocin immunoreactive neurons in the
puts from extrahypothalamic sources, such as
supraoptic and paraventricular neurons fol-
lowing osmotic stress in the rat (46). the ventral lateral geniculate nucleus and the
Afferents from different parts of the nu - paraventricular nuclei of the thalamus. The
cleus solitarius project to the medial and lat- suprachiasmatic nucleus is the pacemaker for
circadian rhythms (104).
eral parabrachial nuclei. Portions of the nu -
cleus solitarius that receive general visceral CORTICOHYPOTHAIAMIC FIBERS
afferents ( located caudally ) project primarily
to the lateral parabrachial nuclei. The lateral Corticohypothalamic fibers are believed to
parabrachial nuclei innervate the medial pre- arise principally from portions of the frontal,
optic region, the paraventricular and dorso- parietal, and occipital cortices (118). Medial
medial hypothalamic nuclei, and the lateral prefrontal cortex lesions in monkeys report-
hypothalamic area . The rostral portion of the edly produce terminal degeneration through-
nucleus solitarius that receives special vis- out the rostrocaudal extent of the lateral hy-
ceral afferents ( taste) projects to the medial pothalamus and in the lateral mammillary
parabrachial nuclei. The medial parabrachial nucleus (87), whereas frontal granular cortex
nuclei project to the substantia innominata, lesions result in anterograde degeneration in
the amygdala, and the posterolateral regions the lateral, dorsal, and posterior hypothala -
of the hypothalamus. Afferent fibers to the mic areas (117). Furthermore, fibers from the
hypothalamus from the brainstem and other cingulate gyrus vocalization area, identified
sources are shown in Figures 17.15 and 17.17. by electrical stimulation, appear to project to
Figure 17.8. Darkfield photomicrograph of retinal fibers and terminals in the suprachiasmatic nuclei of the hamster
demonstrated by transport of horseradish peroxidase (HRP).
17 Hypothalamus 719
7
np .
rpk
1C
V.
4
n5
I ss
ME
S!
Ar
?p>>
HVM
HL
Figure 17.9. Tuberal region of the rodent hypothalamus based upon Golgi preparations. On the reader ’ s left the
general arrangement of dendrites dnd axons is shown, ( f) Dendrites of neurons in the lateral hypothalamus (HQ radi-
ate In the mediolateral and dorsoventral directions. ( 2 ) There is o compression of the dendritic fields of neurons lo-
cated between the fornix ( F ) and the hypothalamic ventromedial nucleus ( HVM ) (3) The dendritic fields of neurons
along the hypothalamic surface are generally parallel with the pia. (4) The long dendrites of HVM extend in all direc -
tions from the nucleus. (5) Small bipolar neurons of the arcuate nucleus ( At ) nestle against the ventricle wall, adja-
.
cent to the median eminence ( ME ). 1C internal capsule
the hypothalamus where they terminate prin- directly involved in the arousal and consum -
cipally in the preoptic region and the dorso- matory phases of behavior. Gustatory projec-
medial hypothalamus along its whole extent tions to the hypothalamus are mediated via
(110). In rodents, direct corticohypothalamic the parabrachial nuclei, whereas the olfactory
inputs have been documented following projections are relayed through the cortical
tract - tracing studies (77, 158, 186 ). These af - and medial amygdaloid nuclei and the peri -
ferents arise primarily from insular, lateral amygdaloid piriform cortex (33, 63, 165, 172 ).
frontal, infralimbic, and prelimbic areas, and
terminate principally in the lateral hypothala - Efferent Connections
mic area .
The efferent connections of the hypothala-
FOREBRAIN AFFERENTS mus appear, in part, to be reciprocal to the af -
ferent systems. There are reciprocal connec-
Broadly stated , the principal forebrain af - tions in the medial forebrain bundle which
ferents to the hypothalamus arise from the provide indirect connections between the lat-
two phylogenetically oldest cortical areas, the eral hypothalamus and the hippocampal for -
piriform cortex and the hippocampal forma- mation (148). Additionally, there are hypo-
tion ( Fig. 17.17) ( 147). In each instance, the thalamic projections to the amygdaloid
cortical projection is reinforced by a corre- nuclear complex via both the stria terminalis
sponding subcortical projection, the amyg- ( Fig. 18.10 ) and the ventral pathway (93). Re-
dala in the case of the piriform cortex, and the ciprocal connections with the midbrain
septum in the case of the hippocampal forma - tegmentum and central gray matter are con-
tion . Each of these subcortical nuclei is recip- ducted by the dorsal longitudinal fasciculus
rocally connected with the overlying cortical and via pathways projecting to and from the
area . Of the phylogenetically newer cortical mammillary bodies. There also are several ef -
areas, the cingulate gyrus appears particu- ferent hypothalamic pathways which have no
larly favored to influence the hypothalamus counterpart among afferent systems.
indirectly through the entorhinal cortex and
the hippocampal formation. The cingulate MEDIAL FOREBRAIN BUNDLE
cortex can , in turn , be influenced by hypo-
thalamic projections to the anterior nuclear This bundle consists of a loose association
group of the thalamus. of poorly myelinated or nonmyelinated fibers
Both the senses of taste and olfaction are that run longitudinally through the lateral
Figure 17.10 . Transverse section through the rat median eminence immunostained with antiserum to neurophysin
demonstrating the zona interna (Z() and the zona externa (ZE) Fibers of the hypothalamo-neurophysiologic tract are
abundant in Zl and a few positive fibers are evident in ZE
hypothalamus to connect the forebrain auto- tegmentum . Some descending fibers in this
nomic and limbic regions with the hypothala - system may extend to the dorsal tegmental
mus and brainstem ( 161 ). Because the degree nucleus ( Fig. 17.16). The ascending compo-
of myelination in the medial forebrain bundle nent of the dorsal longitudinal bundle in -
is so low , it is not possible to reliably trace cludes noradrenergic and serotoninergic
any of its components to their origins or ter- fibers that arborize within various hypothala-
minations in myelin-stained material from mic nuclei.
the human brain . Experiments in laboratory
animals revealed that this bundle conveys MAMMILLARY EFFERENT FIBERS
impulses from the lateral hypothalamus ros-
trally to the nuclei of the diagonal band and These fibers arise from the medial mam-
to the medial septal nuclei ( 55, 148), which in millary nucleus, and to a lesser extent from
turn send fibers to the hippocampal forma - the lateral and intermediate mammillary nu-
tion via the fimbria of the fornix (32). De- clei, forming a well-defined bundle, the fasci-
scending hypothalamic efferents in the me- culus mamillaris princeps ( Figs. 17.2 and 17.14 ).
dial forebrain bundle project through the This bundle passes dorsally for a short dis-
ventral tegmental area to the superior central
nucleus, the ventral tegmental nucleus, and
tance and divides into two components the
mamiuillothalamic trad and the mamillotcgmcn
— -
to parts of the central gray matter ( Fig. 17.14 ) tal tract ( Figs. 17.12, 17.14, and A.20). The
( 28, 55, 115, 176, 183 ). Fibers from the lateral mammillothalamic tract contains fibers from
hypothalamic region follow the ventral path- the medial mammillary nucleus which pro-
way through the substantia innominata to the ject to the ipsilateral anteroventral and an-
amygdala, while those that pass via the stria teromedial thalamic nuclei, and fibers from
terminalis arise from more medial cells ( 118). the lateral mammillary nucleus that pass bi-
laterally to the anterodorsal nucleus (30, 42,
DORSAL LONGITUDINAL FASCICULUS 191 ). Superimposed upon this hypothalamic
relay to the thalamus are projections from the
Together with the medial forebrain bun - hippocampal formation via the fornix to the
dle, the dorsal longitudinal bundle is a major anterior thalamic nuclei (54, 187). Each of
pathway of communication between the hy- the anterior thalamic nuclei in turn projects to
pothalamus and the brainstem . It contains subdivisions of the cingulate cortex ( Figs. 2.6,
poorly myelinated fibers that originate 18.1, and 18.10). Thus, the main neocortical
mostly from medial and periventricular por - projection of impulses from the hippocampal
tions of the hypothalamus and project to the formation and subiculum is to the cingulate
central gray matter, tectum, and midbrain cortex via postcommissural fibers of the
17 Hypothalamus 721
fornix to (a ) the anterior thalamic nuclei, and rectly to the dorsal motor nucleus of the
( b)the mammillary body which relays im - vagus, the medial nucleus solitarius, portions
pulses to the anterior thalamic nuclei ( Fig. of the nucleus ambiguus, and into ventrolat-
17.17). Impulses from the cingulate cortex eral regions of the medulla . Fibers from the
pass back to the hippocampal formation via same hypothalamic nuclei enter the spinal
the entorhinal cortex (150) ( Fig. 17.15). These cord , descend in the lateral funiculus, and
connections appear to form a closed anatomic terminate in the intermediolateral cell col -
circuit often referred to as the Pape / circuit , umnatall levels (Figs. 11.23 and 17.17). These
The iiiamillotegmental tract arches caudally direct hypothalamic fibers influence auto-
into the midbrain tegmentum. Fibers of this nomic functions in the lower brainstem and
tract terminate in the dorsal and ventral at all spinal levels. The existence of these
tegmental nuclei ( Fig. 17.14). pathways in humans can be inferred from the
presence of an ipsilateral sympathetic deficit
DESCENDING HYPOTHALAMIC following injury to the hypothalamus, lateral
PROJECTIONS brainstem tegmentum , or spinal lateral fu -
niculus ( 113).
Hypothalamic fibers descending to the Descending fibers from the paraventricu -
brainstem and spinal cord constitute path - lar nucleus, which forms a part of this sys-
ways whereby cells of the hypothalamus tem , appear to contain both oxytocin and va -
exert regulatory influences on central auto- sopressin ( 119). Paraventricular nucleus cells
nomic neurons (161, 163). Parvicellular ele- projecting to the spinal cord are largely dis-
ments of the paraventricular nucleus, cells of tinct from those sending axons to the poste-
the lateral hypothalamic area, and cells in the rior lobe of the pituitary gland ( 71, 121 ). An-
posterior hypothalamus project fibers di - other descending projection to the spinal cord
# "•
V .
. u'
*>
•' C
i
• • •4• •
i
'
.
* y
* 1
i
'
t
-
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r ^
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>
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'
* 3
r A m
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-
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. * o
A * .•
. .4- B * » •
Figure 17.1 ) . A The immunocytologic localization of somatostatin 14 (SRIF - 14) in the infundibular (arcuate) nucleus
of the human hypothalamus . The arrows point to a few cell bodies which are dispersed among weakly immunola-
beled nerve fibers V. third ventricle x 220 B The localization of corticotrophin releasing factor ( CRF ) immunoreactiv -
ity in the paraventricular nucleus of the human hypothalamus . Several immunostained neurons can be observed
( x 280)
arises from the dopaminergic neurons in the gradely-labeled neurons have been visual-
dorsomedial hypothalamus
'
and zona incerta ized in the lateral tuberal nuclei and in the
( 5, 6, 10, 163). posterior hypothalamic nucleus following in -
jections into the frontal, parietal, and occipital
HYPOTHALAMOCORTICAL FIBERS cortex (76, 101, 143, 184 ). Unfortunately , no
attempt has been made to examine the topo-
Hypothalamic projections to the cerebral graphic organization of these projections.
cortex have been examined with retrograde
transport methods in both rats and monkeys SUPRAOPTIC DECUSSATIONS
( 76, 78, 101, 143, 159, 184 ). In the rat , tuberal
lateral hypothalamic nuclei and the posterior Dorsal to the optic chiasm, several bundles
hypothalamic nucleus project to the entire of fine fibers cross the mid line. These fiber
cerebral cortex ( 161 ). In monkeys, retro- bundles constitute the supraoptic decussa -

Ant commissure
\ Septum pellucidum Mammillothalamic tract
\ \ Fornix
Dorsomedial nucleus
Stria medullaris
Habenular nucleus
- Posterior commissure
Superior colliculus
f —-— Med long fasciculus

4
iiw. Decussation N TH
Optic nerve
Tuber cmereum
/
Mammillary nucleus ^ Ventricle E7
Nucleus N HI
Sup cerebellar peduncle
Nucleus gracilis
Medial lemniscus
Pyramid
Fasciculus gracilis
Figure 17.12. Sagittal section of brainstem through the pillar of fornix, the mammillothalamic tract, and the stria
medullaris (Weigert ' s myelin stain)
17 Hypothalamus 723

Ventral anterior nucleus Lateral dorsal nucleus
Mediodorsal nucleus
Mammillothalamic Fasciculus retroflexus

tract
Anterior commissure
Superior colliculus
Fornix
r Inferior colliculus
Optic chiasm
Mammillary body Cerebellum
Red nucleus
Medial lemniscus
Pyramid
Inferior olive
Figure 17.13. Sagittal section of the brainstem demonstrating the mammillothalamic tract , the anterior thalamic nu-
clei. and thalamic nuclei lateral to those shown in Figure 17.12. (Weigert ' s stain).
tions. Three decussations or commissures are terior lobe of the hypophysis (81, 161 ) ( Figs.
recognized, although little is known concern- 17.4, 17.16, and 17.18). The peptides specific
ing their origin, course, termination or func- for these large neurons, oxytocin and vaso-
tion . The most rostral of these decussations is pressin, were the first brain peptides to be
the anterior hypothalamic commissure (Ganser) isolated and characterized (37). These pep-
( Figs. 17.12 and 17.13). Fibers of this commis- tides are always present in conjunction with a
sure are most readily identified as they pro- class of larger peptides, known as neuro-
ject ventromedially from Forel's field H and physins. As mentioned earlier, the neuro-
arch over the fibers of the fornix. These fibers physins are part of a large precursor ( prohor-
pass ventrally in the hypothalamus, cross the mone) molecule, whose cleavage gives rise to
midline ventral to the third ventricle, and
contralaterally fan out into the lateral preop-
—
both oxytocin and vasopressin neurophysin
I is associated with oxytocin and neurophysin
ticohvpothalamic area ( 118). Fibers of the an- II with vasopressin ( Figs. 17.7 and 17.10).
terior hypothalamic commissure are consid - Neurons containing oxytocin or vasopressin
ered to arise from the reticular formation of and their associated neurophysins are pre-
the rostral pons and to ascend in association sent in both supraoptic and paraventricular
with fibers of the medial longitudinal fascicu - nuclei, but each hormone is synthesized in a
lus (18). Two decussations lie along the dor- distinct set of neurons in each nucleus ( 190 ).
sal aspect of the optic chiasm , the dorsal Cells of the supraoptic and paraventricular
supraoptic decussation ( Meynert ) and the ven - nuclei are neurosecretory neurons. Secretory
tral supraoptic decussation (Gudden ) ( Fig. 16.6). products are synthesized within the cell bod -
The precise origin of both of these bundles is ies, transported along the axonal flow down
obscure. the axons, and liberated by axon terminals
near capillaries in the neurohypophysis. The
Supraopticohypophysial Tract neurosecretory material is contained within
granules 50-200 nm in diameter ( 12, 13, 126 ).
This tract consists of fibers arising from the Oxytocin and vasopressin are stored in dense
magnocellular elements of the supraoptic and core vesicles present in different axonal pro-
paraventricular nuclei that project to the pos- files. The content of these dense core vesicles
Mammillofholamic tract
Stria medulloris
Habenula
Fornix
Pineal
Thalamus, Fasciculus retroflexus
A
C Mammillotegmental tract
Sep' a
bundle _
Medial forebrain
-
Centrol groy
Dorsal tegmental nucleus

|D
Optic chiaSm r '

Ventral tegmental nucleus
Hypophysis
Interpeduncular
nucleus Mammillary peduncle
Mammillary body Superior centra nucleus
Figure 17.14 . Limbic pathways interrelating the telencephalon and diencephalon with medial midbrain structures
The medial forebrain bundle dnd efferent fibers of the mammillary body are shown in black The medial forebraln
bundle orlgindtes from the septal and Idteral preoptlc regions, traverses the lateral hypothalamic area and projects
into the midbrain tegmentum It also includes many ascending fibers. The fasciculus mammillary princeps divides into
two bundles, the mammillothalamic tract and the mammillotegmental tract. Ascending fibers of the mammillary pe-
duncle, arising from the dorsal and ventral tegmental nuclei, are shown in red. Most of fhese fibers pass to the mam-
millary body, but some continue rostrally to the lateral hypothalamus, the preoptlc region, and the medial septal nu-
cleus. Fibers arising from the septal nuclei project caudally in the medial part of the stria medulloris ( blue) to
terminate in the medial habenular nucleus. Impulses conveyed to the habenular nucleus are distributed to midbrain
tegmental nuclei via the fasciculus refroftexus (habenulo-inferpeduncular bundle) ( blue).
is released into perivascular space containing pulses. Stimulation of the cell bodies in the
fenestrated capillaries (168). hypothalamus gives rise to action potentials
A second efferent projection from the conducted in axons that trigger the release of
magnocellular elements of the paraventricu - the hormones.
lar nucleus has been described in the external
zone of the median eminence. Additionally, Tuberohypophysial Tract
high levels of vasopressin have been demon-
strated in the hypophysial portal system . The The tuberohypophysial or tuberoin-
role of vasopressin in the zona externa of the fundibular tract arises from the tuberal re-
median eminence is unresolved , but it may gion, mainly from the arcuate ( or in-
act as a regulator for adrenocorticotropic hor- fundibular ) nucleus ( Figs. 17.1 and 17.21),
mone ( ACTH ) release. Cells of the supra- and can be traced only to the median emi-
optic and paraventricular nuclei also contain nence and the infundibular stem ( Figs.
other biologically active substances, such 17.10, 17.16, and 17.18) ( 62, 79, 161, 183).
as enkephalin , cholecystokinin, glucagon, Cells of the arcuate nucleus are situated in
dynorphin , angiotensin , and corticotrophin the uppermost part of the infundibulum
releasing factor (CRF) ( 134 ) ( Fig . 17.11 ) . ( i.e., the median eminence) and lie directly
Neurosecretory cells in the hypothalamus upon the ependymal lining. Axons of these
retain their capacity to conduct electrical im - cells form the tuberoinfundibular tract,
17 Hypothalamus 725
which projects to the internal and external nence and dopamine is released into the por-
zones of the median eminence, where they tal capillaries. Dopamine in the hypophysial
collateralize ( Figs. 17.10 and 17.21 ). Some portal system inhibits the release of prolactin
cells in the arcuate nucleus have projections, from the anterior pituitary. A short feedback
or collaterals, that extend to other parts of loop suggests that pituitary prolactin inhibits
the hypothalamus, the thalamus, and the dopamine release from the median eminence.
amygdala . Although these fibers accom - Increases in dopamine occur in the arcuate
pany those of the supraoptic hypophysial nucleus in pregnancy, pseudopregnancy, and
tract in part of their course, they end on lactation, suggesting there is little release of
capillary loops near the sinusoids of the hy - the inhibiting factor in these conditions.
pophysial portal system ( Figs. 17.18 and Physiologic stimuli of major importance in
17.14 ). These are fine fibers, but secretory the release of prolactin from the anterior lobe
granules can be demonstrated in their are estrogens and suckling. Dopamine neu -
axons. Fibers of the tuberoinfundibular tract rons in the arcuate nucleus represents the
convey "releasing" or "releasing-inhibiting" group A 12 of Dahlstrom and Fuxe (31 ).
hormones, which are transported via the Dopamine neurons are also present in other
hypophysial portal vessels to the anterior regions of the hypothalamus, including ( a )
lobe of the hypophysis where they modu - the periventricular /one of the posterior hy -
late the synthesis and release of adenohy - pothalamus ( group All ), ( b ) the periventric-
pophysial hormones ( 62, 144, 166 ). Func- ular zone of the anterior hypothalamus
tionally, the tuberoinfundibular tract and (group A 14 ), and the dorsomedial hypothala -
the hypophysial portal system establish the mus and zona incerta ( group A 13) (5, 69, 127,
neurohumoral link between the hypothala - 130, 133, 140, 141 ) ( see Fig. 17.21 and Table
mus and the anterior pituitary . 17.1 ).
Dopamine was the first of many sub- In addition to dopamine, the arcuate nu -
stances identified in the arcuate nucleus ( Fig. cleus contains a number of peptides similar
17.21 ) ( 31, 44 ). Dopaminergic neurons inner- to hormones in the anterior pituitary, such as
vate the external zone of the median emi- -
ACTH , fj-lipotrophin ( p LI’Fl ), and ji-endor-
TABLE 17.1. Location of Principal Catecholamine Cell Groups^
MI DI I I A . -.
. . .
Vrntrnl iU r il medulla and latrr il rrtirul ir nucleus
Dnrsomrdi ll medulla: dorsal vagal nucleus and
AI
A2 NMD
.
Nil I
solitary nucleus
Ventrolateral medulla and lateral reticular nucleus A3 NM
KINS Literal pontine \ i NM

lYriventriculnr region
Ventrolateral pons medial to N. VII, also dorso- AS NM
lateral to superior olive
Locus coeruleus Ah Nl
Nucleus subcoerulcus A7 Nl
MIDBKAIN .
Ketroruhr il midbrain tegmental area AK DA
Substantia nigra pars compacta AS DA
Ventral tegmental area All ) DA
HYPOTIIALAMLS Periventricular /one of posterior hypothalamus All DAt + NM ? l

Median eminence AI 2 DA
Dorsomedial hypothalamus and /ona incerta AH DA
Periventricular /one of anterior hypothalamus AM DA
Olfactory bulb A 1S DA
° These major groups of catecholamine-containing cell bodies and the corresponding alphanumeric desig-
nation were given by the investigators who first described them in fluorescence histochemical study . The
letter A in the second column refers to "adrenergic" cells numbered according to their position in ascend -
ing caudorostral levels of the brainstem, diencephalon, and olfactory bulb In the third column, the subse-
quent identification of the catecholamine is shown . DA , dopamine; NE , norepinephrine ( or noradrena -
line); and E, epinephrine ( or adrenaline). Cells containing the indolamine serotonin ( 5- hvdroxvtrvpt -
amine ) are not included in this table.
Limbic brain stem connections
Cingulate gyrus
y Entorhinal
• Hippocampus
t
*
cortex
» Subicuium
Fornix , y
X Thalamus
/
/ Ant
nuc.
* Habenula
/
/
Central gray
/
/
/
/ i
Anterior \
I Mesencephalic
commissure
/
% Hypothalamus i tegmentum
I
K
,
< •- 1
ri MB
Septal area Medial torebrain bundle
Diagonal band
of Broca r* Amygdala
Figure 17.15 . Major interconnections of structures comprising the limbic system Projection fibers arising from the
subicuium ( blue) project via the fornix to the septal area, hypothalamus and mesencephalic tegmentum. Fibers pro-
jecting in the fornix from the hippocampus are shown in block -dashed lines. Projections from the septal area to the
hippocampus are shown in red, MB Indicates mammillary body.
Periventricular nuclei
Mammillothalamic Thalamus
tract
V
Posterior nucleus
v
Periventricular fibers
( dorsal long fasc . )
Paraventricular
nucleus
— .
l \
Aqueduct
SupraoptjXi Mammillary body
nucleus
Optic tri Hypothalamic

Tuberal
, nuclei reticular fibers
Ant lobe hypophysis

Neurohypophysis
Tuberoinfundibular tract
\
v r
Mammillotegmentol tract
. .
Figure 17.16 Efferent hypothalamic pathways Nuclei in the supraoptic region are In blue Nuclei of the middle or .
tuberal region of the hypothalamus are gray . Nuclei of the caudal or mammillary region are shades of red The pre-
optlc area ( gray ) lies rostral to the supraoptic region. Terminations of the mammillotegmental tract are shown in Fig-
ure 17.14.
Hippocampus Entorhinal
cortex
*
Subiculum
Cingulate
gyrus
;
Septal nuclei
Ant. thalamic
nuclei
Medial hypothalamic nuclei Mammillary Midbrain

nuclei
73
Paraventricular nucleus Pons- medulla
Amygdala *
« Lateral hypothalamic nuclei Spinal cord
Olfactory
\ Pyriform
bulb cortex
Figure 17.17 . Principal fiber connections of the hypothalamus The principal afferents to the hypothalamus from the forebrain
arise from two phylogenetically older cortical areas, the piriform cortex, and the hippocampal formation Each of these projec-
tions is reinforced by d second projection from a related subcortical nuclear mass This secondary projection arises from the
amygdaloid complex in the case of the piriform cortex, and from the septal nuclei in the case of the hippocampal formation
Reciprocal connections exist between the hypothalamus and these subcortical structures . The cingulate gyrus and the piriform
cortex con exert influences upon the hypothalamus via the entorhinal area and the hippocampal formation. The mammillary nu-
clei and the hippocampal formation project to the anterior thalamic nuclei which in turn influence activities in the cingulate
gyrus . Projection pathways from the mammillary nuclei to the cortex and from the hippocampus and subiculum to the hypothal- -
amus are In red , Other connections are shown in blue .
o
TT
Q.
2
r
ro
vj
phin ( (J- END). ACTH and p- LPH in the arcu - HYPOPHYSIAL PORTAL SYSTEM
ate nucleus do not appear to coexist in neu -
rons with dopamine. The heterogeneity of the The hypophysis is supplied by two sets of
substances found in the arcuate nucleus, and arteries, both of which arise from the internal
the presence of releasing factors beyond the carotid artery. The superior hypophysial
limits of this nucleus, suggest it is not the sole artery forms an arterial ring around the
hypophysiotrophic center in the hypotha - upper part of the hypophysial stalk, while the
lamus. inferior hypophysial artery forms a ring
Hypothalamic efferent projections fall into about the posterior lobe and gives branches
five main categories: (a ) fibers that emerge to the lower infundibulum ( Figs. 17.18 and
via the medial forebrain bundle, ( b) neurose- 17.19). Both of these arteries enter the hy-
cretory neurons that convey hormones to the pophysial stalk and break up into a number
neurohypophysis, (c) fibers concerned with of sinusoids (124, 125). Both arteries are in-
releasing hormones into the hypophysial por- nervated by postganglionic sympathetic
tal system , (d ) fibers that arise from the mam - fibers. Blood from these sinusoids collects
millary nuclei that project to the anterior nu- into vessels that pass into the anterior lobe of
clear group of the thalamus and to nuclei in the hypophysis, which receives almost all of
the midbrain tegmentum , and (e ) fibers that its blood supply via these vessels. These ves-
project to the lower brain stem and spinal sels are referred to as the hypophysial portal
cord . vessels (142 ). Anatomic and physiologic evi-
Supraoptic nucleus
Supraopticohypophysial
tract
fsD
Tuberal nuclei
Superior hypophysial
artery
Tuberoinfundibular tract
Hypophysial portal veins — Sinusoids
Vein to dural sinuses
Secondary capillary
plexus
Neurohypophysis
Vein to dural sinuses

Anterior lobe hypophysis
Inferior hypophysial artery
Figure 17.18 . Hypophysial portal system, the tuberoinfundibular tract, and the supraopticohypophysial tract The hy-
pophysis is supplied by the superior and inferior hypophysial arteries. Branches of these arteries form sinusoidal capil-
laries about the infundibulum. Blood from the sinusoids passes to the anterior lobe of the hypophysis via the portal
vessels which give rise to a second capilldry plexus in the anterior lobe. The tuberoinfundibular tract ends in the sinu-
soids of the infundibular stem and transports neurosecretory substances, called releasing/inhibiting hormones or re-
leasing/inhibiting factors, which enter the sinusoids. The supraopticohypophysial tract contains fibers from the
supraoptic and paraventricular nuclei which pass to the neurohypophysis . Neurosecretory products of cells in these
hypothalamic nuclei are conveyed directly to the neurohypophysis. The supraoptic and paraventricular nuclei are
the main source of the hormones vasopressin and oxytocin.
17 Hypothalamus 729
Superior hypophysial arteries
Hypophysial portal
vessels
Cavernous sinus
Adenohypophysis
Neurohypophysis
Inferior hypophysial artery
Figure 17 19 Scanning electron micrograph of vascular casts of the pituitary gland, infundibular stalk, and median
eminence in a monkey The gland is viewed from its posterior aspect The hypophysial arteries and the portal system
of vessels shown in this figure should be compared with the schematic diagram showing a sagittal view in Figure
17 18
dence indicate that hypothalamic influences pophysiotrophic agents or releasing hormones

on the anterior lobe of the hypophysis are and are named according to the hormone
conveyed by humoral substances transported they release.
via the tuberoinfundibular tract to the sinu -
soids and the anterior lobe via the portal sys- HYPOPHYSIOTROPHIC AGENTS
tem . The pattern of blood flow in living ani-
mals is not easily deduced from anatomic These releasing factors have most of the at -
studies of blood vessels. Observations in liv- tributes of hormones and most appear to be
ing animals leave no doubt that blood in the neuropeptides. Hypophysiotrophic agents in -
portal system flows from the median emi- clude corticotrophin -releasing factor (CRF)
nence to the anterior lobe ( 51 ). Hypophys- ( Fig. 17.1 IB ), growth hormone- releasing fac -
iotrophic releasing factors in neuronal termi- tor (GHRF), gonadotrophin hormone- releas-
nals in the median eminence are carried to ing factor ( or luteinizing hormone releasing -
the adenohypophysis via this restricted vas- -
hormone ( FRIT )), thyrotrophin releasing fac-
cular route. tor ( TRF), prolactin-inhibiting factor ( PIF), so-
The hypothalamus is intimately concerned matostatin (somatic inhibiting releasing fac-
with the synthesis and transmission of factors -
tor (SRIF) ), melanocyte releasing hormone
that stimulate and inhibit the secretion of hor- ( MSH ), as well as (i- lipotrophin ( fl- LPH ), and
mones by the anterior pituitary ( 58, 59). Elec- P-endorphin ( fl-END). Neurons of the arcu -
trical stimulation of the hypothalamus can ate nucleus are immunocytochemically posi-
increase the discharges of gonadotrophic hor- tive for ACTH , 0- LPH , and p-END. These
mone and ACTH. Stimulation of the tuberal peptides are derived from a common precur-
region in the rabbit has produced ovulation. sor glycosylated molecule called pro opiome - -
Direct stimulation of the anterior lobe does lanocortin ( POMC ) ( 27 ). Under stressful con -
not elicit these responses, because the hu - ditions CRF is present in the plasma of the
moral part of this pathway is not electrically portal vessels, but it is suspected that all of
excitable. The neurosecretory substances act- these peptides are released . Secretion of
ing on cells of the anterior lobe are called hy- growth hormone (GH ) is regulated by neural
influences both stimulatory and inhibitory. cence. Somatostatin, which also inhibits se-
This is achieved by two hypothalamic releas- cretion of thyrotropin, has been recognized in
ing factors, growth hormone-releasing factor many locations other than the hypothalamus
(GHRF) and growth hormone-inhibiting fac - from which it was originally isolated. Clinical
tor (GHIF), or somatostatin ( 41 ). Secretion of studies confirm the powerful inhibitory ef -
these hormones is regulated by monoamines, fects of somatostatin on growth hormone, as
dopamine ( DA ), norepinephrine ( NE ), and well as on insulin and glucagon.
serotonin (5- HT), all of which appear to have Thyrotropin -releasing factor (TRF) has
stimulating effects. Growth hormone mea - been isolated and synthesized . The synthetic
sured in the plasma is age-dependent and oc- compound has an action greater than the nat-
curs in surges from early puberty to adoles- -
ural secretion on the thyroid stimulating hor-
Bone
Intermediate lobe
Qv Anterior lobe
t
Thyroid Kidney
Thyroxine
and
triiodothyronine
Adrenal
cortex
Corticosteroids
Placenta
Uterine
Ovum ' contractions
Estrogen
Progesterone
Spermatazoa
Testosterone ^
Figure 17.20. Target organs upon which pituitary hormones act Pituitary (hypophysial) hormones are either secreted
or controlled by neurons of the hypothalamus Hormones secreted by cells in the anterior ( blue) and intermediate
lobes ( black ) of the pituitary are regulated by hypothalamic hypophysiotrophic peptides conveyed by the hy-
pophysidl portal system. Hormones of the anterior lobe include (a) growth hormone ( GH ), (b) thyrotropin ( TSH ). ( c )
corticotrophin ( ACTH). (d) follicle stimulating hormone ( FSH). (e) luteinizing hormone ( LH). and (0 prolactin.
Melanocyte stimulating hormone ( MSH) is derived from cells of the intermediate lobe ( black ) of the pituitary The pos
terior ( neural) lobe ( red) of the pituitary contains vasopressin and oxytocin secreted by cells of the supraoptic and
paraventricular nuclei of the hypothalamus. These hormones act upon the kidney tubules, the smooth muscle of the
uterus and glandular tissue of the breast
17 Hypothalamus 731
Figure 17.21 . Frontal section of the rat hypothalamus showing the localization of dopaminergic neurons revealed by
their immunoreactivity for the enzyme tyrosine hydroxylase (TH). The section is oblique in the frontal plane with the
ventral part more cranial than the dorsal part . Immunofluorescent cell bodies are seen in the arcuate nucleus (or)
(A 12 cell group) and in the zona incerta (27) (A 13 cell group). Note the dense plexus of TH-positive fibers in the median
eminence (me), especially the external layer At this level the TH-positive fibers are present in the whole external layer,
whereas at a more caudal level the highest concentrations are found in the lateral parts Note single cell bodies
( arrow ) ventral to the A 13 cell group V. third ventricle (magnification x 170).
mone (TSH ) ( Fig. 17.20). No true antagonist role for 0-END, but it would appear to be in -
of TRF has been reported , but thyroxin is volved in maintaining homeostasis. The
known to inhibit TSH. The luteinizing hor- enkephalins are not derived from 0-
mone-releasing hormone ( LHRH ) and the fol- lipotrophin or 0-endorphin and the cells and
licle-stimulating-releasing factor ( FRH ) ap- -
fibers labeled for 0 endorphin are distinct
pear to be parts of the same molecule. FRH from those labeled by antisera specific for
causes the release of the follicle-stimulating enkephalins.
hormone ( FSH ) from the anterior pituitary, The localization and axonal projections of
which initiates cyclical changes in the ovaries neurons synthesizing the peptides vaso-
and the production of estrogens. The dis- pressin and oxytocin were described earlier.
charge of LHRH liberates the luteinizing hor- The role of these peptides in memory is a
mone, which produces ovulation and the de- subject of active investigation which has al-
velopment of the corpus luteum. Ovulation ready led to the development of new ap-
appears to require both FSH and LH. Neu - proaches to the cell biology of higher mental
ropeptide Y ( NPY ) acts at the level of the me- function. In a number of behavioral tests, va-
dian eminence to stimulate the release of LH. sopressin facilitates and oxytocin diminishes
This peptide also activates postsynaptic mes- memory consolidation and retrieval (19, 35,
senger pathways that complement and rein- 45). These actions appear to involve different
force those affected by noradrenaline, which regions of the peptide, for the covalent ring
as another major neuroregulator of LHRH se- portion of the molecule affects mainly consol-
cretion is released as a cotransmitter with idation and the linear part is implicated in
NPY (74). The medial preoptic area is consid - memory retrieval (34). Indirect evidence indi-
ered responsible for the cyclical nature of the cates that vasopressin may interact with nor-
female reproductive system . adrenergic synapses to influence memory
The prolactin-inhibiting factor ( PIF) ap- consolidation .
pears to be dopamine, which has been identi- Some of the releasing hormones or factors
fied in the arcuate nucleus, the portal vessels, mentioned earlier, as well as several pituitary
and in pituitary receptors ( Fig. 17.21 ). Thy- pro-opiomelanocortin-derived peptides, have
rotropin- releasing factor (TRF) also appears also been identified in extrahypothalamic re-
to potentiate the release of prolactin. Pro- gions of the brain. Their functional signifi-
lactin secretion increases as the effective cance as possible neurotransmitters or modu -
dopamine concentrations at receptor site in lators is not yet established (79).
the anterior pituitary are reduced . The naturally occurring opioid peptide 0-
The naturally occurring opioid peptide 0- endorphin is found in the rat intermediate
endorphin is found in rat anterior and inter- lobe and adenohypophysis and in the brain.
mediate lobes of the pituitary. Cells in the ar- Hypophysectomy does not reduce brain 0-
cuate nucleus of the hypothalamus contain a endorphin , suggesting an endogenous syn-
common 31,000-Dalton precursor ( pro-opi- thesis within the CNS. 0-Endorphin-labeled
omelanocortin or POMC ) of ACTH, 0- cell bodies are at the base of the tuberal re-
lipotrophin ( 0- LPH ), and 0-endorphin ( 0- gion of the hypothalamus, and labeled axons
END), which is cleaved in the anterior and are distributed along the ventricular wall ex-
intermediate lobes. 0-LPH has no opioid ac- tending anteriorly to the level of the anterior
tivity but may be a prohormone for opioid- commissure. The supraoptic, periventricular,
like peptides. 0-endorphin has 5-10 times the paraventricular, and suprachiasmatic nuclei
analgesic potency of morphine, but its effects receive abundant 0-endorphin-labeled fibers
are seen mainly after intracerebral adminis- (11, 27). The cells and fibers labeled for 0-en-
tration and 0-endorphin-labeled axons are dorphin are distinct from those labeled by an-
distributed along the ventricular wall to the tisera specific for the enkephalins (see Chap-
supraoptic, periventricular, paraventricular, ter 5).
and suprachiasmatic nuclei, and some fibers
may reach the thalamus. In severe stress, FUNCTIONAL CONSIDERATIONS
there is a coordinated release of ACTH, 0-
LPH , and 0-END from the anterior pituitary. Coordination of the Autonomic
In syndromes characterized by hypersecre- Nervous System
tion of ACTH, the peptides that form part of
the precursor molecule also are increased . The hypothalamus and immediately ad -
There is, as yet, no well-defined physiologic joining regions are related to all kinds of vis-
17 Hypothalamus 733
ceral activities. The most diverse disturbances thoracic cord is the major origin of sympa -
of autonomic functions, involving water bal- thetic preganglionic neurons. There is a dense
ance, internal secretion, sugar and fat metab- innervation of the intermediolateral column
olism, and temperature regulation, all can be by catecholamine containing terminals, but
produced by stimulation or destruction of hy - their source in the medulla and pons has not
pothalamic areas. Even the mechanism for been definitely established (91 ). Descending
normal sleep may be altered profoundly by -
serotonin (5 HT ) containing axons from the
such lesions. raphe nuclei also reach the intermediolateral
The hypothalamus is the chief subcortical cell column. Anatomic studies emphasized
center for the regulation of both sympathetic the close association between visceral recep-
and parasympathetic activities. These dual tive cells in the solitary nucleus of the
activities are integrated into coordinated re- medulla and the hypothalamus ( 25, 26, 91,
sponses that maintain adequate internal con- 182) and between the hypothalamus and the
ditions in the body. It is improbable that each spinal cord (161, 182). Oxytocin immunoreac -
of the autonomic activities has its own dis- tivity is seen in terminals of laminae I and II
crete center in the hypothalamus. However, a of the dorsal horn and in the intermediolat -
specific function has been established for the eral cell column (119). This information about
supraoptic and paraventricular nuclei. There connectivity and putative transmitters in vis -
is also a fairly definite topographic organiza- ceroceptive and visceromotor regions of the
tion with regard to the two main divisions of central nervous system is leading to new ex-
the autonomic system. Control of parasympa - perimental approaches in the physiologic
thetic activities is related to the anterior and study of cardiovascular regulatory mecha-
medial hypothalamic regions (supraoptic and nisms.
preoptic areas ) and the ventricular portion of
the tuber cinereum. Stimulation of this region REGULATION OF BODY TEMPERATURE
results in increased vagal and sacral auto-
nomic responses, characterized by reduced The coordination of sympathetic and
heart rate, peripheral vasodilation, and in- parasympathetic responses is strikingly
creased tonus and motility of the alimentary shown in the regulation of body temperature.
and vesical walls. This complex function, involving widespread
The lateral and posterior hypothalamic re - physical and chemical processes, is mediated
gions are concerned with the control of sym - by two hypothalamic mechanisms, one con-
pathetic responses. Stimulation of this region, cerned with the dissipation of heat and the
especially the posterior portion from which other with its production and conservation.
many descending efferents arise, activates the Experimental evidence indicates that the an-
thoracolumbar outflow . This results in in - terior hypothalamus is sensitive to increases
creased metabolic and somatic activities char - in blood temperature and sets in motion the
acteristic of emotional stress, combat or flight. mechanisms for dissipating excess heat. In
These responses are expressed by dilatation humans, this consists mainly of profuse
of the pupil, piloerection, acceleration of the sweating and vasodilatation of the cutaneous
heart rate, elevation of blood pressure, in - blood vessels. These actions permit the rapid
crease in the rate and amplitude of respira - elimination of heat by convection and radia-
tion, somatic struggling movements, and in - tion from the surface of the engorged blood
hibition of the gut and bladder. All these vessels, and by the evaporation of sweat. In
physiologic correlates of emotional excite - animals, heat loss is effected mainly by the
ment can be elicited when the hypothalamus rapid warming of successive streams of in-
is released from cortical control. Removal of spired air ( panting ). Lesions involving the an-
the cortex, or interruption of the cortical con- terior part of the hypothalamus abolish the
nections with the hypothalamus, induces neural mechanisms concerned with the dissi-
many of these visceral symptoms, collectively pation of heat and result in hyperthermia .
designated as "sham rage" ( 4, 43). On the Thus, hyperthermia ( hyperpyrexia ) may re-
other hand , destruction of the posterior hypo - sult from tumors in, or near, the anterior hy-
thalamus produces emotional lethargy, ab- pothalamus.
normal sleepiness, and a fall in temperature The posterior hypothalamus, on the other
due to general reduction of visceral and so - hand , is sensitive to conditions of decreasing
matic activities. body temperature and controls mechanisms
The intermediolateral cell column of the for the conservation and increased produc-
tion of heat . The cutaneous blood vessels are water is not clear. Reabsorption of sodium
constricted and sweat secretion ceases, so chloride and bicarbonate ions is followed by
that heat loss is reduced . Simultaneously passive reabsorption of water . This hormone
there is augmentation of visceral activities, also appears to alter the osmotic permeability
and the somatic muscles exhibit shivering. of water in the distal and collecting tubules of
All these activities tremendously increase the the kidney.
process of oxidation, with a consequent pro- There is evidence that a region of the hy-
duction and conservation of heat. Bilateral le- pothalamus is responsible for the regulation
sions in posterior regions of the hypothala- of water intake. Electrical stimulation of ante-
mus usually produce a condition in which rior regions on the hypothalamus in goats
body temperature varies with the environ- creates fantastic "thirst" and results in con -
ment ( poikilothermia ), since such lesions ef - sumption of large volumes of water (3). This
fectively destroy descending pathways con- is probably part of a more extensive system
cerned with both heat conservation and which regulates the consumption of both
dissipation . food and water. An increase in the osmotic
These two intrinsically antagonistic mech- pressure of body fluids may be an effective
anisms do not function independently but are stimulus for water intake. Osmoreceptors
continually interrelated and balanced against probably are situated close to the cells of the
each other to meet changing needs of the supraoptic nucleus which have an abundant
body The coordinated responses always are blood supply (192). Localized lesions in the
directed to the maintenance of a constant op- lateral hypothalamus at the level of the ven -
timum temperature. tromedial nucleus in rats cause a reduction in
water intake without affecting food intake.
MAINTENANCE OF WATER BALANCE Larger lesions in the lateral hypothalamus
may cause adipsia as well as aphagia. The lat-
The supraoptic and paraventricular nuclei eral hypothalamic area can excite cells of the
are specifically concerned with the mainte- supraoptic nucleus, which in turn inhibit the
nance of body water balance ( Figs. 17.2-17.4, lateral hypothalamic area in a negative feed -
17.16, and 17.18). Destruction of these nuclei, back circuit ( 38).
or their hypophysial connections, invariably The paraventricular and supraoptic nuclei
is followed by the condition known as din - also produce oxytocin , which causes contrac -
betes insipidus , in which there is increased se- tions of uterine muscle and myoepithelial
cretion of urine ( polyuria ) without an in- cells surrounding the alveoli of the mammary
crease in the sugar content. The antidiuretic gland ( Fig. 17.21)) (64, 120, 161 ). Surprisingly,
hormone, vasopressin , is secreted directly by the role of oxytocin in the male is still un -
the cells of the supraoptic and paraventricu - known ( 27).
lar nuclei . Vasopressin is transported by the
unmyelinated axons of the supraopticohy - CONTROL OF ANTERIOR PITUITARY
pophysial tract and is stored in terminals in
the posterior lobe of the pituitary (88). The The important role of the hypothalamus in
production of antidiuretic hormone varies in maintaining and regulating the activity of the
accordance with changes in the osmotic pres- anterior lobe of the hypophysis has been de-
sure of the blood . An increase in the osmotic scribed in relation to the hypophysial portal
pressure of the blood that supplies the mag- system ( 59 ) ( Figs. 17.18 and 17.20). This is a
nocellular hypothalamic nuclei increases the humoral control mechanism in which releas-
activity of these neurons and the release of ing hormones are transmitted via the portal
antidiuretic hormone. In states of dehydra- system ( 128). There are no hypothalamic ef -
tion, there is a depletion of the hormone in ferent fibers that reach the anterior lobe of the
the posterior lobe and increased secretory ac- pituitary. The anterior pituitary stands in
tivity in the supraoptic nuclei. After reestab- marked contrast to other endocrine organs,
lishment of water balance, there is a reaccu - such as the ovary , testis, thyroid , and adrenal
mulation of the hormone in the posterior cortex, which may be transplanted to distant
lobe. The antidiuretic hormone is considered sites and still retain their endocrine functions.
to act specifically on the kidneys ( 138), al- The anterior lobe of the pituitary cannot be
though the exact mechanism by which vaso- transplanted to distant locations and retain
pressin brings about the reabsorption of renal its function, because it is dependent upon its
17 Hypothalamus 735
close relationships with the hypothalamus. nadotropin which precedes ovulation (Fig.
The essential hypothalamic features are the 17.20) ( 40, 152, 164). Electrical stimulation of
tuberoinfundibular tract and the hypophysial the preoptic area, or the corticomedial nu-
portal system . clear group of the amygdaloid complex, pro-
The hypothalamus is considered the site of duces ovulation in rabbits and cats. The ef -
elaboration of releasing or releasing-inhibit- fects of preoptic stimulation are abolished by
ing hormones ( peptides) related to go- lesions separating this area from the tuberal
nadotrophic, adrenocorticotrophic ( ACTH ), region of the hypothalamus, while the effects
thyrotrophic (TSH ), and growth hormones of amygdaloid stimulation are blocked by a
( Figs. 17.18 and 17.20). Attempts to determine section of the stria terminalis. These observa-
the loci within the hypothalamus concerned tions suggest a functional linkage between
with particular releasing factors suggest that the amygdala and the medial preoptic area
the neural area related to TSH appears to lie via the stria terminalis, and fiber systems
on either side of the midline between the par- from the medial preoptic area to the tuberal
aventricular nucleus and the median emi- region of the hypothalamus. However, the
nence. Electrical stimulation of the anterior amygdaloid input to the preoptic area is not
median eminence appears to be the most ef - essential for ovulation, for bilateral destruc-
fective site for increasing thyroid activity (60). tion of the stria terminalis does not prevent
Similarly, electrical stimulation of the hypo- ovulation (15).
thalamus in the rabbit can cause the dis- Tumors and other pathologic processes in-
charge of gonadotrophic hormone and ACTH volving the hypothalamus frequently modify
(53, 57, 97). While bilateral lesions in almost sexual development. Such lesions may be as-
any region near the base of the hypothalamus sociated with precocious puberty or hypogo-
reduce ACTH release, the median eminence- nadism associated with underdevelopment of
tuberal region has the most important con- secondary sex characteristics. Although hy-
trolling influence. pergonadism has been attributed to tumors
Hypothalamic neurons that produce re- of the pineal, most tumors of the brain associ-
leasing and releasing-inhibiting factors are ated with precocious puberty actually in-
regulated by various hypothalamic afferents, volve, or impinge on, the hypothalamus.
as well as by hormones of the target organs These lesions frequently destroy the posterior
or pituitary hormones. For example, when hypothalamus and leave the anterior hypo-
the concentration of triodothyroxine in the thalamus intact. The intact hypothalamic re-
blood is high, hypothalamic neurons that gions functioning in the absence of inhibitory
produce thyrotropin-releasing factor (TRF) influences from posterior regions leads to in-
are inhibited . Conversely, if the levels of thy- creased pituitary function .
roid hormones are low, the hypothalamic The preoptic region plays an important
neurons produce more TRF. This stimulates role in regulating the release of gonad -
increased output of thyroid-stimulating hor- otrophic hormones from the anterior lobe of
mone (TSH ) from the pituitary, and the thy- the hypophysis ( Fig. 17.20). In the female, pi-
roid gland , in turn, is induced to synthesize tuitary gonadotropins are released in a cyclic
and release more of its hormone. This hor- manner, the duration of the cycle correspond -
monal negative feedback plays a crucial role ing to the menstrual period . In the male, the
in the control of hypothalamic neurons that gonadotropins are released topically without
produce releasing or releasing-inhibiting regularly occurring fluctuations. Therefore, it
factors. is not surprising that there are differences in
the functional organization of the preoptic re-
CONTROL OF REPRODUCTIVE FUNCTIONS gion in the male and female. A morphologic
expression of this difference has been ob-
The hypothalamus plays an important role served in the preoptic region of the rat , where
in the initiation and coordination of repro- a nucleus of densely stained cells is larger in
ductive functions, and these functions are dif - the male. This nucleus has been termed the
ferent in the two sexes. The tuberal region of "sexually dimorphic nucleus of the preoptic
the hypothalamus appears essential for the area" ( Fig. 17.22 ) (49, 50). The full ontogenetic
maintenance of basal levels of gonadotrophic development of this nucleus, as well as the
hormone, but the integrity of the preoptic male pattern of tonic gonadotrophic release,
area is necessary for the cyclic surge of go- depends on the presence in the circulation of
FEMALE
SON - POA
SDN - POA
FEMALE
SON
Figure 17.22 . Frontal sections through the brain of adult female ( A ) and male ( B) rat sacrificed 2 weeks after go-
nadectomy (thionme stain ) The arrows indicate that portion of the medial preoptic nucleus which exhibits a marked
sexual dimorphism, both at the same magnification . The absence of the suprachiasmatic nucleus ( SCN) in B is an arti -
fact of the plane of tissue sectioning . The localization and magnitude of the sexually dimorphic nucleus of the preop -
tic area (SDN - POA) is shown in the parasagittal (C) and frontal ( D) planes AC. anterior commissure. CC, corpus callo-
. - . .
sum. CPU caudate putamen, FX. fornix; LV lateral ventricle. OC. optic chiasm. S septum; SCN. suprachiasmatic
.
nucleus. SON supraoptic nucleus. III. third ventricle
testosterone during the first week of life (92 ). adult , show the male pattern of gonadotropin
If the testes are removed from the newborn release. As mentioned earlier, a probable ho-
animal, the genetic male will fail to develop mologue of the sexually dimorphic nucleus
the sexually dimorphic nucleus of the preop- was identified in the human preoptic area
tic region. Conversely, a newborn female (68, 177). It is a nucleus that contains approxi -
given exogenous testosterone will , as an mately twice as many neurons in men as in
17 Hypothalamus 737
women. In Ihe male, the equivalent of statin, which inhibits the release of growth
luteinizing hormone promotes the growth hormone, is present in the hypothalamus and
and development of interstitial testicular cells in a variety of other tissues. Chronic hyper-
( Leydig cells), which convert steroid precur- secretion of growth hormone leads to an
sors to testosterone. The role of gonad - overgrowth of bones and soft tissues, which
otrophins in spermatogenesis is complex and produce a highly characteristic syndrome
unclear, but a high level of testosterone ap- (acromegaly ).
pears essential ( Fig. 17.20). Tumors of the adenohypophysis may pro -
Morphologic features in hypothalamic nu- duce symptoms due to their increasing size
clei other than the sexually dimorphic nu- or because they result in alterations of pitu -
cleus can also be affected by fetal or neonatal itary functions (185). Expanding tumors
exposure to androgens. These morphologic cause a ballooning of the sella turcica, may
features include changes in the size of neu - compress fibers in the optic chiasm or optic
ronal nuclei and nucleoli, types of synaptic tract, and frequently produce headaches due
vesicles and terminals, synaptic organization, to traction on the meninges. The most typical
and dendritic branching patterns (92). The visual field defect is a bitemporal hemianop-
mechanisms whereby steroid hormones af- sia due to involvement of the decussating
fect the brain to determine sexual behavior fibers in the optic chiasm, but visual field de -
and patterns of gonadotropin release are fects take many forms dependent on the
complex. For example, implantation of small growth pattern of the tumor. Endocrinopathy
quantities of estradiol into the hypothalamic may take the form of hypersecretion or hy-
ventromedial nucleus ( HVM ) of the rat acti- posecretion depending on the type of tumor.
vates feminine sexual behavior. Estradiol has The pituitary syndrome may be associated
been shown to alter a number of cellular with excess prolactin (amenorrhea-galactor-
properties in the HVM, including induction rhea ), growth hormones (acromegaly ), or
of progestin receptors, decrease of the in- adrenocorticotrophic hormone (Cushing's
hibitory neurotransmitter synthetic enzyme syndrome). Patients with prolactin-secreting
glutamic acid decarboxylase (GAD), in- tumors have been successfully treated with
creased muscarinic cholinergic receptor bind- dopamine agonists, particularly bromocrip-
ing, and a decrease in the type A monoamine tine. Dopamine synthesized in the arcuate
oxidase activity. This example illustrates es- and periventricular nuclei of the hypothala -
trogen regulation of a neurotransmitter, syn- mus and transported via the portal system in-
thetic and degradative enzymes, and neuro- hibits prolactin release.
transmitter receptors (94). Neurons endowed
with specific steroid hormone receptors are CONTROL OF FOOD INTAKE
widely distributed in the hypothalamus (135,
175). These receptors are particularly abun- It has been known for a long-time that cer -
dant in neuronal nuclei, where hormones can tain lesions near the base of the brain are
exert profound genomic effects. The presence associated with obesity. Localized bilateral
of immunoreactivity for estrogen receptors lesions in the hypothalamus involving
on dendrites and axon terminals (9) suggests primarily, or exclusively, the ventromedial
the possibility that steroid hormones may in- nucleus in the tuberal region produce hyper
fluence other aspects of neuronal functioning phagia (67, 73, 173, 174). Such animals eat vora-
by acting at nongenomic sites. ciously, consuming two or three times the usual
amount of food . Obesity appears to be the direct
CONTROL OF GROWTH result of increased food intake. Bilateral lesions
destroying portions of the lateral hypothalamic
Growth hormone-releasing factor acts on nucleus impair, or abolish, the desire to feed in
acidophilic cells of the anterior pituitary that hyperphagic and normal animals (1, 2, 174).
produce the growth hormone (39, 109). These data suggest that the ventromedial nu-
Growth hormone functions synergistically cleus of the hypothalamus is concerned with
with thyroxin, and blood levels fluctuate satiety, while the lateral hypothalamic nucleus
widely. A large part of the daily output of may be regarded as a feeding center. This con-
growth hormone is secreted in bursts follow- cept, though useful, has proved too simplistic
ing the onset of sleep. Strenuous exercise, hy- to incorporate all of the information available
poglycemia , and testosterone also appear to about the appetitive and consummatory
stimulate growth hormone secretion. Somato- phases of ingestive behavior. The study of «-
-
and (J adrenergic receptor mechanisms in
feeding (85, 86 ) and electrophysiologic studies
to a state of supersensitivity ( 23). Further
secondary lesions involving the periaque-
in alert , behaving animals (122 ), have ex- ductal gray and the reticular formation may
tended the concepts based exclusively upon have a "taming" effect on this savage behav-
lesions or knife cuts, and suggest that neural ior ( 72 ). Hypothalamic-induced rage reac-
models that can explain feeding behavior may tions may be blocked by midbrain lesions,
be similar in principle to those used to explain indicating that structures at this level play a
the regulation of blood pressure and respira - role in the expression of savage and aggres-
tion. sive behavior.
It is generally accepted that morphophysio-
CONTROL OF EMOTIONAL BEHAVIOR logic substrates of abnormal and aggressive
behavior involve, in some differential and se-
The hypothalamus is regarded as one of lective fashion, predominantly structures of
the principal centers concerned with emo- the forebrain. This part of the central nervous
tional expression. It is acknowledged that the system contains the neural structures con-
physiologic expression of emotion is depen- cerned with goal-directed behavior, and the
dent on both sympathetic and parasympa - motivational and emotional concomitants that
thetic components of the autonomic nervous make such behavior possible. Impulses gener-
system . The hypothalamus, intimately relat- ated in sensory systems, the cerebral cortex,
ing both of these, probably is involved di - and still undetermined neural structures may
rectly or indirectly in most emotional reac- trigger mechanisms that excite visceral and so-
tions. Stimulation of the hypothalamus in matic systems whose activities in concert pro
unanesthetized cats with implanted elec- vide the physiologic expression of aggressive
trodes provokes responses resembling rage behavior.
and fear, which can t>e increased by graded
stimuli of different intensities ( 48, 66, 98). HYPOTHALAMUS AND SLEEP
These reactions, referred to as "pseudoaffec-
tive," are "stimulus- bound" in that they are Although hypothalamic lesions produce
present only during the period of stimula - somnolence resembling normal sleep ( 21,
tion . Different types of responses are elicited 153), the fact that sleep and sleep-like states
from different parts of the hypothalamus: can be produced by electrical and chemical
flight responses are most readily evoked from stimulation in a variety of structures within
lateral regions of the anterior hypothalamus, the brainstem makes it clear that there is no
while aggressive responses characterized by single "sleep center." The intralaminar and
hissing, snarling, baring of teeth, and biting reticular thalamic nuclei also seem to be con -
are seen with stimulation of the region of the cerned with the modulation of vigilance
ventromedial nucleus. Because the emo - states. Sleep induced by thalamic stimulation
tional reactions provoked by electrical stim - lasts for long periods of time and is compara -
ulation of the hypothalamus are directed, it ble to that occurring naturally. The pontine
seems likely that the cerebral cortex and reticular formation and the raphe nuclei con -
thalamus play important roles in these re- stitute a lower center concerned with the trig-
sponses . In these reactions, the hypothala - gering of paradoxical sleep. Nevertheless, the
mus cannot be regarded as a simple efferent idea that the hypothalamus may be involved
mechanism influencing onlv lower levels of in some aspects of the sleep-waking cycle has
the neuraxis. received support from recent studies by
Observations that selective stimulation Michel Jouvet and his colleagues in Lyon,
and lesions of the ventromedial nucleus of France. Following pharmacologic and electro-
the hypothalamus both produce aggressive physiologic experiments in freely moving
behavior ( 48, 112) raise questions concerning cats, these investigators suggested that neu-
the mechanism. Savage behavior after bilat - rons in the posterior hypothalamus, including
eral lesions of the ventromedial nucleus ( 48, the tuberomammillary nucleus, play an im-
193) cannot be assumed to result from release portant role in the arousal mechanism. Princi -
of inhibitory influences. Because animals with pally involved are neurons that contain hista -
such lesions never show spontaneous out - mine, project widely upon the cerebral cortex,
burst of aggressive behavior and this hyperir- and receive prominent afferents from the
ritable state develops slowly , it has been pos- forebrain and brainstem tegmentum (89, 90,
tulated that destruction of these nuclei leads 157).
17 Hypothalamus 739
References Menschen.| Psychol Neurol 1942; 31. Dahlstrbm A , Fuxe K . Evidence for
51:96-196. the existence of monoamine-con -
1. Anand BK , Brobeck JR . Hypothala -
mic control of food intake in rats
-
15. Brown Grant K , Raisman G. Re
productive function in the rat fol
-
-
taining neurons in the central ner -
vous system . I . Demonstration of
and cats. Yale J Biol Med 1951; lowing selective destruction of af - monoamines in the cell bodies of
24:123-140. ferent fibres to the hypothalamus brain stem neurons. Acta Physiol
2. Anand BK , Brobeck JR . Localiza -
tion of a "feeding center" in the hy-
from the limbic system . Brain Res
1972;46:13-42.
Scand 1%4;62(Suppl 232):l-55.
32. Daitz IIM , Powell TI*S. Studies of
pothalamus of the rat. Proc Soc Exp 16. Brownstein MJ , Mezey E. Multiple the connections of the fornix sys-
Biol Med 1951;77:323 324. - chemical messengers in hypothala- tem I Neurol Neurosurg Psychia -
3. Andersson B. Polydipsia , antidi- mic magnocellular neurons. Prog try 1954;17:75-82.
uresis and milk ejection caused by Brain Res 1986;68:161 - 168. 33. De Olmos JS. The amygdaloid pro-
hypothalamic stimulation. In: 17. Brownstein MJ , Russell JT, Gainer jection field in the rat as studied
Heller H , ed . Neurohypophysis. H . Synthesis, transport and release with cupric-silver method . In:
London: Butterworths, 1957:131- of posterior pituitary hormones. Eleftheriou BF., ed . The neurobiol -
140. Science 1980;207:373-378. ogy of the amygdala . New York:
4. Bard P. Central nervous mecha -
nisms for emotional behavior pat -
18. Bucher VM , Burgi SM . Some obser
vations on the fiber connections of
- Plenum Press, 1972:145-204.
34 . De Wied D. Behavioral actions of
terns in animals. Proc Assoc Res -
the di and mesencephalon in the neurohypophyseal peptides. Proc
Nerv Ment Dis 1939;19:190-218. cat. III . The supraoptic decussa - K Soc Fond ( Biol ) 1980;210:
5. Bjbrklund A, Lindvall O. tions. J Comp Neurol 1953,48: 183-195.
-
Dopamine containing systems in
the CNS. In : Bjbrklund A , I Ibkfelt 19.
355-379.
Buijs RM . Vasopressin and oxy -
35. IX* Wied D. The importance of va
sopressin in memory. Trends Neu
-
-
rosci 1984;7:62-63.
T, eds. Handbook of chemical neu -
roanatomy. Vol. 2. Part 1 : Classical
transmitters in the CNS. Ch. 3. Am -
tocin localization and putative
functions in the brain. Acta Neu -
rochir ( Wien ) 1990;47:86-89.
.
.36. Dreifuss )|, Murphy JT, C loor P.
Contrasting effect of two identified
-
sterdam: Elsevier, 1984:55 122. 20. Cachetto DF, Saper CB. Neuro- amygdaloid efferent pathways on
6. Bjorklund A , Skagerberg G . Evi - chemical organization of the hypo - single hypothalamic neurons. J
dence for a major spinal cord pro - thalamic projection to the spinal Neurophysiol 1968;31:237-248.
jection from the diencephalic A - ll cord in the rat . J Comp Neurol 37. Du Vigneaud V . Hormones of the
dopamine cell group in the rat 1988;272:579-604. posterior pituitary gland : oxytocin
using transmitter -specific fluores
cent retrograde tracing. Brain Res
- 21 . Cairns IF Disturbances of con-
sciousness with lesions of the
and vasopressin . Harvey Lect
1956;50:1-26.
1979;177:170 175. - brain-stem and diencephalon . 38. Emmers R . Interaction of neural
7 Bleier R , Cohn P, Siggelkow IK . A Brain 1952;75:109-146. systems which control body water.
cytoarchitectonic atlas of the hypo - 22. Cannon WB, Britton SW . Studies -
Brain Res 1973;49:323 347.
thalamus and hypothalamic third on the conditions of activity in en- 39. Epelbaum J . Intrahypothalamic
ventricle of the rat . In : Morgane P,
Panksepp J. eds. Handbook of the
docrine glands. XV . Pseudoaffec
tive medulliadrenal secretion. Am
- neurohormonal interactions in the
control of growth hormone secre -
hypothalamus. Vol . I : Anatomy of J Physiol 1925;72:283-294. tion. Ciba Found Symp 1992;168:
the hypothalamus. New' York:
'
23. Cannon WB, Rosenblueth A . The 54-64.
Marcel Dekker, 1979:137-220. supersensitivity of denervated 40. Everett JW. Central neural control
8. Bernard C. Lemons sur les structures. New York : Macmillan , of reproductive functions of the
phenomenes de la vie commune 1949 adenohypophysis. Physiol Rev
aux animaux et aux vegetaux . 24 . Card JP, Moore RY . Organization 1964;44:373-431 .
Paris: Baillfcre, 1878, 1879. of the lateral geniculate- hypothala - 41 . Frohman LA , Jansson JO. Growth
9 Blaustein JD, Lehman MN , Tur - mic connections in the rat J Comp -
hormone releasing hormone. En -
cotte JC, Greene G . Estrogen Neurol 1989;284:135-147. - .
docr Rev 1986;7:223 253
receptors on dendrites and axon 25. Ciriello J , Calaresu FR . Autoradi - 42. Fry W|, Krumins R , Fry FJ , Thomas
terminals in the guinea pig hypo- ographic study of ascending pro - G , Borbely S, Ades II . Origins and
thalamus. Endocrinology 1992; jections from cardiovascular sites distribution of some efferent path
131:281-290. in the nucleus tractus solitarii in ways from the mammillary nuclei
10. Blessing WW , Chalmers JP. Direct the cat . Brain Res 1980;180: 448-453. of the cat . j Comp Neurol
projection of catecholamine ( pre- 26. Ciriello J, Calaresu FR. Monosy - 1963;120:195-258.
sumably dopamine) containing naptic pathway from cardiovascu - 43. Fulton JF, Ingraham FD. Emotional
neurons from hypothalamus to lar neurons in the nucleus tractus disturbances following experimen -
spinal core. Neurosci Lett 1979; solitarii to the paraventricular nu - tal lesions of the base of the brain
11 :35-40. cleus ill the cat . Brain Res 1980; -
( pre chiasmal ) . J Physiol ( Fond )
11 BliH > m FE, Battenberg E, Rossier J , 193;529 533. — 1929;67:27-28.
Ling N , Guillemin R . Neurons con - 27. Cooper JR , Bloom RE, Roth RH . 44. Fuxe K , llokfelt T. Central mono-
taining (i-endorphin jn rat brain The biochemical basis of neu - aminergic systems and hypothala -
exist separately from those contain - ropharmacology. 6th ed . New mic function. In: Martini F, Motta
ing enkephalin: immunocytochem - York: Oxford University Press, M , Fraschini F, eds. The hypothala -
ical studies. Proc Natl Acad Sci 1991. mus. New York : Academic Press,
USA 1978;75:1591-1595. 28. Cowan WM , Raisman G, Powell -
1970:123 138.
12. Bodian D. Cytological aspects of TPS. The connections of the amyg- 45. Gash DM , Thomas GJ . What is the
neurosecretion in opossum neuro - dala. J Neurol Neurosurg Psychia - importance of vasopressin in mem -
hvpophvsis. Bull Johns I lopkins
Hosp 1963,113:57 93. - -
try 1965;28:137 151.
29. Cowan WM , Guillerv RW, Powell
ory processes? Trends Neurosci
1983;6:197-198.
13. Bodian D . Herring bodies and TPS. The origin of the mammillary 46. Giovannelli F, Shiromani PJ ,
-
neuro apocrine secretion in the peduncle and the hypothalamic Jirikowski GF, Bloom FE. Expres-
monkey: an electron microscopic connexions from the midbrain. J sion of c- fos protein by immunohis-
study of the fate of the neurosecre- Anal 1964,•98:345-363. tochemically identified oxytocin
tory product. Bull Johns Hopkins 30. Cruce JAF. An autoradiographic neurons in the rat hypothalamus
Hosp 1966;!18: 282-326. study of the projection of the de- upon osmotic stimulation . Brain
14. Brockhaus IF Beitrage zur nor - scending connections of the mam- Res 1992;588:41-48.
malen Anatomie des Hypothala- millothalamic tract in the rat . Brain 47. Gloor P. Electrophysiological stud -
mus und der Zona incerta beim Res 1975;85:211 - 219. ies on the connections of the amvg-
daloid nucleus in the cat . Elec- the vertebrate hypothalamo-neuro- melanocyte stimulating hormone
troencephalogr Clin Neurophysiol hvpophvsial system. Br M Bull ( alpha - MSIl ) and have cortical
1955,7:243 264 1488;22:227 - 231 projections in the rat . Neurosci Eetl
48 Glusman M . The hypothalamic 85. Hendrickson AE, Wagoner N . 1484;49:39-43.
"savage” syndrome. I rix ASMK
’ Cowan W'M . An autoradiographic 74. krieger DT, l iotta AS. Pituitary
Kes Nerv Mont Dis 1974;52:52- 92 and electron microscopic study of hormom^ in brain: where, how
49. Gorski RA , C Jordon III, Shryne |H, retinohypothalamic connections. and why ? Science 1974;205:
Southam AM . Evidence for a mor- 7. Zellforsch Mikrosk Anat 1472; .388- 372.
phological sex difference within 135:1- 28. 80. kuhlenbeck II Derivation and
the medial preoptic area of the rat 88. Hess WR . Diencephalon, auto- boundaries of the hypothalamus,
brain. Brain Res 1978;148:333- 340. nomic and extrapvramidal func- with atlas ot hypothalamic grisea .
50. Gorski RA , Harlan RE, )acobson tions. New York: Grune & Stratton. In: Haymaker W , Anderson E,
IX , Shryne JE , Soulham AM. Evi- 1954. Nauta WJH, eds. The hypothala -
dence for the existence of a sexu - 87. I letherington AW . Ranson SW . mus Ch. 2 . Springfield, IE: Charles
ally dimorphic nucleus in the pre- I lypothalamic lesions and adipos- C. Thomas, 1989;| 3-80
optic area of the rat . J Comp ity in the rat . Anat Rec 1940,78: 81 . kuptermann I Hypothalamus and
Neurol 1980; 193:529- 534. 144- 172 . limbic system: peptidergic neu-
51 Green )D, Harris GW . Observation 88 1 lotman VIA , Swaab DF. The sexu- rons, homeostasis, and emotional
of the hvpophvsioportal vessels of ally dimorphic nucleus of the pre- behavior. In: kandel ER. Schwartz
the living rat . I Physiol ( Eond ) optic area in the human brain: a 111, Jessell TM, eds. Principle's of
1444; 108: 3 » 3o | .
- comparative morphometric study . neural science. Ch. 47. New York:
52 ( .ross I’Med.. Circumventricular
, | Anat 1484; 184:55-72. .
l Isevier, 1991:735 749
organs and body fluids. Boca 89 Hbkfelt T, Johansson O, l uxe K , 82. Ee Gros Clark WE. The topogra-
Raton, EL: C RC Press, 1987.
'
Goldstein M, Park D. Irnmumv- phy and homologies ot the hvpo-
53. IX * Groot ) , I larrisGW I lypothala- histochemical studies on the thalamic nuclei in man. | Anat
mic control of the anterior pitu- localization and distribution of 1938;70:203-218.
itary gland and bltmd lympho- momximine neuron systems in the 8.3. Le Gros Clark WE. Beattie I , Rid -
cytes. j Physiol ( Eond ) 1950;I 1 E rat brain. I . Tyr» »sine hydroxylase .
doch C, Dott NM. eds . The hypo-
335-340 in the mes- and diencephalon. Mix! thalamus. Edinburgh: Oliver and
54 Guillory RW Degeneration in the Biol I 978;54 :427 4 53. Boyd, 1438.
posterior commissural fornix and 70. Hbkfelt T. Meister B. Villar MJ , et 84 . Lehman MN. Winans SS.
the mammillary peduncle of the al. Hypothalamic neurosecretory Vomeronasal and olfactory path-
rat . | Anat 1458;90:350- 370. systems and their messenger mole- ways to the amygdala controlling
55 Guillery RW Degeneratii»n in the cules. Acta Physiol Scand 1989; male hamster sexual behavior: au-
hypothalamic connections of the 583:105- 111 toradiographic and behavioral
aibinorat. | Anat 1957;91:91- 115 71 llosoya Y , Matsushita M . Identifi- analyses. Brain Res 1982;240:27-11.
58 I lall EA . Efferent connections of cation and distribution of the 85. Eeibowitz SF. Brain calecholamin-
the basal and lateral nuclei of the spinal and hypophyseal projection ergic mechanisms for control of
amygdala in the cat Am | Anat neurons in the paraventricular nu- hunger . In: Novein D, Wvriecka
|403;H 3: 134 151 cleus of the rat : a light and electron W , Bray GA , eds. Hunger: brain
57. Harris GW . Electrical stimulation microscopic study with the horse- mechanisms and clinical implica-
of the hypothalamus and the radish peroxidase moth* !. Exp tions. New York: Raven Press,
mechanism of neural control of the Brain Res 1979;35:315-331.
* 1978:1- 18.
adenohypophysis. | Physiol (Eond ) 72. Ilunsperger RW . Affektreaktionen 88. Eeibowitz SF. 1 lypothalamic neu-
1948;107:418-427. auf elektrische Rei/ung im Hirn- rotransmitters in relation to nor -
58 1 larris GW . Neural control ot the stamm der Kat / e. I lelv Physiol mal and disturbed eating patterns.
pituitary gland. Eondon: Edward Pharmacol Acta 1458;14:70-42. Ann NY Acad Sci 1487;449:
Arnold and Company , 1455 73. Ingram WR . Brain stem mecha- 137 143.
5M | larris GW , George R . Neurohu- nisms in behavior. Eloctrt *n- 87. Leichnetz GR , Astruc I The effer-
moral control ot the adenohypophy- cephalogr Clin Neurophvsiol W52;
* ent projections ol the medial pre-
sis and regulation of the secretion l 397 408 frontal cortex in the squirrel mon -
of TSH, ACT11 and growth hor- 74 . Kalra Sl \ Crowley WR. Neuropep- key (Snitniri sen/ mis). Brain Res
mone . In: Haymaker W , Anderson tide Y: a novel neuroendocrine 1978;104:455-472.
E , Nauta W |l I , eds. The hypothala - peptide in the control of pituitary .
88. I eng ( , Dyball RE, Euckman SM .
Ch. 10. Springfield, IE:
mus. hormone secretion, and its relation Mechanisms of vasopressin secre-
Charles C. Thomas, 1984:328- 388. to luteini / ing hormone. Front Neu - tion. Ilorm Res 1992;37:33-38.
h0 Harris GW , Wtx ds JW The effect
* roendocrinol 1442 ; 13: 1 -48 84. Lin |S, Sakai k , Jouvet M Evidence
ot electrical stimulation of the hy - 75. Kevser A . Development ot the hy - tor histaminergic arousal mecha-
pothalamus or pituitary gland on pothalamus in mammals: an inves- nism in the hypothalamus of
thyroid activity . J Physiol ( Eond ) tigation into its morphological po- cat Neuropharmacology I 988;27:
1958, 143: 248 274
.
sition during ontogenesis. In : - .
111 122
81 . Ilartwig 11C. Electron microscopic Morgane P|, Panksepp I . eds. .
90. Ein |S, Sakai k Vannier - Mercier G,
evidence for a retinohypothalamic Handlxmk of the hypothalamus. louvet M . A critical role of the jx »s-
projection to the suprachiasmatic New York : Marcel IX'kker . 1474: terior hypothalamus in the mecha-
nucleus of Passer ifamrsticus. Cell 85- 138. nisms of wakefulness determined
Tissue Res 1474;153:88- 94 78. Kievit |. Kuypers HC»|M. Basal by microinjection of muscimol in
82 Haymaker W I Ivpothalamo-pitu- forebrain and hypothalamus con- freely moving cats. Brain Res 1984;
itary neural pathways and the cir - nections to frontal and parietal cor - 474:225- 240
culatory system of the pituitary In tex in the rhesus monkey Science 91 Loewy AD Descending pathways
Haymaker W , Anderson E, Nauta 1475;187:880-883. to sympathetic and parasympa -
W |H, ixls The hypothalamus Ch. 77. kita II. Oomura Y An IIRP study thetic preganglionic neurons J
8. Springfield, IE: Charles C ot the afferent connections to the Auton Nerv Svst 1981;3:285- 275.
Thomas, 1484214-250. rat hypothalamic region. Brain Res 42 . MacEusky N|, Naftolin F. Sexual
8.3. Ilcimcr E, Nauta WJII . The hvpo- Bull 1482;8:83-71 . differentiation of the central ner -
thalamic distribution of the stria 78. kohler C, Swanson LW Acetyl- vous system . Science 1981;2I I :
terminalis in the rat Brain Res cholinesterase-containing cells in 1294— 134)2.
1484;| 3 284 247. the lateral hypothalamic area 43 McBride RE . Sutin I Amygdaloid
84 . Heller IE The hormone content of are immunoreactive tor alpha - and pontine projections to the ven-
17 Hypothalamus 741
tromedial nucleus of the hypothal - hamster. Vis Neurosri I 992;8: 124 . Page RB . The anatomy ot the hypo-
amus. J Comp Neurol 1977;174: -
219 230. thalanio- hypophyseal complex. In :
-
377 3%. 109. Muller EH. Neural control of soma- Knobil KH , ed . The physiology ot
94. McEwen BS. Neural gonadal totropic function. Physiol Rev reproduction . New York: Raven
steroid actions. Science 1981 ; -
1987;67:962 1053. Press, 1988: 1161-1233.
211:1303-1311 . 110. Muller - Preuss P, Jurgens U . Projec- 125. Page RB, Bergland RM . The neuro-
95. McKinley MJ, Badoer E, Oldfield tions from the "cingular" vocaliza - hypophyseal capillary bed . I
B|. Intravenous angiotensin II in - tion area in the squirrel monkey. Anatomy and arterial supply . Am J
-
duces Fos immunoreactivity in cir - Brain Res 1975;103:29-43. Anat 1977;148:345-357.
cumventricular organs of the lam - 1 1 1. Nakamori T, Morimoto A , Yam - 12b. Palay SI .. The fine structure of the
ina terminalis. Brain Res 1992;594: aguchi K, Watanabe T, l ong NC, neurohypophysis. In : Waelsch 11,
293-300. Murukami N . Organum vasculo - ed . Ultrastructure and cellular
96 McKinley MJ , Oldfield BJ . Circum- sum laminae terminalis (OVLT ) is chemistry of neural tissue. New
ventricular organs. In : Paxinos G . a brain site to produce interleukin - York: Paul B. Hoeber, 1957:31 344
ed . The human nervous system. l|i during fever. Brain Res 127. Palkovits M . Catecholamines in the
Ch . lb. New York: Academic Press. 1993;618:155-159. hypothalamus: an anatomical re -
97.
1990:415-438.
Markee JE, Sawyer Cl I, Hol -
112. Nakao II . Emotional behavior pro
duced by hypothalamic stimula
-
-
--
view . Neuroendocrinology 1981;
33:123 128.
linshead VVII . Activation of the an -
terior hypophysis by electrical
stimulation in the rabbit . En -
docri nology 194 b; 38: 345-357.
—
tion . Am j Phvsiol 1958;194:
411 118.
113. Nathan PW, Smith MC . The loca
tion of descending fibres to sympa -
-
128 Palkovits M . Peptidergic neuro-
transmitters in the endocrine hy
pothalamus. Ciba Found Symp
1992;168:3-10.
-
98. Masserman JH . Behavior and thetic neurons supplying the eye 129 Pantila P, Airaksinen MS, Pirvola
neurosis. Chicago: University of
Chicago Press, 1943.
and sudomotor neurons supplying
the head and neck. J Neurol Neu -
U, Kotilainen E. A histamine con -
taining neuronal system in human
-
99. Meibach RC, Siegel A . Efferent ri >surg Psychiatry 198b;49: l 87. brain . Neuroscience 1990;34:
connections of the hippocampal 114 . Nauta WJII . An experimental 127-132.
formation in the rat . Brain Res study ot the fornix in the rat . J 130. Parent A. Anatomical organization
1977;124: 197-224 . Comp Neurol 1956;104:247-272. of monoamines- and acetyl -
100. Mesulam V1- M , Geula C, Both well 115. Nauta WJH. Hippt *ampal projec-
'
cholinesterase-containing neuronal
MA , Hersh LB. Human reticular tions and related neural pathways systems in the vertebrate hypothal -
formation: cholinergic neurons of to the midbrain in the cat. Brain amus . In : Morgane PJ, Panksepp |,
the pedunculopontine and lat - 1958;81:319-340. eds. Handbook of the hypothala -
erodorsal tegmental nuclei and 11 b. Nauta WJH. Fibre degeneration mus. Vol . I : Anatomy of the hypo -
some cytochemical comparisons to following lesions of the amyg- thalamus. Newr York : Marcel
forebrain cholinergic neurons. | daloid complex in the monkey . J Dekker, 1979:511-554.
Comp Neurol 1989;283:611-633. -
Anat 19b1 ,95:515-531. 1.31 . .
Parent A Butcher IX. Organiza -
-
101 Mesulam M M , Mufson EJ , Levey 117. Nauta VV|H. Some efferent connection and morphologies of acetyl -
AL Wainer BH. Cholinergic inner - tions of the prefrontal cortex in the cholinesterase-containing neurons
vation of cortex by the basal tore
brain : cytochemistry and cortical
- monkey. In : Warren JM, Akert K ,
eds. The frontal granular cortex
in the thalamus and hypothalamus
of the rat . J Comp Neurol 197b ,
connections of the septal area , di -
agonal band nuclei, nucleus
and behavior. New York: Mc
Graw - Hill , 1964:397-409.
- -
132 .
I 7t ):205-22b.
Parent A , Descarries L, Beau del A
basalis (substantia innominata ) 118. Nauta WJH, Haymaker W . Hypo- Organization of ascending sero-
and hypothalamus in the rhesus thalamic nuclei and fiber connec - tonin systems in the adult rat
monkey. I Comp Neurol 1983; tions. In: Haymaker W , Anderson brain. A radioautographic study
214: 1711-197.
.
102. Millhouse OF. A C olgi anatomy of
I . Nauta W|11 tils The hypothala
,
.
mus. Ch. 4. Springfield IL : Charles
- after intraventricular administra -
tion of TUI 5- hydroxytryptamine .
the rodent hypothalamus. In . Mor - C. Thomas, 1969: 136 209.- Neuroscience 1981 ;6:115- 138
gane P, Panksepp J , eds. Hand - 119. Nilaver G, Zimmerman EA , 13.3. .
Parent A , Poirier LJ Boucher R.
book ot the hypothalamus. Vol. I: Wilkins |, Michaels J , Hoffman I ), Butcher I.I .. Morphological charac -
Anatomy of the hypothalamus. Silverman AJ . Magnocellular hy - teristics of acetylcholinesterase -
New York: Marcel Dekker, 1979; pothalamic projections to the containing neurons in the C NS of
221 2 h 5 . lower brain stem and spinal cord -
DFP treated monkeys. Part II . Di -
103. Moore RY . Retinohvpothalamic of the rat. Ncuroondt >crinologv encephalic and medial telen -
projection in mammals: a compar - 1980;30:150-158.
120. Olivecrona H. Paraventricular nu -
cephalic structure's. J Neurol Sci
1977;32:9-28.
ative study. Brain Re’s 1973;49:
403-409. cleus and the pituitary gland . Acta 134 Pelletier G , Desy L, Cote I , Vnudry
104. Moore RY . The fourth C.U . Ariens Physiol Scand 1957;40:(Suppl II . Immunocytochemical localiza -
Kappers lecture. The organization 136) 1-178. tion of corticotropin - relcasing-fac-
of the human circadian timing sys- 121 . Ono T, Nichino H , Sasaka K , Mu - tor- like immunoreactivity in the
tem . Prog Brain Res 1992;93: ramoto K, Yano I , Simpson A . Par - human hypothalamus. Neurosci
99 113. aventricular nucleus connections Lett 1983;41:259-263.
105. Moore RY , Lenn NJ . A retinohypo - to spinal cord and pituitary. Neu - 135. Pfaff DW, Keiner M . Estradiol -con -
thalamic projection in the rat . J rosci Lett 1978;10:141-146. centrating cells in the rat amygdala
Comp Neurol 1972; 146: 1 -14. 122. Ono T, Oomura Y , Sugimori M, et -
as part of a limbic hypothalamic
10b. Moore RY , Speh JC. GABA is the al . Hypothalamic unit activity re- -
hormone sensitive system . In
principal neurotransmitter of the lated to lever pressing and eating F.leftheriou BE, ed . The neurobiol -
circadian system. Neurosci Lett in the chronic monkey . In : Novin ogy of the amygdala. New York
-
1993;150:112 116. D, Wyrwicka WR , Bray C A, eds . Plenum Press, 1972 : 775- 783
107. Morin I . P, Michels KM . Smale L . Hunger: basic mechanisms and 13b. Phillips Ml , Felix D, Hoffman WE,
Moore RY. Serotonin regulation of clinical implications. New York: -
Ganten A . Angiotensin sensitive
circadian rhythmicitv . Ann NY Raven Press, 1976:159-170. sites in the brain ventricular svs-
Acad Sci 1990;600:418-426. 123. Otori Y, Tominaga K , Fukuhara C, tem . Neurosci Symp 1977;2:
.
108 Morin I P, Blanchard J Moore RY. et al . Substance P- like immunore- 308-339.
Intergeniculate leaflet and supra - activity in the suprachiasmatic nu - 137. -
Pickard GI \ , Silverman A J . Direct
chiasmatic nucleus organization cleus of the rat . Brain Res 1993; retinal projection to the hypothala -
and connections in the golden 619:271-277. mus, piriform cortex, and acres-
sory optic nuclei in the golden 154. Renaud LP, Allen AM, Cunning - Magnocellular neurosecretory sys -
hamster as demonstrated by a sen - ham JT, et al . Synaptic and neuro- te*m . Annu Rev Neurosci 1983;6:
sitive anterograde horseradish per - transmitter regulation of activity in 357 no
oxidase technique. | Comp Neurol mammalian hypothalamic magno- 171 . Silverman AJ , Pickard GE. The hy -
-
1981;196:155 172. cellular neurosecretory cells. Prog pothalamus. In : Emson PC, ed .
138. Pickford M Neurohypophysis an - - Brain Res 1992;92:277-288. Chemical neuroanatomy. New
tidiuretic ( vasopressor ) and oxyto- 155. Rioch DM, YVislocki CB, O' Leary York: Raven Press, 1983:295-336.
cic hormones. In : Haymaker YV, |L . A precis of preoptic, hypothala - 172. Skeen LC, Hall YVC . Efferent pro-
Anderson E, Nauta WJH, eds. The mic and hypophyseal terminology jections of the main and the acces-
hypothalamus. Ch. 13. Springfield, with atlas. In: Fulton JF, ed . The sory olfactory bulb in the tret*
III : Charles C. Thomas, 1969. hypothalamus and central levels of shrew iTupaia ‘y/ /s ). J Comp Neurol
463-505. autonomic function. Assoc Res 1977;172:1-36.
139. Pierson R) .Carpenter MB. Nerv Ment Dis 1939;20:3-30. 173. Stevenson JAF. Effects of hypothal -
Anatomical analysis of pupillary 156 Sadum A A, Schaechter JD, Smith amic lesions on water and energy
reflex pathways in the rhesus mon - LEH . A retinohypothalamic path- metabolism in the rat . Recent Prog
key . j Comp Neurol 1974;158: way in man: light mediation of cir- Horm Res 1949;4:363 394. -
121-143. cadian rhythms. Brain Res 1984; 174. Stevenson JAF. Neural control of
140. Poitras D, Parent A . A fluorescence .302:371-377. food and water intake. In: Hay -
microscopic study of the distribu - 157. Sakai K , Yoshimoto Y, Luppi PH , maker YV, Anderson E, Nauta
tion of moniximines in the hypo- et al . Lower brainstem afferents to YVJH, eels . The hypothalamus. Ch .
thalamus of the cat. J Morphol the cat posterior hypothalamus: a 15. Springfield , IL: Charles C.
1975;145:387-408. -
double labeling study. Brain Res Thomas, 1969:524-621 .
141. Poitras D, Parent A . Atlas of the Bull 1990;24:437-55 175. Stumpf YVE. Estrogen - neurons and
distribution of montximine-con- 158. Saper CB Convergence of auto- estrogens-neuron systems in the
taining nerve cell bodies in the nomic and limbic connections in periventricular brain . Am J Anat
brain stem of the cat . |Comp Neu - the insular cortex of the rat. J 1970;129:207-217.
rol 1978;179:699-718. Comp Neurol 1982;210:163-173. 176. Sutin J . The periventricular struc-
142. I'opa GT, Fielding U . A portal cir - 159 Saper CB. Organization of cerebral tures of the hypothalamus. Int Rev
culation from the pituitary to the cortical afferent system in the rat . N eu re >biologv 1966;9:263-300.
hypothalamic region , j Anat 1930; II . I lypothalamocortical projec - 177. Swaab DF, Fliers E . A sex -
65:88-91 . tions. J Comp Neurol 1985;237: ually dimorphic nucleus in the
.
143 Porrino LJ Goldman- Kakic PS. -
21 46. human brain . Science 1985;228:
Brainstem innervation of pre- 160. Saper CB. Chemical neuroanatomy 1112-1115.
frontal and anterior cingulate cor - of Alzheimer's disease. In : Iversen 178. Swanson LYV , Cowan YVM A note
tex in the rhesus monkey revealed SD, Snyder SH, eds. Handbook of on the connections and develop-
by retrograde transport of HRP ) psychopharmacology . Vol . 20. ment of the nucleus accumbens.
Comp Neurol 1982;205:63-76. New York: Plenum Press, 1988: Brain Res 1975,92:324-330.
144 . Porter jC, Jones JC. Effect of 131-156. .
179. Swanson LYV Cowan YVM . An au -
plasma from hypophyseal-portal
vessel blood on adrenal ascorbic
161 . Saper CB. Hypothalamus. In: Paxi
m >s G, ed . The human nervous sys
-
-
toradiographic study of the organi
zation of the efferent connections
-
acid. Endocrinology 1956;58:62-67. tem. Ch . 15. New York : Academic of the hippixrampal formation in
145. Powell Tl’S, Guillerv RYV, Cowan Press, 1990:389-413. the rat. J Comp Neurol 1977;172:
YVM . A quantitative study of the 162 . Saper CB, German DC. Hypothala - -
49 34.
-
fomix mammillo-thalamic system. mic pathology in Alzheimer ' s dis - 180. Swanson LYV, Cowan YVM , Jones
-
|Anat 1957;91 : 419 432.
146. Price |E , Amaral DC. An autoradi -
ease. Neurosci Lett 1987;74:364-
370.
EG. An autoradiographic study of
the efferent connections of the ven -
ographic study of the projections 16.3. Saper CB, Loewv AD, Swanson tral lateral geniculate nucleus in
of the central nucleus of the mon - LYV , Cowan YVM . Direct hvpothal- the albino rat and the cat. J Comp
key amygdala. J Neurosci 1981;!: -
amo autonomic connections. Brain Neurol 1974;156:143 163. -
1242-1259 Res 1976;117:305-312. 181. Swanson LYV. Kuypers HGJM . The
147. Raisman G. Neural connections of 164 . Sawyer CH . Nervous control of paraventricular nucleus of the hy -
hypothalamus. Hr Med Bull 1966; ovulation . In: Lloyd CW , ed . En- pothalamus: cytoarchitectonic sub-
22.197-201. docrinology of reproduction . New divisions and organization of pro-
148. Raisman G . The connexions of the York : Academic Press, 1959:1 - 18. jections to the pituitary , dorsal
septum. Brain 1966;89:317-348. 165. Scalia F, YVinans SS. The differen - vagal complex, and spinal cord as
149. Raisman G. An evaluation of the tial projections of the olfactory demonstrated bv retrograde fluo-
basic pattern of connections be- bulb and accessory olfactory bulb rescence double-labeling methods.
tween the limbic system and the in mammals. J Comp Neurol 1975; J Comp Neurol 1980;194:555-570.
hypothalamus. Am J Anat 1972; 161:31-56. 182. Swanson LYV, Sawchenko PE. Par-
-
129:197 202. 166. Schally AV , Kastin AJ , Arimura A . aventricular nucleus: a site for the
150. Raisman G, Cowan WM , Powell I lypothalamic hormones: the link integration of neuroendocrine and
Tl’S. The extrinsic afferent, com - between brain and body. Am Sri autonomic mechanisms. Neuroen -
missural and association fibre's of 1977;65:712-719. dtxTinologv 1980;31:410 417. -
the hippocampus. Brain 1965;88: 167. Scharrer E , Scharrer B. Hormones 183. Szentagothai J , Flerko B, Mess B,
%3 996. produced by neurosecretory cells. Halasz B. Hypothalamic control of
151. Raisman G, Cowan YVM, Powell Recent Prog Horm Res 1954 , 10: the anterior pituitary: an experi -
Tl’S. An experimental analysis of -
183 232. mental - morphological study. Bu -
the efferent projections of the hip - 168. Scheithauer BYV , Horvath E, Ko- dapest : Akademiai Kiado, 1968.
pocampus. Brain 1966;89:83-108.
152. Raisman G, Field PM . Sexual di -
vacs K . Ultrastructure of the neu - .
184. Tigges J YValker LC, Tigges M .
Subcortical projections to the oc -
rohypophvsis. Microsc Res Tech
morphism in the neuropil of the -
1992;20:177 186. cipital and parietal lobes of the
preoptic area of the rat and its de- 169. Sehwaber JS, Kapp BS, Higgins chimpanzee brain. J Comp Neurol
pendence on neonatal androgen. GA , Rapp PR . Amygdaloid and 1983;220:106-115
-
Brain Res 1973;54:1 29. basal forebrain direct connections 185. Tindall GT, McLanahan CS. Hv -
153. Ranson SYV . Somnolence caused by with the nucleus of the solitary pertunctional pituitary tumors:
hypothalamic lesions in the mon - tract and the dorsal motor nucleus. pre- and postoperative manage-
key . Arch Neurol Psychiatry 1939; I Neurosci 1982;2:1424-1438. ment considerations. Clin Neuro-
41:1-23. 170. Silverman AJ , Zimmerman EA . surg 1980;27:46-82.
17 Hypothalamus 743
186. Tucker IX ', Saper CB. Neural con - Neurotransmitters of the hypothal- tions of the posterior hypothala -
nections of an infralimbic cortical amic suprachiasmatic nucleus: im - mus in the cynomolgus monkey
pressor area . Soc Neurosci Abst munohistochemical analysis of 25 ( Macaco funicular it ). II . Efferent
1984;10:606. neuronal antigens. Neuroscience connections. ) Comp Neurol 1982;
187. Valenstein FS, Nauta WJII . A com - 1985;15:1049-1086. 207:135-156.
parison of the distribution of the 190. Vandesande F, Dierickx K . The ac- 192. Verney FB. The antidiuretic hor-
fornix system in the rat , guinea tivated hypothalamic magnocellu- mone and factors which determine
pig, cat and monkey. J Comp Neu - lar neurosecretory system and the its release. Proc R Soc Fond ( Biol )
rol 1959;113:337-363.
188. Valverde F. Studies on the piriform
one neuron-one neurohypophysial -
1947;135:25 106.
hormone concept . Cell Tissue Res 193. Wheatley MD. Hypothalamus and
lobe. Cambridge: Harvard Univer- 1979;200:29-33. affective behavior in cats. Arch
sity Press, 1965.
189. Van den Pol AN , Tsujimoto KL.
.
191. Vea / ey RB, Amaral IX’, Cowan
VVM. The morphology anil connec-
Neurol Psychiatry 1944;52: 296-
316.
18
Limbic System
LIMBIC LOBE VERSUS LIMBIC SYSTEM ever, the remarkable increase over the past
ten years in the use of the concept of limbic
On the medial surface of the cerebral system in both experimental and clinical liter-
hemisphere, a large arcuate convolution , ature indicate that such collective terms serve
formed primarily by the cingulate and a useful purpose ( 109).
parahippocampal gvri , surrounds the rostral
brainstem and interhemispheric commis-
Limbic Lobe
sures. These gyri, which encircle the upper
brainstem, constitute what the French neurol - The limbic lobe includes the subcallosal,
ogist Paul Broca referred to as the "grand cingulate, and parahippocampal gyri , as well
lobe limbique" ( limbus is Latin for "border" ) as the underlying hippocampal formation
( Fig. 18.1 ) ( 38) . Interest in the limbic lobe was and dentate gyrus ( Fig. 18.1 ) . The limbic lobe
heightened in 1937 when James Papez, a neu - consists of arcliicortex ( hippocampal forma-
roanatomist at Cornell University, suggested tion and dentate gyrus ), paleocortex ( piriform
that limbic structures form a complex neu - cortex of the anterior parahippocampal
ronal network involved in emotional behav - gyrus ), and juxtnllocortex or mesocortex ( cingu -
ior ( 193). Since that time, the bulk of experi - late gyrus ) . The juxtallocortex or mesocortex
mental data has revealed that the limbic lobe represents a type of cortex that is transitional
has profuse connections with the olfactory between allocortex and neocortex. Some au -
system, the hypothalamus (Chapter 17), the thors have additionally included the cortex of
thalamus (Chapter 16), and various areas of the posterior orbital surface of the frontal
the neocortex (Chapter 20 ) . It is intimately lobe, the anterior insular region , and the tem-
implicated in the higher integration of vis- poral polar region . The striking feature of the
ceral, olfactory , and somatic information, as limbic lobe is that it appears early in phylogen-
well as the patterning of complex long and esis and possesses a certain constancy in
short term homeostatic responses. These re- gross and microscopic structure. As men -
sponses include various types of fundamen - tioned , the extent to which these various cor-
tal behaviors that ensure the survival of the tical areas form a functional unit is not fully
individual and the species (e.g., feeding, mat - understood ( 109, 121 ).
ing, emotional responses, and motivational
states) ( 284 ). Limbic System
The concept of the limbic lobe was later
expanded by Paul MacLean to include other An even more extensive and inclusive des-
structures functionally and anatomically re- ignation is the limbic system . This term is used
lated to those described by Papez (142 ). to include all of the limbic lobe ( Fig. 18.1 ) as
MacLean considered the hypothalamus, the well as associated subcortical nuclei ( Fig .
septal area, the nucleus accumbens ( a part of 18.10), such as the amygdaloid complex, sep-
the striatum ), neocortical areas such as the or- tal nuclei, hypothalamus, epithalamus, vari-
bitofrontal cortex, and the amygdala, as part ous thalamic nuclei, and part of the basal
of what he called the "limbic system" (142, ganglia ( 142, 143). The medial tegmental re-
143). gion of the midbrain also is regarded as a
The terminology applied to structures be- part of the limbic system since this region
longing to the limbic lobe is extremely com- contains both ascending and descending
plex and there is still much controversy re- pathways which directly or indirectly are re-
garding the rational basis for defining the lated to the hippocampal formation and the
limbic lobe or limbic system ( 109, 121 ). How - amygdaloid nuclear complex ( Figs. 18.2 and
744
Figure 18.1 . Medial surface of the hemisphere Shading indicates the limbic lobe that encircles the upper brainstem
Although the cortical areas designated as the limbic lobe have some common structural characteristics, the extent
to which they form a functional unit is not clear
Mommiilotholamic tract
Stria medullaris
Habenulo
y
V\ Pineal
Thalamui _ Fasciculus retroflexus
A / Mammillotegmental tract
Septa i : .C
regjprr '
^
Medial forebrain — Central gray
bundle
Dorsal tegmental nucleus
RiD
Optic chiaSm
; \ \
Ventral tegmental nucleus
\ \
Hypophysis
Interpeduncular V
Mammillary peduncle
nucleus
Mammillary body Superior central nucleus
Figure 18.2. Limbic pathways interrelating the telencephalon and diencephalon with medial midbrain structures .
The medial forebraln bundle and efferent fibers of the mammillary body are shown in black The medial forebrain
bundle originates from the septal and lateral preoptic regions, traverses the lateral hypothalamic area, and projects
into the midbrain tegmentum. Fibers from the midbrain also ascend in the medial forebrain bundle. The mammillary
princeps fasciculus divides into two bundles, the mammillothalamic tract and the mammillotegmental tract. Ascend-
ing fibers of the mammillary peduncle, arising from the dorsal and ventral tegmental nuclei (of Gudden). are shown
In red Most of these fibers pass to the mammillary body, but some continue rostrally to the lateral hypothalamus, the
preoptic regions, and the medial septal nucleus via the medial forebrain bundle. Fibers arising from the septal nuclei
project caudally in the medial part of the stria medullaris ( blue) to terminate in the medial habenular nucleus, Im-
pulses conveyed by this bundle are distributed to midbrain tegmental nuclei via the fasciculus retroflexus .
Limbic brain stem connections
Cingulate gyrus
Entorhinal
r cortex
« Hippocampus
v Subiculum
4
Fornix
Thalamus
//, Ant
* Habenula
/
/ nuc .
^ Central gray
/
/
Anterior / i I 7
%Mesencephalic
commissure / i Hypothalamus tegmentum
i
MB
Septal area
Medial forebrain bundle
Diagonal band
of Broca % Amygdala
Figure 18.3 . Major interconnections of structures that form the limbic system. Projection fibers arising from the subicu-
lum (b/ue) project via the fornix to the septal area, hypothalamus, and mesencephalic tegmentum. Fibers projecting
In the fornix from the hippocampal formation are shown in black -dashed lines. Projections from the septal area to the
hippocampus are shown in red, MB indicates mammillary body .
18.3) (176). Despite the heterogeneity and dif - trast, only 20-30 % of the differentiated cells
fuse nature of the limbic system, there are from presumptive sensorimotor cortex ex-
compelling observations that structures compress LAMP. Thus, most cortical progenitors
prising this system are involved in neural cir- are fated to a limbic or nonlimbic phenotype
cuitry that gives rise to a subcortical continu - early in development, and the decision by
um that begins in the septal area and extends neuronal stem cells to differentiate into neu -
in a paramedian zone through the preoptic rons exhibiting this molecular phenotype oc -
region and hypothalamus into the rostral curs prior to the completion of neurogenesis
mesencephalon (179). This longitudinal con- in the absence of subcortical environmental
tinuum has extensive reciprocal connections cues (67). LAMP is also a valuable marker for
with the amygdala and the substantia innom- limbic structures in monkeys. As shown in
inata. Figure 18.4, the hippocampal formation , the
Molecular biologic studies revealed that hypothalamus, as well as the amygdaloid
structures belonging to the limbic system complex and its dorsal extension , all display
possess a distinct chemical phenotype (134). a strong immunoreactivity for this protein .
These neurons contain the limbic system -asso- The role of the cerebral cortex in the sub-
ciated membrane protein ( LAMP ), which is a jective aspects of emotion has been empha -
cell surface glycoprotein that is expressed sized repeatedly, yet the neocortex appears to
early in development (105). Transplantation have relatively few hypothalamic connec -
studies in the rat suggest that cells in the cere- tions. Both the amygdala and the substantia
bral wall are committed to a limbic or non - innominata have reciprocal connections with
limbic molecular phenotype by embryonic regions of the cerebral cortex, although pro-
day 14 ( E14 ) (23). Furthermore, in vitro exper - jections from these structures to the cortex are
iments have shown that after 4 days in cul- most extensive. These nuclear masses appear
ture, up to 75% of the progenitor cells from to represent the principal interface between
presumptive limbic cortex ( perirhinal area ) visceral and autonomic centers in the hypo-
express LAMP upon differentiation. In con- thalamus and brainstem and broad expanses
Figure 18.4. Darkfield photographs of transverse sections through (A) the basal forebrain and (B) the hippocampal
formation in a cynomolgus monkey, illustrating the distribution of the limbic system-associated membrane protein
(LAMP). This membrane surface glycoprotein, which is specifically expressed in limbic regions of the brain, was visual-
ized with highly specific monoclonal antibodies A Note the intense labeling in the amygdala (AM), hypothalamus
. . .
( H) bed nucleus of the stria terminalis (BST) and the so-called extended amygdala (asterisks) which includes signifi-
cant portions of the substantia innominate and dorsal amygdaloid region. Patches showing moderate LAMP im-
munostaining are seen in both caudate nucleus (CD) and putamen { PUT), but not in the globus pallidus (GP). B Note
. . .
the intense LAMP immunostaining in all three sectors of the hippocampus (CAI CA2 and CAS) and in the dentate
gyrus ( GO) The immunostaining is moderate in the subiculum ( SU) and virtually absent in the entorhinal cortex ( SC)
The letters f and LVindicate fimbria and lateral ventricle, respectively.
of the cortical mantle. These extensive cortical bition of peristalsis, pupillary dilatation, sali-
connections of forebrain nuclei appear to pro- vation , and bladder contraction. Perhaps the
vide part of the mechanism by which sensory most striking effect of stimulating these re-
stimuli and psychic phenomena influence gions is profound inhibition of respiratory
emotional aspects of behavior. These connec- movements ( 245), which involves mainly the
tions may also explain the close adjustment of inspiratory phase, occurs almost instanta -
visceral and somatic activities in emotional neously, and cannot be held in abeyance for
expression . long.
Various visceral, somatic, and behavioral Somatic effects of stimulating the anterior
responses can be obtained by electrical stimu - cingulate and the orbital-insular-temporal
lation of the anterior cingulate cortex and the cortex resemble those obtained by stimulat -
orbital -insular-temporal cortex. Earlier stud - ing the amygdala in awake animals. These re-
ies demonstrated that elevation, as well as sponses include (a ) inhibition of spontaneous
depression, of arterial blood pressure results movements, ( b) chewing, licking, and swal-
from electrical stimulation of these regions in lowing movements, and (c) the "arrest" reac-
experimental animals ( 21, 114 ). Points from tion. The arrest reaction consists of an imme-
which pressor and depressor effects can be diate cessation of other activities, an
obtained, frequently are only a few millime- expression of attention or surprise, and
ters apart. Effects on arterial pressure do not movements of the head and eyes to the oppo-
appear to be secondary to respiratory site side. Animals remain alert during stimu -
changes. Other autonomic responses ob- lations and respond to external stimuli . Stim -
tained in experimental animals include inhi - ulation of posterior cingulate areas may
induce enhanced grooming and seemingly tern are complex and subject to modifying in-
pleasurable reactions. Neither unilateral nor fluences from many sources. Some of these
bilateral ablations of the cingulate cortex, or regions have lost their original olfactory
- -
of the cortex of the orbital insular temporal specificity. For this reason use of the term
polar region, appear to disturb basic somato- "rhinencephalon" should be restricted to
motor or autonomic functions. those structures of the central nervous system
Electrical stimulation of certain subcortical that receive fibers from the olfactory bulb
structures via implanted electrodes in ( 40 ). In this strict sense, the rhinencephalon
unanesthetized rats, cats, and monkeys pro- includes the olfactory bulb, tract , tubercle
duces a patterned self -stimulation behavior and striae, the anterior olfactory nucleus,
( 35, 185, 186 ). In these studies, the experimen - parts of the amygdaloid complex, and parts
tal arrangement is such that the animals can of the piriform cortex. The term rhinen-
deliver an electrical stimulus to localized cephalon , in this restricted sense, is equiva -
areas of their own brains bv pressing a pedal. lent to the paleopalliwn or primitive olfactory
Self -stimulations of the septal region, the an - lobe ( 270).
terior preoptic area , and the posterior hypo- Although the rhinencephalon is large and
thalamus by bar pressing may be at rates as conspicuous in nonprimate species, including
high as 5000 per hour in the rat . The compul - many macrosmatic mammals, in humans it is
sive behavior seen in these situations, where overshadowed and comparatively reduced
the only reward is an electric shock to a local - by the tremendous development of the
.
ized region of the brain, suggests that the iteopallium The archipallium , the oldest corti -
stimulus may provide a primary reinforce- cal derivative, is represented by the hip-
ment for drives related to food or sex. Re- pocampus, the dentate gyrus, the fasciolar
-
peated self stimulation may occur in the gyrus, and the indusium griseum (supracal -
monkey from electrodes implanted in a vari - losal gyrus ). The hippocampal formation
ety of subcortical sites, such as the head of the reaches its greatest development in micros-
caudate nucleus, the amygdaloid complex, matic man and is well-formed in certain
the medial forebrain bundle, and the mid - anosmatic aquatic mammals (e.g., porpoise,
brain reticular formation. Self -stimulation of whale).
certain regions of the thalamus and hypothal -
amus may produce unpleasant or avoidance Olfactory Receptors
reactions, but these regions appear relatively
small in number compared to those from The olfactory membrane is a yellowish
which some gratification appears to result. brown patch of specialized epithelium in the
The limbic lobe and system occupy central upper posterior part of the nasal cavity. Ol -
positions in the neural mechanisms that gov - factory receptors are located in this mem-
ern behavior and emotion. Components of brane ( Fig. 18.5). Slender sensory cells scat-
the limbic system appear to have their main tered among supporting cells in the olfactory
afferent and efferent relationships with two epithelium have two processes, a coarse pe-
great functional realms, the neocortex, and ripheral one, passing to the surface, and a fine
the visceroendocrine periphery. The amyg- central one, projecting through the basement
dala with complex connections, to and from membrane. From the coarse peripheral
the cerebral cortex and with subcortical auto- processes a variable number of fine olfactory
nomic centers, appears to represent the key hairs arise. The delicate central processes,
structure of the system . which constitute the unmyelinated olfnctoria
fila , converge to form small fascicles and pass
OLFACTORY SYSTEM from the nasal cavity via foramina in the crib-
riform plate of the ethmoid bone. These ex -
The term rhinencephalon refers to the olfac- ceedingly small fibers ( mean diameter 0.2
tory brain. Although some authors use this pm ) are unmyelinated , they have a very slow
term broadly to include those regions of the conduction rate, and enter the ventral surface
brain concerned with both the reception and of the olfactory bulb ( Figs. 18.5 and 18.6 ). The
integration of olfactory information , not all olfactory fila , representing the central
regions of the brain in which responses can processes of bipolar cells in the olfactory ep-
be recorded upon olfactory stimulation are ithelium, collectively constitute the olfactory
concerned exclusively with olfactory sense. nerve ( N I ). The incoming olfactory axons are
1 ligher order pathways of the olfactory sys- gathered into bundles of 100-20(1 axons con -
Internal granule cell

Mitral cell
Olfactory
glomerulus
Lateral olfactory stria

Olfactory neuron Nasal mucous membrane
Figure 18.5. Olfactory bulb and tract showing relationship of the olfactory receptors and neurons in the nasal mu-
cosa with cells in the olfactory bulb. Cells of the anterior olfactory nucleus form scattered groups caudal to the olfac -
tory bulb. Centrally projecting fibers from the anterior olfactory nucleus are labeled 8. while a fiber from the contralat -
eral anterior olfactory nucleus Is labeled A .
Gyrus rectui
.Olfactory bulb
Corpus callosum
.
( rostrum )
Olfactory tract
:
Subcallosal area
Paraterminal gyrus
Medial olfactory
stria
Anterior commissure r7 Lateral olfactory
stria
Olfactory trigone t 1 Intermediate
stria
Diagonal band
Anterior perforated
substance
Lamina terminalis
Optic chiasm
Figure 18.6 . Olfactory structures on the inferior surface of the brain The optic nerves and chiasm have been re-
tracted caudally to expose the olfactory area.
tained within one glial (Schwann ) cell . These ceptor is a bipolar neuron with a lifespan of
glial cells contain glial fibrillary acidic protein 30-40 days, depending upon the species.
(GFAP), like central astrocytes but unlike New axons are continually growing into the
Schwann cells of peripheral nerves ( 244). olfactory bulb and forming new synapses.
A notable feature of the sensory neurons When the olfactory fibers are surgically cut as
of the olfactory epithelium is that they are they enter the olfactory bulb (164 ), olfactory
continuously replaced from stem cells receptor axons can regenerate and form new
throughout adult life (81 ). The olfactory re- synapses in the glomeruli of the olfactory
bulb. The normal cyclic loss and formation of fibers of the olfactory tract ( Fig. 18.7). Al -
olfactory receptor axons and their synapses though obvious in fetal stages of develop-
upon mitral cells, and the demonstration of ment , the layers are irregular and indistinct
posttraumatic regeneration in primates, of - in the adult human olfactory bulb. The princi-
fers hope that a means can be devised to min- pal cells of the olfactory bulb are the mitral
imize scar tissue formation and permanent cells , so named because of their resemblance
deafferentation of the bulb in humans with to a bishop's miter ( Figs. 18.5, 18.6, and 18.8).
anosmia due to fractures of the cribriform Their dendrites extend into the glomeruli,
plate. where they are contacted by axons of sensory
The constant turnover of sensory olfactory olfactory cells (215, 243, 244 ) ( Fig. 18.7), and
neurons is one of the rare examples in mam - in the external plexiform layer, where they re-
mals of continued genesis of neurons that ceive input from fibers originating in various
make synaptic connections in the central ner- brain centers (centrifugal fibers ) that ascend
vous system . The molecular basis of this phe- along the olfactory tract . The axons of the mi-
nomenon is not completely known, but most tral cells descend along the olfactory tract and
likely involves the complex interplay of sev- constitute the main output of the olfactory
eral guiding molecules. The olfactory sensory bulb and are recognized as secondary olfactory
neurons contain a special peptide [ olfactory fibers ( Figs. 18.5 and 18.8). Tufted cells are sim -
marker protein ( OMP) ] and are enriched with ilar to the mitral cells, but their smaller so-
the dipeptide carnosine ( (J-alanyl- L-histidine) mata lie more rostrally in the plexiform layer.
( 151, 152). The olfactory axons are known on Both the mitral and tufted cells exert an exci -
the basis of electrophysiologic experiments to tatory effect upon neurons they contact. This
be excitatory, but neither OMP nor carnosine excitatory action appears to be mediated by
have been shown to be neuroactive at their glutamate ( 243, 244 ).
synapses ( 102, 244 ). Numerous studies have The olfactory bulb contains two type of in -
generated monoclonal antibodies to all parts
of the sensory neuronal population , indicat-
—
terneurons the periglomerular cells and the
granule cells. The periglomerular cells have
ing the presence of molecules that may be in - dendrites that receive synaptic input from ol -
volved in the sensory transduction of the olfactory sensory neurons and from centrifugal
factory signals as well as the specificity of fibers. The dendrites also form dendroden -
synaptic connections (166, 167, 244 ). Some of dritic synapses with the mitral cells. The
these molecules appear to be unique to sub- axons of the periglomerular cells course in
sets of olfactory neurons (8). The calcium - the external plexiform layer to contact den-
binding proteins calbindin D- 28 k, parvalbu - drites of mitral cells associated with other
min, and calretinin , are known to occur in glomeruli , which they may excite or inhibit
various combination in the olfactory sensory depending on the postsynaptic receptors ( 25).
neurons of the main olfactory epithelium and Periglomerular cells use dopamine and y-
that of the vomeronasal organ (118). aminobutyric acid (GABA ) as neurotransmit -
ters, and they are also enriched with various
Olfactory Bulb neuroactive peptides and enzyme, such as ni -
tric oxide synthase (37). A large variety of
This flattened , ovoid body, resting on the neuropeptides (substance P, neuropeptide Y,
cribriform plate of the ethmoid bone, is the corticotrophic releasing factor, vasoactive in-
terminal "nucleus" of the olfactory nerve testinal peptide, enkephalin, and somato-
( Figs. 18.5 and 18.6 ) . The olfactory bulb is the statin ) occur in the olfactory bulb, but their
first processing station in the olfactory path - functional significance remains to be eluci -
way. Most of the fibers of the olfactory nerve dated . The granule cells are the most numer-
enter the anterior tip of the olfactory bulb. ous interneurons in the olfactory bulb. These
Structurally, the olfactory bulb has a laminar cells have no axons ( amacrine cells ), are lo-
organization arranged in both radial and tan - cated in the deepest part of the bulb ( Fig.
gential fashion . From the surface progressing 18.7) ( 214 ), and use GABA as inhibitory neu -
toward the central core, the olfactory bulb rotransmitter (96, 149, 223, 244). Their den -
consists of (a ) the olfactory nerve fiber layer, drites receive axodendritic contacts from mi-
( b ) the layer of synaptic glomeruli, (c ) the ex- tral cells and from centrifugal fibers. Other
ternal plexiform layer, (d ) the mitral cell dendrites form dendrodendritic synapses
layer, ( e ) the granule cell layer, and ( f ) the with mitral cell dendrites. The morphologic
Centrifugal
-•—(afferent ) axons
Lateral olfactory
tract
Granule
cell
layer
Mitral
Olfactory cell
bulb layer
i
External
plexiform IT
layer IDS
Glomeruli DDS
W
PG
Mitral dendrite
Cribriform plate Dendritic

j spine
/(gemmule)i
Olfactory
mucosa
Li i° - i i Ajv
'
Granule
cell
dendrite
Figure 18.7. Major classes of cells in the olfactory bulb The sensory receptors (O in the olfactory mucosa are illus-
trated at the bottom of the Figure The central process of the receptor enters the olfactory bulb and synapses upon a
dendritic tuft of a mitral cell to form a complex called a glomerulus Axons of mitral cells ( M ) pass centrally to form the
lateral olfactory tract . Mitral axons also have recurrent collaterals which synapse upon granule cells. The granule cells
( G) have no axons. Their external dendrites have dendritic spines which form reciprocal dendrodendritic synapses
(DDS and insert) on mitral dendrites. Periglomerular cells ( PG ) represent several morphologic types of cells linking mi-
tral cell glomeruli Tufted cells ( 7) are morphologically similar to mitral cells, but their cell bodies are dispersed through-
out the external plexiform layer
features of these junctions suggest reciprocal The olfactory glomeruli are the most charac -
—
synapses one from granule cell to mitral
cell, and one from mitral cell to granule cell
teristic feature of the olfactory bulb in all ver-
tebrates. They represent the reception site as
( Fig. 18.7 ). Granule cells inhibit mitral cells, well as the first stage in the analysis and
and the mitral cells appear to excite the gran - modulation of olfactory information . Within
ule cells ( 76, 244 ). The complex circuitry of these spherical acellular islands, three neu -
the olfactory bulb recalls that of the retina ronal elements interact: (a ) the olfactory axon,
and suggests that, as is the case with visual which represents the input fiber; ( b ) the mi -
images, the olfactory information is partially tral / tufted cell, which represents the princi-
analyzed and modulated before reaching the pal neuron; and (c ) the periglomerular cell,
cerebral olfactory areas ( 25). which represents the intrinsic neuron. These
Olfactory sensory neurons in one side of three basic elements form a synaptic triad that
the nose amount to approximately 50 xl 0h in is characteristic of most brain regions in -
the rabbit, giving rise to as many axons enter- volved in sensory processing ( 244 ). The
ing each olfactory bulb. This large array of synapse between the input and principal ele-
sensory input channels converge onto ap- ments provides the necessary basis for input-
proximately 2000 glomeruli, to which are output transmission, whereas synapses be-
connected about 50,000 mitral cells and tween the principal and intrinsic elements
100,000 tufted cells ( 11 , 12, 14, 244 ) . Thus, the allow for elaboration and control of the
convergence ratios in the olfactory system are input -output transfer. The synaptic triad in
very high : (a ) 25,000:1 onto glomeruli; ( b) the olfactory glomerulus involves synapses
1000:1 onto mitral cells; and (c ) 500:1 onto from the input onto both the principal and
tufted cells ( 244 ). the intrinsic elements. After this initial inter-
Internal granule cells
N.
r*-f - Olfactory bulb
Mitral cells
Anterior olfactory
nucleus
Recurrent
collateral
Lateral olfactory
tract
Anterior commissure
( anterior part )
Figure 18.8 Interconnections of the olfactory bulbs and anterior olfactory nuclei Collaterals of mitral cell axons
synapse upon apical dendrites of pyramidal-shaped cells of the anterior olfactory nucleus These cells give rise to
fibers that cross in the anterior part of the anterior commissure and synapse upon cells in the contralateral anterior ol-
factory nucleus and internal granule cells in the olfactory bulb Recurrent collaterals of axons of the anterior olfactory
.
nuclei project back to the ipsilateral olfactory bulb to terminate upon internal granule cells, which can in turn, acti-
vate mitral cells The principal axons of mitral cells enter the lateral olfactory tract
action , further processing takes place within gic fibers of the dorsal raphe nucleus (1% ),
the glomerulus through the dendrodendritic the noradrenergic fibers of the locus co-
microcircuits. Moreover, the activity in one eruleus ( 32, 95), and the cholinergic fibers
glomerulus can affect that in other glomeruli that arise from the large neurons of the basal
through interglomerular connections medi- lorebrain ( 202).
ated chiefly by the axons of periglomerular Olfactory glomeruli are among the clearest
cells. If glomeruli function as units, then one examples in the brain of the principle of
effect of the interglomerular microcircuits grouping of neuronal elements and synapses.
could be to enhance the contrast between They are, in some ways, analogous to "bar-
glomeruli of different specificities, much like rels" and "clumps" in the cerebral cortex,
intercolumnar interactions in the cerebral cor- representing a higher level of organization
tex ( 243, 244 ). A second level of organization than the synaptic glomeruli in the thalamus
in the olfactory bulb involves interactions be- or the cerebellum ( 244 ). Although the
tween mitral / tufted cells and granule cells, arrangement of afferent fibers in the olfactory
which play a crucial role in the control of the bulb does not appear to be localized in any
output of the olfactory bulb. Finally, it must patterned way (133), a regional organization
be noted that the complex neuronal computa - of olfactory nerve projections to the olfactory
tion that occurs at various levels in the olfac- bulb has been demonstrated in mammals ( 3,
tory bulb is directly under the modulatory in- 130, 131 ). Localized lesions in different re -
fluence of different chemospecific centrifugal gions of the olfactory epithelium produce de-
fiber systems. The most prominent of these generation in specific regions of the glomeru -
centrifugal fiber systems are the serotoniner- lar layer (127 ). Groupings of glomeruli show
rnarked variations in the intensity of degener- neuronal ensembles that spanned the lamina
ation and some normal glomeruli are present of the main olfactory bulb. The complemen -
in regions containing degeneration. It has tary RNA (cRNA )-labeled neuronal groups
been suggested that a selective projection consisted of cells in the glomerular layer that
from receptors in small regions of the olfac- precisely defined the borders of individual
tory epithelium to specific glomeruli, or glomeruli and underlying tufted , mitral, and
groups of glomeruli, could provide the granule cells. The activated fields were much
anatomic basis for selective responses to broader in the granule cell layer than in the
odors. Functional mapping studies with the overlying glomerular layer, and thus exhib-
2-deoxyglucose ( 2- DG ) method indicate that ited a flask-like, as opposed to a columnar,
there are groups of glomeruli with similar contour ( 92).
specificities for a given odor. This implies Caudal to the olfactory bulb are scattered
that the group of mitral, tufted , and groups of neurons, intermediate in size be-
periglomerular cells whose dendrites are con - tween mitral and granule cells, that form the
nected to a given subset of "specific" anterior olfactory nucleus ( Figs. 18.5 and 18.8).
glomeruli will all share this specificity, in a Some cells of this loosely organized nucleus
manner analogous to the functional columns are found along the olfactory tract near the
in the cerebral cortex ( 243, 244 ). Such a view base of the hemisphere. Dendrites of these
is supported by the results of studies that cells pass among the fibers of the olfactory
-
have employed the proto oncogene c fos as a - tract , from which they receive impulses. Col -
physiologic marker (92 ). These investigations lateral branches of axons of mitral and tufted
revealed that the presentation of specific cells terminate in the anterior olfactory nu -
odors to alert rats for as little as 5 minutes in - cleus. Axons of the cells in this nucleus pass
creased c - fos mRNA in radially distributed centrally, cross in the anterior part of the an -
Olfactory bulb
Lateroposterior
quadrant of
orbitofrontal
cortex
Pyriform
cortex
Temporal neocortex
Entorhinal
cortex
Prorhinal
cortex
Figure 18.9. Inferior surface of the frontal and temporal lobes of a primate brain showing olfacto- frontal connec -
tions. The lateroposterior quadrant of the orbitofrontal cortex receives olfactory information which is relayed from the
lateral entorhinal area (perirhinal cortex) The lateral entorhinal area receives olfactory information indirectly from the
piriform cortex .
terior commissure and enter the contralateral stance, which corresponds to the olfactory tu -
anterior olfactory nucleus and olfactory bulb bercle in macrosmatic animals. These fibers
( Fig. 18.8) ( 25, 139, 209, 270). As seen earlier, terminate in the piriform cortex (also termed
this is only one of the populations of centrifu - prepiriform cortex ) and in the corticomedial
gal fibers that project to the olfactory bulb. part of the amygdaloid nuclear complex (11,
Centrifugal fibers synapse principally with 12, 93, 132, 2()9, 213, 216 ). Terminations of
dendrites of the interneurons. these fibers also are present in the nucleus of
the lateral olfactory tract and in parts of the
Olfactory Tract anterior amygdaloid nucleus.
This tract passes toward the anterior per - Olfactory Lobe

forated substance and divides into well -de-
fined lateral and medial olfactory striae. A thin This lobe develops as a longitudinal bulge
covering of gray substance over the olfactory on the basal surface of the hemisphere, where
striae composes the lateral and medial olfactory it is separated from the neocortex by the rhi -
gyri . The lateral olfactory stria and gyrus pass nal sulcus ( Fig. 2.10). It soon differentiates
along the lateral margin of the anterior perfo- into anterior and posterior portions. The an-
rated substance to reach the piriform region terior portion , at first containing an extension
( 124 ) ( Figs. 18.9 and 18.10 ) . Fibers of the lat - of the lateral ventricle, elongates into a tubu -
eral olfactory stria arising in the olfactory lar stalk which becomes solid by the end of
bulb give collaterals to the anterior olfactory the third month, and forms the rudiment of
nucleus and the anterior perforated sub- the olfactory tract and bulb. The posterior
Anterior nucleus of thalamus
Medial forebrain bundle
Anterior commissure Strio medullaris

Habenular nucleus
Septol nuclei
Longitudinal striae
/( Indusium gnseum )
Subcallosal
area
Stria
Paraterminal terminalis
gyrus
Olfactory
tubercle
bulb Fasciolar
gyrus
Fimbria
Olfactory striae
medial Hippocampal
lateral formation
Amygdaloid complex
Rhinal sulcus x ^ Dentate gyrus
Parahippocampal gyrus Interpeduncular nuclei
Diagonal band Mammillotholamic tract

Mammillory body
Figure 18.10. " Phinencephalic " structural relationships as seen in medial view of the right hemisphere Both deep
and superficial structures are indicated
Optic nerve
Column of fornix Optic troct
Anterior commissure Anterior perforoted

substonce
Amygdaloid body
Mommillory body
Fornix Uncus
body —
fimbria —
Hippocompol
formotion
Dentate gyrus
Corpus collosum
Formcal comm (ventral aspect )
Fosciolar gyrus
Lateral ventricle
Indusium griseum —
Lot longitudinal stria
Corpus callosum
( splemum )
Figure 18.11. Dissection of the inferior surface of the brain showing the configuration of the fornix, the hippocampus,
the dentate gyrus, and related structures.
portion differentiates into the olfactory area small region dorsal and rostral to the amyg-
(anterior perforated substance) and certain daloid nuclear complex. The entorhinal area,
other olfactory structures closely related to the most posterior part of the piriform lobe,
the anteromedial portion of the tempo- corresponds to area 28 of Brodmann and
ral lobe, collectively known as the piriform constitutes a major portion of the anterior
lobe. parahippocampal gyrus in humans ( Figs. 18.9
The piriform lobe , so named because of its and 18.10 ). The rostral part of the parahip-
pear shape in certain species, is divided into pocampal gyrus is rolled inward and upward
several regions ( Fig. 18.9). These include the as a consequence of the tremendous develop-
piriform , the periamygdaloid , and the entorhinal ment of the neocortex. The rostromedial pro-
areas. The piriform area , often referred to as trusion of this gyrus is the uncus (160) ( Figs.
the lateral olfactory gyrus, extends along the 2.10 and 18.11 ). Fibers of the lateral olfactory
lateral olfactory stria to the rostral amyg- stria , arising in the olfactory bulb, give collat -
daloid region ( Figs. 18.9 and 18.10). Since its erals to the anterior olfactory nucleus and the
afferent fibers are derived from the lateral ol - olfactory tubercle, and terminate in the piri-
factory stria, it is regarded as an olfactory form cortex and in parts of the amygdaloid
relay center. The periamygdaloid area is a nuclear complex ( 93, 94, 213, 216, 235, 273).
The piriform cortex and the periamyg- anterior perforated substance is a rhomboid -
daloid area , which receive fibers from the lat- shaped region bounded by the medial and
eral olfactory stria , constitute the primary ol - lateral olfactory striae and the optic tract
factory cortex. Olfaction appears to be unique ( Figs. 2.10, 18.6, and 18.11 ). This region is
among the sensory systems, in that impulses studded with perforations made by penetrat-
in this system project to the cortex without ing blood vessels ( Fig. 4.11 ). The posterior
being relayed by thalamic nuclei . The piri- border of this region is formed by the diagonal
form cortex projects fibers to the entorhinal band of Broca ( Fig. 18.6 ).
cortex (area 28), the basal and lateral amyg- The subcallosal area and the paraterminal
daloid nuclei, the lateral preoptic area , the gyrus together constitute the septal area . The
nucleus of the diagonal band , and parts of the term septal area refers to the cortical part of
mediodorsal nucleus of the thalamus (93, 216, this region, beneath which are the septal nu -
244 ). The entorhinal cortex is the secondary ol - clei. The medial and lateral septal nuclei lie ros-
factory cortical area ( Figs. 18.9). Efferent fibers tral to the anterior commissure and the pre-
from the entorhinal cortex are projected to optic area near the base of the septum
the hippocampal formation, and to the ante- pellucidum ( Figs. 18.10 and 18.11 ). The me-
rior insular and frontal cortex via the unci - dial septal nucleus becomes continuous with
nate fasciculus ( Fig. 2.18). No fibers from the the nucleus and tract of the diagonal band
piriform cortex pass to the hippocampal for- and has connections with the hippocampal
mation . formation. Cells of the medial septal nuclei
The lateroposterior quadrant of the or- and the nuclei of the diagonal band are
bitofrontal cortex receives olfactory informa - strongly cholinergic ( Fig. 18.23). The septal
tion via relays in the piriform and entorhinal nuclei receive afferents from the hippocam-
cortex ( 207 ) ( Fig 18.9 ). Additionally, the piri - pal formation via the fornix (175, 176, 217).
form cortex projects to the magnocellular Afferents to the medial septal nucleus ascend
portion of the mediodorsal nucleus ( MDmc ) in the medial forebrain bundle and mammil -
of the thalamus ( 209), which in turn projects lary peduncle ( 90, 91, 180 ) ( Figs. 18.2 and
to the orbitofrontal cortex (see Chapter 16). 18.3). Efferent fibers from the septal nuclei
Different parts of the amygdaloid nuclear project via (a ) the stria medullaris to the me-
complex receive olfactory inputs. Direct pro- dial habenular nucleus, ( b) the medial fore-
jections from the olfactory bulb pass to the brain bundle to the lateral hypothalamus and
cortical and medial amygdaloid nuclei, midbrain tegmentum , and (c) the fornix to
while indirect olfactory impulses pass to the the hippocampal formation ( 52, 217) ( Figs.
basal and lateral amygdaloid nuclei, via re- 17.17 and 18.3).
lays in the piriform cortex. Direct and indi-
rect olfactory pathways to the amygdaloid
complex terminate in different components Vomeronasal System and
that probably influence almost the entire Terminal Nerve
complex. VOMERONASAL SYSTEM
Fibers originating from the cells of the an-
terior olfactory nucleus project (a ) peripher- In addition to receptors in the olfactory ep-
ally to internal granule cells of the ipsilateral
olfactory bulb, and ( b ) via the anterior part of
ithelium , chemosensory receptor cells arc
found in most mammalian species in the
-
the anterior commissure to the contralateral vomeronasal organ (of Jacobson ), which is a bi-
anterior olfactory nucleus and olfactory bulb. lateral , blind -ended tube in the ventral part
Projections from the anterior olfactory nu - on each side of the nasal septum . The recep-
cleus on one side thus reach internal granule tor neurons are similar to those in the olfac-
cells of the olfactory bulb on both sides and tory epithelium, except that they have mi -
the contralateral anterior olfactory nucleus crovilli rather than cilia at their apical
( Fig. 18.8 ). pole. Vascular connective tissue with sympa -
The medial olfactory stria becomes contin - thetic vasomotor innervation separates the
uous with the subcallosal area and the vomeronasal epithelium from the rigid carti-
paraterminal gyrus ( Figs. 18.6 and 18.10 ). laginous wall of the tube. The central
Some of the fibers in this stria may reach the processes of vomeronasal sensory cells form
olfactory tubercle, a prominent structure in the vomeronasal nerve , which passes through
macrosmatic species located immediately the cribriform plate alongside the olfactory
above the anterior perforated substance. The nerves and ends in the so-called accessory ol -
factory bulb located along the dorsal aspect of tivates the main olfactory bulb, whereas urine
the main olfactory bulb. In the accessory ol - in the liquid phase activates the accessory ol -
factory bulb, the axons of the vomeronasal factory bulb only. Thus, the vomeronasal sys-
nerve contact mitral / tufted cells whose axons tem may play an important role that is com -
course in the lateral olfactory tract and termi- plementary to that of the principal olfactory
nate in sectors of the amygdala involved in system.
the control of sexual behavior (see later ). In
several nonprimate mammals, as well as TERMINAL NERVE
in reptiles, the entrance of the vomeronasal
organ is immediately dorsal to the nasopala - The fibers of the tiny terminal nerve
tine foramen, through which the oral and ( nervus terminalis ) lie along the medial side of
nasal cavities communicate ( 25). Activity of the olfactory bulb and olfactory tract. The
the sympathetic nervous system causes con - bipolar neurons that give rise to the terminal
striction of the blood vessels of the nerve occur in small ganglia scattered along
vomeronasal organ, making the connective the course of the nerve. Their distal processes
tissue layer thinner because it contains less pass through the cribriform plate and are dis -
blood . The resulting enlargement of the tributed to the nasal septum ( 25). In experi -
lumen sucks in tiny drops of liquid that have mental animals, the proximal processes have
been either sniffed into the nostrils or placed been traced to the septal and preoptic areas.
by the tongue into the nasopalatine foramen . Evidence obtained in various species indicate
The vomeronasal system plays an impor - that the terminal nerve exerts a strong influ -
tant role in the detection of chemical mes- ence on the reproductive system during de-
sages from other members of the same velopment and in the adult. This influence
species. The compounds ( pheromones ) used as could be mediated , at least in part, by lutein-
sexual attractants and for delineating terri-
tory may be secreted by specialized sweat or
-
izing hormone releasing hormone ( LHRH )
because immunoreactivity for this peptide
sebaceous glands, or they may be excreted in has been visualized in both cell bodies and
the urine ( 25). In animals with well -devel - fibers associated with this nerve ( 182 ).
oped vomeronasal systems, such as snakes The terminal nerve is present, although in
and rodents, transection of the vomeronasal microscopic size, in adult humans. It is often
nerves impairs reproductive behavior (158, called nerve zero because it lies medial, and ,
211 , 289). therefore, perhaps rostral , to the olfactory
In humans, there is no accessory olfactory nerves ( 25). Both the terminal and the
bulb, and the vomeronasal organ has been as- vomeronasal nerves were discovered after
sumed to be vestigial or absent and without the 12 main cranial nerves were given their
functional significance ( 288). However, recent numbers.
studies in humans revealed the presence of
vomeronasal pits in all individuals except Clinical Considerations
those with pathologic conditions affecting the
septum ( 165, 249 ). Electron microscopy of the The ability of the human nose, in concert
adult human vomeronasal organ indicates with the brain, to discriminate thousands of
the presence of two potential receptor ele- different odors is well -known, but the physi-
ments in the pseudostratified epithelial ologic and psychologic bases for such dis-
lining: microvillar cells, and unmyelinated, criminations are not yet entirely known. Ol -
intraepithelial axons. Additionally, unmyeli - factory discrimination is not based on
nated axons are common in the lamina pro- morphologically distinct types of receptors,
pria surrounding the organ . They appear to but there is some evidence that certain odors
constitute the components essential for a may be distinguished bv their effectiveness in
functional chemosensory system, and may stimulating particular regions of the olfactory
thus provide the basis for a pheromone detec- epithelium ( 92, 127, 171 , 244 ). Current theo-
tion system as in other animals ( 211, 249, ries suggest that spatial and temporal factors
288). In some nonhuman primates, the in- probably play important roles in coding of ol -
volvement of the vomeronasal system in the factory responses ( 170 ). Functional mapping
detection of urinary signals has been demon- studies with either 2- DG or c - fos methods re-
-
strated with the use of the 2 deoxyglucose ( 2 - vealed that stimulation with one odor ( e.g.,
DG ) method ( 233). This study has revealed amylacetate, which has a fruity smell ) acti-
-
that urine in the volatile phase specifically ac vates glomeruli in certain regions of the olfac -
tory bulb, whereas stimulation with a differ- It is estimated that the nose of macros-
ent odor (e.g., camphor) activates glomeruli matic mammals can detect and discriminate
in other regions of the olfactory bulb (92, -
10,000 different odor bearing molecules in
244 ). the environment. These constitute by far the
Other evidence indicates that the sense of largest single class of ligands detected by any
smell is based on molecular geometry (19, -
neuronal signal transducing system . Whether
22 ). Molecules identical in every respect, ex- this gigantic task of detection and recognition
cept that one is the mirror image of the other, is accomplished by the presence of a large
may have different odors. Seven primary number of peripheral receptors with high
odors ( i.e., camphoraceous, musky , floral, affinity and specificity for odor ligands or is
pepperminty, ethereal (ether-like), pungent, the result from central processing of the input
and putrid ) are considered to be equivalent to from only a few receptors with overlapping
the three primary colors, because every specificities is still unclear. Recent molecular
known odor can be produced by appropriate biologic studies, however, have led to the
mixtures of primary odors. Molecules with identification of large multigene family,
the same primary odor appear to have partic- which comprises at least 100 distinct gene en -
ular configurations, and these configurations coding specific odorant receptors (43). This
are thought to fit appropriately shaped recep- finding suggests that the receptor neurons are
tors. Molecules that may fit more than one re- the main site of odor discrimination and that
ceptor are considered to signal complex considerable stimulus information can be en-
odors. coded at the peripheral level.
Odor discrimination is mediated via den- From a clinical viewpoint valuable infor-
dritic cilia of olfactory receptor neurons. mation can be obtained by testing olfactory
Odorants traverse the aqueous mucous inter- sense by appropriate methods. Olfaction is
phase that lines the surface of the olfactory tested in each nostril separately by having the
neuroepithelium and interact with odorant patient inhale or sniff nonirritating volatile
receptors, which are members of the super- oils or liquids with characteristic odors. Sub-
family of G-protein-linked receptors. These stances which stimulate gustatory end or-
interactions trigger synthesis of second mes- gans, or peripheral endings of the trigeminal
sengers, including adenosine 3',5'-cyclic nerve in the nasal mucosa , are not appropri-
monophosphate (cAMP) and inositol triphos- ate for testing olfaction. Comparisons be-
phate (IP3). Cyclic AMP opens a cation chan - tween the two sides are of great importance.
nel to elicit the generator current, which de- While the olfactory nerves are rarely the
polarizes the cell and , ultimately, leads to seat of disease, they frequently are involved
action potentials. Inositol triphosphate opens by disease or injury of adjacent structures.
a calcium channel in the ciliary plasma mem- Fractures of the cribriform plate of the eth-
brane. Calcium entering through both this moid bone or hemorrhage at the base of the
channel and the cyclic nucleotide-gated chan- frontal lobes may cause tearing of the olfac-
nel modulates the response to odorants by tory filaments. The same injury may result in
amplifying the generation of cyclic AMP after leakage of the cerebrospinal fluid from the
binding to calmodulin. Calcium is also essen - subarachnoid space into the nasal cavity, so
tial for desensitization of olfactory receptor that the fluid runs from the nose (cere-
neurons. Differential expression of odorant brospinal fluid rhinorrhea ). This abnormal
receptors of diverse ligand specificities by communication with the external environ-
different olfactory neurons, ensures that the ment is dangerous because it provides a route
structures and concentrations of odorants whereby bacteria and viruses may attack the
that reach the chemosensory surface are en- meninges and the brain. Even in normal con-
coded as distinct patterns of neuronal activ- ditions, the olfactory nerve appears to be a
ity. These are relayed to the brain where they privileged route for viral infection and dis-
take shape as characteristic odor sensations semination ( 24, 281 ). The olfactory nerves
( 22 ). Recently, the interplay between guano- may be involved as a consequence of menin-
sine 3' ,5'-cyclic monophosphate (cGMP) and gitis or abscess of the frontal lobe.
nitric oxide ( NO) synthase was involved in Unilateral loss of the olfaction sense or
the triggering of molecular mechanisms, in- anosmia may be of important diagnostic sig-
cluding adaptation processes, which enable nificance in localizing intracranial neoplasms,
the olfactory neuroepithelium to cope with especially meningiomas of the sphenoidal
strong stimuli (37). ridge or olfactory groove. Hypophysial tu -
mors affect the olfactory bulb and tract only These include antibodies to phosphorylated
when they extend above the sella turcica . Ol - and nonphosphorylated neurofilament sub-
factory "hallucinations" frequently are a con - units, tau , and also Alz 50, which is character -
sequence of lesions involving or irritating the istically reactive in Alzheimer's disease but
parahippocampal gyrus, the uncus or adjoin- not in normal conditions. Such accumulations
ing areas around the amygdaloid nuclear of ectopic neurites are present in 81 % of
complex. The olfactory sensations which Alzheimer's disease patients ( 261 ).
these patients experience usually are de-
scribed as disagreeable in character and may ANTERIOR COMMISSURE
precede a generalized convulsion . Such
seizures are referred to as "uncinate fits." The anterior commissure crosses the mid -
Olfactory deficits and degenerative line as a compact fiber bundle immediately in
changes in central olfactory pathways are front of the anterior columns of the fornix
prominent in patients with Alzheimer's dis- ( Figs. 2.14, 2.15, 16.2, 18.2, 18.10, 18.11, and
ease. Degenerative changes occur in the olfac- A.25 in the atlas of the human brain , section
tory bulb, olfactory cortices, as well as in the VII ). Proceeding laterally, it splits into two
olfactory neuroepithelium. Immunohisto- portions. The small anterior, or olfactory por-
chemical studies of nasal tissue taken at au - tion , greatly reduced in man , loops rostrally
topsy reveal extensive degeneration in the and connects the gray substance of the olfac-
sensory epithelium as well as abnormal neu - tory tract on one side with the olfactory bulb
rites that share immunoreactive epitopes of the opposite s i d e ( Fig . is. 12 ) . Fibers i n t h i s
with dystrophic neurites and neurofibrillary part of the anterior commissure arise from
tangles of the brains of Alzheimer patients the anterior olfactory nucleus, cross to the op-
(129, 261 ). The neuritic masses can be stained posite side and project to the contralateral an -
with well -characterized monoclonal antibod - terior olfactory nucleus and to granule cells
ies that do not normally stain olfactory neu - in the olfactory bulb ( Fig. 18.8). It has been
rons but which are very reactive with dys- suggested ( 208) that these centrifugal fibers
trophic neuritic structures and neurofibrillary may subserve reflex control of activity in the
tangles in the brains of Alzheimer patients. olfactory bulb, and in principle may be com-
Fornix
column x
body \
commissure \
Splenium of
crus
Anterior commissure
corpus callosum -
anterior part
posterior part
-Mammillothalamic
tract
Mammillary body
Calcar avis —
Fimbria of hippocampus Flippocampal formation

Inferior horn I
lateral ventricle Choroid plexus
Figure 18.12. Brain dissection showing the hippocampal formation, the fornix system and the anterior and posterior
parts of the anterior commissure , Postcommissural fibers of the fornix are here shown projecting only to the mammil-
lary body.
parable to the efferent system to sensory nu - known. The cortical representation of human
clei at spinal levels. olfactory processing was recently invesfi-
The larger posterior portion forms the gated by comparing cerebral blood flow
bulk of the anterior commissure. From its changes evoked during olfactory stimulation
central region, fibers of the anterior commis - with those of a control task with positron
sure pass laterally and backward through the emission tomography ( PET ) ( 292 ). Significant
most inferior parts of the lateral segment of cerebral blood flow increases were observed
the globus pallidus and putamen, a relation- during olfactory stimulation at the junction of
ship most obvious in sagittal sections of the the inferior frontal and temporal lobes bilat -
brain ( Figs. 19.6, A.31, and A.32 ). Further laterally , corresponding to the piriform cortex,
erallv, the fibers of the anterior commissure and unilaterally, in the right orbitofrontal
enter the external capsule and come into ap- cortex. The results complement and extend
position with the inferior part of the claus- previous data implicating these regions in ol -
trum . On entering the external capsule the factory processing, and indicate that a func-
fibers of the commissure twist so that poste- tional asymmetry exists in the human brain
rior fibers pass ventrally. Fibers of the poste- favoring the right orbitofrontal area in olfac-
rior portion of the anterior commissure tion ( 292 ).
mainly interconnect the middle temporal
gyri, although some pass into the inferior
HIPPOCAMPAL FORMATION
temporal gyrus ( 72, 282).
Anatomic and physiologic investigations Topographic Organization
in experimental animals indicate that olfac-
tion is subserved bv several cortical regions, The hippocampal formation is laid down
but the areas implicated in the human olfac - in the embryo on the medial wall of the hemi -
tory system have not been definitively identi - sphere along the hippocampal fissure. This
tied by functional criteria . Behavioral evi - fissure lies immediately above and parallel to
deuce has suggested that laterally specialized the choroidal fissure, which marks the invagi -
mechanisms for odor processing may exist, nation of the choroid plexus into the ventricle
but the neuroanatomic substrate remains un - ( Fig. 3.13). With the formation of the tempo -
Optic tract
Choroid plexus
Choroidal fissure Caudate nucleus
Fimbria Inferior horn of

lateral ventricle
Hippocampal
fissure Hippocampal
formation
Prosubiculum
Subiculum Alveus
Presubiculum
Dentate gyrus
Collateral sulcus
Parahippocampal
gyrus
1
Occipitotemporal gyrus
Figure 18.13. Transverse section through the human hippocampal formation and parahippocampal gyrus
Dentate gyrus
Polymorphic
Layers - Granular
Molecular Hippocampus
Polymorphic
Pyramidal Layers
Molecular
Lateral geniculate
body
Strio terminalis
Coudate nucleus
Fimbria
Amygdaloid
complex
Alveus
Lateral ventricle
( inferior horn )
Figure 18.14. Sagittal sections through the hippocampal formation in the rhesus monkey showing the relationships of
the hippocampus and dentate gyrus to the inferior horn of the lateral ventricle, the striatum, and the amygdaloid nu-
clear complex In A. the cellular layers of the hippocampus and dentate gyrus are identified, whereas in B the
alveus, fimbria, tail of the caudate nucleus, stria terminalis. amygdaloid complex, and part of the lateral geniculate
body are indicated ( A Nissl stain. 8 B Weil stain. < 9)
*
ral lobe, both these fissures are carried down- nated portion bulges deeply into the inferior
ward and forward , each forming an arch horn of the lateral ventricle and becomes the
extending from the region of the interventric - hippocampus. The lips of the fissure give rise
ular foramen to the tip of the inferior horn of to the dentate and the parahippocampal gt/ ri.
the lateral ventricle ( Fig. 3.17). The various The relationships between the three major
parts of the hippocampal arch do not develop components of the hippocampal formation,
to the same extent . The dorsal portion of the that is, the hippocampus proper (or
hippocampal fissure is invaded bv commis- Ammon 's horn ), the dentate gyrus, and the
sural fibers of the corpus callosum and ulti- subicular cortex, are best illustrated in frontal
mately becomes the callosal fissure. The part sections or in special dissections ( Figs.
of the hippocampal formation that remains
above the corpus callosum , undergoes little
—
18.11 18.13). Proceeding from the collateral
sulcus, the parahippocampal yi/ riis extends to
differentiation; in the adult, it forms a thin the hippocampal fissure, where it dips into
vestigial convolution, the indusium griseum the lateral ventricle to form the hippocampus.
( Figs. 18.10 and 18.11 ). The latter curves dorsally and medially and ,
The temporal part of the arch, which is not on reaching the medial surface, curves in-
affected by the corpus callosum , differenti- ward again to form a semilunar convolution,
ates into the hippocampal formation . As the the dentate yi/ nrs or fascia dentata ( Figs. 18.14
hippocampal fissure deepens, the invagi- and 18.15). The whole ventricular surface of
Alveus
''
Str Or Choroid
:
-*
'Sir
jy
Rad
c«>v;
,- » • I
Vent. Lat. Plexus
\ \
' CA 3 I
Str Lac Mol. i / Infra ' >
C
Supra - / Fimbria
I
/
/
i
I
I
i
I • ' { CM
t
" '
. .- - - Sir. Gran .
\
\
- HiluS. -
I
I I
I - - - ' 'Str Mol 27
I ‘ CA1 \ Area Dentata
*
i
b - - - .4 Subiculum
\
t 49
a t
v
t
i
t
Ipi Ipe
l I
i
i
i /
B // / / 28a
Figure 18.15. Hippocampal region in the rhesus monkey in horizontal section showing the respective layers of the
hippocampal formation and dentate gyrus, as seen on a photograph ( x 20) of a Nissl stained section ( A) and a cor -
responding drawing (B) The borders of the layers and sectors of the hippocampal formation are designated accord-
ing to Lorente de No. 28a. entorhinal area, area 49. parasubiculum; area 27. presubiculum: Str gran . stratum granu-
losum: Sfr. Lac -Mot . stratum lacunosum moleculare: Str Mot . stratum moleculare: Str . Or stratum oriens; Sfr. Pyr .. .
stratum pyramidale; Str Rod. stratum radiatum. supra and infra, suprapyramidal and infrapyramidal limbs of the stra-
tum granulosum. Ipi. lamina principalis interna. Ipe. lamina principalis externa.
the hippocampal formation is covered by a the corpus callosum. These are the medial and
white layer, the alveus , which is composed of lateral longitudinal striae (of Lancisii), which
axons from cells of the hippocampus and constitute the white matter of these vestigial
subicular cortex ( Figs. 18.13-18.15). These convolutions ( Figs. 2.11 and 18.11 ). The indu -
fibers converge on the medial surface of the sium griseum and the longitudinal striae ex-
hippocampus to form a flattened band , the tend the whole length of the corpus callosum,
fimbria , lying medial to the hippocampus and pass over the genu, and become continuous
the dentate gyrus. Fibers from the alveus en- with the paraterminal gyrus, which is in turn
tering the fimbria constitute the beginning of prolonged into the diagonal band of Broca
the fornix system ( Figs. 18.10-18.12). The free, ( Fig. 18.6). Traced forward , the dentate gyrus
thin border of the fimbria is directly continu- extends into the notch between the uncus and
ous with the epithelium of the choroidal fis- hippocampal gyrus. Here it makes a sharp
sure, which lies immediately above it. The dorsal bend and passes as a smooth band
choroid plexus, invaginated into the ventricle across the inferior surface of the uncus. This
along this fissure, partly covers the hip- terminal portion is known as the band of Gia-
pocampus ( Fig. 18.13). The superior portion comini , and the part of the uncus lying poste-
of the parahippocampal gyrus adjoining the rior to it often is designated as the intralimbic
hippocampal fissure is known as the subicu- gyrus.
lum , and the area of transition between it and
the parahippocampal gyrus, is known as the Subicular Cortex and Hippocampus
presubiculum ( Fig. 18.13).
On the basis of phylogenetic observations, The cortical zones from the parahippocam-
the cerebral cortex can be divided into an pal gyrus through the presubiculum, the
older portion, the allocortex, and a newer part, subiculum, and the prosubiculum to the hip-
the isocortex or neocortex. The allocortex con- pocampus and the dentate gyrus show a
sists, in turn, of the archicortex and paleocortex. gradual transition from a six- to three-layered
The presubiculum, subiculum, prosubicu- cellular organization ( Figs. 18.13 and 18.15).
lum, hippocampus, and dentate gyrus have Although the entorhinal region (area 28) is
an archicortical structure, while the piriform six-layered cortex, it represents a transitional
cortex is paleocortical. The larger inferior form not typical of neocortex. In more medial
portion of the parahippocampal gyrus near cortical areas, certain layers of the entorhinal
the collateral sulcus ( Figs. 2.6 and 2.10) has a cortex drop out and undergo rearrangement,
six-layered transitional lamination resem- so that the cortex of the hippocampus has
bling the isocortex. only three fundamental layers. These are the
When the hippocampal fissure is opened polymorphic layer , the pyramidal layer , and the
up, the dentate gyrus is seen as a narrow, molecular layer ( Fig. 18.14). Several secondary
notched band of cortex between the hip- laminae are formed by the arrangement of
pocampal fissure below and the fimbria axons and dendrites of cells within the funda-
above ( Fig. 18.11 ). In sagittal sections ( Fig. mental layers. Immediately beneath the
18.14), the relationships between the hip- ependyma of the lateral ventricle is the
pocampal formation, the dentate gyrus, the alveus. Recognized laminae passing inward
amygdaloid nucleus and the inferior horn of from the alveus are (a ) the stratum oriens, ( b)
the lateral ventricle are readily appreciated . the stratum pyramidale, (c) the stratum radia-
Traced backward , the dentate gyrus accom- tum, (d ) the stratum lacunosum, and (e) the
panies the fimbria almost to the splenium of stratum moleculare ( Figs. 18.15 and 18.18).
the corpus callosum . There it separates from The last three laminae are considered to cor-
the fimbria, loses its notched appearance, respond to the molecular layer of the neocor-
and , as the delicate fasciolar gyrus , passes on tex (140, 141, 199).
to the superior surface of the corpus callosum The most characteristic layer of the hip-
( Fig. 18.11 ). It spreads out into a thin gray pocampal formation is the pyramidal layer
sheet representing a vestigial convolution, consisting of large and small pyramidal and
the indusium griseum or supracallosal gyrus Golgi type II cells ( Fig. 18.16). Large and small
( Figs. 18.10 and 18.11 ). Imbedded in the indu - pyramidal cells exhibit many morphologic dif -
sium griseum are two slender bands of ferences, especially in dendritic development.
myelinated fibers, which appear as narrow Some of the cells are described as double
longitudinal ridges on the superior surface of pyramids because of the rich dendritic
Optic tract
Choroid Caudate nucleus

plexus
Choroidal Inferior horn

fissure lateral ventricle
Alveus
Fimbria
Pyramidal cells
Hippocampal fissure of hippocampus
Subiculum Granule cells of

dentate gyrus
Afferent fibers
from prepyriform
cortex
" Alvear " pathway Collateral sulcus
%0/ c Loteral
tyD
" Perforant
/ °r' ex
" pathway
Figure 18.16. Hippocampal formation, dentate gyrus, and entorhinal area. In the dentate gyrus, only the granular
layer is indicated. In the hippocampus, only pyramidal cells and their axons projecting into the alveus are shown Af-
.
ferent fibers from the prepiriform cortex projecting to the entorhinal cortex are shown in black . Projections of the en-
torhinal cortex to the hippocampal formation follow two pathways: (a) the lateral region gives rise to fibers which fol-
low the so-called " perforant " pathway (red), and (b) the medial region gives rise to fibers which follow the so-called
" alvear " pathway ( blue) Axons of pyramidal cells in the hippocampal formation, including those in the subiculum,
enter the alveus, and pass to the fimbria of the hippocampal formation. The dentate gyrus gives rise to fibers that re-
main within the confines of the hippocampal formation.
plexuses arising from both poles ( Fig. 5.8J ). been divided into outer and inner zones.
Basal and apical dendrites of the pyramidal Cells of the outer zone distribute axons to the
cells enter adjacent layers, while axons of molecular layer. Cells of the inner zone send
these cells pass through the stratum oriens to some axons into the alveus, while others ram-
enter the alveus ( Fig. 18.16). On their way to ify within this layer or pass into the pyrami-
the fornix, branches of pyramidal cell axons, dal layer. The stratum radiatum is made up
called Schaffer collaterals , pass through the largely of interlacing and branching
polymorphic and pyramidal cell layers to processes which appear to radiate from the
synapse in the molecular layer with the den- bordering pyramidal layer. The stratum la-
drites of other pyramidal neurons. Hippocam - cunosum and stratum moleculare, sometimes
pal basket cells , similar to the pyramidal cells, considered as a single lamina , contain a rich
are found mainly near the border between plexus of fibers from other layers.
the stratum pyramidale and the stratum Although the architectonics of the hip-
oriens ( 219). Their axons do not enter the pocampal formation is uniform throughout
alveus, but loop back through the stratum ra - its extent, there are variations in cell mor-
diatum to form a dense basket plexus about phology, differences in the relative develop-
pyramidal cell bodies. The stratum oriens, ment of various cortical regions, and differ-
containing fibers and polymorphic cells, has ences in the pathways followed by various
fiber systems. On the basis of these differ- so-called per foralit path and alvear path (16,
ences Lorente de No (141 ) subdivided the 140, 141 , 221, 286, 287). Fibers of the perforant
hippocampal formation into sectors desig - path originate principally in the lateral part
nated as CA 1 , CA 2, CA 3, and CA 4. The let - of the entorhinal area and follow a complex
ters "CA" are derived from cornu amnionis , an trajectory through the subiculum and across
older descriptive term applied to the hip- the base of the hippocampal sulcus to termi -
pocampus because of its resemblance, when nate in the outer two-thirds of the molecular
seen in cross-section , to the horns of an layer of the dentate gyrus ( Fig. 18.16 ) (16 ).
Egyptian deity that is represented bv a ram 's Fibers of the alvear path originate mainly
head (161 ). The position of these various sec - from the medial aspect of the entorhinal area
tors is shown in Figure 18.15. In humans, the and traverse the subcortical white matter and
CA 4 sector merges imperceptibly with the the alveus to enter the hippocampus from its
dentate gyrus and often is not recognized as a ventricular surface ( Fig. 18.16 ). The perforant
distinct entity ( 16, 59). It has been estimated and alvear pathways are often referred to
that there are about 2.1 x 10*’ neurons in the simply as lateral and medial perforant path -
CA 3 sector and approximately l).22 xl ()h ways ( 41 ). Both pathways innervate chiefly
pyramidal cells in the CA 2 sector of the the dentate gyrus, but also provide direct
human hippocampus ( 241 ). projection to the subiculum, which could be
of great functional importance ( 286 ).
Dentate Gyrus Cells of the dentate gyrus do not project
outside of the hippocampal formation, but
Like the hippocampus, the dentate gyrus send their distinctive axons ( the mossy fibers )
—
consists of three layers a molecular taper , a
granular layer , and a polymorphic layer ( Figs.
to cells of the dentate gyrus own polymor-
phic layer and to proximal dendrites of pyra -
18.14 and 18.15). Layers of the dentate gvrus midal cells of the CA3 sector of the hip-
are arranged in a U - or V-shaped configura - pocampus (16 ). Collaterals of single CA 3
tion in which the open portion is directed to- pyramidal cells project to other levels of CA3,
ward the fimbria in transverse sections ( Figs. to CA 1 , and to subcortical regions, especially
18.13 and 18.16). Thus, layers are present on the septal nuclei . The CA 3 cells contribute the
both sides of sector CA3 of the hippocampus, major input system to CA1 ( the Scheffer col -
which extends into the hilus of the dentate laterals ), which terminate throughout the
gyrus. The molecular layer of the dentate stratum radiatum and stratum oriens (110 ). In
gyrus is continuous with that of the hip- contrast to CA 3 cells, CA 1 pyramidal cells do
pocampus in the depths of the hippocampal not project significantly to other levels of
fissure. The granular layer is made up of CA 1 . Instead , CA1 pyramidal cells predomi -
closely arranged spherical or oval neurons nantly project to the subicular cortex, which
that are termed granule cells and whose in turn projects to the deep layers ( layers V
axons pass through the polymorphic layer to and VI ) of the entorhinal cortex ( Fig. 18.17).
terminate upon dendrites of pyramidal cells Cells in the deep layers of the entorhinal cor-
in the hippocampus. Dendrites of granule tex in turn project to the superficial layers,
cells enter mainly the molecular layer. It has and the latter give rise to the perforant path -
been estimated that the human dentate gyrus way fibers.
contains 9 x 10*’ granules cells ( 241 ). Cells of The intrinsic circuitry of the hippocampal
the polymorphic layer are of several types, formation appears to be organized into a
including modified pyramidal cells and so- closed loop that enables unidirectional flow
called basket cells. The dentate gyrus does of information ( 16, 41 ). This unidirectional
not give rise to fibers passing beyond the hip- feedforward neuronal system involves the
pocampal formation (220). classic trisvnaptic pathway, which consists of
successive excitatory projections from the en -
Intrinsic Connections torhinal cortex to the dentate gyrus, from
granule cells of the dentate gyrus to the CA 3
The dentate gyrus can be considered as the pyramidal cell region , and from CA 3 to the
first step in the intrinsic hippocampal cir- CAT pyramidal cell region . Results of more
cuitry . Its major input comes from cells lo- recent studies, however, provide a different
cated primarily in layers II and III of the en - conceptualization of the functional organiza -
torhinal cortex (area 28) that give rise to the tion of the hippocampus with respect to the
Figure 18.17. Transverse section of the hippocampal formation showing the anatomic circuitry allowing information
to flow In a serial, unilinear manner in this structure so as to form a closed loop This loop involves a series of projections
leading from ( 1) the entorhinal cortex to the dentate gyrus. (2) the dentate gyrus to the CA3 sector. (3) the CA3 sec -
tor to the CA 1 sector. (4) the CA 1 sector to the subiculum. and (5) the subiculum back to the entorhinal cortex The
first three segments of this loop constitute the classic trisynaptic pathway that has been extensively studied in regard
to learning and memory functions and their physiologic correlate, long-term potentiation ( LTP) CA. cornu ammonis.
CS. collateral sulcus; EC. entorhinal cortex; F. fimbria; GD dentate gyrus; SU subiculum
. .
propagation of activity through its intrinsic multiple populations of specific local circuit
pathways. This novel scheme underlines the neurons ( 234).
fact that input from the entorhinal cortex ini - The hippocampal formation has a unique
tiates a two-phase feedforward excitation of and highly distributed network of intrinsic
pyramidal cells, with the dentate gyrus pro- connections, and much remains to be known
viding feedforward excitation of CA3, and about the principles of organization that gov-
with both the dentate and CA3 providing ern information flow through this system.
feedforward excitation of CA 1 ( 290). Other The notion that information processing in the
studies emphasized the multiple similarities hippocampal formation is segregated in au -
that exist between the hippocampus tonomous chips or lamellae, however, ap-
( Ammon's horn ) and dentate gyrus with re- pears to be inconsistent with the extremely
gard to the organization of the intrinsic cir- divergent nature of many of the intrinsic con-
cuitry , and pointed out the importance of nections (15).
local interactions and parallel processing
( 234 ). The idea of serial processing of afferent
Extrinsic Connections
information, from one hippocampal subre-
gion to the next, appears to be inadequate The fornix constitutes the main efferent
and based on an oversimplification of the cir- fiber system of the hippocampal formation.
cuitry. Information processing undoubtedly This bundle contains about 1.2 million fibers
occurs over parallel, as well as serial path- in humans ( 210). It includes both projection
ways, with an important contribution from and commissural fibers ( Figs. 18.11 and
18.12 ). It is composed of axons of cells of the inating in the subiculum and presubiculuni
subicular cortex ( presubiculum, subiculum, provide the major extrinsic input to the mam -
and prosubiculum ) and of pyramidal cells of millary nuclei. The lateral mammillary nu -
the hippocampus ( 16, 156, 157, 229, 255-257), cleus is innervated by the subiculum and pre-
which spread over the ventricular surface as subiculum and the median mammillary
the alveus and then converge to form the fim- nucleus is innervated by the subiculum ( 16).
bria . Proceeding backward, the fimbriae of Other efferent fibers from the subicular cortex
the two sides increase in thickness. On reach - project directly to the medial frontal cortex,
ing the posterior end of the hippocampus, the caudal cingulate gyrus, and the parahip-
they arch under the splenium of the corpus pocampal gyrus. Some postcommissural
callosum as the crura of the fornix, at the fornix fibers descend caudally beyond the
same time converging toward each other. In mammillary bodies to enter the midbrain
this region , a number of fibers pass to the op- tegmentum ( 16, 90, 175, 176 ). Caudally con -
posite side, forming a thin sheet of crossing tinuing fibers of the fornix are joined by nu -
fibers, the fornical commissure ( hippocampal merous fibers from the septal nuclei to form a
commissure, or psalterium) a structure rather large part of one of the most massive roots of
poorly developed in humans ( Figs. 18.11 and the medial forebrain bundle (Zuckerkandl's
18.12). In nonhuman primates, only the ros- "olfactory bundle of Ammon 's horn").
tral (or uncal ) part of the hippocampus and Precommissural fornix fibers constitute a
associated dentate gyrus are connected by smaller, less compact group of fibers that can -
commissural fibers. The presubiculum in not be detected grossly . These fibers originate
monkeys gives rise to a substantial commis- from pyramidal cells in the hippocampus
sural projection, which terminates in layer III proper and to a lesser extent from the subicu -
of the contralateral entorhinal cortex (16). The lum and entorhinal cortex. They are distrib-
two crura then join to form the body of the uted principally to the septal nuclei, the lat-
fornix , which runs forward under the corpus eral preoptic area, the anterior part of the
callosum to the rostral margin of the thala - hypothalamus, and the nucleus of the diago-
mus ( Fig 16.2 ). Here the bundles separate nal band ( 175, 176 ).
again , and , as the anterior columns of the fornix , The nucleus accumbens also receives a
arch ventrallv in front of the interventricular projection through the fornix that arises in
foramina and caudal to the anterior commis - the subicular and entorhinal cortex. The
sure. The fimbriae, thin bands of fibers situ - subiculum and entorhinal cortex give rise to
ated laterally, accompany the fornices additional projections to the caudate nucleus
throughout most of their extent ( Figs. 18.11 and the putamen (16, 88). The hippocampal
and 18.12 ), but rostrally they become incor- formation is also reciprocally connected with
porated within the anterior columns of the the amygdala and the claustrum through the
fornix. The largest number of the fibers de- subicular and entorhinal cortex ( 4, 16, 122 ).
scend caudal to the anterior commissure as The septal and surpramammillary areas also
the postcommissural fornix ( 52, 210). Remain - project to the hippocampal formation. The
ing fibers of the fornix pass rostral to the an - septohippocampal projection, first demon -
terior commissure as the precommissural strated in the early 1950s (52, 168), arises from
fornix. cholinergic and , to a lesser extent, CiABAergic
Postcommissural fornix fibers , originating neurons in the medial septal nucleus and the
from the subicular cortex, traverse the hypo- nucleus of the diagonal band of Broca . The
thalamus en route to the mammillary body - axons of these neurons course in either
In their course, they give off fibers to the thal - the fimbria , dorsal fornix, supracallosal striae,
amus (16, 157, 256 ). Fibers leaving the post - or along a ventral route through the amyg-
commissural fornix in the rostral hypothala - dala , and arborize in virtually all fields of the
mus are distributed to the lateral septal nuclei hippocampal formation, but are most promi -
and the anterior and lateral dorsal thalamic nent in the dentate gyrus and the CA 3 field of
nuclei ( 16, 90, 175, 269 ). The anterior nuclei of the hippocampus ( 16). The entorhinal cortex
the thalamus receive as many direct fibers also is innervated by cholinergic neurons of
from the fornix as from the mammillothala- the medial septal nucleus and the nucleus of
mic tract ( 210 ). Presubicular fibers innervate the diagonal band of Broca .
the anteromedial, anteroventral, and lateral The major hypothalamic projection to the
dorsal nuclei of the thalamus, and fibers orig- hippocampal formation arises from a popula-
tion of large neurons located dorsal and lat- and 46 ), (e) the infralimbic and prelimbic por -
eral to the mammillary bodies in the so-called tions of the medial frontal cortex (areas 25
supramammillary area . This projection termi- and 32) and the cingulate cortex (area 24 ),
nated principally in sectors CA 2 and CA 3 of and ( 0 the retrosplenial cortex (107 ). In turn,
the hippocampus, and in the rostral entorhi - the entorhinal cortex appears to project back
nal cortex ( 16, 108). This projection could pro- to most of these cortical areas (16 ). Through
vide a reciprocal link between the mammil - these connections, the hippocampal forma-
lary bodies and the subiculum, which tion is able to influence widespread areas of
projects heavily upon the medial and lateral the temporal, parietal, and frontal lobes. The
mammillary nuclei. parahippocampal gyrus, in particular, pro-
-
Recent tract tracing studies have revealed jects to virtually all association cortices of the
hitherto unknown projections from the thala - brain ( 272 ).
mus to the hippocampal formation (108). While the entorhinal cortex is the major
These projections arise from all divisions of anatomic interface between the hippocampal
the anterior thalamic nuclear complex and as- formation and the cerebral cortex, the subicu -
sociated lateral dorsal nucleus, as well as lar cortex is also reciprocally linked to the
from the midline thalamic nuclei (e.g.,
parataenial , centralis medialis, and reuniens
neocortex. The various regions of the subicu
lar complex in nonhuman primates receive
-
nuclei ). The nucleus reuniens projects pri - projections from, and project to, the perirhi-
marily to the stratum lacunosum- moleculare nal cortex, the parahippocampal gyrus, the
of CA1, in portions of the subicular cortex, cingulate gyrus, and the medial frontal and
and in the entorhinal cortex (16, 108 ). Projec- medial orbitofrontal cortices.
tions to the entorhinal cortex from the dor - All the extrinsic anatomic connections de-
somedial portion of the pars medialis of scribed earlier indicate the complex pathways
the pulvinar nucleus have also been docu - whereby signals from the hippocampal for-
mented ( 108 ). mation can be projected to different parts of
The neuronal activity in the hippocampal the neuraxis. Both direct and indirect path -
formation is also modulated by inputs origi - ways connect the hippocampal formation
nating in various brainstem nuclei, princi - with the septal nuclei, the thalamus, the hy-
pally the ventral tegmental area, the locus pothalamus, and widespread regions of the
coeruleus, and the midbrain raphe nuclei. cerebral cortex and the midbrain reticular for-
The locus coeruleus gives rise to the major mation ( Figs. 18.3 and Fig . 18.10 ).
noradrenergic input to the hippocampal for-
mation ( 198), whereas the midbrain raphe Chemical Anatomy
nuclei, chiefly the median (or central supe-
rior ) nucleus, provides a prominent sero- Studies of the localization of neurotrans-
toninergic innervation ( 265 ). Both of these mitters with histochemical and immunohisto-
nuclei project to most of the hippocampal for- chemical methods provide important clues
mation , with a particularly dense innervation concerning the neural computation that oc-
of the dentate gyrus. There is also experimen - curs in the hippocampal formation ( 104 ). A
tal evidence for the existence of a dopaminer-
gic projection to the hippocampus that ap-
-
large variety of small molecule transmitters
and neuroactive peptides have been detected
pears to originate in the midbrain ventral at the hippocampal level. GABA is believed
tegmental areas ( 16 ). to be the main inhibitory transmitter,
The entorhinal and subicular cortex are in whereas noradrenaline, serotonin, and acetyl -
close reciprocal relationship with the sur - choline are widely distributed neuromod -
rounding cerebral neocortex. In monkeys, the ulators. Glutamate is the most important ex-
entorhinal cortex receives prominent projec- citatory neurotransmitter in this region ( 41 ).
tions from (a ) several areas of the temporal A multitude of neuroactive peptides are
lobe, particularly areas TF and Til of the also present in the hippocampal formation
parahippocampal gyrus, the perirhinal cortex (e.g., somatostatin, galanin, substance I’,
( area 35), the temporal polar cortex ( area TG ), enkephalin, histamine, cholecystokinin, neu -
the dorsal bank of the superior temporal ropeptide Y, dynorphin , angiotensin, vasoac-
gyrus, ( b ) the ventral or agranular insular tive intestinal peptide, and corticotropin - re-
cortex, ( c ) the posterior orbitofrontal cortex, leasing factor ), but their exact functional
( d ) the dorsolateral frontal cortex (areas 9, 10, significance is still uncertain. Enkephalin oc-
curs in some axons that emerge from the hilar ents and serotoninergic input from the me-
region of the dentate gyrus and terminate as dian raphe nucleus converge onto distinct
mossy fibers on proximal apical dendrites classes of hippocampal interneurons. These
of hippocampal pyramidal cells, as well as interneurons can be differentiated from one
in other axons of the lateral perforant path - another by the type of calcium binding pro-
way ( 74 ) . tein they contain; some are enriched with cal -
GABA is believed to be the primary trans- bindin D-28k, while others contain parvalbu -
mitter released by inhibitory interneurons min ( 163). At the synaptic level , the action of
that synapse onto both the soma and den- acetylcholine on hippocampal neurons ap-
drites of pyramidal and granule cells. As else- pears to be mediated by the muscarinic sub-
where in the brain, its action depends on the type of cholinergic receptor.
class of postsynaptic receptors to which it The noradrenergic input from the locus
binds. The two main GABA receptor subcoeruleus is also known to play an important
types, GABAA and GABAb, are differentially modulatory role at the hippocampal level,
distributed in the hippocampus. The GABAA principally at the hilus of the dentate gyrus
subtype, which is coupled to a slow potas- and the stratum lucidum of the CA 3 sector,
sium conductance, is preferentially found on where the innervation is most dense ( 240) .
the soma of hippocampal neurons, whereas Noradrenaline applied to the CA 1 region has
GABA|t, which is coupled to a fast chloride at least two different effects: (a ) a decrease of
conductance, is preferentially located on den- pyramidal cell inhibition, possibly through
drites of hippocampal neurons ( 111 ) . GABA an inhibitory effect on the inhibitory in-
can interact with other neurotransmitters or terneurons mediated via an a , receptor, and
neuromodulators in the hippocampus. For ( b) a direct effect on pyramidal neurons me-
example, glutamate enhances the GABAA re- diated through 31 receptor, probably to
sponse, and serotonin and GABAlt can inter- enhance the response to excitation and re-
act via potassium channels that are coupled duce accommodation . Although noradrena -
to the same G -protein . Inhibitory postsynap- line plays an important role in the control of
tic potentials evoked by both GABAA and cell excitability in the CA 1 sector, there is no
GABA (i can be reversibly blocked by evidence that it has any direct effect on long-
enkephalin ( 41 ). GABA is not confined to hip- term potentiation (discussed later) at the
pocampal interneurons, but is also present in Schaffer collateral synapse in this region ( 41 ) .
some hippocampal afferent fibers, particu- Glutamate is known to exert its excitatory
larly those from the septal region ( 162 ). Addi - action at the hippocampal level by activat -
tionally , this inhibitory neurotransmitter ap- ing two distinct conductances, one mediated
pears to coexist with the excitatory by N-methyl - D-aspartate ( NMDA ) receptors
neurotransmitter glutamate in mossy fiber and the other by non-NMDA ( kainate-
terminals ( 232). quisqualate ) receptors. In contrast to ionic
Acetylcholine exerts various modulatory channels associated with non - NMDA recep-
effects in the hippocampus. As mentioned tors, the NMDA receptor-gated channels
earlier, the cholinergic fibers to the hip- have a high permeability to calcium, and it is
pocampus arise mainly from neurons in the the calcium current through these channels
medial septal nucleus and the nucleus of the that appears to trigger long - term potentiation
diagonal band of Broca . They terminate in all induction (41 ) . The molecular properties of
hippocampal regions, but are most promi - the NMDA receptor-gated channels are espe-
nent in the dentate gyrus and the CA3 sec- cially important in regard to the activity-de-
tor of the hippocampus. Lesions of the fim- pendent neuronal modifications that occurs
bria / fornix system produce a substantial loss at the hippocampal level during learning and
of the cholinergic innervation of the hip- information storage procedures.
pocampus, as shown by the pioneering stud -
ies of Lewis and Shute (135, 136). This loss of Functional Considerations
cholinergic input can be alleviated by trans-
plantation of embryonic cholinergic neurons Anatomic and physiologic evidence indi -
from the septal area into the hippocampus of cate that the hippocampus has no significant
adult animals, a brain grafting procedure that olfactory function ( 39). The hippocampus
also restores learning ability in monkeys with and dentate gyrus are well -developed in
fornix lesions ( 224) . Cholinergic septal affer- cetaceans that are said to be completely anos-
matic and lack olfactory bulbs and nerves (1, structures but, in most instances, quickly re-
225). Although not directly involved in the cruit the whole anterior cortex. Selective
processing of olfactory information, the hip- amygdalo-hippocampectomy is an alterna-
pocampal formation is believed to play im- tive approach when a clear mediobasal limbic
portant roles in learning and memory, as well focus has been repeatedly demonstrated by
as in the control of emotional behaviors and intracranial recording (187).
neuroendocrine functions. The hippocampus appears to be concerned
Our knowledge of the functions of the hip- particularly with recent memory (86 ). Rela -
pocampal formation is largely based upon tively large bilateral lesions of the hippocam-
the results of lesion studies in experimental pus (58, 77, 239, 278, 279) are associated with
animals and on clinical observations of pa - profound impairment of memory for recent
tients with hippocampal lesions. Bilateral events (short-term memory ) and with rela-
damage to the hippocampus can occur when tively mild behavioral changes. Memory for
a head injury causes the temporal poles to remote events (long-term memory ) usually is
strike the greater wings of the sphenoid bone, unaffected . Although general intellectual
which form the anterior wall of the middle functions may remain at a fairly high level,
cranial fossa. Loss of hippocampal function these patients demonstrate an inability to
can also occur as a result of cerebral anoxia . learn new facts and skills. These findings are
The large pyramidal cells of the CA1 sector of in accord with those found after bilateral re-
the hippocampus are exceptionally sensitive section of the medial parts of the temporal
to oxygen deprivation and die after only a lobe in cases of epilepsy (187). According to
few minutes without a supply of fresh arter- Scoville and Milner ( 239 ), lesions of the most
ial blood . Pathologists refer to area CA 1 as anterior portion of the temporal lobe do not
the Sommer 's sector . Many patients resusci- impair memory , which occurs only when the
tated after cardiac arrest of more than a few lesions extend far enough posteriorly to in -
minutes' duration are left with defective volve the hippocampal formation, the dentate
memory for this reason (25). Degenerative gyrus, and parts of the parahippocampal
changes, including neurofibrillary tangles, gyrus. It is generally believed that loss of
neuritic plaques, and amyloid deposits, are memory occurs only if lesions of the hip-
particularly prominent in this hippocampal pocampal formation and parahippocampal
area in patients suffering from Alzheimer's gyrus are bilateral ( 200), but some patients
disease, which is initially characterized by the may show mild verbal disorders or distur-
inability to form new memories. bances of memory following resections of
Localized lesions in the hippocampus and parts of the temporal lobe of the dominant
local stimulation of this structure in con - hemisphere.
scious experimental animals tend to produce Experimental studies in the monkey indi-
similar phenomena (83, 84). Behavioral cate that bilateral removals of the amyg-
changes observed in these animals resemble daloid complex and portions of the hip-
those occurring in psychomotor epilepsy, and pocampal formation, including perirhinal
it seems likely that the abnormal fears, hyper- and parahippocampal cortices, impair mem -
esthesia , and pupillary dilatation seen may ory and learning that depend upon visual,
represent fragments of a seizure. The behav- auditory, and tactile discriminations (189,
ioral changes noted initially after lesions tend 248, 250, 253, 294 ). The type of behavioral test
to disappear but recur at a later time. The used to measure retention following tempo-
hippocampus has an exceedingly low thresh - ral lobe lesions is very important. When rhe-
old for seizure activity (83, 86, 143, 144 ), and sus monkeys are tested for their ability to dis-
seizure discharges tend to spread from the criminate between pairs of visual stimuli
hippocampus to other parts of the limbic lobe presented concurrently, anterior inferotem-
and ultimately to the neocortex. Amygdalo- poral cortex lesions impair learning. This is
hippocampectomy is a surgical procedure also true when the lesions extend more
that is often used for the treatment of tempo- deeply to include the hippocampus. With the
ral lobe epilepsy (187). It allows removal of extension of the lesions into the hippocam-
an ample amount of epileptogenic tissue and pus, the animals show an additional impair-
is not accompanied by significant intellectual ment of learning for tactile stimuli (169, 253).
deficit . It takes into account the fact that tem- These complexities in analyzing the involve-
poral seizures usually arise in the limbic ment of the hippocampus and other temporal
lobe structures in mechanisms of memory ronal plasticity. From these studies emerge
make it difficult to draw broad generaliza- the idea that long-term potentiation ( LTP)
tions from the experimental and clinical liter- could be the synaptic mechanism responsible
ature related to lesions (103, 248, 294 ). for rapid learning in mammals (33). This fas-
Even though the fornix contains most of cinating form of synaptic plasticity has been
the efferent fibers from the hippocampal for- most thoroughly studied in the mossy fiber-
mation, evidence that interruption of these synaptic input to CA3 sector and the Schaffer
fibers produces memory loss is still contro- collateral synaptic input to CA1 sector (41 ).
versial (6, 7, 57, 75, 169, 258). The mammillary LTP is an increase in synaptic efficiency that
bodies, like the fornix, seem to be implicated -
follows a few seconds of high frequency ac-
in memory, but available experimental data tivity of presynaptic terminals. For example,
do not always concur with such a view. Re- brief repetitive stimulations of fornix or en-
cent clinical and experimental findings, how- torhinal afferent axons leads to a prolonged
ever, suggest that the fornix system is indeed increase in the responsivity of hippocampal
involved in mnemonic functions in both hu- pyramidal cells or dentate granule cells (33).
mans (73) and monkeys (224). Furthermore, it The concept of increased synaptic efficiency
seems that the hippocampal connections with referred to a reduction in the number of affer-
the entorhinal cortex (16, 229) are important ent impulses and , therefore, of the amount of
for associative learning involving more than neurotransmitter needed to depolarize the
one modality (169). postsynaptic cells. Depending upon the con -
In rats, bilateral destruction of the hip- ditions of stimulation, the effect may last sev-
pocampus, the fornix, and mammillary bod - eral hours or days and typically lead to in -
ies produces a severe disturbance in maze creased activity of affected postsynaptic
learning (115). Chronic single hippocampal neurons. In normal conditions, LTP can be in -
neuron recordings in freely behaving rats induced at the level of certain pyramidal and
dicate that these cells encode the animals' granule cells following a suitable pattern of
specific position in its environment (183). It activity in hippocampal afferent axons. The
has been hypothesized that the hippocampus affected recipient cells will continue to trans-
contains an internal "cognitive map" of be- mit impulses more frequently than before,
haviorally significant features of the environ- even though the original external stimuli
ment ( 184). Single unit recordings in the rab- have ceased ( 25, 41 ).
bit hippocampus show a high correlation Although LTP is likely to serve as a mech-
between pyramidal cell discharge in CA1 and anism for the storage of recent memories by
CA3 and the acquisition of a conditioned re- the hippocampus, the formation of perma -
sponse (31). nent memory traces is likely to involve the
Much more information is needed about synthesis of new proteins and the formation
the location of neurons that are essential for of new synapses (42, 117). The consolidation
learning a specific task before it will be possi- of recent memories may occur during sleep,
ble to understand the mechanisms of learn- when the serotoninergic raphe neurons that
ing. It can be reasonably argued from the project to the hippocampus are active. In
available literature that memory and learning deep sleep, when the electroencephalogram
are distributed processes, involving neuron ( EEG ) recorded over the neocortex displays
assemblies in many regions of the brain. If regular, synchronized rhythms, the hip-
this is true, progress on the problem of mem- pocampal EEG is desynchronized . In the
ory will require new strategies to relate bio- waking state, the neocortical record is desyn -
physic and biochemical events at the cellular chronized and the hippocampus generates a
level to the properties of distributed neuronal typical, slow regular rhythm, that is termed
networks ( 45, 116, 117). the theta rhythm . The theta rhythm is a 5-12
It has been hypothesized that short- and Hz pattern of electrical activity observed in
long-term learning and memory is related to the hippocampal region that is correlated
morphologic or functional changes in with certain behavioral states in the freely
synapses. The association of the hippocampal moving animal. It is most pronounced when
formation with learning, together with its the animal is alert and interested by what is
highly ordered arrangement of cells and happening in its immediate environment; it
input axons ( Fig. 18.18), has led to a large fades when external stimuli are repeated. The
number of experiments dealing with neu- theta rhythm is believed to reflect the "gat-
Stratum
moleculare
_
Entorhinal cortex
(perforant path)
Recurrent (Schaffer )
collaterals of hippocampal
pyramidal cells in CA 3
Stratum
lacunosum
Raphe , septal region
Stratum -*
radiatum Commissural axons; intrinsic
short axon cells
Mossy fibers
from dentate fascia
Stratum-* Basket cells

pyramidale
Short axon cells;

commissural axons
Stratum-*
oriens
Alveus-*
Figure 18.18. CA 1 sector hippocampal pyramidal neuron indicating the regions of the cell that receive specific -
af
ferent inputs Specific cell layers of the hippocampal formation can be related to specific parts of the pyramidal
cell
and are shown on the left Afferent inputs from several sources are indicated on the right . Afferent fibers
synapse in
specific locations upon dendritic shafts, dendritic spines, the cell body, and the basal dendrites of
the pyramidal cell
ing" of information through the hippocampal from the cortex reach the hypothalamus. Im -
circuits ( 41 ). pulses reaching the hypothalamus are pro-
The hippocampal circuitry displays a re - jected caudally through the brainstem to ef -
markable degree of morphologic plasticity . fector structures, as well as rostrally to
This feature renders the hippocampal forma - thalamic and cortical levels. The "central
tion particularly suitable for playing a role in emotive process of cortical origin " is consid -
memory and learning. The hippocampus ered by Papez to be formed in the hippocam -
shows reactive synaptogenesis following in- pal formation and transmitted to the mam -
terruption of some of its afferent fiber sys- millary bodies, the anterior nuclei of the
tems. This morphologic plasticity has been thalamus, and the cingulate gyrus. The cingu -
studied extensively in the dentate gyrus fol - late cortex is regarded as the receptive corti -
lowing interruption of perforant pathway cal region for impulses concerned with emo-
fibers from the entorhinal cortex ( 46, 47). Uni- tion . Signals transmitted from the cingulate
lateral entorhinal cortical ablation leads, over gyrus to other cortical regions are believed
a period of weeks, to the formation of new to add emotional coloring to the psychic
synapses in the denervated area of the ipsilat - process (193).
eral dentate gyrus. Many of the new synapses
are formed by growth of collaterals from
axons originating in the contralateral entorhi- AMYGDALA
nal cortex, and by sprouting of septohip- Nuclear Organization
pocampal axons. Like the original perforant
pathway projection, the newly formed The amygdala ( or amygdaloid nuclear
synapses may sustain long-term potentiation complex ) is a gray mass situated in the dorso-
following repetitive stimulation ( 285). medial portion of the temporal lobe, in front
Korsakoff s sipidrome (amnestic confabula- of , and partly above the tip of the inferior
torv syndrome) appears as a sequel to Wer- horn of the lateral ventricle ( Figs. 2.10, 2.16,
nicke's encephalopathy and probably is re- 18.10, 18.11, 18.14, 18.19, and 18.20 ). It is cov-
lated to a thiamine deficiency associated with ered by a rudimentary cortex and caudally is
alcoholism. This syndrome is characterized continuous with the uncus of the parahip-
by severe impairment of memory without pocampal gyrus ( Figs. 2.6, 2.10, and 18.19 ).
clouding of consciousness, confusion, and The amygdaloid complex is divided into
contabulatory tendencies. Lesions in this syn- two main nuclear masses: ( a ) a corticomedial
drome almost always involve the mammil - nuclear group and ( b ) a basolateral nuclear
lary bodies and adjacent areas ( 259 ). Patients group (50, 51, 79, 270 ). A central nucleus,
suffering from the Korsakoff 's syndrome, in - which can be divided into a medial and a lat -
sert remembered events from the remote past eral part, is regarded as a separate subdivi -
into fluent, but blatantly untrue, stories, at - sion , but sometimes is included as part of the
tempting to compensate for the absence of corticomedial group, basolateral nuclear
more recent memories ( 25). Amnesia is said group, or the so-called extended amygdala.
to be present in this syndrome, especially if The extended amygdala concept is based on
there is additional involvement of certain recent evidence that supports the view held
thalamic nuclei, chiefly the mediodorsal nu - by Johnston (112) that the bed nucleus of the
cleus ( 277, 280 ). stria terminalis and the central and medial
Particularly prominent among concepts re- amygdaloid nuclei constitute a single
lating the hippocampal formation to emotion anatomic entity. This concept, which is sup-
is the theory proposed by James Papez in ported by the strikingly uniform staining of
1937 ( 193). Realizing that the term "emotion" this group of structures with various neu -
denotes both subjective feelings and the ap- ronal molecular markers, particularly the lim -
propriate autonomic and somatic responses, bic system -associated membrane protein
Papez concluded that ( a ) the cortex is essen - ( LAMP) ( Fig. 18.4 ), has gained wide accep-
tial for subjective emotional experience, and tance (55).
( b ) emotional expression must be dependent In humans, the corticomedial nuclear group
on the integrative actions of the hypothala- occupies the dorsomedial aspect of the amyg-
mus. The hippocampal formation and its daloid complex due to a medial rotation of
principal projection system, the fornix, pro- the temporal lobe. Nuclear subdivisions of
vides the main pathway by which impulses the corticomedial group include (a ) the ante-
Caudate nucleus
I
-
Corpus callosum
Anterior nuclear group of thalamus
Putamen
Ventral anterior nucleus
Globus pallidus —
Fornix
Substantia mnominata
Optic tract
Uncus
Amygdaloid nuclear complex
Figure 18 19 Transverse section through the thalamus, basal ganglia, and amygdaloid nuclear complex The sub-
stantia innominata lies ventral to the globus pallidus and dorsal to the amygdala Human brain, Weil stain.
Corpus callosum
Genu
/^
^Rostrum
Caudate nucleus
(head)
Internal '
capsule Putamen
ant . limb
Anterior «
Cingulate gyrus
comm .
Nucleus accumbens
septi
Substantia
innominata Amygdala
Hippocampus
Dentate gyrus
Figure 18 20. Section cut parallel to the longitudinal axis ot the brainstem through the genu of the corpus callosum
the head of the caudate nucleus, the putamen. the substantia innominata. the amygdala, and the hippocampal
formation The sections reveal the nucleus occumbens. ventromedial to the head of the caudate nucleus The sub-
stantia innominata lies in the subcommissural region, ventral to the basal ganglia, and contains the large hyper -
chromic neurons known as the basal nucleus of Meynert Cells of the basal nucleus are the major source of choliner -
.
gic innervation of the entire cerebral cortex and the amygdala Human brain Weigert ' s myelin stain
rior amygdaloid area , ( b ) the nucleus of the fibers of the stria terminalis (stria semicircu -
lateral olfactory tract, (c ) the medial amyg- laris) collect at the ventromedial portion of
daloid nucleus, and (d ) the cortical amyg- the caudal amygdala and arch along the en -
daloid nucleus, whose dorsalmost portion is tire medial border of the caudate nucleus
termed periamygdaloid cortex . The nucleus near its junction with the thalamus ( Fig. 16.7).
of the lateral olfactory tract is the least well- Rostrally, these fibers pass into and terminate
developed of the amygdaloid nuclei in hu - in the bed nuclei of the stria terminalis lo-
mans. The anterior amygdaloid area, repre- cated lateral to the columns of the fornix and
senting the most rostral part of the dorsal to the anterior commissure ( 54, 99).
amygdaloid complex, is rather poorly differ- Other fibers of the stria terminalis end in the
entiated (70). The corticomedial amygdaloid anterior hypothalamic area , and some may
nuclear group lies closest to the putamen and join the medial forebrain bundle.
tail of the caudate nucleus. In contrast to previous beliefs ( 48, 54, 70,
The largest and best differentiated part of 97, 125, 220, 270 ), these two bundles do not
the amygdaloid complex in humans is the ba- carry distinct sets of fibers, and fibers from
solateral nuclear group. Subdivisions of this nu - one bundle appear to join fibers in the other
clear group are (a ) the lateral amygdaloid nu - bundle throughout their trajectory. For exam -
cleus, ( b ) the basal amygdaloid nucleus, ple, fibers which initially run in the ventral
-
which can be divided into magno and parvi - amygdalofugal pathway have been observed
cellular parts, and (c) the accessory basal to run into the internal capsule to join the
amygdaloid nucleus, which can also be di- stria terminalis. Efferents from most of the
vided into magno- and parvicellular parts. amygdaloid nuclei generally exit the amyg-
Caudally, the amygdala is in contact with the dala via both the stria terminalis and the
tail of the caudate nucleus, which sweeps ros- amygdalofugal pathway ( 18). These two
-
trally in the roof of the inferior horn of the lat well -delineated pathways are primarily sub-
eral ventricle ( Figs. 2.13,18.14 , and 19.37). cortical fiber systems. The amygdalocortical
The extended amygdala , a term that was interconnections, which are prominent in pri -
coined by Alheid and Heimer (9), includes mates, are established mostly via the internal
principally ( a ) the central amygdaloid nu - capsule. In primates, this fiber system is as
cleus, ( b) the bed nucleus of the stria termi - prominent as the subcortical fiber systems.
nalis, and (c) the sublenticular portion of the The amygdala also contains several small in -
substantia innominata , through which the trinsic fiber bundles. Most of them are part of
medial and central amygdaloid nuclei are what Johnston (112 ) described as "longitudi-
linked with the bed nucleus of the stria terminal association bundles."
nalis. In some descriptions, the medial amyg -
daloid nucleus also is considered as part of Cytochemical Features
the extended amygdala ( 53).
The amygdala contains a multitude of
Major Fiber Bundles neurotransmitters and neurotransmitter-
related molecules. A detailed review of the
The amygdala is commonly regarded as enormous amount of literature on the chemi-
ventral amygdalofugal pathway and the stria
—
having two major extrinsic fiber systems the cal anatomy of the amygdala is beyond the
scope of this chapter. The interested reader is
terminalis. Fillers forming the ventral amyg - referred to the comprehensive reviews on
dalofugal pathway emerge from the dorsome- this topic by de Olmos (55) and , principally,
dial edge of the amygdala and spread medi - Amaral, et al. ( 18). In the following section, a
ally and rostrally beneath the lentiform brief description of the localization of the
nucleus ( 48, 78, 177). They pass through the major classes of neuromediators is provided
substantia innominata ( Figs. 18.19 and A.22) because this type of information is crucial for
and enter the lateral preoptic and hypothala- understanding the functional organization of
mic areas, the septal region , and the nucleus the amygdala .
of the diagonal band ( of Broca ). Amygdalofu -
gal fibers, bypassing the preoptic region and AMINO ACIDS
hypothalamus, enter the inferior thalamic pe-
duncle ( Fig. 16.9) and project to the magno- The primate amygdala contains high lev-
cellular part of the dorsomedial nucleus of els of the inhibitory transmitter GABA , and
the thalamus ( 71, 122, 177, 206). In contrast, the distribution of GABA-immunoreactive
neurons in the amygdaloid complex of mon- amygdala . Glutamate-immunoreactive termi-

keys were recently documented ( 148). nals that make asymmetric synaptic contacts
GABAergic neuronal subpopulations appear with dendritic shafts and spines of pyramidal
to exist in each amygdaloid nucleus in mon - neurons have been visualized in the lateral
keys. The pattern of GABA immunoreactivity amygdaloid nucleus of the rat (65), but simi -
varies in different amygdaloid regions and is lar information is not yet available in pri-
very similar to that described in the rat . In mates.
both basolateral and corticomedial nuclear
-
groups, GABA positive cells are of the non- MONOAMINES
pyramidal type and often arranged in clus-
ters. These GABA- positive nonpyramidal The primate amygdala contains moderate
neurons represent about 25% of the total neu - levels of noradrenaline and serotonin, which
ronal population of the basolateral and corti- arise respectively from the locus coeruleus
comedial amygdaloid nuclei. Numerous and the midbrain raphe nuclei ( 155, 181 ). The
GABA - positive puncta, resembling axon ter- central, medial, and cortical (or periamyg-
minals, are scattered in the neuropil, while daloid cortex ) nuclei receive a moderate nora -
others closely surround the perikarya of drenergic innervation, whereas nuclei of the
GABA - negative pyramidal cells. A very basolateral group contain relatively few nora-
dense field of GABA-positive puncta occur in drenergic fibers ( Fig. 18.21 ) ( 231 ). A substan -
the central and medial amygdaloid nuclei . tial intranuclear variability in the density of
There are numerous GABA- positive neurons innervation exists within several of the amyg-
in the lateral subdivision of the central nu - daloid nuclei. The serotoninergic innervation
cleus and fewer cells in the medial nucleus of primate amygdala is overall more mas-
and medial subdivision of the central nu - sive than the noradrenergic innervation .
cleus. Many immunoreactive puncta contact Fairly dense serotonin-immunoreactive fiber
the perikarya and dendrites of GABA- posi- plexuses occur in the lateral nucleus, parvi -
tive cells in these regions (148). It is worth cellular division of the basal nucleus, magno-
noting the presence of benzodiazepine / cellular division of the basal accessory
GABAA receptor complex in the primate nucleus, central nucleus, and the amygdalo-
amygdala (18). Benzodiazepines are the most hippocampal transition area ( Fig. 18.21 ) ( 231 ).
widely used anxiolytic drugs and the pres- The serotoninergic receptor of the 5- HT, sub-
ence of receptors for such molecules in the type is particularly abundant in the lateral ,
amygdala is in agreement with the concept basal, and cortical amygdaloid nuclei ( 18).
that this structure is involved in the control of The dopaminergic innervation of the mon -
emotional behavior. Also worth mentioning key amygdala overall is moderate, but a par-
is the recent demonstration of intrinsic ticularly dense innervation can be noted in
GABAergic neurons in the extended amyg- the lateral and central nuclei ( 231 ). In the
dala of the rat ( 251 ). basal nucleus, the most profuse innervation
The amygdala in monkeys also contains occurs in the lateral part of the parvicellular
high concentrations of the excitatory trans- division. The dopaminergic innervation of
mitters glutamate and aspartate, but our the amygdala in primates arises principally
knowledge of the nuclear distribution and from neurons in the ventral tegmental area
specific origin of these amino acids is still and in the dorsal tier of the substantia nigra
limited . Studies with tritiated aspartate as a pars compacta ( 138, 155, 181, 268, 274 ). The
retrograde tracer have identified the sources dopaminergic axons reach the amygdala
of some amygdaloid afferents that may use through the stria terminalis, as well as via
aspartate and / or glutamate as an excitatory ventral sublenticular pathways.
neurotransmitter in monkeys (17). These in- Some of the adrenergic neurons located in
clude ( a ) neurons in layers III and V of the the lower medulla project to the central nu -
frontal, cingulate, insular and temporal cor- cleus of the amygdala in the rat ( 141 ), but this
tices, ( b ) neurons in the CA 1 region of the projection is rather weak in primates ( 231 ).
hippocampus and in the deep layers of
the entorhinal cortex, and ( c) neurons in the ACETYLCHOLINE
claustrum and the midbrain peri peduncular
nucleus. These findings suggest the existence High levels of the cholinergic enzymes
of numerous extrinsic excitatory inputs to the acetylcholinesterase ( AChF ) and choline
Figure 18.21 . Transverse section through the middle third of the amygdala in the squirrel monkey illustrating the distri
bution of monoaminergic fibers and terminals A. Principal subdivisions of the amygdala B. C, and D. Fibers ( sinuous
lines) and terminals ( dots ) displaying immunoreactivity respectively for (B) tyrosine hydroxylase (( TH) indicative of
. —
dopaminergic elements). (C) serotonin (5-hydroxytryptamine 5-HT); and (D) dopamine-p hydroxylase (DBH) indica-
tive of noradrenergic elements)) AAA, anterior amygdaloid area; ABI, accessory basal nucleus, lateral part, ABm, ac
. . . .
cessory basal nucleus, medial part. AC anterior commissure Bmg basal nucleus, magnocellular part flpc basal nu-.
. . . . .
cleus parvicellular part; C central nucleus, CL claustrum, GPi globus pallidus, internal part GPe globus pallidus
. . . .
external part; / intercalated nuclei; L lateral nucleus; M medial nucleus; NLOT nucleus of the lateral olfactory tract;
. . . .
OC optic chiasm; PAC periamygdaloid cortex. PUT putamen, SO supraoptic nucleus
acetyltransferase (ChAT) are found in the a ventrodorsal decreasing gradient of fiber

amygdala of monkeys, and these two en - density is observed. In the central nucleus,
zymes are he terogeneou sly distributed the lateral division contains more somato-
throughout the various nuclei (18, 194 ). A statin immunoreactive cells and fibers than
high density of ChAT-immunoreactive fibers the medial division ( Fig. 18.22 ) (18, 58 ).
and terminals is observed in the basal nu - Neuropeptide Y ( NPY ) is also present in
cleus, parvicellular division of the accessory high concentrations in the amygdala and im -
-
basal nucleus, amygdalo hippocampal area, munoreactive cell bodies, fibers, and termi -
and the nucleus of the olfactory tract. These nals displaying immunoreactivity for this
cholinergic fibers originate in the basal nu - peptide were shown to be widely distributed
cleus of Meynert , specifically in the anterolat- in this structure ( 247). Since somatostatin and
eral portion of the nucleus (18). A smaller neuropeptide Y are colocalized in several cor-
number of cholinergic inputs arise from neu - tical and striatal neurons ( 246), it is likely , al -
rons in the anteromedial and intermediate though not yet demonstrated, that these two
portions of the basal nucleus and in the hori - peptides are also colocalized in neurons of
zontal limb of the diagonal band . In human the amygdala . Regarding the role of the
amygdala, the basolateral nucleus and the amygdala in the control of emotions, it is
lateral part of the central nucleus receive the worth noting that neuropeptide Y exerts an
most prominent cholinergic innervation (62). anxiolytic action at the amygdala level (98).
The lateral nucleus displays a relatively low Vasopressin-immunoreactive fibers, which
density of ChAT-positive fibers, and there are are likely to arise from the magnocellular
only rare ChAT-immunoreactive fibers in the neurosecretory nuclei of the hypothalamus,
medial nucleus. The other amygdaloid nuclei terminate in the medial amygdaloid nu -
contain a moderate number of ChAT-positive cleus, whereas enkephalin -immunoreactive
fibers. The cholinergic innervation of the fibers and terminals abound in the central
amygdaloid complex in humans is severely amygdaloid nucleus ( 27, 28, 60, 63, 89, 106,
affected in cases of Alzheimer's disease ( 62). 126 ). In the rhesus monkey, opiate receptors
The action of acetylcholine at the level of the are distributed widely throughout the
amygdala is most likely mediated through a amygdala (126). The locations of enkephalin
,
muscarinic ( M ) receptor subtype, but the and opiate receptors generally parallel each
distribution of this receptor does not exactly other, but there are some regions, such as
correspond to the distribution of the ChAT- the amygdala , in which differences ( mis-
immunoreactive fibers. matches) occur.
Numerous neurotensin-immunoreactive
NEUROACTIVE PEPTIDES fibers and terminals occur in the human
amygdala ( 30). The neurotensin-immunore-
A plethora of neuroactive peptides occur active elements are particularly abundant in
at the amygdala level in primates. Among the the central nucleus followed by the medial
most abundant ones are ( a ) somatostatin, ( b) nucleus and intercalated masses. The anterior
neuropeptide Y, (c) neurosecretory peptides amygdaloid area, basal nuclear complex, cor-
( vasopressin, neurophvsin , and oxytocin), (d ) tical nucleus, cortical-amygdaloid transition
opiate peptides (enkephalin and dynorphin ), area , and amygdalo-hippocampal area con -
(e) corticotropin -releasing factor, ( f ) vasoac- tain moderate densities of immunoreactivity.
tive intestinal peptide, ( g ) cholecystokinin , The accessory basal and lateral nuclei exhib-
( h ) galanin , ( i ) neurotensin, and ( j ) calcitonin ited scant neurotensin- positive fibers and ter-
gene-related peptide (18). minals. Immunoreactive cell bodies were
The levels of somatostatin in the primate found only within the anterior amygdaloid
amygdala are among the highest in the brain area and the central, medial, and intercalated
and appear to have an intrinsic origin . The nuclei. The distribution of neurotensin-
distribution of somatostatin immunoreactiv- immunoreactive processes and cell bodies
ity shows both internuclear and intranuclear within selected regions of the amygdala pro-
variability ( Fig. 18.22 ). In the lateral nucleus, vides an anatomic substrate that may explain ,
the density of immunoreactive fibers is high- in part, the neuromodulatory actions of neu -
est in the ventrolateral part, whereas the rotensin upon autonomic, endocrine, and
number of immunoreactive cells is greater in memory systems. Of particular interest is the
the dorsomedial portion . In the basal nucleus, finding that neurotensin-immunoreactivity is
Figure 18.22. Camera lucida drawings of transverse section through the rostral (A , B) and middle (C, D) third portions
of the amygdala in the squirrel monkey illustrating the distribution of somatostatin (SRIF)-immunoreoctive terminals
( small dots on the right ) and cells bodies ( filled circles on the left) Specific polyclonal antibodies raised against so-
matostatin-28 and somatostatin 28 (1-12) were used and both antibodies gave similar results. AAA, amygdaloid ante-
.
rior area; AC, anterior commissure. AS accessory basal nucleus; ABI, accessory basal nucleus, lateral part; ABm. ac-
.
cessory basal nucleus, medial part; ABvm. accessory basal nucleus, ventromedial part; 8. basal nucleus BMA. basal
. . .
medial nucleus; Bmg basal nucleus, magnocellular part 8pc, basal nucleus, parvicellular part C, central nucleus;
. ..
CL claustrum; GPi globus pallidus, internal segment; HYP, hypothalamus / intercalated nuclear masses; L lateral nu-
. .
cleus. M. medial nucleus of amygdala. NLOT nucleus of lateral olfactory tract; OC, optical chiasm PAC periamyg- .
. .
daloid cortex St substantia innominata.
markedly decreased in the amygdala in cases amygdaloid complex, NADPU-d cells and
of Alzheimer' s disease (24). processes occur in large number in the baso-
lateral group and in moderate number in the
OTHER SUBSTANCES corticomedial group. The central amygdaloid
area is characterized by minimal NADPH-d
The amygdala in monkeys and humans histochemical staining (36). In contrast to sev-
contains numerous cell bodies and fibers eral other types of amygdaloid neurons,
that express the enzyme nicotinamide ade- those that stain for NADPH-d do not appear
nine dinucleotide phosphate diaphorase Alzheimer's disease.
to be affected in cases of
( NADPH-d) (18, 36, 266). In the human Furthermore, colocalization experiments re-
veal that numerous amygdaloid neurons that nate principally in the corticomedial nuclear
contain NADPH -d also express neuropeptide group, including the nucleus of the lateral ol -
and / or somatostatin in humans ( 266 ). factory tract ( 2, 13, 18, 35, 7l >, 132, 20*) ). Fibers
The enzyme NADPH-d is a nitric oxide concerned with the vomeronasal organ that
synthase that produces the highly toxic mole- originate in the accessory olfactory bulb also
cule nitric oxide ( NO) in response to changes terminate in the corticomedial nuclear group
in intracellular free calcium levels. In the . No fibers from the lateral olfactory tract
( 218)
amygdala, calcium levels appear to be con- appear to enter the basolateral nuclear group,
-
trolled by two calcium binding proteins, but this group receives an indirect olfactory
namely calbindin D-28k and parvalbumin. input via relays in the piriform cortex ( 18, 55,
Immunohistochemical studies have revealed 204, 270 ). Thus, nearly all parts of the primate
the presence of parvalbumin ( 203) or cal - amygdaloid nuclear complex receive either
bindin D-28 k ( 204 ) in distinct sets of amyg- direct or indirect olfactory pathways. In turn,
daloid neurons in monkeys. neurons in the nucleus of the olfactory tract
and in other components of the corticomedial
Intrinsic Connections nuclear group send fibers to the olfactory
bulb (18, 55).
The complexity and functional importance
of the inter-and intranuclear amygdaloid con - BASAL FOREBRAIN
nections have been underestimated in the
past largely because of the lack of adequate The amygdala is reciprocally linked with
methodologic procedures to study the intrin - the basal forebrain. This projection is directed
sic microcircuitry of the amygdala . The rela - principally , although not exclusively, toward
tively recent use of neuronal tracers that are the magnocellular basal forebrain nuclei , in -
not taken up, at least in significant amount , cluding the basal nucleus of Meynert and the
by fibers of passage ( e.g., tritiated amino nucleus of the diagonal band (of Broca ). The
acids and various plant lectins ), has allowed efferent projection from the amygdala arises
the gathering of some new information re- primarily from the parvicellular division of
garding the intrinsic circuitry of the amyg - the basal nucleus, the magnocellular division
of the accessory basal nucleus, and the central
dala .
In monkeys, as in nonprimates species, the nucleus. Many of these amvgdalofugal fibers
major intra -amygdaloid connections arise in appear to contact only en pussant the magno-
the lateral and basal nuclei and terminate in cellular nuclei on their way to the thalamus,
the more medially located nuclei . The acces- hypothalamus, and brainstem ( 230 ). In turn ,
sory basal nucleus also projects to the central, neurons in the anterolateral part of the basal
medial , and cortical nuclei and the amygdalo- nucleus of Meynert project to the amygdala
hippocampal area . By comparison, the projec - where they terminate massively in the mag -
tion from the medial, cortical, or central nu - nocellular division of the basal nucleus and
clei back to the nuclei of the basolateral less abundantly in the magnocellular division
group are relatively weak. This pattern of of the accessory basal nucleus. As mentioned
connectivity indicates that the processing of earlier, this projection arises in large part
information within the amygdala is basically from cholinergic neurons of the basal nucleus
unidirectional and follows a lateromedial di- of Meynert ( Fig. 18.23), with a smaller contri -
rection ( 18). bution from GABAergic neurons in the same
nucleus. The cholinergic projection to the
magnocellular division of the amygdaloid
Subcortical Connections basal nucleus is, in fact, considered to be one
OLFACTORY SYSTEM of the most massive cholinergic projections of
any forebrain region ( 18).
The amygdala in primates is not domi -
nated by olfaction as in some macrosmatic STRIATUM
nonprimate species (e.g., rodents). Nonethe -
less, it has substantial interconnections with The existence of a substantial projection to
several components of the olfactory system. the ventral part of the striatum, principally to
Fibers originating in the olfactory bulb and the nucleus accumbens and deep layers of the
coursing in the lateral olfactory tract ternii - olfactory tubercle (collectively termed the
ventral striatum ), has been known for some projects to the region of the orbitofrontal cor-
time (87, 178). More recent studies, however, tex that receive direct amygdalocortical pro-
revealed that the amygdala projects much jections (122). Besides this prominent projec-
more profusely to the striatum than previ - tion, there is a projection from the central and
ously believed . Amygdalostriatal fibers ter- medial amygdaloid nuclei that terminates in
minate in the ventral and medial parts of the the midline thalamic nuclei, particularly the
caudate nucleus and putamen that border the nucleus reuniens and the caudal part of the
nucleus accumbens, but also in the ventral centralis nuclear complex. A light projection
part of the putamen and in the sector of the from the central amygdaloid nucleus to the
body and tail of the caudate nucleus that bor- medial part of the pulvinar has also been
ders the stria terminalis (230 ). The amyg- identified (18).
dalostriatal projection arises mainly, if not Surprisingly, the main thalamic recipient
solely, from the basal and accessory basal nu- of the amygdala projection, the MDmc, does
clei (197, 230). The parvicellular division of not project back to the amygdala . The midline
the basal nucleus projects preferentially to the thalamic nuclei, however, do project back to
medial part of the nucleus accumbens, while the amygdala, particularly to the central nu -
the magnocellular division projects more ex- cleus and adjoining portion of the basal nu-
tensively to the body and tail of the caudate cleus (155, 190, 275). In the rat and cat, cells
nucleus and to the ventral putamen ( 230 ). surrounding the medial geniculate nucleus in
Thus, the amygdalostriatal projection should the posterior thalamus project to the lateral,
be considered as one of the most substantial accessory basal, medial, and central amyg-
efferents of the amygdala in primates (18). daloid nuclei. Since these posterior thalamic
areas receive auditory inputs from the infe-
HIPPOCAMPUS rior colliculus, their projections to the amyg-
dala have been implicated in conditioned
As mentioned in the earlier section dealing emotional responses to auditory stimuli (128).
with the hippocampal formation, there are
prominent interconnections between the HYPOTHALAMUS
amygdala and the hippocampus. The amyg-
dalo- hippocampal projection arises princi- As mentioned earlier, the bed nucleus of
pally from the lateral nucleus, the parvicellu- the stria terminal is considered by many in-
lar division of the basal nucleus, and the vestigators as forming a morphologic and
magnocellular division of the accessory basal functional continuum termed the extended
nucleus. The main projection arises from the amygdala (154). Like the central and medial
lateral nucleus and terminates in the rostral amygdaloid nuclei, the bed nucleus of the
entorhinal cortex. Other, less massive, projec- stria terminalis forms a relay for projections
tions are directed to the hippocampus and from the amygdala to the hypothalamus.
the proximal portion of the subiculum. Caudal to the bed nucleus, fibers originating
By comparison, the hippocampo-amyg- in the corticomedial nuclear group terminate
daloid projection is meager, consisting essen- in the anterior hypothalamus, with some of
tially of a projection from the CA1 /subicu- them appearing to contact the dendrites of
lum border zone and the entorhinal cortex to cells in the supraoptic and paraventricular
the parvicellular division of the basal nucleus hypothalamic nuclei. A more substantial
-
(18). The fact that amygdalo hippocampal amygdalohypothalamic projection terminates
in and around the ventromedial hypothala-
projections are more prominent than hip-
pocampo-amygdaloid projections suggests mic nucleus. Fibers originating in the amyg-
that the amygdala exerts a more powerful in- dalo-hippocampal transitional area and the
fluence upon the hippocampal formation adjacent ventral subiculum terminate in the
than vice versa. cell-sparse shell around the ventromedial nu -
cleus, whereas other fibers arising from the
THALAMUS medial and accessory amygdaloid basal nu -
clei terminate in the cellular core of the nu-
The amygdala projection to the magnocel- cleus (99, 147). Fibers originating in the cen-
lular portion of the mediodorsal thalamic nu - tral amygdaloid nucleus also arborize
cleus ( MDmc) is particularly well-docu - throughout the rostrocaudal extent of the lat-
mented (18, 155, 206). In turn, the MDmc eral hypothalamus. Some fibers of the central
nucleus also innervate the tuberomammillary the dorsal raphe nucleus. In contrast to the
and supramammillary nuclei, before continu- mesoamygdaloid dopaminergic projections,
ing into the midbrain tegmentum. the adrenergic, noradrenergic, and serotonin-
Hypothalamoamygdaloid projections are ergic amygdaloid afferents do not appear to
not particularly prominent . Most of them have reciprocal amygdalofugal projections.
arise in the ventromedial nucleus and the
more caudal parts of the lateral hypothalamic Amygdalocortical Connections
area, and terminate in the central, medial,
and accessory basal nuclei and parvicellular The primate amygdala is massively inter-
division of the basal nucleus (18, 48, 222, 260). connected with the neocortex (100, 123, 125,
150, 177, 192, 270, 271, 282), and a detailed re-
BRAINSTEM view on the organization of the amygdalocor-
tical connections has been published (18). In
The central amygdaloid nucleus is the brief, the amygdala can be said to receive uni-
major source of inputs to the brainstem, but modal sensory input from the visual, audi-
the bed nucleus of the stria terminalis has es- tory, and somatosensory cortices, the affer-
sentially similar projections. Fibers from the ents arising from high stages in the hierarchy
central nucleus descend through the mid - of sensory processing (5). For example, the
brain, pons, and medulla, with some fibers amygdala is not innervated by the primary
extending as far down as the spinal cord . visual cortex or even by the peristriate cortex
Along their course these fibers distribute nu- but receives input primarily from the infer-
merous collaterals within structures impli- otemporal cortex (area TE). There exist
cated in autonomic control, including the per- prominent return projections from the amyg-
iaqueductal gray, the parabrachial nucleus, dala to unimodal sensory cortices, and these
the dorsal nucleus of the vagus nerve, and projections are surprisingly much more wide-
the reticular formation. Many of these struc- spread than the corticoamygdaloid projec-
tures send reciprocal ascending projections to tions. In the visual system, the amygdala pro-
the central nucleus (155, 181 ). jects to virtually all visually related areas of
In the midbrain , fibers from the central the temporal and occipital cortex. This find -
amygdaloid nucleus arborize in the ventral ing suggests that the amygdala could modu-
tegmental areas and in the lateral part of the late sensory processing at every stage in the
substantia nigra pars compacta , thus recipro- cortical hierarchy (18). It is interesting to note
cating the dopaminergic mesoamygaloid pro- that the reciprocal connections between the
jection described earlier. In the pons, fibers cerebral cortex and the amygdala are not or-
from the central amygdaloid nucleus termi- ganized in a cell-to-cell manner. For example,
nate massively in the medial and lateral visual inputs to the amygdala terminate prin-
parabrachial nuclei bordering the superior cipally in the lateral nucleus, whereas projec-
cerebellar peduncle, whereas in the medulla tions back to the visual cortex originate
the amygdalofugal fibers terminate most chiefly in the basal nucleus. Thus, one or
heavily in the nucleus of the solitary tract and more stages of intrinsic neuronal processing
dorsal motor nucleus of the vagus nerve. The in the amygdala are needed to close the
parabrachial nuclei send direct reciprocal amygdala-cortex-amygdala loop.
fibers to the central amygdaloid nucleus (155, There are also substantial interconnections
181, 190, 291 ), but the nucleus of the solitary between the amygdala and polysensory and
tract projects only indirectly to the central nu- limbic association areas, including the cingu-
cleus via a relay in the parabrachial nuclei late gyrus, temporal pole, superior temporal
(18, 26) sulcus, insula, perirhinal and frontal cortices.
The central nucleus of the amygdala, as These projections arise from the lateral and
well as other amygdaloid nuclei, receive as- basal amygdaloid nuclei (18).
cending prominent monoaminergic inputs, These findings on the amygdalocortical
besides the dopaminergic projections just de- projections reveal that the amygdala receives
scribed . These include (a ) adrenergic projec- an enormous array of convergent sensory in-
tions from neurons in the lower medulla, (b) formation. Given its numerous subcortical
noradrenergic projections from the locus projections to regions such as the hypothala-
coeruleus, and (c) serotoninergic projections mus, basal forebrain, ventral striatum, and
from the midbrain raphe nuclei, principally various autonomic centers in the brainstem,
the amygdala represents an important relay Stimulation of the amygdaloid region in

whereby external stimuli can influence and humans produces feelings of fear, confu -
activate emotions. Furthermore, through its sional states, disturbances of awareness, and
extensive projections back to the cortex, the amnesia for events taking place during the
amygdala can modulate sensory processing stimulation (53, 66, 80, 172 ). Although rage is
according to affective states (5). the most common behavioral response to
amygdaloid stimulation in animals, it rarely
Functional Considerations is associated with temporal lobe seizures (80).
Bilateral lesions of the amygdaloid com -
Even though the amygdaloid complex re- plex in animals consistently produce distur -
ceives an olfactory input, the exact role of this bances of emotional behavior (5, 20, 79, 82, 85,
structure in the processing of olfactory infor- 113, 205, 212, 228, 264 ). Animals become
mation is still not clear. Early observations placid and display no reactions of fear, rage,
that the amygdaloid complex is well -devel - or aggression. Previously dominant and abu -
oped in anosmatic aquatic mammals and that sive animals became tame and did not retali -
bilateral destruction of this complex does not ate to the threats or molestations of other ani -
impair olfactory discrimination ( 10, 254 ), led mals. Hypersexuality has been noted as a
to the conclusion that the amygdala is not prominent feature in some experimental
closely related to olfaction . Detailed func - studies. Hypersexual behavior may occur
tional studies are obviously needed before only when the lesions concomitantly involve
any conclusion can be drawn about the in - the piriform cortex, since amygdaloid lesions
volvement of the amygdala in olfaction . sparing this region do not alter sexual be-
Pronounced behavioral changes are havior.
elicited by stimulation of the amygdala in -
The Kliiver Bucy syndrome is characterized
unanesthetized animals. The most common by conversion of wild intractable monkeys to
response to amygdaloid stimulation under docile beasts, which show no evidence of
such conditions is an "arrest" reaction in fear, rage, or aggression (119, 120 ). These ani-
which all spontaneous ongoing activities mals display apparent " psychic blindness," a
cease as the animal assumes an attitude of compulsion to examine objects visually, tac -
aroused attention ( 79 , 113, 146 ) . The "arrest" tually, and orally, bizarre sexual behavior,
reaction appears as the initial phase of flight and certain changes in dietary habits. Almost
or defense reactions. Flight ( fear ) and defen- all objects are examined , smelled , and
sive ( rage and aggression ) reactions, termed mouthed , and if the object is not edible, it is
agonistic behavior, have been elicited from discarded . Hypersexuality is characterized by
different regions of the amygdaloid complex the indiscriminate partnerships sought with
( 53). In the amygdaloid complex, the inten - both male and female animals, animals of
sity of the stimulus determines the magni- other species, and even inanimate objects.
tude of the response, which builds gradually Observations in humans concerning the ef -
and outlasts the period of stimulation ( 293). fects of bilateral lesions in the amygdaloid
The fact that long-term potentiation can be complex indicate that these lesions cause a
induced in the amygdala ( 44) could explain decrease of aggressive and assaultive behav-
-
the long lasting aspect of this response. In - ior ( 137, 153, 262, 263). Stereotaxic lesions in
tense reactions of fear and rage are associated the amygdaloid complex in humans produce
with pupillary dilatation, piloerection, growl- a marked reduction in emotional excitability
ing, hissing, unmistakable signs of emotional and tend to normalize social behavior in indi-
involvement , and activity of the autonomic viduals with severe behavior disturbances
nervous system. Electrical stimulation of the (173, 174, 228). Unilateral lesions in some
stria terminalis, or of the ventral amygdalofu - cases proved sufficient to bring about im -
gal fibers, produces components of the de- provement. Bilateral lesions did not produce
fense reaction, but lesions of the stria termi- the signs and symptoms suggestive of the
nalis do not alter the response obtained by Kliiver- Bucy syndrome.
stimulating the amygdala (101 ). After com - Visceral and autonomic responses include
pletely interrupting the ventral amygdalofu - alterations of respiratory rate, rhythm, and
gal projections, defense reactions can no amplitude, as well as inhibition of respira -
longer be obtained by stimulating the amyg- tion . The most common response of amyg -
daloid complex ( 293). daloid stimulation in unanesthetized animals
j
4?
,- '
SI
/
'
si
• t 1
c . '
i x.
D
3*
Figure 18.23. Cells in the septal nuclei and the substantia innominata immunoreactive to choline acetyltransferase
(ChAT) in the rhesus monkey A and B Cells in the medial septal nucleus (MSN) C and D ChAl immunoreactive cells
in portions of the substantia Innominata (SO ventral to the medial (internal) pallidal segment (MPS) . Collections of
large cholinergic neurons in this complex constitute the basal nucleus ot Meynert . The substanta innominata extends
. . .
rostrally beneath the anterior commissure AC anterior commissure AL ansa lenticularis; Fx, ibers of the fornix SP.
.
septum pellucidum, V anterior horn of the lateral ventricle Scale bars represent 1 mm
is an acceleration of the respiratory rate asso- stitute an insignificant part of the syndrome
ciated with a reduction in amplitude ( 113). produced by lesions in this complex.
Cardiovascular responses involve both in- Endocrine responses to stimulation of the
creases and decreases in arterial blood pres- amygdaloid nuclear complex include the re-
sure and alterations in heart rate. Pressor release of ad renocorticotropin ( ACTH ) and go-
sponses appear to predominate following nadotrophic hormone, and lactogenic re-
amygdaloid stimulation in the unanes- sponses. Stimulation of the amygdaloid areas
thetized animal . Gastrointestinal motility and that produce arousal and emotional re-
secretion may be inhibited or activated , and sponses also produce increased adrenocorti-
both defecation and micturition may be in - cal output (113, 295). Bilateral lesions in the
duced . Piloerection , salivation , pupillary medial amygdaloid nuclei produce an eleva -
changes, and alterations of body temperature tion of serum levels of ACTH , presumably
can occur. These responses may be either due to release of an inhibitory influence on
sympathetic or parasympathetic in nature. the secretion of ACTH (61 ). Stimulation of the
Somatic responses obtained by stimulation corticomedial division of the amygdala may
of the amygdaloid complex include turning induce ovulation, but this response is abol -
of the head and eyes to the opposite side, and ished by transection of the stria terminalis
complex rhythmic movements related to (64, 242, 276). The corticomedial amygdaloid
chewing, licking, and swallowing. The varied nuclei in the female appear to have estrogen
somatic and autonomic effects of electrical concentrating neurons which are part of a
stimulation of the amygdaloid complex con- system of similar cells extending into hypo-
thalamic and limbic structures ( 201 ). The projections from the primary taste cortex in
amygdala also is concerned with the luteiniz- monkeys, offering a route whereby it could
ing ( LH ) and follicle-stimulating ( FSH ) hor- gain access to the gustatory information re-
mones ( 113). It is quite clear that the amyg- quired to guide feeding behavior. Neurons in
dala participates with the hypothalamus in the amygdala are implicated in mediating he-
the control and regulation of hypophysial se- donic appreciation , emotional expression,
cretions. and conditioning, particularly as these relate
The amygdaloid complex also plays a role to feeding ( 238). The amygdala appears to
in food and water intake ( 238). Bilateral abla - exert its influence upon feeding by modulat -
tions of the amygdala may result in striking ing the activity of hypothalamic mechanisms
hyperphagia, or in hypophagia . Lesions of (147, 250) ( Fig. 18.24 ).
the basolateral nucleus of the amygdala re- The role of the amygdala as an integrator
sult in hyperphagia ( 68 ), while stimulation of of autonomic and visceral functions through
this part of the amygdala produces an arrest its reciprocal connections with the hypothala -
of feeding behavior (69). It has been postu - mus and visceral nuclei of the brainstem is
lated that this part of the amygdaloid com - widely accepted . It has become increasingly
plex inhibits the lateral hypothalamic area, evident that the amygdala also is involved in
which is regarded as the feeding center of the complex cognitive functions that influence
hypothalamus (113, 188). The corticomedial emotion and behavior in a global fashion (5,
part of the amygdaloid complex is a facilita - 228). These functions appear to involve virtu -
tory area concerned with food intake. Stimu - ally all regions of the cerebral cortex and all
lation of this region produces increases in sensory modalities. Cortical inputs to the
food intake ( 226, 227). The amygdala receives amygdala derived from modality specific as-
Cm
VXi\
\ Cl \
L *
~ y 0
VM:
;
_
Bl
Bm ,
'
jc Me
—
: ClX
\E
•
> N
'
* 6
\ Cm
B
Figure 18.24. Amygdala of the cat at the level of the tuberal region (A) and the optic chiasm ( B) The major nuclear
boundaries are shown with dashed lines. On the right side are the locations of cell bodies labeled by retrograde
transport of horseradish peroxidase injected into three locations in the hypothalamus: open circles, ventromedial nu-
.
cleus: filled squares, lateral hypothalamus; filled circles, preoptic area. Bl basolateral amygdaloid nucleus (magno-
. .
cellular part): Bm basomedial amygdaloid nucleus (parvicellular part); Cl central amygdaloid nucleus, lateral part .
. .
Cm, central amygdaloid nucleus, medial part; Co cortical amygdaloid nucleus, E entopeduncular nucleus (homo-
. . .
logue of the internal pallidal segment of primates); F fornix; 1C internal capsule; L lateral amygdaloid nucleus; Me .
. .
medial amygdaloid nucleus; VM ventromedial hypothalamic nucleus: S stria terminals.
sociation areas appear unique among central ( together with that of the hippocampal for -
limbic structures. It has been suggested that mation ) is markedly reduced in schizophren -
the amygdala represents the interface be- .
ics (34) Further evidence comes from the
tween the hypothalamus and brainstem vis- connectivity between the amygdala and the
ceral centers, and regions of the cerebral cor- other brain regions that show pathologic
tex concerned with cognitive functions. The changes in schizophrenia, that is, the hip-
Kluver-Bucy syndrome provides an example pocampus, entorhinal cortex, parahippo-
of this interrelationship. In the presence of le- campal gyrus, cingulate gyrus, and frontal
sions in the amygdala , monkeys respond to cortex (159).
visual stimuli in a bizarre fashion because the The connections between the amygdala
visual stimuli have no meaning. This may and the frontal cortex appear particularly rel -
also apply to other sensory modalities whose evant here because frontal lobe dysfunction is
cortical inputs to the amygdala are discon- believed to be a central feature of schizophre-
nected by destruction of the amygdalae. nia (5). Results of various neurochemical
Broadly stated , impulses generated in sen- studies also suggest a possible involvement
sory systems, the cerebral cortex, and proba - of the amygdala in schizophrenia. For exam-
bly still-undetermined neural structures, trig- ple, the therapeutic action of most neurolep-
ger mechanisms that excite visceral and tic drugs given to schizophrenics depends on
somatic systems whose activities in concert their action as antagonist of dopamine D2 re-
provide the physiologic expression of emo- ceptors. It is, therefore, relevant that the
tion and goal-directed behavior. Reciprocal amygdala is reciprocally connected with mid -
connections between areas of the cerebral brain dopaminergic neurons giving rise to
cortex and the amygdala appear essential to the mesolimbic dopaminergic pathway. It has
the correlation of emotional expression and been hypothesized that an increase in the ac-
meaningful behavior. tivity of this mesolimbic dopaminergic path-
The involvement of the amygdala in emo- way, which innervates also the ventral stria-
tion may have an important bearing on sev- tum and the frontal cortex, is a key
eral forms of dementia . In Alzheimer's dis- neurochemical feature of schizophrenia .
ease, the amygdala suffers from severe While it is unlikely that the malfunctioning of
neuronal loss and displays numerous neu- any one brain region will prove sufficient to
rofibrillary tangles and senile plaques ( 237, produce the complex array of cognitive, emo-
267). There is also a marked volumetric de- tional, and attentional disorders associated
crease of the amygdala in Alzheimer's dis- with schizophrenia, the link between the
ease ( 236). These changes are severe and amygdala and emotional changes in schizo-
occur early in the course of the disease. Be- phrenia is worth further study.
sides a marked memory impairment, demen-
tia of the Alzheimer type is characterized by SUBSTANTIA INNOMINATA
changes in emotional behaviors (e.g., in-
creases in passivity and in agitated and self - The substantia innominata is part of a het -
centered behavior, and a loss in spontaneity erogeneous group of telencophalic structures
and esthetic appreciation ) (5). These negative on the medial and ventral aspect of the cere-
mood changes associated with dementia are bral hemispheres, which collectively are re-
somewhat similar to the hypoemotionality ferred to as the basal forebrain. Despite the
noted in monkeys with amygdala damage. location of these structures near the surface of
Furthermore, the emotional changes can be the brain, they lack a cortical organization.
unrelated to the memory loss, a finding that The basal forebrain extends from the olfac-
suggests a clear dissociation between amyg- tory tubercle rostrally to the hypothalamic re-
dala (emotion ) and hippocampus ( memory ) gion caudally and overlaps the area known as
functions (5). the anterior perforated substance ( Fig. 18.6).
The amygdala may also be involved in the Although the precise boundaries of the basal
emotional changes observed in schizophre- forebrain are not clearly defined, it is gener-
nia . Patients suffering from schizophrenia ally agreed to include the septal area, the ol-
often display inappropriate mood or lack of factory tubercle, parts of the amygdala , and
affect , and they also have difficulty identify- the area under the anterior commissure
ing the emotional status of other people. It is known as the substantia innominata ( Figs.
also known that the volume of the amygdala 18.19 and 18.20). The large neurons scattered
within the basal forebrain are often referred ansa lenticularis, the ansa peduncularis, and
to as the magnocellular basal forebrain neu - the inferior thalamic peduncle.
rons. The subcommissural region contains a In the subcommissural region, the most
number of cell groups in contact with fiber conspicuous cells are a group of magnocellu -
bundles traversing the region, which include lar hyperchromic neurons, known as the basal
the diagonal band (of Broca ), the anterior nucleus (of Meynert ) or nucleus busalis ( Fig.
commissure, the medial forebrain bundle, the 18.23). The term substantia innominata is
Figure 18.25. Transverse section through the basal forebrain showing the distribution of neurons intensely stained for
acetylcholinesterase ( dots) in a normal human brain (A; age 84) and In a typical case of senile dementia of the
Alzheimer type (B; age 75). Note that the basal nucleus in the Alzheimer diseased brain (B) displays a marked cell loss,
whereas the actetylcholinesterase-rich neurons in the putamen are not affected. This indicates that cholinergic neu-
. .
rons in the basal nucleus are specifically altered in Alzheimer ' s disease. AC, anterior commissure FX fornix, GPe, ex -
. . . .
ternal pallidum; GPi internal pallidum; 1C internal capsule; LH lateral hypothalamus; MH medial hypothalamus; NB,
.
basal nucleus of Meynert; 07 optic tract; PUT, putamen; SO, supraoptic nucleus.
used inconsistently and frequently as a syn- sense, the basal nucleus appears analogous to
onym for the basal nucleus, but the term the raphe nuclei and the locus coeruleus,
"basal nucleus" should be restricted specifi - which constitute the major sources of sero-
cally to the clusters of magnocellular ele- tonergic and noradrenergic innervation, re-
ments that are scattered throughout the sub- spectively, to widespread regions of the cere-
stantia innominata . Large basophilic neurons bral cortex .
with morphologic characteristics similar to Interest in the basal nucleus is related to
those of the basal nucleus of Meynert are pre- the discovery that neurons in this nucleus se-
sent in the medial septum , vertical and hori - lectively degenerate in Alzheimer's disease
zontal parts of the nucleus of the diagonal and its variant , senile dementia of the
band , and in largest numbers along the ven - Alzheimer's type, the most common demen -
tral and lateral margins of the pallidal seg- tia occurring in middle and late life ( Fig.
ments ( Fig . 18.23) . Similar cells are present in 18.23 ) ( 49, 193, 283 ) . The loss of cholinergic
parts of the medullary laminae of the globus input from neurons in the basal nucleus ap-
pallidus. In the basal nucleus, most neurons pears to be a highly significant factor in the
are cholinergic . Clusters of small GABA - im- well -documented cortical cholinergic defi -
munoreactive cells are scattered among the ciency that occurs in these patients ( 49) .
large cholinergic neurons of the basal nu - Alzheimer's disease usually develops be-
cleus. Afferents to the substantia innominata tween the ages of 40 and 61 ) and is character-
and the basal nucleus arise mainly from the ized by progressive dementia with apraxia
amygdala, portions of the insular and tempo- and speech disturbances. There is loss of
ral cortex, and from the piriform and entorhi - memory , slurred speech , and disorientation .
nal cortices. About 90% of the cholinergic The pathologic picture is associated with dif -
neurons in the basal nucleus project to wide- fuse degeneration of the cerebral cortex in -
spread regions of the cerebral cortex . It has volving all layers, senile amyloid plaques in
been suggested that the basal nucleus may be the cortex , intraneuronal fibrillary tangles,
the single major source of cholinergic inner- and selective degeneration of the cells in the
vation of the entire cerebral cortex . In this basal nucleus .
References New York: Plenum Press, pal formation. In: Paxinos G, ed .

1488:297-318. The human nervous system. Ch.
1 . Addison YVHF. On the rhinen- 4. Alheid GF, Heimer L. New per - 21. New York: Academic Prev*,
cephalon of Dclphinum lielpltis. | spectives in basal forebrain organi- 1440:711-735.
Comp Neurol 1915;25:497-522. zation of special relevance for neu - 17. Amaral DC , Insausti R . Retrograde
2. Adev WR , Meyer M. Hippocampal ropsychiatric disorders: the -
transport of D Pl 11-aspartate in -
and hypothalamic connexions of striatopallidal , amygdaloid , and jected into the monkey amyg -
the temporal lobe in the monkey. corticopetal components of sub- .
daloid complex Exp Brain Res
Brain 1952;75:358-384. stantia innominata . Neuroscience 1442;88:375-388.
3. Adrian ED. Olfactory reactions in 1988;27: 1-39. 18. Amaral DC, Price JL, Pitkanen A ,
the brain of the hedgehog. J Phvs- 10. Allen YVE. Effect of ablating the Carmichael ST . Anatomical organi -
iol 1942;100:459-473.
( Lond ) -
pyriform amygdaloid areas and zation of the primate amygdaloid
4 Aggleton JP. A description of the hippocampi on positive and nega - complex . In: Aggleton JP, ed . The
«» m vgd ah> h i ppoca m pa 1 -
in tercon tive olfactory conditioned reflexes amygdala: neurobiological aspects
nections in the macaque monkey . and on conditioned olfactory dif - of emotion , memory , and mental
Exp Brain Res I 986;64:515 526. ferentiation . Am J Physiol 1941 ; dysfunction. New York: YVilev -
5. Aggleton IP. The contribution of
the amygdala to normal and ab-
132:81 92
11 . Allison AC. The structure of the ol- 19.
-.
1 iss. 1992;] 66
Amt Hire JF. Johnston JVV Jr, Rubin
normal emotional states Trends factory bulb and its relationship to VI . The stereochemical theory of
Neurosci 1493;16:328-333. the olfactory pathways in the rab - odor. Sci A n 1984 ;210:42-44.
6. Akelaitis AJ . Study of language bit and the rat . J Comp Neurol 20. Anand BK Brobeck JR . Eood in -
function ( tactile and visual lexia -
1953;98:309 353. take and spontaneous activity
and graphia ) unilaterally follow - 12. Allison AC. The morphology of the or rats with lesions in the amyg -
ing section of the corpus callosum . olfactory system in the vertebrates. daloid nuclei. I Neurophysiol
I Neuropathol Exp Neurol 1443; Biol Rev 1953;28:195-244 . 1952;15:421 -430.
2:226-262. 13. Allison AC. The secondary olfac- 21 . Anand BK , Dua S. Circulatory and
7. Akelaitis AJ , Risteen YVA , Herren tory areas in the human brain. J respiratory changes induced by
RY, Van Wagenen WP. Studies on Anal 1954;88:481-488. electrical stimulation of limbic sys-
corpus callosum : Contribution to 14. Allison AC, YVarwick R . Quantita - -
tem ( visceral brain ) . J Neurophvs
study of dyspraxia and apraxia fol - tive observations on the olfactory iol 1956;19:393-400.
lowing partial and complete sec- system of the rabbit . Brain 22. Anholt RR Molecular neurobiol -
tion of corpus callosum. Arch Neu - 1949;72:186-197. ogy of olfaction. Crit Rev Neuro -
8.
-
rol Psychiatry 1942;47:971 1008.
Akeson RA . Primary olfactory neu -
15. Amaral DG . Emerging principles biol 1993;7:1 -22 .
of intrinsic hippocampal organiza - 23. Barbe ME, Levitt P . The early com -
ron subclasses. In : Margolis FL., tion. Curr Opin Neurobiol mitment o fetal neurons to the
Gretchell TV, eds Molecular neu - 1993;3:225-229. limbic cortex . J Neurosci 1991;!1:
robiology of the olfactory system . 16. Amaral DG, Insausti R I lippocam- 519 533 .
24. Barnett EM , Perlman 5. The olfac - 37. Breer H, Shepherd GM . Implications 52. Daitz HM, Powell TPS. Studies of
-
tory nerve and not the trigeminal
nerve is the major site of CNS
of the NO / cGMP system for olfac-
tion. Trends Neurosci 1993;16:5-9.
the connections of the fornix sys
tem . J Neurol Neurosurg Psychia -
-
entry for mouse hepatitis virus, 38. Broca P Anatomie comparee des try 1954;17:75-82.
strain JHM. Virology 1993;194: circonvolutions cerebrales: le 53. Davis M . The role of the amygdala
185-191. grand lobe limbique et la scissure in fear and anxiety. Annu Rev
25. Barr ML, Kiernan JA . The human limbique dans la serie des mam - Neurosri 1992;15:353-375.
nervous system . 6th ed . Philadel - miferes. Rev Anthropol (Ser 2 ) 54. De Olmos )S. The amygdaloid pro-
phia : J . B. Lippincott, 1993. 1878;1:384-498. jection field in the rat as studied
26. Beckstead RM , Morse JR, Norgren 39. Brodal A . The hippocampus and -
with the cupric silver method . In :
R . The nucleus of the solitary tract the sense of smell Brain 1947; Eleftheriou BE, ed . The neurobiol -
in the monkey: Projections to the 70:179-222. ogy of the amygdala . New York:
thalamus and brainstem . J Comp 40. Brodal A . General discussion of Plenum Press, 1972:145-204 .
Neurol 1980;190:259-282 . the terminology of the rhinen - 55. De Olmos JS. Amygdala . In. Paxi -
-
27. Ben Ari Y, Le Gal La Salle G, cephalon . In : Bargmann W, Schade nos G, ed . The human nervous sys-
Kanazawa 1 . Regional distribution JP, eds. The rhinencephalon and tem . Ch. 20. New York: Academic
of substance P within the amyg - related structures. Progress in Press, 1990:583-710.
daloid complex and bed nucleus of brain research . Vol. 3. Amsterdam : 56. Desjardins C, Parent A . Distribu -
the stria terminalis. Neurosci Lett Elsevier, 1963:237-244. tion of somatostatin immunoreac -
1977 299 102 41 . Brow'n TH , Zador AM . Hippocam - tivity in the forebrain of the squir -
*
-
28. Ben - Ari Y , Zignumd RE, Shute
CCD, Lew is PR . Regional distribu
tion of choline acetyltransferase
-
pus. In: Shepherd GM , ed . The
synaptic organization of the brain .
. .
3rd ed Ch II, New York: Oxford
rel monkey . Basal ganglia and
amygdala . Neuroscience I 992;47:
115-133.
57. Dott NM . Surgical aspects of the
and acetylcholinesterase within the University Press, 1990:346-388.
amygdaloid complex and stria ter- 42. Browning M , Dunwiddie T, Ben - hypothalamus. In: Le Gros Clark
minalis system . Brain Res 1977;
120:435-445.
nett W, .
( ispen W , Lynch (,
Synaptic phosphoproteins: Specific
WE , ed . The hypothalamus. Edin -
burgh : Oliver and Bovd , 1938:
29. Benzing WC, Mufson EJ , Jennes L, changes after repetitive stimula - 131-185.
Armstrong DM . Reduction of neu - tion of the hippocampal slice. Sci - 58. Drachman DA , Arbit J . Memory
rotensin immunoreactivity in the -
ence 1979;203:60 62. and the hippocampal complex . II .
amygdala in Alzheimer's disease. 43. Buck L, Axel R . A novel multigene Is memory a multiple process?
Brain Res 1990;537:298-302. family may encode odorant recep - -
Arch Neurol 1966;!5:52 4*1.
30. Benzing WC, Mufson E ) , Jennes L , tors: a molecular basis for odor 59. Duveroov HM . The human hip-
Stopa EG , Armstrong DM . Distri- recognition. Cell 1991;65:175-187. pocampus. Miinchen : J .G. Berg-
bution of neurotensin immunore- 44 . Chapman PF, Kairiss EW , Keenan man Verlag , 1988.
activity within the human amyg- CL, Brow' n TH . Long- term synap- 60. Elde R , libkfelt T, Johansson O,
daloid complex: a comparison with tic potentiation in the amygdala . Terenius L . Immunohistochemical
-
acetylcholinesterase and Nissl - Synapse 1990;6:271-278. studies using antibodies to leucine-
stained tissue sections. I Comp 45. Cooper LN . Distributed memory enkephalin : initial observations on
Neurol 1992;317:283-297. in the central nervous system: pos - the nervous systems of the rat .
31 . Berger TW , Thompson RF. Identifi - sible test of assumptions in visual Neuroscience 1976;1:349-351
cation of pyramidal cells as critical cortex. In: Schmitt FO, Worden FG, 61. Eleftheriou BE , Zolovick AJ , Pearse
elements in hippocampal neuronal Adelman G, Dennis SG, eds. The R . Effects of amygdaloid lesions on
- -
plasticity during learning. Proc
Natl Acad Sci USA 1978;75:
-
1572 1576.
.
organization of the cerebral cortex ,
c ambridgG M .-v MIT Press,
1981:479-503.
pituitary adrenal axis in the deer
mouse. Proc Soc Exp Biol Med
1966;122: 1259.
32. Bjorklund A, Lindvall O. 46. Cotman C, Gentry C, Steward O. 62. Emre M , Heckers S, Mash DC,
-
Dopamine containing systems in Synaptic replacement in dentate Geula CG, Mesulam M - M . Cholin -
the CNS. In: Bjorklund A, Hdkfelt gyrus after unilateral entorhinal le- ergic innervation of the amyg-
T , eds. Handbook of chemical neu - sion: electron microscopic analy - daloid complex in the human brain
roanatomv . Vol . 2. Part 1: Classical sis of extent of replacement of and its alteration in old age and
transmitters in the CNS. Ch . 3. synapses by remaining entorhinal Alzheimer's disease. J Comp Neu -
Amsterdam: Elsevier, 1984:55-122. cortex. J Neurocvtol 1977;6:455 - -
rol 1993;336:117 134.
33. Bliss T, Lomo T. Long lasting po- 464. 63. Epclbaum I , Arancibia I T, Kordon
tentiation of synaptic transmission 47. Cotman CW , Nadler JV . Reactive C, Ottersen OP, Ben - Ari Y. Re-
in the dentate area of the anes- synaptogenesis in the hippocam - gional distribution of somatostatin
thetized rabbit following stimula - pus. In : Cotman CW , ed . Neuronal within the amygdaloid complex of
tion of the perforant path . J Physiol plasticity. New York: Raven Press, the rat brain . Brain Res 1979;
( Lond ) 1973;232:331-356. 1978;227-265. 174:172-174.
34. Bogerts B, Lieberman JA , Ashtari 48. Cowan WM , Raisman G Powell. 64 . Everett |W . Neuroendocrine mech -
M , et al Hippocampus-amygdala TPS. The connexions of the amyg- anisms in control of the mam -
volumes and psychopathology in dala . J Neurol Neurosurg Psychia - malian ovary. In : Gorbman A , ed .
chronic schizophrenia . Biol Psychi - try 196528 137-151. Comparative endocrinology. New
atry 1993;33:236-246. 49. Coyle JT, Price DL, DeLong MR York : John Wiley & Sons, 1959:
35. Brady JV . Temporal and emotional Alzheimer's disease: a disorder of -
168 174.
effects related to intracranial elec- cortical cholinergic innervation . 65. Farb C, Aoki C, Milner T, Kaneko
trical self -stimulation . In: Ramey
SR , O' Doherty DS, eds. Electrical
-
Science 1983;219:484 1190.
50. Crosby EC, Humphrey T. Studies
T, I.eDoux J . Glutamate im -
munoreactive terminals in the lat -
studies on the unanesthetized of the vertebrate telencephalon. II eral amygdaloid nucleus: a pos -
brain . Ch. 3. New York: Paul B The nuclear pattern of the anterior sible substrate for emotional
Hoeber, 1960:52 77.- olfactory nucleus, tuberculum ol - memory . Brain Res 1992;593:
36. Brady DR , Carey RG , Mufson EJ . factorum and the amygdaloid 145-158.
Reduced nicotinamide adenine complex in adult man . J Comp 66. Feindel W , Penfield W . Localiza -
-
dinucleotide phosphate diaphor - -
Neurol 1941;74:309 352. tion of discharge in temporal lobe
-
ase ( NADPH d ) profiles in the 51 . Crosby EC, Humphrey T, Liuer automatism . Arch Neurol Psychia -
amygdala of human and New EW. Correlative anatomy ot the -
try 1954;72:603 639.
World monkey ( Saimiri sciureus ). nervous system . New York: 67. Ferri RT, Levitt P. Cerebral cortical
Brain Res 1992;577: 236-248 Macmillan Company, 1962. progenitors are fated to produce
-
region specific neuronal popula - 82. Green JD. The rhinencephalon : as - aminobuty'ate autoradiography of
tions. Cereb Cortex 1993;3: pects of its relation to behavior and the rat olfactory bulb: hypothetical
187-198. the reticular activating system . In: grain analysis of the distribution of
68. Fonberg E. The role of the amyg- Jaspers HH , Proctyoror LP, silver grains. Neuroscience 1981;6:
daloid nucleus in animal behav- Knighton RS, et al., eds. Reticular 473-479.
iour . Prog Brain Res 1968; 22: formation of the brain. Henry Ford 97. Hall EA . Efferent connections of
273-281 . Hospital International Sympo- the basal and lateral nuclei of the
69. Fonberg E, Delgado JMR . Avoid - sium . Boston: Little, Brown and amygdala in the cat . Am j Anat
ance and alimentary reactions dur - Company, 1958:607-619. 1963;113:139-151.
ing amygdala stimulation . J Neu - 83. Green |D. The hippocampus. In : 98. Heilig M , McLeod S, Brot M , et al .
rophysiol 1961;24:651-664. Field J , ed . Handbook of physiol - Anxiolvtic- like action of neuropep -
70. Fox CA . Certain basal telen - ogy . Vol. II , Sec. I . Ch. 56. Wash - tide Y : mediation by Y 1 receptors
cephalic centers in the cat . J Comp ington , DC: American Physiologi - in amygdala , and dissociation
-
Neurol 1940;72:1 62. cal Society, 1960:1373-1389. from food intake effects. Neu-
71 . Fox CA . The stria terminalis, longi - 84. Green JD. The hippocampus. Phys - ropsychopharmacology 1993;8:
tudinal association bundle and iol Rev 1964 ,44:561 608 -
357 363.
precommissural fornix fibres in the 85. Green JD, Clemente CA, De Groot 99. Heimer L, Nauta WJH. The hypo -
cat I - Comp Neurol 184 J . Rhinencephalic lesions and be - thalamic distribution of the stria
277 29 ,. havior in cats. J Comp Neurol terminalis in the rat . Brain Res
72. Fox CA, Fisher RR , DeSalva SJ . The 1957;108:505-545. 1969;13:284-297.
distribution of the anterior com - 86. Green JD, Shimamoto T. Hip- 100. Herzog AG, Van Hoesen GW .
missure in the monkey ( Macaco pocampal seizures and their prop- Temporal neocortical afferent con -
mulatta ). Experimental studies. J agation . Arch Neurol Psychiatry nections to the amygdala in the
Comp Neurol 1948;89:245-277 1953;70:687-702. rhesus mcnkev . Brain Res 1976;
73. Gaffan D, Gaffan EA . Amnesia in 87. Groenewegen HJ , Becker NFHM , -
115:57 70.
man following transection of the Lohman AHM . Subcortical affer- 101. Hilton SM . Zbrozyna A . Defense
fornix . A review. Brain 1991 ,114: ents of the nucleus accumbens reaction from the amygdala and its
2611 2618.
74. Gall C, Brecha N , Karten HJ .
septi in the cat, studied with retro
grade axonal transport of horse
-- afferent connections. J Physiol
-
( Lond ) 1% VI 65:160 173.
Chang K -J . Localization of .
radish peroxidase and bisbenz - 102. Hirsch ) D Grille M , Margolis FL.
.
-
enkephalin like immunoreactivity imid Neuroscience 1980;5: Ligand binding studies in the
to identified axonal and neuronal 1902-1916. mouse olfactory bulb: identifica -
populations of the rat hippocam - 88. Groenewegen HJ , Room P, Witter tion and characterization of a L-
pus . J Comp Neurol 1981 ;198: MP, Lohman AHM . Cortical affer - pHIcamos ne binding site. Brain
-
335 350. ents of the nucleus accumbens in Res 1978;158:407-422 .
75. Garcia - Bengochea F, Corrigan R, the cat , studied with anterograde 103. Horel J . TFe neuroanatomy of am -
Morgane P, Russell D, Heath R and retrograde transport tech - nesia: a cr tique of the hippocam -
Studies on the function of the tem - niques. Neuroscience 1982;7: 977- pal memory hypothesis. Brain
poral lobes. I . The section of the
fornix . Trans Am Neurol Assoc
995.
89. Gros C, Pradelles P, Dray F, Le Cal . 1978;101:403 445. -
104. Hdrtnagl H , Berger ML, Sperk G,
-
1951;76:238 239. -
La Salle G , Ben Ari Y . Regional Pifl C. Regional heterogeneity
76. Getchell TV , Shepherd GM . Short
axon cells in the olfactory bulb:
- -
distribution of met enkephalin
within the amygdaloid complex
in the distribution of neurotrans
mitter markers in the rat hip
-
-
dendrodendritic synaptic interac- and bed nucleus of the stria termi - pocampus. Neuroscience 199 l ;45:
tions. J Physiol (Lond ) 1975;251 : nalis. Neurosci Lett 1978;10: 261-272.
523-548. 193-1%. 105. Horton HL, Levitt P. A unique
77. Glees P, Griffith HB. Bilateral de- 90. Guillery RW . Degeneration in the membrane protein is expressed on
struction of the hippocampus posterior commissural fornix and early developing limbic system
(cornu ammonis ) in a case of de- the mammillary peduncle of the axons and cortical targets. J Neu -
mentia . Monatsschr Psychiatr Neu - -
rat . J Anat 1956,90:350 370. rosci 1988;8:4653-4661.
rol 1952;123:193-204 . 91 Guillery RW . Degeneration in the 106. Inagaki S, Parent A . Distribution of
78. Gloor P Electrophysiological stud - hypothalamic connexions of the al - -
enkephalin immunoreactive neu -
ies on the connections of the amyg - -
bino rat | Anat 1957,41:91 115. rons in the forebrain and upper
daloid nucleus in the cat . Elec - .
92. Guthrie KM Anderson AJ Leon . brainstem of the squirrel monkey
troencephalogr Clin Neurophysiol
1955;7:243-264.
79. Gloor P. Amygdala. In: Field J , ed.
-
M , Gall C . Odor induced increases
in c-fos mRNA expression reveal
Brain Res 1965
^ - .
267 280
107. lnsausti R , Amaral DG, Cowan
an anatomical "unit" for odor pro- WM . The entorhinal cortex of the
Handbinik of physiology . Vol. II, cessing in olfactory bulb. Proc Natl monkey . II . Cortical afferents. J
Sec. 1. Ch. 57. Washington , DC: Acad Sci USA 1993;90:3329-3333. Comp Neurol 1987;264:356-395.
American Physiological Society , .
93. Haberly LB. Olfactory cortex. In. 108. lnsausti R Amaral DG, Cowan
-
1960:1395 1420. Shepherd GM , ed . The synaptic or - WM . The entorhinal cortex of the
80. Gloor P. Temporal lobe epilepsy: ganization of the brain. 3rd ed . Ch. monkey. III . Subcortical afferents. J
its possible contribution to the un - 11. New York: Oxford University Comp Neurol 1987;264:396-408.
derstanding of the functional sig - Press, 1990:317-345. 109. Isaacson RL. A fuzzy limbic sys-
nificance of the amygdala and of 94. Haberly LB, Price JL. The axonal tem. Behav Brain Res 1992;52:
its interaction with neocortical
temporal mechanisms. In : Elefthe
-- projection patterns of the mitral 129-131.
and tufted cells of the olfactory 110. Ishizuka N , Weber |, Amaral DG .
riou BE , ed . The neurobiologv of bulb in the rat . Brain Res 1977 ; Organization of intrahippocampal
the amygdala . New York : Plenum -
129:152 157. projections originating from CA 3
-
Press, 1972:423 457. 95. Halasz N , Ljungdahl A , Hokfelt T. pyramidal cells in the rat . J Comp
81 . Graziadei PPC, Monti Graziadei Transmitter histochemistry of the Neurol 19< );295:580-623.
*
GA . Neurogenesis and neuron re- rat olfactory bulb . II . Fluorescence 111 . Janigro D, Schwartzkroin PA . Ef -
generation in the olfactory system h istochem ica I, autoradiographic fects of GABA on CA3 pyramidal
of mammals. 1 . Morphological as - and electron microscopic localiza- cell dendrites in rabbit hippocam-
pects ol differentiation and struction of monoamines. Brain Res pal slices Brain Res 1988;453:
tural organization of the olfactory -
1978;154:253 272.
9n . Halasz N, Parry DM , Blackett NM ,
265-274
sensory neurons. J Neurocvtol 112. Johnston JB. Further contributions
1979;8: 1 -18. Ljungdahl A, Hokfelt T. |'H|y- to the study of the evolution of the
forebrain . J Comp Neurol 192335: Curr Opin Neurobiol 1992;2: cal stimulation of the hippocam -
-
337 481. 191-197. pus in unrestrained animals . II Be-
113. Kaada BR . Stimulation and re- 129. Lee JH, Goedert M , Hill WD, Lee havioral findings. AMA Arch Neu -
gional ablation of the amygdaloid VM, Trojanowski JQ. Tau proteins rol Psychiatry 1957;78:128-142.
complex with reference to func- are abnormally expressed in olfac- 145. MacLean PD. The triune brain in
tional representations. In: F.lefthe- tory epithelium of Alzheimer pa - evolution. New York: Plenum
riou BE, ed . The neurobiology of tients and developmentally regu - Press, 1989.
the amygdala . New York: Plenum lated in human fetal spinal cord. 146. MacLean PD, Delgado JMR . Elec -
-
Press, 1972:205 281 . Exp Neurol 1993;121:93-105. trical and chemical stimulation of
114. Kaada BR , Pribram KH, Epstein 130. I.e Gros Clark WF.. The projection fronto-temporal portion of limbic
JA. Respirator)' and vascular re- of the olfactory epithelium on the system in the waking animal . Elec -
sponses in monkeys from temporal olfactory bulb in the rabbit . J Neu - troencephalogr Clin Neurophysiol
pole, insula , orbital surface and rol Neurosurg Psychiatry 1951; -
1953;5:91 100.
cingulate gyrus. J Neurophysiol 14:1-10. 147. McBride RL, Sutin ) . Amygdaloid
-
1949;12347 356. 131 Le Gros Clark VVE . Inquiries into and pontine projections to the ven -
115 Kaada BR . Rasmussen EW , Kveini the anatomical basis of olfactory tromedial nucleus of the hypothal -
O. Effects of hippocampal lesions discrimination. Proc R Soc Lind amus. J Comp Neurol 1977;!74:
on maze learning and retention in ( Biol ) 1957;146:299-319. 377-3%.
rats. Exp Neurol 1961;3:333-355. McDonald AJ , Augustine JR . Lo -
116. Kandel E . Cellular insights into be-
havior and learning . In: The I lar -
132. Le Gros Clark WE, Meyer M The
terminal connexions of the olfac-
tory tract in the rabbit 's brain.
148.
. -
calization of C ABA like im
munoreactivity in the monkey
-
vey Lectures, Series 73. New York: Brain 1947;70:304-328. amygdala . Neuroscience 1993;52:
Academic Press, 1979.19-92 . 133. Le Gros Clark WE, Warwick RT. 281 -294 .
117. Kandel HR . Cellular mechanisms
of learning and biological basis of
The pattern of olfactory innerva
tion. J Neurol Neurosurg Psychia -
- 149. McLennan II The pharmacology
of inhibition of mitral cells in the
individuality. In: Kandel ER, try 1946;9:101-111. olfactory bulb. Brain Res 1971 ,29:
Schwartz JH , Jessell TM , eds . 134. Levitt P. A monoclonal antibody to 177-184 .
Principles of neural science. Ch . 65. limbic system neurons. Science 150. Macchi G , Bentivoglio M , Rossini
New York: Elsevier, 1991: 1984;223:299-301 . P, Tempesta E. The basolateral
1009-1031. 135. Lewis PR , Shute CCD. The cholin- amygdaloid projections to the neo -
118. Kishimoto J , Keverne FB, Emson ergic limbic system: projections to cortex in the cat . Neurosci Lett
PC. Calretinin , calbindin - D28k hippocampal formation , medial 1978;9:347-352.
-
and parvalbumin like immunore- cortex , nuclei of the ascending 151 Margolis FL. Camosine in the pri -
mary olfactory pathway . Science
activitv in mouse chemoreceptor cholinergic reticular system, and
neurons. Brain Res 1993;610: the subfornical organ and supraop - 1974;84:909-911 .
119.
-
325 329.
Kltiver H. Brain mechanisms and 136.
- -
tic crest . Brain 1%7,90:521 540.
Lewis PR , Shute CCD, Silver A .
152. Margolis FL . Molecular cloning of
-
olfactory specific gene products.
behavior with special reference to Confirmation of choline acetylase In : Margolis FL, Getchell TV, eds.
the rh inencephalon . Lancet analyses of massive cholinergic in - Molecular neurobiology of the ol -
1952;72:567-574. nervation to the rat hippocampus. factory system . New York: Plenum
120. Kluver H, Bucy P. Preliminary -
J Physiol ( Lond ) 1%7;191.215 224. Press, 1988:237-265.
analysis of functions of the tempo- 137. Lilly R, Cummings JL, Benson F . 153. Marlowe WB, Mancail EL, Thomas
ral lobes in monkeys. Arch Neurol Frankel M. The human Kliiver- -
JJ . Complete KJiiver Bucy syndrome
Psychiatry 1939;42:979-1000. Bucy syndrome. Neurology 1983; in man . Cortex 1975;!1:53-59.
121 . Kbtter R , Meyer N . The limbic sys - 33:1141-1145. 154 . Martin LJ , Spicer DM , Lewis MH ,
tem : A review of its empirical 138. l.indvall O, Bjdrklund A. Organi - Gluck JP, Cork LC. Social depriva -
foundation. Behav Brain Res zation of catecholamine neurons in tion of infant rhesus monkeys al -
1992;52:105-127. the rat central nervous system . In: ters the chemoarchitecture of the
122. Krettek JE, Price JL. Projections Iversen LL, Iversen SD, Snyder SH, brain : I Subcortical regions. J Neu-
from the amygdaloid complex to eds. Handbook of psychopharma - rosci 1991 ;11:3344-3358.
the cerebral cortex and thalamus in cology' . Vol. 9. New York: Plenum 155. Mehler VVR . Subcortical afferent
the rat and cat . J Comp Neurol Press, 1978:139-231. connections of the amygdala in the
1977;172:687-722. 139. Lohman AIIM . The anterior olfac - monkey . J Comp Neurol 1980;190:
123. Krettek JE, Price JL. Projections tory lobe of the guinea pig . Acta -
733 762.
from the amygdaloid complex and Anal ( Basel ) l 963;53:(Suppl 49 ): 156. Meibach RC, Siegel A . The origin
adjacent olfactory structures to the -
1 109. of fornix fibers which project to the
entorhinal cortex and to the 140. Lorente De No R . Studies on the mammillary bodies in the rat: a
subiculum in the rat and cat . J structure of the cerebral cortex. 1 . horseradish peroxidase study.
Comp Neurol 1977;172:723-752. The area entorhinalis. J Psychol Brain Res 1975;88:508-512.
124 . Krieg WJS. Functional neu -
roanatomy . New York : Blakiston 141.
-
Neurol 1933;45:381 138.
Lorente de No, R. 1934. Studies on
157. Meibach RC, Siegel A . Efferent
connections of the hippocampal
Company, 1953. the structure of the cerebral cortex. formation in the rat . Brain Res
125. l âmmers HJ . The neural connec- II . Continuation of the study of the 1977;124:197-224.
tions of the amygdaloid complex ammonic system. J Psychol Neurol 158. Meredith M. Sensory processing in
in mammals. In: Eleftheriou BE, 46:113-177. the main and accessory olfactory
ed . The neurobiologv of the amyg- 142. MacLean PD. Some psychiatric im - systems: comparisons and con-
dala . New York: Plenum Press, plications of physiological studies trasts. J Steroid Biochem Mol Biol
1972:123-144. on frontotemporal portions of lim - 1991;39:601-614 .
126. Li Motte CC, Snowman A , Pert bic system ( visceral brain ). Elec- 159. Mesulam M - M, Geschwind N . On
CB, Snyder SH. Opiate receptor troencephalogr Clin Neurophvsiol the possible role of neocortex and
binding in rhesus monkey brain : 1952;4:407-418. its limbic connections in the
Association with limbic structures. 143. MacLean PD. Chemical and electri - process of attention and schizo -
Brain Res 1978;155:374-379. cal stimulation of the hippocam - phrenia: clinical cases of inatten -
127. Lind LJ . Localized projection of ol - pus in unrestrained animals. I . tion in man and experimental
factory nerves to rabbit olfactory Methods and elect roencephalo- anatomy in monkey . J Psychiatr
-
bulb . Brain Res 1973;63:153 166. graphic findings. AMA Arch Neu - Res 1978;14:249-260.
128. LeDoux JE . Brain mechanisms of -
rol Psychiatry 1957;78:113 127. 160. Mettler FA . Neuroanatomy. 2d ed .
emotion and emotional learning. 144 MacLean PD. Chemical and electri - St . Louis: C.V. Mosby, 1948.
161. Meyer A . Historical aspects of 178. Nauta WJH . Neural associations of 193. Papez JW . A proposed mechanism
cerebral anatomy . London: Oxford the amygdaloid complex in the of emotion. Arch Neurol Psychia -
.
l m \ CVlIty Press . 1971 monkey. Brain 1962;85:505-520. try 1937;38:725-743.
162. Miettinen R , Freund TF. Neu - 179. Nauta WJH . The central viscero- 194. Parent A . Comparative histochem-
-
ropeptide Y containing interneu - motor system: a general survey. In: ical study of the amygdaloid com -
rons in the hippocampus receive Hockman CH, ed . Limbic system plex . J Himforsch 1971;13:89-96.
synaptic input from median raphe mechanisms and autonomic func- 195. Parent A, Csonka C, Etienne P.
and GABAergic septal afferents. tion . Ch . 2. Springfield , IL: Charles The occurrence of large acetyl -
-
Neuropeptides 1992;22:185 193. C. Thomas, 1972:21 33. - -
cholinesterase containing neurons
163. Miettinen R, Freund TF. Conver - 180. Nauta WJH , Kuvpers HGJM . Some in human neostriatum as disclosed
gence and segregation of septal ascending pathways in the brain in normal and Alzheimer diseased -
and median raphe inputs onto dif - stem reticular formation. In: Jasper brains. Brain Res 1984;291:154-158.
ferent subsets of hippocampal in - .
HH , Proctor LP Knighton RS, et al., 1%. Parent A , Descarries L, Beaudet A .
hibitory intemeurons. Brain Res eds. Reticular formation of the brain. Organization of ascending sero-
-
1992;594:263 272. Henry Ford Hospital International tonin systems in the adult rat
164 Monti Graziadei GA, Karlan MS, Symposium. Ch. 1. Boston: Little, brain. A radioautographic study
Bernstein JJ , Graziadei PPC. Rein- Brown and Company, 1958:3-30. .
after intr ventricular administra -
nervation of the olfactory bulb
after section of the olfactory nerve
181 . Norita M , Kawamura K . Subcorti -
cal afferents to the monkey amyg -
-
tion of l 'H| 5 hydroxytryptamine.
Neuroscience 1981;6:1 i 5 138.-
in monkey ( Saimiri mciureus ). Brain dala : an HRP study. Brain Res 197. Parent A, Mackey A, De Belle-
Res 1980;189:343-355. 1980;190:225-230. feuille L. "he subcortical afferents
165. Moran DT, Jafek BW , Rowley JC 182. Oelschlager HA , Northcutt RG. to caudate nucleus and putamen in
3d The vomeronasal (Jacobson's) Immunocytochemical localization primate: a fluorescence retrograde
organ in man: Ultrastructure and of luteinizing hormone- releasing double-labeling study . Neuro-
frequency of occurrence. J Steroid hormone ( LHRH ) in the nervus science 1983;10:1137-1150.
-
Biochem Mol Biol 1991;39:545 552. terminalis and brain of the big 198. Pearson J, Halliday G, Sakamoto
166. Morgan Jl . Monoclonal antibody brown bat , Eptesicus fuscus. J Comp N , Michel JP. Catecholaminergic
mapping of the rat olfactory tract. Neurol 1992;315:344-363. neurons. In: Paxinos G, ed . The
In : Margolis FL, Gretchell TV, eds. 183. O' Keefe J , Conway DH. Hip- human nervous system. Ch. 31.
Molecular neurobiology of the ol - pocampal place units in the freely New York: Academic Press, 1990:
factory system . New York : Plenum moving rat: why they fire where -
1023 1049.
Press, 1988:269-296. they fire. Exp Brain Res 1978; 199. Peele TL. The neuroanatomical
167. Mori K . Molecular and cellular 31:573-590. basis for clinical neurology. New
properties of mammalian primary 184. O' Keefe J , Nadel L. The hippocam - York:McGnw Hffl,1961 .
olfactory axons . Microsc Res Tech pus as a cognitive map. Oxford : 200. Penfield W , Milner B. Memory
1993;24:131-141 . Oxford University Press, 1978. deficit produced by bilateral le-
168. Morin F. An experimental study of 185. Olds J . Differentiation of reward sions in the hippocampal zone.
hypothalamic connections in the systems in the brain by self -stimu - AM A Ar:h Neurol Psychiatry
guinea pig. J Comp Neurol lation technics. In: Ramey SR , 1958;79:475-497.
-
1950;92:193 213. O' Doherty DS, eds. Electrical 201 . Pfaff DW , Keiner M . Atlas of estra -
169. Moss M , Mahut H, Zola - Morgan S. studies on the unanesthetized diol concentrating cells in the cen -
Concurrent discrimination learn - brain. Ch . 2. New York: Paul B. tral nervous system of the female
ing of monkeys after hippocampal, Hoeber, I 960: 17-51. rat . J Comp Neurol 1973;151:
entorhinal , or fornix lesions. J Neu - 186. Olds J , Milner P. Positive reinforce - -
121 159.
rosci 1981;1:227-240. ment produced by electrical stimu - .
202. Phelps PE, Houser CR Vaughn JE.
170. Moulton DG, Beidler I.M . Struc- lation of septal area and other re - Small cholinergic neurons within
ture and function in the peripheral gions of the rat brain. J Comp fields of cholinergic axons charac-
olfactory system . Physiol Rev
’
Physiol Psychol 1954;47:419-427. -
terize olfactory related regions of
1967;47: 1-52 187. Olivier A . Temporal resections in rat telencephalon . Neuroscience
171. Mozell MM . Olfactory discrimina -
tion : electrophysiological spatio-
temporal basis. Science 1964:143:
the surgical treatment of epilepsy .
Epilepsy Res (Suppl ) 1992;5:175-88
188. Oomura Y, Ono T, Ooyama H. In-
1992;48:121-136.
.
203. Pitkanen A, Amaral DC'. Distribu -
tion of parvalbumin-immunoreac-
-
1336 1337. hibitory action of the amygdala on tive cells a ad fibers in the monkey
172. Mullan S, Penfield W. Illusions of the lateral hypothalamic area in temporal lobe: The amygdaloid
comparative interpretation and rats. Nature 1970;228:1108-1110. complex . J Comp Neurol 1993331:
emotion. AMA Arch Neurol Psy- 189. Orbach J , Milner B, Rasmussen T. —
14 36.
204 . Pitkanen A, Amaral DG. Distribu -
chiatry 1959;81:269-284 . Learning and retention in monkeys
173. Narabayashi H . Stereotaxic amyg - -
after amygdala hippocampus re- -
tion of calbindin D28k immunore -
dalotomy . In: Eleftheriou BE , ed . section . Arch Neurol 1960;3: activity in the monkey temporal
The neurobiology of the amygdala . 230-251. lobe: the amygdaloid complex. J
New York: Plenum Press, 1972: 190. Ottersen OP, Ben- Ari Y. Pontine Comp Neurol 1993331:199-224
459-483. and mesencephalic afferents to the 205. Poirier LJ . Anatomical and experi -
174. Narabayashi H , Nagao T, Saito Y , central nucleus of the amygdala of mental studies on the temporal
Yoshida M, Nagahata M . Stereo - the rat . Neurosci Lett 1978; pole of the macaque. J Comp Neu -
taxic amygdalotomy for behavior -
8:329 34. rol 1952;96:209-248.
disorders. Arch Neurol 1963; 191. Palkovits M, Mezey E, Skirboll LR , 206. Porrino LJ . Crane AM Goldman . -
9:1-16. Hokfclt T. Adrenergic projections Rakic PS. Direct and indirect path -
175. Nauta WI1J . An experimental from the lower brainstem to the ways from the amygdala to the
study of the fornix in the rat . J hypothalamic paraventricular nu - frontal lob*.* in rhesus monkeys. J
Comp Neurol 1956;104:247-272. cleus, the lateral hypothalamic Comp Neurol 1981;198:121-136.
176. Nauta WJH . Hippocampal projec - area and the central nucleus of the 207. Potter H , Nauta WJH . A note on
tions and related neural pathways amygdala in rats. J Chem Neu - the problem of olfactory associa -
to the midbrain in the cat Brain roanat 1992:5:407^115. tions of the orbitofrontal cortex in
1958;81:319-340. 192. Pandya DN , Van Hoesen GW , the monkev . Neuroscience 1979;4:
177. Nauta WJH. Fibre degeneration Domesick VB. A cingulo-amyg- 361 369
following lesions of the amyg - daloid projection in the rhesus 208. Powell TI*S, Cowan WM . Centrifu -
daloid complex in the monkey. J monkey . Brain Res 1973;61: gal fibers in the lateral olfactory
Anal 1961 ;95:319- 340. -
369 373. tract . Nature 1963; 19^:1296- 1297.
209. Powell TPS, Cowan VVM , Raisman 225. Ries EA, Langworthy OR . A study Levin G . Actions of norepineph -
G. The central olfactory connex - of the surface structure of the brain rine in the rat hippocampus. Prog
ions. J Anat 1965;99:791-813. of the whale ( Balacnoptcr physolus Brain Res 1991;88: 323-330.
210. Powell TPS, Guillery RW, Cowan and Phystcr caUnion ). J Comp Neu - 241 . Seress L . Interspecies comparison
VVM . A quantitative study of the rol 1937;68:1-47. of the hippocampal formation
fomix- mammillo- thalamic system. 226. Robinson BW , Mishkin M. Alimen - shows increased emphasis on the
- .
I Anat 1957;91:419 432 tary responses evoked from fore- regio superior in the Ammon 's
211 . Powers JB, Fields RB, Winans SS. brain structures in Macaco mulatto. horn of the human brain. J Hirn -
Olfactory and vomeronasal system
participation in male hamsters at -
Science 1962;136:260-261 .
227. Robinson BW, Mishkin M. Alimen - 242.
-
forsch 1988;29:335 340 .
Shealy CN , Peele TL. Studies on
traction to female vaginal secre- tary responses to forebrain stimu - amygdaloid nucleus of cat. J Neu -
tions. Physiol Behav 1979;22:77-84. lation in monkevs. Exp Brain Res rophysiol 1957;20:125-139.
212. Pribram KH , Bagshaw M. Further 1968;4:330-366. 243. Shepherd GM . Principles of speci -
analysis of the temporal lobe syn - 228. Rolls ET. Neurophysiology and ficity and redundancy underlying
-
drome utilizing fronto temporal functions of the pnmate amygdala . the organization of the olfactory
ablations. ) Comp Neurol 1953; In: Aggleton JP, ed . The amygdala : system . Microsc Res Tech 1993;
99:347-375. neurobiological aspects of emo- 24:106-112.
213. Price JL. The central olfactory and tion , memory , and mental dys - 244 . Shepherd GM , Greer CA . Olfac -
accessory olfactory systems. In : function . New York: Wilev Liss,- tory Bulb. In : Shepherd GM , ed .
Finger TE, Silver VVL, eds. Neuro - 1992:143-165. The synaptic organization of the
biologv of taste and smell . New 229. Rosene DL, Van Hoesen GW . Hip - brain . 3rd ed . Ch . 5. New York:
-
York: John Wiley, 1987:179 203.
214 . Price|L , Powell TPS. The morphol -
pocampal efferents reach wide-
spread areas of cerebral cortex and
Oxford University Press, 1990;
133-169.
ogy of the granule cells of the ol
factory bulb | Cell Sci I * >70;7-
- amygdala in the rhesus monkey
-
Science 1977;198:315 317.
- 245. Smith WK . The functional signifi -
cance of the rostral cingular cortex
91 - 124 230. Russchen FT, Amaral DG , Price JL. as revealed by its responses to elec-
215. Price JL, Powell TPS. The mitral The afferent connections of the trical excitation . J Neurophysiol
and short axon cells of the olfac - substantia innominata in the mon - 1945;8:241-255.
tory bulb. | Cell Sci, 1970,7: .
kev Macaco fascicularis. J Comp 246. Smith Y, Parent A . Neuropeptide
631-652. Neurol 1985;242:1-27. Y-immunoreactive neurons in
216. Price JL, Russchen FT, Amaral DG . 231. Sadikot A, Parent A. The striatum of cats and monkeys:
The limbic region . 11 : The amyg - monoaminergic innervation of the morphological characteristics, in-
daloid complex . In : Bjorklund A , amygdala in the squirrel monkey: trinsic organization and co- local-
Hdkfelt T, Swanson LW, eds. an immunohistochemical study. ization with somatostatin. Brain
Handbook of chemical neu - Neuroscience 1990;36:431 -447. Res 1986;372:241-252.
roanatomy. Vol . 5, Part 1: Inte- 232. Sandler R , Smith AD. Coexistence 247. Smith Y, Parent A , Kerkerian L,
grated Systems in the CNS. Ams- of GABA and glutamate in mossy Pelletier G. Distribution of neu -
terdam: Elsevier, 1987:279-381 . fiber terminals of the primate hip- ropeptide Y-immunoreactivity in
217. Raisman G. Neural connexions of pocampus: an ultrastructural the basal forebrain and upper
hypothalamus. Br Med Bull 1966; studv. J Comp Neurol 1991;303: brainstem of the squirrel monkey
22:197-201 . 177-192. .
( Saimiri sciureus ) J Comp Neurol
218. Raisman G. An experimental study 233. Schilling A, Serviere J , Gendrot G, 1985;236:71-89.
of the projection of the amygdala Perret M . Vomeronasal activation 248. Squire LR , Zola - Morgan S. The me-
to the accessory olfactory bulb and by urine in the primate Microcebus dial temporal lobe memory sys -
its relationship to the concept of a -
murinus: a 2 DG study - Exp Brain tem . Science 1991;253:1380-1386.
dual olfactory svstem . Exp Brain Res 1990;81:609-618. 249. Stensaas LJ , Lavker RM, Monti -
Res 1972;14:395-408. 234. Schwart / kroin PA , Scharfman HE, Bloch L, Grosser Bl , Berliner DL.
219. Raisman G, Cowan VVM , Powell Sloviter RS. Similarities in circuitry Ultrastructure of the human
TPS. The extrinsic afferent , com- between Ammon 's horn and den - vomeronasal organ. J Steroid
missural and association fibres of tate gyrus: local interactions and Biochem Mol Biol 1991;39:553-560.
the hippocampus. Brain 1965,88: parallel processing. Prog Brain Res 250. Stepien LS, Cordeau JP, Ras-
-
963 996 . .
220. Raisman C , Cowan VVM , Powell
1990;83:269-286.
235. Scott JW, McBride RL, Schneider
mussen T . The effect of temporal
lobe and hippocampal lesions on
TPS. An experimental analysis of SI*. The organization of projections auditory and visual recent mem -
the efferent projections of the hip - from the olfactory bulb to the piri - ory in monkeys. Brain I 960;
pocampus Brain 1966;89:83 108.- form cortex and olfactory tubercle 83:470-489.
221. Ramon y Cajal S. Histologic du in the rat. J Comp Neurol 1980; 251. Sun N, Cassell MD Intrinsic
Systeme Nerveux de LHomme et 194:519-534. GABAergic neurons in the rat cen -
des Vertebres. ( Azoulay L, trans. ) 236. Scott SA, DeKosky ST, Scheff SW. tral extended amygdala . J Comp
Paris: Maloine, 1909, 1911 . Volumetric atrophy of the amyg- Neurol 1993;330:381-404.
( Reprinted Consejo Superior de In- dala in Alzheimer's disease: quan - 252. Sutin J , McBride RL. Anatomical
vestigaciones Cientificas, Instituto titative serial reconstruction . Neu - analysis of neuronal connectivity.
Ramon y Cajal. Madrid , 1972. ) rology 1991;41 :351-356. In : Myers RD, ed . Methods in psy-
222. Renaud LP, Hopkins DA. Amyg-
dala afferents from the mediobasal
237. Scott SA , DeKosky ST, Sparks DL,
Knox CA, Scheff SW . Amygdala
chobiology. Vol. 3. New York: Aca -
demic Press, 1977:1-26.
hypothalamus: an electrophysiolog - cell loss and atrophy in Alz - 253. Suzuki WA , Zola - Morgan S, Squire
ical and neuroanatomical study in heimer's disease. Ann Neurol LR , Amaral DG. Lesions of the
the rat. Brain Res 1977;121: 201-213.
223. Ribak CE, Vaughn JE, Saito L , Bar-
-
1992;32:555 563. perirhinal and parahippocampal
238. Scott TR , Karadi Z, Oomura Y, et cortices in the monkey produce
ber R , Roberts E. Glutamate decar - al. Gustatory neural coding in the long -lasting memory impairment
boxylase in neurons of the olfac - amygdala of the alert macaque in the visual and tactual modali -
tory bulb. Brain Res 1977;126: 1- 18. ties. J Neurosci 1993;13:2430-2451 .
224. Ridley RM , Thornlev HD, Baker
HF, Fine A . Cholinergic neural
monkey J Neurophvsiol 1993;69:
-
1810 1820.
239. Scoville WB, Milner B. Loss of re -
254. .
Swann HC . The function of the
brain in olfaction. II. The results of
transplants into hippocampus recent memory after bilateral hip- destruction of olfactory and other
store learning ability in monkevs pocampal lesions. J Neurol Neuro- nervous structures upon the dis -
with fornix transections. Exp Brain surg Psychiatry 1957;20:11-21. crimination of odors. J Comp Neu -
Res 1991;83:533-538. 240. Segal M , Markram II , Richter - rol 1934;59:175-201.
255. Swanson LW , Cowan WM . Hip- rat brain . Acta Physiol Scand AW , Coyle JT Delong MR . .
pocampal - hypothalamic connec- (Suppl ) 1971;367:1 -48. Alzheimer disease: Evidence for
tions: Origin in subicular cortex, 269. Valenstein ES, Nauta WJH . A com - selective oss of cholinergic neu -
not Ammon's horn . Science parison of the distribution of the rons in the nucleus basalis. Ann
1975;189:303 304.- fornix system in the rat , guinea Neurol 1981;10:122 126. -
256. Swanson LW , Cowan WM . An au - pig, and monkev . I Comp Neurol .
284. Williams PL Warwick R Func -
toradiographic study of the organi - -
1959.113:337 369. tional neuroanatomy of man .
zation of the efferent connections 270. Valverde F. Studies on the piriform Philadelphia : W.B. Saunders, 1975.
of the hippocampal formation in lobe. Cambridge: Harvard Univer - 285. Wilson RC, l ew WB Steward O. .
the rat . J Comp Neurol 1977; sity Press, 1965. Functiona effects of lesion-
172:49-84 271. Van Alphen HAW . The anterior induced plasticity : long- term po-
257. Swanson LW, Sawchenko PE, commissure of the rabbit . Acta tentiation in normal and lesion - in -
Cowan WM . Evidence for collat - Anat ( Basel ) 1969;74(Suppl 57): duced tern porodentate connec-
eral projections by neurons in
Ammon's horn , the dentate gyrus
-
9 111 . .
272. Van Hoesen GW. The parahip- 286. Witter MP, Griffioen AW . Jor-
-
tions Bon i Re 1979;176 65 28
*
and the subiculum: a multiple ret - pocampal gyrus. New observa- ritsma - Bvham B, Krijnen JOM . En-
rograde labeling study in the rat J tions regarding its cortical connec- torhinal projections to the hip-
-
Neurosci 1981;1:545 559. tions in the monkey . Trends pocampal CA 1 region in the rat: an
258. Sweet WH, Talland GA, Ervin FR . -
Neurosci 1982;5:345 350. underestimated pathway. Neu -
Loss of recent memory following 273. Van Hoesen G , Mesulam M- M, rosci Lett 988:85:193- 198.
section of the fornix. Trans Am .
Haaxma R. Temporal cortical pro- 287. Witter MP Van I loosen GW, Ama -
Neurol Assoc 1959;84:76-82.
259. Symonds C. Disorders of memory .
jections to the olfactory tubercle in
the rhesus monkev . Brain Res
.
ral DC . Topographical organiza
tion of the entorhinal projection to
-
Brain 1966;89:625-644. 1976;109:375-381. the dental? gyrus ot the monkey . J
260. Szentagothai J , Flerko B, Mess B, 274. Vankova M , Arluison M, Leviel V , Neurosci 1989;9:216-228.
Halasz B Hypothalamic control of Tramu G. Afferent connections of 288. Wysoeki CJ . Neurobehavioral evi -
the anterior pituitary: an experi
-
mental morphological study. Bu
-- the rat substantia nigra pars later-
alis with special reference to pep-
dence for the involvement of the
vomeronasal system in mam -
dapest : Akademiai Kiado, 1968. -
tide containing neurons of the malian repn >duction . Neurosci
261 . Talamo BR , Feng WH, Perez Cruet - amygdalo- nigral pathway. J Chem Behav Rev 1979;3:301- 341.
M , et al . Pathologic changes in ol - Neuroanat 1992;5:39-50. 289. Wvsocki CJ , Meredith VI . The
factory neurons in Alzheimer's dis - 275. Veening JG . Subcortical afferents vomeronasal system. In: Finger TF.,
ease. Ann NY Acad Sci 1991; of the amygdaloid complex in the Silver WI , eds. Neurobiology of
.
640:1-7. -
rat : an HRP study Neurosci Lett taste and smell . New York: Wiley -
262. Terzian H . Observations on the 1978;8:197-202. Interscienie, 1987:125-150.
clinical symptomatology of bilat - 27b. Velasco ME, Taleisnik S. Release of 290. Yeckel MF, Berger TW . Feedfor -
eral partial or total removal of the gonadotropins induced by amyg - ward excitation of the hippocam -
temporal lobe in man . In : Baldwin daloid stimulation in the rat . En - pus by afferents from the entorhi -
M , Bailey P, eds. Temporal lobe docrinology 1969;84:132 139. - nal cortex: redefinition of the role
epilepsy. Springfield , 1L: Charles 277. Victor M . Functions of memory of the trisvnaptic pathwav. Proc
C. Thomas, 1958:510-529. and learning in man and their rela - Natl Acad Sci USA 1990;87:
263. Terzian H , Ore GD. Syndrome of tionship to lesions in the temporal 5832-5836.
Kluver and Buev reproduced in lobe and diencephalon . In : Brazier 291 . Zaborsky , Feminger A , Palkovits
man by bilateral removal of the MAB. ed . Brain function . Vol . Ill : M . Afferent brain stem connec-
temporal lobes . Neurology RNA in brain function: memory tions of the central amygdaloid
1955;5:373-380. and learning. Washington , DC: nucleus. Verh Anat Ges 1979;73:
264 . Thomson AF, Walker AE. Behav - American Institute of Biological 1117-1120.
ioral alterations following lesions Sciences, 1964. 292. Zatorre RJ , Jones-Gotman M ,
of the medial surface of the tempo- 278. Victor M , Angevine JB Jr, Mancall Evans AC, Meyer E. Functional lo-
ral lobe. AMA Arch Neurol Psychi - EL, Fisher CM. Memory loss with calization and lateralization of
atry 1951;65:251-252. lesions of hippocampal formation. human olfactorv cortex. Nature
265. Tork 1, Hornung JP. Raphe nuclei Arch Neurol 1961;5:244-263. 1992;360:339-340.
and the serotonergic system. In : 279. Von Bechterew WV. Demonstra - 293. Zbrozyna AW . The organization of
Paxinos G, ed . The human nervous tion eines Gehims mit Zerstdrung the defense reaction elicited from
system. Ch. 30. New York : Acade- der vorderen und inneren Theile amygdala and its connections. In :
-
mic Press, 1990;1001 1022. der Hirnrinde beider Schlafenlap- Eleftheriot BE. ed . The neurobiol -
266. Unger JW. Lange W NADPH -di - .
peil Neurol Zentrabl 1900 : 19; ogv of tht amygdala . New York:
-
aphorase positive cell populations 990-991 . Plenum Press, 1972:597-606.
in the human amygdala and tem- 280. Von Cramon DY, Hebei N , Schuri -
294 . Zola Morgan S, Squire LR The
poral cortex: neuroanatomy, pep- U . A contribution to the anatomi - neuropsychology of memory. Par -
tidergic characteristics and aspects cal basis of thalamic amnesia . allel findings in humans and non -
of aging and Alzheimer's disease. Brain 1985;!08:993-1008. human primates. Ann NY Acad Sci
Acta Neuropathol ( Berl ) 281. Wada Y , Fujinami RS. Viral infec- 1990;608:434-450.
1992;83:636-646. tion and dissemination through 295. Zolovick AJ . Effects of lesions and
267. Unger JW , Lapham LW , McNeill the olfactory pathway and the lim- electrical stimulation of the amyg-
TH, Eskin TA , Hamill RW. The bic system bv Theiler's virus. Am J dala on hypothalamic-hypophy -
amygdala in Alzheimer's disease: -
Pathol 1993;143:221 229. seal regulation . In F.leftheriou BE ,
neuropathology and Alz 50 im - 282. Whitlock DG, Nauta WJH . Subcor- ed . The neurobiology of the amyg-
munoreactivity. Neurobiol Aging tical projections from the temporal dala . New York: Plenum Press,
-
1991;12:389 399. neocortex in the Macaco mulatto. J 1972:643-633.
2n8 Ungerstedt U . Stereotaxic mapping Comp Neurol 1956;106: 183-212.
of the monoamine pathways in the 283. Whitehouse PJ , Price DL, Clark
19
Basal Ganglia
NOMENCLATURE Karl Friedrich Burdach ( 37), whose contribu -

tion to this area of neuroanatomy was partic-
The basal ganglia are large subcortical ularly important ( 247 ).
structures classically considered to be de- In primates, the globus pallidus is divided
rived largely, but not exclusively, from the tel- into an internal and an external segment by
encephalon . These huge nuclear masses are the fibers of the internal medullary lamina
in close relationship to the diencephalon, but ( Fig. 19.3). In nonprimate species, the term
separated from it by the internal capsule globus pallidus refers to the equivalent of the
( Figs. 19.1 and 19.2). The anatomic nomencla - external pallidal segment only, while the en -
ture applied to the basal ganglia is confused topeduncular nucleus is generally regarded
-
and reflects much uncertainty and inconsis as the homologue of the internal pallidal seg -
tency . The situation is due in part to the fact ment (see Table 19.1 ). The term "corpus stria-
that, much like the limbic system , terms such tum ," first defined by Willis in 1664 ( 371 ), has
as "basal ganglia" or "extrapyramidal sys - survived to the present day, although its orig-
tem" have no precise limits. The use and inal meaning changed considerably through
abuse of the epithet "striatum" has also con- the years. It is now' occasionally used to des-
tributed to the inconsistency, particularly in ignate the caudate nucleus, putamen , and
the comparative neurology literature, which globus pallidus together ( 43, 124 ) or the cau -
is cluttered with terms such as "archistria - date nucleus and the putamen without the
tum ," "paleostriatum," "hyperstriatum," and globus pallidus ( 239 ).
"epistriatum ," whose intended meanings In the following account we have adapted
-
vary markedly ( 273). In the following ac the nomenclature commonly used by clini -
count, the terms archi-, paleo-, and neostria - cians, in which the term basal ganglia is re-
tum w'ill be avoided when referring to the stricted to a few key structures whose in -
human basal ganglia because these names, so volvement in psychomotor behavior is
commonly used in neuroanatomic textbooks, well-established or strongly suspected . This
are based on a misinterpretation of the phylo- restricted definition of the basal ganglia in -
genetic evolution of the basal ganglia. cludes the caudate nucleus and putamen,
The term bn>til ganglia , as generally used w hich together are referred to as the striatum,
by anatomists, refers to some or all of the the globus pallidus or pallidum , and the
major telencephalic subcortical nuclear closely related subthalamic nucleus and sub-
masses lying at the base of the forebrain [see stantia nigra . Other nuclei in the thalamus
the excellent historical review by Lewy ( 223) ). and mesopontine tegmentum can also be con -
These nuclei include (a ) the caudate nucleus sidered as important links in the basal gan -
and the putamen ( together referred to as the glia circuitry. The striatum and pallidum
neostriatum or simply the striatum ), ( b ) the form the core structures of the basal ganglia .
globus pallidus or the pallidum ( the paleo- The other nuclei are reciprocally connected
striatum of older literature), (c ) the amyg - w'ith these core structures through closed an -
daloid complex ( or archistriatum of older lit- cillary loops that are typical of the basal gan -
erature), and (d ) the claustrum. The putamen glia circuitry . These structures are thought to
and the globus pallidus together form a topo- exert a profound modulatory influence on the
graphic unit that is often designated the core structure of the basal ganglia ; thus, they
lentiform or lenticular (lens-shaped ) nucleus. are referred to here as control structures (see
The lentiform nucleus, as well as the globus Table 19.1 ).
pallidus, claustrum, and amygdala , were first Lennart Heimer and his colleagues intro-
clearly identified by the German anatomist duced the terms ventral striatum and ventral
795
Cavum septum pellucidum

Corpus callosum
Column of fornix Lateral ventricle
Caudate nucleus
Globus pallidus
Internal capsule
External capsule
Putamen
Lateral sulcus Claustrum
Extreme capsule
Insular cortex
Olfactory area
Uncus Anterior commissure
Amygdaloid complex
Figure 19.1. Frontol section of the human brain passing through the columns of the fornix and the anterior commis-
sure. At this level the putamen and the external (lateral) pallidal segment he beneath the insular cortex .
Thalamus
Ant. nuc . group -

Med nuc group Corpus callosum
Vent tier nuc Fornix
/
Caudate nucleus
Internal capsule
Putamen
\
»
V
a
>
-
Globus pallidus
Extreme capsule
External capsule
Claustrum Amygdaloid complex
Mammillary body
Figure 19.2. Frontal section of the human brain at the level of the mammillary bodies In this section, the main nu-
clear groups of the thalamus are identified, and portions of all components of the basal ganglia are present The
amygdaloid nuclear complex lies in the temporal lobe Internal to the uncus and ventral to the lentiform nucleus
Putamen Internal capsule Lateral dorsal nucleus
Medlodorsal
nucleus
Ventrolateral
nucleus
Lateral pallidal / Accessory medullary Medial pallidal segment

segment / lamina of pallidum
Substantia innominata
Figure 19.3. Frontal section of the human brain through the basal ganglia, internal capsule and thalamus Seg-
ments of the globus pallidus are separated by the Internal medullary lamina and the accessory medullary lamina di-
vides the internal or medial pallidal segment into inner and outer parts The substantia innominata lies ventral to the
globus pallidus and extends rostrally Wiegert s myelin stain
Table 19.1. The Basal Ganglia A Synopsis of the Nomenclature

used in the Present Account
CORE STRUCTURES CONTROL STRUCTURKS
A STRIATUM A. SUBSTANTIA NIGRA

(Riviprcx:i
« l connection with striatum)
Caudate nucleus
Putamen ] Forming a single
entity in rodents
Pars compacta
Pars recticulata
Pars lateralis
Ventral striatum (comprising nucleus
accumbens c *r fundus striati )
B VENTRAL TEGMENTAL AREA
B PALLIDUM or GLOBUS PALLIDUS (Reciprocal connection
with ventral striatum)
External segment ( or globus pallidus in

C SUBTHALAMIC NUCLEUS
non - primates ) (Reciprocal connection with pallidum )
Internal segment ( or en topeduncular
D. THALAMUS and BRAINSTEM
nucleus in non-primates)
Centromedian / parafascicular complex
Ventral pallidum of the
( comprising part Midbrain dorsal raphe nucleus
substantia innominata ) IVdunculopontine tegmental nucleus
pallidum to designate the ill-defined ventral- mission of neurotransmitters involved in stri-

most portions of the striatum and pallidum atal functions constitute one important fea-
which encroach upon the basal forebrain lim- ture of metabolic disturbances associated
bic structures (11, 132, 158, 159). The ventral with two relatively common forms of dyski-
striatum of Heimer and coworkers comprises nesia (disturbances of movement ), namely,
the nucleus accumbens septi ( the fundus Parkinson's disease and Huntington's chorea .
striati of Hassler (143) ) and the deepest part The globus pallidus forming the smaller,
of the olfactory tubercle (anterior perforated most medial part of the lentiform nucleus
substance in humans), while the ventral pal- consists of two cytologically similar segments
lidum refers to part of the substantia innomi- that have input systems with both common
nata, which these authors consider a ventral and distinctive neurotransmitters. Each palli-
extension of the pallidum. These terms are re- dal segment gives rise to different projec-
tained here because of their usefulness in de- tions. The projections of the internal pallidal
scribing these poorly known regions of the segment are principally to ipsilateral thalamic
basal ganglia . nuclei, which in turn have access to motor re-
The claustrum and the amygdala are part gions of the cerebral cortex. The external pal-
of the basal ganglia by the extended topologic lidal segment projects massively to the sub-
definition. As far as we know, however, the thalamic nucleus. Reciprocal connections
claustrum has no major connections with the interrelate portions of the external pallidal
core structures of the basal ganglia as defined segment and the subthalamic nucleus. The
earlier, and it has never been directly in- output systems of the corpus striatum arise
volved in any of the characteristic diseases of from the internal pallidal segment and from
the basal ganglia. Essential knowledge about the pars reticulata of the substantia nigra.
this structure will, nevertheless, be reviewed
briefly. The amygdala, on the other hand , is
STRIATUM
generally regarded as part of the limbic sys-
tem and was examined in detail in Chapter Topographic Organization
18. This structure occupies a crucial position
at the interface between the basal ganglia and The striatum consists of two distinctive
the limbic system and may play an important parts, the caudate nucleus and putamen,
role in the integration of these two sets of which are partially separated by fibers of the
neural structures. This possibility is explored anterior limb of the internal capsule. These
to a certain extent in the present chapter. two striatal components represent a single
The striatum is the major receptive compo- anatomic and functional entity, which for em-
nent of the basal ganglia . In rodents, the stria- bryologic reasons has a particular configura-
tum forms a single mass striated by the dis- tion. Both portions of the striatum arise from
persed corticofugal and corticipetal fibers. In a thickening of the lateral telencephalic vesi-
primates, it is separated into two distinct enti- cle known as the striatal ridge ( Fig. 3.15).
—
ties the caudate nucleus and the putamen —
by the corticofugal and corticipetal fibers that CAUDATE NUCLEUS
form the internal capsule ( Fig. 19.4). The
striatum receives massive inputs from (a ) The caudate nucleus is an elongated,
broad regions of the cerebral cortex, (b) the arched gray mass related throughout its ex-
centromedian-parafascicular (CM-Pf ) nuclear tent to the surface of the lateral ventricle. Its
complex, (c) the substantia nigra, (d ) several enlarged anterior portion, or head , lies rostral
smaller mesencephalic nuclei, and (e) por- to the thalamus and bulges into the anterior
tions of the lateral amygdala. Most of the stri- horn of the lateral ventricle ( Figs. 2.13, 2.14,
atal afferent systems are associated with spe- 19.5, and 19.6). The head of the caudate nu-
cific neurotransmitters. The neural activities cleus and the putamen are separated by fibers
of the striatum involve a large number of dis- of the anterior limb of the internal capsule,
tinctive cell types and a multitude of different except rostroventrally where continuity is
neurotransmitters, which include acetyl- maintained . The body of the caudate nucleus
choline, monoamines, peptides, and amino extends along the dorsolateral border of the
acids. The striatum is reciprocally linked with thalamus, from which it is separated by the
individual cytologic subdivisions of the sub- stria terminalis and the terminal vein ( Figs.
stantia nigra . Impaired synthesis and trans- 19.2 and 19.5). This part of the caudate nu -
Figure 19 4. Frontal sections of the brain of the squirrel monkey ( Saimiri sciureus) (A) and the rat (B) showing the rela-
tive proportion of the striatum (dark areas ) in materiol prepared for the demonstration of acetylcholinesterase
(AChE) Note that in monkeys the striatum is divided into two parts, the coudate nucleus (CD) and the putamen
.
(PUT), by the fibers of the internal capsule (fC) while in rodents it forms a single mass. In both primates and rodents,
the striatum has a ventral extension, the ventral striatum ( VS), which comprises the nucleus accumbens (AS), ventral
to the septum (S). and the deep portions of the olfactory tubercle (OTU)
Cleft for
internal capsule
Head of Thalamus
caudate nucleus
Lateral
geniculate
- body
Putamen
Tail of caudate
Amygdaloid nucleus
nucleus
Figure 19.5. Isolated striatum, thalamus, and amygdaloid complex showing (a) the continuity of the putamen and
head of the caudate nucleus rostrally. and (b) the relationships between the tail of the caudate nucleus and the
amygdaloid nuclear complex . The cleft occupied by fibers of the Internal capsule Is indicated. The anterior limb of
.
the internal capsule is situated between the caudate nucleus and the putamen while the pos eriot limb of the inter -
nal capsule lies between the lentiform nucleus and the thalamus
Caudate nucleus Posterior limb interna capsule
Anterior limb .Slria terminalis

internal capsule
Fimbria of
hiopocampus
Pulvinar
Putamen —
Lateral
Anterior geniculate body
commissure
Globus pallidus / Optic tract Crus cerebri

lateral segment
medial segment
Figure 19.6 . Sagittal section through the basal ganglia, internal capsule, and thalamus in a human brain Note the
relationship of the caudate nucleus to the fibers of the anterior limb of the internal capsule . Weigert ' s myelin stain.
Anterior limb internal capsule

\ Caudate nucleus ( head ) / Column of fornix
-
^ Putamen
Claustrum
Globus pallidus
Posterior limb
internal capsule
Reticular nucleus
Ventral tier
thalamic nuclei
Pulvinar
Caudate nucleus
Dorsomedlal nucleus
Stria medullaris
Figure 19.7. Horizontal section of the thalamus internal capsule and basal ganglia in a human brain Weigert ' s
myelin stain.
cleus is regarded as suprathalamic. The tail of gray cellular bridges pass across the poste-
the caudate nucleus is the attenuated caudal rior limb of the internal capsule ( Figs. 16.8,
portion that sweeps into the temporal lobe in 19.3, and 19.4 ) At levels of the septum pellu-
the roof of the inferior horn of the lateral ven- cidum , the nucleus accumbens (or fundus
tricle and comes into relationship with the striati of 1 lassler (143) ) lies adjacent to me-
central nucleus of the amygdaloid complex dial and ventral portions of the striatum . The
( Figs. 2.13, 16.38, 18.19, and 19.5). nucleus accumbens is ontogenetically more
closely related to the caudate nucleus and
PUTAMEN putamen than to the septal nuclei, and has
projections to both the globus pallidus and
The putamen, the largest and most lateral the substantia nigra ( 341 ).
portion of the corpus striatum , lies between
the external capsule and the lateral Intrinsic Organization
medullary lamina of the globus pallidus
( Figs. 2.13, 16.38, 19.1 , 19.2, and 19.5-19.7). Cytologically, the caudate nucleus and the
Most of the putamen is situated medial to the putamen appear identical and are composed
insular cortex and is separated from it by the of enormous numbers of cells that exhibit no
extreme capsule, the claustrum, and the ex- lamination . However, the striatum is not as
ternal capsule. In transverse sections, the uniform as it appears because in its develop-
lightly stained putamen is traversed by ment cells of different types migrate in clus-
myelinated fibers coursing ventromedially, ters, histochemical activity has a patchy dis-
which are bundles of striatopallidal fibers tribution , and efferent neurons show some
( Figs. 16.8 and 19.2 ) . The caudate nucleus segregation ( 384, 385).
and putamen are continuous rostroventrally, Although small cells were considered to
beneath the anterior limb of the internal cap- outnumber large cells by ratios of 20:1 or 60:1
sule, and in dorsal regions where slender (99, 364 ), a morphometric and statistical
analysis of the human striatum indicated that into two categories: ( a ) those with spiny den -
(a ) the mean numerical density of small stri - drites, and ( b) those with smooth dendrites (1,
atal neurons is approximately 11,000 cells per 82, 101, 103, 190, 194, 195, 288).
mnv\ while the mean numerical density of the
large striatal neurons is about 65 cells / mm1, SPINY NEURONS
and ( b) the ratio of small to large striatal neu -
rons averages about 170:1, with a range from The spiny neurons are by far the most nu-
130:1 to 258:1 ( 323). On average, the putamen merous striatal cells. They are round or oval
is about 13% larger than the caudate nucleus
in humans. Golgi and electron microscopic
-
medium sized cells, emit multiple primary
dendrites covered with spines, and have long
observations indicate that striatal neurons fall axons ( Fig. 19.8). Two types of spiny striatal
Figure 19.8 . Major types of striatal neurons such as seen In Golgi preparations of the brain of rhesus monkeys Three
types of aspiny neurons (At. All, and Alll ) and two types of spiny cells are illustrated There exist several other classifica-
tions of striatal neurons (see text). Arrowheads indicate the initial segment of the axons.
neurons are recognized (82 ). Type I spiny l

50 /inn
neurons, present in very large numbers, have
smooth somata and proximal dendrites that
distally become laden with spines. The den
drites radiate into spherical space of about
-
- t - i -i— i
200 pm ( Figs. 19.9 and 19.10). Long axons of

these cells give rise to both proximal and dis-
tal collaterals. Spiny type 11 striatal neurons
commonly are larger neurons with spiny
dendrites that extend 600 pm from the so-
mata . Axons of spiny II neurons are long and
give off collaterals near the somata. Spiny
striatal neurons sene as both receptive and
projection neurons. Most afferents from vari -
ous sources terminate on spiny processes of
these neurons (189, 192, 193, 196), and all
fibers projecting beyond the striatum arise
from spiny striatal neurons (126, 205, 206,
288). «
Virtually all medium spiny neurons use y-
aminobutyric acid (GABA ) as their main neu -
rotransmitter ( 307) ( Fig. 19.11 ), but also coex-
press a number of neuroactive peptides (16,
122, 292 ) such as substance P (SP), enkephalin
( ENK ), dynorphin ( DYN ), and neurotensin
( NT ) ( Fig. 19.12 ). Not all of these peptides are
found in every spiny striatal neuron . Instead ,
specific combinations of neuropeptides and X.
GABA characterize particular subsets of
striatal projection neurons. In individual
medium spinv neurons, GABA coexists with
either ENK or SP and / or DYN (122, 127). The
coexistence of GABA with a given peptide in
a spiny striatal neuron is in correlation with
its target site. Compared to the well-docu -
mented inhibitory action of GABA, the physi -
ologic role of the different peptides remains
to be established. Also worth noting is the i
presence of the calcium-binding protein cal -

bindin D-28k in virtually all medium spiny
projection neurons of the striatum ( Fig.
19.13). In contrast, striatal interneurons are
devoid of calbindin, but many of them con-
tain parvalbumin, another calcium-binding
protein .
Figure 19.9. Spiny type II striatal neuron in a Golgi
ASPINY NEURONS preparation of the rhesus monkey . These pyramidal cells
give rise to four to six primary dendrites with relatively low
These neurons are intrinsic striatal ele- spine densities, and have an axon which emerges from
the soma or a proximal dendrite Axons of these neurons
ments with short axons (82, 103) ( Fig. 19.7). take a straight course and have been followed for 300
Golgi studies revealed a great diversity of in- (im without narrowing or forming terminal arborizations
terneurons in the striatum, but most of these The axon (arrows) is directed toward the globus pallidus
interneurons share a common characteristic, and appears to give rise to collaterals (Full scale.
50 (im.)
that is the absence or rarity of spines on their
dendrites. This is in striking contrast with the
highly spinous dendrites of the projection
neurons. The striatal intemeurons can be
Figure 19.10. A. Spiny striatal neuron in a Golgi preparation of the rhesus monkey 'Boutons en passage " of afferent
fibers ( AF) cross over its dendrites. The open arrow and the closed arrows indicate the spine- free dendritic trunk and
.
the initial, spine- free dendritic branches, respectively (Golgi, x 700 ) B. A large aspiny striatal neuron A axon; My, ini-
. .
tial segment of myelin sheath; C axon collateral; SN spiny striatal neurons . (Golgi, x 300 ) C. A large aspiny neuron in
.
the putamen (Golgi, < 300 ) D. A spidery aspiny neuron In the putamen. (Golgi x 300.)
CD
Figure 19.11. Frontal halt sections through the forebrain of the squirrel monkey illustrating the distribution of >-
aminobutyric acid (GABA)-immunoredctive neurons ( filled circles) in the core structures of the basol ganglia In the
striatum and pallidum, the GABA -contdlning neurons are scattered among innumerable GABA -lmmunoreactive
. .
axon terminals ( dots) The sections are displayed in a rostrocaudal order AC anterior commissure, AS nucleus ac
. . . .
cumbens; CD caudate nucleus; GP globus pallidus; GPe external segment of GP; GPi internal segment of GP 1C . .
. . . .
Internal capsule; ICA islands of Callejo; OC optic chiasm, OT, optic tract; OTU olfactory tubercle; PUT putamen, RN
. .
reticular thalamic nucleus; SI substantia innominata; THAL. thalamus; VP ventral pallidum
Figure 19.12. Frontal sections through the forebrain of the squirrel monkey illustrating the distribution of enkephalin-
Immunoreactive axon terminals ( dots on the left ) and cell bodies ( filled circles on the right ) , Note the dense
enkephalinergic innervation of the external segment of the globus pallidus . The sections are displayed in a rostrocau-
.
dal order AM. amygdaloid nuclear complex; AS. nucleus accumbens; CD caudate nucleus; DR diagonal band of
Broca; GPe. external segment of globus pallidus; GPi. internal segment of globus pallidus; HYP. hypothalamus; 1C in-.
. . .
ternal capsule; LS lateral septal nucleus. MS medial septal nucleus. OC, optic chiasm; OTU olfactory tubercle; PUT.
putamen; SI, substantia Innomlnata; SO, supraoptic nucleus.
Figure 19.13. Frontal half sections through the basal ganglia of the squirrel monkey illustrating the distribution of par -
-
valbumin (A) and calbindin D 28k (B) in the striatum and pallidum . These two calcium- binding proteins have a striking
complementary distribution in the basal ganglia . Calbindin specifically labels the multitude of striatal projection neu-
rons. whereas parvalbumin marks subsets of striatal intemeurons. At pallidal levels, virtually all neurons contain parval -
bumin but are devoid of calbindin . AC. anterior commissure; CD. caudate nucleus; GP. globus pallidus. 1C. internal
capsule; MS. medial septal nucleus; PUT. putamen; SI. substantia innominate; VP. ventral pallidum .
grouped in two broad categories: the giant than 2% of all striatal cells ( 295). Originally
aspiny interneurons [corresponding to the thought to be projection neurons (101, 194,
aspiny II cells of DiFiglia , et al. (82) 1, and the 195), they were later shown by retrograde la -
medium-sized intemeurons [ corresponding beling techniques not to project to the major
to the aspinv I and III cells of DiFiglia , et al. recipient structures of the striatum (126, 284,
(82)1. 374).
The giant aspiny intemeurons have elon- The medium-sized interneurons are usu -
gated cell bodies (50 or 60 gm X 15-25 gm ) ally divided into two categories on the basis
from which emerge a few stout dendrites that of their neurotransmitter content . The first
branch radially with some dendrites extend - type displays intense GABA immunoreactiv-
ing up to 750 gm from the soma. The axon ity and also contains parvalbumin ( Fig. 19.13)
arises from the dendritic trunk, branches ex- ( 62, 63, 188, 204, 208). These intrinsically or-
tensively, with the resulting arborization con - ganized cells, which represent approximately
sisting of a dense plexus of extremely fine ax- 1% of the striatal neuronal population, are
onal branches that fill the region of the characterized by a round cell body (14-15
dendritic field and sometimes go beyond . gm ) with five to eight varicose and often
These giant neurons, which were demon- curved dendrites that branch close to the cell
strated to be the striatal cholinergic neurons body. Their axon is short and beaded and
( Fig. 19.14 ) ( 30, 200, 222, 295 ), represent less form a rich local plexus. These interneurons
V . vft
' /
.
' v '
30 fim
A
Figure 19.14. Striatal cholinergic interneurons in the squirrel monkey as seen at two different magnifications The neu-
rons were visualized with a pharmacohistochemical technique for acetylcholinesterase (AChE) (A) and immunohisto-
chemlcal methods for choline acetyltransferase (ChAT) (B) These cholinergic neurons are the largest striatal ele -
ments. They have a triangular or ovoid cell body from which emerge 3-5 thick primary dendrites. Their axon remains
confined to the striatum
correspond to spiny type I of DiFiglia, et al. Striatal Compartments

(82 ). The second type of interneuron displays
immunoreactivity for both somatostatin ( 78, There is considerable evidence that the
81 , 348 ) and neuropeptide Y (333), but they striatal neuropil is organized into a mosaic of
do not contain mRNA coding for GABA de- chemically distinct compartments related to
carboxylase (GAD) (55) ( Figs. 19.15 and the organization of afferent and efferent con -
19.16 ) , The neurons also contain the enzyme nections and to particular transmitter sub-
nicotinamide adenine dinucleotide phos- stances (118, 122, 123) ( Figs. 19.15A , B , 19.16,
-
phate ( NADPl t ) diaphorase (358, 359), which
is a nitric oxide synthase involved in the pro-
and 19.17). Every major striatal afferent sys-
tem studied has been shown to terminate in a
duction of nitric oxide ( NO), a short-lived patchy fashion. A histochemical compart -
radical believed to be a novel messenger mol - mentalization of the striatum was demon -
ecule ( 32, 165). The somatostatinergic in- strated for a variety of neuropeptides and
terneurons have a spheroid cell body with a -
transmitter related enzymes. Acetylcho-
mean diameter of approximately 12 pm . linesterase ( AChE ) staining has been particu -
They possess three or four rather straight and larly useful in dramatically demonstrating
relatively long (150 pm ) dendrites that ex - these compartments (122, 123) ( Fig. 19.17).
hibit spine-like appendages and fine tufted The two major compartments of the striatum
terminations. Their axon is relatively short, are referred to as "striosomes" (or patches)
but displays extensive local arborization. and extrastriosomal "matrix." Striosomes ( or
They correspond to the aspinv III neurons of striatal bodies) are characterized by high lev -
DiFiglia , et al . (82 ). els of opiate receptors, substance P (SP), neu -
0.5 mm
Figure 19.15. Striatal interneurons displaying neuropeptide Y (NPY) immunoreactivity A B. Comparison of the distri-
bution of NPY -immunoreactive cell bodies and fibers in the caudate nucleus of the cat (A ) and the squirrel monkey
(B) Note that NPY -immunoreactive profiles are more heterogeneously distributed in the caudate nucleus of the cat
than In the monkey C Typical example of a NPY-positive neuron in the putamen of the squirrel monkey D A NPY
immunoreactlve neuron and a retrogradely labeled neuron (arrowhead) in the caudate nucleus of the squirrel mon-
key as seen after injection of wheat germ agglutinin-conjugated horseradish peroxidase (WGA -HRP) into the substan-
tia nigra. Note the absence of black WGA -HRP granules in the NPY -positive neuron, which displays only a diffuse, light
brown immunostaining. This finding indicates that striatal NPY - immunoreactive neurons do not send their axon to the
substantia nigra. 1C indicates the internal capsule.
Figure 19.16. Distribution of somatostatin immunoreactivity in the basal ganglia of the squirrel monkey in a rostrocau-
dal sequence A and C represent the Immunoreactive terminals ( fine dots ), whereas B and D show the distribution of
.
immunoreactive cell bodies ( filled circles) as seen on the same section AC. anterior commissure CC, corpus callo-
. .
sum; CD caudate nucleus. GPe external segment of globus pallidus; GPi. internal segment of globus pallidus: HYP.
. .
hypothalamus, 1C. internal capsule. OC. optic chiasm. OTU olfactory tubercle. PUT. putamen SI. substantia innoml-
nata. THAI, thalamus .
rotensin ( NT ) and tyrosine hydroxylase (TH ) AChE is largely in the matrix (122, 350 ) ( Fig.
(122). The extrastriosomal matrix is identified 19.17). Opiate receptors, diffusely distributed
with high levels of AChE, calbindin somato- prenatally, are found postnatally in the
statin (SRIF), neurotensin receptors, and ter- patches. Chemical compartmentalization of
minals of thalamic projections. Prefrontal, the striatum appears to be a mammalian evo -
cingulate, and motor cortical areas project to lutionary phenomenon that expresses func-
both patches and matrix. tional differences in groups of striatal neu -
Striking changes occur in organization of rons.
striatal compartments during early develop-
ment. In the fetus, AChE and dopamine are
A further subdivision of the dual strio -
some / matrix system has been proposed on
in register in the patches, but postnatally -
the basis that cortico striatal fibers ( as well as
Figure 19.17. Muscarinic cholinergic receptor binding sites in the caudate nucleus (CN) and putamen ( P) of a 22-
week -old human fetus Areas rich in binding sites appear as light patches (striosomes) GE indicates the ganglionic
eminence Scale bar 1 0 mm
other striatal afferents) form distinct clusters intralaminar thalamic nuclei, and the sub-
within the neurochemically homogeneous stantia nigra are profuse and topographically
matrix ( 122, 230 ). Interestingly, the output organized ( Fig. 19.18 ). Additionally, the stria -
cells of the matrix have also been shown to be tum , or parts of it , receive projections from
grouped in clusters in relation to the different cells of the amygdala and dorsal nucleus of
projection systems leading from the striatum the raphe ( 384, 383) .
to the external and internal segment of the
globus pallidus, as well as to the substantia CORTICOSTRIATAL PROJECTIONS
nigra (75, 96, 97, 116, 122, 180). These clusters
are termed "matrisomes" (122 ) and are con- Among the various striatal afferents, those
sidered as functional modules that could be arising from the cerebral cortex are by far the
related to the physiologically defined mi- most prominent. The corticostriatal projec-
croexcitable zones described by Alexander tions are of utmost importance, as they im-
and DeLong (6, 7). pose on the striatum a pattern of functional
regionalization that is maintained throughout
Afferent Connections the whole basal ganglia .
The entire cerebral cortex is known to pro-
Because it receives dense projections from ject topographically to the striatum . Input
a wide variety of sources, the striatum is con- from the sensorimotor cortex is extensive and
sidered to be the major receptive and integra - bilateral, whereas that from the visual cortex
tive component of the basal ganglia. Afferent is minimal. Earlier degeneration studies em -
systems arising from the cerebral cortex, the phasized the high degree of overlap of corti -
Corticostriatal
fibers
Nigrostriatal Thalamostriatal
fibers fibers
Figure 19.18 Major striatal afterent systems Corticostriatal projections arise trom broad regions of the cerebral cor-
.
tex are topographically organized, and are distributed to both the caudate nucleus and the putamen. Corticostri-
.
atal fibers arise mostly from pyramidal cells in the upper half of lamina V and those from area 4 project bilaterally
and somatotopically upon the putamen These projections have glutamate as their neurotransmitter . Nigrostriatal
.
fibers arise from cells of the pars compacta of the substantia nigra and convey dopamine to terminals in the cau-
date nucleus and putamen. Thalamostriatal fibers arise largely from the centromedian-parafascicular nuclear com-
plex. Not shown are striatal afferents from serotoninergic cell groups in the midbrain dorsal raphe nucleus. CM , cen-
tromedian thalamic nucleus; DM dorsomedial (or mediodorsal) thalamic nucleus: GP, globus pallldus; 1C, internal
. . .
capsule: PUT putamen R, red nucleus; SN substantia nigra; VPL and VPM. ventral posterolateral and ventral postero-
medial thalamic nuclei.
costriatal projections ( 39, 193, 366, 367). How - from limbic and paralimbic cortical areas ter-
ever, the results of more recent autoradi- minate largely in the ventral portion of the
ographic studies reveal that the sensorimotor striatum, including the deep layers of the ol-
cortex in monkeys projects exclusively to the factory tubercle, and the ventral part of both
putamen, where a somatotopic representa - the caudate nucleus and the putamen .
tion of the leg, arm , and face occurs in the Based on the organization of its cortical af -
form of obliquely arranged strips ( 71 , 72, 211, ferents, the striatum can be subdivided into
224 ). In contrast, associative areas of the pre- three major functional sectors termed the as-
frontal , temporal, parietal, and anterior cin- sociative, sensorimotor, and limbic striatal
gulate cortices appear to project almost exclu - territories ( 274 ) (Fig. 19.19). The associative
sively to the caudate nucleus in monkeys territory comprises most of the head of the
( 117, 303, 323). These findings suggest that caudate nucleus and a large portion of the
the caudate nucleus in primates is more rostral, precommissural putamen . The senso-
closely related to complex and associative rimotor territory includes most of the post -
types of behavior, whereas the putamen ap- commissural putamen , the dorsolateral rim
pears more directly involved in sensorimotor of the head of the caudate nucleus, and the
aspects of forebrain mechanisms. Afferents lateral aspect of the body of the caudate nu -
AS SM |1 LI
Figure 19.19. Localization of the associative (AS), sensorimotor (SM). and limbic (U) striatal territories in primates. The
.
drawings are set out in a rostrocaudal order and double hatched areas Indicate zone of overlap AC anterior com-
missure; AS, nucleus accumbens; CD. caudate nucleus; GPe. external segment of globus pallidus. GPI. internal seg-
ment of globus pallidus; 1C. Internal capsule; LH. lateral hypothalamic area. OTU. olfactory tubercle. PUT, putamen.
VP. ventral pallidum.
cleus, whereas the limbic territory comprises termination in the striatum ( 357, 379, 380 ).
the ventral striatum ( 274 ). Neurons in the as- The latter finding supports the view that the
sociative, sensorimotor, and limbic territories corticostriatal system is organized according
are concerned with the treatment of informa - to general functional affiliation of cortical
tion deriving from association , sensorimotor, areas rather than their topographic location
and limbic / paralimbic cortices, respectively . (124 ). However, it appears that many recipro-
Since overlap exists among the different corti - cally connected areas of the association cortex
cal projections, these three territories should project to spatially distinct, rather than over-
be viewed more as a functional continuum lapping, areas of the striatum (119 ). In mon -
rather than striatal subdivisions with strict keys, various areas of the association cortex
boundaries. project to longitudinal sectors that occupy re-
Terminals from corticostriatal axons are stricted mediolateral domains of the striatum .
not uniformly distributed in striatal tissue, Convergence of inputs within these elon -
but appear as patches or clusters of various gated parasagittal bands is not governed by
sizes ( 211 ). Furthermore, the cortical areas reciprocity of corticocortical connectivity but
reciprocally connected via corticocortical con- ranges from complete segregation to overlap.
nections tend to share common zones of fiber Even in areas where overlap occurs, the ter-
minal fields of different association cortices referring to the small-celled part of the cen-
do not intermix but form complex interdigita - tromedian-parafascicular (CM -Pf ) complex
tion patterns ( 325). which, along with the putamen, is very en-
The first successful attempts to label the larged in monkeys and humans and receives
cells of origin of the corticostriatal projection a massive projection from the motor cortex
by retrograde transport of horseradish perox - ( 238, 243, 262 ). The Vogts' suggestion was
idase ( HRP ) led to the conclusion that these confirmed by a cell degeneration study ( 300 )
fibers arise from a neuronal population dis- that showed that virtually all intralaminar
tinct from those giving rise to other corticofu - nuclei in primates project to the striatum , the
gal systems (183, 185). This massive projec - parafascicular and central lateral nuclei pro-
tion was believed to arise almost exclusively viding input to the caudate nucleus and the
from small pyramidal cells in the upper half anterior intralaminar nuclei to the nucleus ac-
of layer V in all cortical areas. In contrast, in - cumbens. Anterograde labeling studies re-
tracellular recording studies suggest that vealed that the projections from the centro-
larger pyramidal cells in layer V , which can median nucleus terminate principally in the
be activated antidromically by stimulation of sensorimotor striatal territory, whereas those
the thalamus or cerebral peduncle, have a col - from the parafascicular nucleus terminate in
lateral that terminates in the striatum (83, the associative territory ( 283, 319, 320). In
181 ), as originally suggested by Ramon y both of these territories, fibers from the in -
Cajal (304). Such branched neurons have been tralaminar nuclei form distinct patches or
identified by means of intracellular HRP in- elongated bands whose exact relationship
-
jection (83) or retrograde double labeling ex - with the mosaic-like arrangements of the cor-
periments (316). ticostriatal projection is not yet known ( Fig.
Other findings suggest that the corticostri- 19.20) (160, 320, 321 ).
atal fibers arise from both supragranular Single- and double-retrograde labeling
(laminae 1, II , III ) and infragranular ( laminae studies confirmed that the CM - Pf complex is
V , VI ) cortical layers ( 205, 206, 267, 315). Neu - the major source of thalamic afferents to the
rons located in lamina VI are reported to pro- striatum ( 182 , 184, 283 ) . These studies further
ject principally to the striosomes ( patches), showed that the thalamostriatal projection is
whereas neurons in other cortical layers pro- topographically organized , with a rostrocau-
ject chiefly to the matrix compartment (113). dal and dorsoventral correspondence be-
Retrograde double-labeling studies reveal tween the intralaminar nuclei and their main
that cortical neurons projecting bilaterally to termination sites in the striatum. It was also
the striatum are few in number compared to demonstrated that, in addition to prominent
those projecting ipsilaterally or contralater- afferents from the “ nonspecific" intralaminar
ally (95, 316). nuclei, the striatum receives a significant
The massive striatal afferents from the input from "specific" thalamic nuclei such as
cerebral cortex terminate principally on the the ventral anterior, ventral lateral, and lat -
head of the dendritic spines of the spiny pro- eral posterior nuclei ( 273).
jection neurons, where they make asymmet - Earlier electrophysiologic and HRP stud -
ric synapses ( 108, 337). The corticostriatal ies suggested that the thalamostriatal fibers
fibers exert an excitatory influence on striatal issue collateral to the cerebral cortex (184,
projection neurons, most probably through 306). The existence of such collaterals was
the use of glutamate as a neurotransmitter confirmed by retrograde double-labeling and
( 100, 198, 338). antidromic invasion studies (181 , 229 ). These
branched neurons abound in rostral intralam -
THALAMOSTRIATAL PROJECTIONS inar nuclei, but are rather few in number in
the centromedian nucleus, where neurons
The thalamostriatal projection is the sec - projecting to the cerebral cortex are confined
ond most prominent striatal group of affer- to the lateralmost portion of the nucleus
ents ( Figs. 19.18 and 19.34 ). Its existence was ( 320 ). Collaterals of thalamostriate fibers pro-
first detected in human material by Cecile jecting to broad cortical areas end in laminae
and Oskar Vogt in Germany, who suggested V and VI .
that the intralaminar nucleus known as the The thalamostriatal fibers terminate prin-
centromedian projects densely and selec - cipally on the shafts and , less abundantly, on
tively to the putamen ( 361 ). The authors were the dendritic spines of the medium spiny
Figure 19.20. Patch-like terminal fields of the thalamostriatal projection in the squirrel monkey, as seen at low (A) and
high power (B) magnifications The pathway was traced following injection of the highly sensitive anterograde tracer
Phaseolus vu/garis-leucoagglutinin (PHA -L) in the centromedian nucleus. As seen at low power (A), the thalamostri-
atal fibers terminate in a highly heterogeneous manner in the putamen and mediodorsal border of the caudate nu-
cleus These areas correspond to the sensorimotor striatal territory At higher magnification (B). thalomostriatal fibers
can be seen to form elongated bands in the dorsolateral portion of the putamen Scale bar 1 mm In A and 300
(im in B
projection neurons ( Fig. 19.21 ) (101, 321 ). cells of the pars compacta [SNc, group A9 of
These fibers form asymmetric synapses and Dahlstrom and Fuxe (66)1. Other neurons lo-
are thought to exert an excitatory influence cated in the ventral tegmental area I ( VTA,
that is mediated probably through glutamate. group AH) of Dahlstrom and Fuxe ( 66 ) )|and
in the retrorubral area |( RRA , group A8 of
NIGROSTRIATAL PROJECTIONS Dahlstrom and Fuxe ( 66 ) ) ] also contribute to
the nigrostriatal projection. Neurons in the
Evidence concerning nigrostriatal fibers VTA give rise to the mesolimbocortical sys-
has, for a long time, been based almost en - tem, whose fibers terminate principally in the
tirely upon retrograde cell changes produced ventral striatum ( limbic striatal territory ) and
in the substantia nigra following large striatal the frontal cortex, whereas those in the SNc
lesions (93, 94, 242, 363). Attempts to trace and RRA project via the nigrostriatal path-
fiber degeneration from lesions in the sub- way to the bulk of the striatum ( 48). The ni-
stantia nigra to the striatum in Marchi prepa - grostriatal pathway is partially crossed but
rations and silver-impregnated material ( 2, the number of nigrostriatal neurons project -
49, 57, 90) either failed to demonstrate these ing contralaterally does not exceed 5% of
fibers or indicated that they were sparse. those projecting ipsilaterally and there are
However, the histofluorescence technique for apparently very few neurons in the SNc and
the demonstration of monoamines (38, 88) re- VTA that project bilaterally ( 273). Further-
vealed that cells in the pars compacta of the more, some 10% of nigrostriatal fibers are
substantia nigra send axons to the striatum said to be nondopaminergic, but their cells of
that convey dopamine to their terminals (12, origin are uncertain (130)
13, 23, 67, 109, 164, 167, 354). Striatal Neuroanatomic data from various sources
dopamine is stored in regularly spaced indicate that the nigrostriatal projection is
swellings or varicosities along the terminal topographically organized in different spe-
portions of the axons. Dopaminergic fibers cies. In monkeys, the rostral two- thirds of the
appear as a distinct matrix of fine varicose substantia nigra is related to the head of the
axons which form thick sworls around both caudate nucleus, whereas nigral neurons pro-
small and large striatal neurons ( 330 ). jecting to the putamen are more caudally lo-
Dopamine is synthesized in the pigmented cated and display a rostrocaudal topography
Figure 19.21. Ultrastructural features of PHA-L anterogradely labeled elements In the caudate nucleus (A) and puta-
men (B) following PHA -L injections in the parafascicular nucleus and the centromedlan nucleus, respectively . PHA -
L-labeled boutons (containing a dark precipitate) form asymmetric synapses (arrowheads) with dendritic shafts
( d) (A) and. more rarely , with spines (SpP ) (B) Note the presence of two large dense-core vesicles ( arrows) in the
PHA - L -labeled boutons in A and a nonimmunoreactive bouton (asterisk) that forms an axosplnous synapse ( arrow -
head) in B
( 259,347 ) ( Fig. 19.22 ). A mediolateral topo- to both the caudate nucleus and the putamen .
graphic relationship between the SNc and The functional significance of the complex in-
the striatum is also proposed, with an appar- trinsic organization of the SNc remains to be
ent inverse relationship along the dorsoven- investigated , but it may reflect the highly het-
tral axis ( 346, 347 ) . Additionally, projection erogeneous and mosaic-like arrangement of
fields of the nigrostriatal pathway are pur- the various neuronal elements within the
ported to overlap significantly in all planes, striatum itself .
possibly accounting for the apparent lack of Autoradiographic studies have revealed
precise organization of the nigrostriatal sys- that nigrostriatal fibers terminate in patches,
tem ( 347 ). although these patches are less distinct in
In contrast, retrograde double-labeling adults than those of the corticostriatal and
studies in primates revealed that nigral neu - thalamostriatal projections (115, 375). The
rons projecting to the caudate nucleus and patches of nigrostriatal axons are closely in -
those projecting to the putamen are orga- termingled with the patches of the thalamo-
nized in the form of closely intermingled striatal projection ( 20 ). Immunohistochemi -
clusters of various sizes and distributed cal studies with antibodies raised against
throughout the entire SNc in a complex and tyrosine hydroxylase ( TH ), the rate-limiting
precise mosaic-like pattern ( Fig . 19.23) ( 283). enzyme in the synthesis of catecholamines,
Only a few nigral neurons appear to project showed that the striosomes are rather
B
I .H ' 94
Figure 19.22. Comparison of the efferent projections of the substantia nigra pars compacta (SNc) ( A ) and the sub-
stantia nigra pars reticulata (SNr) (B). as seen in the sagittal plane Fibers from dopaminergic neurons of the SNc form
.
a feedback projection to the caudate nucleus (CD) and putamen ( PUT ) Distinct neurons in the SNc also project to
.
the globus pallidus where they arborize more extensively in the internal (GPr ) than in the external ( GPe) pallidal seg-
ment By contrast, the SNr is a major output nucleus of the basal ganglia Fibers from SNr neurons branch profusely to
.
(a) the ventral tier thalamic nuclei ( VA nucleus ventral anterior and VLm / VLo nucleus ventral lateral pars magnocel-
lular and oralis), (b) the superior colliculus ( SCO), and (c) the pedunculopontine nucleus ( PPN ) AC. anterior commis-
. . .
sure; CM centromedian thalamic nucleus; ICO inferior colliculus; ML medial lemniscus, Ol optic tract; Pul pulvinar;
.
STN subthalamic nucleus; Zl, zona incerta.
poorly innervated in adult monkeys by It is generally accepted that dopamine has

comparison to the extrastriosomal matrix an inhibitory action on striatal neurons ( 28,
(Fig. 19.24A) ( 2201 . 162, 228, 330) . However, the effect of
Lesions in the substantia nigra cause con - dopamine can be multifarious as it is medi -
spicuous reductions in striatal dopamine ipsi - ated through a family of dopaminergic recep-
lateraUy ( 13, 109, 164, 298, 354 ), whereas large tors that contains at least five members. The
striatal lesions produce distinct increases in two most well-characterized dopaminergic
dopamine in the SNc cells which decrease as receptors in the striatum are designated as D ,
the cells undergo chromatolysis. and D: subtypes. The pattern of binding for
SNc
SNr
° « » '
<
CP
Sj :V=\
* °
oo°0o° °
•••' ‘'
"
- o°0°
'P1° : ooo°;0
0 0
OO
&T V
i
CP y/.i* .° />
PO
B
Figure 19.23. Frontal sections through the rostral (A) and middle (B) thirds of the substantia nigra of the squirrel mon-
key illustrating the mosaic-like distribution of the pars compacta (SNc) neurons projecting to the caudate nucleus
(open circles) and putamen ( filled circles), as seen after injection of one retrograde fluorescent tracer in the caudate
.
nucleus and the other in the putamen on the same side of the brain. CP cerebral peduncle; PO, pontine gray SNr , .
.
substantia nigra pars reticulata; III oculomotor nerve root fibers
,
both D and D2 receptors in the striatum does synergistically to modulate neuronal activi-
not match the patchy heterogeneity seen with ties.
acetylcholinesterase staining, but areas of Ultrastructural studies revealed that nerve
greatest receptor density are found in the ma - terminals containing dopamine have small
,
trix . Activation of D receptors reduces mem- clear vesicles, with a few large dense-core
brane excitability , while activation of D2 re- vesicles (76, 164). The dopaminergic nerve
ceptors causes a decrease in the release of terminals make symmetric synapses with the
transmitter substance at synaptic terminals. dendritic shafts and spines of striatal spiny
,
Although D and D2 receptors can be distin- neurons (31, 107). A large proportion of the
guished , these receptors appear to function dopaminergic synapses occur on the neck of
I
p in
?)» •»
*
>
v; v SNC
Gi 'r' - 1 ^D \**4V*
' '
,V'
Figure 19.24. Features of the dopaminergic innervation of the basal ganglia in the squirrel monkey as revealed with
immunohistochemical staining for the enzyme tyrosine hydroxylase ( TH ) A Patches of poor TH immunostainmg sur -
rounded by zones of intense immunoreactivlty in the caudate nucleus ( CD) near the Internal capsule ( 1C ) B Numer-
ous TH-positive fibers In the external pallidum (GPe) and Innumerable TH axon terminals in the adjoining putamen
( PUT ) C Dense TH-immunoreactive fiber bundles emerging from the substantia nigra pars compacta ( SNc ) and
coursing within the zona incerta near the subthalamic nucleus ( STN ) D Higher power view of the TH-positive fiber
bundles located dorsal to the SNc corresponding to the inserfin C Scale bars 500|im (A, C) and 300 p.m (B D)
-
' .1 O CD -
LV
(
%
%
I
PUT
)
1 i
/' V
. * ICA
:
'
V AC
AS
X.%. ,
V
A
Figure 19.25. Frontal sections through the rostral ( A) middle (B). and cauddl (C) thirds of the basal ganglia of the
squirrel monkey illustrating the distribution of serotonin-immunoreactive fibers (sinuous lines) and axon terminals ( dots )
Note the highly heterogeneous distribution of serotonin-positive profiles in the striatum and the dense serotoninerglc
innervation of the internal pallidal segment and the substantia nigra. AC. anterior commissure; AS. nucleus accum-
bens. AV. anterior ventral thalamic nucleus, CD. caudate nucleus: CeM. centromedial thalamic nucleus. ; CP cere- .
. .
bral peduncle. F. fornix: GPe. external segment of globus pallidus: GPi internal segment of globus pallidus: 1C internal
.
capsule, ICA. island of Calleja. L lenticular fasciculus: LD. laterodorsal thalamic nucleus, LV lateral ventricle; OT. optic
tract: PUT. putamen; RN. reticular thalamic nucleus. SNnr. substantia nigra pars reticulata. SNnc. substantia nigra pars
compacta, STM. subthalamic nucleus; fM, mammillothalamic nucleus. VA, VL and VP. ventral anterior , ventral lateral,
and ventral posterior thalamic nuclei. Zl. zona incerta .
spines whose head receives asymmetric con- tion of the dopaminergic nigrostriatal projec-
tacts from what appears to be corticostriatal tion results in a marked increase in the level
fibers. Thus, dopamine terminals are ideally of mRNA coding for enkephalin and con-
positioned to control or modulate the excita - comitant decrease in levels of mRNA coding
tory information from the cerebral cortex as it for substance P ( 17, 122).
flows through the striatal spiny projection
neurons ( Fig. 19.26 ) ( 107). AFFERENTS FROM THE RAPHE NUCLEI
Dopamine also may influence the activity
of intrinsic and extrinsic striatal neuronal ele- These afferents originate principally from
ments through nonjunctional appositions (31, the dorsal raphe nucleus and use serotonin
76, 133, 296, 350 ). Furthermore, in addition to -
[5 hydroxytryptamine ( 5- HT )| as a neuro -
its ionotropic action mediated through clas- transmitter (19, 29, 58, 162, 173, 218, 278, 351 ).
sic axospinous or axodendritic synapses, The dorsal raphe-striatal projection is mainly
dopamine can alter neuronal membrane ipsilateral and arborizes profusely within the
properties and exert a marked metabotropic entire striatum, but slightly more heavily in
and genomic influence on striatal projection the ventrocaudal region ( Fig. 19.25). Retro-
neurons. For example, dopamine plays an -
grade double labeling studies in rodents
important role in the regulation of peptide showed that dorsal raphe neurons projecting
expression in striatal spiny neurons. Destruc- to the striatum also send axon collaterals to
GLU GLU
y CORTEX THALAMUS
z
LT
H
x DA
DA
SNc
SNc
THAL
y
CO
2 ACh
oc DA
Large
Z Interneurons
GABA
Medium-sized
Interneurons
Figure 19.26. Hierarchy of the various intrinsic and extrinsic inputs to the medium spiny projection neuron of the stria-
tum. Note that extrinsic inputs tend to terminate on the distal dendritic tree while intrinsic inputs favor the proximal so-
matodendritic domain The insert illustrates the crucial position occupied by the dopaminergic Input ( DA ) on spines
that receive cortical afferent . The spiny striatal neuron is the major integrative element, as well as the principal output
. . - .
cell of the striatum ACh acetylcholine: CTX. cerebral cortex. DA dopamine; GABA, y - aminobutyrlc acid GLU gluta- .
.
mate. SNc substantia nigra pars compacta: THAL, thalamus .
the substantia nigra (355). Serotoninergic stri- (SNr). Striatonigral projections that establish
atal afferents form asymmetric synapses on synaptic relationships with cells of the SNr
dendritic spines or shafts of medium spiny and the GABAergic neurons of the SNr to-
striatal neurons (15, 289, 290, 336). Only gether constitute part of the output system
10-15% of 5-HT varicosities, however, exhibit from the basal ganglia . Striatopallidal fibers
a typical synaptic junction in the striatum of terminating in the internal pallidal segment
rats (15, 336). Although 5- HT terminals dis- (GPi) and the GABAergic pallidal neurons
play asymmetric synapses, which is usually that project to the thalamus form the largest
indicative of excitatory effect, the electrical output system from the basal ganglia . Major
stimulation of the dorsal raphe nucleus was projections from the SNr and the GPi are to
reported to produce inhibitory, as well as ex- different rostral ventral tier thalamic nuclei,
citatory , responses on spiny neurons (248, which have projections to different regions of
269, 287, 340). This wide variety of responses the cortex concerned with motor function.
may be explained by the existence of junc-
tional and nonjunctional modes of innerva- STRIATOPALLIDAL PROJECTIONS
tion, as well as by a wide variety of 5-HT
receptors (218). Of particular interest is Striatopallidal fibers are topographically
the existence of important functional and organized in both dorsoventral and rostro-
anatomic interactions between 5-HT and caudal sequences and radiate into various
dopaminergic afferents and the cholinergic parts of the pallidum like spokes of a wheel
(64, 260, 344) ( Figs. 16.8 and 19.6). Striatopal-
system in the striatum (19, 77, 173, 175, 263).
lidal fibers originating from the caudate nu -
cleus and the rostral part of the putamen ( i.e.,
AMYGDALOSTRIATAL PROJECTIONS
the associative striatal territory ) pierce the in-
Although the amygdala and the striatum ternal capsule and penetrate the globus pal-
are parts of anatomically and functionally lidus through its dorsal surface. These
distinct basal forebrain neuronal systems (i.e., caudatopallidal fibers arborize in the form of
the limbic system and basal ganglia ), experi- dense plexuses principally in the rostral pole
mental data suggest a close functional rela - of the external pallidal segment and , more
tionship between parts of these structures. caudally, in the dorsomedial third of both the
Projections from the basolateral amygdala external (GPe) and internal pallidal segment
terminate massively in the ventral striatum (GPi ) ( Fig. 19.27). Striatopallidal fibers arising
and less abundantly in the head of the cau - from the postcommissural putamen ( i.e., the
date nucleus and the rostral portion of the sensorimotor striatal territory) form several
putamen (318). The densest terminal field of distinct fascicles [ termed Wilson's pencils
the amygdalostriatal projection overlaps that after Kinnier Wilson (372)], that pierce the ex-
of the limbic and paralimbic cortical areas ternal medullary lamina to reach the globus
and corresponds to the limbic striatal terri- pallidus through its lateral border. In both
tory . Neurons in this striatal sector are be- segments of the pallidum, the putamenopalli-
lieved to be chiefly concerned with the con- dal fibers arborize in elongated bands aligned
trol of the emotional and motivational parallel with the medullary laminae. These
aspects of various types of motor behavior. bands are confined to the ventrolateral two-
thirds of both pallidal segments and do not
Efferent Connections significantly overlap the areas containing the
plexuses formed by caudatopallidal fibers.
The striatum receives input from a wide These findings indicate that axons of striatal
variety of sources, including the cerebral cor- neurons located in the associative or sensori-
tex, thalamus, and brainstem. In contrast, this motor striatal territory remain rather well-
major receptive component of the basal gan- segregated from one another at pallidal levels
glia is much more limited in its efferent pro- ( 274, 384, 385).
jections, as the vast majority of striatofugal Anterograde labeling studies in monkeys
fibers terminate only in the pallidum and reveal that the axons emerging from a small
substantia nigra ( Figs. 19.27 and 19.28). group of striatal neurons form several band-
Different populations of spiny striatal neu - like terminal fields (or plexuses) that are dis-
rons containing different combinations of the tributed according to a highly specific rostro-
same neurotransmitters (GABA, SP, and caudal sequence in the globus pallidus (150).
ENK ) project to both the globus pallidus and Furthermore, anterograde double-labeling
the pars reticulata of the substantia nigra studies show that the band -like terminal fields
INJECTION IN STRIATAL INJECTION IN STRIATAL

SENSORIMOTOR TERRITORY ASSOCIATIVE TERRITORY
Figure 19.27. Frontal half -sections through the rostral (A , D), middle (B , E), and caudal (C E) thirds of the striatopalli-
,
dal complex of the squirrel monkey comparing the distribution of anterogradely labeled fibers resulting from injec -
tions of PHA - L in the sensorimotor ( A- C) and associative (D-F) striatal territories . Fibers emerging from the head of the
caudate nucleus terminate in the form of plexuses in the dorsolateral portion of the globus pallidus, whereas those
from the postcommissural putamen form bands in fhe ventrolateral two-thirds of the pallidum. AC, anterior commis-
. . .
sure; CD, caudate nucleus GPe. external segment of globus pallidus GPi internal segment of globus pallidus; 1C In- .
ternal capsule, PUT, putamen.
INJECTION IN STRIATAL INJECTION IN STRIATAL

SENSORIMOTOR TERRITORY ASSOCIATIVE TERRITORY
r ft
Figure 19.28. Frontal half - sections through the rostral (A D) middle (B E). and caudal (C E) third of the substantia
nigra of the squirrel monkey comparing the distribution of anterogradely labeled fibers resulting from injections of
PHA L in the sensorimotor ( A -C) and associative (D-F) striatal territories Note that fibers emerging from the head of
the caudate nucleus are much more abundant than those from the postcommissural putamen Both types of fibers
form dense plexuses that are distributed along the lateromedial extent of the substantia nigra according to a precise
sequence Many of these plexuses lie at the basis of the pars compacta cell columns that impinge deeply upon the
. . .
pars reticulata CP. cerebral peduncle SNc substantia nigra pars compacta SNr. substantia nigra pars reticulata III . .
oculomotor nerve root fibers
arising from two adjacent striatal neuronal The band -like terminal fields formed by
groups do not overlap but remain well -segre- putamenopallidal fibers are composed of stri-
gated at pallidal levels ( Fig. 19.29) (150 ). These atopallidal fibers and their axon collaterals,
findings indicate that the striatopallidal pro- many of which closely entwine the dendrites
jection is a highly patterned neuronal system of pallidal neurons. The resulting profile,
whereby information from the striatum can be which is typically composed of several thin
conveyed and integrated in a remarkably pre- striatopallidal axons wrapped around an un -
cise and ordered manner ( 281, 384, 385). stained core ( the pallidal dendrite), has often
Figure 19.29. Frontal half -sections through the striatopallidal complex of the squirrel monkey illustrating the distribu-
.
tion of anterogradely labeled fibers originating from two adjacent sites in the putamen one injected with PHA -L
(.blue) and the other with biocytln ( red) The two types of anterogradely labeled fibers remain segregated at pallidal
levels . They form elongated terminal fields that often lie close to one another but do not intermix . This finding under -
lines the high degree of specificity in the organization of the striatopallidal projection system in primates. AC. anterior
.
commissure; CD, caudate nucleus; GP globus pallidus; GPe, external segment of GP; GPi. internal segment of GP; 1C .
.
Internal capsule; PUT, putamen; PN reticular thalamic nucleus; THAL thalamus.
been referred to as "woolly" fibers (133). ments, which arise from intrinsic GABAergic
Studies of the termination of striatopallidal neurons. Comparisons of normal human
fibers at the ultrastructural level indicate that brains with those from patients with Hunt -
pallidal dendrites are studded with axonal ington 's disease indicate substantial reduc-
terminals ensheathed with glia. Less frequent tions of SP and ENK in the globus pallidus
axosomatic synapses are seen. Cell bodies and substantia nigra (86).
have a wrapping of glial processes except
over axon terminals (191, 194, 195). The STRIATONIGRAL PROJECTIONS
striatopallidal fibers form GABA - positive
synapses of the symmetric type with higher These fibers originate from spiny striatal
order dendrites of pallidal neurons. neurons and project topographically, mainly
It has long been assumed that a single stri- on cells of the pars reticulata of the substantia
atal efferent system supplies both the globus nigra (SNr ) (36, 126, 199, 260, 343, 344, 345).
pallidus and the substantia nigra through Fibers from the head of the caudate nucleus
axon collaterals ( 104, 105, 197). Retrograde project to rostral parts of the substantia nigra .
double-labeling studies in primates, how - Putamenonigral fibers passing to more cau -
ever, have revealed that striatal projections to dal parts of the substantia nigra are arranged
the GPe, the GPi, and the substantia nigra so that dorsal parts of the putamen project to
arise principally from separate neurons ( Fig. lateral parts of the SNr and ventral parts of
19.30) ( 91, 275, 286). These findings reveal the putamen are related to medial parts of the
that the striatofugal system is not a mono- SNr. Striatonigral fibers arise from a different
lithic entity but , instead, appears to be com- population of spiny neurons than striatopalli -
posed of distinct striato-GPe, striato-GPi , and dal fibers but have the same neurotransmit -
striatonigral subsystems. These findings are ters, namely '
, GABA , SP, ENK , DYN , and NT
in agreement with data on the distribution of ( 51 , 68, 87, 110, 113, 122, 171, 186, 268, 273)
various neuropeptides at both pallidal and ( Figs. 19.30-19.32 A , B ) . Almost all striatoni -
nigral levels. gral fibers terminate in the SNr, but fibers im -
As mentioned earlier, all striatal spiny munoreactive for SP have been identified in
neurons use GABA as an inhibitory neuro- both the SNr and the SNc. Neurons in the
transmitter ( 227, 301, 335). These projection pars reticulata have smooth dendrites radiat -
neurons can, nevertheless, be distinguished ing rostrocaudally. Virtually all cells of the
from each other by their neuroactive peptide SNr are GABAergic ( 335) and GABAergic
content. For instance, striatal neurons project - fibers and terminals occur in all parts of the
ing to the GPe contain enkephalin, whereas SNr. These GABAergic striatonigral fibers
striatal cells projecting to the GPi are en - form a synapse of the symmetric type with
riched with substance P (and dynorphin ) the dendrites of either GABAergic SNr neu -
( Figs. 19.31 and 19.32 A , B ) . Regional differ- rons or dopaminergic SNc cells.
ences in the distribution and concentration of Anterograde double-labeling studies in
these two peptides are evident in both palli- monkeys revealed that the striatonigral fibers
dal segments. Substance P immunoreactivity terminate in the form of clusters uniformly
in fibers is particularly dense in the apical re- scattered throughout the SNr ( Fig. 19.28)
gion of the GPi and enkephalin ( ENK ) im - ( 282 ). These plexuses are often located at the
munoreactive fibers appear most numerous basis of the dopaminergic cell columns of the
in ventral regions of the GPe caudally ( Fig. SNc. As for the band -like terminal fields
19.32 A , B ). The ventral pallidum contains nu - formed by putamenopallidal fibers, the stria-
merous SP-, ENK -, and DYN -immunoreac- tonigral fiber plexuses are multiple and dis-
tive fibers ( 131, 134 ). It is believed that SP, tributed according to a very precise rostro-
FNK , and DYN fibers, distributed differen - caudal sequence. This finding underlines the
tially in the two segments of the globus pal - highly ordered nature of the organization of
lidus, play different roles in modifying the the striatonigral projection ( 282, 384, 385).
distinctive efferent systems of these seg- The GABAergic neurons of the SNr give
Figure 19.30. Injection sites ( hatched and stippled areas) and the rostrocaudal distribution of ttie retrogradely la-
beled cells observed in the striatum after injections of fast blue in the substantia nigra and nuclear yellow in the
globus pallidus of the squirrel monkey The striatal neurons containing the tracer injected in the pallidum are repre-
sented by open circles, those containing the trocer injected in the substantia nigra by filled circles, and the double -
- -
labeled neurons by asterisks The small number of double labeled cells encountered after such a double injection ex -
periment indicates that striatopallidal and striatonigral projections arise largely from distinct striatal populations in
primates.
° *0 r
PUT . ,o
•• • .#
I
\o o o oO
O %
1
/
/ 1
I
§
*o ° °o °
0
1C I
o o o
I
*
o
o o o
o •y N( \
y
o o
o
o r \
\ O . '
O •
/
' f
STN
o
o o
(
o ° ° o
o SN
7e ° O
° •• •
u ••
•
:
CD
GABA -ENK
GABA - SP-DYN
°O GABA
( ENK - SP-DYI
GABA-SP- DYN
GABA \
;- SP-DYN) \
\
GPe X
\
GPi
Figure 19.31 . Neurochemical content ot the striatopallidal and striatonigral pathways Virtually all striatofugal neu -
rons use y ammobutyric acid (GABA) as inhibitory neurotransmitter Several subsets of striatal neurons can neverthe-
less be distinguished on the basis of their content in neuroactive peptides and their site of termination At pallidal lev-
els. GABAerglc striatal neurons containing enkephalin ( ENK) project principally to the external pallidal segment
(GPe). whereas those containing substance P (SP) and dynorphin ( DYN) project mainly to the internal pallidal seg-
ment ( GPi ). GABAergic striatonigral neurons are of several sorts, some containing enkephalin, substance P, or dynor -
.
phin or combinations of these peptides. The dotted line in the pallidum traces the limit between the associative palli-
dal sector dorsomedially and the sensorimotor pallidal sector ventrolaterally CD. caudate nucleus; PUT putamen,.
SN. substantia nigra
rise to nigrothalamic projections that have GLOBUS PALLIDUS

large numbers of collaterals terminating in
middle layers of the superior colliculus and Topography , Development and Intrinsic
in the midbrain tegmentum . Nigrothalamic Organization
fibers terminate in the ventral anterior nu -
cleus ( VAmc ) , parts of the ventral lateral nu - This nuclear complex, forming the smaller
cleus ( VLm ), and in parts of the mediodorsal and inner part of the lentiform nucleus, lies
nucleus ( MDpl ) . These thalamic nuclei do not medial to the putamen throughout most of its
receive afferents from any other part of the extent . The dorsomedial margin of the pal -
basal ganglia . lidum borders the posterior limb of the inter-
t fe;
. l * T\
• m
W'
'
*L A
*:
c ml
Figure 19.32. Immunohistochemical features of the globus pallidus in the rhesus monkey . A Substance P- immunore -
active fibers confined to the internal pallidal segment are more intensely stained in the apical region B Enkephalin -
immunoreactive fibers and terminals are limited to the external pallidal segment . In the middle third of the external
pallidum, immunoreactive fibers are most intense ventrally and near the medullary lamina C Large cholinergic neu
rons (choline acetyltransferase (ChAT)-immunoreactive) are abundant in the medullary lamina caudally These neu-
rons represent a dorsal extension of the basal nucleus of Meynert ChAT-positive aspiny cells are evenly distributed in
the striatum D A large GABA immunoreactive neuron characteristic of virtually all pallidal neurons in both segments
nal capsule. A thin lateral medullary lamina lies velopment the anlnge of the corpus subthala-
on the external surface of the pallidum at its micum and both segments of the pallidum
junction with the putamen. A medial are arranged in a linear fashion with the an-
medullary lamina divides the globus pallidus lage of the external (or lateral ) pallidal seg-
into internal (GPi ) and external (GPe) segment most rostral , that of the subthalamic nu-
ments ( Figs. 19.2, 19.6, 19.33, and 19.34 ). The cleus most caudal, and that of the internal
two major pallidal subdivisions are also pallidal segment ( or entopeduncular nucleus
termed medial and lateral segments by some in nonprimates ) in an intermediate position.
authors. A less distinct accessory medullary In the third month of fetal life, the external
lamina ( 214 ) divides the internal ( or medial ) pallidal segment migrates rostrolaterally to
pallidal segment into outer and inner por- contact the medial surface of the putamen .
tions, which appear to give rise to efferent The entopeduncular nucleus follows the ex -
fibers that have distinctive courses ( Fig. ternal pallidal segment rostrolaterally and as-
19.33). sumes an adjacent medial or internal posi-
Classically, the globus pallidus is consid - tion , where it is called the internal ( or medial )
ered to be a telencephalic derivative (136). pallidal segment. The most caudal anlage in
Studies of the ontogenetic development of the this longitudinal hypothalamic zone, the sub-
globus pallidus and subthalamic nucleus, thalamic nucleus, is pushed medially by in -
however, suggest that these structures are di- vading fibers of the hemispheric stalk and be-
encephalic derivatives ( 309). During early de - comes separated from the pallidum by the
HORIZONTAL TRANSVERSE
o '
^-v-
TH
1C
Ansa Lent . Mammillo-
Lent . Fasc. thalamic tr .
Lent
Fasc. GPe A
OPK
a F
B Ansa
Lent . V
Figure 19.33. Origin and course of pallidothalamic fibers forming the ansa lenticularis and lenticular fasciculus as
seen In horizontal (A) and transverse (B) sections Fibers of the ansa lenticularis (red) arise from the outer portion of the
infernal pallidal segment (lateral to the accessory medullary lamina, dashed line) and course rostrally. ventrally and .
medially . Fibers of the lenticular fasciculus (blue) arise from the inner portion of the internal pallidal segment (medial
to the accessory medullary lamina, dashed line) and course dorsally and medially through the fibers of the internal
. . .
capsule. F, fornix; 1C internal capsule; GPe. external pallidal segment; GPi internal pallidal segment, SN substantia
.
nigra; STN, subthalamic nucleus; TH thalamus.
Caudate Reticular
nucleus nucleus
Internal
capsule Stria medullaris
Thalamostriatal — Third ventricle

fibers
Centromedian
Putamen nucleus
Globus pallidus Thalamic

external fasciculus H-|
internal Lenticular
fasciculus H2
Subthalamic
fasciculus Fornix
Subthalamic
nucleus
Ansa
lenticularis Optic tract
Figure 19.34. Pallidofugal fiber systems in a transverse plane Fibers of the ansa lenticularis (red) arise from the outer
portion of the internal pallidal segment, pass ventrally. medially and rostrally around the internal capsule and enter
the prerubral field. Fibers of the lenticular fasciculus (H2, black ) issue from the dorsal surface of inner part of the inter -
nal pallidal segment, traverse the posterior limb of the internal capsule, and pass medially dorsal to the subthalamic
nucleus to enter the prerubral field The ansa lenticularis and the lenticular fasciculus merge in the prerubral field (field
,
H of Forel, not labeled here) and project dorsolaterally as components of the thalamic fasciculus (H ). Fibers of the
,
thalamic fasciculus (H ) pass dorsal to the zona incerta (// ) The subthalamic fasciculus ( blue) consists of pallidosub-
thalamlc fibers arising from the lateral pallidal segment, and subthalamopallidal fibers that terminate in arrays parallel
to the medullary lamina in the two pallidal segments. Both components of the subthalamic fasciculus traverse the in-
ternal capsule Thalamostriatal fibers from the centromedian nucleus ( black ) project to the putamen, as part of a
feedback system
internal capsule. Anatomic connections be- tensions of the basal nucleus of Meynert ,
tween the subthalamic nucleus and the pal - which lies ventral to the globus pallidus ( Fig.
lidum are maintained during these migra - 19.320 ( 120, 246, 280 ).
tions by fibers which traverse the peduncular
part of the internal capsule. Afferent Connections
Many bundles of myelinated fibers tra -
verse the globus pallidus, which in fresh Major afferent fibers to the globus pallidus
preparations give it a paler appearance than arise from the striatum and the subthalamic
the putamen or caudate nucleus. A morpho- nucleus. Unlike the striatum, the globus pal -
metric analysis of the human globus pallidus lidus does not receive massive projections
indicates that the GPe constitutes 70% of the from the cerebral cortex or the thalamus.
total volume of the pallidum and has cell
densities which are greater than those for the STRIATOPALLIDAL PROJECTIONS
GPi ( 323). However, the mean volume of The striatopallidal fiber system is by far
nerve cells in the GPi is 10% higher than in the most massive afferent projection to the
the GPe. Estimates of the total number of pal- globus pallidus. As seen earlier, this projec-
lidal neurons indicate a range of 465,000 to tion is topographically organized: efferents
540,000 for the GPe and 143,000 to 171 ,000 for from the caudate nucleus occupy the dorso-
the GPi . Golgi studies reveal that pallidal medial third and those from the putamen the
neurons are large ovoid or polygonal cells, entire ventrolateral two-thirds of the pal-
35-50 p.m in their long axis, with long, thick, lidum . The pallidal region receiving putame-
relatively smooth dendrites (102). nal afferents contain neurons whose activity
The dendrites of the large ( principal ) pal - is closely related to body movement (8, 14,
lidal neurons are sparsely branched and 71 ). The striatopallidal fibers are arranged in
often have complex appendages, referred to the form of bands, parallel to the medullary
as "thin processes" or "complex endings" laminae, a pattern that reflects the discoidal
( 106). The mean value for the total dendritic
organization of the dendritic domain of palli-
length of the large pallidal neurons is about dal neurons. The remarkable length of the
7600|un ( 139, 378) . The dendritic arboriza - disk -like dendritic fields in planes perpendic-
tion of the pallidal neurons in primates is ular to the striatopallidal border suggest that
characteristically discoidal, with a mean di- there is a large degree of convergence in the
mension of 1500 x 1000 x 250 gm ( 378). These striatopallidal system ( 287, 294). However,
large neurons with disk -like dendritic fields the fact that efferents from the caudate nu -
are particularly numerous laterally near the cleus and those from the putamen occupy
medullary laminae, while the more medial distinct pallidal sectors would indicate that
pallidal neurons display an oval dendritic output from the associative striatal territory
field ( 287 ). These dendritic disks lie parallel and that from the sensorimotor territory are
to the border of the pallidum , that is, with processed largely independently in the
their largest surface perpendicular to the globus pallidus ( 274, 281 ).
incoming striatal axons. They are ideally
positioned to intercept the entire proximal SUBTHALAMOPALLIDAL PROJECTIONS
arborization of the striatopallidal axons
( 287, 378). Subthalamopallidal fibers are topographi -
A rich plexus of afferent fibers invests the cally organized and project to both segments
long dendrites with an array of longitudinal of the pallidum in arrays parallel to the
fibers that bear "boutons en passage." The medullary laminae ( 44, 45, 49, 258, 331 ) ( Fig.
most prevalent synaptic endings contain 19.41 C, D ). The largest number of fibers arise
large pleomorphic vesicles and a few large from cells in the lateral two-thirds of the sub-
dense-core vesicles. These endings make thalamic nucleus and project to well -defined
symmetric contacts on dendrites of pallidal laminae in dorsal regions of the GPe. Termi-
neurons (144 ). No morphologic or chemical nals in the GPe closely surround arrays of
differences are evident in the large neurons of neurons that project back to the subthalamic
the GPi and the GP all large neurons nucleus. Reciprocal relationships appear to
within both segments of the globus pallidus exist between rostral and central portions of
.
are C ABAergic ( Fig. 19.32 D ) . Axons of the
pallidal neurons have few collaterals. Large
the GPe and the lateral two-thirds of the sub-
thalamic nucleus. A much smaller number of
cholinergic neurons in portions of the medial cells in medial regions of the subthalamic nu -
and lateral medullary laminae constitute ex- cleus project to the GPi .
Anterograde double-labeling studies in and 19.38). Thus, the GPi can be viewed , to-
monkeys indicate that the band -like terminal gether with the SNr, as a major output com-
fields formed by the subthalamopallidal ponent of the basal ganglia. In contrast, the
fibers are in register with those of the stri- GPe has long been considered as having
atopallidal fibers. Furthermore, both inputs more limited efferent projections than the
converge upon the same pallidal neurons GPi. It is reciprocally linked with the subthal-
(151, 152, 154 ) ( Fig. 19.43). In contrast to the amic nucleus, thus forming part of the well-
striatopallidal fibers whose inhibitory action known pallido-subthalamo-pallidal loop, one
is mediated through GABAergic synapses of of the many closed ancillary systems that are
the symmetric type, the subthalamopallidal so characteristic of the basal ganglia circuitry
fibers exert an excitatory influence that is me- (273). Anterograde and retrograde labeling
diated through glutamatergic synapses of the studies, however, have shown that the GPe
asymmetric type ( Fig. 19.41 E, F) (334 ). Thus, project to a wide variety of structures, includ -
the firing pattern of pallidal neurons is the re- ing the substantia nigra ( 277, 283), the stria -
sult of a complex interplay between these two tum ( 285), the reticular thalamic nucleus
functionally opposite inputs ( 281 ). (148), and the GPi ( Fig. 19.39) (155). The latter
Retrograde double-labeling studies and in- projection forms large, GABAergic, symmet-
tracellular labeling experiments in the rat ric synapses around the cell bodies and proxi-
suggested that virtually all neurons of the mal dendrites of pallidal neurons ( Fig. 19.40).
subthalamic nucleus project to both the The GPe is thus in an ideal position to modu-
globus pallidus and the SNr ( 202, 356). Simi- late and even shunt the activity of the output
lar studies in the primate indicate that only neurons of the GPi. Moreover, this GPe-GPi
about 10% of the cells in the subthalamic nu- projection allows the striatum to exert a dou -
cleus project to both the globus pallidus and ble effect on GPi neurons (a ) a direct in-
the substantia nigra ( Figs. 19.41 A , B, and hibitory effect upon the distal dendrites of
19.42) (285). pallidal neurons mediated through the direct
striatopallidal projection, and ( b) an indirect
OTHER PALLIDAL AFFER 2NTS disinhibitory effect upon the soma and proxi-
mal dendrites of pallidal neurons mediated
The globus pallidus of the monkey receives through a relay in the GPe ( 281 ) ( Fig. 19.43).
a dense innervation of dopaminergic fibers In light of these findings, the GPe can no
that arborize mainly in the GPi. These longer be considered as a mere relay in the
dopaminergic fibers appear to originate from pallido-subthalamo-pallidal loop. Instead , it
cells throughout the SNc ( 220). This projection should be regarded as a structure that exerts
to the GPi is considered distinct from that of an important control upon the information
dopaminergic neurons projecting to the stria- that flows along the main axis of the basal
tum ( Fig. 19.22) (332). The GPi also receives a ganglia .
serotonergic projection derived from ascend - The efferent fibers from the two pallidal
ing 5- HT fiber bundles ( Fig. 19.25) (53, 218). segments can be divided into four main bun-
Although cells of the two pallidal segments dles: (a ) the ansa lenticularis , (b) the lenticular
are morphologically and chemically similar, fasciculus , (c) the fwllidotegmental fibers , and
the activities of GABAergic neurons in each (d ) the pallidosubthalamic fibers. The first three
segment appear subject to modulations by of these arise exclusively from the GPi ( Figs.
different chemospecific afferents. '
19.33-19.35) (42, 49, 199 244, 260, 305). Palli-
dosubthalamic fibers arise exclusively from
Efferent Connections the GPe ( Figs. 19.33 and 19.36A ) ( 44, 45, 226).
Pallidofugal fibers are arranged in a rostro-
Because they are composed of neurons caudal sequence with the ansa lenticularis
that are morphologically and chemically most rostral, the lenticular fasciculus in an in-
identical and receive similar inputs, the two termediate position and pallidosubthalamic
pallidal segments cannot be readily distin - fibers most caudal.
guished from another. However, the two pal-
lidal segments markedly differ on the basis of ANSA LENTICULARIS
their efferent projections. Fibers arising from
cells of the GPi project to thalamic nuclei, the Fibers of the ansa lenticularis arise from
lateral habenular nucleus, and via a descend - lateral portions of the GPi and form a well-
ing tegmental bundle to a cell group in the defined bundle on the ventral surface of the
mesopontine tegmentum ( Figs. 19.36B, 19.37, pallidum ( Figs. 19.33-19.35). Fibers sweep
Zona incerta
Mammillothalamic Lenticular
tract Thalamic fasciculus
fasciculus
Optic tract \ Nucleus of

Ant. hypothalamic ansa lenticularis
commissure ( Ganser ) Dorsal supraoptic
commissure ( Meynert)
Figure 19.35. Lenticular fasciculus in a decorticate rhesus monkey Fibers of this bundle can be seen passing through
the degenerated internal capsule. At this level, immediately rostral to the subthalamic nucleus, the lenticular fascicu-
lus lies on the inner aspect of the internal capsule ventral to the zona incerta. (Weigert ' s myelin stain.)
ventromedially and rostrally around the pos- fasciculus ( Ford ’s field HI ) located dorsal to
terior limb of the internal capsule and then the zona incerta ( Figs. 14.34 and 19.35).
course posteriorly to enter Forel's field H . Investigations of the origin of pallidothala -
mic fibers in the monkey indicate that fibers
LENTICULAR FASCICULUS emerging via the ansa lenticularis and the
lenticular fasciculus arise from specific por-
These fibers arise from inner portions of tions of the GPi ( 42, 214 ). These data indicate
the GPi, emerge from the dorsomedial margin that fibers of the ansa lenticularis arise pre-
of the pallidum, slightly caudal to the ansa dominantly from the outer part of the GPi
lenticularis, and traverse ventral parts of the ( i.e., from that part of the GPi lateral to the ac-
internal capsule in a number of small fascicles cessory medullary lamina ). These fibers
( Figs. 19.33-19.35). Fibers cross through the course rostrally , ventrally and medially, and
internal capsule immediately rostral to the traverse portions of the GPi ( Fig. 19.33).
subthalamic nucleus and form a discrete bun - Fibers of the lenticular fasciculus arise largely
dle ventral to the zona incerta ( Fig. 19.35). Al - from the inner part of the GPi ( i.e., from the
though most of the lenticular fasciculus lies portion medial to the accessory medullary
rostral to the subthalamic nucleus, some fibers lamina ). These fibers course dorsally, ros-
of this bundle course along its dorsal border. trally and medially and traverse the pedun-
Fibers of the lenticular fasciculus are referred cular part of the internal capsule ( Fig. 19.33).
to as Forel's field 112. While fibers of the
lenticular fasciculus pursue a distinctive THALAMIC FASCICULUS
course through the internal capsule, they pass
medially and caudallv to join fibers of the Pallidofugal fibers from Forel's field H
ansa lenticularis in Forel's field ( H ) ( prerubral pass rostrally and laterally along the dorsal
field ). Fibers of the lenticular fasciculus ( H 2 ) surface of the zona incerta where they form
and the ansa lenticularis, which merge in part of the thalamic fasciculus ( Figs. 19.34
Forel's field H, ultimately enter the thalamic and 19.35). Some of the fillers of the lenticular
fasciculus merely make a C-shaped loop 384, 385). These contralateral pallidothalamic
around the medial part of the zona incerta fibers arborize in patterns that are similar to
and enter the thalamic fasciculus ( Figs. 19.34 those disclosed ipsilaterally (see Chapter 16).
and 19.36 B ) . The thalamic fasciculus contains
pallidothalamic fibers, as well as ascending PALLIDOHABENULAR PROJECTIONS
fibers from the contralateral deep cerebellar
nuclei. This composite bundle projects dorso- Fibers from the Gl’i projecting to the lat-
laterally over the zona incerta to terminate in eral habenular nucleus separate from the
specific nuclear subdivisions of the rostral ansa lenticularis and the lenticular fasciculus
ventral tier thalamic nuclei ( 260 ). In the rein Forel's field H and course through and
gion dorsal to the zona incerta , where fibers around the medial part of the internal cap-
of this bundle are distinct and separate from sule to enter the stria medullaris ( 47, 260 ).
those of the lenticular fasciculus ( Figs. 19.34 Autoradiographic studies in the cat stress the
and 19.35), the thalamic fasciculus is desig- substantial nature of this bundle and the di-
nated as bundle HI of Forel. verse routes followed by different compo-
nents ( 217, 257). Injections of 11 RI’ confined to
PALLIDOTHALAMIC PROJECTIONS the lateral habenular nucleus in the rat label
large numbers of cells in the entopeduncular
Pallidothalamic fibers project to the ven- nucleus ( the homologue of the primate GPi )
tral anterior ( VApc, pars principalis) and ven- and lesser numbers of cells in the lateral hy -
tral lateral ( VLo, pars oralis ) thalamic nuclei pothalamus, the nuclei of the diagonal band ,
( Figs. 16.13, 19.36 B , and 19.38A ) and give off the substantia innominata and the lateral pre-
collaterals to the centromedian (CM ) nucleus optic area (161, 217). In primates, however,
( Figs. 19.34 and 19.38 B ) . Pallidal projections the pallidohabenular projection is much less
to the rostral ventral tier thalamic nuclei are prominent than in rats and cats ( 272, 279). It
topographically organized (199, 214 ). Palli - arises from a small subset of pallidal neurons
dothalamic terminations do not overlap the distributed peripherally in the Gpi ( Fig.
crossed projections from the deep cerebellar 19.37). These neurons are distinct from those
nuclei or the ascending projections from the giving rise to the pallidothalamic fibers ( 276).
substantia nigra ( 169 , 170, 293, 352, 353). Each The habenular nuclear complex is an epi -
of these ascending systems terminates in sep- thalamic structure considered to be an inte-
arate divisions of the thalamic nuclei. The gral part of the limbic system (see Chapters
ventral lateral thalamic nucleus, particularly 16 and 18). In the habenular complex , the en -
the pars oralis ( VLo), projects to the supple - zyme glutamic acid decarboxylase (GAD) is
mentary motor area on the medial aspect of contained in terminals about cells of the lat-
the hemisphere and to the lateral premotor eral nucleus (121 ). Sources of GABAergic
area (area 6 ). fibers projecting to the lateral habenular nu -
Retrograde labeling studies in monkeys cleus are multiple and include pallidohabe-
confirmed that pallidal projections to the ven - nular fibers and fibers in the stria medullaris.
tral tier nuclei of the thalamus and the CM Histofluorescent, histochemical, and sensitive
nucleus arise largely from the axon collaterals biochemical microassay techniques reveal
of the same neurons in the GPi ( 276). These
branched neurons are located in the central
several neurotransmitters and their synthe -
sizing enzymes in the habenular nuclei, in-
portion of the GPi ( Fig. 19.37). Anterograde cluding catecholamines, serotonin, choline
labeling studies in nonhuman primates acetyltransferase, acetylcholine, and sub-
showed that the pallidothalamic fibers that
reach the ventral tier nuclei arborize accord-
stance P, in addition to GAD. It has been sug -
gested that projections of the GPi to the lat-
ing to a pattern that is strikingly different eral habenular nucleus may be involved in a
from that of the fibers terminating in the CM circuitry that functions in conjunction with
nucleus (149). Pallidothalamic fibers form the limbic system ( 257).
multiple small clusters in the VA / VL nuclei,
whereas they display a much more linear pat- PALLIDONIGRAL PROJECTIONS
tern , indicative of terminals en passant , in the
CM nucleus. Furthermore, there is a signifi- Most of the evidence supporting a palli-
cant proportion (approximately 10-20% ) of the donigral pathway has been based upon the
GPi efferent fibers that cross the midline to retrograde transport of HRP from the sub-
reach the contralateral ventral tier nuclei (149, stantia nigra to theGPe ( 36, 126, 187, 226, 277,
Area 4
Figure 19.36 . Afferent projections of the subthalamic nucleus (A) and efferent projections of the internal pallidal seg-
ment (B) shown in a sagittal plane The subthalamic nucleus (STN) receives afferents from a wide vdriefy of sources,
.
including the motor areas of the cerebral cortex ( black ) and the external segment of the globus pallidus (GPe) (red),
.
The internal segment of the globus pallidus (GPi) is together with the substantia nigra pars reticulata, a major output
nucleus of the basal ganglia. Its neurons send axons (red and blue) that branch to the ventral tier and centromedian
thalamic nuclei ( VA. VLo. and CM), and to the pedunculopontine nucleus ( PPN ) AC. anterior commissure; CD. cau-
. .
date nucleus; GPe external segment of globus pallidus; 1C internal capsule. ICO. Inferior colliculus; ML medial lem-
. .
niscus; OT. optic tract; Pul pulvinar. PUT. putomen; SCO. superior colliculus; SI, substantia innominata; SN substantia
.
nigra; Zl zona incerta.
Figure 19.37 . Output organization ot the globus pallidus in primates based on its main efferent projections as re-
vealed by fluorescent retrograde double-labeling studies. The various stippled and hatched areas indicate the zones
of origin of the major pallidal efferents. CM. centromedian thalamic nucleus; F. fornix. GPe. external segment of
globus pallidus; GPi. internal segment of globus pallidus; HB. habenula. LH. lateral hypothalamus. PPN. pedunculo-
pontine nucleus; SI. substantia innominata; SN. substantia nigra; SIN. subthalamic nucleus; STR. striatum; VA and VL
ventral anterior and ventral lateral thalamic nuclei
283). Retrograde transport studies suggest PALLIDOTEGMENTAL PROJECTIONS

that most pallidonigra fibers terminate in the
SNr . Autoradiographic studies in the rat em - These fibers ( Fig. 19.39 B ), derived from the
-
ploying 6 hydroxydopamine ( 6-OHDA ) to GPi ( 214, 260 ), become identifiable as a sepa -
produce degeneration in cells of the SNc sug- rate bundle dorsomedial to the subthalamic
gest that pallidonigral fibers terminate prefer - nucleus. The fibers of this bundle descend
entially upon dopaminergic cells in the sub- along the ventrolateral border of the red nu -
stantia nigra (146). Pallidonigral fibers are cleus and , in the caudal midbrain tegmen-
considered to have GABA as their neuro- tum , they sweep dorsolaterally to terminate
transmitter ( 147, 227 ). These fibers are dis- principally upon large cells of the pedunculo-
tinguished from striatonigral fibers, which pontine nucleus ( PPN ). This nucleus is par -
also have GABA as their neurotransmitter, tially embedded in fibers of the superior cere-
by their termination mainly upon cells of bellar peduncle ( 271 ). Studies in monkeys
the SNr. indicate that cells in the GPi have di-
chctomizing axons that project the same sig- tral division of the GPe ( flanking the GPi )
nal to thalamic nuclei and to the PPN ( 277). project to the lateral third of the subthalamic
Although the pedunculopontine nucleus nucleus throughout most of its rostrocaudal
receives its largest input from the medial pal- extent. Pallidosubthalamic fibers traverse
lidal segment, it also receives projections ventromedial and caudal parts of the internal
from the cerebral cortex (142, 215) and the capsule, caudal to both the ansa lenticularis
substantia nigra ( 21, 44, 45, 157, 166, 174, 252 ). and the lenticular fasciculus ( Fig. 19.34 ). Palli -
Projections of the PPN appear to be mainly dal neurons projecting to the subthalamic nu -
ascending, with the largest number of as- cleus are GABAergic. Sensitive anterograde
cending fibers projecting to the SNc, although tracing techniques indicate that neurons in
a significant number of fibers project to the the GPe projecting to the subthalamic nucleus
GPi and the subthalamic nucleus ( Fig. 19.20) emit collaterals that arborize in lateral parts
( 21 , 44, 45, 79, 174, 219, 252, 264 ). Connections of the SNr.
between the pedunculopontine nucleus and Subthalamopallidal fibers also traverse the
the substantia nigra are not reciprocal in the ventromedial and caudal parts of the internal
strict sense, since nigrotegmental fibers arise capsule but in the opposite direction. They
from cells of the SNr and ascending projec- are distributed to both pallidal segments
tions from the pedunculopontine nucleus end where they terminate in the form of vertically
upon cells of the SNc ( 21 , 219, 252 ).
Large cells in the PPN are strongly cholin -
ergic. In the rat, cholinergic cells of PPN are
considered to project mainly to the ventrolat-
eral thalamic nuclei. Noncholinergic neurons
in and around this nucleus are described as
projecting to the basal ganglia and related nu -
clei ( 221 ). In monkeys, the major projection of
the PPN is to the ipsilateral substantia nigra
and this projection is at least in part choliner-
gic ( 219). Glutamate is also present in neu -
rons of the PPN, including the cholinergic
neurons ( 219). Thus, the PPN may exert a
dual cholinergic and glutamatergic excitatory
effect upon nuclei of the basal ganglia . Spe-
cial interest in the PPN region centers around
locomotor activity produced by electrical
stimulation . Also worth noting is the demon -
stration of a direct projection from the deep
cerebellar nuclei to the PPN in monkeys
( 153). This projection indicates that the PPN
may act as an important functional interface
between the two major subcortical systems
involved in the control of motor behavior,
that is, the cerebellum and the basal ganglia .
SUBTHALAMIC FASCICULUS
The subthalamic fasciculus consists of pal- Figure 19.38 . Sections through the diencepholon in a
lidofugal fibers that pass through the internal rhesus monkey demonstrating transport of (3H) amino
capsule to enter the subthalamic nucleus, and acids from the internal (or medial) pallidal segment
(IMPS) to thalamic nuclei A Transported radioactive
of fibers from the subthalamic nucleus that
label is distributed in a patchy fashion to the pars oralis
project back to the globus pallidus. of the ventral lateral (VLo) and to the principal part of
Pallidosubthalamic fibers , arising only from the ventral anterior nuclei ( VApc) of the thalamus B The
the GPe, project upon cells of the subthalamic central region of the injection in the medial pallidal seg-
nucleus ( 44, 45, 47, 49, 260, 305). These fibers ment and modest transport of the label to the centro-
median nucleus (CM) of the thalamus Rodioactive
are topographically organized . Rostral parts label also is seen In Forel 's field H and in lateral parts of
of the GPe project to medial and rostral parts the subthalamic nucleus (STN ) Put indicates putamen
of the subthalamic nucleus. Cells in the cen- Cresyl violet. x 3.5.
Figure 19.39. Efferent projections of the external pallidal segment ( GPe) This structure, once believed to be locked
In a closed loop with the subthalamic nucleus (STN), is now known to be the source of projections to the substantia
. .
nigra (SN) striatum (putamen ( PUT ) and caudate nucleus (CD)), reticular thalamic nucleus ( PN ) STN, and the inter-
nal segment of the globus pallldus ( GPi )
elongated bands ( 44, 45, 49, 258, 331 ). As ( Forel's field H 2), the thalamic fasciculus
-
mentioned earlier, the band like terminal
fields formed by the subthalamopallidal
( Forel's field HI ), and the subthalamic fasci
culus ( Fig. 19.34 ).
-
fibers are in register with those of the stri-
atopallidal fibers, and both subthalamopalli- Subthalamic Nucleus
dal and striatopallidal fibers converge upon
the same pallidal neurons (151, 152, 281 ). The subthalamic nucleus ( corpus Luysi ), lo-
cated on the inner surface of the peduncular
SUBTHALAMIC REGION portion of the internal capsule, has the shape
of a thick biconvex lens ( Figs. 2.29, 16.5, 16.6,
The subthalamic region lies ventral to the 16.10, 16.11, 19.34, 19.38, and A .20 ). Caudally,
thalamus, medial to the internal capsule, and the medial part of the nucleus overlies rostral
lateral and caudal to the hypothalamus ( Figs. portions of the substantia nigra .
2.29, 16.5, 16.6, and 19.34 ). Nuclei found The subthalamic nucleus is considered to
within the subthalamic region include the be derived from the dorsocaudal part of the
subthalamic nucleus, the zona incerta, and lateral hypothalamic cell column ( 209, 210).
the nuclei of the tegmental fields of Forel ( nu - Richter (309 ) describes the subthalamic nu -
cleus campi Foreli, Forel's field H ). Fiber bun - cleus as arising from the "subthalamic longi-
dles passing through this region include the tudinal zone," along with both segments of
ansa lenticularis, the lenticular fasciculus the pallidum . The anlage of the subthalamic
successively in an ellipsoidal domain parallel

with the rostrocaudal axis of the nucleus (302,
377 ) . While subthalamic nucleus neurons in
rat and primate are similar, their relation
ships to the nucleus as a whole have evolved
-
to confer upon the primate the potential for a
much more specific organization.
The subthalamic nucleus receives a rich
blood supply derived from branches of the
posterior communicating, posterior cerebral,
and anterior choroidal arteries ( 98). It has a
consistent distribution in mammals, being
rudimentary in rodents and carnivores, but
well -developed in primates. While the nu -
cleus is small in monkeys, its relative size is
essentially the same as in humans (362, 369 ). '
Cells of the subthalamic nucleus were
shown to contain glutamate and to exert exci -
tatory effects on pallidal and nigral neurons
( Fig. W .4 I E , F ) (334). This structure is consid -
ered as one of the "driving forces" of the
basal ganglia ( 203, 384, 385) .
. v- K Connections of the Subthalamic
Nucleus
Figure 19.40 . Dense pericellular innervation formed by
the pallido (GPe)-pallidal (GP/) projection at light ( A)
AFFERENT CONNECTIONS
and electron microscopic (B) levels Axons of neurons in
the external segment of the globus pallidus (GPe) give
The major afferent projections to the sub-
rise to large terminal boutons that closely surround the
soma and proximal dendrites of neurons in the Internal thalamic nucleus are derived from ( a ) the
segment of the globus pallidus (GP/ ) These large termi- precentral motor cortex and other regions of
nal boutons ( arrowheads in B) can be seen to be closely the frontal lobe, ( b ) the GPe, and (c ) the pe -
apposed to the soma ( S) of a GPi neuron at the electron
microscopic level Scale bars 10 nm (A) and 4 |im (B)
dunculopontine nucleus. Other less promi -
nent afferents arise from the midbrain raphe
-
nuclei and the CM Pf complex of the thala -
mus ( Fig. 19.36 ) .
nucleus, caudal to that of both pallidal seg - Autoradiographic studies in the monkey
ments, is said to mature before either the reveal that the precentral motor cortex pro-
globus pallidus or the substantia nigra . jects somatotopically upon a restricted lateral
Cells of the subthalamic nucleus are spin - part of the subthalamic nucleus (3, 141 ). In
dle-shaped , pyramidal , or round with this projection, fibers from the face area ter -
branching processes, but form a single popu - minate laterally within the nucleus, while
lation of neurons (377). Fusiform cells are fibers from the leg area end in a more medial
seen near the margins of the nucleus, ori - region . Less substantial projections from the
ented parallel to capsular fibers. All cells con - premotor and prefrontal cortex end in more
tribute to an extremely rich neuropil, and medial parts of the subthalamic nucleus ( 168,
there are mediolateral differences in cell size 212, 213, 339 ). Thus, as is the case for the
and concentrations (99, 207). The principal el - striatum, the topographically organized corti -
ements of the subthalamic nucleus are long - cosubthalamic projection imposes upon the
axoned projection neurons whose sparsely subthalamic nucleus a specific functional sub-
spined dendrites extend for more than 750 division . Indeed , this nucleus can be divided
pm ( 302 ). In some ways, they resemble nigral into a large dorsolateral sector corresponding
and pallidal neurons except that their den - to the sensorimotor territory and a smaller
drites are much thinner ( 106, 294, 302 ). Each ventromedial sector corresponding to the as-
neuron of the subthalamic nucleus gives rise sociative territory ( Fig. 19.42). Cells in the
to six or seven stem dendrites that branch dorsolateral sector of the subthalamic nucleus
1 .
' v '
"f
•* .
*
V
Figure 19.41 . A , B Darkfield photomicrographs showing the large number of retrogradely labeled cells observed In
the dorsolateral (sensorimotor) sector subthalamic nucleus (SFN) after WGA -HRP injections in the left putamen ( A)
compared to a much smaller number of labeled cells in the ventromedial (associative) portion of the nucleus after in-
jection in the right caudate nucleus (B) in the squirrel monkey C D Examples of PHA -L injection site in the core of the
subthalamic nucleus (C) and of the type of anterograde fiber labeling it has produced In the internal (GPi ) and ex -
ternal (GPe) pallidal segments (D) E F Examples of immunohistochemical staining for GABA (E) and for glutamate (F)
in the subthalamic nucleus Note that cell of the subthalamic nucleus are closely surrounded by numerous GABA-im-
munoreactive terminals but do not themselves display GABA immunoreactivity (E) By contrast, cells of the subthala -
.
mic nucleus are strongly immunoreactive for glutamate (F). 1C internal capsule: IML internal medullary lamina: Zl .
zona incerta Scale bars 500 |im (A-C) 50 (im (D). and 30 run (E. F)
PUT / GP
Figure 19.42. Major organizational features of the subthalamic nucleus in primates as revealed after study of the ef -
ferent projections of this nucleus with retrograde double-labeling methods The relative proportion (%) occupied by
each major sector of the subthalamic nucleus, including the area of overlap between the sensorimotor and associa-
tive territories, is indicated. The medial tip of the nucleus is believed to represent the limbic territory CD, caudate nu-
. . .
cleus; GP. globus pallidus. PUT putamen. SN substantia nigra; VP ventral pallidum
change their discharge rate during skeletal ber of subcortical afferents to the subthalamic
movements and in response to somatosen- nucleus ( 44, 45, 47, 79, 226, 260). Cells in the
sory stimulation (70, 114), whereas those in GPe are arranged in arrays parallel to the lat -
the ventromedial sector are activated princi- eral medullary lamina and in monkeys have a
pally during visuo-oculomotor tasks ( 237). rostrocaudal organization in which fibers
Thus, the dorsolateral sector (sensorimotor from (a ) the rostral division of the GPe ( i.e.,
territory ) of the subthalamic nucleus appears the part rostral to the medial medullary lam -
more specifically involved in the control of ina ) project to the medial two-thirds of the
skeletomotor behavior, whereas the ventro- subthalamic nucleus, and ( b) the central divi-
medial sector (associative territory ) is more sion of the GPe ( i.e., the part lateral to the me-
concerned with oculomotor and associative dial medullary lamina ) project to the lateral
aspects of motor behavior ( 237). The medial third of the nucleus ( 44, 45, 47). These fibers
tip of the nucleus, which receives projections traverse the GPi and the peduncular part of
from limbic cortices and ventral (subcommis- the internal capsule en route to the subthala -
sural ) pallidum (125), could represent the mic nucleus. Retrograde transport studies
limbic territory of this structure. using HRP in the cat suggest a mediolateral
Electron microscopic studies indicate that topographic relationship between the sub-
cortical influences upon subthalamic nucleus thalamic nucleus and the GPe ( 226 ).
neurons are mediated by thin myelinated and The pedunculopontine nucleus ( PPN ),
unmyelinated axons that terminate in small which receives inputs from the cerebral cor -
round boutons on spines and small dendrites tex, the internal pallidal segment, and the
( 314 ). Attempts to determine the lamina of SNr, projects directly to the subthalamic nu -
origin of corticosubthalamic projections in cleus ( Fig. 19.36 A ) ( 44, 45, 219, 252, 264, 311) .
the cat and monkey by retrograde transport This projection is rather massive in monkeys
of HRP have been inconclusive ( 226, 311 ), but and involves the entire subthalamic nucleus
the corticosubthalamic projection appears to ( 219 ). The presence of numerous cholinergic
be composed mainly of collaterals of fibers fibers in the human subthalamic nucleus
destined to other loci. ( 240 ) indicates that cholinergic neurons of the
The GPe is the source of the largest num- PPN may participate in this projection .
The subthalamic nucleus also receives a pear to exert a glutamate-mediated excita -

dense serotoninergic innervation in monkeys. tory effect upon neurons of the subthalamic
Numerous serotonin-immunoreactive fibers nucleus ( 253).
and axon terminals occur throughout the en-
tire subthalamic nucleus in primates ( 218). EFFERENT PROJECTIONS
These fibers most likely belong to neurons of
the midbrain dorsal raphe nucleus. In con- Efferent fibers from the subthalamic nu -
trast , the subthalamic nucleus in monkeys is cleus traverse the internal capsule, enter cau -
only poorly innervated by catecholaminergic dal parts of the GPi, and radiate into all parts
neurons ( 220 ). of the globus pallidus. This massive projec-
A relatively small , but definite, projection tion is composed of fibers that are arranged
from the centromedian / parafascicular nu - in arrays parallel to the medullary laminae of
clear complex (CM - Pf ) has been established the pallidum ( Fig. 19.41 C, D ) ( 44, 45, 258,
in the monkey, cat , and rat (92, 317, 319, 331 ). Retrograde transport studies using 11 RP
320 ) . These thalamosubthalamic fibers ap- indicate the topographic organization of this
O STR
o
Distal dendritic Proximal Distal dendritic

domain somatodendritic domain
domain
Figure 19.43. Location of terminal boutons deriving from various sources and apposed to different regions of an in-
ternal pallidal (GPi) neuron that can be regarded as a typical output element of the basal ganglia The inputs from
the striatum ( STR ), the external pallidum (GPe). and the subthalamic nucleus (STN) are illustrated in white, black , and
hatched black , respectively The net effects of each of these inputs upon the output neuron are indicated by plus
(glutamate-mediated excitation) and minus (GABA-mediated inhibition) signs. The drawing emphasizes the complex
interplay between the opposite actions of STN and STR inputs on the same basal ganglia output neuron. It also indi-
cates the crucial position occupied by the GPe-GPi proiection, which could modulate or even shunt the effects of
other inputs to the GPi neuron. Some important connections between various basal ganglia components, such as
the massive and reciprocal relation between STN and GPe. are deliberately omitted from the diagram to keep it
readable
projection ( 44, 45). Cells in medial and caudal thalamostriatal axons are scattered over wide
parts of the subthalamic nucleus project areas of both the caudate nucleus and the
mainly to the GPi, while cells in the central putamen . These fibers are long, varicose, and
third of the nucleus project to the GPe. Few poorly branched . In rodents, subthalamostri -
cells in the lateral third of the subthalamic atal fibers appear to target specifically the so-
nucleus project to any part of the globus pal- matostatinergic cells of the striatum . This glu -
lidus. The observation that subthalamic affer- tamatergic input may play a role in the
ent and efferent fibers terminate and arise in regulation of the activity of striatal neurons,
different parts of the nucleus suggest that this in conjunction with the more massive cortical
relatively small structure is not homogeneous and thalamic excitatory afferents.
and that reciprocal circuits between the GPe In humans, relatively discrete lesions in
and the subthalamic nucleus probably in - the subthalamic nucleus, usually hemor-
volve interneurons. rhagic, give rise to violent, forceful, and per-
Subthalamic nucleus neurons also project sistent choroid movements, referred to as
fibers to the SNr ( 73, 137, 187, 258, 331, 369 ). hemiballismus. These unusually violent invol -
A fluorescent retrograde double-labeling untary movements occur contralateral to the
study in the rat suggests that single subthala - lesion and involve primarily axial and proxi-
mic nucleus neurons project fibers to both the mal musculature of the upper and lower ex -
globus pallidus and the substantia nigra tremities, although they may involve the fa -
(356). In monkeys, however, subthalamic pro- cial and cervical musculature as well (65, 176,
jections to the pallidum and the substantia 232, 249, 365, 368).
nigra appear to originate from distinct cell
populations in the subthalamic nucleus (285, Zona Incerta
286 ). Ultrastructural studies in rats reveal
that the subthalamic nucleus terminals in the The zona incerta is a strip of gray matter
substantia nigra form asymmetric synapses situated between the thalamic and lenticular
mainly with dendritic shafts and , to a lesser fasciculi ( Figs. 16.6, and 19.34-19.36). It is
extent, with the soma of SNr neurons. Synap- composed of diffuse cell groups that laterally
tic boutons of subthalamic origin contain are continuous with the thalamic reticular
small pleomorphic vesicles and display gluta - nucleus. Neurons of the zona incerta can be
mate immunoreactivity (52, 203, 312 ). Be- distinguished from those of the reticular thal -
cause the subthalamic nucleus projects to amic nucleus by the fact that they display im -
both the globus pallidus and the SNr, it is be- munoreactivity for the calcium-binding pro-
lieved to modulate the activities of neurons tein calbindin D-28k ( 250). Neurons of the
which collectively constitute the output sys- reticular thalamic nucleus are immunoreac -
tem of the entire basal ganglia . Electrophysio- tive for the calcium-binding protein parval -
logic studies in the rat have suggested that bumin but not for calbindin . The zona incerta
the efferent projections of the subthalamic receives corticofugal fibers from the precen -
nucleus control the initiation of movement by tral cortex.
setting the physiologic conditions ( i.e., mem-
brane potential or modulatory effects on Prerubral Field (Forel ’ s Field FI )
synaptic transmission ) of pallidal and nigral
neurons to the appropriate level prior to the Forel's field H ( prerubral field ) contains pal -
arrival of striatal signals ( 201, 384, 385). lidofugal fibers and scattered cells that consti-
The subthalamic nucleus also gives rise to tute the nucleus of the prerubral field ( nu -
efferents that arborize within the striatum . cleus campi Foreli ). The nuclei of the
The subthalamostriatal projection is relatively prerubral field ( Figs. 16.6 and 16.10), together
scarce by comparison with the subthalamo- with similar cells scattered along pallidofugal
pallidal and subthalamonigral projections pathways, are collectively referred to as the
( 203, 331 ). In monkeys, neurons of the sub- subthalamic reticular nucleus.
thalamic nucleus that project to the caudate The lenticular fasciculus, ansa lenticularis,
nucleus and the putamen lie respectively and thalamic fasciculus constitute the largest
within the associative and sensorimotor terri- and best -defined fibers of passage in the sub-
tories of the subthalamic nucleus ( Fig. 19.42). thalamic region. Scattered along and between
Anterograde tract - tracing studies with the the fibers of the ansa lenticularis are strands
plant lectin Phaseolus vulgaris ( PHA - L ) reveal of cells which collectively constitute the so-
that, despite their relatively low density, sub- called nucleus of the ansa lenticularis ( 310).
VENTRAL STRIATOPALLIDAL COMPLEX inata. The results of histochemical and im-

munohistochemical studies in the rat clearly
Ventral Striatum demonstrate that the globus pallidus extends
in a rostral and ventral direction toward the
During the last few years, it became well - surface of the brain in the region of the olfac-
established that both the striatum and pal -
lidum extend to the ventral surface of the tory tubercle (89, 342). Thus, the ventral ex -
tension of the striatum ( ventral striatum ) is
brain in the region of the olfactory tubercle or
the anterior perforated substance in primates accompanied by a ventral extension of the
(10, 11 ). Taking into account the fact that both pallidum ( ventral pallidum ), and the topo-
graphic relationship between the striatum
the nucleus accumbens and the olfactory tu - and the pallidum at dorsal levels is main -
bercle have striking embryologic, cytologic,
tained throughout the ventral extension of
histochemical, and hodologic features in
the striatopallidal complex in the olfactory tu -
common with the striatum , Lennart 1 leimer
bercle and the substantia innominata ( 158).
and colleagues proposed that the two struc-
tures be referred to as the ventral striatum
Although the concept of a striatopallidal
(10, II , 132, 158, 159) . Because of a similar
complex was formulated following observa -
tions and experiments on the rat brain , the
pattern of extrinsic connections, the ventro-
ventral striatum and ventral pallidum appear
medial portion of the striatum proper is
to exist in all mammals, including human
also included in the concept of the ventral
and nonhuman primates ( 11, 132).
striatum .
Ventral Pallidum Connections

The ventral pallidum was originally de- There is a remarkable parallel between the
fined on the basis of its cytologic and ultra - neuronal connections of the ventral stri-
structural features, and delimited by map- atopallidal complex and those of the striatum
ping the terminal fields of its afferents from and pallidum ( Fig. 19.44 ). For instance, inputs
the two major components of the ventral from the cerebral cortex, thalamus, and mid -
—
striatum the nucleus accumbens and the ol -
factory tubercle ( 158, 159). The ventral pal -
brain converge on the ventral striatum, which
is thus the major receptive component of the
lidum occupies a rather extensive area be- ventral striatopallidal complex. The ventral
neath the anterior commissure, which is striatum largely corresponds to the limbic
generally referred to as the substantia innom - striatal territory defined earlier .
SENSORY
MOTOR
CINGULATE
PREFRONTAL
ALLO-
CORTEX
Figure 19.44. Sagittal view ot the circuitry ot the ventral striatopallidal complex which parallels that of the dorsal stri -
,
.
atopallidal system (see text for further details) GP globus pallidus. MD. mediodorsal thalamic nucleus; PPN . pedun-
.
culopontine nucleus. STR striatum. VA and VL ventral anterior and ventral lateral thalamic nuclei; VP. ventral pal-
lidum. VS, ventral striatum
Cortical projection to the ventral striatum, pallidum are known to reach the so-called
that is, the olfactory tubercle and the nucleus mesencephalic locomotor region ( MLR ) lo-
accumbens, are complementary to those ter- cated in the pedunculopontine area (111, 112,
minating in the striatum proper. They arise 251 ). This projection supports the hypothesis
mostly from the prefrontal, insular, primary that limbic structures, such as the hippocam-
olfactory, perirhinal, entorhinal, subicular, pus, can influence somatomotor activities by
and hippocampal cortices (11 ). Hence, the in - way of the nucleus accumbens and its effer-
puts that are channeled through the ventral ent projections to the ventral pallidal area
striatum come not only from the hippocam- ( 376 ).
pus and olfactory cortex, but also from other
limbic cortices and the temporal association Chemical Anatomy
cortex. These projections are thus part of a
more global corticostriatal system that in- The concept of the ventral striatopallidal
cludes the entire cortical mantle (158). As complex has received strong support from
seen earlier, the olfactory tubercle and the nu - studies of neurotransmitter localization
cleus accumbens also receive projections within the basal forebrain . These investiga -
from the basolateral amygdaloid nuclei. tions reveal that the ventral striatum and ven -
Thalamic projections to the ventral stria- tral pallidum are distinct among basal fore-
tum arise principally from the paraventricu- brain structures in their high content of
lar and medial parafascicular nuclei and from neurochemicals. For example, the ventral
various midline nuclei (178). The major mid - striatum displays among the highest levels of
brain afferent to the ventral striatum origi- acetylcholinesterase and dopamine of the en -
nates from the dopaminergic neurons of the tire forebrain (89). Additionally, high levels
ventral tegmental area. A smaller contribu - of the enzyme choline acetyl transferase
tion from neurons of the medial substantia (ChAT ), glutamic acid decarboxylase (GAD ),
nigra , the retrorubral area , and the dorsal the neuropeptide cholecystokinin (CCK ), and
raphe nucleus has also been reported . neurotensin occur in the ventral striatum
In turn, the ventral striatum projects mas- (273). Neurotensin and CCK are largely re-
sively to the ventral pallidum, substantia lated to the ascending neuronal systems in
nigra , ventral tegmental area, and mesopon- the ventral tegmental area .
tine tegmentum. The efferent projections of The ventral pallidum is characterized by
the ventral striatum, particularly those of the high iron content, and the distribution of fer-
nucleus accumbens, are said to largely avoid ric iron in the basal forebrain of rats provides
the GPi, except its medial tip, and to termi- evidence that the globus pallidus indeed ex -
nate in a region of the substantia nigra-ven- tends rostroventrally beneath the anterior
tral tegmental area complex considerably commissure and into the olfactory tubercle
larger than that from which it receives nigro- ( 342 ). The presence of dense plexuses of
striatal fibers ( 261 ). This suggests that the GAD, substance P, and enkephalin -immu -
nigro-striato-nigral loop associated with the noreactive fibers is also highly characteristic
ventral striatum may not be organized in a of the ventral pallidum (133, 342 ). It is be-
mode of point - to- point reciprocity . lieved that these immunoreactive fibers origi-
As noted earlier, the ventral pallidum re- nate from the adjoining ventral striatum
ceives a massive projection from the ventral (133). Furthermore, there is both pharmaco-
striatum. Like the GPi , the ventral pallidum logic and electrophysiologic evidence sup-
projects to the thalamus ( 381 ). Its major ter- porting the GABAergic nature of projections
mination site, however, is not the ventral tier from the ventral striatum to the ventral pal-
nuclei but the mediodorsal nucleus, which in lidum and substantia nigra .
turn projects to the prefrontal cortex and
other limbic cortical areas known to send in - Possible Roles
puts to the ventral striatum (360). Further-
more, there is evidence for descending pro- The corticosubcortical loop through the
jections from the ventral pallidum, similar to ventral striatopallidal complex and the
the prominent pallidotegmental system aris- mediodorsal thalamus closely parallels
ing from the GPi and terminating in the pe- the more classic loops through the main dor -
dunculopontine nucleus ( Fig. 19.44 ) ( 251 ). In sal part of the basal ganglia and ventral tier
rats, descending projections from the ventral -
thalamic nuclei. This input to the ventral stri
atopallidal system is largely related to the ol - fields in the monocular segment of the vi-
factory and limbic systems, while the rest of sual field .
the striatopallidal system is more closely The corticoclaustral projection arises from
linked to the sensorimotor and association pyramidal cells in cortical layer VI , and fibers
cortices (11, 158). The ventral striatopallidal projected by the claustrum terminate most
system is believed to exist in parallel with the densely in layer IV of the cortex ( 270, 291,
dorsal striatopallidal system for the planning 326, 327). Cells of layer VI of the visual cortex
and initiation of movements. More specifi - projecting to the claustrum are distinct from
cally, the dorsal striatopallidal system is those projecting to the lateral geniculate nu -
thought to play a prominent role in initiating cleus. Much like the reticular nucleus of the
motor behavior that stems from cognitive ac - thalamus, the claustrum is composed of dis-
tivities, while the ventral striatopallidal sys- crete somesthetic, visual, and auditory zones.
tem is involved in initiating movements in re- The claustrum also receives projections
sponse to stimuli that are motivationally and from the lateral hypothalamus, the centro-
emotionally significant (158). median thalamic nucleus, and the locus
coeruleus ( 383).
CLAUSTRUM
The claustrum is a thin strip of gray matter FUNCTIONAL CONSIDERATIONS
that lies in the white matter of the hemi- Disinhibition in Basal Ganglia Functions
sphere between the lentiform nucleus and the
insular cortex . It is separated from these The basal ganglia and related nuclei exert
structures by the external capsule medially their influences on motor activities by way of
and the extreme capsule laterally ( Figs. 2.13, thalamic neurons that project on regions of
19.1, and 19.2 ). Although situated close to the the frontal cortex that influence motor func-
striatum, its principal connections are with tion . Motor cortical neurons, whose activities
the cerebral cortex and this structure bears are modulated by thalamic neurons, project
striking resemblance with the thalamus. Two fibers to, and exert motor control, at all levels
distinct parts of the claustrum are recognized: of the neuraxis, mainly contralaterally . Nei-
( a ) an insular part composed of large cells un- ther the basal ganglia nor anatomically re-
derlying the insular cortex, and ( b ) a tempo- lated brainstem nuclei project directly to
ral part located between the putamen and the spinal levels.
temporal lobe (33, 256 ). The striatum, pallidum , subthalamic nu -
The cerebral cortex projects in a gross cleus, substantia nigra , and pedunculopon-
topographic fashion upon the claustrum (84, tine nucleus are interrelated with each other
85, 256 ) and may be the site of convergence by an orderly linkage and with specific parts
of polymodal afferents from the sensory cor - of the neuraxis that can modulate somatic
tex . Observations based upon the retrograde motor activities. The striatum , representing
transport of HRP indicate that cells in the the receptive component of the basal ganglia ,
claustrum project to widespread regions of receives inputs from broad regions of the
the cerebral cortex ( 265, 308). These observa - cerebral cortex, the intralaminar thalamic nu -
tions suggest a reciprocal relationship be- clei, the substantia nigra , and the midbrain
tween the claustrum and sensory areas of raphe nuclei, mediated by a variety of neuro-
the cortex. Studies indicate that projections transmitters. Striatal output originates from
from the striate and peristriate cortex end in different populations of spiny neurons that
restricted dorsolateral regions of the claus- project selectively to the GPe, GPi , and SNr .
trum with evidence of a retinotopic organi - GABA is the principal neurotransmitter in
zation ( 179, 327, 383). Comparison of the re- striatopallidal and striatonigral fiber systems,
ceptive field properties of claustral neurons but fibers in both projections contain en-
with those of visual cortical neurons indi- kephalin or substance P.
cates that most claustral neurons respond The output systems of the basal ganglia
best to appropriately oriented bars of light, arise from morphologically similar cells in
have little spontaneous activity and respond the GPi and the SNr. Thalamic projections of
poorly to stationary light stimuli ( 326, 327). the GPi and the SNr are distinctive without
Claustral neurons respond equally well to overlap. Nuclear subdivisions of the thala-
stimulation of either eye, and those domi- mus receiving these outputs do not exert
nated by the contralateral eye have receptive their major effects on the primary motor cor-
tex . The output of the GPi appears to project striking contrast in activity between the two
to the premotor and supplementary motor constituents of this double inhibitory chain .
areas. Most physiologic data suggest that pal- When animals are at rest, most striatal neu -
lidothalamic and nigrothalamic projections rons (90% ) are mute, while SNr and GPi neu -
exert primarily inhibitory effects on thalamic rons emit a regular and sustained flow of im-
neurons. The inhibitory influences of neurons pulses up to 100 spikes per second . Increased
in the GPi and SNr projecting to the thalamus firing of striatal cells inhibits GPi and SNr
may result in disinhibition of thalamic neu- neurons and produces disinhibition in thala -
rons that act on the cortical neurons. mic, collicular, and tegmental neurons. For
Disinhibition has been proposed as the example, pharmacologically induced striatal
basic mechanism in the expression of striatal activity readily produces a phasic silencing of
functions ( Fig. 19.45) (56). Medium spiny the tonically active nigral neurons, accompa -
neurons, which are the main striatal efferents, nied by a robust firing in the superior collicu-
are GABAergic and inhibit the nigro- and lus and ventral tier thalamic nuclei ( Fig.
pallidofugal neurons, which are themselves 19.45). This disinhibitory process does not, of
GABAergic and inhibitory. An important itself , excite, but merely releases a tonic hy-
clue to the understanding of this system is the perpolarization and allows convergent excita-
STRIATUM
Q
THAL
w - GABA
SCO A SNr
o >- GABA - GABA
o STRIATUM
OTHAL
V
SCO
o>
11. *
Figure 19.45 . Disinhibition mechanism involved in the functional organization of fhe strlatonigrofuga! pathway to the
ventral tier thalamic nuclei (THAL) and the superior colliculus ( SCO). These circuits are composed of two serial
GABAergic inhibitory links ( inset ) Frequency histograms In the main diagram illustrate the sequence of electrophysio-
logic events underlying the disinhibitory influence of the striatum. A striatal spike discharge, evoked by local applica-
tion of glutamate, induces a silencing of the tonically active nigral ( SNr ) neurons. Released from the potent nigral inhi-
bition. collicular and thalamic cells discharge vigorously in response to various incoming inputs and exert a strong
excitatory effect upon tectospinal and cortical motor neurons.
tory inputs to control cell firing. During ni- ( bradykinesia ). Hypokinetic disorders are
gral silencing produced by intranigral appli- usually accompanied by muscular rigidity
cation of GABA , a procedure that mimics the and tremor at rest . By contrast, hyperkinetic
consequence of a striatal discharge, the reac- disorders are characterized by excessive
tivity of thalamocortical and colliculospinal motor activity in the form of involuntary
neurons to their cerebellar and sensory inputs movements (dyskinesia ) and varying degrees
is considerably increased . Thus, the arousing of hypotonia. Types of dyskinesia occurring
message that the striatum sends to the motor in association with basal ganglia diseases in-
system must be regarded as a gating signal. clude tremor , athetosis , chorea , and ballism ( or
By using a disinhibitory mechanism instead hemiballismus ). These and other forms of
of a direct synaptic excitation to arouse pre- dyskinesia occur with a constellation of re-
motor networks, the striatum exerts a dual in - lated somatic, visceral, and behavioral distur-
fluence on them . When striatal cells are silent, bances resulting from progressive degenera -
which is the case for long periods of time, tive disease, genetic defects, and vascular
premotor systems are kept under an in- lesions. The metabolic disturbances associ-
hibitory constraint, shielding them from any ated with these disease processes often result
disturbing noise. In contrast, when active, in deficiencies in one or more neurotransmit -
striatal cells enable premotor circuits to work ters essential for normal function .
( 56 ) .
The substantia nigra receives inputs from Dyskinesia
the two core structures of the basal ganglia
( i.e., striatum and pallidum ) and from all TREMOR
closely related subcortical nuclei ( i.e., the sub- Tremor, the most common form of dyski-
thalamic nucleus, the pedunculopontine nu - nesia, is a rhythmic, alternating, abnormal,
cleus, and the dorsal nucleus of the raphe). involuntary activity having a relatively regu -
Dopaminergic neurons in the SNc provide a lar frequency and amplitude. A major clinical
major feedback to the striatum and also have criterion used to describe and classify differ-
a small projection to the GPi . The output sys- ent tremors is whether the tremor occurs "at
tem of the substantia nigra arises from rest" or during voluntary movement. The
GABAergic neurons in the SNr, which pro- type of tremor commonly seen in paralysis
jects to thalamic nuclei and via collaterals to agitans ( Parkinsonism ), involves primarily
the tectum and the pedunculopontine nu- the digits, the head , and the lips, and occurs
cleus. during the absence of voluntary movement.
The subthalamic nucleus, in contrast to the During voluntary movements the tremor
substantia nigra, receives major inputs from ceases. Tremor classically associated with
only two sources, the GPe and the motor cor- cerebellar lesions becomes evident during
tex. Cortical projections to the subthalamic voluntary and associated movements, and
nucleus probably represent collaterals of cor- ceases when the patient is "at rest." Although
ticofugal fibers destined for other structures. this criterion is of importance in clinical neu -
A single type of subthalamic nucleus neuron rology, it is acknowledged that tremor "at
projects fibers to both pallidal segments, but a rest" and tremor during voluntary movement
small number of these cells project collaterals sometimes occur together in various degrees
to the SNr. The cells in the subthalamic nu - in association with diseases involving pri-
cleus contain glutamate and are regarded as marily either the basal ganglia or the cerebel -
exerting excitatory influences on their projec- lum. Tremor also is seen in association with
tion targets. weakness ( paresis), emotional excitement,
Movement disorders associated with basal and as a side effect of a variety of drugs. In
ganglia dysfunction comprise a spectrum of general, tremor is exaggerated when the pa -
abnormalities that ranges from hypokinetic dis- -
tient is anxious, self conscious, or exposed to
orders (of which Parkinson's disease is the cold . Tremor disappears during sleep and
best known example) at one extreme to the under general anesthesia .
hyperkinetic disorders exemplified by Hunting-
ton's disease and ballism at the other (69). ATHETOSIS
Hypokinetic disorders are characterized by
significant impairments in movement initia- This term (140 ) is used to designate slow,
tion (akinesia ) and reduction in the ampli- writhing, vermicular involuntary movements
tude and velocity of voluntary movement involving particularly the extremities. It may
also involve axial muscle groups and the 373). Characteristics common to these dyski -
muscles of the face and neck. The movements nesias include ( a ) variable amplitude and fre-
blend with each other to give the appearance quency, ( b) occurrence of movements in im -
of a continuous mobile spasm . Athetoid mediate and delayed sequence, (c ) variations
movements involving primarily the axial in the duration of single movements, and (d )
musculature produce severe torsion of the a highly integrated, complex activity pattern .
neck, shoulder girdle, and pelvic girdle. This While each of these types of involuntary
form of the disturbance, referred to as torsion motor activity is specialized to a degree, there
spasm or torsion dystonia , is considered as a are indications that athetosis, chorea , and bal-
variant (9, 177) of athetosis. Differences be- lism may form a spectrum of choreoid activ -
tween torsion dystonia and athetosis are ity in which athetosis and ballism represent
considered to be due largely to inherent me- extreme forms.
chanical differences between axial and ap- Although it is customary to associate in -
pendicular musculature. creased muscle tonus with most syndromes
of the basal ganglia , this is not always found .
CHOREA The initial symptom of Parkinsonism is fre-
quently a rigidity of the muscles, which grad -
Chorea is a brisk, graceful series of succes- ually increases over a period of years. The
sive involuntary movements of considerable augmentation of muscle tone is not selective,
complexity that resemble fragments of pur- as in hemiplegia, but is present to a nearly
poseful voluntary movements. These move- equal degree in antagonistic muscle groups
ments involve primarily the distal portions of ( i.e., in both flexor and extensor muscles). The
the extremities, the muscles of facial expres- rigidity in the early stages can be demon -
sion , the tongue, and the deglutitional mus- strated by passively flexing or extending the
culature. Most forms of choreoid activity are muscles of the extremities, or by attempting
associated with hypotonus. Sydenham' s chorea to rotate the hand in a circular fashion at the
occurs in childhood in association with wrist . These movements are interrupted by a
rheumatic heart disease, and most patients series of jerks, referred to as the cogwheel phe-
recover from the chorea in a relatively short nomenon . In later stages of the disease, rigid -
time. Huntington' s chorea is inherited through ity may be so severe as to completely inca -
an autosomal-dominant gene localized on pacitate the patient.
chromosome 4. The symptoms usually do not Athetosis usually is associated with vari-
begin until adult life, are progressive, and are able degrees of paresis and spasticity. It is
characterized by choreiform activity in the suggested that the slow, writhing character of
face and hands and severe behavioral distur- this dyskinesia may be due in part to the
bances with dementia . Not every family spasticity. Although muscle tone is increased
member carries the defective gene. greatly during athetoid movements and per-
sists after the completion of the movement ,
BALLISM muscle tone may thereafter gradually dimin-
ish (163). Chorea and ballism usually arc
Ballism, a violent, forceful, flinging move- associated with variable degrees of hypo-
ment, involves primarily the proximal appen - tonus ( 232 ).
dicular musculature and muscles about the
shoulder and pelvic girdles. It represents the Neural Mechanisms Involved in
most violent form of dyskinesia known . Bal- Dyskinesia
lism is almost invariably associated with dis-
crete lesions in the subthalamic nucleus or its The various types of dyskinesia and ex-
connections. In cases of unilateral lesion of cesses of muscle tone associated with dis-
the subthalamic nucleus, the dyskinesia oc- eases of the basal ganglia are regarded as
curs contralateral to the lesion and the condi- positive disturbances, since they involve an
tion is referred to as hemiballism or hemiballis- excess of neural activity and the expenditure
mus. Ballism is always associated with of energy ( 233). Such disturbances cannot
marked hypotonus. arise directly from destruction of specific
Although athetosis, chorea and ballism neural structures, but must represent the
each present distinguishing features, basic re- functional capacity of surviving intact struc-
semblances among these forms of dyskinesia tures. Accordingly, positive disturbances,
are greater than their differences ( 41, 54, 245, such as tremor, athetosis, chorea , and ballism,
are believed to be the result of release phenom- GABA. In Parkinson's disease, there is an im-
.
em This theory implies that a lesion in one balance between ACh and dopamine that fa-
structure removes the controlling and regu- vors ACh. This imbalance can be modified by
lating influences which that structure previ- elevating dopamine levels by giving L-dihy-
ously exerted upon another neural mecha- droxyphenylalanine ( L-dopa ), a precursor of
nism. This concept forms the basis for dopamine that passes the blood -brain barrier
neurosurgical attempts to alleviate dyskine- ( Fig. 1.15), or by reducing the action of ACh
sia and excesses of muscle tone without pro- with cholinergic receptor antagonists. This
ducing paresis. However, not all of the dis- rationale forms the basis for giving L-dopa in
turbances associated with diseases of the Parkinson's disease. The effectiveness of L-
basal ganglia can be regarded as positive dopa can be enhanced by the use of a periph-
phenomena . Patients with Parkinson's dis- eral decarboxylase inhibitor, which prevents
ease ( paralysis agitans ) also exhibit a mask- systemic decarboxylation of L-dopa to
like face, infrequent blinking of the eyes, a dopamine. Recently, the implantation of fetal
slow dysarthric speech, a stooped posture, a nigral cells within the denervated striatum of
slow shuffling gait, loss of associated move- Parkinsonian patients has been used as a
ments (e.g., swing of the arms while walk- source of dopamine (225). Animal experi-
ing ), slowness of movement ( bradykinesia ), ments reveal that this grafting procedure can
and general poverty of movement. These dis- restore dopaminergic functions in the stria-
turbances can be regarded as negative symp- turn and alleviate the motor deficits caused
toms. The negative symptoms of Parkinson- by dopamine loss ( Fig. 5.42). Despite claims
ism largely concern disorders of postural of improvement in some Parkinsonian pa-
fixation, equilibrium, locomotion, phonation, tients, however, the usefulness of this novel
and articulation, and are considered to be approach for the treatment of idiopathic
deficits due to destroyed structures ( 232, 234). Parkinsonism remains to be demonstrated .
In most forms of dyskinesia categorized as
"extrapyramidal," the basal ganglia suffer se- ATHETOSIS
vere pathologic alterations, but specific brain-
stem nuclei and parts of the cerebral cortex Athetosis most frequently is associated
may be affected also. with pathologic processes involving the stria-
tum and cerebral cortex, though lesions are
PARKINSONISM sometimes found in the globus pallidus and
thalamus (40). Hemiathetosis may develop
In Parkinson's disease, pathologic changes after a hemiparesis, or in association with it,
most consistently affect the substantia nigra , as a consequence of a necrotizing cerebrovas-
but significant alterations may be found also cular lesion destroying portions of the inter-
in the globus pallidus, the cerebral cortex, nal capsule and striatum. Athetoid activity
and the brainstem reticular formation (4, 25, occurs contralateral to the lesion.
74, 156). In this syndrome, the synthesis and
transmission of dopamine from cells of the CHOREA
SNc is greatly impaired . Terminals contain-
ing dopamine synapse mainly on dendrites With respect to chorea, there is relatively
and dendritic spines of spiny striatal neurons, little information available, except that con-
and their effect is mediated by a variety of ceming chronic progressive chorea, or Hunt-
specific receptors (e.g., D, and D, receptor ington's chorea . This hereditary disease, due
subtypes). Spiny striatal neurons also receive to a gene defect on chromosome 4 (129), is
extrinsic excitatory inputs from the cortex characterized by an insidious onset in adult
and thalamus ( Fig. 19.26). Intrinsic choliner- life. Pathologic changes are widespread but
gic striatal neurons form symmetric synaptic have a special predilection for the cerebral
endings on all parts of spiny striatal neurons, cortex and striatum. In brains of patients
The special importance of intrinsic choliner- dying with Huntington's chorea, it was
gic neurons concerns their modulating influ- demonstrated that striatal neurons reduced
ences on spiny striatal neurons known to pro- concentrations of the enzymes GAD, GABA,
ject to the substantia nigra . Dopamine and ChAT (27). GAD is the enzyme responsi-
tonically inhibits the release of acetylcholine ble for the biosynthesis of GABA and is local-
( ACh ) in the striatum , whereas ACh, or choli- ized mainly in inhibitory neurons that release
nomimetic drugs, enhance the release of GABA as their neurotransmitter (5, 172). In
these same patients, concentrations of tyro- nature and occur mainly in elderly hyperten -
sine hydroxylase ( TH ) and dopamine were sive individuals ( 368). The dyskinesia has a
normal in the striatum. The most consistent sudden onset, occurs contralateral to the le-
neurotransmitter disturbance in Hunting- sion , usually involves both upper and lower
ton's chorea appears to be a loss of GABA - extremities, and displays a forceful , flinging,
containing neurons in the striatum, which repetitive pattern. Affected limbs exhibit a
causes an imbalance in striatal levels of marked hypotonus.
GABA and dopamine in favor of dopamine.
The large cholinergic striatal neurons are in- Animal Models of Basal Ganglia
volved in this imbalance because dopamine Disorders
inhibits ACh and ACh enhances the release
of GABA . It is well - known that L-dopa given SUBTHALAMIC DYSKINESIA
in large doses to patients with Parkinson's
disease may cause choreiform movements to Attempts to produce dyskinesia in experi-
mental animals by creating lesions in parts of
-
appear. L dopa also tends to exacerbate cho-
the basal ganglia have been notoriously un -
reiform activity in patients with Huntington 's
successful ( 241 , 372). The principal form of
chorea . The most effective drugs for amelio - dyskinesia, aside from cerebellar tremor,
rating choreiform dyskinesia are those which
deplete catecholamines, such as reserpine produced in an experimental animal is that
and dopamine receptor antagonists. The resulting from discrete lesions in the subthal-
presence of normal dopaminergic systems in amic nucleus. This dyskinesia closely resem-
association with reduced availability of bles that which occurs in humans with le-
sions in the same nucleus. In the monkey,
GABA and acetylcholine may be the key neu - violent choreoid and ballistic activity occurs
ropharmacologic feature of Huntington's dis-
ease (5, 27). Clinical attempts to overcome de- contralateral to localized lesions in the sub-
ficiencies of GABA and acetylcholine by thalamic nucleus that (a ) destroy approxi
mately 20% of the nucleus, and ( b ) preserve
-
administering GABA-mimetic drugs or in-
hibitors of acetylcholine hydrolysis have so the integrity of surrounding pallidofugal
far met with limited success ( 328, 329). This fiber systems (50, 369 ). This abnormal invol-
has been explained by the inability of untary activity has been called subthalamic
GABA or the GABA agonists to cross the dyskinesia and becomes apparent immedi -
blood - brain barrier in sufficient concentra - ately upon recovery from anesthesia . Sub-
tions ( 324 ) . thalamic dyskinesia in the monkey is endur -
The biochemical changes that characterize ing, associated with distinct hypotonus, and
Huntington 's chorea in humans can be mim- can be ameliorated or abolished contralater -
icked in the rat by striatal injections of kainic ally by subsequent stereotaxic lesions in the
acid , an analogue of glutamate (80, 231, 236, GPi, the ventral lateral nucleus of the thala-
324 ). After injections of kainic acid , the GAD mus, and the motor cortex. Similar subthala -
and ChAT activities were reduced , whereas mic dyskinesia has been produced in the
the activity of TH was increased . The striatal monkey by kainic acid lesions involving the
content of dopamine was unchanged . The subthalamic nucleus, but its onset usually is
neurotoxic effects of kainic acid appear re- delayed (138). A transitory form of similar
lated to the excessive stimulation of gluta - dyskinesia has been produced in the awake
mate receptors that result in degeneration primate by injections of GABA antagonists
( picrotoxin and bicuculline methiodide) into
-
(80, 147, 231, 324 ) . The long term effects of
the subthalamic region (65, 249 ). The site of
striatal kainic acid lesions and the reduction
in activities of GABAergic and cholinergic action of these antagonists remains unclear .
neurons are not as severe as those in Hunt - Original studies of subthalamic dyskinesia in
ington 's disease (382). the monkey suggested that lesions of the sub-
thalamic nucleus resulted in a removal of in -
BALLISM OR HEMIBALLISMUS hibitory influences acting on cells of the GPi .
Physiologic observations indicating that sub-
This neurologic disorder appears to be the thalamic nucleus efferents are excitatory sug -
only form of dyskinesia resulting from a dis- gest more complex neural mechanisms. There
crete, destructive lesion. Small lesions con- is general agreement that the cells of the sub-
fined to the subthalamic nucleus, or its imme- thalamic nucleus do not contain GABA but
diate connections, usually are vascular in that GABAergic terminals of pallidal projec-
tions closely surround individual cells ( Fig. some illicit drugs (cocaine, meperidine).
19.41 ). When given intravenously in concentrations
Surgical attempts to ameliorate and abol - of 2.5-3%, this neurotoxin produces a chronic
ish various forms of dyskinesia and excesses form of Parkinsonism in both humans and
of muscle tone are based on the thesis that nonhuman primates ( 216). This compound
these disturbances are the physiologic ex- was first identified as the product of a clan-
pression of release phenomena. This implies destine laboratory attempting to synthesize
that disease or pathologic alterations of cer - l - methyl-4- phenyl-4- propionoxypiperdine
tain neural structures have removed in - ( MPPP ). Individuals taking this drug pre-
hibitory influences normally acting on other sented with a classic picture of Parkinson 's
intact neural structures, and that this overac- disease. In a patient who died of a drug over-
tivity , or excessive function, is responsible for dose, destruction within the substantia nigra
the dyskinesia . Attention has focused mainly was comparable in severity with that seen in
on the globus pallidus and the ventral lateral idiopathic Parkinsonism. All patients exhibit -
nucleus of the thalamus, since these struc- ing this syndrome responded to L-dopa and
tures appear to be of greatest importance in carbidopa. MPTP is converted in the brain to
the subcortical integration of nonpyramidal the highly toxic compound MPP + , which is
motor function . In some instances, localized then taken up into nigrostriatal neurons.
lesions produced by different techniques in How MMP selectively destroys nigral dopa-
'
these structures have abolished , or signifi- minergic neurons is still uncertain, but there
cantly reduced , various forms of dyskinesia is evidence for interference with mitochondr-
( 46, 50, 59-61 , 145, 235, 254, 255, 266, 313, ial oxidation and redox reactions. Monkeys
349 ). Stereotaxic surgery in humans is often treated with MITT develop signs virtually
unpredictable, unless carefully controlled by identical to those in humans with Parkinson's
physiologic studies and sophisticated imag- disease, including akinesia , bradykinesia ,
ing techniques. flexed posture, muscular rigidity, and pos-
The cerebral cortex is acknowledged to tural tremor ( 22).
play an important role in the neural mecha - In recent years, the use of such animal
nisms of all forms of dyskinesia. Almost all models has yielded data that clarify some of
forms of abnormal involuntary movement the pathophysiologic mechanisms underly-
cease during sleep and are abolished by gen - ing hypokinetic (as well as hyperkinetic) dis-
eral anesthesia. Most forms of dyskinesia are orders. These disorders can be explained
exaggerated in situations where the patient using a functional model of the basal ganglia-
-
becomes self conscious, overly anxious, or thalamocortical "motor" circuit that incorpo-
excited . The fact that ablations of the motor rates current data from several experimental
cortex or interruption of the corticospinal fields ( Fig. 19.46) (5, 8, 69, 128, 322 ). The so-
tract at various locations abolish dyskinesia called motor circuit, like other basal ganglia-
suggests that impulses responsible for the thalamocortical circuits, is viewed as a reen-
dyskinesia probably are transmitted to seg- trant pathway through which influences
mental levels via the corticospinal tract emanating from sensorimotor areas of the
(35, 46). cortex are returned to some of the same corti -
cal areas after intermediate processing within
EXPERIMENTAL PARKINSONISM the basal ganglia and thalamus ( Fig. 19.46 )
(69, 370). Parts of the putamen constitute the
Symptoms of Parkinsonism, particularly input stage of the basal ganglia , receiving
tremor, can be produced by electrolytic le- projection from the precentral motor areas.
sions of the ventromedial portion of the mid - The GPi and the SNr are the major output nu-
brain tegmentum in monkeys ( 297, 299). clei of the basal ganglia circuitry. Between
However, the deficits observed after such le- input and output structures, two major pro-
sions are highly variable and the different —
jection systems the so-called direct and in -
neural structures involved are difficult to
identify . A more faithful model of Parkinson -
—
direct pathways have been identified , aris-
ing from separate populations of putamen
ism has became available following the dis- neurons. The inhibitory direct pathway arises
covery of the neurotoxin MPTP ( l -methyl-4- from putamen neurons that contain GABA
phenyl-4- l ,2,5,6- tetrahydropyridine). MPTP and substance P and project monosynapti-
is a meperidine-analogue that can be found in cally to the motor portion of the GPi and SNr.
" MOTOR " " ASSOCIATIVE "

CIRCUIT CIRCUIT
SMA FRONTAL
MOTOR -SENSORY CORTEX ASSOCIATION
I
PUTAMEN STRIATUM
i
CAUDATE NUCLEUS
CAUDO- CAUDAL PALLIDUM ROSTRO- ROSTRO-

VENTRAL LATERAL S. NIGRA DORSAL MEDIAL
I
VLo VLm THALAMUS VApc VAmc
J L L
Figure 19 44. Comparison of the organization of the so-called sensorimotor and associative circuits of the basal gan
glia, which can be distinguished electrophysiologically and anatomically. GP. internal pallidal segment; SMA. supple-
mentary motor area: SNr. substantia nigra pars reticulata; VAmc. ventral anterior nucleus pars magnocellular: VApc.
ventral anterior nucleus pars parricellular. VLm ventral lateral nucleus pars medians; Wo ventral lateral nucleus pars
oralis
The indirect \mthum/, on the other hand , arises direct pathways and the resulting alterations
from putamen neurons that contain GABA in the GPi / SNr are thought to account for the
and enkephalin and whose influence is con- hypo- and hyperkinetic features of basal gan -
veyed to GPi / SNr polysynaptically through a glia disorders (69 ). It appears that enhanced
sequence of connections involving the GPe conduction through the indirect pathway
and the subthalamic nucleus. This sequence leads to hypokinesia by increasing the
of connections comprises ( a ) an inhibitory GABAergic pallidothalamic inhibition . By
connection between the putamen and the contrast, reduced conduction through the di-
GPe, ( b ) an inhibitory connection between the rect pathway results in hyperkinesia by re-
GPe and the STN, and (c) an excitatory con - duction of pallidothalamic inhibition ( Fig.
nection between the STN and GPi / SNr ( Fig. 19.47).
19.47). According to the proposed functional
In the striatum, dopamine appears to have model of the motor circuit , the motor distur -
differential effects on the activity of the direct bances of Parkinson's disease are postulated
and the indirect pathway, facilitating trans- to result in large part from increased thalamic
mission via the direct pathway and decreas- inhibition due to excessive excitatory drive
ing the activity of the indirect pathway . These from the STN to the output nuclei of the basal
opposite actions of dopamine are believed to ganglia (GPi / SNr ). It may, therefore, be pre-
be mediated by different types of dopamine dicted that a lesion or inactivation of the STN
receptors, with D; receptors located on neu - in Parkinsonian subjects would improve
rons projecting to the GPe and D , receptors some of the motor impairments. This hypoth -
on neurons projecting to GPi / SNr (113). Bal- esis has been tested by selective lesioning of
ance between the activity in the direct and in - the STN with the fiber-sparing excitotoxin
CORTEX CORTEX
GLU GLU
+ +
GLU GLU
+ +
STRIATUM STRIATUM
DA © © DA
—//— + © ©
GABA GABA GABA GABA
ENK SP/DYN THALAMUS ENK SP/DYN THALAMUS
VA / VL VA / VL
GABA GABA GABA GABA i
GABA GABA I
A
GABA GLU
+
B
GABA
STN J GLU
+
Figure 19 47. Major basal ganglia circuits, particularly the indirect and direct stridtofugal pathways, and their activity
under normal conditions (A) and following lesion of the substantia nigra pars compacta (B) In normal conditions, the
balance between the effects of the direct and indirect pathways is maintained by the opposite action that
dopamine ( DA) exerts upon neurons giving rise to each of these two pathways The loss of striatal dopamine ( DA)
causes a release of the inhibition on the GABA / enkephalin striatal neurons that project to the external pallidum
( GPe) The GPe thus comes under a strong striatal inhibition and Is no longer able to exert its inhibitory action on the
subthalamic nucleus ( STN) This results in a marked increase of the excitatory action of the STN on the two output
structures of the basal ganglia, namely the internal pallidum ( GPi ) and the pars reticulata of the substantia nigra
( SNr ) In turn, the GPi/SNr augment their inhibitory constraint upon the premotor neurons of the thalamus ( VA/VL ven-
tral anterior and ventral lateral nuclei) The net effect of this cascode of events is a marked decrease of the excita-
tory influence that thalamocortical neurons exert upon cortical neurons involved in the initidtion and execution of
movements Clinically, this leads to bradykinesia or akinesia.
ibotenate in monkeys rendered Parkinsonian ( 100-130 Hz ) ofthe subthalamic nucleus ( 24 ),

after MPTP administration . Such lesions re- which is believed to produce a reversible
portedly produce an immediate and dramatic physiologic lesion of the nucleus, and after
reduction of akinesia and bradykinesia , as injection of antagonisms of excitotoxic amino
well as tremor and rigidity in the contralat- acids in the GPi ( 34 ) . These results provide a
eral limbs ( 18, 26 ). Improvements in motor direct support for the postulated positive role
functions of Parkinsonian monkeys also can of the STN and the indirect pathway in the
be obtained by high frequency stimulation pathogenesis of hypokinetic disorders.
References 5. Albin RL, Young AB, Penney IB. 8. Alexander GE, DeLong MR , Strick
The functional anatomy of basal PL. Parallel organization of func-
1 . Adinolfi AM , Pappas GD. The fine ganglia disorders. Trends Neurosci tionally segregated circuits linking
structure of the caudate nucleus of
the cat . I Comp Neurol 1968;133:
-
1989;12:366 375.
6. Alexander GE, DeLong MR . Mi-
basal ganglia and cortex . Ann Rev
-
Neurosci 1966;9:357 381.
-
Ib7 184. crostimulation of the primate neo- 9. Alexander L. The vascular supply
.
2. Afifi A Kaelber WE . Efferent con - striatum. I Physiological properties of the striopallidum . Proc Assoc
nections of the substantia nigra in of striatal microexcitable zones. J Res Nerve Ment Dis 1942;21:
the cat. F. xp Neurol 19e*S;1 : 474-482. Neurophysiol 198533: 1401 -1416. -
77 132.
3. Atsharpour S Topographical pro- 7. Alexander GE, DeLong MR. Mi - 10. Alheid GF, Heimer L. New perspec-
jections of the cerebral cortex to the crostimulation of the primate nett- tive in basal forebrain organization
subthalamic nucleus |Comp Neu - striatum II Somatotopic organiza - of special relevance for neumpsychi *
rol 1985;236:14-28. tion of striatal microexcitable a trie disorders: the striatopaliidal,

4 Agid V Parkinson 's disease: zones and their relation to neu - amygdaloid , and corticopetal com-
pathophysiology . Lancet 1991;337: ronal response properties. I Neurit- ponents of the substantia innomi -
1321-1324. physiol 198533:1417-1430. nata . Neuroscience 1988;27: 1 - 39
.
11. Alheid GF Hamer L, Switzer RC way: a correlative study based on field, 1L: Charles C. Thomas, 1958:
III Basal ganglia. In: Paxinos G, ed . neuroanatomical and neurochemi- 271-293.
The human nervous system. Ch. cal criteria in the cat and monkey. 36. Bunney BS, Aghajanian GK . The
1^. New York : Academic Press, Exp Neurol 1969;25:365-377. precise localization of nigral affer -
1490:483-582. 24. Benazzouz A , Gross CH, Feger J, ents in the rat as determined by a
12. Anden N-E, Carlsson A, Boraud T, Bioulac B. Reversal of retrograde tracing technique. Brain
Dahlstrom A, Fuxe K, I lillarp N- A, rigidity and improvement in motor Res I976;117:423 435.
Larsson K . Demonstration and performance by subthalamic high 37. Burdach KF. Vom Ban und Leben
mapping out of nigro-neostriatal frequency stimulation in MPTP- des Gehims. Leipzig: Dyksche
dopamine neurons. Life Sci 1964; treated monkeys. Eur I Neurosci Buchhandlung, 1819 1824 -
3:523- 530 1993;5:382-389. 38. Carlsson A, Falck B, I lillarp NA .

13. Anden N-E, Dahlstrom A , Fuxe K,
Larsson K, Olson L, Ungerstedt U.
25 .
Benda CE Cobb S. On the patho-
genesis of paralysis agitans
Cellular localization of brain
momximines. Acta Physiol Scand
Ascending monoamine neurons to (Parkinson's disease). Medicine 1462;56(Suppl 196 ):I 28.
the telencephalon and dien- 1942;21:95-142. 39. Carman JB, Cowan WM, Powell
cephalon. Acta Physiol Scand 26. Bergman II, Wichmann T, DeLong FI’S. The organization of cortico-
1966;67:313-326 . MR . Reversal of experimental striate connexions in the rabbit
14 Anderson ME, llorak FB. Influence Parkinsonism by lesion of the sub- Brain 1963;86:525- 562
of the globus pallidus on arm thalamic nucleus. Science I990;249: 40. Carpenter MB. Athetosis and the
movements in monkeys. III. Tim- 1436-1438. basal ganglia. Arch Neurol Psychi-
ing of movement -related informa - 27. Bird ED, Iversen LL. Huntington's atry 1950;63:875-901.
tion. ) Neurophvsiol 1985;53: chorea: Post -mortem measure- 41. Carpenter MB. The neuroanatomi-
1417- 1430. ments of glutamic acid decarboxy - cal basis of dyskinesia. In: Fields
15. Arluison M, De la Manche IS. lase, choline acetyltransferase and WS, ed . Pathogenesis and treat -
-
Iligh resolution radioautographic dopamine in the basal ganglia. ment of Parkinsonism. Ch. 2.
study of the serotonin innervation Brain 1974;97:457-472. Springfield, IL : Charles C. Thomas,
of the rat corpus striatum after in- 28. Bloom FE, Costa E, Salmoiraghi 1958:50-85 .
traventricular administration of C»C. Anesthesia and responsive- 42. Carpenter MB. Anatomical organi -
I ’llI 5-hydroxytryptamine. Neuro- ness of individual neurons of the zation of the corpus striatum and
science 1980;5:229-240. caudate nucleus of the cat to related nuclei. In: Yahr MD, ed.
16. Aronin N, DiFiglia M, Grave- acetylcholine, norepinephrine and The basal ganglia. New York:
land GA, Schwartz VVJ, Wu J- Y. dopamine administered by micro- .
Raven Press 1976:1 36.
Localization of immunoreactive electrophoresis. J Pharmacol Exp 43. Carpenter MB. Anatomy of the
enkephalins in GABA synthesizing Ther 1%5;150:244-252. corpus striatum and brain stem in-
neurons of the rat neostriatum. 29. Bobillier P, Petitjean F, Salvert D, tegrating systems. In: Brooks V , ed.
'
Brain Res 1984;300:376-380. Ligier M, Seguin S. Differential HandbiH>k of physiology. Vol. II,
17. Augood SJ, Emson PC. Pertussis projections of the nucleus raphe Sec. I. Motor control. Ch. 19.
toxin administration increases the dorsalis and nucleus raphe cen- Washington, DC: American Physi-
expression of proneurotensin and tralis as revealed by autoradiogra - ological Society, 1981:947-995.
preproenkephalin A mRNAs in rat phy. Brain Res 1975;85:205-210. 44. Carpenter MB, Batton RR III, Car -
striatum. Neuroscience 1942;47: 30. Bolam JP, Ingham CA, Smith AD. leton SC, Keller JT. Interconnec-
317-324. The section-Golgi-impregnation tions and organization of pallidal
18 Aziz TZ , Peggs D, Sambrook MA, procedure-3. Combination of and subthalamic nucleus neurons
Crossman AR. Lesion of the sub- Golgi -impregnation with enzyme .
in the monkey J Comp Neurol
thalamic nucleus for the alleviation histochemistry and electron mi- 1981;197:579-603.
of 1 - methvl -4-phenyl-l,2,3,6- tetra - croscopy to characterize acetyl- 45. Carpenter MB, Carleton SC, Keller
hydropy ridine (MITP) - induced choiinesterase-containing neurons JT, Conte P. Connections of the
Parkinsonism in the primate. Mov in the rat neostriatum Neuro- subthalamic nucleus in the mon-
Disord 1991;6:288-293 . science 1984;12:687 709. key . Brain Res 1981;224: 1 -29.
19. Azmitia EC, Gannon Pj. The pri - 31. Bouyer JJ, Park DH, Joh TH, Pickel 46. Carpenter MB, Correll JW, Hin-
mate serotonergic system: A re- VM. Chemical and structural man A . Spinal tracts mediating
view of human and animal studies analysis of the relation between subthalamic hyperkinesia. Physio-
and a report on Macaca fascicular is . cortical inputs and tyrosine hy - logical effects of partial selective
.
In: Fahn S ed. Advances in neurol - droxylase-containing terminals in cordotomies upon dyskinesia in
ogy. New York: Raven Press, rat neostriatum. Brain Res 1984; the rhesus monkey. J Neurophysiol
'
1986:407-468. 302:267-275. 1960;23:288-304.

20. Beckstead RM . Complementary 32. Bredt DS. 1twang PM, Snyder S 11 47. Carpenter MB, Fraser RAR, Shriver
mosaic distribution of thalamic Localization of nitric oxide syn- JE. The organization of pallidosub-
and nigral axons in the caudate nu- thase indicating a neural role for thalamic fibers in the monkev.
cleus of the cat : double antero- nitric oxide. Nature 1990;347: Brain Res 1968,11:522-559.
grade labeling combining autora - 768-770. 48. Carpenter MB, Peter P Nigrostri -
diography and wheat germ - MRP 33 Brockhaus H. Die Cyto-und Mve- atal and nigrothalamic fibers in the
histochemistry. Brain Res 1985;335: loarchitektonik des Cortex daus- rhesus monkey . J Comp Neurol
15 3 tS9. tralis und des Claustrum beim 1972;144:93-116 .
21 Beckstead RM, Domesick VB, menschen. J Psvchol Neurol 49. Carpenter MB, Strominger NL. Ef -
Nauta WILL Efferent connections 1940,49:249-348. ferent fibers of the subthalamic nu -
of the substantia nigra and ventral 34. Brotchie JM, Mitchell IJ, Sambrook cleus in the monkey: a comparison
tegmental area in the rat. Brain Res MA, Crossman AR. Alleviation of of the efferent projections of the
1479;175:191 - 217. parkinsonism by antagonism of subthalamic nucleus, substantia
22. Bedard PJ, Boucher R, Gomez
Mancilla B, Blanchette P. Animal
- excitatory aminoacid transmission
in the medial pallidal segment of
nigra and globus pallidus. Am |
Anal 1967;121:41-72.
models of Parkinson' s disease. In: the globus pallidus in the rat and 50. Carpenter MB, Whittier JR, Mettler
Boulton A, Baker G, Butterworth primate. Mov Disord 1991;6: FA . Analysis of choreoid hyperki-
R , eds. Animal models of neuro- 133-138. nesia in the rhesus monkey : surgi -
logical disease. Totowa, NJ: Hu- 35. Bucy PC The cortico spinal tract cal and pharmacological analysis of
mana Press, 1992:154- 173. and tremor . In: Fields WS, hyperkinesia resulting from lesions
23. Bedard P, Larochelle L, Parent A , ed . Pathogenesis and treatment in the subthalamic nucleus of Luys.
Poirier LJ. The nigrostrialal path- of Parkinsonism. Ch. II. Spring- J Comp Neurol 1950;92:293-332 .
51 Castel MN, Morino P, Frev P, Tere- 66 Dahlstrom A . Fuxe K . Evidence for 79. DeVito JL, Anderson ME, Walsh
nius L, Hoklelt T. Immunohisto- the existence of mom»amine-con- RF. A horseradish peroxidase
chemical evidence for a neu- taining neurons in the central ner - study of afferent connections of the
rotensin striatonigral pathway in vous system. I Demonstration of globus pallidus in Macaco mulatto .
the rat brain. Neuroscience monoamines in the cell bodies of Exp Brain Res 1980;38:65-73.
1 W 455.83 V 847. brain stem neurons. Acta Physiol 80. DiFIglia M. Excitotoxic injury of
52. Chang IIT, Kita II, Kitai ST. The Scand 1964;62( Suppl 232): 1-55. the neostriatum: a model for I lunt -
ultrastructural morphology of the 67. Dahlstrom A , Fuxe K . Evidence for ington' s disease . Trends Neurosci
subthalamonigral axon terminals the existence of monoamines in the 1990;13:286-289.
intracellularly labeled with horse- central nervous system. II Experi- 81 . DiFiglia M, Aronin N. Ultrastrue-
radish peroxidase . Brain Res mentally induced changes in the tural features of immunoreactive
1984 ;299: 182- 185. intraneuronal amine levels of bul- somatostatin neurons in the rat
53. Charara A , Parent A . Brainstem bospinal neuron systems. Acta caudate nucleus. | Neurosci 1982;2.
dopaminergic, cholinergic and Physiol Scand 1965;64(Suppl 1267-1274.
serotoninergic afferents to the pal- 247): 1-36. 82. DiFiglia M. Pasik P, Pasik T. A
lidum in the squirrel monkev. 68. Davies J , Dray A . Substance P in Golgi study of neuronal types in
Brain Res 1994;640:155- 170. the substantia nigra . Brain Res the neostriatum of monkeys. Brain
34 . Charcot )M. Lectures on the dis- 1976;107:623-627. Res 1976 , 114:245-256.
eases* of the nervous system. Siger - 69. DeLong MR. Primate mixlels of 83. Donoghue JP, Kitai ST . A collateral
son G, trans. Philadelphia: Henrv movement disorders of the basal pathway to the neostriatum from
<. Lea, 1879 ganglia . Trends Neurosci 1990;13: corticofugal neurons of the rat sen-
55 Chesselet MF . Robbins E. Charac- 281-285. sory-motor cortex: An intracellular
terization of striatal neurons ex- 70. DeLong MR , Crutcher MD, Geor - HRP study. J Comp Neurol
pressing high levels of glutamic gopoulos AP . Primate globus pal- 1981;201 : 1 - 13.
acid decarboxylase messenger lidus and subthalamic nucleus: 84 . Druga R Cortico-claustral connec-
RNA . Brain Res 1989;492:237-244. functional organization . | Neuro- tions. 1 Fronto-claustral connec -
56. Chevalier G, Deniau JM. Disinhibi- phvsiol 1985;53:530-543. tions. Folia Morphol ( Praha )
tion as a basic process in the ex- 71 DeLong MR , Georgopoulos AP. 1966;14:391-399.
pression of striatal functions. Motor functions of the basal gan- 85. Druga R . Cortico-claustral connec-
Trends Neurosci 1990;13:277- 280. glia . In: BriH>khart JM , Mountcastle tions. II . Connections from the
57. Cole M, Nauta WJH, Mehler WR . VB, Brooks VB, Geiger SR , eds. parietal, temporal and occipital
The ascending efferent projections Handbook of physiology . Sec. 1: cortex to the claustrum. Folia Mor -
of the substantia nigra . Trans Am The nervous system. Vol . II: Motor phol ( Praha ) 1968; 16: 142- 149
Neurol Assoc 1964 ;89:74-78. control. Part 2. Bethesda, MD: 86. Emson IX. , Arregui A , Clement -
'
58. Conrad LCA , Leonard CA, Pfaff American Physiological Society, Jones V , Sandberg BFB, Rossor M.
DW . Connections of the median 1981: 1017- 1061 Regional distribution of methio-
and dorsal raphe nuclei in the rat 72. DeLong MR , Georgopoulos AP, nine- enkephalin and substance P-
an autoradiographic and degener - Crutcher MD. Cortico-basal gan - like immunoreactivity in normal
ation study. J Comp Neurol glia relations and coding of motor human brain and in 1 luntington' s
1974;156:170-206. performance. Exp Brain Res Suppl disease. Brain Res 1980;|99;
59. Cooper IS. Neurosurgical allevia - I9B3;7 'MI 40. 147- 160.
tion of Parkinsonism. Springfield, 73. Deniau JM , Hammond C, Cheva- 87. Fahn S, Cote L) . Regional distribu -
IL: Charles C Thomas, 1936. lier G, Feger J . Evidence for tion of -y -aminobutyric acid
60. Cooper IS. Neurosurgical relief of branched subthalamic nucleus pro- (GABA ) in brain of the rhesus
intention tremor due to cerebral jections to substantia nigra, en- monkey . J Neurochem 1968; 15:
disease and multiple sclerosis. topeduncular nucleus and globus 209- 213.
Arch Phvs Med Rehabil I 960;41: pallidus. Neurosci Lett 1978 -9: . 88. Falck B. Observations on the possi-
1 -4. 117- 121 . bilities of the cellular localization
61 . Cooper IS. Bravo GJ. Ante- 74 . Denny- Brown D. The basal ganglia of monoamines by a fluorescence
rior choroidal artery occlusion, and their relation to disorders of method . Acta Physiol Scand
chemopallidectomv and chemothal- movement . London: Oxford Uni- 1962;56(Suppl 197):I - 25 .
amectomy in parkinsonism: a con- versity Press, 1962. .
89. Fallon JH. Loughlin SE Ribak CE.
secutive series of 700 operations. 75. IVsban M, Gauchy C, Kernel ML, The island of Calleja complex of
In: Fields WS, ed. Pathogenesis Besson Ml , Glowinski J . Three-di- the rat basal forebrain. III . Ilisto-
and treatment of Parkinsonism. mensional organization of the chemical evidence fora striatopall-
Ch 15. Springfield, IL : Charles C striosomal compartment and idal system. J Comp Neurol
Thomas. 1958:325- 352. patchy distribution of striatonigral 1983;218:91-120.
62. Cote P- Y, Sadikot AF, Parent A . projections in the matrix of the cat 90. Faull RLM, Carman |B. Ascending
Complementary distribution of caudate nucleus. Neuroscience projections of the substantia nigra
calbindin D- 28k and parvalbumin 1989;29:551- 566. in the rat . I Comp Neurol
in the basal forebrain and mid- 76. Descarries L, Bossier O, Berthelet 1968;132:73-92.
brain of the squirrel monkev . Eur J F. Desrosiers MH. Dopaminergic 91 . Feger J , Crossman AR. Identifica -
Neurosci 1991;3:1316- 1329. nerve endings visualized bv high tion of different subpopulations of
6.3. Cowan RL. Wilson CJ, Emson IXT , resolution autoradiography in neostriatal neurones projecting
Heizmann CW . Parvalbumin-con- adult rat neostriatum. Nature to globus pallidus and sub-
taining GABAergic interneurons in 1980;284:620-622. stantia nigra in the monkey: a ret -
the rat neostriatum. J Comp Neu- 77. De Simoni MG, Dal Toso G, Fo- rograde fluorescence doubie- label -
rol 1990;302:197-205. dritto F, Sokola A , Algeri S. Modu- ing study. Neurosci Lett 1984;49:
64 Cowan WM, Powell TIN. Striopal- lation of striatal dopamine metabo- 7-12.
lidal projection in the monkey. | lism by the activity of dorsal raphe 92. Feger J , Mouroux M . Mise en evi-
Neurol Neurosurg Psychiatry serotoninergic afferents. Brain Res dence de I'effet excitateur de ref -
1966;29:426 -439. 1987;411:81-88. erence thalamo-subthalamique
65. Crossman AR , Feger | , Hammond 78. Desjardins C, Parent A . Distribu- issue du noyau parafasciculaire
C, Jackson A, Sambrook MA . Stud- tion of somatostatin immunoreac- CR Acad Sci III 1991;313:447^452.
ies on site specificity of intracere- tivity in the forebrain of the squir- 93. Ferraro A . Contributa sperimentale
bral injection in the production ot rel monkey: basal ganglia and alio studio della substantia nigra
experimental hemiballismus. I amygdala . Neuroscience 1992;47: normale e dei suoi rapporti con la
Physiol ( London ) 1981;319: 109- 110 115- 133. corteccia cerebrale e con il corpo
striato. Arch Gen Neurol Psychia - central monoamine neurons with Fiber connections of the basil gan -
-
try 1925;6:26 117. special reference to the nigro- neo- glia . In: Cuenod M , Kreutzberg
94. Ferraro A . The connections of the striatal dopamine neuron system . GW, Bloom FE, eds. Development
pars suboculomotoria of the sub- In: Costa E, ed . Biochemistry and and chemical specificity of neu -
stantia nigra. Arch Neurol Psychia - pharmacology of the basal ganglia . rons. Amsterdam : Elsevier, 1979:
try 1928;19:177-180. New York: Raven Press, 1966: 239-283.
95. Fisher R$, Shiota C, Levine MS, 123-129. 125. Groenewegen HJ , Berendse HW.
Hull CD, Buchwald NA . Inter - 110. Gale K , Hong J -S, Guidotti A. Pres- Connections of the subthalamic
hemispheric organization of corti - ence of substance 1’ and GABA in nucleus with ventral striatopallidal
cocaudate projections in the cat: a separate striatonigral neurons. parts of the basal ganglia in the rat .
retrograde double-labeling study.
Neurosci Lett 1984;48:369-373. 111.
Brain Res 1977;36:371-375.
Garcia- Rill E. The basal ganglia
| ( omp Neurol 1990;294:607 622
-
126. Grofova I . The identification of
.
96. Flaherty AVV, Graybiel AM . Two and the locomotor regions. Brain striatal and pallidal neurons pro-
input systems for btxly representa - -
Res Rev 1986;11:47 63. jecting to substantia nigra : an ex -
tions in the primate striatal matrix : 112. -
Garcia Rill E. The pedunculopon - perimental study by means of ret -
experimental evidence in the squir - tine nucleus. Prog Neurobiol 1991; rograde axonal transport of
rel monkey . J Neurosci 1993;!3: -
36:363 389. horseradish peroxidase. Brain Res
1120-1137. 113. Gerfen CR. The neostriatal mt >saic: 1975;91 : 286-291 .
97. Flaherty AW , Graybiel AM . Out - Multiple levels of compartmental 127. Guevara Guzman R , Kendrick KM ,
put architecture of the primate organization in the basal ganglia. Emson PC . Effect of substance P on
putamen . | Neurosci 1993;13: Annu Rev Neurosci 1992,15: acetylcholine and dopamine re-
3222-3237. 285-320. lease* in the rat striatum : a micro-
98. Foix C, Hillemand J . Irrigation de
la couche optique. CR Soc Biol
114 . Georgopoulos AP, DeLong MR ,
Crutcher MD. Relations between 622: 147-154 .
.
dialysis study Brain Res 1993;
( Paris ) 1925;92:52-54. parameters of step- tracking move- 128. Guridi J , Luquin MR , Herrero MT,
99. Foix C, Nicolesco J . Les noyaux ments and single cell discharge in Obeso JA. The subthalamic nu -
gris centraux et la region mesen -
-
cephalo sous-optique. Paris: Mas-
the globus pallidus and subthala -
mic nucleus of the behaving mon-
cleus: a possible target for stereo
taxic surgery in Parkinson's dis-
-
son , 1925. key. J Neurosci 1983;3:1586-1598. ease. Mov Disord 1993;8:421-429.
-
100. Fonnum F, Storm Mathisen J. High 115. Giguere M, Marchand R , Poirier 129. Gusella JF, Waxier NS, Conneally
affinity uptake of glutamate in ter - LJ . The nigrostriatal nervous path - -
P M , et al . A polymorphic DNA
minals of corticostriate axons. Na - way in the brain of the cat : An au - marker genetically linked to Hunt -
ture 1977;266:377-378. toradiographic study In: Hassler ington's disease. Nature 1983;
101 . Fox CA, Andrade AN , Hillman RG, Christ JF, eds. Advances in 306:234-238.
DE, Schvvyn RC. The spiny neu - neurology. New York: Raven 130. Guyenet PG , Crane JK . Non -
rons in the primate striatum : a Press, 1984:77-83. dopaminergic nigrostriatal path -
Golgi and electron microscopic 116. Gimenez - Amava JM, Graybiel AM . way. Brain Res 1981213:291-305.
study. J Himforsch 1971;13: Compartmental origins of the stri - 131. Haber SN , Elde R . Correlation be-
181-201 atopallidal projection in the pri - tween met -enkephalin and sub-
102. Fox CA, Andrade AN , Lu Qui I , mate. Neuroscience 1990;34:111- stance P immunoreactivity in pri -
Rafols JA . The primate globus pal - 126. mate globus pallidus. Neuro -
lid us: A Golgi and electron micro- 117. Goldman PS, Nauta WJH. Colum - -
science 1981;6:1291 1297.
scopic study , j Himforsch 1974;15: -
nar distribution of cortico cortical -
132. Haber SN , Lynd Balta E, Mitchell
-
75 93. fibres in the frontal association, SJ . The organization of the de-
103. Fox CA , Andrade AN , Schwvn RC, limbic and motor cortex of the de - scending ventral pallidal projec-
Rafols JA . The aspinv neurons and veloping Rhesus monkey. Brain tions in the monkey J Comp Neu -
the glia in the primate striatum: a -
Res 1977;122:393 413. rol 1993,329:111-128
Golgi and electron microscopic
study . J Himforsch 1971 / 1972:
-
118. Goldman Rakic PS. Cytoarchitec- 133. Haber SN , Nauta WJH . Ramifica -
tonic heterogeneity of the primate tions of the globus pallidus in
13:341 -362. neostriatum: subdivision into is - the rat as indicated bv patterns of
104. Fox CA, Rafols JA. The radial land and matrix cellular compart - immunohistochemistry Neuro-
fibers in the globus pallidus. J ments. | Comp Neurol 1982:205: science 1983;9:245-260.
Comp Neurol 1975;159:177 200. - 398-413. 134. I laber SN, Watson SJ . The compar-
105. Fox CA, Rafols JA, Cowan WM . 119. Goldman - Rakic PS. Mix!ular orga - ative distribution of enkephalin,
Computer measurements of axis nization of prefrontal cortex . dynorphin and substance P in the
cylinder diameters of radial fibers Trends Neurosci 1984;7:419-424 . human globus pallidus and basal
and "comb" bundle fibers. J Comp 120. Gorry JD. Studies on the compara - forebrain . Neuroscience 1985;14:
Neurol 1975;159:201-224. tive anatomy of the ganglion 1011 - 1024.
106. Francois C, Percheron G, Yelnik J . basale of Mevnert. Acta Anat 135. I lame! E, Beaudet A . Opioid recep-
A Golgi analysis of the primate -
( Basel ) 1963;55:51 104. tors in rat neostriatum: Radioauto-
globus pallidus. I . Inconstant 121 . Gottesfeld A, Massari VJ , Muth graphic distribution at the electron
processes of large neurons, other EA, Jacobowitz DM . Stria microscopic level . Brain Res 1987;
neuronal types, and afferent medullaris: a possible pathway 401:239-257.
axons. J Comp Neurol 1984;227: containing GABAergic afferents to 136. Hamilton WJ , Mossman HW.
182-189 the lateral habenula . Brain Res Human embryology . Baltimore:
107. Freund TF, Powell JF, Smith AD. 1977;130:184-189. Williams & Wilkins, 1972.
Tyrosine hvdroxylase-immunore- 122. Graybiel AM . Neurotransmitters 137. Hammond C, Deniau JM , Ri / k
active boutons in synaptic contacts and neuromodulators in the basil A, Feger J . Flectrophysiological
with identified striatonigral neu - ganglia . Trends Neurosci 1990;13: demonstration of an excitatory
rons, with particular reference to -
244 254. subthalamonigral pathway in the
dendritic spines. Neuroscience 123. Graybiel AM , Ragsdale CW Jr. rat . Brain Res 1978;151 :235-244 .
1984;13:1189-1216. Histochemically distinct compart - 1.38. Hammond C, Feger J , Bioulac B,
108. Frotscher M , Rinne V , Hassler R , ments in the striatum of human, Souteyrand JP. Experimental
Wagner A . Termination ot cortical monkey and cat demonstrated by hemiballism in the monkey pro -
afferents on identified neurons in acetylcholinesterase staining. Proc duced bv unilateral kainic acid le -
the caudate nucleus of the cat. Exp Natl Acad Sci USA 1978;75: sion in corpus Luysii . Brain Res
-
Brain Res 1981 ;41:329 337.
109. Fuxe K , Anden NE. Studies on the
5723-5726.
124. Graybiel AM, Ragsdale CW Jr.
1
^ :171 : 577-580.
139. Hammond C, Yelnik J . Intracellu -
lar labelling of rat subthalamic 153. Hazrati L -N, Parent A . Projection and monkev. Neurosci Lett 1976;2:
neurones with horseradish peroxi-
dase: Computer analysis of den -
from the deep cerebellar nuclei to
the peduncuiopontine nucleus in
-
253 199 .
167. Hornvkiewicz O. Metabolism of
drite and characterization of axon the squirrel monkey Brain Res brain dopamine in human parkin -
*
arborization. Neuroscience 1983#: 1992;585:267-271. sonism: neurochemii ai and clinical
781-790. .
154 Hazrati L -N Parent A. Striatal and aspects. In: Costa E. ed Biochem-
140. Hammond VVA . A treatise on dis- subthalamic afferents to the pri- istry and pharmacology ol the
eases of the nervous system. New mate pallidum: interactions be- basal ganglia. New York: Raven
York: D. Appleton, 1871:653-662. tween two opposite chemospecific .
Press 1966:171 -185.
141 Hartmann- von Monakow K, Akert neuronal systems. In: Arbuthnott 168. Huerta MF. Krubitzer l A. Kaas III
K, Kunzle H. Projections of the GW, Emson PC, eds. Chemical sig- Frontal eve field a* defined by in-
precentral motor cortex and other nalling in the basal ganglia. Vol. 6. tracortical microstimulation in
cortical areas of the frontal lobe to Prog Brain Res 1993;99:89-104. squirrel monkeys, owl monkeys,
the subthalamic nucleus in the . .
155 Hazrati L - \ Parent A Mitchell S, and macaque monkeys. I Subcorti-
.
monkey Exp Brain Kes 1978;33: Haber SN. Evidence for intercon- cal connections | Comp Neurol
395-403. nections between the two seg- 1986;253:415-439
142. Hartmann- von Monakow K, Akert ments of the globus pallidus in pri- 169. Ilinskv 1 A , Kultas- llinskv K Sagit -
K, Kunzle H. Projections of the mates: a PHA - L anterograde tal cytoarchitectonic maps of the
precentral and premotor cortex to tracing study Brain Res 1990;533: Maaicu mulatto thalamus with a re-
the red nucleus and other mid- 171-175. vised nomenclature of the motor
brain areas in Macaco fascicular is . 156 . Heath JW. Clinicopathologic as- related nuclei validated by obser -
Exp Brain Kes 1979;34:91-105. pects of Parkinsonian states. Arch vations on their connectivity. I
143. llassler R. Striatal control of loco-
motion, intentional actions and of 157. Hedreen JC. Separate demonstra -
-
Neurol Psychiatry 1947;58:484 497. Comp Neurol 1987:262:331 Vvl
170. Ilinskv 1A , Tourtellotte WG, Kul-
integrating and perceptive activity. tion of dopaminergic and non- tas- llinsky K . Anatomical distinc -
| Neurol Sd 1978.36: 187 -224 dopaminergic projections of the tions between the two basal gan-
144 Ilassler K, Chung Y-M. Identifica- substantia nigra in the cat . Anat glia afferent territories in the
tion of eight types of synapses in Rec 1971:169:338. primate motor thalamus. Stereo-
the pallidum externum and inter - 158. Heimer, L., Switzer, R .C., III, and tact Funct Neurosurg 1993;6(l
num in the squirrel monkey Van Hoesen, G.W . 1982. Ventral 62-69.
( Niw /irj scmrcu < ) . Act a Anat ( Basei ) striatum and ventral pallidum: 171. Inagaki S, Parent A . Distribution ot
1984;118:65-81. Components of the motor system? substance P and enkephalin like -
14 s llassler K, Reichert T, Mundinger -
Trends Neurosci 5:83 87. immunoreactivitv in the substantia
.
E, L' mbach VV Cangleberger JA.
Physiological observations in
..
159 Heimer L Wilson, R.D. 1975 The
subcortical projections of the allo-
nigra of rat, cat and monkev Brain
Res Bull 1984;13:319-329.
stereotaxic operations in extra - cortex: Similarities in the neural as- 172. Iversen LL. The uptake, storage,
pvranudal motor disturbances. sociation of the hippocampus, the release and metabolism ot GABA
Brain 1960 3:337 380 pyriform cortex, and the neocortex. in inhibitory nerves. In : Snyder SII,
*
146 Hatton T, Fibiger HC, McGeer PL
IVmonstration of a pallidonigral
In M. Santini, ed. Golgi Centennial
Symposium. New York: Raven
ed . Perspectives in neuropharma
cologv. London: Oxford University
-
projection innervating dopaminer - Press, 177-193. Press, 1972:75- 111.
gic neurons. J Comp Neurol 160. Herkenham, M. 1978. Intralaminar 173. Jacob BL, Azmitia EC. Structure
1975;162 487-804 and parafascicular efferents to the *
and function of the brain serotonin
147 Hattori T. McGeer PL, Fibiger HC . striatum and cortex in the rat : An system. Phvsiol Rex !992;72:
McC»eer EG. On the source of autoradiographic studv. Anat Rec 165-229.
GABA -containing terminals in the 190:420. 174. Jackson A, Crossman AR. Basal
substantia nigra: electron micro- 161. Herkenham M, Nauta WJIL Affer- ganglia and other afferent projec -
scopic autoradiographic and buv ent connections of the habenular tions to the peribrachial region in
chemical studies. Brain Res 1973; nuclei in the rat : a horseradish per- the rat: a studv using retrograde
54:103-114. oxidase study, with a note on the and anterograde transport of
148 llazrati L-N, Parent A . Projection fiber-of -passage problem J Comp horseradish peroxidase. Neuro-
trom the external pallidum to the Neurol 1977;173:123-145. science 1983;6:1537- 1549
reticular thalamic nucleus in the 162. Herz A, Zieglgansberger W . The 175. Jackson D, Bruno JP, Stachowiak
squirrel monkev. Brain Res 1991; influence of microelectrophoreti- MK, Zigmond MJ. Inhibition ol
550:142-146. cally applied biogenic amines, striatal acetylcholine release by
149 Hazrati L -N. Parent A C ontralat - cholinomimetic and procaine on serotonin and dopamine after the
eral palhdothalamic and palli - *
synaptic excitation in the corpus intracerebral administration of 6-
dotegmental projections in pri- striatum. Int | Neuropharmacol hvdroxvdopamine to neonatal rats.
mates: an anterograde and 1968;7:221-230. Brain Res 1988:457:267 273
retn>grade labeling study. Brain 163 Herz E. Die amyostatischen Un- 176. Jakob A . Die Extrapvramidalen
Res 1991;567:212-223. ruheerschelnungen. J Psychol Neu- Erkrankungen. Berlin : lulius
150. Hazrati L-N, Parent A. The stri- rol 1931;43:3-182. Springer, 1923
atopallida! projection displays a 164 . Hdkfelt T, Ungerstedt U. Electron 177. Jakob A . The anatomy, clinical syn-
high degree of anatomical speci- and fluorescence microscopical dromes and physiology ot the ex -
ficity in the primate Brain Res studies on the nucleus caudatus trapvramidal system. Arch Neurol
1992;592:213-227 putamen of the rat after unilateral Psychiatry 1925;13:596-620.
151. Hazrati L-N, Parent A. Conver- lesions of ascending nigro-neostri- 178. Jayaraman A . Organization of thal -
gence of subthalamic and striatal atal dopamine neurons. Acta Phys- amic projections to the nucleus ac -
afferents at pallidal level in pri-
mates: an anterograde double- la -
-
iol Scand 1969;76:415 426.
165 Hope BT, Michael G, Knigge KM,
cumben and the caudate nucleus
*
in cats and its relation with hip-
beling study with biocvtin and Vincent SR. Neuronal NADPH di- pocampal and other subcortical af -
PHA -L Brain Re* 1992;569 aphorase is a nitric oxide synthase. ferent . | Comp Neurol 1985;23 L
336-340. Proc Natl Acad Sri USA .396-420.
*
152. Hazrati L-N, Parent A Differential 1991;88:2811-2814. 179. Jayaraman A, Updvke BV . Organi -
patterns of arborization ot striatal 166 Hopkins DA , Niessen LW . Sub- zation of visual cortical projections
and subthalamic libers in the two stantia nigra projections to the to the claustrum in the cat Brain
pallidal segments in primates. reticular formation, superior col- Res 1979;178:107 115
Brain Res 1992:598:311 315 liculus and central gray in rat, cat . .
180. Jimenez -Castellano* I Gravbiel
AM . Compartmental origins of method . Phil Trans R Soc Lond from precentral motor cortex to the
striatal efferent projections in the ( Biol )1971;262:429-439. putamen and other parts of the
-
cat . Neuroscience 1989;32:297 321. 197. Kemp JM , Powell TIN. The con - basal ganglia: an autoradiographic
181 . linnai K , Matsuda Y . Neurons of nexions of the striatum and globus study in Macaco fascicularis. Brain
the motor cortex projecting com - pallidus: synthesis and specula - Kes 1975;88:195-209.
monly on the caudate nucleus and tion . Phil Trans R Soc Lond ( Biol ) 212 . Kunzle H . An autoradiographic
the lower brain stem in the cat. 1971;262:441 ^457. analysis of the efferent connections
Neurosci Lett 1979;26:95-99. 198 Kim J -S, Hassler R , Haug P, Paik from premotor and adjacent pre -
182. Jones EG. The thalamus. New KS. Effect of frontal cortical abla - frontal regions ( areas 6 and 9) in
.
York: Plenum 1985. tion on striatal glutamic acid levels Macaco fascicular is. Brain Behav
183. Jones EG, Coulter ID, Burton II , in rat . Brain Res 1977;132:370-374. Evol 1978;15:185-234.
Porter R. Cells of origin and termi- 199 . Kim R , Nakano K , Jayaraman A , 213. Kunzle H , Akert K . Efferent con -
nal distribution of corticostriatal Carpenter MB. Projections of the nections of cortical area 8 ( frontal
-
fibers arising in the sensory motor globus pallidus and adjacent struc - eye field ) in Macaco fascicularis: a
cortex of monkeys. J Comp Neurol tures: an autoradiographic study reinvestigation using the autoradi-
1977;173:53-80. in the monkey . J Comp Neurol ographic technique. J Comp Neu -
184 . Jones EG , Leavitt RY. Retrograde 1976;169:263 289 - rol 1977;173:147-164.
axonal transport and the demon - 2( H ). Kimura H , McGeer PL, Peng Jll, 214 . Kuo J -S, Carpenter MB. Organiza -
-
stration of non specific projections McGeer EG. The central choliner - tion of pallidothalamic projections
to the cerebral cortex and striatum gic system studied by choline in the rhesus monkey . J Comp
from thalamic intralaminar nuclei acety11ransferase i mm u m > h ist o- Neurol 1973,151 :201-23b
in the cat , rat and monkey. J Comp chemistrv in the cat . J Comp Neu - 215. Kuypers HGJM, Lawrence DC.
Neurol 1974, 154:349-378. rol 1981;200:151-201. Cortical projections to the red nu -
185. Jones EG, Wise SP. Size, laminar 201 . Kita 11. Responses of globus pal - cleus and the brain stem in the rhe -
and columnar distribution of effer - lidus neurons to cortical stimula - sus monkey. Brain Res 1967;4 :
-
ent cells in the sensory motor cor- tion : intracellular study in the rat . 151-188.
tex of monkeys. J Comp Neurol Brain Res 1992;589:84-90. 21 b. Langston JW , Ballard P, Tetrud JW,
1977;175:391-438. 202. Kita H , Chang HT, Kitai ST. The Irwin I Chronic parkinsonism in
18b. Kanazawa I, Emson PC, Cuello morphology of intracellularlv la - humans due to a prinluct of
AC. Evidence for the existence of beled rat subthalamic neurons: a meperidine-analog synthesis. Sci-
substance P-containing fibers in light microscopic analysis, J Comp ence 1983;249:979-980.
striatonigral and pallidonigral Neurol 1983;215:245 257. - 217. Larsen KD, McBride RL. The orga -
pathways in rat brain . Brain Res 203. Kita H , Kitai ST. Efferent projec - nization of feline entopeduncular
1977;119: 447-459. tions of the subthalamic nucleus in nucleus projections: anatomical
187. Kanazawa I , Marshall GR , Kelly the rat . light and electron micro - studies. ) Comp Neurol 1979;184:
JS. Afferents to the rat substantia scopic analysis with the PHA- L 293-308.
nigra studied with horseradish method . J Comp Neurol 1987;260: 218 Lavoie B, Parent A . Immunohisto-
peroxidase, with special reference 435-452. chcmica ) study of the serotoniner -
to fibers from the subthalamic 204 . Kita H , Kosaka T, Heizmann gic innervation of the basal ganglia
nucleus. Brain Res 1976,115: -
CW. Parvalbumin immunoreactive in the squirrel monkey J Comp
485-491 . neurons in the rat neostriatum : a Neurol 1990;299:1-16.
188 Kawaguchi Y. Physiological, mor- light and electron microscopic 219. Lavoie Br Parent A . The peduncu -
phological , and histochemical study . Brain Res 1990;536:1-15. lopontine nucleus in the squirrel
characterization of three classes of 205. Kitai ST, Koscis JD, Preston RJ , monkey . Cholinergic and gluta -
interneurons in rat neostriatum . J Sugimori M. Monosynaptic inputs matergic projections to the sub -
-
Neurosci 1993;13:4908 4923. to caudate neurons identified by stantia nigra . J Comp Neurol
189. Kemp J . An electron microscopic intracellular injection of horserad - 1994;344:232-241.
study of the termination of afferent ish peroxidase. Brain Res 1976; 220. Lavoie Br Smith Y, Parent A .
fibres in the caudate nucleus. Brain -
109:601 606. Dopaminergic innervation of the
Res 1968;11:464-467. 206. Kitai ST, Kocsis JD, Wood J . Origin basal ganglia in the squirrel mon -
190. Kemp J . Observations on the cau - and characteristics of the cortico - key as revealed by tyrosine hy -
date nucleus of the cat impreg - caudate afferents: an anatomical droxylase immunohistochemistry ,
nated with the Golgi method . and electrophvsioli »gical study. J Comp Neurol 1989;289: 36 52.-
Brain Res 1968;11:467-470. Brain Res 1976;118:137-141 . 221 . Lee HJ , Rye DB, Hallanger AF. .
191 . Kemp JM . The termination of stri- 207. Kodama S. Uber die sogenannten Levey Al, Wainer Bll . Cholinergic
opallidal and strionigral fibers. Basalganglien . II . Pathologis- vs noncholinergic efferents from
-
Brain Res 1970;17:125 128. chanatomische Untersuch ungen the mesopontine tegmentum to the
192. Kemp JM . The site of termination mit Bezug auf die sogenannten extrapvramidal motor system nu -
of afferents fibers on the neurones Basalganglien and ihre Adnexe. clei . J Comp Neurol 1988;275:
of the caudate nucleus. | Phvsiol Schweiz Arch Neurol Psvchiatr 469 -PC
( Lond ) 1970;210:17-18. 1928;23:38-1(X);179-265. 222. Levey Al , Wainer BH , Mufson EJ ,
193. Kemp JM , Powell TPS. The cortico- 208. .
Kubota Y Kawaguchi Y. Spatial -
Mesulam M - M. Co localization of
striate projection in the monkey . distributions of chemically identi - acetylcholinesterase and choline
Brain 1970;93:525-546. fied intrinsic neurons in relation to acetyltransferase in the rat cere -
194. Kemp JM , Powell TPS. The struc- patch and matrix compartments of brum . Neuroscience 1983;9:9 22 -
ture of the caudate nucleus of the rat nei >striatum. J Comp Neurol 223. Lewv EH . Historical introduction.
cat: light and electron microscopy . 1993;332:499-513. In : The basal ganglia and their Dis-
Phil Trans R Soc Lond ( Biol ) 209 Kuhlenbeck H. The derivatives of eases . Res Publ Ass Nerv Ment Dis
1971;262:383-401 . the thalamus ventralis in the 1942;21:1-20.
195 . Kemp JM , Powell TIN The synap- human brain and their relation to 224 . Lili*s SL, Updyke BV. Projection of
tic organization of the caudate nu - the so-called subthalamus. Milit the digit and wrist area of precentral
cleus. Phil Trans R Soc Lond ( Biol ) Surg 1948;102:433-447. gyrus to the putamen: relation be-
1971262:403 412 210. Kuhlenbeck H , Haymaker W . The tween topography and physiological
196. Kemp JM , Powell TPS. The termi - derivatives of the hypothalamus in properties of neurons in the puta -
nation of fibres from the cerebral the human brain: their relation to men Brain Res 19B$33fc245 255.
cortex and thalamus upon den - the extrapvramidal and autonomic 225. I indvall O, Brudin P, Widner 11, et
dritic spines in the caudate nu - systems. Milit Surg 1949;105:25-52. al . Grafts of fetal dopamine neu -
cleus: a study with the Golgi 211 Kunzle H . Bilateral projections rons survive and improve motor
function in Parkinson's disease. bral cortex. 1. Thalamo-cortical studied with horseradish peroxi -
Science 1940;247:574-577. connections. J Comp Neurol dase: an evaluation of a retrograde
22b. McBride RL, Larsen KD. Projec - 1947;86:95-117. neuroanatomical research method
tions of the feline globus pallidus 244 . Mettler FA. Neuroanatomy. St. Brain Res 1974 7:219 238
Brain Res 1980;148:3-14. Louis: C. V . Mi >sby, 1948 . .*
260. Nauta YVJH Mehler W' R. Projec -
227 McGeer PL, Fibiger HC Maler L . . 245. Mettler FA . The experimental tions of the lentiform nucleus in
I Litton T, McGeer EG. Evidence anatomo- physiologic approach to the monkey. Brain Res 1966;1:3-42.
for descending pallidonigral the study of diseases of the basal 261 . Nauta WJH , Smith GP, Faull RLM ,
-
GABA containing neurons. Adv
Neurol 1974;5:153-160.
ganglia . I Neuropathol Exp Neurol
1455;14:115- 141 .
Homesick YB. Efferent connections
and nigral afferents of the nucleus
228. McLennan 11 . York D11 The action 246. Mettler FA . Anatomv ol the basal accumbens septi in the rat . Neuro -
of dopamine on neurons of the ganglia . In : Vinken PI , Bruyn GW , science 1478;3:385-401 .
caudate nucleus. | Physiol ( Lond ) eds . Handbook of clinical neurol - 262. Nauta W 1 H , Whitlock DG . An
-
I %7;189:393 402. ogy . Vol. 6. Amsterdam: North - anatomical analysis of the non -spe-
229 Macchi G , Bentivoglio M , Mol man llolland Publishing Company , cific thalamic projection system . In
.
M Minciacchi D. The thalamo cau -- 1968: 1-55. Delafresnaye IF, ed. Brain mecha -
date versus thalamo-cortical prtv 247. Meyer A . Karl Friedrich Burdach nisms and consciousness. Oxford:
lections as studied in the cat with and his place in the history of neu - Blackwell Scientific Publications,
fluorescent retrograde double - roanatomv. j Neurol Neun >surg 1454:81-98.
labeling. Exp Brain Res 1984; 54: Psychiat 1470;33:553-561 . 263. Nicolaou NM , Garcia - Munoz M,
225-239. .
248. Miller JJ Richardson TL, Fibiger Arbuthnott GW, Fccleston D In -
23t ). Malach R , Graybiel AM. Mosaic ar - HC , McLennan H Anatomical and teractions between serotoninergic
chitecture of the somatic sensory - elect rophy siologica1 iden t i fica lion and dopaminergic systems in rat
recipient sector of the cat 's stria - of a projection from the mesen - brain demonstrated by small uni -
tum . | Neurosci 1986;6:3436-3458. cephalic raphe to the caudate puta - lateral lesions of the raphe nuclei .
231 . Martin JB, Beal ML. Huntington’s men in the rat . Brain Res Furop J Pharmacol 1979;57:
disease and neurotoxins. Ann NY 1975;97:133-138. 295-305.
Acad Sci 1992;648: l 64475. 249. Mitchell | l , Jackson A , Sam brook 264 Nomura S, Mizuno N , Sugimoto T
232 Martin JP Hemichorea resulting MA . Crossman AR . Common Direct projections from the pedun -
from a local lesion of the brain neural mechanisms in experimen - culopontine tegmental nucleus to
( The syndrome of body of Luys. ) tal chorea and hemiballismus in the subthalamic nucleus in the cat
-
Brain 1927;50:637 651. the monkey. Evidence from 2 de- - -
Brain Res 1980;196:223 227.
233 Martin JP. Remarks on the func - oxyglucose autoradiography Brain 265. Norita M . Demonstration ol bilat -
tions of the basal ganglia Lancet Res 1985;339:346-350 -
eral claustro cortica! connections
1959; 1 :949 -1005. 250. Mitrofanis J . Calbindin immunore - in the cat with the methiKl of retro-
234 Martin|P, Hurwit / l| . . Locomotion activity in a subset ol cat thalamic grade axonal transport of horse -
and the basal ganglia . Brain reticular neurons. J Neurocvtol radish peroxidase. Arch Histol Jpn
1962;85:261-276. 1992;21:445-505. 1977;40: 1 -10.
235. Martin IP, McCaul IR . Acute 251 . Mogenson G ) , Swanson LW , Wu 266. Ohye C. Dynamic aspects of the
hemiballismus treated by ventro- M Evidence that projections of the stnatothalamic connection studied
lateral thalamolvsis Brain |459;82: substantia innominata to zona in - in cases with movement disorders.
104-108. certa and mesencephalic locomotor In : Narabavashi H , Nagatsu T,
236. Mason ST, Fibiger 11C . Kainic acid region contribute to locomotor ac- Yanagisawa N , Mizuno Y, eds. Ad -
lesions ol the striatum: behavioral tivity Brain Res 1985, 334:65 76. vances in neurology . New York :
seijuelae similar to Huntington's 252. Moon Edley S, Graybiel AM The Raven Press, 1493:784*3.
chorea. Brain Res 1978;155: afferent and efferent connections 267. Oka 11. Organization of the cortico -
-
313 329. of the feline nucleus tegmenti pe - caudate projections. A horseradish
237. Matsumura M . Kojima J , Gardiner dunculopontinus, pars compacta . J peroxidase study in the cat . Exp
TW , Hikosaka O. Visual and ocu - Comp Neurol 1983;217:187-215. -
Brain Res 1480;40: 203 208.
lomotor functions of monkey sub- 253. Mouroux M , Feger|. Evidence that -
268. Okada Y , Nitch Hassler C, Kim JS,
thalamic nucleus. | Neurophysiol the para fascicular projection to the B»ik l|, Hassler R . The role of y-
1992;67:1615-1632 subthalamic nucleus is glutamater - aminobutvric acid ( GABA ) in the
238. Mehler VVR Further notes on the gic. Neuroreport 1993;4:613-615. extrapvramidal motor system . I
center median nucleus ol Luys. In 254 . Narabavashi II . Role of stereotaxic Regional distribution of GABA in
Purpura DP, Yahr MD, eds. The surgery in treatment of Parkin - rabbit, rat and guinea pig brain .
thalamus. New York: Columbia son 's disease. In: Nagatsu T, Exp Brain Res 1471 ;13:514-518.
University Press, 1466:104-127. Narabavashi II , Yoshida M. eds. 264. Olpe H R , Koella WP. The re-
239 Mehler VVR The basal ganglia
circa 1482. Appl Neurophvsiol
— Parkinson's disease: from clinical
aspects to molecular basis Wien :
sponse of striatal cells upon stimu -
lation of the dorsal and median
1981.44: 261 -290 -
Springer Verlag, 1991: 187- 199 raphe nuclei . Brain Res 1977;
240 Mesulam M - M , Mash D, Hersh L, 255. Narabavashi 11. Okuma T, Shikiba 122:357-360.
Bothwell M , Geula C . Cholinergic S. Procain oil blocking of the 270. Olson CR , Graybiel AM . Sensory
innervation of the human striatum , globus pallidus. AM A Arch Neu - maps in the claustrum of the cat .
globus pallidus, subthalamic nu - rol Psychiatry 1956;75: 36-48. -
Nature 1980;288:474 481 .
cleus, substantia nigra , and red nu - 256. Narkiewicz O. Degenerations in 271 . Olszewski J , Baxter D. Cytoarchi -
t inis | Comp Neural 1992.323 the claustrum after regional neo - tecture of the human brain stem.
252-268. cortical ablations in the cat |Comp Philadelphia : J B. Lippincott , 1954
241 Mettler FA . Relation between -
Neurol 1964;123:335 356. 272. Parent A. Identification of the pal -
pyramidal and extrapvramidal 257. Nauta HJW. Evidence of a pal lido- lidal and peripallidal cells project -
function. Proc Assoc Res Nerv habenular pathway in the cat. J ing to the habenula in monkey.
-
Ment Dis 1942;21:150 227. Comp Neurol 1974 ;156: 19-28. Neurosci Lett 1979;15: 159-164.
242 . Mettler FA Extensive unilateral 258 Nauta HJW, Cole M . Efferent pro - 273 Parent A . Comparative neurobiol -
cerebral removals in the primate: jections of the subthalamic nu - ogy of the basal ganglia . New
physiologic effects and resultant cleus: An autoradiographic study York: John Wiley & Sims, I 486.
degeneration j Comp Neurol
, in monkey and cat . J Comp Neurol 274 . Parent A . Extrinsic connections ol
1943;79:185-243 1978 180:1 - 16.
; the basal ganglia. Trends Neurosci
243. Mettler FA Extracortical connec - 259. Nauta HJW , Pritz MB, Lasek R| 1990;13:254-258.
tions of the primate frontal cere - .
Afferents to the rat caudoputamen 275. Parent A Bouchard C, Smith Y .
The stri <itop<iltidal and striatoni - Saavedra jP. Serotonergic innerva - tochemistry . Brain Res 1981;208:
gral projections: two distinct fiber tion of the monkey basal ganglia : 259-266.
systems in primate. Brain Res an immunocvtochemical study . In : 304. Ramon v Cajal S. Histologie du
-
1984;303:385 390. McKenzie JS, Kemm RH , Wilcock Systeme Nerveux de I' Homme et
276. Parent A, De Bellefeuille L. Organi- LN , eds. The basal ganglia : struc- des Vertebres. ( Azoulay L , trans . )
zation of efferent projections from ture and function . Plenum Press, Paris: Maloine, 19(19, 1911 .
the internal segment of the globus New York, 1984:115-129. ( Reprinted , Consejo Superior de
pallidus in primates as revealed by 290. Pasik P, Pasik T, Saavedra JP. Im - Investigaciones Cientificas, Insti -
fluorescent retrograde labeling munocytochemical localization of tuto Ramon v Cajal, Madrid , 1972. )
method . Brain Res 1982;245: serotonin at the ultrastructural .305. Ranson SW , Ranson SW Jr. Effer -
201 214 . level. J Histochem Cvtochem ent fibers of the corpus striatum .
277. Parent A , De Bellefeuille L. The 1982;30:760-764. Proc Assoc Res Nerv Ment Dis
pallidointralaminar and pallido- 291. Pearson RCA, Brodal P, Gatter KC, 1942;21:69-76.
migral projections in primate as Powell TPS. The organization of 306. Rasminsky M , Mauro A , Albe Fes--
studied with retrograde double- la - the connections between the cortex sard D. Projections of medial thala -
beling method. Brain Res 1983; and the claustrum in the monkey. mic nuclei to the putamen and
278:11-27. Brain Res 1982;234:435-441. frontal cerebral cortex in the cat .
278. Parent A , Descarries L, Beaudet A . 292. Penney JB Jr, Young AB. Striatal Brain Res 1973;61 :69-77.
Organization ol ascending sero- in homogeneities and basal ganglia .307. Ribak CE, Vaughn JE, Roberts E .
tonin systems in the adult rat function. Mov Disord 1986;1 :3-13. The GABA neurons and their axon
brain . A radioautographic study 293. Percheron G. The thalamic terri - terminals in the rat corpus stria -
after intraventricular administra - tory of cerebellar afferents and the tum as demonstrated by GAD im -
-
tion of |'H|5 hydroxytryptamine. lateral region of the thalamus of .
munocytochemistry J Comp Neu -
Neuroscience 1981 ;6:115-138. the macaque in stereotaxic ventric - rol 1979;187:261- 284 .
279. Parent A, Gravel S, Boucher R . The ular coordinates. J Himforsch 308. Riche D, Lanoir J . Some claustro -
origin of forebrain afferents to the 1977;18:375-400. cortical connections in the cat and
habenula in rat , cat and monkey. 294. Percheron G, Yelnik |, Francois C. baboon as studied by retrograde
Brain Res Bull 1981;6:23-38. A Golgi analysis of the primate horseradish peroxidase transport . J
280. Parent A, Gravel S, Olivier A . The globus pallidus. III. Spatial organi - Comp Neurol 1978;177:434-444.
extrapvramidal and limbic systems zation of the striatopallidal com - 309. Ritcher E. Die Fntwicklung des
relationship at the globus pallidus plex . J Comp Neurol 1984;227: Globus Pallidus und des Corpus
level : a comparative histochemical 214-227. Subthalamicum . Berlin: Springer -
study in the rat , cat , and monkey. 295. Phelps PE, Houser CR, Vaughn JE. .
Verlag , 1965
.
In : Poirier Lj, Sourkes TL Bedard Immunocvtochemical localization 310. Riley HA. An atlas of the basal
PJ, eds. Advances in neurology. of choline acetyltransferase within ganglia, brain stem and spinal
New York: Raven Press, 1978:1-11. the rat neostriatum: A correlated cord . Baltimore: Williams &
281. Parent A, Ha / rati L- N . Anatomical light and electron microscopic Wilkins, 1943.
aspects of information processing study of cholinergic neurons and 311 Rinvik F , Grofova I , Hammond C,
in primate basal ganglia . Trends synapses. J Comp Neurol 1985; Feger J , Deniau JM A study of the
Neurosci 1993;16:111-116. 238:286-307. afferent connections of the subtha -
282. Parent A , Hazrati L- N . Multiple .
296. Picket VM , Beckley SC Joh TH, lamic nucleus in the monkey and
striatal representation in primate Reis DJ . Ultrastructural immuno - cat using the HRP technique. In:
substantia nigra I Comp Neurol cvtochemical localization of tyro- Poirier l .J , Sourkes TL, Bedard PJ,
-
1994;344:305 320. sine hydroxylase in the neostria - eds. Advances in neurology. New
283. Parent A, Mackey A , De Belle- tum. Brain Res 1981;225: 373-385. York: Raven Press, 1979:53-70 .
feuille L. The subcortical afferents 297. Poirier l.J , Parent A, Roberge AG. 312. Rinvik F, Ottersen OP. Terminals of
to caudate nucleus and putamen in The striopallidal system: its impli- subthalamonigral fibres are enriched
primate: a fluorescence retrograde
double labeling study. Neuro-
cation in motor disorders. In :
loachim HL, ed . Pathobiology an -
-
with glutamate like immunoreactiv
ity: an electron microscopic, im-
-
science 1983;10:1137-1150. nual. New York: Appleton -Cen - munogold analysis in the cat. J
-
284. Parent A , O'Reilly Fromentin ) , -
tu rv C rof ts, 1975:339-367. Chem Neuroanat 1993,-6: 19-30.
Boucher R . Acetylcholinesterase - 298. Poirier LJ , Sourkes TL. Influence of 313. Roeder F, Orthner II . Frfahrungen
containing neurons in cat neostria - the substantia nigra on cate- mil stereotaktischen Eingriffen . 1 .
tum: a morphological and quanti - cholamine content of the striatum. Mitteilung: Zur Pathogenese und
tative analysis. Neurosci Lett Brain 1965;88:181-192. Thera pie extrapyramidal - mo-
1980;20:271-276. 299. Poirier LJ , Sourkes TL, Bouvier G, torischer Bewegungsslorungen. Er-
285. Parent A , Smith Y . Organization of Boucher R, Scarabin S. Striatal folgreiche Behandlung eines Fa lies
efferent projections of the subthal - amines, experimental tremor and schwerem I lemiballismus mil
amic nucleus in the squirrel mon - the effect of harmaline in the mon - gezielter Flectrokoagulation des
key as revealed by retrograde kev. Brain 1966;89:37-52. Globus pallidus. Dtsch Z Nervenh
labeling methods. Brain Res 300. Powell TI *S, Cowan WM. A study 1956;175:419-434.
1987;436:296-310. -
of thalamo striate relations in the 314. Romansky KV, Usunoff KG,
286. Parent A, Smith Y, Filion M , monkey. Brain 1956;79:364-390. Ivanov DP, Galabov GP. Cortico-
Dumas J . Distinct afferents to inter - 301. Pycock C, Horton RVV , Marsden subthalamic projection in the cat :
nal and external pallidal segments CD. The behavioural effects of ma - an electron microscopic study.
in the squirrel monkev. Neurosci nipulating GABA function in the Brain Res 1979;163:319 -322.
Lett 1989;96:140-144. globus pallidus. Brain Res 315. Royce GJ . Laminar origin of corti -
287. Park MR , Falls WM, Kitai ST. An 1976;116:353-359. cal neurons which project upon the
intracellular HRP study of the rat 302. Rafols J , Fox CS. The neurons of caudate nucleus: a horseradish
globus pallidus. I Responses and the primate subthalamic nucleus: a peroxidase investigation in the cat.
light microscopic analysis J Comp Golgi and electron microscopic |Comp Neurol 1982;2( )5:8 29.
Neurol 1982;211 : 284-294 . study. J Comp Neurol 1976;168: 316. Royce GJ , Bromley S. Fluorescent
288. Pasik P, Pasik T, Di Figlia M . 75-112. double labeling studies of thala -
Quantitative aspects of neuronal 303. Ragsdale CVV Jr, Graybiel AM. mostriatal and corticostriatal neu -
organization in the neostriatum of The fronto-striatal projection in rons. In : McKenzie JS, Kemm RE,
the Macaque monkey. PRK ASSOC - the cat and monkey and its rela - Wilcox LN , eds. The basal ganglia:
Res Nerv Ment Dis 1976;55:57-89. tionship to inhomogeneities estab- structure and function . New York:
289. Pasik P, Pasik T, Holstein C R . . lished by acetylcholinesterase his- Plenum Press, 1984: 131 - 146.
317. RoyceGJ , Mourey R| Efferent con - Proc Assoc Res Nerv Ment Dis 345. Szabo ) . Projections from the body
nections of the centromedian and 1978;55:227-247. of the caudate nucleus in the rhe-
parafascicular thalamic nuclei: an 331 . Smith Y, Hazrati LN, Parent A . Ef - sus monkey. Exp Neurol 1970;
autoradiographic investigation in ferent projections of the subthala - -
27:1 15.
the cat. J Comp Neurol 1985; mic nucleus in the squirrel monkey 346. Szabo J . Distribution of striatal af -
235:277-300. as studied by the PHA - L antero-
318. Russchen FT, Bask 1, Amaral IX ,
Price DL. The amygdalostriatal
.'
grade tracing method . J Comp
-
Neurol 1990;294:308 323.
ferents from the mesencephalon in
the cat . Brain Res 1980;188:3 21.
347. Szabo J . Organization of the as
-
-
projection in the monkey. An an - 332. Smith Y , Lavoie B, Dumas J , Parent cending striatal afferents in mon -
terograde tracing study . Brain Res A. Evidence for a separate ni - keys. | Comp Neurol 1980;189:
-
1985;329:249 257. gropallidal dopaminergic projec- -
307 321.
319. Sadikot AF, Parent A , Francois C. tion in the squirrel monkey. Brain .348. Takagi H , Somogvi P. Somogyi J ,
The centre median and parafascic- Res 1989:482: 381-388. Smith AD. Fine structural studies
ular thalamic nuclei project respec- 333. Smith Y , Parent A. Neuropetide Y - on a type of somatostatin -im -
tively to the sensorimotor and as- immunoreactive neurons in the munoreactive neuron and its
-
sociative limbic striatal territories striatum of cat and monkey: mor- synaptic connections in the rat
in the squirrel monkey. Brain Res phological characteristics, intrinsic neostriatum : a correlated light and
1990;510:161-165.
320. Sadikot AF, Parent A, Francois C.
-
organization and co localization
with somatostatin . Brain Res
electron microscopic study . J
Comp Neurol 1983;214: 1 - 18.
Efferent connections of the centro - 1988;372:241 252.- .349. Talairach j, Paillas .
JE David M
median and parafascicular thala - 334 . Smith Y , Parent A . Neurons of the Dyskinesie de type heniiballique
mic nuclei in the squirrel monkey: subthalamic nucleus in primates trait tv par cortectomie Irontale
-
a PHA L study of subcortical pro- display glutamate but not GABA limitee, puis par coagulation de
jections. J Comp Neurol I 992;315: immunoreactivity. Brain Res 1988; l'anse lenticulaire et de la portion
137 159
- -
453:353 356. interne du globus pallidus. Rev
321 . Sadikot AF, Parent A, Smith Y, 335. Smith Y , Parent A , Seguela P, Neurol ( Paris) 1950;83:440-451.
Bolam |P. Efferent connections of Descarries L. Distribution of 350. Tennyson VM, Barrett RE, Cohen
the centromedian and parafascicu
lar thalamic nuclei in the squirrel
- GABA immunoreactive neurons in
the basal ganglia of the squirrel
.
G Cote L, Heikkila R . Mytilineou
C. The developing neostriatum of
monkey: a light and electron mi- monkev ( Saitniri >ciureus ). J Comp the rabbit : correlation of fluores-
croscopic study of the thalami»stri - Neurol 1987;259:50-65. cence histochemistry, electron mi -
atal projection in relation to striatal 3.36 Soghomonian J -J , Descarries L, croscopy , endogenous dopamine
heterogeneity. 1 Comp Neurol Watkins KC. Serotonin innervation levels, and fill dopamine uptake.
-
1992;320:228 242. in adult rat neostriatum. II . Ultra - Brain Res 1972;48:251 -285.
322. Scheel - Kruger J . Dopamine-GABA structural features: a radioauto- 351 . Ternaux JP, Hery F, Bourgoin S,
interaction : evidence that GABA graphic and immunocytochemical Adrien |, Clowinski ) , llamon M
transmits, modulates and mediates study . Brain Res 1989;481:67-88. The topographical distribution of
dopaminergic functions in the 337. Somogyi P, Bolam JP, Smith AD serotoninergic terminals in the
basal ganglia and the limbic sys- Monosynaptic cortical input and neostriatum of the rat and the cau -
tem . Acta Neurol Scand 1988; KkaI axon collaterals of identified date nucleus of the cat Brain Res
73(Suppl 107): I -49. striatonigral neurons. A light and 19771121311-326
323. Schrikler KF, Hopf A, Lange H, electron microscopic study using 352. Thach WT, Jones EG. The cerebel -
Thorner G. Morphometnsch statis- -.
che Strukturanaiysen des Striatum
-
the Golgi peroxidase transport de
generation procedure. J Comp
- - lar dentatothalamic connection:
terminal field , lamellae, rikis and
Pallidum und Nucleus subthalami - -
Neurol 1981;195:567 584.
cus beim Menschen . J Himforsch 338. Spencer HJ . Antagonism of cortical
somatotopy. Brain Res 1979;189:
188-172.
1975;16:333-350. excitation of striatal neurons by 353. Tracey Dj, Asanuma C, Jones EG,
324 . Schwarcz R , Coyle JT. Striatal le- glutamic acid diethyl ester : evi - Porter R . Thalamic relay to motor
sions with kainic acid : Neuro - dence for glutamic acid as an exci -
tatory transmitter in the rat stria -
cortex: afferent pathways from
chemical characteristics. Brain Res brain stem , cerebellum , and spinal
1977;127:235-249. -
tum Brain Res 1976;102:91 101. cord in monkeys. J Neurophvsiol
-
325. Selemon LD, Goldman Rakic PS. 339. Stanton GB, Goldberg ME, Bruce -
1980;44:532 553.
Longitudinal topography and in - CJ . Frontal eye field efferents in the 354 . Ungerstedt U . Stereotaxic mapping
terdigitation of corticostriatal pro- macaque monkey. II: Topography of the monoamine pathways in the
jections in the rhesus monkey . I of terminal fields in midbrain and rat brain . Acta Physiol Scand
Neurosci 1985;5:778-794. pons. I Comp Neurol I 988;271 : (Suppl ) 1971;387:1-48.
326. Sherk H . The claustrum and the 493-506. 355. Van der Koov D, Hatton T . Dorsal
cerebral cortex. In : Jones EG , Peters .340. Stefani A , Surmeier DJ , Kitai ST . raphe cells with collateral projec -
A, eds. Cerebral cortex. Vol . 5. Serotonin enhances excitability in -
tions to the caudate putamen and
New York: Plenum Press. 1984: neostriatal neurons by reducing substantia nigra: a fluorescent ret -
487-499. -
voltage dependent potassium cur- rograde double labeling study in
327 Sherk H, Levay S. Visual claus- rents . Brain Res 1990;529:354-357 . the rat Brain Res 1980;188:1 7. -
trum topography and receptive .341. Swanson LW , Cowan WM. A note 358. Van der Kooy D, Hatton T. Single
field properties in the cat . Science on the connections and develop- subthalamic nucleus neurons pro-
1981 ;212:87-89. ment of the nucleus accumbens . ject to both the globus pallidus and
328. Shoulson I , Chase TN . Hunting - -
Brain Res 1975;92:324 330. substantia nigra in rat . J Comp
ton’s disease. Annu Rev Med 342. Switzer RC III , Hill J , Heimer L. Neurol 1980;192:751-788
1975;26: 419^126 The globus pallidus and its rostriv- 357. Van Hoesen GW, Yeterian EH ,
329 Shoulson 1, Kartzinel R , Chase TN . ventral extension into the olfactory -
Lavizzo Mourey R . Widespread
Huntington 's disease: treatment tubercle of the rat : a cyto- and corticostriate projection from tem -
with dipropylacetic acid and chemoarchitectural study. Neuro - poral cortex of the rhesus monkey.
gamma -aminobutyric acid . Neu - science 1982;7:1891 - 1904 J Comp Neurol 1981;199:205-219
rology 1976;26:6 l 4>3. .343. Szabo |. Topical distribution of the 358. Vincent SR , Johansson O, Hokfelt
.
3.30 Siggins GR Hoffer BJ , Bloom FE , striatal efferents in the monkey -
T, et al . NADPH diaphorase: A se-
Ungerstedt U . Cvtochemical and Exp Neurol 1962;5:21-36. lective histochemical marker for
electrophvsiological studies of 344. Szabo J . The efferent projections of striatal neurons containing both
dopamine in the caudate nucleus. the putamen in the monkev Exp somatostatin - and avian pancreatic
In : Yahr MD. ed . The basal ganglia . -
Neurol 1967;19:463 476. -
polypeptide ( APP ) like immunore -
activities. I Comp Neurol 1983; thalamicus; corpus Luysi ). Arch 1. 77. Yelnik J , Perchcron G. Subthalamic
217:252-263. Neurol Psychiatry 1947;58:672-692. neurons in primates: A quantita -
354. Vincent SR . Staines WA , Fibiger .169. Whittier JR, Mettler FA . Studies on tive and comparative analysis.
HC. Ilistochemical demonstration the subthalamus of the rhesus -
Neuroscience 1979;4:1717 1743.
of separate populations of somato- monkey. II Hyperkinesia and 378. Yelnik J , Percheron G, Francois C.
statin and cholinergic neurons in other physiologic effects of sub- A Golgi analysis of the primate
the rat striatum . Neurosci Lett thalamic lesions with special refer- globus pallidus. II . Quantitative
1983;35:111 - 114 . ence to the subthalamic nucleus of morphology and spatial orienta -
1. 60. Vives F, Mogenson GJ . Elect ro - Luvs. J Comp Neurol 1949;90: tion of dendritic arborizations . I
phvsiological evidence that the -
319 372. Comp Neurol 1984;227:200 213. -
mediodorsal nucleus of the thala - 370. Wichmann T, DeLong MR . Patho - 379. Yeterian Ell , Pandya ON Prefron -
mus is a relay between the ventral physiology of parkinsonian motor tostriatal connections in relation to
pallidum and the medial pre- abnormalities. In: Narabavashi II . cortical architectonic organization
frontal cortex in the rat. Brain Res Nagatsu T, Yanagisawa N , Mizuno in rhesus monkeys.|Comp Neurol
-
1985;344:320 337. Y, eds. Advances in neurology. -
1991;312:43 67.
361. Vogt C, Vogt O. Thalamusstudien New York: Raven Press, 1991; 380. Yeterian HU, Van Hoesen GW .
-
I Ill. I. Zur Einfurung, II. Ho
moginat und Grenzgestaldung der
- 60:53-61 .
371. Willis T. Cerebri Anatome, cui Ac-
-
Cortico striate projections in the
rhesus monkey: the organization
Grisea des Thalamus, 111. Das Gri - cessit Nervorum Descriptio et -
of certain cortico caudate connec -
seum centrale (centrum medianum Usus. London : Martyn and -
tions. Brain Res 1978;139:43 63.
Luvs ). | Psychol Neurol ( Leipzig ) AUestry, 1664 . 381. Young WS, Alheid GF, Heimer L.
194 I ;50:3 M 54 . 372. Wilson SAK . An experimental re- The ventral pallidal projection to
362. Von Bonin G, Shariff GA . Ex - search into the anatomy and physi - the mediodorsal thalamus: a study
trapyramidal nuclei among mam - ology of the corpus striatum . Brain with fluorescent retrograde tracers
mals. | Comp Neurol 1951 ,94: 1914;36:427-492. and immunofluorescence. J Neu -
427-438. 373. Wilson SAK . Disorders of motility rosci 1984;4:1626-1638.
163 Von Monakow C. Experimentelle and muscle tone with special refer - 382. Zaczek R , Schwarcz. R , Coyle JT
und pathologisch-anatomische Un - ence to the corpus striatum (Crixrn- Long term sequelae of striatal
tersuchunger iiber die Haubenre- ian lectures ). Lancet 1925; 2:215-291. kainate lesion . Brain Res 1978;
gion . den Sehhugel und die Regio 374. Woolf NJ , Butcher LL. Cholinergic -
152:626 632.
subthalamica. Arch Psychiatr Ner - neurons in the caudate-putamen 1. 83. Carey LJ. Visual system. In : Paxi -
venkr 1895;27:1-219. complex proper are intrinsically nos G, ed . The human nervous sys-
1. 64 . Von Namba M . Cytoarchitektonis- organized: a combined Evans blue tem . Ch . 28. New York: Academic
che Untersuchungen am Striatum . and acetylcholinesterase analysis. Press, 1990:945-977.
I Himforsch 1957;3: 24-48 Brain Res Bull 1981;7:487 507. 384. Parent A , Hazrati LN . Functional
1. 65. Von Santha K. Zur Klinik und 375. Wright AK, Arbuthnott GW . The anatomy of the basal ganglia . 1
Anatomie des Hemiballismus. pattern of innervation of the -
The cortico basal ganglia - thalamo -
Arch Psychiatr Nervenkr 1928;84: corpus striatum by the subcortical loop. Brain Res Rev 1995;
664 -6/ 8. stantia nigra . Neuroscience 1981 ;6: 20:91-127.
-
366. Webster KE. Cortico striate interre-
lations m the albino rat . 1 Anat
2063-2067.
376. Yang CR, Mogenson GJ . An elec-
385. Parent A , Hazrati LN . Functional
anatomy of the basal ganglia . II .
1961;95:532-544. trophysiological study of the The place of subthalmic nucleus
.167. Webster KE. The cortico-striatal neural projection from the hip- and external pallidum in basal
projection in the cat . J Anal pocampus to the ventral pallidum ganglia circuitry. Brain Res Rev
1965',99:329-337. and subpallidal area by way of the -
1995;20:128 154.
168. Whittier |R Ball ism and the sub-
. nucleus accumbens. Neuroscience
thalamic nucleus ( nucleus hvpo - 1985;15:1015-1024.
20
Cerebral Cortex
STRUCTURE OF THE CORTEX The cerebral cortex in humans has an area

of approximately 2200 cm 2 ( 2.5 square feet ),
The cerebral cortex develops from the tel - and a total volume of about 500,000 mm'.
encephalon, which in early stages of histoge- -
Only one third of the cerebral cortex is found
nesis resembles other parts of the embryonic on the free surface of the brain; the remaining
neural tube. The suprastriatal portion of the cerebral cortex is hidden in the depths of the
early telencephalic vesicle is composed of sulci. The thickness of the cortex varies from
three concentric zones in its smooth-surfaced about 4.5 mm in the precentral gyrus to about
( lissencephalic) stage: (a ) a germinal zone sur-
1.5 mm in the depths of the calcarine sulcus.
rounding the lateral ventricle, ( b ) the interme- The cortex is always thickest over the crest of
diate zone , which becomes the white matter of a convolution and thinnest in the depth of a
the cerebral hemispheres, and (c) a marginal sulcus. It has been estimated that besides
zone , which becomes the cortical zone or nerve fibers, neuroglia , and blood vessels, the
plate. The original columnar epithelial cells cerebral cortex contains about 15-20 billion
extend through all zones (338). At the end of neurons (368). With a mean incidence of
the second month , cells migrate from the in- 0.6 X llT synapses per mm', there are roughly
termediate zone into the marginal zone, 3 xl 014 morphologically differentiated in -
where they form a superficial gray layer, the terneuronal contacts in human cerebral cor -
cerebral cortex . As the cerebral cortex gradu - tex. This number corresponds to the number
ally thickens by the addition and differentia- of milliseconds that have elapsed in the last
tion of the migrating cells, as well as by the 10,000 years, that is, since the beginning of
arrival of afferent fibers, it assumes a lami- the Neolithic period (60 ).
nated appearance. As cells become organized The cerebral cortex contains (a ) afferent
into horizontal layers, between the sixth and fibers and terminals from other parts of the
eighth months, six such layers may be distin - nervous system ( e.g., thalamocortical fibers),
guished ( 44 ). The deeper pyramidal layer, ( b ) association and commissural neurons whose
rich in cells, forms layers II to VI , while the axons interrelate cortical regions of the same
outermost layer, composed mostly of fibers, or opposite hemisphere, and (c) projection
becomes the molecular layer ( I ). Cells formed neurons whose axons conduct impulses to
at the same time tend to remain in the same other parts of the neuraxis (e.g., corticospinal,
layer, and newly formed cells migrate corticoreticular, or corticopontine fibers).
through these layers to more superficial loca - Most projection fibers arise from the deeper
tions (10). This "inside-out" sequence of neu - layers of the cortex, while the association and
ronal migration applies to the majority of cor- commissural fibers arise mainly from the
tical cells (see Chapter 3 for details on the more superficial ones (179 ). A striking feature
migration of cortical cells during develop- of pallial structure is the relatively small
ment ). This six-layered cellular arrangement number of projection fibers compared with
is characteristic of the entire neopallial cortex, the enormous number of cortical neurons.
which is referred to as neocortex , isocortex
( 371 ), or homogenetic cortex ( 44 ). The paleopal-
Cortical Cells and Fibers
litim (olfactory cortex ) and the archipallium
( hippocampal formation and dentate gyrus) Although the cerebral cortex contains an
do not show six layers in either the develop- enormous number of cells, the number of cell
ing or adult stage. The paleopallium and types is small (59, 80, 381 , 414 ). The principal
archipallium together constitute the allocortex types of neurons found in the cortex are pyra -
or heterogenetic cortex . midal cells and the stellate or granule cells
864
( Figs. 5.8, 20.1, and 20.2). The pyramidal cells fusiform cells found in the most superficial
( including a variant form , the fusiform cell ) cortical layer and their long axons run hori -
are the major projection neurons of the cere- zontally for considerable distances and ar-
bral cortex, whereas the stellate cells act as in- borize within that layer. Martinotti cells,
terneurons. present in practically all cortical layers, are
The pyramidal cells , which are most charac- small triangular cells whose axons are di -
teristic of the cortex, have the form of an rected toward the surface. Some fibers ar -
isosceles triangle whose upper pointed end is borize in the same layer, while others send
continued toward the surface of the brain as collaterals to a number of layers.
the apical dendrite ( Fig. 20.2). Besides the api - Apart from the subdivision of cortical cells
cal dendrite, a number of more or less hori- into projection neurons (Golgi type I ) and in-
zontally running basal dendrites spring from terneurons (Golgi type II ), there exists an -
the cell body and arborize in its vicinity. The other classification based on the presence or
axon emerges from the base of the cell and absence of spines on the dendrites of cortical
descends toward the medullary substance, ei - neurons (80, 381 ). Spiny pyramidal cells are
ther terminating in the deeper layers of the found in most cortical layers, except layer I ,
cortex, or entering the white matter as a pro- whereas stellate spiny cells occur principally
jection , or association fiber. Pyramidal cells in layer IV. The aspiny cortical cells comprise
have large vesicular nuclei, prominent Nissl several types of interneurons distributed
granules, and usually are classified as small, throughout the different layers of the cortex.
medium, and large. The height of the cell Spiny and aspiny cortical neurons are be-
body varies from 10-12 pm for the smaller lieved to be respectively excitatory and in-
neurons to 45-50 (xm for the larger ones. The hibitory, but there could be some exceptions
giant pyramidal cells of Betz, found in the to this generalization (80).
precentral gyrus may be more than 100|xm in Fibers in the cerebral cortex are disposed
height . both radially and tangentially. Radially
Stellate or granule cells are small , polygonal arranged fiber bundles run vertically from
or triangular, and have dark-staining nuclei the medullary substance toward the cortical
and scanty cytoplasm. These cells, ranging surface ( Fig. 20.1 ). They include axons of
from 4-8 pm , have a number of dendrites pyramidal, fusiform, and stellate cells, which
passing in all directions and a short axon leave the cortex as projection or association
which ramifies close to the cell body (Golgi fibers, and the entering afferent and associa -
type II ) ( Fig. 20.2). Other larger stellate cells tion fibers, which terminate within the cortex .
have longer axons that may enter the Ascending axons of the Martinotti cells like-
medullary substance. Some resemble pyrami- wise have a vertical course. Tangential fibers
dal cells in that they have an apical dendrite run parallel to the cortical surface. These fiber
that extends to the surface. These cells are bundles are composed of (a ) the terminal
known as stellate or star pyramidal cells ( 239). branches of the afferent and association
Stellate cells are found throughout all layers fibers, ( b) the axons of the horizontal and
of the cortex but are especially numerous in granule cells, and (c) the terminal branches of
layer IV. collaterals from the pyramidal and fusiform
The fusiform or spindle cells are found cells. Horizontal fibers in large part represent
mainly in the deepest cortical layer, with terminal portions of radial fibers that bend
their long axis vertical to the surface ( Fig. horizontally to come into synaptic relation
20.2 ). The two poles of the cell are continued with cortical cells. Tangential fibers are not
into dendrites, with the lower dendrites ar- distributed evenly throughout the cortex but
borizing within the layer, while the upper are concentrated at varying depths into hori-
ones ascend toward the surface. The axon zontal bands separated by layers with rela -
arises from the middle or lower part of the tively few fibers ( Fig. 20.1 ). The two most
cell body, and enters the white matter as a prominent bands are known as the bands of
projection fiber. The large fusiform cells have Baillarger , which form delicate white stripes
been classified as "modified pyramidal" cells in sections of the fresh cortex ( Fig. 20.1 ).
( 337).
Other cell types found in the cortex are the Cortical Layers
horizontal cells of Cajal , and the cells with as-
cending axons, known as the cells of Mar- In Nissl-stained sections the cell bodies are
tinotti ( Fig. 20.4 ). The former are small arranged in superimposed horizontal layers.
I Tangential layer
II Dysfibrous layer
III Suprastriate layer
| IV Ext . band of BaiIlarger

y / lnterstriate layer
xInt. band of BaiI larger
VI Infrastriate layer
Subcortical white matter

Nissl Weigert
Figure 20 1 Cell layers and fiber arrangement ot the human cerebral cortex
IVa
IVb
VI
Figure 20.2 Dendritic and axonal branchings ot several types of cortical neurons with descending axons t Pyrami
dal cells of superficial layers 2. pyramidal cells from ganglionic layer. 3, spindle cells; 4 stellate cells; a axon
Each layer is distinguished by the types, den- cells from the deeper layers, and the ax-
sity, and arrangements of their cells. The lam - onal endings of Martinotti cells. These
ination seen in myelin sheath-stained sections dendritic and axonal branches form a
is determined primarily by the disposition of fairly dense tangential fiber plexus ( Fig.
the horizontal fibers, which vary in the differ- 20.1 ) .
ent layers ( Figs. 20.1, 20.2, and 20.4 ). The II . The external granular layer consisting of
neopallium ( neocortex or isocortex ), which numerous closely packed small granule
forms 90% of the hemispheric surface, has six cells whose apical dendrites terminate in
fundamental layers (44 ). Some of these layers the molecular layer and whose axons de-
are divided into sublayers. scend to the deeper cortical layers. This
The following layers are distinguished in layer is poor in myelinated fibers.
the neocortex in passing from the pial surface III . The external pyramidal layer comprising
to the underlying white matter: I , molecular; two sublayers of pyramidal neurons: a
II , external granular; III , external pyramidal; superficial layer of medium cells and a
IV, internal granular; V, internal pyramidal; deeper layer of large ones. Their apical
and VI, multiform ( Figs. 20.1, 20.3, and 20.4 ). dendrites go to the first layer, while most
of their axons enter the white matter,
I . The molecular layer containing cells with chiefly as association or commissural
horizontal axons and Golgi type II cells. fibers (164, 165, 179, 355). Intermingled
Within it are the terminal dendritic rami - with the pyramidal neurons are granule
fications of the pyramidal and fusiform and Martinotti cells. In the most superfi -
Cortical A B
layers
I
II
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in
iv
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VI
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Projections Projections Commissural Association

corticothalamic corticostriate Projections Projections
corticoclaustral corticopontine corticocortical corticocortical
corticobulbar
corticospinal
Figure 20.3 Major projection neurons in different layers of the cerebral cortex Cortical layers are indicated on the
left by Roman numerals and columns A B. C. and D depict individual projection neurons in different layers which
have separate targets. Subcortical projections of neurons in column B arise from pyramidal cells located in different
parts of layer V. with corticostriatal neurons most superficial, and corticospinal neurons in the deepest part , Intracorti-
cal ramifications of dendrites and axonal collaterals are shown. Projections axons (a) are indicated as they enter the
white matter.
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Figure 20.4 Intracortical circuits Synaptic junctions are indicated by loops. Red afferent thalamocortical fibers.
. . .
blue, efferent cortical neurons, black, intracortical neurons; G granule cell H. horizontal cell. M Martinotti cell; P .
.
pyramidal cell; S stellate cell Mode of termination of afferent cortical fibers are shown on the right
cial part of the layer, a number of hori - cells. The horizontal fiber plexus in the
zontal myelinated fibers constitute the deeper portion of this layer constitutes
band of Kaes- Bechterew. the internal band of Baillarger.
IV . The internal granular layer composed of VI . The multiform or fusiform layer containing
closely packed stellate cells, many of predominantly spindle-shaped cells
which have short axons ramifying within whose long axes are perpendicular to the
the layer. Other larger cells have de- cortical surface. Like pyramidal neurons
scending axons that terminate in deeper of layer V , the spindle cells vary in size.
layers, or may enter the white substance. The larger ones send dendrites into the
The whole layer is permeated by a dense molecular layer, while the dendrites of
horizontal plexus of myelinated fibers, the smaller ones ascend only to layer IV,
forming the external band of Baillarger or arborize within the fusiform layer. The
( Fig. 20.1 ). dendrites of many pyramidal and spin -
V . The internal pyramidal layer consisting of dle cells from layers V and VI come into
medium and large-size pyramidal neu - direct relation with the endings of sen-
rons intermingled with granule and Mar - sory thalamocortical fibers, which ramify
tinotti cells. Apical dendrites of large chiefly in the internal granular layer.
pyramidal cells ascend to the molecular Axons of the spindle cells enter the white
layer, while dendrites of small pyramidal substance mainly as projection fibers.
cells ascend only to layer IV, or may even Some of the short arcuate association
arborize within this layer ( Figs. 20.2 and fibers connecting adjacent convolutions
20.4 ). Axons of these cells enter the white are furnished by the deep stellate cells of
matter chiefly as projection fibers, al- layer VI ( 239 ). The multiform layer may
though a small number of callosal fibers be divided into an upper sublayer of
are furnished by the smaller pyramidal densely packed large cells, and a lower
one of loosely arranged small cells. The which contain the synaptic junctions through
whole layer is pervaded by fiber bundles which nerve impulses are transmitted . An
which enter or leave the medullary sub- understanding of the neuronal relationships,
stance ( Fig. 20.4 ). and of intracortical circuits, can be obtained
from (a ) classic Golgi studies, ( b ) intracellular
Besides the horizontal cellular lamination, injection experiments, ( c) electron micro-
the cortex also exhibits a vertical or radial scopic studies of various types of synaptic
arrangement of the cells, which gives the ap- relationships, and (d ) electron microscopic re-
pearance of slender vertical cell columns ex - construction of clearly identified Golgi-
tending the whole thickness of the cortex stained neurons. The distribution of dendritic
( Figs. 20.14 and 20.15). These vertical and axonal terminals has been studied with
columns are quite distinct in the parietal, oc- the Golgi technique by a number of investiga -
cipital, and temporal lobes, but are practically tors, notably Ramon v Cajal ( 312 ) and Lorente
absent in the frontal lobe. The columnar de N 6 ( 239). The latter author gave a detailed
arrangement of cells in the cerebral cortex ap- account for the elementary pattern of cortical
pears to be determined largely by the mode organization that is applicable to the parietal,
of termination of corticocortical afferents temporal, and occipital isocortex. The
rather than specific sensory afferents (355). arrangement of the axonal and dendritic
Corticocortical afferents are distributed branching forms one of the most constant fea -
throughout all layers of the cortex in colum- tures of cortical organization . Most cortical
nar modules 200-300 (xm in diameter, while interneurons also are highly specific with
terminals of specific sensory afferents usually respect to their pattern of axonal arboriza -
are restricted to layer IV. It is remarkable that tions and their synaptic contacts with other
columnar units of corticocortical afferents are cortical neurons which form local networks
all nearly the same size and have dimensions ( 24, 80 ) .
similar to physiologically identified columnar The afferent fibers to the cortex include
units in the specific sensory cortex (122, 123, projection fibers from the thalamus, associa -
140, 266, 276, 355). The arrangement into ver- tion fibers from other cortical areas of the
tical cell columns is produced by the radial same hemisphere, and commissural fibers
fibers of the cortex, just as the horizontal lam- from the opposite side. The thalamocortical
ination is largely determined by the distribu - fibers, especially the specific afferent ones
tion of the tangential fibers. from the ventral tier thalamic nuclei and the
The internal granular layer, which receives geniculate bodies, pass unbranched to layer
the main specific afferent projections and is IV ( Figs. 11.1, 11.6, 11.7, 13.30, 15.22, 16.13,
best developed in the primary sensory areas, and 16.14 ). These axons form a dense termi -
has been used to distinguish supragranular nal plexus in layer IV ( 59, 165) and some of
and infragranular layers. The supragranular them extend to layer III where they arborize
layers ( II and III ) are the last to arise, the most ( Fig. 20.4 ). Specific afferent fibers in layer IV
highly differentiated, and the most extensive establish both axodendritic and axosomatic
in humans ( 184 ). These layers are considered synapses upon stellate neurons, which are re-
to be concerned mainly with associative corti- markably profuse on some cells ( Fig. 20.5)
cal functions. The infragramilar layers ( V and ( 59). F'stimates of the number of synaptic con -
VI ), well -developed in all mammals, give rise tacts upon neurons in the motor and visual
to subcortical projection fibers concerned cortex in the monkey indicate as many as
with efferent mechanisms. The supragranular 60,000 synapses per neuron in the motor area
layers are not present in the archipallium or and 5,600 in the striate cortex ( 65). Addition -
paleopallium. ally, these cells receive synaptic contacts from
intracortical neurons.
Interrelation of Cortical Neurons Fibers of the so-called nonspecific thala -
mocortical system , related to the intralaminar
The structure of the cerebral cortex as seen thalamic nuclei and indirectly to the ascend -
-
in Nissl or myelin sheath stained sections is ing reticular activating system , project to
incomplete. These stains show only the type broad regions of the cerebral cortex (172 ). The
and arrangement of cell bodies, or the course potent effects of the stimulation of the in-
and distribution of myelinated fibers. These tralaminar thalamic and the brainstem reticu-
methods give no information regarding ter - lar formation upon electrocortical activity
minal dendritic and axonal arborizations, probably are mediated by these diffuse pro-
Figure 20.5 Stellate cell in the fourth layer of the striate cortex of the cat. Arrows indicate the large number of
synaptic contacts 05000)
jections. According to Jasper (161), the synap - response, recorded from the surface of the
tic termination of fibers of this nonspecific cerebral cortex, is regarded as a reflection of
system in the cortex is chiefly axodendritic dendritic electrical activity, which implies
and widely distributed in all layers, but the that it is a graded response not dependent
principal physiologic effects appear to be on the all-or-none firing of cortical cells
within the superficial layers. The recruiting ( 310 ).
Commissural fibers arise from cells in all and short pyramidal cells, whose dendrites
cortical regions and interconnect homologous all ramify in layer V ( Fig. 20.2 ). The spindle
cortical areas via the corpus callosum . Excep- cells of layer VI have similar branches. The
tions to this generalization are found in the axons of pyramidal and spindle neurons, and
regions of the primary motor (area 4) and some axons of deep stellate cells are contin -
somesthetic cortex (S-I) that represent the ued as projection fibers. All of these axons
hand and foot (171, 179, 186), in the visual send horizontal collaterals to layers V and VI,
cortex (area 17) ( 146, 401, 402, 413), and parts where they contribute to the horizontal
of the auditory cortex ( 77). Commissural cells plexuses, especially those of layer V ( internal
are large pyramidal cells in deep parts of band of Baillarger ). Additionally, one or
layer III (179). Cortical afferents from com- more recurrent collateral ascends unbranched
missural neurons extend throughout all corti- to arborize in layers II and III , and some even
cal layers and fill a column about 200-300 gm extend to the molecular layer ( Fig. 20.2).
in diameter ( 355). Not all callosal fibers termi- The horizontal laminar arrangement of the
nate in the entire columnar space and some cerebral cortex has served as a major criteria
collaterals terminate preferentially in particu- to map the distinctive cytoarchitectonic areas.
lar layers. Association fibers in the same This lamination also serves to segregate dif -
hemisphere arise from the supragranular ferent efferent projections from the cortex.
layers (179). Ipsilateral corticocortical fibers Each of the major efferent pathways emanat -
arise from cells in more superficial parts of ing from sensory-motor cortex has a specific
layer III and from parts of layer II . Terminal laminar or sublaminar origin (179 ). The so-
branches of association fibers are distributed mata of the majority of cells whose axons are
mainly to layers III and IV but they have distributed intracortically ( both ipsilaterally
been identified in deeper layers as well and contralaterally ) lie in the supragranular
(174). layers ( layers II and III ). Most of the cortical
The cortical neurons may be grouped into neurons whose axons project to subcortical
cells with descending, ascending, horizontal, structures lie in the infragranular layers, par-
and short axons. The last three types provide ticularly layer V and VI . In the supragranular
only intracortical connections ( Fig. 20.4). The layers, cells whose axons are distributed ipsi-
cells with descending axons ( pyramidal, laterally as corticocortical fibers lie superficial
fusiform, and larger stellate cells) furnish all to cells projecting axons to the cortex of the
the efferent projection and association fibers, opposite hemisphere, and cells with shorter
and their axonal collaterals form extensive in- axons tend to lie superficial to those with
tracortical connections. Some descending longer axons. In the infragranular layers ( lay-
axons that do not reach the medullary sub- ers V and VI ), the majority of the somata of
stance have only intracortical branches. corticostriate neurons lie in the most superfi -
The pyramidal cells of layers II , III , and IV cial part of layer V while somata giving rise
have a similar pattern of dendritic and axonal to corticospinal and corticotectal fibers are in
branchings ( Fig. 20.2 ). They have a number of the deepest part of the same layer . Somata of
basilar dendrites that arborize in the same neurons giving rise to corticorubral, cortico-
layer, and an apical dendrite that ends in the pontine, and corticobulbar fibers lie in inter-
molecular layer. Their descending axons in mediate regions of layer V, between corticos-
part terminate in the deeper layers of the cor- triate and corticospinal neurons. Cells in
tex and , in part, are continued as association layer VI of the cortex give rise to corticothala -
or callosal fibers. They give off a few recur- mic projections. Cells giving rise to a particu -
rent collaterals to their own layers, chiefly II lar set of efferent connections are of nearly
and III , and numerous horizontal collaterals the same size and do not vary in their laminar
to layers V and VI, where they contribute to distribution. Only neurons giving rise to cor-
the horizontal plexuses. ticospinal fibers show great variation in cell
The pyramidal and fusiform cells of layers size. Cells of particular efferent systems occur
V and VI have a characteristic pattern of den - in single or multiple strips oriented mediolat-
dritic and axonal branchings. All the pyrami - erally across the cortex.
dal cells of layer V give off basilar dendrites
to their own layer and an apical dendrite ex- Functional Columnar Organization
tending to the molecular layer. There are,
however, medium-sized pyramidal neurons, Although the most striking feature of
whose apical dendrites terminate in layer IV, Nissl -stained sections of the cerebral cortex is
its horizontal lamination , physiologic studies izontally and involve a progressively larger
of the somatosensory and visual cortex indi - number of vertical units ( Fig. 20.4 ). Thus, a
cate that a vertical column of cells, extending specific afferent fiber may not only fire verti-
across all cellular layers, constitutes the ele- cal columns of cells in its immediate vicinity ,
mentary functional cortical units ( 24, 123, 124, but may reach other units through Golgi type
142, 143, 266, 268, 309). This conclusion in the II cell relays. These vertical units are funda -
somatosensory cortex is supported by these mentally similar in all mammals. However,
facts: (a ) neurons of a particular vertical col - the columns of cells with short relays increase
umn are all related to the same, or nearly the in complexity in primates, especially humans.
same, peripheral receptive field ; ( b ) neurons According to Ramon y Cajal, the unique mor-
of the same vertical column are activated by phologic feature of the human cortex is the
the same peripheral stimulus; and (c) all cells enormous number of Golgi type II cells, con-
of a vertical column discharge at more or less sidered to interrelate vertical cell columns.
the same latency following a brief peripheral The cerebral cortex has been envisaged as
stimulus. The topographic pattern present on a mosaic of columnar units of remarkably
the cortical surface extends throughout its similar internal structure (355). In addition to
depth. Studies of the visual (striate ) cortex the functional columnar arrangement de-
demonstrate similar discrete functional scribed in the sensory cortical areas, there are
columns extending from the pial surface to corticocortical columns delineated primarily
the white matter that are responsive to a spe- by the pattern of termination of association
cific kind of retinal stimulation in the form of and commissural fibers. Columnar units of
long narrow rectangles of light ("slits" ), dark corticocortical afferents and the functional
bars against a light background , or straight - columns of the sensory cortex are roughly the
line borders, all of which have a particular same size. In the corticocortical columns,
axis of orientation ( 142, 143). Functional there is a convergence of afferent fibers from
columns are arranged radially, perpendicular multiple modular units that create a vast mo-
to the cortical layers and display variations in saic of cortical connections. Neurons within
size and cross-sectional area , but most fall the cortical column are conceived of as being
within the 200-500 pm range ( 143). The re- arranged in microcolumns, smaller than the
ceptive field axis of orientation varies in a larger units, concerned primarily with the
continuous manner as the surface of the cor- vertical connectivity within each column. Ex -
tex is traversed . Columns of cells in the striate citatory inputs from the thalamus and other
cortex are of two tvpes, ocular dominance cortical areas are considered to be processed
columns and orientation columns ( 386, 387). through a column-oriented circuitry com -
Ocular dominance columns receive their posed of both excitatory and inhibitory neu -
input predominantly from one eye, while ori- rons. Most interneurons in the cerebral cortex
entation columns are concerned with the re- are highly specific with respect to (a ) the neu -
ceptive field axis ( Fig. 20.26). rons from which they receive inputs, ( b) the
Anatomically, an elementary functional arborization pattern of their axons, and (c )
unit of the cortex, represented by a column of the specific sites at which they establish
cells, must contain the afferent, efferent, and synapses on other neurons. The vast majority
internuncial fiber systems necessary for the of stellate or granular cells belong to the het -
formation of a complete cortical circuit ( 276). erogeneous group, referred to as Golgi type II
In the basic columnar units, the internal cir- cells, which do not project fibers beyond the
cuitry must vary with differences in cytoar- cerebral cortex. Many unresolved problems
chitecture. The convergence of specific affer- remain concerning synaptic relationships of
ents upon cells in the columnar unit appears cells within the cortex, but electron micro-
to imprint a specific sensory modality which scopic evidence, based upon the types of
is relayed by intracortical connections to synaptic contact , suggests that the majority of
other cells in the column . The complex axonal cortical interneurons are excitatory , forming
branching suggests that intracortical circuits synapses of the asymmetric type with spheri-
involve cells in all parts of the column. These cal synaptic vesicles. Interneurons identified
vertical circuits are interconnected by short as putative inhibitory cells in the cortex con -
neuronal links, represented primarily by the stitute only a minority of the known in-
short axons of granule cells. Through these terneuron types. Both excitatory and in-
short links cortical excitation may spread hor- hibitory influences within the cerebral cortex
<ire exerted upon selected segments of pyram - major sites of termination of the recurrent
idal cells that represent the principal cortical collaterals is the spines of other pyramidal
output neurons. cells in layers III and V, the two major output
layers of the cortex ( 197). The vertically ori -
ented recurrent collaterals appear to set up
CHEMICAL ANATOMY OF THE CORTEX
local excitatory patterns and play a recruit -
Excitatory Amino Acids ment role ( 117, 118), while the horizontally
oriented ones serve to integrate the activity of
Glutamate (Glu ) and aspartate ( Asp ) are columnar modules.
the two major excitatory neurotransmitters in The excitatory interneurons are often re-
the central nervous system . Although Glu is ferred to as spiny stellate cells. They abound
involved in basic cellular metabolism, it satis- in layer IV of the visual cortex and are infre-
fies the criteria for classification as a neuro- quent or even absent in other cortical areas,
transmitter ( 91 , 288, 348 ). When exogenously particularly the primary motor cortex. The
applied , they both evoke a rapid spiking ac- axon of the spiny stellate cell forms a radial
tivity associated with membrane depolariza - link between layer IV, the major thalamo-
tion . There are strong indications that Glu recipient layer, and layers III , V, and VI , the
and Asp are the principal neurotransmitters major projection layers. The spiny stellate cell
of most cortical projection neurons, forming appears to be specialized in the reception and
corticospinal, corticostriate, corticothalamic, local dissemination of thalamic inputs (80,
and corticopontine pathways ( Fig. 20.6) (120, 264).
121 ). Glutamatergic synapses are all symmet- The thalamocortical and corticocortical
ric and the vast majority of them contact projections provide the major excitatory
dendritic spines and shafts. Axon collaterals input to the neocortex and are believed to use
of pyramidal cells are likelv also to be part of glutamate and / or aspartate as their neuro-
the cortical glutamatergic system . At the transmitter. These amino acids are quick act -
synaptic level, glutamate acts via several ing, potent , excitatory neurotransmitters that
pharmacologically characterized receptors, are well -suited for neuronal systems such as
including NMDA ( N- methyl - D-aspartate), thalamocortical circuits that convey precise,
kainate, AMI’A («-amino-3-hydroxy-5 methyl - topographically organized information that
- -
4 isoxazolepropionic acid ), AP4 ( L amono - requires a high degree of synaptic security to
phosphonobutyric acid ), and metabo tropic - maintain the level of fidelity necessary for the
receptors (80). These receptors have a differ - transmission of sensory information. As seen
ential distribution in the cerebral cortex: earlier, thalamocortical input terminates prin -
kainate receptors are denser in layer V-VI , cipally in layer IV , while corticocortical pro-
whereas AMPA and NMDA receptors are jections are mainly to layers II and IV if they
concentrated within layers 1 and III . are characterized as forward projections, and
The pyramidal cell is the key excitatory layers more superficial and deep if they are
neuronal class in the neocortex. All cortical characterized as feedback projections. The
output is mediated through pyramidal cells, thalamocortical and corticocortical fibers
and , as such, the intrinsic neocortical activi- form asymmetric synapses principally on
ties can be viewed simply as a means to regu - spines of pyramidal and stellate cells, as well
late pyramidal cell activity ( 264 ). The gluta- as on inhibitory interneurons.
mate / aspartate excitatory inputs to the
pyramidal cells can be divided into intrinsic y - Aminobutyric Acid
afferents such as recurrent collaterals from
other pyramidal cells and excitatory interneu - While there are multiple excitatory inputs
rons, and extrinsic afferents which derive to drive a pyramidal cell, there are also sev -
from the thalamus and other cortical regions. eral inhibitory afferents that regulate the fir-
Recurrent collaterals of pyramidal cells ing rate of pyramidal cells. These inhibitory
give rise to both a vertical and horizontal sys- influences come almost entirely from local in -
tem of excitatory fibers that appears to paral - terneurons that lack spines and utilize y-
lel the vertical and horizontal system of in - aminobutyric acid (GABA ) as their neuro-
hibitory projections that arise from cortical transmitter ( 129, 137). The GABAergic
interneurons and use y-aminobutyric acid neuronal population comprises a wide vari-
(GABA ) as a neurotransmitter. One of the ety of intrinsic nonpyramidal cortical neu -
f
4 A ’*
Figure 20.6 Layer V of the primary motor cortex (M- l) in the rat processed immunocytochemically for glutamate (A)
and aspartate (B). Colloidal gold coupled with enzymatically Inactive horseradish peroxidase conjugated to wheat
germ agglutinin (WGAapoHRP - Au) injected into the spinal cord retrogradely labels corticospinal neurons ( black
granules). Three types of neurons can be seen: (a) cells immunoreactive for glutamate or aspartate only (arrows), (b)
cells retrogradely labeled only with WGAapoHRP- Au (arrowheads), and (c) cells retrogradely labeled with
WGAapoHRP- Au and immunoreactive for either glutamate or aspartate ( tailed arrows). Calibration bar : 50 |im
rons (e.g., basket cell, chandelier or axoaxonic pyramidal output neurons irrespective of
cell, bitufted cell, and clutch cell ) whose as- their sources of excitation . Thus, the in-
piny dendrites form both vertical and hori - hibitory nature of GABA action can be under-
zontal arborizations. The unique feature of stood in terms of control of the cortical inte-
GABAergic cortical interneurons is their ex- gration and regulation of information
tensive synaptic contacts with receptive sur- processing with small cortical domains (80,
faces of pyramidal neurons ( Fig. 20.7). These 241 ).
intrinsic neurons are organized to inhibit The various types of GABAergic interneu-
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-> ~ «+ r
*
-
'
~ * • family on cortical neuronal activity is largely

;• <• >
i •
^
*
•' * v
' mediated by the GABAA receptor subtype
(80 ) . Cortical sites identified as the focus of
V * >
^ chronic epileptiform activity, demonstrate
significant loss of GABA in cells and termi -
nals. Barbiturates and anticonvulsant drugs
are considered to potentiate GABAergic inhi -
bition .
v rm ~ *
•• >r t0 -
Neuroactive Peptides
- / vv- > Peptides present in the cerebral cortex in -
i ./
*
'
.1
' •
- clude cholecystokinin (CCK ), vasoactive in -
testinal polypeptide ( VIP), neuropeptide Y
( NPY ), somatostatin (SS), substance P (SP ),
and corticotrophin releasing factor (CRF)
(84). Many of these peptides are colocalized
with GABA in cortical interneurons. The cel -
lular action of the peptides is poorly under -
stood , but they are presumed to function as
modulators of excitatory amino acids, GABA,
i -v v * and / or monoamine effects. For example,
when iontophoretically applied on cortical
neurons, SS appears to increase acetylcholine
excitatory action through the inhibition of
* • V v^ ,
second messengers (e.g., adenylate cyclase
, / ^ and G protein ). Another example is the inter-
/4 4
^ ' action between VIP and noradrenaline. VIP -

Figure 20.7 Glutamic acid decarboxylase (GAD)-im-
containing neurons in the cortex form a ho-
munoreactive terminals (arrows) on the soma and proxi- mogeneous population of intracortical ,
mal dendrites of a pyramidal neuron in the motor cortex bipolar neurons, that are devoid of GABA .
of a rhesus monkey . The material was photographed Noradrenaline and VIP act synergistically to
with IMomarski optics. Calibration bar: 20 (im. increase cAMP levels in neocortex. Noradren -
aline, by activating specific oil receptor sub-
type, potentiates the increases in cAMP
elicited by VIP. When VIP and noradrenergic
rons act at specific levels on the pyramidal neurons are simultaneously active, they may
cell via synapses of the symmetric type. Some act in a functionally coordinated manner to
of these neurons (e.g., basket cells) are the generate a "cortical hot-spot" where cAMP
principal source of horizontally directed in - levels are drastically increased in comparison
hibitory inputs to the soma, proximal den- to surrounding regions to activate those in -
drites, and apical shafts of pyramidal neu - tracellular processes that are regulated by
rons, while others (e.g., chandelier cells ) -
cAMP dependent phosphorylation . Thus,
synapse exclusively on the initial axon seg- sensory stimulation within certain contexts
ment of pyramidal cells. A large proportion ( i.e., heightened vigilance ) could trigger the
of the GABAergic interneurons contain the synergistic interaction between VIP and nora -
-
calcium binding protein parvalbumin, as drenaline within the terminal field of thalam -
well as a variety of neuroactive peptides such ocortical afferents in primary sensory cortex
as cholecystokinin, somatostatin , neuropep- (84, 264 ).
tide Y , substance P, and corticotrophin releas- Besides their role in neurotransmission,
ing factor. The action of GABA in the neocor - some of the neuroactive peptides present in
tex is mediated by two types of receptors the cerebral cortex may play a role in the con -
GABAA and GABAlt. The GABAA receptor is trol of local metabolism and blood flow . Such
characterized by a competitive site and by a is the case for neurons containing NPY or
VIP, which are found in superficial layers ventral tegmental area ( VTA ) complex at the
close to capillaries. VIP is a potent vasodilator base of the midbrain ,
and NPY is a vasoconstrictor ( Fig. 20.8). The ascending monoaminergic projections
are highly divergent systems in that a given
Monoamines nucleus or individual neuron can innervate a
vast expanse of neocortex (92, 237, 241 , 261,
There are distinct noradrenergic ( NA ), 293). The cortical termination patterns of
serotoninergic (5- HT ), and dopaminergic these extrathalamic systems differs funda -
( DA ) projections to the cerebral cortex. To- mentally from that of thalamocortical and
gether with the cholinergic cortical projec- cortical afferents. The well-known columnar ,
tions, these monoaminergic neurons form radial organization of the neocortex that is
an important extrathalamic afferent system driven by the thalamo- and corticocortical af -
that circumvents the presumed obligatory ferents, differs markedly from the tangen-
synapse in the thalamus to directly reach the tially organized extrathalamic afferents in
cerebral cortex . The NA projection originates which single axons may innervate not only
in the locus coeruleus ( LC ) located in the dor - different columns within a functional region
somedial portion of the pontine tegmentum but different functional areas ( 264). The thal-
( Figs. 13.35 and 13.36). The 5- HT projection -
amo and corticocortical projections are in -
arises from the dorsal and median raphe nu - volved in both serial and parallel processing
clei in the medial portion of the caudal mid - of information through precise excitatory ac-
brain tegmentum. The DA projection origi- tions on specific subsets of cortical neurons,
nates from the substantia nigra (SN ) and In contrast, the monoaminergic ascending
A K
R
9 4 V A i
Figure 20.8 Neuropeptide Y (NPY)-immunoreactive neurons in the deep layers ot the frontal cortex (A) and in the
hilus (H) of the dentate gyrus (B) of the squirrel monkey In B note the dense NPY - immunoreactive terminal field in the
external portion of the molecular layer (M). which contrasts with the relatively poor innervation of the granular layer
(G). NPY has been shown to coexist with somatostatin in some cortical neurons in the rat and humans. Calibration
bars 50 |im (A) and 100 |im (B) A and B are darkfield and brightfield photomicrographs, respectively .
projections are able to modulate various frontal and parietal lobes, than in prefrontal ,
state-dependent cortical activities through temporal, and occipital lobe areas (92, 237,
their general effect on vast neuronal assem - 241, 261 ). Furthermore, detailed analysis of
blies. cortical areas subserving a particular modal -
ity such as vision indicates that functional re-
NORADRENERGIC INNERVATION lated regions tend to share common and dis-
tinguishable densities of NA innervation
Axons from individual LC neurons ar- ( 264 ).
borize within multiple cortical areas that are Locus coeruleus neurons are most active
often distributed over widely separate re - during waking, less active during slow-wave
gions. These highly divergent axons run prin - sleep, and silent during rapid -eye-movement
cipally in layer VI where they form a continu - ( REM ) sleep. Within the waking state, the
ous sheet of longitudinal fine fibers overlying mean discharge rates of LC neurons increases
the white matter ( Fig. 20.9 ). Along their ros- proportionally with increases in the level of
trocaudal trajectory through the cortical behavioral arousal or vigilance. Electrophysi -
hemisphere, these noradrenergic axons pro- ologic studies indicate that noradrenaline en -
vide numerous collateral branches to various hances evoked activity relative to sponta -
cortical areas. In primates, the NA innerva - neous activity such that it increases the
tion of the cortex is much more prominent in "signal - to- noise" characteristics of cortical
primary motor and somatosensory cortices, neurons. Noradrenaline can also enhance the
and their related association regions in the effect of iontophoretically applied GABA or
ChAT DBH
Figure 20.9 Cholinergic and monoaminergic innervation of the primary auditory cortex of a macaque monkey An-
.
tisera against choline acetyltransferase (ChAT). serotonin (5-HT) dopamine-|i-hydroxylase and tyrosine hydroxylase
were used to visualized immunohistochemically the cholinergic, serotoninergic. noradrenergic, and dopaminergic
fibers, respectively .
ACh , suggesting that it can enhance both in - explained by the existence of up to seven dis-
hibitory and excitatory inputs. Coactivity of tinct serotoninergic receptors (5- HT , to 5-1 IT;
LC terminals appears to "enable" other sys - subtypes) ( 282). The most common response
tems converging on the same target neuron to to iontophoretically applied 5- HT or electrical
transmit more effectively during the period stimulation of the median raphe nucleus,
of simultaneous activity regardless of however, is marked inhibition of sponta -
whether the primary effect is inhibition or ex- neous activity. Additionally, it has been sug-
citation (13, 92, 241 , 264 ). gested that 5-HT, like NA , may have primar-
Four types of adrenergic receptors have ily a modulatory role, rather than a classical
been pharmacologically characterized in the inhibitory or excitatory action . Serotoninergic
primate brain : al , « 2, [31 , and [32. In the neurons exhibit activity that is most strongly
human cerebral cortex, «1 receptors abound correlated with behavioral "state" while no-
-
in the external layers ( I -ll ) and layer VI. Re radrenergic neurons display more phasic
ceptors of the [i subtype have a lower concen- fluctuations, associated with "attentiveness"
tration than u receptors, but they also pre- ( 241 , 264).
dominate in the superficial layers. Overall,
adrenergic receptors are more abundant in DOPAMINERGIC INNERVATION
prefrontal, motor, and somatosensory regions
than in parietal, temporal, and occipital areas. Earlier biochemical and fluorescent histo-
chemical studies in rodents emphasized the
SEROTONINERGIC INNERVATION propensity for midbrain dopaminergic ( DA )
neurons to terminate more massively in
The 5- HT innervation of the cerebral cor - frontal cortex than in other cortical regions.
tex is more profuse than the noradrenergic Immunohistochemical studies using antibod -
innervation and involves all cortical layers. In ies against tyrosine hydroxylase (TH ) sug-
primates, the regional and laminar specializa - gested that the DA innervation extends
tion of the 5- HT innervation is greater than in throughout the four lobes of the primate neo-
nonprimates. This has been demonstrated by cortex, with striking regional variations that
detailed studies of the primary visual cortex. coincide with cytoarchitectonic and func-
The 5- HT innervation is particularly dense in tional subdivisions. In both New World and
layer IV , which is the primary recipient of Old World monkeys, the density of TH -im -
thalamocortical afferents ( Fig. 20.9 ). Two munoreactive fibers is greatest in primary
classes of 5- HT fibers can be found in the neo- motor cortex and decreases in the more ros-
cortex: very fine, highly tortuous fibers with tral prefrontal regions. It decreases markedly
very small varicosities, and larger caliber across the central sulcus from motor to pri -
fibers with larger, more beaded varicosities. mary somatosensory cortex, but increases
Each type of fiber appears to originate from again caudally in the parietal and temporal
distinct raphe subnuclei and has differential cortices. The primary visual cortex possesses
vulnerability to amphetamine derivatives the lowest density of TH - positive fibers.
( 242). In primary visual cortex, serotoninergic Overall, The DA innervation of the primate
fibers terminate principally on distal den - cerebral cortex is such that fibers preferen -
drites of both pyramidal and nonpyramidal tially innervate motor relative to sensory re-
neurons. Thus, the 5- HT system is well-situ - gions, limbic and high level sensory associa -
ated to modulate the activity of both in- tion relative to primary sensory areas, and
terneurons and projection neurons that sub- auditory association relative to visual associ -
serve visuospatial analysis. ation areas ( 264).
In unanesthetized , behaving animals, 5- The laminar pattern of fibers in a given re -
1 IT neurons in the dorsal raphe nucleus ex - gion is correlated with fiber density . In very
hibit slow , regular discharge patterns during sparsely innervated regions, DA fibers are
quiet waking, and increases in firing with limited to layer 1, and areas of an intermedi -
phasic arousal. Furthermore, mean discharge ate density have DA fibers in layers I , II , su -
rates decrease during slow-wave sleep and perficial III , and deep V -VI layers ( Fig. 20.9 ).
raphe neurons become almost silent during The primary motor cortex displays fibers in
RFM sleep ( 16, 159, 241 , 261 ). Different re- all layers, while layer IV has the lowest den-
sponses can be obtained from cortical neu - sity of innervation throughout the neocortex.
rons following iontophoretic application of 5 - Thus, the DA ascending system appears to be
-
HT. These various effects of 5 1 IT may be in a position to influence the activity of corti -
cocortical and possibly corticostriatal circuits overall density of innervation in motor cortex
rather than thalamocortical circuits, and of primates suggests that cells of origin of
high-order integrative processes rather than major descending motor pathways are also
the more analytic'
aspects of sensory process- innervated by dopamine.
ing ( 232, 233). Dopamine is also likely to play an impor-
The action of dopamine is mediated tant role in cognitive and affective brain func-
through a large family of specific receptors tions. For instance, psychopharmacologic
,
( D to Dd, the most well-characterized mem- studies reveal that performance on cognitive
bers of which are the D, and D2 receptor sub- tasks dependent on the integrity of the pre-
types. Ligand binding studies suggest that frontal cortex are affected by manipulation of
the D, receptor is far more abundant than the the DA system (45, 124). Furthermore, follow-
D: receptor in monkey neocortex, and that D, ing a suggestion by the Scandinavian phar-
binding is generally highest in layers l-III and macologist Arvid Carlsson (53), several stud -
D: is generally highest in layer V (80, 234 ). ies found that, despite their differences in
Because of the lack of cellular resolution of chemical structure, antipsychotic agents
the current ligand binding methods, there re- ( neuroleptics) block dopamine receptors. It
mains much uncertainty regarding the exact was, therefore, thought that an excess of
cellular location (on pre- or postsynaptic dopamine transmission underlies at least
neural elements, or even on glial cells ) of some aspects of the pathogenesis of schizo-
these receptors. It is, nevertheless, believed phrenia . Schizophrenia is a devastating men -
that different dopamine receptor subtypes tal illness that comprises both positive and
may predominate on different classes of negative symptoms. The positive symptoms
pyramidal neurons. This is supported by data characterize the psychotic period of the dis-
from molecular biology showing, for exam- ease and include distinctive behaviors, such
ple, that virtually all of the giant Betz cells of as bizarre delusions, prominent hallucina-
the monkey and human motor cortex express tions, and disordered thoughts. The negative
„
mRNA coding for D D2, and Ds receptor or residual symptoms are encountered in the
subtypes. nonpsychotic phase and refer to the absence
In unanesthetized behaving animals, DA of normal social and interpersonal function.
neurons in the substantia nigra pars com- The introduction of antipsychotic drugs in
pacta -ventral tegmental area complex (SN - the 1950s has markedly improved the treat -
VTA ) discharge more rapidly during height - ment of the psychotic phase of schizophrenia .
ened motor activity, but unlike NA and 5- HT Antipsychotics can be divided into two major
neurons, they do substantially decrease their groups that act on different dopamine re-
activity during or after various stressful or ceptors. The first group is termed typical
arousing stimuli. The most striking change is antipsychotics and include phenothiazine de-
a prolonged suppression of activity that ac- rivatives (e.g., chlorpromazine), butyrophe-
companies orientation toward and fixation of nones ( haloperidol ), and thioxanthene deriv-
a novel or meaningful stimulus. Iontophoreti- atives (e.g., chlorprothixene). The typical
cally applied dopamine elicit both excitation antipsychotic drugs bind to D2 receptors and
and inhibition of cortical neurons while elec- produce basal ganglia side effects such as tar-
trical stimulations of SN-VTA neurons atten- dive dyskinesia . The second group is referred
uate the excitatory effect on cortical neurons to as atypical antipsychotics and include princi-
of thalamic stimulation. pally the dibenzodiazepines (e.g., clozapine ).
The regional and laminar distribution of The atypical antipsychotic drugs bind to D4
DA fibers suggest that the pyramidal cells of and D4 receptors and do not produce tardive
origin of both corticocortical and corticostri - dyskinesia. The D, and Ds receptors are ex-
atal systems are likely targets of DA innerva - pressed in neurons of the cortex and hip-
tion ( 232, 233). Indeed , DA synapses on pocampus and have a low affinity for most
spines of layer III pyramidal cells in the pre- types of antipsychotic drugs. The D2 recep-
frontal cortex have been visualized by using a tors are expressed by neurons of the striatum
combined Golgi-EM-immunohistochemical and limbic structures such as the nucleus ac-
approach (125). Such layer II pyramidal cells cumbens, the amygdala , the hippocampus, as
are very likely to be corticocortical projection well as the cerebral cortex. They have a high
neurons, suggesting that dopamine may be in affinity for typical antipsychotic drugs. The
a position to modulate the activity of circuits D4 and D4 dopamine receptors are restricted
linking association cortices. Furthermore, the in their expression to limbic structures and
cerebral cortex, and are only weakly ex- damental cellular pathology of the cerebral
pressed in the basal ganglia . This selective cortex. However, a clear and reproducible
distribution may explain why atypical an- cellular pathology as impressive as that
tipsychotic agents, such as clozapine, that found in Parkinson's disease, Alzheimer's de-
bind selectively to D, and D4 receptors, do mentia, or Huntington's chorea has not yet
not produce basal ganglia side effects (340, emerged from studies of schizophrenic
366 ). brains. Dopamine may also act in conjunction
The "dopamine hypothesis" of schizo- with several other chemospecific neuronal
phrenia has received support from two sets systems. In this perspective, it is worth noting
of findings in humans. First , drugs that in- that the addictive drug phencyclidine ( PCP,
crease the level of dopamine (e.g., L-DOPA, also known as angel dust ) produces psy-
cocaine, and amphetamine) cause a psychosis chotic behavior by binding to NMDA recep-
that resembles the paranoid subtype of schiz- tors. Furthermore, a reduction in the number
-
ophrenia. Second, the brains of schizophrenic of 5-HT2 receptors and 5 HT reuptake sites
patients studied at autopsy contain an in- has been found in the prefrontal cortex of
creased number of D2 receptors in the cau- schizophrenic patients (282). These findings
date nucleus and the ventral striatum. This indicate that psychotic behavior can probably
increase is particularly prominent in patients be produced by interfering with several
with positive symptoms and has been transmitter systems other than dopamine, ei-
demonstrated in positron emission tomogra- ther alone or in combination (54).
phy ( PET) scans of living patients (185). How-
ever, these changes in D2 receptors might be Acetylcholine
secondary to disturbances elsewhere in the
brain that are mediated by dopamine recep- Cholinergic axons in the cerebral cortex
tor mechanisms. Moreover, there is still no have been visualized by both acetyl-
evidence that excessive activity of DA cells cholinesterase ( AChE) histochemistry and
actually contributes to the defect underlying choline acetyltransferase (ChAT) immunohis-
schizophrenia . tochemistry ( 204). Although ChAT is consid -
The most widely accepted version of the ered a more reliable marker than AChE for
DA hypothesis of schizophrenia suggests that cholinergic neurons, both procedures reveal a
there are two different disturbances in similar pattern of innervation by cortical
dopaminergic transmission: (a ) an increase in cholinergic fibers (253). In primates, choliner-
activity of the mesolimbic subcortical compo- gic fibers innervating the cortex arise princi-
nent of the dopaminergic system, which ac- pally from neurons in the basal nucleus of
counts for the positive symptoms and re- Meynert (252) (group Ch 4 of Mesulam, et al.
sponds to antipsychotic drugs that probably ( 254)), which lies ventral to the globus pal-
act via D2, D5, and D4 receptors, and ( b) a de- lidus, and less abundantly from neurons in
crease in the activity of the mesocortical com- the vertical limb of the diagonal band of
ponent of the DA system, which accounts for Broca in the septal area (group Ch 2). The
the negative symptoms and does not respond cholinergic neurons in the medial septal nu -
effectively to antipsychotic drugs (376). It is cleus project specifically to the hippocampal
proposed that the mesocortical DA pathway formation (254) (see Chapter 18). Like the no-
to the prefrontal cortex normally inhibits the radrenergic and serotoninergic systems, the
mesolimbic component by feedback inhibi- cholinergic fibers innervate virtually the en-
tion, and that the primary defect in schizo- tire cortical mantle in a highly divergent
phrenia is a reduction in prefrontal activation manner. However, different subdivisions of
by the mesocortical pathway, which leads to the basal nucleus project preferentially to
disinhibition and overactivity in the mesolim- major regions of the cortex, revealing the ex-
bic pathway (376). istence of a crude topography in the organi-
The DA hypothesis of schizophrenia is ob- zation of the cholinergic cortical afferents.
viously of great interest and appears to be The cholinergic cortical innervation dis-
supported , at least in part, by data derived plays specific regional patterns. There is a
from animal studies. However, there is a high density of cholinergic innervation of the
clear lack of evidence from human studies to limbic cortex, less dense but very substantial
fully support this theory. The involvement of innervation of primary sensory and motor
dopamine in schizophrenia could be sec- cortex, and still less dense innervation of as-
ondary to, or strongly linked , to a more fun- sociation cortex. In all cortical areas, layer I is
the most densely innervated, followed by lay- Electrophysiologic recordings from neu -
ers II and III . In association cortex, the deep rons of the basal nucleus of Meynert in be-
layers ( V and VI ) are more densely inner- having monkeys, reveal that some neurons
vated than the deep portion of layers III and exhibit a phasic change in discharging during
IV . This is not the case in densely innervated delivery of food reward or show a short la -
primary sensory areas such as primary audi- tency of response when the monkey is given
tory and visual cortices, where there is a very a food stimulus ( 72 ). These and other findings
dense innervation of layers I and IV , rela- suggest that, in contrast to the overlying pall -
tively dense innervation of layers II and III , idal neurons whose neuronal activity is
and sparse innervation of layers V and VI. tightly coupled to body movement, neurons
This laminar pattern suggests that in primary of the basal nucleus may play a role in re-
sensory areas cholinergic neurons are able to ward , learning, and attentional mechanisms.
modulate activity in the same layer and per- The basal nucleus of Meynert has attracted
haps on the same neurons as those receiving much attention because of its possible in-
direct thalamic input . volvement in the pathophysiologic mecha -
The action of acetylcholine at the cortical nisms underlying the severe memory and
level is mediated by both muscarinic and cognitive function disorders that occur in se -
nicotinic cholinergic receptors ( 204, 241, 244 ) . nile dementia of the Alzheimer type. Two
In the human cerebral cortex, the two sub- major lines of evidence support this involve-
types of muscarinic receptors ( M , and M 2) are -
ment: (a ) compared to age matched controls,
relatively uniformly distributed among the the cerebral cortex and hippocampus in pa -
different cortical regions, with higher density tients with Alzheimer's disease ( AD) show
in layer IV . The cortex shows higher densities 60-90 % reduction of the cholinergic markers
,
of M binding sites, but the deep layers show ChAT and AChE ( 69, 303); and ( b) compared
relatively higher M 2 sites than the upper lay - -
to age matched controls, the basal nucleus in
ers. Furthermore, the M 2 receptor subtype is AD patients show a 70-95% cell loss (64, 382 ).
preferentially associated with the primary These two lines of evidence led to the devel -
sensory areas and is much denser in these opment of a model for the pathogenesis of
areas than the M , sites ( 244, 264 ). Immunohis- neuritic (or senile) plaques ( 64). The abun -
tochemical studies have shown the presence dance of neuritic plaques, as well as the pres-
of either muscarinic or nicotinic receptors on ence of neurofribillary tangles and granulo-
the soma and apical dendrites of pyramidal vacuolar degeneration, are neuropathologic
cells in layers II - III and V . Knowledge about hallmarks of Alzheimer's disease. In this
the exact location of these two types of model, a neuron of the basal nucleus would
cholinergic receptors on cortical neurons is first show cytoskeletal abnormalities in the
important functionally, since muscarinic and distal intracortical axons due to an unidenti -
nicotinic receptors have different effectors at fied pathologic factor or process. The axon
the molecular level and could thus differen- then deteriorates toward the cell body
tially influence the activity of specific sub- -
(dying back phenomenon ), and clusters of
groups of pyramidal projection cells. The dystrophic AChE-rich neurites form the im-
nicotinic response is mostly ionotropic ( i.e., mature plaques. With time some of the neu -
glutamate-like ), whereas the muscarinic site rites degenerate and eventually disappear,
is linked to second messengers. leaving an amyloid plaque as the only evi -
Although data on receptors suggest that dence of this process. Ultimately, the entire
pyramidal cells are the prominent target of neuron would degenerate ( 64 ). This complex
cholinergic fibers, both pyramidal and non - sequence of events, involving the death of
pyramidal cells were seen to receive choliner - multiple neurons over time, can indeed lead
gic synapses. These synapses are predomi - to serious impairment of memory and cogni-
nantly of the asymmetric type and occur on tion , a high density of plaques in the cortex, a
dendritic spines and shafts of cortical cells. marked reduction of the cholinergic markers
The light and electron microscopic data cur- at cortical levels, and severe loss of cells in
rently available indicate that the primary the nucleus basalis.
synaptic target of the cholinergic fibers are Although the loss of cholinergic neurons
distal dendritic shafts in the superficial layers in the basal nucleus in cases of AD appears
( particularly layer I ) and the more proximal highly specific ( 292 ), it is far too simplistic to
dendrites of layer IV neurons in primary sen - consider this disease exclusively a cholinergic
sory areas. dysfunction. In fact, other neurotransmitters
or neuromodulators, particularly noradrena - the arrangements and types of cells, as well

line, serotonin, somatostatin, and neuropep- as the patterns of myelinated fibers, have
tide Y, are also depleted in AD. Furthermore, been used to construct several fundamentally
attempts to develop cholinergic pharma - similar maps of the cortex composed of dis-
cotherapies to alleviate the cognitive and be- tinctive cytologic areas ( Fig. 20.10). Campbell
havioral deficits in AD have been largely (52) described some 20 cortical areas, whereas
unsuccessful (87). It appears that , both struc- Brodmann ( 44 ) increased the number to 47
turally and functionally, AD is predomi- and von Economo ( 368) to 109. The Vogts
nantly a disease of the cerebral cortex, in ( 371 ) parceled the human cerebral cortex into
which specific cortical cell populations are af - more than 200 areas. Even the last number is
fected . There is evidence that the pyramidal apparently insufficient, since other investiga -
cells that furnish the corticocortical projec -
tors have found a number of distinctive cy-
tions and use glutamate as their neurotrans- toarchitectural areas in regions previously
mitter are particularly vulnerable in AD. Data considered homogeneous ( 20, 325). The brain
from several sources support the notion that map of Bailey and von Bonin (18) utilizes var-
AD involves a global cortical disconnection ious colors to distinguish distinctive cytoar -
syndrome, in which each cortical region func -
chitectural features. These authors felt that
tions in isolation rather than in a cohesive the concept of absolutely sharp areal bound -
and synthetic manner. Such a condition aries was carried to absurd lengths and that
would be particularly devastating in the most brain maps failed to properly represent
human brain , given the dependence on cor- transitional areas. Brodmann's chart , which is
ticocortical connections of functions such as the most widely used for reference, is shown
cognition ( 264 ). in Figure 20.10. This cytoarchitectural map of
the human cortex can be compared with the
CORTICAL AREAS lateral view of the brain shown in Figure
20.11 .
The cerebral cortex does not have a uni - According to von Economo (368), all corti-
form structure. It has been mapped and di- cal structure is reducible to five fundamental
vided into a number of distinctive areas that types, based primarily on the relative devel -
differ from each other in total thickness, in opment of granule and pyramidal cells.
the thickness and density of individual lay -
Types 2, 3, and 4, known respectively as the
ers, and in the arrangement of cells and frontal, parietal, and polar types, are homo-
fibers. Structural variations are so extreme in typical and constitute by far the largest part
-
some areas that the basic six layered pattern of the cortex. Types 1 (agranular ) and 5 (gran -
is practically obscured . Such areas are termed ular ) are heterotypical and limited to smaller
heterotypical cortex , as opposed to homotypical , specialized regions ( Figs. 20.12 and 20.13).
which refers to cortex in which the six layers Agranular type cortex ( type 1 ) is distin -
are easily distinguished ( 44 ). Differences in guished by its thickness and the virtual ab-
Figure 20.10 Cytoarchitectural map of human cortex A. Convex surface. B . medial surface
sence of granule cells ( Figs. 20.12 and 20.14 ). its thinness, its well-developed granular lay-
Pyramidal cells of layers III and V are well- ers, and its comparative wealth of cells.
developed and large. Even the smaller cells in Granular type cortex or koniocortex ( type 5)
layers II and IV are predominantly pyrami- is extremely thin and is composed mainly of
dal-shaped , making it difficult to distinguish densely packed granule cells ( Figs. 20.12 and
individual layers. The agranular type cortex 20.15). These are found not only in layers II
is represented classically by the cortex of the and IV, but the other layers, especially layer
precentral gyrus. III, show large numbers of such small cells
Frontal type cortex ( type 2) is relatively and a consequent reduction of the pyramidal
thick and shows six distinct layers ( Fig. cells. The most striking example of this type
20.14 ). Pyramidal cells of layers III and V are is the calcarine cortex ( Fig. 20.15).
large and well-developed , as are the spindle The general distribution of these five types
cells of layer VI ( Fig. 20.12 ). Although the of cortex is shown in Figure 20.13. The agran-
granular layers are distinct, they are narrow ular type cortex covers the caudal part of the
and composed of loosely arranged small tri- frontal lobe in front of the central sulcus, the
angular cells. anterior half of the cingulate gyrus, and
Parietal type cortex ( type 3) is characterized the anterior portion of the insula . A narrow
by even more distinctive cortical layers due strip also is found in the retrosplenial region
to the greater thickness and cell density of the of the cingulate gyrus and is continued along
granular layers ( Figs. 20.12 and 20.15). In this the parahippocampal gyrus and uncus. Since
type of cortex, the pyramidal layers are thin- the chief efferent fiber systems arise from
ner and their cells are smaller and more irreg- these regions, especially from the precentral
ularly arranged . gyrus, the agranular cortex may be consid -
Polar type cortex ( type 4), found near the ered as efferent or motor type cortex ( Figs.
frontal and occipital poles, is characterized by 11.13 and 12.27). The koniocortex may be re-
Central sulcus — Postcentral sulcus

Precentral sulcus - Sup. parietal lobule
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Sup frontal sulcus - Inf. parietal lobule

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1. Sup frontal gyrus 7. Angular gyrus

2. Middle frontal gyrus a Lateral occipital gyrus
3. Inf. frontal gyrus a Sup. temporal gyrus
4. Precentral gyrus 10.Middle temporal gyrus
5. Postcentral gyrus 11. Inf. temporal gyrus
6 Supramarg. gyrus 12.Cerebellum
Figure 20.11 Lateral view of human brain with identification of the major gyri and suloi
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Figure 20.12 The five fundamental types of cortical structure 1 agranular. 2 frontal 3 parieta 1 4 polar and 5
granulous (koniocortex)
Figure 20.13 Distribution of the five fun-

damental types of cortex (Fig 20.12) over
the convex (A) and the medial (B) sur -
faces of the hemisphere The agranular,
frontal, parietal, polar, and granulous (ko-
niocortex) type of cortex are indicated by
various shades of gray
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Figure 20.14 Cytoarchitectural pictures of several representative cortical areas
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Figure 20.15 Cytoarchitectural pictures of several representative cortical areas

garded as primarily sensory in character, SENSORY AREAS OF THE CORTEX

since it is found only in the areas receiving
the specific sensory thalamocortical projec- Primary Sensory Areas
tions. These areas include the anterior wall of
The localized cortical regions to which
the postcentral gyrus, the banks of the cal-
carine sulcus, and the transverse temporal
impulses concerned with specific sensory
modalities are projected constitute the pri -
gyri ( Heschl, Figs. 2.11 and 13.13).
By far the largest part of the hemispheric mary sensory areas of the cerebral cortex. Al -
surface is covered by homotypical cortex.
though certain aspects of sensation probably
enter consciousness at thalamic levels, the
Frontal type cortex is spread over the larger
anterior part of the frontal lobe, the superior
primary sensory areas are concerned espe-
parietal lobe, the precuneus, and most of the cially with the integration of sensory experi-
ence and with the discriminative qualities of
middle and inferior temporal gyri . Parietal
sensation . With the exception of olfaction, im-
type cortex includes chiefly the inferior pari -
etal lobule, the superior temporal gyrus, the pulses involved in all forms of sensation
reach localized areas of the cerebral cortex via
occipitotemporal gyrus, and the anterior
convex parts of the occipital lobe. Polar type thalamocortical projections. The organization
of the thalamus is such that all of the specific
cortex, as the name implies, covers the
frontal and occipital poles. The thalamic
sensory relay nuclei are located caudally in
the ventral tier ( Figs. 16.13 and 16.14 ). The
connections of these areas are mainly with
the association nuclei, such as the dorsome-
cortical projections of the specific sensory
dial, lateral dorsal, lateral posterior, and the relay nuclei are to localized areas in the pari -
etal, occipital, and temporal lobes. Although
pulvinar.
there is probably a primary cortical receptive
Practically every part of the cerebral cortex area for each sensory modality, each modal-
is connected with subcortical centers by affer-
ent and efferent projections. Strictly speaking, ity is not represented separately, and the pri-
there are no circumscribed cortical areas
mary sensory areas for some forms of sensa-
tion are poorly defined . Established primary
which are purely associative or projective in
character. However, there are regions from
sensory areas in the cerebral cortex are (a ) the
which the more important descending tracts
somesthetic area (somesthetic area I , S- I ), con-
sisting of the postcentral gyrus and its medial
arise, which directly or through intercalated
extension in the paracentral lobule (areas 3, 1,
centers reach the lower motor neurons for the
and 2), (b) the visual or striate area ( visual area
initiation and control of both somatic and vis-
I , V-l ), located along the lips of the calcarine
ceral activities ( 298). These primarily efferent
sulcus ( area 17), and (c) the auditory area (au -
or motor areas, from which muscular move-
ments can be elicited by electrical stimula- ditory area I , A - l ) , located on the two trans-
verse gyri ( Heschl ; areas 41 and 42; see Figs.
tion , are concentrated chiefly in the precen -
tral part of the frontal lobe. Similarly, cortical
'
2.6, 2.8, 2.11, 13.13, 16.14, and 20.10). The gus -
regions that receive direct thalamocortical
tatory area is localized to the most ventral part
(opercular ) of the postcentral gyrus (area 43).
sensory fibers from the ventral tier thalamic
The primary olfactory area , consisting of the
nuclei and from the geniculate bodies repre-
sent the primary receptive or sensory areas.
allocortex of the prepiriform and periamyg-
The remaining cortical areas, which consti - daloid regions, is not assigned numbers
under the Brodmann parcellation.
tute the largest part of the cerebral cortex in
humans, are referred to as "association
areas." Although the primary sensory and Secondary Sensory Areas
motor areas are predominant in nonprimates
in that they constitute unusually large parts The primary sensory areas of the cerebral
of the neocortex, there is considerable inter- cortex undoubtedly receive the principal pro-
mingling of functions. In primates, the pri - jections of the specific sensory relay nuclei of
mary sensory and motor areas become more the thalamus, and are the focal regions in the
specific, and there is an absolute increase in cerebral cortex where specific sensory modal -
the association cortex ( 404). Afferent fibers to ities are most extensively and critically repre-
the association areas are derived from associ- sented . Evidence suggests that near each pri-
ation nuclei of the thalamus and from pri - mary receptive area there are cortical zones
mary sensory areas of the cortex. which may receive sensory inputs directly
20 Cerebral Cortex 887 -
from the thalamus, from the primary sensory 20.10 and 20.16 ) ( 49, 173). In the postcentral
area, or from both ( 49, 98, 145). Cortical region , there is a definite anteroposterior gra -
zones, adjacent to primary sensory areas, blit dient of morphologic change, but the gradi -
outside of the principal projection area of the ent is not uniformly gradual . The anterior
specific sensory relay nuclei of the thalamus, part, area 3, is clearly distinguishable from
are referred to as the secondary season/ areas. the posterior part, while areas 1 and 2 show
Secondary sensory areas have been defined more gradual morphologic changes. Area 3
primarily in animals by recording evoked po- lies along the posterior wall of the central sul -
tentials in response to sensory stimuli (3, 49, cus. Its transition with area 4 anteriorly is not
145, 165, 305, 359, 379, 407, 409 ). Secondary sharp and most of it lies in the depths of the
sensory areas are smaller than the primary central sulcus ( Fig. 20.16). Cortical area 3 is
sensory areas, and the sequence of represen- characterized by its thinness and by the fact
tation is the reverse, or different from that that layers 11, III , and IV tend to fuse with
found in the primary areas. Ablations of sec- each other (308) and are composed of densely
ondary sensory areas produce relatively packed granule cells (368). It lies along the
minor sensory disturbances compared with posterior wall of the central sulcus and is di -
those resulting from ablations of primary sen- vided into two parts, 3b on the posterior wall
sory areas. of the sulcus and 3a in the depths of the cen -
Secondary sensory areas, defined primar- tral sulcus ( Fig. 20.17). Areas 1 and 2 forming,
ily in experimental animals, include (a ) a sec- respectively, the crown and posterior wall of
ond somatic sensory area (somatic sensory area -
the postcentral gyrus, have a six layered
II , S-1I ), located ventral to the primary sen
sory and motor areas along the superior lip of
- structure characteristic of homogenetic cortex
( Fig. 20.16 ) . The most marked differences be-
the lateral sulcus ( 49, 319, 384, 404 ) ( Figs. tween area 3 and area 1 are found in layer Ill
20.19 and 20.20 ), ( b) a secondary auditory area where cells all become pyramidal in shape
(auditory area II, A- II ), located ventral to the and there is a reduction in cell density. The
primary auditory area ( A - l ) in the cat (1, 251, transition from area 1 to area 2 is not sharply
275, 324 ), and (c) a secondary visual area ( visual defined , but is characterized by an increase in
area II , V- II ), described in the rabbit, cat, and the thickness of the cortex and an increase in
monkey (9, 145, 356, 359, 365, 403) as antero- the number of large pyramidal cells in layers
lateral to visual area I ( V - I ), and identical to III and V . The transition from area 2 to areas 5
the area defined anatomically as area 18 ( Fig. and 7 is gradual . In the latter areas, layers II
20.19). The primary and secondary visual and IV are sharply demarcated and a pro-
areas are often termed striate and extrastriate nounced columnar arrangement of cells is
areas, respectively. A second somatic sensory seen .
area has been demonstrated in humans ( 299), The postcentral gyrus receives the thala -
stimulation of which produces various sensa - mic projections from the ventral posterior nu -
tions in the upper and lower extremities. clei ( VPLc and VPM ), which relay impulses
Representation of the extremities is chiefly from the medial lemniscus, the spinothalamic
contralateral, although ipsilateral representa - tracts, the secondary trigeminal tracts, and
tion also is present. In humans, no cortical ascending gustatory pathways from the nu -
representation for the face, tongue, mouth , or cleus of the solitary tract . The majority of the
throat has been found in S-Il . Because of the cells of the ventral posterior nuclei project to
intimate functional relationships between the area 3. In the ventrobasal complex ( VB ) of the
primary and secondary sensory areas, these thalamus ( VPLc and VPM ), the central core
are discussed together. region receives cutaneous input and a thinner
outer shell receives input from receptors in
Primary Somesthetic Area (S- l) deep tissues. The inner part of the central
core project to area 3b, while the outer part of
The cortical area subserving general so- the central core (cutaneous) projects to areas
matic sensibility, superficial as well as deep, 3b and 1 ( Fig. 20.17). The narrower outer shell
is located in the postcentral gyrus and in the concerned with input from deep receptors
posterior part of the paracentral lobule. His- projects to areas 3a and 2. All thalamocortical
tologically, the gyrus is composed of three projections from the VB complex to the pri -
narrow strips of cortex (areas 3, 1, 2) which mary somesthetic cortex are somatotopically
differ in their architectural structure ( Figs. organized ( 170). Cortical area 3a in the depths
Central sulcus Postcentral sulcus
Intraparietal sulcus
Principal sulcus
Lunate sulcus
Superior temporal sulcus
Arcuate sulcus'" -
Lateral sulcus
A
%
Area 3 Area 1 Area 2
100 T
75 -
Neurons activated by
50 - - Joint movement
Cutaneous stimuli
25- -
B
Figure 20.16 A. Lateral surface of the macaque monkey cerebral hemisphere showing the extent of areas 3. 1 and .
.
2. which compose the primary somesthetic cortex Area 3 which forms the posterior wall of the central sulcus, is hid-
.
den except for a small dorsomedial region indicated in the diagram Areas 1 and 2 form the crown and posterior
wall of the postcentral gyrus. B Bar graph indicating the relative prevalence of neurons activated by cutaneous stim-
uli and|oint movement in each cytoarchitectural area of the postcentral gyrus.
of the central sulcus receives input from Although most of the information con-
group la muscle afferents ( muscle spindles). cerning thalamocortical projections is based
In the somatosensory cortex, most of the thal - upon retrograde cellular degeneration (225,
amic afferents terminate in layer IV . Area 1, 22 b, 318, 372 ), studies of discrete lesions in
however, receives exclusive projections of the ventral posterior thalamic nuclei reveal
about 3( YZ of the cells in these nuclei, but it that coarse fibers project profusely to area 3
also receives collaterals of fibers passing to while fibers projecting to areas 1 and 2 are of
area 3. Most of the fibers projecting to area 2 fine caliber and distribute terminals sparsely
appear to be collaterals of fibers passing pri - throughout these two areas (177, 178). Au -
marily to areas 3 and 1 . toradiographic studies of the projections of
Central
sulcus
Postcentral gyrus
5
LP
Deep Medial
r lemniscus
Spinothalamic
Deep VPLC . -Cutaneous tracts
cerebellar X
nuclei
Figure 20.17 Sagittal plane showing projections of thalamic subdivisions to the sensorimotor cortex Neurons in the
.
ventral posterolateral nucleus (VPLc ) (and the ventral posteromedial nucleus VPM, not shown) form a central core
(b/ue) responsive to cutaneous stimuli. An outer shell ( white) of neurons in these nuclei is responsive to deep stimuli
Input to VPLc is via the medial lemniscus and the spinothalamic tracts, while input to VPM is via trigeminothalamic
projections (not illustrated). These thalamic afferents terminate somatotopically . Cells in the outer shell project to cor -
tical area 3a (muscle spindles) and to area 2 (deep receptors) Cells in the inner central core ( blue) project to areas
3b (cutaneous). Cells in the outer central core ( lined blue) project to areas 3b and 1 (cutaneous) Input to the ventral
.
posterolateral nucleus, pars oralis ( VPLo) and the ventral lateral nucleus, pars caudalis ( VLc ) ( red), is from the con-
tralateral deep cerebellar nuclei. Cerebellar input to these thalamic nuclei is considered to terminate somatotopi-
cally in the same fashion as sensory input in VPLc and VPM. VPLo and VLc project somatotopically upon the primary
motor area (area 4)
the ventral posterior thalamic nuclei confirm receptors), while the majority of neurons in
the substantial projection to area 3, but do not area 3 are activated only by cutaneous stim -
resolve the question concerning collateral uli . Different neurons in area 1 are related to
projections to areas 1 and 2 (163-165). Be- either cutaneous or deep receptors. This dif -
cause neurons in area 3 respond preferen - ferential representation of sensory modalities
tially to light tactile stimuli and cells in areas is closely correlated with the gradient of mor-
1 and 2 are excited mainly by deep stimuli phologic change that characterizes these
and joint movement, it is expected that differ- three cytoarchitectural areas. Afferent im -
ent populations of thalamic neurons will pro- pulses from receptors in joint capsules and
ject to areas 3, 1 and 2 ( 308, 378). In the so- pericapsular tissues, stimulated by joint
matosensory cortex most of the thalamic movement, are conveyed by the posterior
afferents terminate in layer IV , but some end columns, the medial lemniscus, and thalamic -
in deep parts of layer Ill (163). relay neurons to particular cell columns in
Studies in monkeys by V .B. Mountcastle the postcentral gyrus ( Fig. 11.1 ) ( 271 ). Im -
and T. P.S. Powell indicate that the majority of pulses conveyed by this system subserve po-
neurons in the postcentral gyrus are activated sition sense and kinesthesis. Cell columns of
by mechanical stimulation, and are selec- the postcentral gyrus responsive to cutaneous
tively excited by stimulation of receptors stimuli have constant unchanging receptive
within either skin or deep tissues, but not by fields on the body surface. The majority of
stimulation of both ( Fig. 20.16) ( 268, 270, 271 ). cortical neurons driven by cutaneous stimuli
Over 90 % of the neurons in area 2 are related adapt quickly to steady stimuli. This is a sys-
to receptors in deep tissues of the body ( joint tem of great synaptic security, poised for ac-
tion at high frequency levels, and possessing S- ll , and motor cortex related to the same
the neural attributes required for discrimina - periphery are interconnected . Commissural
tive functions. connections also exist for the somatic sensory
Stretch receptors in muscles and tendons cortex. The S-l has connections with its coun-
probably do not provide information useful terpart and with S-Il on the opposite side. S- ll
in perception of joint position. Although most projects to its counterpart on the opposite
of the afferent impulses from stretch recep- side, but only to the region of S- l that repre-
tors are projected to the cerebellum ( 284, 285), sents perioral regions (176 ). Only S- I projects
the margin of the primary somesthetic area , to parietal cortex and this projection is re-
designated as area 3a , receives impulses from stricted to area 5.
la muscle afferents via the ventrobasal com- The various regions of the body are repre-
plex ( 286 ). The medullary relay centers for sented in specific portions of the postcentral
group I muscle afferents are in the rostral gyrus, the pattern corresponding to that of
part of the nuclei gracilis and cuneatus and the motor area ( Fig. 20.18) (86, 306, 354 ).
project only to the ventral posterolateral nu - Thus, the face area lies in the most ventral
cleus pars caudalis ( VPLc) ( 362 ). This region part of the postcentral gyrus, while above it
is considered a part of the somesthetic cortex. are the sensory areas for the hand , arm ,
Although fibers of the spinothalamic tract trunk, leg, and foot in the order named . The
project to the ventral posterolateral nucleus lower extremity extends into the paracentral
( VPLc) of the thalamus, fibers of this system lobule or the medial surface of the brain ( Fig.
also project bilaterally upon portions of the 2.6). The cortical areas representing the hand ,
intralaminar and posterior thalamic nuclei face and mouth regions are disproportionally
( 27, 28 , 31, Ml , 164, 165, 167, 194, 247 , 383)
'
.
large. The digits of the hand, particularly the
Cells of the VPLc project to areas 3, I and 2 thumb and index finger, are well - repre-
(S- l ), as well as to the second somatic area (S- sented . The cortical area related to sensations
II ) ( Figs. 20.19 and 20.20) ( 175-178). Both of from the face occupies almost the entire
these cortical projections are topographically lower half of the postcentral gyrus. The
organized. Studies in monkeys disclose that upper part of the face is represented above,
-
S- I and S Il are reciprocally and topographi- while the lips and mouth are represented
cally connected with each other within the below . The tongue and pharyngeal region are
same hemisphere. The remarkable feature of localized in more ventral areas. The distorted
these somatic sensory areas is the interlock - representation of the body surface in the pri-
ing of topographic subdivisions. Parts of S- l , mary sensory area is said to reflect the pe-
Figure 20 18 Somatotopic localization of parts of the body in the motor cortex Parts of the body are drawn in pro -
.
portion to the extent of their cortical representation The resulting disproportionate figure is called the motor 'ho-
munculus . " A similar pattern of localization with respect to somesthetic sense is found in the postcentral gyrus
ripheral innervation density. Those regions of crude sensory modalities, such as pain , ther-
the body with higher densities of receptor el- mal sense, and mere contact. In regard to
ements have extensive cortical representa- pain perception, experiments in animals have
tion, while those regions with relatively few revealed that the number of neurons in S-l
receptors have a minimal representation. Ac- that can be activated from nociceptors is rela -
cording to Penfield , sensations from intra-ab- tively low, considering that no other cortical
dominal structures are represented near the area appears to contain more of them then S-
opercular surface of the postcentral gyrus. I . Although pain sensation was elicited by
Most of our information concerning the pat- electrical stimulation of S-I in humans, this is
tern of representation in the somesthetic cor- an infrequent effect of such stimulation. Ab-
tex in humans was obtained from stimulating lation of S- I does not necessarily reduce pain
this region in patients operated upon under perception, and only occasionally has it been
local anesthesia (297-299). In attempts to pre- reported to relieve chronic pain. The central
sent a readily apparent visual pattern of the processing from nociceptors is far less under-
sequence of sensory representation in the stood than the processing of signals from
cerebral cortex, Penfield has drawn the "sen- other kind of receptors. The massive and reci-
sory homunculus" relating different parts of procal thalamocortical connections, as well as
the body to appropriate areas of the cortex. the thalamus itself, may play a crucial role in
The "sensory homunculus" corresponds to the perception of nociceptive and thermal
the "motor homunculus" ( Fig. 20.18). sensotry modalities.
Stimulation of the postcentral gyrus in hu - Microelectrode multiunit mapping of the
mans produces sensations described by the S-I cortex in monkeys suggests that the repre-
patient as numbness, tingling, or a feeling of sentation of the body surface may be far more
electricity. Occasionally, the patient may re- complex than indicated by earlier studies
port a sensation of movement in a particular ( 249). These earlier studies suggest two large
part of the body, though no actual movement systematic representations of the body sur-
is observed . A sensation of pain is rarely pro- face, each of which is activated by low thresh -
duced by these stimulations. Sensations are old stimuli. One representation of the body
referred to contralateral parts of the body, ex- surface is coextensive with area 3 and the
cept in response to stimulation of the face other with area 1. Each of these somatotopic
area . The face and tongue are represented bi- transformations of the skin surface has some
laterally. Position sense and kinesthetics are discontinuities. While the two fields of cuta-
represented only contralaterally in the cere- neous representation are basically similar
bral cortex. Sensory deficits caused by lesion and are approximate mirror images of each
in the postcentral gyrus are detectable only other, they differ in size and in the relative
on the opposite side. proportion of cortex devoted to the represen-
Some neurons in the primary motor cortex tation of various body parts. Because the pro-
(area 4) respond to sensory stimuli, particu- portions in each representation differ, both
larly proprioceptive inputs, at short latency. cannot be simple reflections of peripheral in-
The finding that section of the posterior nervation density. Area 2 is considered to
columns of the spinal cord in monkeys causes contain a systematic representation of deep
disappearance of peripheral receptive fields body structures. Studies in monkeys suggest
of motor cortex neurons (34, 35) led to the that the somatotopic organization of area 2
view that the medial lemniscal system could only roughly parallels area 1, and some parts
gain direct access to the motor cortex (11 ). of the body are represented in more than one
However, the distribution of medial lemnis- location. The three distinctive cytoarchitec-
cus in the thalamus is such that the possibil- tonic areas that compose the postcentral
ity of its fibers gaining synaptic access to thal- gyrus may each represent different aspects of
amocortical neurons projecting to area 4 is somatic sensation.
quite remote (165) (see Chapter 16). It is pos- Many neurons in S-I are activated only or
sible that lemniscal inputs reach the motor most easily from one receptor type, that is,
cortex via corticocortical connections from they are modality-specific. There are also neu-
areas 1 and 2, but such projections have not rons in S-I with more complex properties
yet been identified anatomically. such as large receptive fields, indicating that
The primary somesthetic cortex is not con- they receive convergent inputs from many
cerned primarily with the recognition of primary sensory neurons. For example, many
neurons are activated by movement of just the figurines for S- l . The efferent cortical con-
one joint in one direction, while others are ac- nections of S-l I are with S-l and with the pri-
tivated by several joints. Some neurons in S- l mary motor area within the same hemisphere
require a specific combination of receptor in- (165, 174, 175).
puts to be activated. Thus, some processing In addition to the S- U , there are a number
of the raw sensory information has already of small areas in the parietal and insular cor -
taken place in S- l , which appears to be more tex that respond in various ways to cuta -
than a simple receiver of sensory informa- neous stimulation ( 320). Of these, the retro-
tion . insular area seems especially significant
because it receives projections from the me-
Secondary Somesthetic Area (S- ll) dial part of the posterior thalamic nucleus
(50). Physiologic observations indicate that
This area lies along the superior bank of cells in the retroinsular cortex are activated
the lateral sulcus and extends posteriorly only from small, well-defined , contralateral
into the parietal lobe ( 404 ). In monkeys, the receptive fields located in the hand and foot
greater part of S- II lies buried in the lateral (319) . These findings raise important ques-
sulcus ( 165, 175-177 ). Representation of the tions concerning the notion that cells in the
various parts of the body is depicted in re- posterior thalamic nucleus may be specifi -
verse sequence to that found in the primary cally involved in relaying impulses con -
somesthetic area with the two face areas ad - cerned with pain and noxious stimuli to re-
jacent ( Fig. 20.19). Representation of the gions of the cerebral cortex (165, 305). They
body is bilateral in S- II , although contralat- cast doubt upon the concept that impulses
eral representation predominates. In unanes- concerned with painful and noxious stimuli
thetized monkeys, two distinct portions of S- are relayed to S- l I or the retroinsular cortex
II were identified physiologically: (a ) an via the posterior thalamic nucleus. It was
anterior part described as responding to bi- suggested that some of the response charac-
lateral low threshold somatic stimuli in teristics attributed to neurons in S- l I may be
which body regions were arranged in the se- those of cells in neighboring cortical areas,
quence of their dermatomes, and ( b ) a poste- perhaps the area referred to as 7b in the infe-
rior region responding to nociceptive stim
uli , related to asymmetric receptive fields
- rior parietal lobule (319 ).
The S- Il has been described in humans, but
and lacking a definite topographic organiza- face, mouth , and tongue regions have not
tion ( 384 ). been identified , presumably because of prox-
The boundaries of S- U in different animals imity to the primary face area ( 299 ). Stimula -
are not easily defined physiologically ( 49, tion of S- ll in the unanesthetized patient pro-
165, 319-321 , 384 ). Anatomically, S- ll is the duces sensations in the extremities similar to
area on the superior bank of the lateral sulcus those obtained by stimulating S- I.
(or buried in it ) that receives afferents from
( a ) the ventral posterior nucleus of the thala -
Primary Visual Area (V - l)
mus ( 49, 50, 177, 178), and ( b ) both the ipsilat -
eral and contralateral S- l ( 49, 98, 175, 176 ). Area 17 ( primary visual area or V- l ) is lo-
Anatomic and physiologic studies of the so
matotopic organization of S- ll in primates in -
- cated in the walls of the calcarine sulcus. It
occasionally extends around the occipital
dicate that the different body regions are rep- pole on to the lateral surface of the hemi-
resented in successive, obliquely oriented , sphere ( Figs. 16.14 and 20.10). The exceed -
cortical strips parallel with the lateral sulcus ingly thin cortex of this area (1.5-2.5 mm ) is
( 49, 48, 165, 319 ). Neurons with trigeminal re- the most striking example of the heterotypi-
ceptive fields were found rostrally in S- II and cal granulous cortex ( type 5). Layers II and
responded to bilateral stimuli ( Fig. 20.20). Re- III are narrow and contain numerous small
gions representing the hand were posterior to pyramidal cells that are hardly larger than
the face area and formed the largest compo- typical granule cells ( Fig. 20.150. A thick
nent . Regions related to the arm , trunk , and layer IV is subdivided by a light band into
hindlimbs follow in a rostrocaudal sequence. three sublayers ( Fig 20.26). The upper and
These cortical strips representing various lower sublayers are packed with small gran -
parts of the body in S- ll do not form a topo- ule cells. In the middle, lighter layer, fewer
logic map of the body surface as depicted in small cells are scattered between the large
] Primary sensory area |

j Secondary sensory area
Figure 20.19 Primary and secondary sensory areas in the cortex of the cat and monkey Somatotopic representa-
tion of different parts of the body are indicated in the primary and secondary somatic sensory areas: F, face area; l
trunk; FL forelimb; HL hindlimb Primary and secondary auditory (A -l and A -ll) and visual (V -l and V -ll) areds in the cat
brain are shown. The medial aspect of the cat brain is represented above.
stellate cells ( giant stellate cells of Meynert ). are isolated large pyramidal neurons whose
The middle layer contains the greatly thick- cell bodies may reach a height of 60 (im ( Fig.
ened outer band of Baillarger, here known as 20.150.
the band of Gennari , and is visible to the The visual cortex contains numerous
naked eye in sections of the fresh cortex ( Fig. GABAergic interneurons and fibers in layers
20.21 ). The band of Gennari has given to this II and III which exhibit a periodicity sug-
region the name area striata (or striate cortex ). gesting a correlation with the functional
Layer V is relatively narrow and poor in columnar subdivision (129, 137, 339 ). These
small cells, but scattered among these cells small neurons make symmetric, inhibitory,
Maxillary region
Central sulcus l_ . Mandibular
Intraparietal sulcus
* V region
Foot
Teeth
Leg
Arm
^-
/
/ Digits
and hand
/ C Trunk (upper )
, rm
Lateral sulcus
~Trunk (lower )
Tongue and '
intraoral structures
Foot
K'-'
B lervical region
Face Mandibular
region
Figure 20.20 Position and somatotopic organization of the secondary somesthetic area (S-ll) in the cynomolgus
monkey (Macaco fascicularis) Most of S-ll lies burled in the depths of the lateral sulcus and has been identified on
the basis of its cytoarchitecture and connections with the ventrobasal complex and projections from the primary
somesthetic cortex (S-l). In A S-ll is shown in a flattened view on the cortical surface In B. the body representation in
S-ll is outlined as determined from recordings in awake monkeys. Different regions of the body are represented by a
series of oblique strips parallel to the lateral sulcus, with the face and intraoral structures most rostral . The area In blue
represents the digits and hand, while the areas in red represent the foot . Areas designated C are regions with poorly
defined receptive fields,
Line of Gennori 16.41 ). Geniculocalcarine fibers pass in the ex-

Colconne sulcus
tcrnal sagittal stratum , separated from the wall
of the inferior and posterior horns of the lat -
eral ventricle by the internal sagittal stratum ,
and by fibers of the corpus callosum desig-
nated as the tapetum ( Fig. 2.22 ). Fibers of the
internal sagittal stratum are corticofugal
fibers passing from the occipital lobe to the
superior colliculus and the lateral geniculate
nucleus or lateral geniculate body ( LGB) (102,
103, 135, 187, 392, 400). The optic radiation
projects topographically upon the striate cor -
tex so that cells in (a ) the medial half of the
LGB, representing upper retinal quadrants
( lower quadrants of the visual field ) project to
the superior bank of the calcarine sulcus, and
( b) the lateral half of the LGB, representing
Figure 20.21 Frontal section through calcarine cortex lower retinal quadrants ( upper quadrants of
(striate cortex) showing extent of line of Gennari the visual field ) project to the inferior bank of
Welgert ' s myelin stain, the calcarine sulcus ( Figs. 16.28 and 16.41 ).
The macular fibers terminate in the caudal
third of the calcarine area , and those from the
synapses with the apical and basilar den- paracentral and peripheral retinal areas end
drites of pyramidal cells. in respectively more rostral portions. Parts of
The striate cortex ( V-I ) receives the genicu - each macular area are represented only in the
localcarine tract, whose course and exact pro- visual cortex of one hemisphere. The repre-
jection were discussed in Chapter 16 ( Fig. sentation of the macular area in the occipital
Light
' on center
"off ' ' center
a
B
••
•• *
»
Figure 20.22 A. Receptive fields of retinal ganglion cells and lateral geniculate neurons are concentric with either
an 'on" (excitatory) center and an “ off " (inhibitory) surround, or the reverse. In a, a spot of light (red) filling the “ on ”
center causes the cell to fire vigorously . If the spot of light strikes the surrounding " off " zone, firing of the neuron is sup-
.
pressed until the light is turned off. In b the responses of a cell with an “ off " center and an “on” surround are the re-
verse. B . Simple cells of striate cortex receive their input from sets of lateral geniculate neurons whose “ on" or “off "
centers are arranged in straight lines . The receptive field axis of orientation varies for simple cells, as in a, b, and c,
with excitatory areas represented by red dots and inhibitory areas by black dots. Although simple cells always have
excitatory and inhibitory areas parallel and in a straight line, these areas may be asymmetric as in d and e.
cortex appears relatively large compared surround ( 205). Retinal ganglion cells fire at a
with the macular area of the LGB ( Figs. 16.28, fairly steady rate even in the absence of stim-
16.29, and 16.41 ). Clinically, sparing of macu - ulation . An "on" response is characterized by
lar vision associated with vascular lesions in - an increased firing rate of the cell to a light
volving the occipital cortex usually is attrib- stimulus. In an "off" response, the cell's firing
uted to collateral circulation provided by rate diminishes when the light stimulus de-
branches of the middle cerebral artery ( Fig. creases. The physiologic basis for the "on"
4.8). Following occlusion of the posterior and "off " retinal responses are the concentric
cerebral artery, these collateral vessels may receptive fields with either an "on" or "off "
be sufficient to preserve some macular vi- center and the reverse type of surround ( Fig.
sion . Similar collateral circulation apparently 20.22 ). Lighting the entire retina diffusely
is not present in the cortical area represent - does not affect retinal ganglion cells as
ing paracentral and peripheral parts of the strongly as a small circular spot of light that
retina . covers only the excitatory center of the recep-
Complete unilateral destruction of the vi - tive field .
sual cortex in man produces a contralateral Cells of the LGB have physiologic charac-
homonymous hemianopia in which there is teristics similar to retinal ganglion cells, in
blindness in the ipsilateral nasal field and the that (a ) each cell is driven from a circum-
contralateral temporal field . Thus, a lesion scribed retinal region ( receptive field ), and ( b)
in the right visual cortex produces a left each receptive field has either an "on" or
homonymous hemianopsia ( Fig. 16.43). Le- "off " center with an opposing surround ( 141 ).
sions involving portions of the visual cortex, Lateral geniculate neurons are more special-
such as the inferior calcarine cortex, produce ized than retinal ganglion cells in that they
an homonymous ijuadrantanopsia , in which are more sensitive to the differences in retinal
blindness results in the superior half of the illumination than to the illumination itself .
visual field contralaterally . Homonymous Cells in different laminae of the LGB are
hemianopsia can result from lesions involv- driven from receptive fields in one eye, either
ing all fibers of either the optic tract or the ipsilaterally or contralaterally, depending
optic radiations ( Fig. 16.430, but lesions in upon the uncrossed or crossed connections
these locations tend to be incomplete and the ( 141 ). Visual processing by the brain begins
visual field defects in the two eyes are rarely in the LGB.
identical . Patients frequently are unaware of The striate cortex, anatomically far more
an existing homonymous hemianopsia and complex than the retina or LGB, does not have
complain of bumping into people and objects cells with concentric receptive fields. Cells of
on the side of the visual field defect . the striate cortex show marked specificity in
An image falling upon the retina initiates a their responses to restricted retinal stimula -
tremendously complex process that results in tion ( 140, 142, 143, 147). The most effective
vision . The transformation of a retinal image stimulus shapes are long, narrow rectangles
into a perceptual image occurs partly in the of light ("slits" ), dark bars against a light
retina but mostly in the brain . An impressive background ("dark bars"), and straight line -
series of studies by David Hubei and Torsten borders separating areas of different bright -
Wiesel in cats and monkeys provided the first ness ( "edges" ). A given cell responds vigor-
real insight into the functional organization ously when an appropriate stimulus is shone
of the visual cortex (140, 142, 143, 147 ). on its receptive field or moves across it , pro-
The receptive field of a cell in the visual vided the stimulus is presented in a specific
system is defined as the region of the retina orientation . This orientation is referred to as
( or visual field ) over which one can influence the " receptive field axis of orientation" and it is
the firing of that cell . In the retina , the recep- critical and constant for any particular cell ,
tive field comprises those receptor sets ( i.e., but it differs for other cells in the locations.
rods and cones) and other retinal neurons Cells with the same receptive field axis of
which influence the firing of one retinal gan - orientation are arranged in columns extend -
glion cell . Receptive fields of retinal ganglion ing from the cortical surface to the white
cells are circular, vary somewhat in size, and matter.
are of two types: (a ) those with an "on" ( exci- The cortical columns of the striate cortex
tatory ) center and an "off " ( inhibitory ) sur- may be looked upon as the structural expres-
round , and ( b ) those with an "off " (in - sion of the necessity to encode more than two
hibitory ) center and an "on" (excitatory ) variables. The two surface coordinates ( ec-
centricity from fovea and distance above or row slit of light that just fills the elongated
below the horizontal meridian ) encode topo- "on" region produces a powerful "on" re-
graphic representation in the visual fields. sponse. Stimulation with a slit of light having
Engrafted upon this representation are two a different orientation produces a weaker re-
more variables in columnar form concerned sponse, because it includes part of the antag-
with receptive-field orientation and ocular onistic "off " regions. A slit of light at right an -
dominance. The topographic representation gles to the optimum orientation for a
of the retinae upon the striate cortex is pri - particular cell usually produces no response
mary and for each position in the visual field 20.23) ( 138). Thus, a large spot of light
( Fig .
there is neuronal machinery for each orienta - covering the whole retina evokes no response
tion and for each eye (150 ). In the striate cor- in "simple" cortical cells, because "on " and
tex , there exist two independent and over- "off " effects balance. A particular cortical
lapping systems of columns referred to as cell's optimum receptive field axis of orienta -
orientation columns and ocular dominance tion appears to be a functional property built
columns ( 147 ). Ocular dominance columns into the cells by its anatomic connections. The
are parallel sheets or slabs arranged perpen - receptive field axis of orientation differs from
dicular to the cortical surface which are sub- one cell column to the next , and may be verti-
divided into a mosaic of alternating left eye cal, horizontal, or oblique. There is no evi-
and right eye stripes 250-500 pm in width dence that any one orientation is more com -
( 149 ) . Orientation columns are an order of mon than any other.
magnitude smaller than the ocular domi- "Simple" cells, located in layer IV, receive
nance columns ( Fig. 20.26 ). The horizontal their impulses directly from the LCB ( 142 ). A
distance corresponding to a complete cycle of typical "simple" cell receives an input from a
orientation columns, representing a rotation large number of lateral geniculate neurons
through 180°, is roughly equal to a set of left whose "on" centers are arranged in a straight
plus right ocular dominance columns with a line which corresponds to the receptive field
thickness of 0.5-1 mm ( 151 ). orientation of the "simple" cell ( Fig. 20.22 B ) .
Thus, for each area of the retina stimulated ,
ORIENTATION COLUMNS each line, and each orientation of the stimu -
lus, there is a particular set of "simple" striate
The visual cortex is subdivided into dis- cells to respond . Changing any of the stimu -
crete columns extending from the surface to lus arrangements will cause an entirely new
the white matter, with all cells within each and different population of "simple" striate
column having the same receptive field axis cells to respond .
of orientation. The many varieties of cells in "Complex" type cells, like "simple" cells,
the striate cortex have been grouped into two respond best to "slits," "bars," or "edges,"
main functional types, but it is apparent that provided the orientation is suitable. Unlike
other subtypes or varieties also exist . The "simple" cells, these cells respond with sus-
main functional cell types are referred to as tained firing as the slits of light are moved
" simple" and " complex .” across the retina , preserving the same recep-
"Simple"-type cells respond to slits of light tive field axis of orientation (142 ). These cells
having the proper receptive field axis of ori- have peculiar characteristics in that a slit of
entation . A slit of light , oriented vertically in light with the appropriate receptive field axis
the visual field , may activate a given "sim - of orientation can cause cells to fire vigor-
ple" cell, whereas the same cell will not re- ously as it moves across the retina in one di -
spond , though other cells will, if the orienta - rection , but reversing the direction of move-
tion of the slit of light is moved out of the ment of the light stimulus may produce a
vertical position . The retinal region over diminished, or different, response.
which a "simple" type cell can be influenced Although "complex" cells in the striate
is, like the receptive fields of retinal and cortex have some characteristics similar to
geniculate cells, divided into "on " and "off " those of "simple" cells, their receptive fields
areas ( Fig. 20.22 ). In "simple" cells, these cannot be mapped into antagonistic "on" and
"on" areas are not circular but are narrow "off " regions. A "complex" cell receives its
rectangles, adjoined on each side by larger input from a large number of "simple" cells,
"off " regions. The magnitude of the "on " re- all of which have the same receptive field axis
sponse depends upon how much of the "on" of orientation . Most "simple" cells in the stri-
region is covered bv the stimulus light . A nar - ate cortex are stellate cells located in layer IV
Light
Light spot
off on off
/ \
8
u I
b
Light slit
Figure 20.23 Functional characteristics of ‘simple' cells in the striate cortex

In A a small circular spot of light (o)
shone on the excitatory part of the receptive field ( red ) of a simple
cortical cell produces a weak response . A larger
spot of light ( b) shone on the inhibitory surround produces no response.
Small spots of light (a) produce vigorous re-
sponses in retinal ganglion cells and lateral geniculate neurons. The receptive
field of the simple cell shown above is
similar to a in Figure 20 22B In B a narrow slit of light shone perpendicu
lar to the receptive field axis of orientation
( red) produces virtually no response In C, tilting the slit of light produces
a weak response . In D a vertical slit of light,
which corresponds to receptive field axis of the simple striate cell, produces vigorous
a response
( Fig. 20.26 ) . The

majority of "complex" and Attempts have been made to determine
"hypercomplex" cells are pyramidal neurons the geometry and sequence of the orientation
lying in layers superficial or deep to layer IV columns in the primate striate cortex (150).
( 147, 188). "Hypercomplex" cells have the Orientation columns appear to have the form
properties of two or more "complex" cells of narrow slabs, as do ocular dominance
from which they are believed to receive their columns. The arrangement of the columns is
input . Most cells in layer IV are driven by highly ordered and recordings made along a
only one eye while cells in other layers are tangential microelectrode penetration show
driven binocularlv ( 147). There are a few cells that the preferred orientations of cells change
in layer 111 of the striate cortex that have a in a systematic fashion , in either a clockwise
-
center surround field organization, but their or counter-clockwise direction with advance-
behavior is much more complex than cells in ment of the electrode ( Fig. 20.26). There is a
the LGB. continuous variation in the preferred orienta -
These findings imply that a vast network tion with horizontal distance along the cor-
of intracortical connections relate "simple" tex. When the electrode crosses from a left -
and "complex" cells in the striate cortex in a eye region to a right-eye region , there is no
very specific fashion, and that similar noticeable disturbance in the sequence of ori -
arrangements must exist for all receptive field entation columns, which suggests a degree of
axes of orientations. Since columns of cells independence for the two systems ( Fig.
constitute the fundamental functional units of 20.26 ). The horizontal distance along the cor-
the cortex, each small region of the visual tex corresponding to a complete cycle of ori-
field must be represented in the striate cortex entation columns, representing rotations
many times, in column after column of cells through 180°, is said to be of the same size as
with different receptive field orientations. a set of left and right ocular dominance
5.0mm
'
Figure 20.24 Autoradiographic mapping of the visual system in a monkey using 2 ( CJdeoxyglucose Coronal sec -
tions of the striate cortex in an animal with the right eye occluded. The alternate dark and light striations, each 0.3-0 4
mm in width, represent ocular dominance columns. These columns are darkest in a band which corresponds to layer
IV, but they extend the entire thickness of the cortex . Arrows A and 8 point to regions without ocular dominance
columns These regions receive only monocular input . The region indicated by arrow A is contralateral to the oc -
cluded eye. The region indicated by arrow B is ipsilateral to the occluded eye and shows no evidence of radioactiv-
ity . Both arrows indicate loci believed to be the cortical representation of the blind spots
columns (0.5-1 mm ). Orientation columns are

arranged with great regularity so that a probe
moving along the cortex horizontally gener-
ally can be expected to encounter all values of
orientation in a regular sequence before any
one value is repeated (151 ). In young mon -
keys deprived of vision by suturing the eye-
lids closed , the same highly ordered sequence
of orientation columns is found in the striate
cortex ( 150 ). This finding indicates that the
orientation column system is innately deter-
mined and not the result of early visual expe-
rience.
- disc
OCULAR DOMINANCE COLUMNS
Recording from single cells at various lev -
els of the visual system offers a direct means
of determining the site of convergence of im -
pulses from the two eyes. In the LGB, the first
point at which convergence is possible, no
binocularly influenced cells have been ob-
served ( 141 ). No crossed and uncrossed optic
tract fibers overlap in layers of the LGB ( 102,
104, 128, 151 ). It has long been recognized
that the primary visual cortex receives projec- 269 L
tions via the LGB from both eyes. The recep-
tive fields of all binocularly influenced corti-
Figure 20.25 Autoradiographic montage of tangential
cal cells occupy corresponding sites in the sections of area 17 on the left in a monkey whose right
two retinas ( Fig . 16.27 ). About 80 ' , of cells in eye was removed as an adult . The left eye was injected
the striate cortex are influenced indepen - 4 months later with pH) proline. The montage shows the
normal mosaic pattern of ocular dominance columns
dently by the two eyes (142). In a binocularly
with uniformly labeled bands alternating with unlabeled
influenced cell , the two receptive fields have bands The uniformly labeled area (disc) represents the
the same organization and axis of orientation, monocular area which covers the blind spot (optic disc)
and a summation occurs when corresponding of the enucleated right eye Calibration bar : 1 mm.
parts of the two retinas are stimulated simul-
taneously .
In monkeys, binocular convergence in area gion where the other eye dominates (152). In
17 is delayed beyond the first and second layer IV the responses are monocular, while
synaptic stages ( 147, 152). Projections of the cells in other layers respond binocularly, but
LGB terminate in deep parts of layer IV with definite dominance by one eye. The
where they are segregated into a series of widths of the ocular dominance columns in -
parallel alternating stripes, one set connected nervated by the ipsilateral or contralateral
with the left eye and the other to the right eye are the same (0.5-1 mm ) (151 ). Ion-
eye. Although input to deep parts of layer IV tophoretic application of the GABA antago-
is essentially monocular, ocular dominance nist bucucullin to the visual cortex cancels the
columns extend vertically from the pial sur- "on" and "off " subregions of "simple" cells
face to the white matter, and show alternate and abolishes orientation selectivity. It also
preference for left and right eyes ( Figs. 20.24 produces a shift in ocular dominance
and 20.26 ). This columnar arrangement is columns from one eye to the other. These ef -
demonstrated by vertical electrode penetra- fects are reversible and appear correlated
tions of the striate cortex in which there is no with the loss of GABAergic inhibition .
change in eye preference ( Fig. 20.26 ). In tan - The striate cortex is organized into both
gential penetrations of the striate cortex, the vertical and horizontal systems. The vertical
electrode moves from a region in which one or columnar system is concerned with retinal
eye gives the best response to an adjacent re- position, line orientation, ocular dominance,
and perhaps detection of direction of move- generation ( 149 ). Combined physiologic stud -
ment . These functional features are mapped ies and a reduced silver staining method
in sets of superimposed, but independent show that the boundaries of ocular domi-
mosaics ( Figs. 20.24 and 20.25). The horizon- nance columns correspond with a mosaic pat -
tal system segregates cells of different orders tern of dark bands seen in tangential sections
of complexity. Cells of the lowest order (sim- of the striate cortex ( 227). Autoradiographic
ple cells), located in layer IV, are driven methods, using the principle of transneuronal
monocularly, while those of higher orders transport or 2-| l 4C|deoxyglucose ( 2- DG ) as a
(complex and hypercomplex cells), located in metabolic marker to measure glucose utiliza -
the other layers, are driven by impulses from tion, also reveal the characteristic pattern of
both eyes ( Fig. 20.26 ). ocular dominance columns ( Figs. 20.24 and
Ocular dominance columns in the striate 20.25) ( 193, 387). Two regions of the striate
cortex have been demonstrated by a variety cortex do not contain ocular dominance
of neuroanatomic techniques. After a discrete columns: (a ) the region representing the blind
lesion in a single layer of the LGB, degener- spot of the retina, and ( b) the cortical region
ated fibers can be traced to a region of the representing the monocular temporal cres-
striate cortex where bands of degenerated cent of the visual field . These regions of stri-
fibers in layer IV ( 250-500 pm ) are separated ate cortex, receiving only monocular visual
from interbands of the same extent free of de- inputs, have been identified with the 2-DG
—
Left Right
I 0.5 mm 0.5 mm Ocular
Layer dominance column
Binocular
responses -
with dominance
..
- Ft
! - Complex ' cells
4
; .V: i; .
‘i * *;
„ - *
I
T '
Monocular
responses
1 . . -rr 4r fmf j « >
A
.
A
— Simple cells
Binocular
responses
with dominance
-
f -Complex cells
•Orientation
columns
Orientation axis
Figure 20.26 Organization of ocular dominance and orientation columns in the striate cortex Ocular dominance
columns (0.25-0.5 mm) are an order of magnitude larger than orientation columns and a pair of left -right ocular
dominance columns (0.5- 1 mm) are roughly equal to a set of orientation columns representing a complete cycle ot
orientations through 180“ Input from the lateral geniculate body to layer IV is strictly monocular and consists of a se-
ries of parallel and alternating stripes, one for the left eye and one for the right eye Most of the cells in layer IV are
"simple " cells Binocularly influenced cells are predominantly " complex " cells in layers above and below layer IV A
.
recording electrode inserted tangential to the pial surface, as in arrow A will detect responses to successive stimuli
with different orientations, first with right eye dominance and then with left eye dominance , A recording electrode in-
serted vertically, as in 8, will indicate responses only to stimuli presented in one axis of orientation. About 50% of the
cells above and below layer IV will respond to binocular stimuli, but with consistent left dominance When the elec -
trode is in layer IV. monocular responses will be recorded.
/
i
j
\ !
J
\
Left
V
^
Blind spot Retinal area

corresponding
to blind spot
of left eye
Ocular dominance
columns \
Left striate — Both eyes intact

cortex
— Right eye removed
or right optic nerve
Representation of sectioned
blind spot
Figures 20.27 and 20.28 Ocular dominance columns and the blind spot in the striate cortex with the 2- ( ‘1C) -de-
,
oxyglucose metabolic mapping technique in macaque monkeys . In the animal with an intact visual system, silver
grains are distributed throughout the striate cortex with greatest concentrations In layer IV Neither the blind spot or
ocular dominance columns can be demonstrated Following removal of the right eye or section of the right optic
nerve (heavy black line ), silver grains are distributed evenly in the representation of the blind spot on the left (Figs.
20 24 A and 20.27) but no isotope is evident in the blind spot on the right (Figs . 20.24B and 20 28) Other regions of the
striate cortex demonstrated ocular dominance columns on both sides. Fibers from the ipsilateral temporal retina nor-
mally cover the blind spot of the opposite eye.
metabolic mapping technique and other au- shows a similar pattern of striped columns
toradiographic methods ( Figs. 20.24, 20.25, but no evidence of metabolic activity in the
20.27, and 20.28). The area of the optic disc in cortical area representing the blind spot ( Figs.
the nasal half of each retina transmits no vi- 20.24, 20.27, and 20.28). The cortical area rep-
sual impulses to the contralateral striate cor- resenting the monocular crescent of the right
tex. This region of striate cortex receives its visual field , which lies in the left striate cor -
sole input from the temporal half of the ipsi- tex, would not contain isotope because all of
lateral retina . its afferent input is crossed .
When an animal is deprived of vision in
the right eye and the 2- DG method is em - VISUAL DEPRIVATION
ployed as a metabolic marker (a ) the left stri-
ate cortex shows the striped pattern of ocular Studies in very young, visually inexperi -
dominance columns, except in the represen- enced kittens and monkeys, deprived of all
tation of the blind spot where metabolic ac- vision from birth by visual occluders, have
tivity is evidenced by a continuous band of shown that responses in the striate cortex in -
isotope uptake, and ( b ) the right striate cortex dicate that orientation columns are as highly
Retinal area Blind spot

corresponding
to blind spot
of right eye
Ocular dominance
columns
Both eyes intact —

Right striate
Right eye removed— cortex
or right optic nerve
sectioned Representation of
blind spot
Figure 20.28 Continued .
ordered as in the adult ( 144, 386). The connec- (385). Similar visual deprivation in older kit -
tions responsible for the highly organized tens or in adult animals produced less severe,
function of the visual cortex must be present or no detectable, histologic changes in the
at birth and appear to be genetically deter - LGB. In young kittens, most of the geniculate
mined . The surprising finding in young mon - neurons with inputs from the deprived eye
keys deprived of binocular vision for a few had abnormal receptive fields, and the over-
weeks after birth was the marked reduction all activity of cells in these layers was dimin -
in number of cells in the striate cortex that ished . Single unit recordings from the striate
could be influenced by both eyes. Depriva- cortex in these animals indicated that the ma -
tion of binocular vision for a few weeks after jority of cortical cells were driven only from
birth may result in deterioration of innate the normal eye ( 385). Kittens deprived from
cortical connections subserving binocular vi- birth for 2-3 months showed profound visual
sion . defects in the deprived eye, although pupil-
Unilateral visual deprivation, accom - lary light reflexes were normal . Thus, monoc-
plished by suturing the eyelids closed or ular visual deprivation in kittens from birth
placing a contact occluder over the cornea , in can result in severe visual defects and unre-
very young kittens results in marked histo
logic changes in the layers of the LGB receiv-
- sponsiveness of cortical neurons to stimula -
tion of the deprived eye. Physiologic defects
ing fibers from the deprived eye, but no obvi- following unilateral visual deprivation ap-
ous histologic changes in the retina , optic pear to result from disruption of cortical con-
nerves, superior colliculi, or striate cortex nections present from birth .
Ocular dominance columns in monkeys types: (a ) lower order hvpercomplex cells

are only partially formed at birth and un - that behave as though their input was de-
dergo rapid development during the first 6 rived from two sets of complex cells, one ex-
weeks of life ( 152, 228). The process of left citatory and one inhibitory, and ( b) higher
and right eye segregation of afferent fibers in order hypercomplex cells that behave as
layer IV of the striate cortex occurs in the though they receive their input from a large
presence or absence of visual experience. number of lower order hvpercomplex cells.
Monocular visual deprivation during the first In visual area II , 5-10% of the cells are lower
six postnatal weeks causes ocular dominance order hvpercomplex cells, while in visual
columns in the deep parts of layer IV related area III they comprised about half of the cells.
to the open eye to be greatly expanded , while Area 18 is a six-layered granular cortex
dominance columns related to the closed eye which lacks the band of Gennari and rostrally
appear to shrink . Thus, monocular visual de- merges with area 19 without distinct demar-
privation in very young monkeys causes a cation ( Figs. 20.10 and 20.15). Large pyrami-
redirection of cortical afferents into sets of dal cells in the third layer of area 18 are use-
columns of unequal width. The eye prefer - ful in establishing its medial and lateral
ence of neurons in layers of the striate cortex borders, and coarse, irregular, often oblique,
superficial and deep to layer IV also changes fibers are seen in the deep cortical layers in
as a consequence of monocular deprivation. myelin-stained sections (145). Otsuka and
In young animals deprived of vision bilater- Hassler ( 287) have provided a comprehensive
ally, cells in upper and lower layers of the study of the visual areas in the cat. Area 18
striate cortex responding binocularly are interrelates areas 17 and 19 of the same and
greatly reduced ( 386 ). Monocular eyelid su - opposite hemispheres by association and
ture in the adult animal does not result in de - commissural fibers.
tectable anatomic or physiologic defects in The retinotopic organization of area 18 in-
the striate cortex ( 228). These studies indicate dicates that the border between areas 17 and
normal visual binocular experience, particu - 18 corresponds to the representation of the
larly in the first 6 weeks of life, is necessary vertical meridian of the visual hemifield ( con -
for the maintenance of cortical connections tralateral half of the visual field ). Thus, as
beyond the deep parts of layer IV of the stri - successive recordings are made moving from
ate cortex that subserve binocular vision . area 17 to area 18 there is a reversal of the re-
ceptive fields ( i.e., from peripheral to central
Secondary Visual Areas (V - ll and V - III) followed by a central to peripheral sequence)
about the vertical meridian. The isoelevation
A second visual area ( visual area ID has lines running through both areas 17 and 18
been mapped in a number of different ani - are roughly perpendicular to the representa -
mals by recording the potentials evoked by tion of the vertical meridian (145, 365). Visual
photic stimulation of the retina ( 356, 359, area II ( area 18) represents roughly the cen-
403). Visual area II is a smaller mirror image tral 50° of the visual hemifield which corre-
representation of the primary visual area ( V - sponds to the binocular overlap zone. In area
I ) and is identified as area 18 ( Fig. 20.19 ). Lat- 19 ( V - III ), the visual hemifield is represented
eral to V - l and V - ll is a third systematic pro- basically as a mirror image of area 18 with the
jection of the contralateral visual field ( visual vertical meridian for area 19 on its lateral bor-
area 111, V - III ), which corresponds to area 19 der. If a recording electrode were moved lat-
( 145). Areas 18 and 19 are often collectively erally from the border of areas 17 and 18, suc-
termed extrastriate cortex ( Fig. 20.10). cessive lateral positions in area 18 would
Cells in V- II and V - III respond to slits, represent more peripheral regions of the vi-
dark bars, and edges that have a specific re- sual field . When the medial border of area 19
ceptive- field orientation . The majority of cells is reached , the visual receptive fields would
( about 90% ) in V - II are "complex," whereas begin to move centrally toward the vertical
in V - III , only about half of the cells are com - meridian . The manner in which the contralat -
plex (145). Other cells in the extrastriate cor- eral visual hemifield is represented in areas
tex are referred to as "hypercomplex" cells 18 and 19 has been referred to as a second
because of more elaborate properties. These order transformation, which means that some
cells, however, differ in the precise position adjacent points in the visual field are not rep-
and arrangement of receptive fields. Hyper- resented bv adjacent points on the cortex
complex cells have been divided into two ( 8, 9 ) .
Cells of the six layers of the dorsal division sive, area 18 appears ideally suited for pro-
of the LGB project mainly upon area 17 but cessing visual information concerned with
some fibers also reach areas 18 and 19 ( 102). stereoscopic depth perception and may play
Larger cells in the dorsal nucleus of the LGB a special role in the analysis of retinal dispari -
project to area 18, while cells of all sizes pro- ties (148, 365). Area 18 contains a representa -
ject to area 17. Some of the larger cells may tion of the entire binocular visual field .
project collaterals to both areas 17 and 18. The
inferior pulvinar and the adjacent part of the Auditory Areas ( A - l and A - ll)
lateral pulvinar, each containing a represen-
tation of the contralateral visual hemifield , In humans, the primary auditory area
project retinotopically upon areas 18 and 19. (areas 41 and 42) is located on the two trans-
Pulvinar fibers end upon cortical layers IV, verse temporal gyri ( Heschl ) which lie on the
III , and 1 in the extrastriate cortex, and in the dorsal surface of the superior temporal gyrus
supragranular layers of the striate cortex and is buried in the floor of the lateral sulcus
(313). Fibers projecting to area 18 and 19 from (Figs. 2.8, 2.11 , and 20.10). The middle part of
these parts of the pulvinar appear to consti - the anterior transverse temporal gyrus consti-
tute important links in the extrageniculate vi- tutes the principal auditory receptive area
sual projection . Additionally, area 17 has (area 41 ). Remaining parts of the posterior
been demonstrated to project association transverse gyrus and adjacent portions of the
fibers to areas 18 and 19 ( 145, 243). Although superior temporal gyrus compose area 42,
there are few commissural connections be- largely an auditory association area . To visu -
tween areas 17 in the two hemispheres, both alize these gyri in an intact brain, it is neces-
anatomic and physiologic findings indicate sary to separate widely the banks of the lat-
that commissural fibers interconnect the junc- eral sulcus ( Fig. 2.8). Area 41 is a typical
tional region at the border between areas 17 koniocortex ( primary sensory cortex ), resem-
and 18 ( 146, 243, 401, 402, 413). These fibers bling that of areas 3 and 17. Granular cells are
arise mainly from the cells in layer III . Cells arranged in perpendicular columns. Area 42
situated at the boundary between areas 17 is a six-layered cortex of the parietal type
and 18 functionally represent the vertical ( type 3) ( Fig. 20.12 ), distinguished by a num -
meridian of the visual hemifield . Thus, the ber of large pyramidal cells in layer III .
vertical meridian of the visual field is bilater- The cortical auditory area receives genicu-
ally represented in the visual cortex. This bi- lotemporal fibers (auditory radiation ) from
lateral representation ensures a uniform vi- the medial geniculate body ( MGB ) ( Fig. 2.11 ).
sual field free of interruptions along the The auditory radiation reaches its cortical
vertical midline (146, 401 ). projection site by passing through the sub-
In V-11 I there are columns in which some lenticular portion of the internal capsule ( Fig.
cells have one receptive field orientation, oth- 16.39 ). The greater part of the auditory radia -
ers with an orientation at 90° to the first, and tion projects to area 41.
still others that respond to both of these ori- The ventral laminated part of the MGB has
entations. The majority of cells in V-ll and V- a tonotopic organization with high frequen-
III are driven from both eyes. Thus, there ap- cies represented medially and low frequen-
pears to be as much binocular representation cies laterally ( 4, 5, 46, 101 , 127, 157 ) . The audi -
in V - II and V- III as in V- I . tory radiation arises from the ventral
A separate representation of the contralat - laminated nucleus of the MGB ( Fig. 16.23)
eral visual hemifield ( V- II ) adjacent to the pri- and projects to the primary auditory cortex
mary visual (striate) cortex and with a com- where there is a spatial representation of
mon vertical meridian ( junction of areas 17 tonal frequencies ( 4, 46, 57, 275, 283, 311, 393).
and 18 ) has been found in every mammalian These fibers, passing to the primary auditory
species studied (365). The fact that all mam - cortex, constitute the core projection ( Figs.
mals appear to have an area 18 suggests that 20.29 and 20.30 ).
this area may be homologous in different The medial geniculate body also has two
species, although all connections may not be nonlaminated divisions which receive audi-
identical . In contrast, representation of the tory inputs. These divisions of the MGB, re-
contralateral visual hemifield in V - III (area ferred to as dorsal and medial ( magnocellu-
19 ) has not been found in all species and its lar ) ( 263), project ipsilaterally via the auditory
organization differs from species to species. radiation to at least five cytoarchitectonic
Although the function(s) of area 19 are elu - areas forming a cortical belt around the pri-
Figure 20.29 Auditory areas In the cat

The primary auditory area A- 1 has a tono-
toplc organization with high frequencies
(H) represented rostrally and low frequen -
cies ((.) caudally The dashed vertical lines
represent isofrequency bands. The primary
auditory area is surrounded by a belt of
secondary auditory cortex designated as
SF. suprasylvian fringe, partially in the
depth of the suprasylvian sulcus. EP. the
.
posterior ectosylvian area. A -ll the sec -
. -.
ondary auditory area S ll the secondary
.
somesthetic area, I the insular area and
T. the temporal area
mary auditory area (4, 46, 275, 283, 311, 393). 20.30). Best frequencies in the full auditory
Fibers arising from the nonlaminated parts of range for the monkey were represented in an
the MGB passing to the secondary auditory orderly fashion in the primary auditory area .
areas constitute the belt projection (38, 311, This is a cytoarchitectonic field coextensive
393). There appears to be very little overlap of with the koniocortex. Lowest frequencies
the auditory projections to the belt area sur- were represented rostrally and laterally,
rounding the primary auditory cortex, except whereas highest frequencies were found cau -
for the projection arising from the caudal part dally and medially ( Fig. 20.30 ). A cortical re-
of the medial division of the MGB ( 283). The gion immediately rostral to A - I has a cvtoar -
medial magnocellular division appears to chitecture similar to that of A- I and appears
project to the entire cortical area receiving to respond as vigorously to acoustic stimula -
fibers from the MGB, although the laminar tion ( 158). This rostral field , smaller than A- I,
distribution of fibers in the cortex is differ - contains a complete and orderly representa -
ent . The caudal part of the medial nucleus tion of the audible frequency spectrum with
projects primarily upon layer VI , while lower frequencies represented rostrally and
other subdivisions of the MGB project pri - higher frequencies represented in progres -
marily upon cells in layer IV and to parts of sively more caudal and medial regions ( Fig.
layer 111. 20.30). The A - I and the field rostral to it , des-
In the cat , two auditory areas were defined ignated R, appear to constitute the central
originally on the lateral aspect of the hemi- core of the auditory cortex in primates. The
sphere below the suprasylvian sulcus, desig- primary auditory cortex in monkeys is sur-
-
nated auditory area 1 ( A l ) and auditory area rounded by a belt of auditory cortex which is
II ( A - ll ) (4, 46, 409 ) ( Fig. 20.29). Frequency not cytoarchitectonically uniform . This cor -
representation in A- I indicates a series of tical belt , which represents the secondary
isofrequency strips oriented vertically, in auditory areas, has been divided topo-
which high frequencies are represented ros- graphically into three or more auditory
trally and low frequencies caudally ( 250, 251 ). fields ( Fig. 20.30). In the fields which form
In A- ll , no clear tonotopic representation has this cortical belt , units are less responsive to
been established because of the broad tuning acoustic stimulation and the frequency or -
curve of its neurons. Auditory area II receives ganization is more complex than in A - l or R .
most of its fibers from the medial magnocel - The organization and tonotopic localization
lular nucleus of the MGB. The other sec- in the A - I appears to be very similar in mon -
ondary auditory areas receive their inputs via keys, apes, and humans. Within this field
the belt projection from the nonlaminated low frequencies are represented rostrolater -
parts of the MGB. allv and higher frequencies extend caudo -
The primary auditory cortex in monkeys medially.
lies caudal to the superior surface of the supe- The functional architecture of the auditory
rior temporal gyrus and can be exposed by cortex appears similar to that of the visual
resection of the overlying parietal cortex ( Fig . and somesthetic cortex in that cells in the
Figure 20.30 A Lateral aspect of the rhe-

sus monkey brain with dashed line indicat -
ing region excised to expose the superior
temporal plane B. Dorsal view of the right
hemisphere exposing the auditory region
in the superior temporal plane. In the
primary auditory area. A-l ( blue), low
frequencies are represented rostrally and
laterally and high frequencies are repre-
sented caudally and medially . The area
designated R ( black ) has a cytoarchitec -
ture similar to A-l, an orderly representa-
tion of the auditory spectrum, and re-
sponds vigorously to auditory stimuli.
Auditory areas A -l and R are surrounded
by a belt of secondary auditory cortex
( shaded) designated as a. L and CM.
same column share the same functional prop- One of the distinctive features of the audi-
erties (5405). The functional columns in the tory system, in contrast to other sensory sys-
auditory cortex appear less discrete, do not tems, is the large number of actual and poten -
have sharp boundaries, and are considered to tial sites at which impulses from one side can
be much smaller units than in other sensory be transmitted to contralateral relay nuclei.
areas. The isofrequency strips oriented across The largest and most important fiber crossing
the primary auditory cortex probably repre- is in the trapezoid body, but others also are
sent, or are composed of , isofrequency cell present ( Fig. 13.13), including fibers from au -
columns ( 248, 251 ). In these columns, units ditory cortical areas that cross in the corpus
throughout the depth of the cortex respond to callosum ( 255). The commissural connections
the same frequency . Both binaural and of the auditory cortex in the cat project to ho-
monaural cell columns have been described mologous areas in the opposite hemisphere
(156). With the exception of some neurons re- (77). Auditory area I projects contralaterally
sponding only to binaural stimulation, to A- I and A-II, while A -II sends fibers only
monaural responses were classified as con- to A-II. Within each subdivision of the audi-
tralateral dominant, ipsilateral dominant, or tory cortex there are some areas which re-
equidominant. Most neurons in the same perceive only small numbers of terminal fibers,
pendicular column display the same aural the region of A- I representing the low fre-
dominance and binaural interaction. quency range being a clear example. Audi-
Electrical stimulation of the cortical areas tory commissural connections differ greatly
in the temporal lobe near the A- I ( i.e., areas from those of the visual cortex (area 17)
42 and 22) in humans produces sounds de- which are absent except near the border
scribed as the noise of a cricket, a bell, or a of area 18. Association fibers in the auditory
whistle. These sounds are elementary tones cortex of the cat reciprocally interconnect
that may be high or low pitched, continuous primary and secondary areas with each
or interrupted, but always are devoid of com- other ( 78).
plicated or changing qualities ( 299 ). Most of Each cochlea is represented bilaterally in
these auditory responses are referred to the the auditory cortex, although some slight dif -
contralateral ear . ferences exist between the two sides ( 2, 4, 46,
327, 409, 410). The cortical effects of sound the tongue, but separate from the nongusta-
stimulating each ear separately are nearly the tory lingula area.
same, but significant differences occur when In cats and monkeys, the taste pathway as-
the position of the stimulus is varied with re- cends ipsilaterally. Taste impulses arising in
spect to both ears (327). When sound is pre- the nucleus of the solitary fasciculus, which
sented on one side, the cortical response is receives primary gustatory afferents, are con-
greatest contralaterally . If sound is presented veyed by the chorda tympani and glossopha-
in a median plane, the cortical activity in the ryngeal nerves and projected to the ventral
two hemispheres is equal. Although these ob- posteromedial nucleus, pars parvicellularis
servations suggest that localization of sound ( VPMpc) of the thalamus ( 25, 81, 83). Cells in
in space is dependent upon the relative rostral regions of the nucleus of the solitary
amounts of neural activity at higher levels of fasciculus project fibers ipsilaterally to the
the auditory system, this conclusion is not VPMpc, while cells in more caudal regions
correct. Localization of sound in space in- project ascending fibers to both the VPMpc
volves a two-stage process: (a ) convergence and parabrachial nuclei in the rostral pons
and comparison of auditory input from the ( the so-called "pontine taste area") ( Figs.
two ears, and ( b) a distribution of this com- 12.19 and 16.21 ) ( 22, 278, 279 ). Cells in the
puterized analysis to the appropriate side of parabrachial nuclei, in turn, project upon
the system ( 199, 245). The trapezoid body is VPMpc, as well as to regions of the hypothal-
the only auditory commissure essential to amus and ventral forebrain structures ( 277,
sound localization (162, 273); above this level 279, 314). Thalamic cell groups subserving
mechanisms for detecting sound localization taste in the VPMpc are distinct from neurons
are present only on one side (contralateral to related to other sensory modalities of the
the source). Attempts to physiologically iden- tongue ( 25, 82, 83, 280). The VPMpc projects
tify a place map for sound direction have to both the insular and parietal opercular cor-
been elusive, but most evidence suggest it is tex (318).
likely to be in the deep layers of the superior Lesions in either VPMpc or the parietal op-
colliculus, or the brainstem tegmentum . erculum cause loss of gustatory sensation .
Because audition is represented bilaterally Ablations of the precentral and postcentral
at a cortical level, unilateral lesions of the au - opercula in the monkey and chimpanzee re-
ditory cortex cause only a partial deafness. portedly cause a loss of taste ( 26, 295). Similar
The deficits, however, are bilateral, and the lesions involving the anterior insular cortex,
greatest loss is contralateral. Brodmann 's area the postcentral operculum , and the anterior
22, bordering the primary auditory area ( Fig. supratemporal cortex in the monkey impair
20.10) and representing typical six-layered taste sensibility (17). Stimulation of the pari-
isocortex, receives fibers from areas 41 and 42 etal operculum ( 297) and adjacent insular cor-
and has connections with areas of the pari- tex (299) in conscious patients produces gus-
etal, occipital, and insular cortex (19, 352, tatory sensations.
353). Lesions in Brodmann 's area 22 in the
dominant hemisphere produce word deaf - Vestibular Representation
ness or sensory aphasia . Although hearing is
unimpaired by such lesions, patients cannot In the cerebral cortex vestibular sense is
interpret the meaning of the sounds. In hu- poorly defined in comparison with other sen-
mans, there are considerable variations in the sory modalities. In humans, electrical stimu -
size and convolutional patterns of Heschl's lation of portions of the superior temporal
—
gyrus in the two hemispheres the gyrus on
the left is frequently unpaired , larger, and
gyrus, particularly regions rostral to the audi-
tory area, provoke sensations of turning
longer than on the right side (369, 399). movements and dizziness (299). These sensa-
tions are mild compared with the vertigo pro-
Gustatory Area duced by direct stimulation of the labyrinth.
Less distinct illusions of body movement
Taste sensibility is represented in the pari- have been reported following stimulation of
etal operculum (area 43) and in the adjacent parietal cortex ( 296).
parainsular cortex ( Fig. 20.10) (17, 29, 30, 299). Two cortical areas have been identified as
Gustatory representation in the parietal oper- receiving vestibular input in cats and mon-
culum is adjacent to the somesthetic area for keys (94, 96, 200). These are area 3a and the
posterior margin of area 2, which is desig- systems occur in single or multiple strips
nated as area 2v (95). The common feature of 0.5-1 mm wide oriented mediolaterally
these areas is the convergence of vestibular across the cortex.
inputs and signals from deep somatic recep- Three principal motor areas are recog-
tors. Area 3a also receives inputs from muscle nized in the cerebral cortex: (a ) the primary
spindles and area 2v receives inputs from ( precentral ) motor area , ( b ) the premotor area ,
joint receptors ( 96, 334 ). Thalamic projections and (c) the supplementary motor area ( Figs.
to these cortical areas originate from portions 20.32 and 20.33). The primary motor area ( M -
of the ventrobasal complex and are not local - I ) is preeminently concerned with voluntary
ized to a single division ( i .e., VPLc, VPM, and motor activity. The premotor area , rostral to
VPI ) ( 235). Vestibular projections to the cor- M - l , is concerned with voluntary motor func-
tex are bilateral with contralateral domi - tion dependent upon sensory stimuli . The
nance. Regions of the vestibular complex pro- supplementary motor area, on the medial as-
jecting to the thalamus are poorly understood pect of the frontal lobe, participates in the
( 51, 70, 235). programming and planning of motor activi-
ties, and perhaps their initiation . The premo-
MOTOR AREAS OF THE CORTEX tor and supplementary motor areas are soma-
totopically organized and are interconnected
Corticofugal fibers arise from all regions of with each other and with M - l . Still further
the cerebral cortex . These projections convey rostral, in Brodmann's area 8, are the frontal
impulses concerned with motor function, eye fields which, as their name implies, are
modifications of muscle tone and reflex activ- concerned with movements of the eyes. Fi -
ity, modulation of sensory input , and alter - nally, the posterior parietal cortex, comprising
ations of awareness. Corticofugal fibers, orig - Brodmann 's areas 5 and 7, appears to be in -
inating mainly from the deeper cortical volved in programming directed movements
layers, can be grouped under these designa - of the limbs and eyes to targets in space.
tions: ( a ) corticospinal, ( b ) corticobulbar, (c)
corticoreticular, (d ) corticopontine, (e) corti - Primary Motor Area (M - l)
cothalamic, ( f ) corticostriate, and (g ) corti-
conuclear, a composite grouping of fibers that Area 4 of Brodmann, commonly desig -
project to brainstem nuclei at different levels nated as the primary motor area ( M - I ), is lo-
(e.g., corticosubthalamic, corticorubral, corti - cated on the anterior wall of the central sul-
cotectal, and projections to various sensory cus and adjacent portions of the precentral
and cerebellar relay nuclei ). gyrus ( Figs. 20.10 and 20.11 ). This area is
The somata of the cells of origin of particu - broad at the superior margin of the hemi -
lar corticofugal fiber systems have a specific sphere, but near the inferior frontal gyrus, it
laminar or sublaminar distribution ( Fig. 20.3) is practically limited to the anterior wall of
( 179). Corticospinal neurons lie in the deepest the central sulcus. On the medial surface of
part of layer V, occur in clusters, and show the hemisphere, it comprises the anterior por-
great variation in cell size, particularly in area tion of the paracentral lobule ( Fig. 2.6). The
4. Corticostriate fibers principally form the unusually thick cortex of M - I ( 3.5-4.5 mm ) is
smallest group of pyramidal cells in superfi - agranular in structure, and its ganglionic
cial regions of layer V. Corticopontine, corti- layer contains the giant pyramidal cells of
cobulbar, and corticorubral neurons lie in Betz, whose cell bodies may reach a height of
middle regions of layer V . The majority of 60-120 |j.m ( Figs. 5.9 and 20.14 B ) . These cells
corticothalamic cells are found in layer VI, are largest in the paracentral lobule, and
but some of these neurons are located in deep smallest inferiorly in the opercular region.
parts of layer V. The somata of cortical associ- The density of Betz cells also varies in differ-
ation and commissural neurons lie in the ent parts of area 4 ( 214 ). Approximate per-
supragranular layers of the cortex. Associa - centages of Betz cells in different topographic
tion neurons giving rise to ipsilateral cortico- subdivisions of area 4 are 75% in the leg area ,
cortical projections are superficial ( layers II 18% in the arm area , and 7% in the face area .
and III ) to neurons giving rise to commissural Approximately 34,000 giant pyramidal cells
connections ( layer III ). These observations with cross-sectional areas between 900 and
based upon retrograde transport of HRP indi- 4100 gnr have been counted in area 4 in the
cate that cells contributing to distinctive fiber human brain ( 214, 215). Cytoarchitecturally,
area 4 represents a modification of the typical nal labeling in the spinal gray matter follow-
six-layered isocortex in which the pyramidal ing injections of different cytoarchitectonic
cells in layers 111 and V are increased in num- areas (63). Isotope injected into cortical areas
ber and the internal granular layer is ob- 3, 1, 2, and 5 label terminals in parts of the
scured . For this reason the cortex is called posterior horn which correspond to Rexed's
agranular . laminae III and IV , while injections into areas
The corticospinal tract, considered to 4 and 3a label terminals largely in Rexed 's
transmit impulses for highly skilled volitional lamina VII, but with extensions into regions
movements to lower motor neurons, arises in of spinal motor neurons. No corticospinal
large part from area 4. The larger corti- neurons project into Rexed's laminae 1 and II .
cospinal fibers are the axons of giant pyrami - Some corticospinal neurons in area 4 end di -
dal cells as these cell undergo chromatolysis rectly upon anterior horn cells in the brachial
following section of the pyramids ( 136, 231 ). and lumbosacral enlargements in the monkey
Since the number of fibers in the human corti- ( 212, 238). Some corticospinal axons inner-
cospinal tract at the level of the pyramid is vate more than one spinal segment, but axons
approximately 1 ,000,1)00, axons of the giant supplying motor pools innervating distal
cells of Betz could account for only a little limb muscles have fewer collaterals (336).
over 3% of these fibers, assuming that each This arrangement is considered to be related
cell gives rise to a single corticospinal fiber to discrete contraction of individual distal
( 214 ). The fiber spectrum of the human corti - limb muscles. Anatomically , the corticospinal
cospinal tract indicates about 30,000 fibers tract is not somatotopically organized . Pyra -
with diameters between 9 and 22 gm ( 217, midal tract cells located posterior to the cen-
219, 220 ), supporting the view that these tral sulcus tend to terminate more dorsally in
fibers are the parent axons of the giant pyra- the spinal cord among interneurons relaying
midal cells. Approximately 907, of the fibers peripheral input from afferent fibers to mo-
of the corticospinal tract range from 1-4 gm toneurons and higher centers. This postcen-
in diameter. Of the total number of fibers in tral component of the pyramidal tract may be
the tract , about 40% are poorly myelinated. involved in regulating sensory function by
Earlier retrograde and anterograde degen - presynaptic modulation of transmission of af -
eration studies have revealed that virtually ferent impulses.
all fibers of the corticospinal tract arise from Electrical stimulation of M - l evokes dis-
area 4, area 6, and parts of the parietal lobe crete isolated movements on the opposite
(329 ) . Approximate percentages of corti - side of the body. Contractions usually in-
cospinal fibers arising from these areas, as de- volve functional muscle groups concerned
termined in earlier retrograde degeneration with specific movements, but individual
studies, are (a ) area 4, 31 % , ( b) area 6, 29%, muscles may be contracted separately. While
.
and ( c) parietal lobe, 40% . Complete decorti - the general pattern of excitable foci is nearly
cation, or hemispherectomy, causes all fibers the same for all mammals, the number of
of the corticospinal tract to degenerate in hu - such foci, and hence the number of discrete
mans ( 216, 218) and nonhuman primates movements, is increased in humans. Thus,
( 256, 329 ) . More recent retrograde HRP trans- flexion or extension at a single finger joint,
port studies in monkeys indicate that corti - twitching at the corners of the mouth, eleva-
cospinal fibers arise from cells widely distrib- tion of the palate, protrusion of the tongue,
uted in the sensorimotor cortex, all of which and even vocalization, all may be evoked by
are located in layer V (62, 179). Labeled corti - careful stimulation of the proper areas.
cospinal neurons in the deep parts of layer V Charts of motor representation have been
are found in areas 6, 4, 3a , 3, 1, 2, and 5, and furnished by a number of investigators (89,
in S- II . Although these neurons show great 90, 297, 298, 299, 331 ). Data concerning the
variation in size, all are pyramidal cells. The human brain were collected during neurosur-
largest cells are seen in area 4, while smaller gical procedures in which patients were oper-
cells are evident in other areas. Cells giving ated upon under local anesthesia ( Fig . 20.31 ).
rise to corticospinal projections occur in clus- The location of centers for specific move-
ters aligned to form strips oriented mediolat- ments may vary from individual to individ -
erally across the cortex. Anterograde autora - ual, but the orderly sequence of motor
diographic tract - tracing studies suggest that representation appears constant, lpsilateral
major differences exist in the pattern of termi- movements have not been observed in hu-
Figure 20.31 Representation of parts of the body in the motor area on the lateral surface of the hemisphere. The leg
usually is represented only in the anterior part of the paracentral lobule.
mans, but bilateral responses occur in the nization in the motor cortex is a single contin-
muscles of the eyes, face, tongue, jaw, larynx, uous, distorted representation of the body
and pharynx. The center for the pharynx parts within M - l . This pattern of organiza -
(swallowing ) lies in the most inferior opercu - tion, represented by the motor homunculus
lar portion of the precentral gyrus (297), fol- or its equivalent ( Fig. 20.18), has been extrap -
lowed , from below upward, by centers for olated from studies in which movements
the tongue, jaw, lips, larynx, eyelid , and have been produced by surface stimulation in
brow, in the order named ( Fig. 20.18). Next a variety of animals and in humans ( Fig.
come the extensive areas for finger move- 20.31 ). The summation of cortical representa -
ments, the thumb being lowest and the little tion depicted in a single line drawing is re-
finger highest, followed by areas for the garded as an oversimplification because it
hand , wrist, elbow, and shoulder. Finally, in rarely takes into account the extent of overlap
the most superior part are the centers for the of various body regions, which is a character -
hip, knee, ankle, and toes. The last named are istic feature of the motor cortex ( 408). Studies
situated at the medial border of the hemi- indicating a double representation of the
sphere and extend into the paracentral lob- body surface within cytoarchitectonic areas 3
ule, which also contains the centers for the and 1 in monkeys (249) have raised questions
anal and vesicle sphincters ( Fig. 20.18). concerning multiple representations of body
The movements elicited by electrical stim- parts in the regions of overlap in M-l (350).
ulation of M-I probably are not equivalent to The possibility of multiple representation of
voluntary movements, although they are in- the body in motor cortex was explored in the
terpreted by the patient as "volitional." Re- squirrel monkey in which none of M-I is
sponses are never skilled movements, compa- buried in the central sulcus (350). Microstim-
rable to complex acquired movements, but ulation at depths coincident with layer V re-
consist largely of either simple flexions or ex- vealed a discrete double representation of the
tensions at one or more joints. The threshold hand and wrist with the second hand zone lo -
in different topographic parts of area 4 varies. cated rostrally . Although all regions of the
The thumb region appears to have the lowest motor cortex have not been explored in de-
threshold, while the face area has the highest. tail, the possibility of dual representation of
Excessive stimulation of area 4 produces ei- motor function appears to have some founda -
ther a focal seizure, or one resembling a Jack- tion. However, it seems unlikely that these
sonian convulsion. systems could be entirely independent. Ear-
The classical view of the somatotopic orga- lier physiologic studies indicated that repeti -
tive microstimulation at various depths in the and Hans Kuypers ( 222 ) of monkeys with bi -
motor cortex can either facilitate or inhibit lateral pyramidal lesions also indicate that
monosynaptic reflexes (12). Although there is considerable recovery of independent limb
little evidence that cells in the motor cortex movement occurs, but recovery of individual
are organized into functional cell columns as finger movement never returns. All move-
in the somesthetic and visual cortex , micro- ments are slower and the muscle fatigue is
stimulation in a vertical column produces the more rapid than in normal animals. These
same response in all layers ( 164-166 ). findings indicate that corticospinal pathways
Ablations of the motor cortex in mammals conduct impulses concerned with speed and
produce greater neurologic deficits in pri- agility of movement, and fractionation of
mates than in nonprimates (373). In cats, movements, as exemplified by individual fin -
removal of the motor cortex, or even ger movements. Motor function remaining
hemidecortication, does not impair the ani- after bilateral pyramidotomy must be medi-
mal's ability to walk upon recovery from ated by brainstem pathways projecting to
anesthesia . Ablations of area 4 in monkeys spinal levels. These findings have been con -
produce a contralateral flaccid paralysis, firmed in young monkeys ( 221 ). Relatively in-
marked hypotonia, and areflexia . Within a dependent finger movements are not present
relatively short time myotatic reflexes reap- in young monkeys until approximately 8
pear, along with withdrawal responses to no- months of age, as such finger movements de -
ciceptive stimuli (99 ). There is recovery of velop gradually in parallel with the spinal
some motor function in both proximal and connections of the corticospinal system. Fol -
distal musculature, but skilled movements lowing bilateral pyramidal tract lesions a few
are performed slowly with deliberation (363). weeks after birth, relatively independent fin-
No significant spasticity developed in these ger movements failed to develop in a 3-year
animals. period of observation .
Because the precentral gyrus gives rise to a Lesions of the motor cortex in humans
large number of nonpyramidal fibers, and is produce neurologic deficits similar to those
the source of only a part of the corticospinal described in primates. Ablations limited to
tract, it is instructive to compare the motor the "arm" or "leg" area of the precentral
deficits described earlier with those which gyrus result in a paralysis of a single limb
follow surgical section of the pyramids. Selec- ( i.e., monoplegia ). The ultimate loss of move -
tive pyramidotomy in monkeys and apes, ac - ment is always greatest in the distal muscle
complished by an anterior approach, pro- groups, but motor recovery in the affected
duces a contralateral paresis which is limb usually is more complete than that asso -
somewhat more severe in apes than in mon- ciated with nearly total lesions of the motor
keys ( 360, 361 ). In neither animal group is the area (48). Immediately after complete or par -
paresis so severe that the effected limbs are tial lesions of the precentral gyrus, there is a
useless. The relatively stereotyped move- flaccid paralysis of the contralateral limbs or
ments of progression are impaired , and there limb, marked hypotonia, and loss of superfi -
is a severe poverty of movement . The usage cial and myotatic reflexes. Within a relatively
which survives is stripped of all the finer short time, the Babinski sign can be elicited .
-
qualities which contribute to the skill, preci The myotatic reflexes generally return early
sion, and versatility of motor performance. in an exaggerated form .
Although remaining stereotyped movements
are useful, execution of purposeful move- Premotor Area
ments appears to require deliberation and
critical attention. Pyramidotomy is associated The region designated as 6a u on the lateral
with hypotonia and loss of superficial ab- convexity of the hemisphere is considered the
dominal and cremasteric reflexes. The my- premotor area . The part of area 6aa on the
otatic reflexes are increased in threshold and medial aspect of the hemisphere is the sup-
somewhat pendular. Tonic neck reflexes are plementary motor area ( M - II ) ( Figs. 20.10 and
absent , and clonus does not occur . A forced 20.32 ) (90, 377 ) . Histologically, the premotor
grasp reflex is prominent and may be so se- area resembles the M - I. It is composed princi -
vere as to interfere with climbing. In apes, a pally of large pyramidal cells, but there are
persistent and enduring Babinski sign can be no giant cells of Betz ( Fig. 20.14 A ). Pyramidal
elicited . Observations by Donald Lawrence cells in layers III and V and the narrowness of
layer IV make it difficult to distinguish an in- by the pioneering studies of C. N . Woolsey

ternal granular layer. For this reason area 6, and his colleagues ( 406, 408). The sequential
like area 4, is referred to as agranular frontal representation of body parts in M - I I is shown
cortex. in Figure 20.33. The main features of the
The premotor area has a specific role in anatomic and physiologic organization of this
sensory guided movements. Units of the pre- cortical area were reviewed recently ( 34, 183,
motor area are activated in response to vi- 389, 390).
sual, auditory, and somatosensory stimuli. Movement-related neurons in M - I I (cells
Like the M-I , units are clearly related to vol - firing during movement ) are of three types:
untary motor function . The premotor area (a ) cells related to proximal movement , ( b )
differs from M - I in that it has a higher thresh - cells related to distal movement, and ( c ) cells
old and its neurons are activated by visu - activated throughout a motor task . The ma -
ospatial signals (88, 89, 377). The premotor jority of cortical neurons in this area ( 94 % ) ex -
area discharges via the corticospinal tract . hibit movement-related activity regardless of
Unilateral ablations of area 6, not involving whether the motor task is performed with the
the primary or supplementary motor areas, contralateral or ipsilateral limbs ( 394 ). The
do not produce paresis, grasp reflex, or hy - threshold for stimulation of M - ll in human
pertonia . and nonhuman primates is slightly higher
than for the precentral region . Motor re-
Supplementary Motor Area (M - ll) sponses obtained by stimulating M - ll are
abolished by ablation of M - I . The somato-
Observations by early investigators indi - topic features of M - ll also are distinct after
cated that motor responses in different parts ablation of M - I.
of the body could be elicited by electrical Unilateral ablations of M - ll in human and
stimulation of a portion of the frontal lobe nonhuman primates produce no permanent
rostral to M - l and termed the supplementary deficit in the maintenance of posture or the
motor area ( M - ll ) ( 299, 301 ). In human and capacity for movement. In monkeys, removal
nonhuman primates, M - II occupies the me- of M - II in combination with M - I on the same
dial surface of the superior frontal gyrus ros- side results in a contralateral spastic hemi-
tral to area 4 and corresponds to the medial paresis in which marked hypertonus devel-
part of area 6 (area 6a (i ) ( Fig. 20.32 ). Detailed ops in both proximal and distal muscles ( 100,
descriptions of somatotopic representation 132, 190, 191, 192, 364 ). Combined ablations
within M - II of monkeys have been provided of M -II and M - I in monkeys with longitudinal
Figure 20.32 The areas of electrically excitable cortex on the lateral surface of the human brain The motor area is
shown in block, and the so-called " extrapyramidal areas " of the frontal lobe are gray stippled areas of different in-
tensities. except for the eye fields, which are hatched.
] Precentral motor ] Supplementary
Figure 20.33 Precentral and supplementary motor areas in a macaque monkey The somatotopic representation ot
. .
different parts of the body are shown: F face area. 1. trunk. FL forelimb; HL hindllmb The precentral motor area on
the lateral convexity extends over onto the medial aspect of the hemisphere The outlined area shown posterior to
the central sulcus represents cortex hidden in the depths of the central sulcus. The supplementary motor area, largely
on the medial aspect of the hemisphere, is shown above
section of the corpus callosum ( i.e., split - their activity before the onset of movement
brain preparations) result in more pro - and large numbers of neurons in this area
nounced spasticity, suggesting that part of discharge during movement of either arm .
the bilateral influences of M - II involve fibers Only a small number of cells in this area re-
that cross in the corpus callosum. spond to peripheral stimuli and the re-
Cortical projections from M - II are ipsilat - sponses are weaker than in M -l (33, 34, 357,
eral to areas 4, 6 ( lateral part ), 5, and 7, and to 394, 395).
—
contralateral M - II (164 166, 169, 175, 394).
Connections between M -II and these cortical
While M - ll , as described in humans and
monkeys, is recognized as a distinct and sep-
areas are almost completely reciprocal ( 289, arate motor area with striking bilateral influ -
370 ). Approximately 5% of the neurons in M- ences upon both proximal and distal muscu-
11 project directly to the spinal cord with a bi- lature, it precise contribution to motor
lateral disposition ( 23, 33, 34, 394 ). Subcorti - function has not been defined . The supple-
cal projections of M -ll are profuse to parts of mentary motor area ( M- II ) is considered to be
the caudate nucleus and putamen (168, 189 ) involved in mechanisms that influence mus-
and to thalamic nuclei ( ventral anterior, cle tone and modify posture, the automatic
VApc, ventral lateral, VLO, and mediodorsal, grasp reflex response, bimanual coordination,
MD) (76, 390, 391 ). Afferents to M - I , the pre- and voluntary movement. There appears to
motor area , and M - II have distinctive features be general agreement that neurons in M - ll
and are discussed together in the section "In- modify the activities of cells in M -l and prob-
puts to Motor Cortical Areas." ably are involved in the programming of
Studies in conscious, behaving monkeys learned skilled motor sequences. Some evi-
indicate that neurons in M - II are related to dence suggests that M - II may play a role in
movements on both sides of the body and in - initiating voluntary movement . Studies in
volve distal and proximal musculature humans indicate that lesions in M - II are asso-
equally. Most of the neurons in M - ll increase ciated with a reduction of voluntary motor
activity (akinesis) and poverty of sponta- synaptic terminations largely in three cortical
neous speech. layers: (a ) layer 1(18% ), (b) layer III (66% ),
and (c) layer VI (13% ) (351 ). Fibers terminat-
Inputs to Motor Cortical Areas ing directly in layer V were relatively sparse
(3% ). The majority of thalamocortical projec-
Although impulses generated in neurons tions synapse on dendrite spines of cells in
of M-I are responsible for movement, changes layer III, the apical dendrites of motor neu-
in muscle tone, and certain cortical reflex re- rons ( Betz cells of layer V ), and on interneu -
sponses, these motor activities are initiated rons in layer III (163).
by inputs that arise from the thalamus, other The primary motor area ( M-I ) also receives
cortical regions, and peripheral receptors. inputs from SI and M -II (174, 175, 178). Area
Particular potent drives on the motor cortical 4 has reciprocal connections with areas 1, 2,
areas are derived from all divisions of the -
and parts of area 5 (164 166, 169, 349, 370,
ventral lateral ( VLc and VLo), and the ventral
posterolateral, pars oralis ( VPLo) thalamic
-
412 ). These cortical inputs to M - I are of an in
terlocking nature in that somatotopic subdi-
nuclei (73, 317, 347, 348, 362). Crossed projec- visions are connected with each other. The
tions from the deep cerebellar nuclei termi - supplementary motor area ( M-II ) receives
nate somatotopically in VPLo and in the cell- input from the same sensory areas (areas 1, 2,
sparse region of the ventral lateral thalamic and parts of area 5), but has reciprocal con -
nuclear complex, which includes the ventral nections only with area 4 ( M-I ). Neither
lateral nucleus ( VLc) and area X (155, 166, M- I nor M-II receives input from any part of
196, 210, 272, 302, 358, 362). The M -I is the area 3.
major target of the VPLo and cell-sparse re- It has been postulated that area 5 contains
gion of the ventral lateral thalamic nuclear the "command apparatus" for limb and hand
complex (56, 195, 318, 347). movements in immediate extrapersonal space
The pallidothalamic fibers, originating (268, 269). Neurons in area 5 have been ob-
from the internal pallidal segment, project to served to discharge only when an animal
the ventral anterior ( VApc), ventral lateral moves its arm toward a desired object or ma-
( VLo), and the centromedian (CM ) thalamic nipulates an object with its hand . The "com-
nuclei (see Chapter 19). Pallidal puts to the mand " hypothesis suggests that the cortical
rostral ventral tier thalamic nuclei do not pathway from area 5 to area 4 is involved in
overlap cerebellothalamic terminations. The initiating limb and hand movements.
-
cortical projections of VLo are to M II and the Physiologic studies indicate that M -I re-
lateral premotor area (area 6aa ) ( Figs. 20.32 ceives inputs from both cutaneous and deep
and 20.33). The thalamic terminations of pro- receptors (326, 388). Impulses from joint re-
jections from the substantia nigra are distinct ceptors projecting to areas 1 and 2 appear to
from those arising from the deep cerebellar have access to M -I and M - II directly and via
nuclei and the globus pallidus. The cortical area 5. Inputs from cutaneous receptors may
projections of the magnocellular division of be involved in instinctive grasping as well as
the ventral anterior ( VAmc) and the in the startle reaction (388).
mediodorsal ( MDpl) thalamic nuclei, which
receive nigral terminations, appear to exclude Cortical Eye Fields
area 4, and probably project to frontal areas
rostral to area 6 (see Chapter 19). Rostral to the premotor area is a cortical
Neurons of the ventral posterolateral nu- region particularly concerned with voluntary
cleus ( VPLo) and the cell sparse zone of the eye movements. The frontal eye field in hu-
ventral lateral nucleus ( VLc) show increased mans occupies principally the caudal part of
activity prior to any movement (348). This the middle frontal gyrus (corresponding to
finding suggests that these neurons may play parts of area 8, shown in Figs. 20.10 and
a role in initiating activity in muscles that ef- 20.32). The entire frontal eye field does not lie
fect discrete movements and control posture. within a single cytoarchitectonic area. Cy-
-
Thalamic neurons that project to M - I, M II, toarchitecturally, area 8 is typical six-layered
and the premotor cortex are distinct and sep - isocortex of the frontal type in which the
arate from those that terminate in somatic granular layers are distinct ( Fig. 20.12). Elec-
sensory areas. Electron microscopic evidence trical stimulation of the frontal eye field in
in the cat indicates that fibers from VLc and humans causes conjugate deviation of the
VPLo projecting to the motor cortex make eyes, usually to the opposite side (88, 299).
This cortical field is believed to be a center for the superficial layers (67, 102, 104, 153, 154,
voluntary eye movements, independent of vi - 392 ).
sual stimuli. The conjugate eye movements
commonly are called "movements of com- NONPYRAMIDAL CORTICOFUGAL FIBERS
mand ,” since they can be elicited by instruct-
ing the patient to look to the right or left (58). These cortical projection fibers consist
The frontal eye field participates in the initia - largely of corticoreticular, corticopontine,
tion of purposeful saccades ( rapid eye move- corticothalamic, and corticonuclear fibers.
ments to targets of behavioral importance)
and is implicated in the coordination of Corticoreticular Fibers
eye movement necessary for accurate gaze
changes. These fibers originate from all parts of the
The concept of an occipital eye center for cerebral cortex, but the largest number arise
conjugate eye movements is based on the fact from the motor and premotor areas (328). In-
that stimulation of occipital cortex produces ferior cortical areas ( basal ) and parts of the
conjugate eye movements to the opposite cortex on the medial surface of the hemi -
side, and lesions in this area are associated sphere also contribute to the corticoreticular
with transient deviation of the eyes to the projection , but few fibers arise from the audi-
side of the lesion . Unlike the frontal eye field , tory and visual areas. Corticoreticular fibers
the occipital eye center is not localized to a descend in association with fibers of the corti-
small area. Eye responses can be obtained cospinal tract, but they leave this bundle to
from a wide region of the occipital lobe in enter specific areas of the brainstem reticular
monkeys, but the lowest threshold is found in formation . The number of corticoreticular
area 17 ( 574 ). The occipital eye centers sub- fibers is not large, and most of these fibers
serve movements of the eyes induced by vi- terminate in two fairly well circumscribed
sual stimuli , such as following moving ob- brainstem areas: (a ) the nucleus reticularis gi -
jects. These pursuit eye movements are gantocellularis in the medulla, and ( b ) the nu -
largely involuntary, although they are not cleus reticularis pontis oralis in the pons ( Fig.
present in young infants. Parts of the occipital 11.22 ). Unilateral cerebral lesions produce an
eye centers are interconnected by fibers pass- approximately equal distribution of degener-
ing in the splenium of the corpus callosum . ated corticoreticular fibers on both sides of
The threshold for excitation is higher in the the reticular formation. Some corticoreticular
occipital eye center than in the frontal eye fibers also reach reticular cerebellar relay nu -
fields, the latency of responses is longer, and clei, such as the reticulotegmental nucleus,
eye movements tend to be smoother. With a the lateral reticular nucleus, and the parame-
lesion of the occipital eye field the patient dian reticular nuclei of the medulla .
may have difficulty following a slow moving
object, but on command can direct the eyes to Corticopontine Fibers
a particular location. Eye movements on com -
mand are impaired by lesions in the frontal These fibers arise from frontal, temporal,
eye field , particularly in the dominant hemi- parietal , and occipital regions of the cerebral
sphere. cortex ( 21, 39^41 , 281 ). In monkeys, the
The pathways by which responses from largest number of corticopontine fibers arise
the frontal eye fields are mediated involve from areas 4, 3, 1, 2, 5, and parts of the visual
multiple subcortical loci, chief among which areas (42, 43, 179). This contingent of corti-
are the rostral interstitial nucleus of the me- cofugal fibers, which originate from pyrami-
dial longitudinal fasciculus ( RiMLF), the in- dal cells in layer V lying superficial to the
terstitial nucleus of Cajal, the pontine para- giant pyramidal cells, is larger than other cor-
median reticular formation ( PPRF ), and layer tical efferent systems except the corticospinal
IV of the superior colliculus ( 159, 155, 154, projection . Corticopontine fibers arising from
208, 209 ). These structures are known to have the visual cortex are from regions represent -
direct and indirect influences on eye move- ing the peripheral visual field . Contributions
ments (see Chapter 14 ). The occipital eye cen - to this system from temporal and prefrontal
ter appears to influence eye movements via cortex are relatively modest. Most of the
substantial and highly organized direct pro- fibers from the prefrontal areas arise from
jections from the visual cortex to the superior areas 9 and 8 (14, 39 ). On reaching the mid -
colliculus, even though this projection is to brain , the frontopontine tract forms the most
medial part of the crus cerebri, and is distrib- central or prefrontal cortex. Corticothalamic
uted to the medial pontine nuclei ( Fig. 14.1 fibers from the precentral gyrus are wide-
and 15.26). In cats, corticopontine fibers from spread and include projections to VLo, VLc,
sensorimotor areas project in a somatotopic and VPLo, as well as to portions of the in -
manner onto two longitudinally oriented cell tralaminar thalamic nuclei ( 133, 223, 229, 230,
columns in the pontine nuclei ( 37, 39). One 257, 258, 316, 317, 367). Cortical projections
cell column is located medial and one is lat - from area 4 to parts of VL and VPLo are re-
eral . Within the medial column, the hindlimb ciprocal and topographically arranged . Pro-
is represented ventrally and the face dorsally, jections from area 4 to VLc are not as impres -
while in the lateral column, the hindlimb is sive as those from area 6 ( 207 ). These data
represented caudally and the forelimb ros- indicate that corticofugal fibers from the pre-
trally. Thus, fibers from particular regions of central gyrus project to thalamic nuclei which
the cerebral cortex end within columnar receive selective inputs from the deep cere-
zones of pontine nuclei which are separated bellar nuclei, the globus pallidus, and the
from each other. Although the synaptic rela - substantia nigra .
tionships of corticopontine fibers are incom - Efferent fibers from the parietal cortex
pletely known, most of these fibers appear to pass via the sensory radiations to the ventral
end only upon dendrites of pontine neurons posterolateral ( VPLc) and posteromedial
(61 ). There appears to be considerable over - ( VPM ) thalamic nuclei . Corticothalamic fibers
lap in the terminations of corticopontine from the primary somesthetic cortex project
fibers from some cortical areas. Most cortico- to the ventral posterolateral ( VPL ) and pos-
pontine fibers exert a monosynaptic excita - teromedial ( VPM ) nuclei, and are described
tory action upon pontine neurons (7). as ending in a somatotopic fashion within
Through the synaptic linkage of cortico- these nuclei (174, 203). Corticothalamic pro-
pontine and pontocerebellar fibers, impulses jections from areas 3, 1 , and 2 are confined to
from the cerebral cortex are brought into as- the ventrobasal complex, except for small
sociation with the regulating influences of the projections to the reticular and central lateral
cerebellum . The patterns of this disynaptic thalamic nuclei (180). No fibers from parietal
linkage are complex, but there is no doubt areas project to VPLo. It is considered likely
that this is the most massive input system to that reciprocating corticothalamic fibers in -
the cerebellum . volving the ventrobasal complex may influ -
ence the transmission of impulses to the cor-
Corticothalamic Fibers tex in a way similar to that exerted by
corticofugal fibers upon the posterior column
A large and impressive group of corticofu - nuclei and neurons of the trigeminal nuclear
gal fibers arise from specific regions of the complex.
cortex and project upon particular thalamic Parts of the auditory cortex project back to
nuclei . In general , cortical areas receiving the medial geniculate body nucleus or medial
projections from particular thalamic nuclei geniculat 4e body ( MGB ) via the sublenticular
give rise to reciprocal fibers which pass back segment of the internal capsule ( 202, 291, 315,
to the same nuclei. The granular frontal cor- 375 ). The cortical projections from the pri -
tex has reciprocal connections with the dorso- mary and secondary auditory areas are back
medial nucleus pars parvicellularis ( MDpc ) to the subdivisions of the MGB from which
of the thalamus (6, 195, 224 ). Particularly they receive inputs (57, 283). The primary au -
prominent among these fibers are those aris- ditory cortex has reciprocal connections with
ing from frontal areas 9 and 10. The frontal the ventral laminated part of the MGB, both
eye field (area 8) has reciprocal connections geniculocortical and corticogeniculate fibers
with the paralaminar part of the mediodorsal being ipsilateral ( 79, 93). Although cortical
( MDpl ) and the magnocellular part of the projections to the MGB do not participate in
ventral anterior ( VAmc) thalamic nuclei ( 208, the descending auditory pathways that influ -
209, 335). Area 6 projects fibers to the ventral ence auditory relay nuclei at lower levels of
anterior ( VA ), ventral lateral ( VLc), ventral the brainstem, projections from auditory cor-
posterolateral ( VPLo), and mediodorsal tex to the inferior colliculus ( pericentral nu -
( MDpl ) nuclei, as well as to "area X " and the cleus ) are involved in this activity ( 57, 79, 283,
para fascicular nucleus of the thalamus. In 322 ).
general, the premotor area shows projections The striate cortex ( area 17) sends fibers to
to thalamic nuclei related to either the pre- the LGB, the superior colliculus, the pretec-
turn , and the inferior pulvinar ( 119, 135, 240). commissural fibers and association fibers.
Corticofugal fibers from area 17 project to all The commissural fibers interconnect different
layers of the LGB. Fibers from area 17, pro- regions of the two cerebral hemispheres
jecting retinotopically to all layers of the LGB, across the medial plane. These fibers com -
arise from small and medium-sized pyrami- prising the corpus callosum are discussed
dal cells in layer VI (135, 240 ). Cells in layer V later in the section pertaining to interhemi-
of the striate cortex project to the superior spheric transfer. The association fibers , also re-
colliculus and the inferior pulvinar. Although ferred to as the arcuate fibers , interconnect
corticogeniculate and geniculocortical fibers different cortical regions of the same hemi -
are topographically organized , they are not sphere. There are both short and long arcuate
reciprocal in the true sense since they arise fibers. The short arcuate fibers comprise in-
and terminate in different layers of the striate tracortical as well as subcortical axons. The
cortex. Cells in the magnocellular layers of intracortical short arcuate fibers are entirely
the LGB have no cortical projection . confined to the cortical gray matter. They
While reciprocal relationships exist be- form bands of both myelinated and unmyeli-
tween the principal thalamic nuclei and their nated fibers within certain cortical layers that
cortical projection sites, a different relation- interconnect adjacent gyri. The subcortical
ship pertains to the reticular and intralaminar short arcuate fibers leave the cortical gray
thalamic nuclei. The reticular nucleus of the matter to invade the white matter where they
thalamus receives afferents from all areas of form U -shaped loops that curve upward to
the cerebral cortex but does not project back join the gray matter of an adjacent gyrus. The
to the cortex ( 55, 163, 333). Collaterals of thal - long arcuate fibers form bundles of various
amocortical fibers destined for specific corti- sizes that course deeply in the subcortical
cal areas, however, terminate in particular white matter and link widely separated gyri .
parts of the reticular nucleus (55, 163). Also, The most prominent of these association bun -
corticothalamic fibers give collaterals to the dles are ( a ) the uncinate fasciculus, ( b) the
same portions of the reticular nucleus as the cingulum , (c) the superior longitudinal fasci -
thalamic nucleus which receives the main culus, and ( d ) the inferior longitudinal fasci-
cortical projection. Thus, the reticular nucleus culus.
of the thalamus is strategically situated to The uncinate fasciculus can be divided into
sample activities passing in both directions a ventral and a dorsal component . The ven-
between the cerebral cortex and thalamic tral component links the orbital gyri of the
relay nuclei . This complex arrangement sug- frontal lobe to the parahippocampal gyrus
gests that the reticular nucleus of the thala- and other gyri of the medial surface of the
mus, composed of heterogeneous cell types, temporal lobe. The dorsal component con-
may serve to integrate and modulate in- nects other gyri on the superolateral aspect of
trathalamic activities. the frontal lobe with gyri on located the more
The intralaminar thalamic nuclei, like the lateral aspect of the temporal lobe near the
thalamic reticular nucleus, receive corticofu - temporal pole. The uncinate fasciculus arches
gal fibers. The prefrontal cortex project on the around the lateral sulcus and this trajectory
rostral intralaminar nuclei, while the premo- gives to this bundle a hook-shaped appear-
tor and motor cortex send fibers respectively, ance.
to the parafascicular ( Pf ) and centromedian The cingulum is a prominent collection of
(CM ) nuclei ( 6, 15, 206, 207, 274, 304, 307, association fibers that courses along the me-
316 ). The parietal and occipital cortex do not dial aspect of the hemisphere and forms
project fibers to the intralaminar nuclei. Thus, much of the white matter of the cingulate
the intralaminar thalamic nuclei, particularly gyrus. It courses along the corpus callosum
the CM - Pf complex, receive substantial pro- and links the subcallosal and paraolfactory
jections from the precentral and premotor gyri rostrally with the parahippocampal
cortex, but these nuclei project diffusely upon gyrus caudally.
broad regions of the cortex in a fashion that The superior longitudinal fasciculus lies deep
cannot be regarded as reciprocal (6, 172, 195). within the white matter of the cerebral hemi-
sphere and courses along the dorsolateral
ASSOCIATION FIBERS border of the lentiform nucleus. Along the
rostrocaudal axis, fibers of this prominent
In addition to projection fibers, the white bundle emerge from the frontal lobe and ex-
matter of the cerebral cortex also contains tend backward over the insula and through
the parietal lobe to the occipital lobe, where language that are said to be commonly asso-
they arch downward and forward to disperse ciated with imperfectly developed cerebral
within the temporal lobe. As it is the case dominance. These include improper develop-
with all association bundles, however, the su- ment of reading, writing, and drawing abili-
perior longitudinal fasciculus contains fibers ties, poor spatial judgment, and imperfect di -
that course in both rostrocaudal and cau - -
rectional control (411 ). In true right handed
dorostral directions. The superior longitudi- individuals, it is nearly always the left hemi -
nal fasciculus is often referred to as the arcu - sphere that is dominant and governs lan -
ate fasciculus because of the arching nature of guage and related processes. Even in left -
the caudal portion of the this bundle. handed individuals, the left hemisphere is
The inferior longitudinal fasciculus joins the most often dominant for language, but this
primary and secondary visual cortices (areas function may be represented bilaterally. The
18 and 19) in the occipital lobe with the supe- degree of cerebral dominance appears to vary
rior, middle, and inferior temporal gyri, and widely, not only among individuals, but with
the parahippocampal gyrus of the temporal respect to different functions.
lobe. It runs near the lateral walls of the tem- Although a degree of "cerebral ambilater-
poral and occipital horns of the lateral ventri- ality" would appear to be a distinct advan -
cle and is separated from them by the optic tage with respect to recovery of speech fol -
radiation. Like other arcuate or association lowing a unilateral cerebral injury, it carries
bundles, the inferior longitudinal fasciculus the risk, or possibility, of difficulty in learn-
ensures interconnections between several dis- ing to read , spell, and draw. The relationship
tinct functional cortical areas in the same between handedness and speech is perhaps a
hemisphere. Lesions of such bundles lead to more natural one than is commonly realized ,
serious impairment of cognitive functions. since gesturing often accompanies speech
and in certain situations may substitute for it.
Most clinicians relate handedness and speech
FUNCTIONAL CONSIDERATIONS to the dominant hemisphere.
Cerebral Dominance The dominant hemisphere, usually the
left, is primarily concerned with processing
Although the two cerebral hemispheres language, arithmetic, and analytic functions,
appear as mirror images of each other, many while the nondominant hemisphere is con -
functions are not represented equally at corti- cerned with spatial concepts, recognition of
cal levels. This appears true even though (a ) faces, some elements of music, and many as-
impulses from receptors on each side of the pects of emotion (343). Ideographic ( picto -
body seem to project nearly equally, though graphic) languages (e.g., Japanese Kanji ) may
largely contralaterally, to symmetric cortical be processed by the nondominant hemi-
areas, and (b) information received in the cor- sphere because of its spatial and pictorial
tex of one hemisphere can be transferred to features, while grammatic languages (e.g.,
the other via interhemispheric commissures Japanese Kana ) using script depend upon the
(114, 115, 260). dominant hemisphere. Visual sign language
In certain higher functions, believed to be used by deaf persons appears to be processed
cortical in nature, one hemisphere appears to primarily in the left hemisphere.
be the "most competent" and , in this sense, is It has been suggested that the normal
referred to as the dominant hemisphere. With -
neonate in a sense has a split brain because
respect to most of the higher functions, cere- the corpus callosum is incompletely devel -
bral dominance appears to be one of degree oped and not fully functional (105, 106 ).
(411). Cerebral dominance probably is most Thus, interhemispheric communication at
complete in relation to highly evolved as- birth probably is slight, but it increases with
pects of language (112-115, 130). Handedness development of the corpus callosum which
also is related to cerebral dominance, though becomes reasonably complete about the sec-
its relationship is less clear-cut than has been ond or third year of life. Until this level of de-
assumed . It seems likely that handedness is a velopment is reached, each hemisphere may
graded characteristic. Left-handedness, in process and record some linguistic informa -
particular, is less definite than right-handed - tion . Hand use probably reinforces hemi-
ness, and less regularly associated with domi - sphere use, and the development of a special
nance in either hemisphere. There also ap- competence in one hemisphere results in a
pears to be a group of disturbances related to mutual reinforcement that establishes a life
pattern. The major differences between the the body image in which the patient (a ) fails
right and left hemispheres concern the analy- to recognize parts of his or her own body, ( b)
sis of language and the ability to speak. The fails to appreciate the existence of hemipare-
fact that large left hemisphere lesions in sis, and (c) neglects the part of the body that
young children do not cause total disruption is denied (66). Lesions of the angular and
of speech indicates that the right hemisphere supramarginal gyri in the dominant hemi-
has some linguistic competence. Surgical sec- sphere produce devastating neurologic dis-
tion of the interhemispheric commissure turbances of a curious nature. Disturbances
sheds light on certain problems of cerebral in the Gerstmann syndrome include (a ) finger
dominance, and indicates that in the adult the agnosia (inability to name and identify indi-
left hemisphere speaks for both hemispheres. vidual fingers), (b ) agraphia (inability to
Cerebral dominance is considered to have write), (c) acalculia (impaired ability to make
a genetic basis, but its hereditary determina - simple mathematical calculations), and (d )
tion probably is not absolute. Pathologic and right-left disorientation. Patients with this
psychologic factors also influence handed - syndrome can copy written material and
ness, but most determining factors remain write their name but cannot convert spoken
unknown. Theoretic arguments suggest that words to script.
variations in levels of testosterone, and per- Positron emitting tomography ( PET) can
haps other hormones, during pregnancy may be of great help in the study of the functional
alter the patterns of migrations of cortical organization of the human brain in living in-
neurons. Every neuron in the cerebral cortex dividuals and in identifying brain regions
has migrated during fetal life from the germi- involved in specific higher cognitive and af -
nal zone of the neural tube to its final loca- fective functions. The use of ' sF-labeled de-
tion. The brain of the male matures later than oxyglucose reveals the patterns of utilization
in the female and the left hemisphere matures of glucose in different brain regions when a
later than the right. If fetal levels of testos- given individual is at rest or while perform-
terone are altered by maternal stress or other ing various complex tasks (e.g., talking, read-
factors, the right hemisphere may become ing, or listening to music ). The brain regions
more developed and assume functions for most active during these tasks become read -
language and handedness which the left ily visible with PET scans because they utilize
hemisphere cannot support. The effects of more glucose than quiescent brain regions.
testosterone on brain development is most This method has been extensively applied by
pronounced in the male, which may account Per Roland and his colleagues in Sweden to
for the higher incidence of left-handedness, identify cortical regions involved in various
dyslexia ( reading problems), and stuttering complex cognitive tasks ( 323). The same pro-
in the male. Anomalous cerebral dominance cedure can be used to detect various brain
appears to be a major factor in learning disor- pathologies that interfere with higher mental
ders, even in individuals not totally left- functions.
handed . The left dominant hemisphere is par-
ticularly concerned with ability to handle Interhemispheric Transfer
sequential information , such as language,
musical rhythms, Morse code, and complex Although the corpus callosum is the
spatial tasks. largest of the interhemispheric commissures,
Many cortical functions are concerned relatively little was known of its functions
only with contralateral regions of the body, until recently. The first convincing evidence
and unilateral lesions affecting these areas regarding its function was the demonstration
produce contralateral disturbances, regard - of its importance in interhemispheric transfer
less of cerebral dominance. This appears par- of visual discrimination learning in cats with
ticularly true of the primary motor and sen- longitudinal section of the optic chiasm ( 260).
sory areas. It is also the case with lesions of Following section of the optic chiasm and
the parietal cortex which result in astereogno- corpus callosum, cats trained with one eye
sis , or inability to recognize the form, size, masked were unable to remember simple vi-
texture, and identity of an object by touch sual discriminations learned with the first
alone. In lesions of the inferior parietal lob- eye. The untrained eye could be trained to
ule, particular deficits occur more commonly make a reverse type of discrimination with-
in the nondominant hemisphere. One such out interfering with the patterned discrimina-
syndrome is characterized by a disorder of tion learned on the opposite side. This func-
tional independence of the surgically sepa- guage, both spoken and written, was found
rated cerebral hemispheres with respect to to be represented in both hemispheres, with
learning, memory, and other gnostic activity the nondominant hemisphere less proficient.
is the stimulus for considerable investigation In an analysis of the visual fields, with fixa-
(267). The results originally suggested that tion assured , subjects verbally described only
section of the corpus callosum prevented the those small spots of light presented in the
spread of learning and memory from one right half of the visual field (105). A similar
hemisphere to the other. It was as if each light stimulus present in the left half of the vi-
hemisphere existed independently and had a sual field produced no verbal responses.
complete amnesia for the experience of the With double field stimulation, only spots of
other ( 342). Extension of these transfer stud - light falling in the right visual field were re-
ies in monkeys from visual to somesthetic ported. In these subjects, the visual fields
and motor learning (105, 106, 341, 342 ) have stopped exactly in the midline and no macu-
indicated that the independence of the surgi- lar sparing was evident. Thus, it would ap-
cally separated hemispheres may be less pear that no visual information can be trans-
clear-cut than originally supposed. In hu - ferred from one hemisphere to the other after
mans and monkeys, a subcallosal route may section of the corpus callosum.
be active in transmitting high-order tactile in- Certain lesions involving portions of the
formation . Furthermore, both hemispheres corpus callosum, or association areas of the
may learn to discriminate simultaneously, cortex which give rise to commissural fibers,
one via a contralateral sensory system and produce disturbances of higher brain func-
the other by an ipsilateral sensory system tions collectively recognized as disconnection
(105). syndromes (110-113). Word blindness without
Observations of the functional effects of agraphia presumably results from lesions
surgical separation of the hemispheres in hu - which interrupt fibers from the visual associ-
mans (106-108) by complete transection of ation areas which cross in the splenium of the
the corpus callosum, anterior and hippocam- corpus callosum and project to the left angu -
pal commissures, and separation of the thala- lar gyrus. Pure word deafness may result
mic adhesion ( massa intermedia ) have been from subcortical lesions in the left temporal
-
reported . These "split brain" patients show a lobe which interrupt the left auditory radia-
striking functional independence of the gnos- tion, as well as callosal fibers from the con-
tic activities of the two hemispheres. Percep- tralateral auditory region. Similar syndromes
tual, cognitive, mnemonic, learned , and voli - manifested by various forms of agnosia or
tional activities persist in each hemisphere, apraxia may result from lesions involving
but each can proceed outside the realm of portions of the corpus callosum and associa -
awareness of the other hemisphere. Subjec - tion fiber systems.
tive experiences of each hemisphere are Recent postmortem studies undertaken by
known to the other only indirectly through Sandra Witelson and her colleagues have
lower level and peripheral effects. Disconnec - shown variations in the morphology of the
tion of the hemispheres produces little distur- corpus callusum associated with hand prefer-
bance of ordinary, daily behavior, tempera - ence and sex in humans (397, 398). In these
ment, or intellect. Functional deficits tend to studies, the size of the corpus callosum was
be compensated for by development of bilat- measured along the sagittal plane in relation-
eral motor control from each hemisphere, as ship to (a ) hand preference, that is, consis-
well as by the bilaterality of some sensory tent-right-hand preference versus noncon-
pathways. Information perceived exclusively, sistent - right -hand preference, and (b) sex.
or generated exclusively, in the nondominant Individuals with nonconsistent-right-hand
( right ) hemisphere could not be communi - preference were found to have a larger over-
cated in speech or in writing; it was ex- all callosal area , with the greatest difference
pressed entirely by nonverbal responses. occurring in the posterior body segments, es-
There was no detectable impairment of pecially the isthmus. The isthmus is the nar-
speech or writing with reference to informa- row segment of the most posterior part of the
tion processed in the dominant (left ) hemi- body of the corpus callosum, just anterior to
sphere. Linguistic expression was found to be the splenium. This callosal segment includes
organized almost exclusively in the dominant fibers whose neurons of origin and termina-
hemisphere (106, 113). tion are in posterior parietal and superior
In contrast to this, comprehension of lan- temporal cortical gyri (74, 290), that is, re-
gions of the human brain which are involved and sleep behavior is not absolute. During
in the asymmetric representation of lan - slow-wave sleep, tone remains in the neck
guage, motor, and spatial cognitive skills ( 47). muscles, spinal reflex activity is present, and
These findings are in keeping with the fact changes in autonomic activity are minimal.
that left - handers, who are believed to have After a time, this state is succeeded by a to-
greater bihemispheric representation of cog- tally different sleep state, known as paradoxi-
nitive functions than do right -handers ( 47), cal sleep.
display a larger callosal area that may ac - Paradoxical sleep is characterized by an EEG
count for greater interhemispheric communi- - -
pattern with low voltage fast activity which
cation (3%). resembles that of the alert , waking state. This
Interestingly, sex differences were found sleep state occurs intermittently after variable
in several aspects of callosal anatomy. For ex - periods of slow -wave sleep and has precise
ample, the foregoing studies revealed that the behavioral criteria: (a ) abolition of antigravity
callosal size was greater in individuals with muscle tone (especially in cervical muscles),
nonconsistent -right-hand preference in men ( b) depression of spinal reflex activity, (c )
—
only there was almost no difference be
tween hand groups in women ( 397). The lat -
- characteristic autonomic changes ( i .e., reduc
tion in blood pressure, bradycardia, and ir
-
-
ter result was said to be consistent with the regular respiration ), and (d ) bursts of rapid
general hypothesis of females having less eye movements ( REM ). The fact that para -
clear lateralization than males (397). The lack doxical sleep is "deeper" than slow-wave
of relationship between callosal size and sleep, but associated with an EEG pattern
handedness in women also suggests that the similar to that of the waking state, gave rise
developmental mechanisms leading to cal- to the term paradoxical sleep. Rapid eye
losal anatomic variation in relation to lateral - movements of 50-60 per minute occur in a
ization and brain functional asymmetry are stereotypical pattern different from that seen
influenced by sex hormones (397, 398). in the waking state. These rapid eye move-
ments are associated with subcortical and
Sleep cortical activity, which have been termed pon -
togeniculo-occipital ( PGO) activity . These high
Sleep has been considered a unique pas- voltage phasic activities can be recorded from
sive state, interpreted physiologically as the the pontine reticular formation, the LGB, and
expression of functional deafferentation of the occipital cortex. This activity occurs tran-
the ascending reticular activating system . The siently during slow-wave sleep, and always
awake state was explained in terms of in - precedes paradoxical sleep. During paradoxi -
creased activity of this ascending activating cal sleep, PGO waves are fairly constant
system , while sleep was correlated with pas- (about 60 waves / min ), and it has been sug-
sive dampening of this system . Recent ad - gested that electrical events are triggering
vances indicate that sleep is an active, com - both these activities and REM ( 182 ). In fact,
plex neural phenomenon initiated by pontine-generated phasic activity is thought
sleep-inducing structures and mediated , in to be a pacemaker that drives many of the
part, by chemospecific neuronal systems. phasic events of REM sleep, including muscle
Sleep is not a single phenomenon , but a series twitches, changes in respiration , and surges
of successive functionally related states, in heart rate and coronary blood flow, in ad -
which depend upon different active mecha - dition to eye movements. The REM sleep
nisms, some of which can be selectively mod - ( paradoxical sleep) occurs periodically dur-
ified or suppressed (181, 182, 198, 236). In ing a night of sleep, with longer periods dur-
mammals, two recurring, distinctive, and re - ing the latter part of the night . If the subject is
lated sleep states can be readily recognized . awakened during or immediately after a pe-
These are referred to as slow-wave sleep and riod of rapid eye movements, 80'1 of the sub-
paradoxical sleep. jects will report that they have been dream -
Slou' -wave sleep is characterized in the elec- ing, and can relate the content of the dream
troencephalogram ( EEG ) by synchronized (236).
cortical activity consisting of spindles (11-16 Despite innumerable studies, anatomic
cycles / sec) and high voltage slow waves. structures and physiologic mechanisms
There are no specific behavioral criteria for involved in the control of the sleep-wak -
slow-wave sleep because the relationship being cycle are still uncertain. The pioneering
tween synchronized , or slow cortical activity, investigations of Giuseppe Moruzzi and
Horace Magoun in the late 1950s refuted the gic neurons thought to be involved in the
passive view of sleep as a functional deaf - control of sleep-waking cycle lie in the area of
ferentation regulated by the ascending reticu - the pedunculopontine tegmental nucleus.
lar activating system. Their studies clearly es- The cholinergic neurons of the pedunculo -
tablished that sleep is an active process that pontine tegmental nucleus project massively
involves (a ) a population of neurons in the to the intralaminar nuclei of the thalamus,
rostral brainstem reticular formation whose which are known to send profuse projections
activity is required for wakefulness, and (b) a to widespread areas of the cerebral cortex.
group of neurons in the caudal brainstem There is strong physiologic evidence for a
whose activity is necessary for the induction role of this disynaptic pathway, which com-
of sleep ( 265). prises a cholinergic pedunculothalamic and a
Early studies suggested that the sleep- glutamatergic thalamocortical segment, in the
inducing "center" in the brainstem might be -
control of the sleep waking cycle (344). Fur -
the serotoninergic raphe nuclei, while the no- thermore, the cholinergic neurons of the basal
radrenergic neurons of the locus coeruleus forebrain, particularly those of the basal nu -
could play a role in paradoxical sleep (181, cleus of Meynert which project diffusely
182). In support of this concept, is the demon- upon the cortex, may also contribute to the
stration that reserpine, which depletes both modulation of vigilance states. The complex
serotonin and norepinephrine, produces a neuropharmacologic events which underlie
tranquil state and suppresses both-slow wave -
paradoxical and slow wave sleep involve a
and paradoxical sleep for different periods of variety of neurotransmitters and neural struc -
time. Furthermore, pharmacologic inhibition tures, not all of which are known .
of serotonin synthesis at the level of trypto-
phane hydroxylase leads to total insomnia Integrated Cortical Functions
which is reversible. Injections of the immedi-
ate precursor of serotonin (5-hydroxytryp- One of the most striking and unique fea-
tophan ) causes a return to normal sleep. Like- tures of the human brain is its elaborate
wise, nearly total destruction of serotonin- neural mechanisms for complex correlations,
containing neurons in the raphe system also sensory discriminations, and the utilization
produces insomnia. One of the problems with of former experiences and reactions. These
the "monoaminergic hypothesis" of sleep is mechanisms involve associative memory and
that serotoninergic neurons in the dorsal mnemonic reactions. The ability to retain, mod -
raphe nucleus and noradrenergic neurons in ify, and reuse neuronal circuits probably pro-
the locus coeruleus fire maximally during vides the basis of conscious and unconscious
waking, drastically reduce their firing rate memory.
during slow-wave, and become totally silent In a general way, the central sulcus di-
during REM sleep (16, 159). Thus, these struc- vides the cerebral cortex into a posterior re-
ture are unlikely to play a crucial role in sleep ceptive portion and an anterior part related to
induction. motor functions. The posterior part contains
The firing pattern of serotoninergic neu- all the primary receptive areas that receive
rons nevertheless fits with the suggestion that specific sensory signals from the brainstem
these cells may normally suppress PGO and spinal cord. Hence, this large region re-
waves. In the transition from slow-wave to ceives inputs indirectly from the peripheral
REM sleep, most raphe neurons specifically sensory receptors. Impulses entering these
cease firing prior to PGO spikes, and remain primary areas produce sensations of a
silent throughout REM episodes. It was sug- sharply defined character, such as distinct vi-
gested that these neurons normally inhibit sion and hearing, sharply localized touch and
phasic REM events and that their silence dur- accurate sensations of position and move-
ing REM sleep indicates a termination of this ment. These sensations, however, probably
inhibition. have not attained the perceptual level neces-
Recent studies by Mircea Steriade, Allan sary for the recognition of an object. This re-
Hobson, Robert McCarley, and their col- quires the integration of primary stimuli with
leagues, led to the suggestion that an intrinsic other neural information. Regions immedi-
pattern of alternating activity between nor- ately adjacent to the receptive centers, known
adrenergic and cholinergic cells in the brain- as parasensory areas , serve for the combination
stem might account for the cyclicity of REM and elaboration of the primary impulses into
and slow-wave sleep (134, 345). The choliner- more complex sensory perceptions which can
be recalled under appropriate conditions. In of the supramarginal gyrus in the left cerebral
the more distant association areas , the various hemisphere, which probably is the dominant
sensory fields overlap (e.g., the inferior pari- hemisphere for tactile recognition.
etal lobule) and form the basis for multisen- -
Visual agnosia is a failure to recognize ob
sory perceptions. The interaction of different jects that cannot be attributed to a defect of
sensory modalities initiated by "feeling" and visual acuity or to intellectual impairment.
"seeing” an object or person excite memory Although a patient with visual agnosia is un-
constellations which lead to recognition. The able to recognize an object by sight, he or she
arousal of associative mnemonic complexes may recognize it by other sensibilities, and he
has been termed "gnosis," and it forms the or she can still recognize people. The disabil-
basis of understanding and knowledge. Dis- ity usually is limited to small objects and
orders of these mechanisms caused by lesions varies somewhat from day to day. In some in-
in association areas of the cerebral cortex are stances, the visual agnosia may extend to sur-
known as gnostic disturbances, or agnosias. In roundings, in which case it is associated with
these conditions, tactile, visual, or auditory spatial disorientation. Lesions associated
stimuli may no longer evoke appropriate with visual agnosia involve the lateral visual
memory constellations. When these gnostic association areas in the dominant hemi-
disturbances involve the associative mecha- sphere. The term alexia denotes a special form
nisms underlying the comprehension of lan - of visual agnosia in which the patient is un -
guage, they form part of the complex known able to read because he or she fails to recog -
as the aphasias. nize written or printed words. Lesions in this
Closely related to both agnosia and apha - syndrome interrupt pathways conveying im-
sia is another group of disorders character - pulses from the visual cortex of both sides to
ized by difficulty in performing skilled , the angular gyrus of the left hemisphere.
learned movements even though no paralysis Auditory agnosia is the term to describe the
or sensory loss is present. Disorders that af - condition in which a patient with unimpaired
-
fect the motor side of sensory motor integra- hearing fails to recognize or distinguish what
tion are referred to as the apraxias. There are he or she hears. This type of agnosia may in-
only two ways a patient can show that he or volve speech , musical sounds, or familiar
she recognizes an object: (a ) by naming or de- noises, such as the telephone bell or running
scribing the object, or (b) by demonstrating water. One form of auditory agnosia , known
its use. If the patient can demonstrate the use as word deafness, constitutes a type of recep -
of an object but is unable to name it, the indi- tive aphasia. Lesions associated with audi -
vidual has an aphasia. If the patient can name tory agnosia involve parts of the superior
the object , or describe it, but does not know temporal gyrus posteriorly (area 22) in the
how to use it, he or she has an apraxia . The dominant hemisphere; these disturbances are
above examples demonstrate that agnosia more severe when the injury is bilateral.
partially underlies both aphasia and apraxia .
APHASIA
AGNOSIA
This disorder is characterized by receptive
Agnosia means a failure to recognize. Var- and expressive disturbances in the use of
ious types of agnosias have been defined ac- symbols and signs to communicate. It results
cording to the particular sensory modality from organic neural lesions involving cere -
effected . Of the many types of agnosia bral memory mechanisms for language, with -
classified on this basis with respect to both out impairment of cortical or subcortical
objects and space, three may properly be con - structures essential for the relay of impulses
-
sidered here, namely tactile agnosia , visual ag or the innervation of speech organs (i.e., the
nosia , and auditory agnosia . muscles of the larynx, tongue, and lips). The
Tactile agnosia is a failure to recognize ob- three major types of aphasia are (a ) receptive
-
jects by means of tactile and kinesthetic sensi or sensory aphasia , (b) expressive or motor
bilities when both of these sensory modalities aphasia , and (c) conduction aphasia (68). Re-
are normal in the part of the body being ceptive aphasia was characterized by the Ger-
tested . Astereognosis is the inability to recog- man neurologist Carl Wernicke in 1908 (380),
nize objects owing to sensory impairment at a while motor aphasia was first described by
cortical level. According to Brain (32 ), tactile the French neurologist Paul Broca as early as
agnosia is associated especially with lesions 1865 (36). Thus, sensory and motor aphasias
are often termed Wernicke's and Broca's symptoms of aphasic patients rarely fall into
aphasias. one category or another simply because le-
Receptive or Wernicke' s aphasia involves im - sions producing cortical damage are rarely
pairments in the appreciation of the mean- coextensive with a functional site ( 32, 300).
ings of both spoken and written words. The
lesion primarily affects Wernike's area , that APRAXIA
is, the left portion of the temporal lobe, or
Brodmann's area 22, although it often ex- The inability to perform certain learned
tends to the superior portion of the temporal complex movements, in the absence of paral -
lobe (areas 39 and 40 ) and interiorly to area ysis, sensory loss, or disturbance of coordina-
37 ( big. 20.10 ). When the lesion is extensive, tion, is known as apraxia . Since complex vol -
comprehension of both visual and auditory untary movements require the utilization of
language input is severely impaired . In con- cerebral processes in formulating the nature
trast , speech is fluent but often "empty." Lan - of the act to be performed , movements of this
guage is normal in rate, rhythm, and melody, nature are considered separate from those
although patients may use wrong words which are more or less automatic. Formula -
( paraphasia ). tion of these movement complexes is largely
In expressive or Broca' s aphasia the language unconscious and appears to depend upon
is not fluent but comprehension is usually memory constellations of similar acts previ-
preserved . Patients have damage to the ously performed. Complex learned move-
motor association cortex in the frontal lobe, ment patterns are organized in space and
usually extending to the posterior portion of time, and follow sequences requiring close at -
the third frontal gyrus ( Brodmann 's areas 44 tention . Multiple sensory systems contribute
and 45) which forms part of the pars opercu - to the skill of these movement patterns.
laris and triangularis ( Broca ’s area ). In severe Apraxia has been regarded as a disorganiza-
cases, there is also damage to the surround - tion of the underlying complex movement
ing premotor and prefrontal regions (areas 6, patterns. Many varieties of apraxia have been
8, 9, 10, and 46). The deficit in language pro- proposed as distinct entities, although some
duction ranges from almost muteness to a tend to have common features.
slowed , deliberate speech constructed from Kinetic apraxia is characterized by an in -
very simple grammatic structures. Patients ability to execute fine acquired motor move-
with Broca 's aphasia use only key words ments; there is no paresis, and automatic and
( 246 ). associated movements can be carried out.
Condnction aphasia involves lesions in the This disturbance may be confined to one
arcuate or superior longitudinal fasciculus, limb. It has been interpreted as an expressive
which is composed of association fibers that defect, most frequently associated with le-
link Broca 's and Wernicke's areas. This bun- sions of the precentral gyrus. The defect usu -
dle can be injured with lesions involving the ally occurs contralateral to the lesion ( 71 ).
supramarginal gyrus of the parietal lobe, or, Ideomotor apraxia is caused by an interrup-
less frequently, the posterior and superior tion of pathways between the centers for for-
parts of the left temporal lobe ( 68). Patients mulation of a motor act and the motor areas
with conduction aphasia are fluent and their necessary for its execution . Although patients
comprehension is relatively good . The major may know what they want to do, they are un-
deficit concerns the ability to repeat words. able to do it . Patients can perform many com -
These patients also make many paraphasic plex acts automatically, but may fail to
errors, substituting incorrect sounds or perform the same acts on command . Sponta -
words for correct ones. Naming is also se- neous gestures may be normal. Ideomotor
verely impaired . Reading aloud is abnormal, apraxia is often bilateral and affects the ex -
but patients can read silently with good com - tremities equally. It is said to be associated
prehension . with lesions of the parietal lobe, particularly
The division of the aphasias into three the supramarginal gyrus, in the dominant
types is an oversimplification since common hemisphere.
disturbances of memory and language must Ideational apraxia is the term used to de-
be involved in both types. While relatively scribe loss of ability to formulate the
pure receptive or expressive forms of aphasia ideational plan for the execution of the com -
do occur, mixed varieties are the most com - ponents of a complex act . While simple iso-
mon . Clinical experience reveals that the lated movements may be performed nor-
mally, the component movements of a com- interoceptive and exteroceptive information

plex act are not synthesized into a purposeful they receive so as to select appropriate motor
plan and individual movements may be per- responses from many available ( 211).
formed in a faulty sequence. Since kinesthetic The frontal lobe can be subdivided into
memory and appreciation of the act to be per- multiple functional subregions. However, ex-
formed are defective, ideational apraxia may perimental studies in monkeys suggest that it
be a variety of agnosia. This form of apraxia is composed of two main regions: (a ) the pre-
has been considered to result from lesions in frontal cortex proper, located on the dorsolat-
the dominant parietal lobe, or in the corpus eral surface of the frontal lobe, and (b) the or-
callosum (116), but frequently it is associated bitofrontal cortex, located on the medial and
with rather diffuse pathologic processes. ventral surface of the brain. Both regions re-
Constructional apraxia is a disorder charac- ceive a massive input from the mediodorsal
terized by loss of visual guidance, impair- thalamic nucleus, whose fibers terminate in
ment of the visual image, and disturbances of layer IV. Tire prefrontal and orbitofrontal cor-
revisualization. A patient suffering from this tices are sometimes referred together as
form of apraxia is unable to reproduce simple frontal granular cortex, in distinction to the
geometric figures by drawing or by the agranular cortex of the motor and premotor
arrangement of blocks. Although construc- areas. The frontal granular cortex is con-
tional apraxia is included with expressive nected by the cingulum and the uncinate fas-
disorders of motor function, it is rarely a pure ciculus with anterior portions of the temporal
motor disorder. As a rule the patient is un- lobe and , directly or indirectly, with parietal
aware of his inability to perceive spatial rela - and adjacent occipitotemporal association
tionships. This variety of apraxia appears to areas. It was recently discovered that the pat-
be related to interruption of pathways be- tern of termination of intercortical connec-
tween the occipital and parietal cortex (66). tions between regions of association cortex of
Curious combinations of agnosia and the parietal lobe and frontal lobe is organized
apraxia occur as a consequence of lesions in- into distinct, vertically oriented columns
volving primarily the inferior parietal lobule, (123). These columns are 200-500 jim wide
usually in the dominant hemisphere (66, 109). and extend across all layers of cortex. Thus,
This syndrome (Gerstmann' s syndrome ) is columnar organization is not unique to sen-
characterized by (a ) finger agnosia, ( b) right- sory or motor cortices, but appears to be a
left disorientation, (c) agraphia or dys - general feature of all neocortex.
graphia , and (d ) acalculia or dyscalculia. Pa- The two major parts of the frontal lobe
tients suffering from Gerstmann's syndrome have somewhat distinct functions. Whereas
have difficulty in differentiating their fingers, the prefrontal cortex is involved in the strate-
in naming the individual fingers, and in gic planning of higher motor actions, includ -
pointing to particular fingers. Right -left dis- ing cognitive tasks, the orbitofrontal cortex
orientation, unlike finger agnosia, may affect appears mainly concerned with emotional be-
all parts of the body , as well as inanimate ob- havior. The orbitofrontal cortex is part of the
jects and other individuals. The disturbance limbic association cortex; it has direct connec-
in writing does not extend to copying, which tion with limbic structures, such as the amyg-
can be accomplished without difficulty. In - dala . The functions of the premotor cortex ap-
ability to solve arithmetic problems is most pear largely dependent upon various forms
evident with written figures, but it involves of short-term memories, such as the working
mental calculations as well. memory, a temporary storing of information
used to guide a future action (123). Pioneer-
Prefrontal Cortex ing investigations in the 1930s by Carlyle
Jacobsen have greatly helped our under-
The frontal lobe rostral to area 6 is particu- standing of the frontal lobe functions in pri-
larly well -developed in primates, especially mates. These studies revealed, among other
in humans. These areas of cortex, including things, that lesions involving the prefrontal
that on the orbital surface, are referred to as cortex impair the ability to perform a task in-
the prefrontal cortex. They consist of associa- volving delayed spatial response. In contrast,
tion areas whose major function is related to frontal lobe lesions involving the orbito-
the capacity of the organism to weigh the frontal and anterior cingulate cortex produce
consequences of future actions and to plan a marked alteration of the emotional respon -
accordingly. The frontal lobes integrate the siveness of monkeys, in addition to a deficit
in delayed responses. In cases where damage which could be attributed to the operation,
is limited to the orbitofrontal cortex, the nor- and they probably were responsible for the
mal aggressiveness and emotional respon - successful abolition of morbid anxiety and
siveness of primates is reduced (160). obsessional states (97).
A procedure known as frontal lobotomy or Intellectual damage is especially difficult
leucolomy was used widely some years ago in to evaluate. General memory returns rapidly,
attempts to modify the behavior of severely and standard psychometric tests are accu -
psychotic patients. The basic operation in- rately performed . Capacity for abstract
volved bilateral sectioning of the fiber con- thought is reduced and patients develop a
nections to and from the prefrontal area. The more concrete attitude. Easy distractibility is
frontal lobotomy, introduced by the Por- common, judgment is poor, and initiative is
tuguese neuropsychiatrist Egas Moniz ( 262), reduced . Mental concentration and the capac-
was performed in the United States and else- ity for sustained intellectual effort are im -
where in the 1940s (97). This neurosurgical paired , especially with respect to solving
procedure permitted many institutionalized complex problems. The most reliable data
patients to return home and even to resume concerning the effects of lobotomy upon in-
their former activities. Moreover, a consider - telligence are those obtained from nonpsy-
able number of lobotomies were performed chotic patients in whom this procedure was
-
for the relief of chronic intractable pain of or done for relief of pain . On the basis of thor-
ganic origin when other measures, such as ough studies of patients before and after op-
massive doses of narcotics and even cordot - eration, Rvlander (330) concluded that intel -
omy, had proved of no avail (85, 97, 332). lectual and emotional deterioration may be
After the operation, the patient no longer severe. The results of the operation necessar-
complained spontaneously of pain and no ily depend upon the intelligence of the
longer appeared to be in distress, although patient and the extent of the operative pro-
when asked patients acknowledged that pain cedure. This conclusion appears to be sup-
was still present. Relief apparently was due ported by others ( 201 ). Other forms of frontal
to removal of the anxiety and fear usually as- (or prefrontal ) lobe surgery, such as topec -
sociated with pain. Since frontal lobotomy, tomy and orbitofrontal lobotomy, were not
and numerous technical variations of it (126, reported to produce such severe impairment
259 ), was performed on a large number of pa - of intellectual function (126, 213). The fact
tients, it afforded an opportunity to study the that the extent of intellectual deterioration
associated intellectual and behavioral effects following prefrontal lobotomy cannot be
of these lesions. measured in specific terms, reflects the ex-
The results of numerous lobotomies have ceedingly complex nature of what is called
been critically reviewed in a number of publi - intellect, and suggests that the criteria used to
cations (75, 97, 294 ). These studies are diffi- evaluate it may not be adequate. The unpre-
cult to evaluate because of lack of agreement dictable effects of the procedure upon intel-
concerning the extent of the changes in be- lect and severe personality changes associ-
havior and intellect. Most striking are the al- ated with the irreversible nature of surgery
terations in emotional behavior, which were caused this procedure to be rarely used .
characterized by Freeman and Watts as a Despite the difficulties in evaluating the
lessening of "consciousness of the self ," and a behavior changes and the intellectual alter-
narrowing of the patient's mental horizon to ations of prefrontal lobotomy, some patients
the immediate present and to his own person . were considered to have benefited from the
The patient was easily amused , careless in operation. Perhaps the greatest problem, and
personal habits, unconcerned in social rela - one of the reasons why this form of psv -
tions, and affected little by criticism. His chosurgery is now rarely done, was the diffi -
emotional reactions were abrupt, transient, culty in determining preoperatively which
and superficial, and they often were accom- patients might be expected to be improved by
panied by outspoken tactlessness. Pain and it. Another important factor in the decline of
hardship were not associated with anxiety, psychosurgery wras the introduction of tran -
nor was there much concern about financial quilizing drugs which facilitated the treat -
or domestic difficulties. There was inability to ment of severe behavioral disorders.
gauge or appreciate the gravity of a situation The human nervous system has evolved
and to maintain a responsible attitude toward slowly, and although many of the details of
it . These were the most enduring changes its anatomic structure appear firmly estab-
lished , concepts concerning the functional proach in versatility or scope the fantastic po-
significance and interrelation of its various tentialities of the human brain . The human
subdivisions change as a result of continuing brain is unique in that it provides its own
research . Many so-called "electronic brains" programming. In fact, it is programmed
or "artificial intelligence" devices have been throughout life by daily experiences. It seems
constructed which can perform certain func- likely that manmade neuronal machines will
tions faster and more efficiently than the in the future perform many more of the func-
human brain . The more complex the per- tions now performed by human brains, but
formed function, the more elaborate the pro- this change must be regarded as a redistribu -
gramming of the computer must be . Such tion of labor. These computerized versions of
computerized networks are impressive in ap- the brain are, after all , only one of the expres-
pearance and function, vet they do not ap- sions of the ingenuity of the human brain .
References sensory inputs to the motor cortex. rophysiology of the cerebral cor-
Prog Neurobiol 1981 ;16:241-262. tex . Austin: University of Texas
I Ades IIW. Central auditorv mech - 12 . Asanuma II . Sakata II . Functional .
Press 1981.
25. Blomquist A ) , Benjamin KM , Em-
anisms. In . Field J , ed . HandKxik organization of a cortical efferent
.
of physiology Vol. I Sect. I . Ch. system examined with focal depth itters K Thalamic localization ot af -
24 Washington, (X : American stimulation in cats. I Neurophysiol ferents from the tongue in squirrel
Physiological Society , 195W ; -
1967;30:35 54. monkey ( Saimiri miumis ). ) Comp
585-613. 13. Aston -Jones G, BliH > m FE. Activity Neurol 1 %2;118:77-87.
2. Ades MW , Brookhart JM . The cen - ol norepinephrine-containing locus 26. Blum M , Walker AH , Ruch TC. Lo -
tral auditory pathway. ) Ncuriv coeruleus neurons in behaving rats calization of taste in the thalamus
phvsiol 1950;13:189-205. exhibit pronounced responses to of Macaco mulatto. Vale J Biol Met!
3. Adrian HD. Afferent discharges to
the cerebral cortex from peripheral
non - noxious environmental stim -
uli . ) Neurosci 1981;1 :887-9( )t ).
-
1943;16: 175 182
27. Boivie J . Terminations of the cervi-
sense organs. I Physiol ( Lond ) 14 . Astruc |. Corticofugal connections cothalamic tract in the cat: an ex -
-
1941;100:159 191 . of area 8 ( frontal eye field ) in perimental study with silver im -
4. Aitkins LM , Irvine DKF, Webster Macaco mulatto . Brain Res 1971; pregnation methods. Brain Res
WR . Central neural mechanisms of -
33:241 256. 1970;19:333-360.
-
hearing. In: Darian Smith I . ed 15 Auer ) Terminal degeneration in 28. Boivie J An anatomical reinvesti -
Handbook of physiology Sect . I the diencephalon after ablation of gation of the termination of the
the nervous system . Vol. Ill frontal cortex in the cat . J Anal spinothalamic tract in the monkey.
Bethesda , MD: American Physio-
logical St*iety , 1984:675-737.
1956;90:30 41.-
16. A / mitia EC, Gannon P) . The pri -
|Comp Neurol 1979;186:343 370.-
29 . Bornstein WS. Cortical representa -
5. Aitkins I . M , Webster W' K . Medial mate serotonergic system : a review tion of taste in man and monkey . I .
and geniculate bt*lv of the cat: or - of human and animal studies and a Functional and anatomical rela -
ganization and responses to tonal
stimuli of neurons in the ventral
report on Macaco fascicular In :
Fahn S, ed . Advances in neurol- ^. tions of taste, olfaction and somatic
sensibility - Vale I Biol Med 1940;
division . I Neurophvsiol |972;35: ogy New York: Raven Press, 12:719-736.
.365- .380. -
1986:407 468. 30. Bornstein WS. Cortical representa -
6. Akert K . I lartmann - von Monakow 17 Bagshaw MU , Pribram KH. Corti - tion of taste in man and monkey.
K Relationships of precentral, pre
motor and prefrontal cortex to the
- cal organization in gustation
( Macaco mulatto ). I Neurophysiol
II . Localization of cortical taste
area in man and method of mea -
mediodorsal and intralaminar nu - 1953;16:499-508. suring impairment of taste in man
clei of the monkey thalamus. Acta 18. Bailey P, von Bonin G. The isocor - Yale J Biol Med 1940;13:133-156.
Neurobiol Exp ( Wars/ ) I 980;40: tex of man . Urbana: University of 31. Bowsher D. The termination of sec -
7 25 Illinois IVcss , I9$t ondary somatosensory neurons
7. Allen Gl, Korn II , Oshima T, 19. Bailev P, von Bonin G, Carol HW , within the thalamus of Macaco mu -
Toyama K The mode of synaptic McCulloch WS. Functional organi - latto : an experimental degeneration
linkage in the cerebroponto cere - - zation ot temporal lobe of monkey studs I Comp Neurol P »ol ; 177 :
bellar pathway of the cat II Re- ( Macaco mulatto ) and chimpanzee -
213 227.
sponse's of single cells in the pon
tine nuclei. Exp Brain Res 1975;
- ( Pan saM/ rus ). J Neurophvsiol 1943;
6:121- 128.
32. Brain R . Speech disorders. Apha -
.
sia apraxia and agnosia . London:
24:15-36. 20. Beck E . Die myeloarchitektomsche Butterworths, 1961 .
8. Allman |M . Evolution of the visual Felderung in der Sylvischen 33. Brinkman C, Porter K Supplemen -
system in the early primates. In : Furche gelegenen Teiles des men - tary motor area in the monkey: ac-
Sprague JM, Epstein A , eds schlichen Schlafenlappens. ) Psv - tivity of neurons during perfor -
Progress in physiological psychol - chol Neurol 1929; 36:1 21 mance of a learned motor task . |
ogy. Vol . 7. New York: Academic 21. Bock E . The origin , course and ter- Neurophysiol 1979;42:681-709.
Press, 1977:1 -53.
9. Allman JM. Kaas II 1. The organiza -
-
mination of the prefronto pontine 34. Brinkman C. Porter K . Supplemen-
tract in the human brain. Brain tary motor area and premotor area
tion ot the second visual area ( VII ) 1950;73:368 391. - of monkey cerebral cortex: func-
in the owl monkey : a second order 22. Beckstead RM , Morse |R , Norgren tional organization and activities
transformation of the visual hemi-
field . Brain Res 1974;76: 247-265.
R . The nucleus of the solitary tract
in the monkey: projections to the
of single neurons during perfor
mance of a learned movement. In :
-
10. Angevine JB |r , Sid man RL. Au - thalamus and brain stem nuclei. J Desmedt JC, ed . Motor control
toradiographic study ol cell migra Comp Neurol 1980;190:259 282. - mechanisms in health and disease
tion during histogenesis ot the 23. Bertrand G. Spinal efferent path New York: Raven Press, 1983:
cerebral cortex in the mouse. Na -
ture 1961;192:766-768
ways from the supplementary -
393 420.
motor area . Brain 1956;79:461 -473. 35. Brinkman J , Bush BM , Porter K .
11 . Asanuma II Functional role of 24 Bindman L, l ippold RL. The neu - Deficient influences of peripheral
stimuli on precentral neurones in 52. Campbell AW . I listological studies thalamus. II . Vestibulopropriocep-

monkeys with dorsal column le - on the localization of cerebral func- tive convergence at thalamic neu -
36. —
sions. j Phvsiol ( Lond ) 1978;276:
27 18.
Broca P. Sur le siege de la faculte
du lan age articule. Bull SIK AIV
tion. New York : Cambridge Uni -
versity Press, 1905.
53. Carlsson A . Antipsychotic drugs
and catecholamine synapses. J Psy -
71 .
rons. Exp Brain Res 1977;30:
219-232.
DeJong R \ . The neurological ex -
amination . 4 th ed . New York:
^ -
thropol 1865;6:377 393. ^
chiat Res 1974;11 :57 64 . Harper & Row , 1979.
37. Brixial A . The oliviKerebellar pro - 54. Carlsson M , Carlsson A. Interac- 72 DeLong MR . Activity ol pallidal
jection in the cat as studies with tions between glutamatergic and neurons during movement. J Neu -
the methixl of retrograde axonal monoaminergic systems within the rophysiol 1971; 34:414-427.
transport of horseradish peroxi- basal ganglia: implications for 73 Dekker ||, Kievit |, Jacobson S,
dase. II . The projection of the schizophrenia and Parkinson's dis- Kuypers HGJM . Retrograde ax -
ease. Trends Neurosci 1990;13:
38 —
uvula . ) Comp Neurol 1976, 166:
417 126.
Brodal A . Neurological anatomy in
relation to clinical medicine. 3rd
272-276.
55. Carman JB, Cowan WM, Powell
TI*S. Cortical connexions of the
onal transport of horseradish per -
oxidase in the forebrain of the rat ,
cat and rhesus monkey. In : Santini
M , ed . Prospectives in neurobiol -
ed . New York : Oxford University thalamic reticular nucleus. J Anat ogv. Golgi centennial symposium .
Tress. 1981 . 1964;98:587-598. New York: Raven Press, 1975:
3*1. Brodal P. The corticopontine pro- 56. Carmel PW . Efferent projections of 201 -208.
jection in the cat . I . Demonstration the ventral anterior nucleus of the 74. IX* Lacoste MG, Kirkpartrick JB,
of a somatotopically organized thalamus in the monkey. Am J Ross ED. Topography of the
projection from the primary senso- Anat 1970;128:159-184 . human corpus callosum . J Neu -
rimotor cortex . Exp Brain Res 1968; 57. Casseday JH, Diamond IT, Harting ropath Fxp Neurol I 985;44:
5: 212 237. |K Auditory pathways to the cor - 578-591 .
40. Brixial P. The corticopontine priv .
tex in Ttiiwtti $lis J Comp Neurol 75. Denny - Brown D. The frontal lobes
jection from the visual cortex in the 1976;166:303- 340. and their functions. In: Feiling A ,
cat . I . The total projection and the 58. Cogan DC». Neurology of the oeu - ed . Mixlern trends in neurology .
projection from area 17. Brain Res lar muscles. 2d ed . Springfield, IL: New York . Paul B. I loeber, 1951 :
1972;39:297-317. Charles C. Thomas, 1956 . -
13 89.
41 . Brixial P. The corticopontine pro- 59. Colonnier M . The fine structural 76 DeVito JL, Smith OA |r Pro|ections
jection from the visual cortex in the arrangement of the cortex. Arch from the mesial frontal cortex ( sup-
cat . II . The projection from areas 18 Neurol 1967;16:651-657. plementary motor area ) to the cere-
and 19. Brain Res 1972;39:319-335. 61) . Colonnier M . The electron micro- bral hemispheres and brain stem ol
42. Brodal P. Principles of organiza - scopic analysis of the neuronal or - the Mminn mulatln.|Comp Neurol
tion of the monkev corticopontine ganization of the cerebral cortex . 1999;]11261 2
projection . Brain Res 1978;148: In : Schmitt FO, Worder FG , Adel - 77. Diamond IT, Jones EG, Powell
214-218. man G , Dennis SG, eds . The orga - TPS. Interhemispheric fiber con-
43. Bnxla l P. The corticopontine pro - nization of the cerebral cortex. nections of the auditory cortex in
jection in the rhesus monkey: ori - Cambridge, MA: MIT Press, 1981: the cat Brain Res 1968;11:177-193.
gin and principles of organization . 125-152. 78. Diamond IT, Jones EG, Powell
Brain 1978;101:251-283 61. Cooper Mil , Beal JA . The neurons TPS. The asstxiation connections
44. Brixlmann K. Vergleichende and the synaptic endings in the of the auditory cortex of the cat.
Lokalisation lehre der Crosshirn - primate basilar pontine gray. I Brain Res 1968; I 1 : 560-579.
rinde in ihren Prinzipien Comp Neurol 1978;180: 17-42. 79 Diamond IT, |ones EG, Powell
dargestellt aut Grund des Zellen-
baues. Leipzig: J. A. Barth , 1909.
62. Coulter JD, Ewing l , Carter C. Ori -
gin of primary sensorimotor corti -
-
TPS The projection of the auditory
cortex upon the diencephalon and
45 Brozoski TJ , Brown RM , Rosvold cal projections to lumbar spinal brain stem in the cat. Brain Res
I IF., Goldman l *S. Cognitive deficit cord of cat and monkey. Brain Res -
1969;15:305 340.
cause by regional depletion of 1976;103:366-372. 80. Douglas R|, Martin KA . Neocortex.
dopamine in prefrontal cortex of 6.3. Coulter JD, Jones EG. Differential In : Shepherd CM , ed . The synaptic
rhesus monkey. Science 1979;205: distribution of corticospinal projec- organization ot the brain . Chap. 12.
929-932. tions from individual cytoarchitec - New York: Oxford University
46. Brugge JF, Reale RA . Auditory cor - tonic fields in the monkey. Brain .
Press 1990:389-438.
tex. In : Peters A , Jones F.G, eds. Res 1977;129:335-340. 81 . Fmmers R. l.ixalization of thala -
Cerebral cortex . Vol. 4. New York: 64. Coyle JT, Price DL, DeLong MR . mic projection of afferents from the
Plenum Press, 1985:229-271 . Alzheimer's disease: a disorder of tongue in the cat Anal Res 1964 ;
47 Brvden MP. Laterality : functional cortical cholinergic innervation . 148:67-74 .
asymmetry in the intact brain. Science 1983;219:1184-1190. 82. Enimers R . Separate relays ol tac -
New York: Academic Press, 1982 . 65. Cragg BG . The density of synapses tile, thermal and gustatory nnxlali -
48. Bucy PC. Effects of extirpation in and neurones in the motor and vi - ties in the cat thalamus. Prix Six
man . In : Buev PC, ed . The precen - sual areas of the cerebral cortex . J Exp Biol Med 1966; 121:527-531
tral motor cortex . 2d ed . Ch. 14. Ur- Anat 1967;101:639-654. 83. Emmers R, Benjamin RM ,
bana : University of Illinois Press, 66 Critchley M . The parietal lobes. BlonK|uist AJ . Thalamic lixaliza -
-
1949:353 394. London: Edwrard Arnold , 1953 tion of afferents from the tongue in
49. Burton II Second somatosensorv 67. Cvnader M , Berman N . Receptive- albino rat . J Comp Neurol 1962;
cortex and related areas. In : Jones field organization of monkey supe - 118:43-48.
EG , Peters A, eds. Cerebral cortex . rior colliculus. | Neurophysiol 84 . Emson IV, Hunt SP. Peptide -con -
Vol . 5. New York: Plenum Press, -
1972;35:187 201. taining neurons of the cerebral cor -
1986:31-98. 68. Damasio AR, Geschwind N . The tex. In : Jones EC, Peters A , eds
50. Burton H . Jones EG. The posterior neural basis of language. Annu Cerebral cortex . Vol . 2. New York:
thalamic region and its cortical Rev Neurosci 1984;7: 127-147 Plenum Press, 1984;145-169.
projection in new world and old 69. Davies P, Maloney A|R . Selective 85. Falconer MA . Relief of intractable
world monkeys J Comp Neurol loss of central cholinergic neurons pain of organic origin by frontal lo-
1976;168: 249 -302. in Alzheimer's disease. Lancet botomy. Proc Assoc Res Nerv
51 Buttner U , I lenn V . Thalamic unit
activity in the alert monkey during
1976;2:140-3.
70 Deecke L, Schwarz DWF, Fredrick -
-
Ment Dis 1948;27:706 722.
86 Felleman DJ , Nelson R|, Kaas JIL
natural vestibular stimulation. son JM . Vestibular responses in the Representations of the body sur -
Brain Res 1976;103:127-132. rhesus monkey ventroposterior face in areas 3b and I of postcentral
cortex of cebus monkeys. Brain Res relay sites of the visual pathway. J primate prefrontal cortex and reg-
1983:268:15-26. Neurol Neurosurg I’sychiatrv 1968; ulation of behavior by representa -
87. Fibiger HC . Cholinergic mecha - -
31:135 157. tional memory. In: Plum F, Mount -
nisms in learning, memory and de- 104 Garey LJ , Powell TPS. The projec - castle VB, eds. Handbook of
mentia : a review of recent evi -
dence. Trends Neurosci 1991 , 14:
tion of the retina in the cat. J Anat
1968;102:189-222 .
physiology. Vol. V : Higher func
tions of the brain. Part 1, Sect . 1:
-
220-223. 105. Gazzaniga MS. The bisected brain. The nervous system . Bethesda ,
88. Foerster O. The cerebral cortex in New York: Appleton Century - - MD: American Physiological
man Lancet 1931;2:309 312. -
89 Foerster O. Motor cortex in man in
Crofts, 1970.
106. Gazzaniga MS. Organization of the
-
Society, 1987:373 417.
-
124. Gold man Rakic PS. Topography of
the light of Hughlings Jackson's human brain. Science 1989;245: cognition: parallel distributed net -
doctrines. Brain 1936;59:135-159. 947-952. works in primate association cor -
90. Foerster O. Svmptomatologie der .
107. Gazzaniga MS Bogen JE, Sperry tex. Annu Rev Neurosci 1988;11 :
Erkrankungen des Grosshims. Mo- RW . Observations on visual per - 137-136.
torische Felder und Bahnen. In : ception after disconnexion of the -
125. Goldman Rakic I *S, Leranth C ,
Bumke O, Foerster O, eds. Fland - cerebral hemispheres in man . Brain Williams SM . Dopamine synaptic
buch der Neurologie. Vol. 6. -
1965;88:221 236. complex on pyramidal neurons
Berlin: Julius Springer, 1936:1-357. 108. Gazzaniga MS, Sperry RW . Lan - in primate cerebral cortex. Proc
91 Fonnum F. Glutamate: a neuro- guage after section of the cerebral Natl Acad Sci USA 1989;86:
transmitter in mammalian brain . J commissures. Brain 1%7,^0:131- 9015-9019.
Neurochem 1984;42:1 - 11. 148. 126. Green JR , Duisberg REH . McGrath
92. Finite SI ., Morrison Jll . Extrathala - 109. Gerstmann J . Syndrome of finger WB. Orbitofrontal lobotomy with
mic modulation of cortical func- agnosia : disorientation for right reference to effects on 55 psychotic
tion . Ann Rev Neurosci 1987;10: and left, agraphia and acalculia. patients. J Neurosurg 1952;9:
67-95. Arch Neurol Psychiatry 1940;44 : -
579 587.
93. Forbes BF, Moskowitz N . Projec - 398-408. 127. Gross NB, Lifschitz WS, Anderson
tions of auditory responsive cortex 110. Geschwind N . Disconnexion syn - DJ The tom>topic organization of
in the squirrel monkev . Brain Res dromes in animals and man . I . the auditory thalamus of the squir -
1974;67:239-254. Brain 1965;88:237-294. rel monkey ( Saimiri sdureus ). Brain
94 . Fredrickson |M , Figge U, Scheid P, 111 . Geschwind N . Disconnexion syn - Res 1974;65:323-332.
Kornhuber 1111 Vestibular nerve dromes in animals and man . II 128. Hay how WR The cytoarchitecture
projection to the cerebral cortex of Brain 1965;88:585-644. of the lateral geniculate body in the
the rhesus monkey. Exp Brain Res 112 Geschwind N . The organization of cat in relation to the distribution of
-
1966;2:318 327. language and the brain . Science crossed and uncrossed optic fibers.
.
95. Fredrickson JM Kornhuber HH, 1970;170:940-944. I Comp Neurol 1958;110:1-64.
Schwarz DWF. Cortical projections 113. Geschwind N . Specialization ot the 129. Hendrickson AF., Hunt SP, Wu J -Y.
of the vestibular nerve. In : Kornhu - human brain. Sci Am 1979;24 l : lmmunocytochemical localization
ber II , ed . Handbook of sensory 180-199. of glutamic acid decarboxylase in
physiology. Vol. 6. Berlin : 114 . Geschwind J , Galaburda AM monkev striate cortex. Nature
-
Springer Verlag, 1974 : 565-582. Cerebral dominance: the biological 1981;292:605-607.
96. Fredrickson ) M , Rubin AM . foundation . Cambridge, MA : Har - 130. Henschen SE. On the function of
Vestibular cortex . In : Jones EG , Pe - vard University Press, 1984 the right hemisphere ot the brain
ters A , eds. Cerebral cortex . Vol . 5. 115. Geschwind N , Galaburda AM . in relation to the left in speech ,
New York : Plenum Press, 1986: Cerebral lateralization: biological music and calculation. Brain 1926;
99- HI mechanisms, associations and 49:110-123.
97. Freeman W , Watts JW. Psy- pathology . Cambridge, MA : MIT 131 . Hickey TL, Guillery RW. An au-
chosurgery Intelligence, emotion Press, 1987. toradiographic study of retino-
and st >cial behavior following pre- 116 Geschwind N, Kaplan E. A human gcniculate pathways in the cat and
frontal lobotomy for mental disor - cerebral deconnection syndrome. the fox. J Comp Neurol 1974;
ders. 2d ed. Springfield , IL: Charles Neurology 1962;12:675-685. 156:239-254.
C. Thomas, 1949. 117. Gilbert CD. Horizontal integration 132. Hines M. The "motor" cortex. Bull
98. Friedman DP, Jones EG. Burton H in the visual cortex. Trends Neu- Johns Hopkins Hosp 1937;60:
Representation pattern in the sec- rosci 1985;8:160-165. 313-336.
ond somatic sensory area of the 118 Gilbert CD. Horizontal integration 133. Hines M . Significance of the pre-
monkev cerebral cortex . J Comp and cortical dynamics. Neuron central motor cortex. In : Buev PC ,
Neurol 1980;192:21 -41. 1992;9:1-13. ed . The precentral motor cortex .
99. Fulton JF, Keller AD. The sign of 119 . Gilbert CD, Kelly Jl*. The projec- Ch. 18. Urbana : University of Illi-
Babinski . A study of the evolution tion of cells in different layers of nois Press, 1949 461 -494 .
of cortical dominance in primates. the cat 's visual cortex . J Comp 134 Hobson JA , Steriade M . Neuronal
Springfield , IL : Charles C. Thomas. Neurol 1975;163:81-106. basis of behavioral state control. In:
1932. 120. Giuffrida R , Rustioni A . Glutamate BUKMTI FE, ed. I landbook of physi-
100. Fulton JF, Kennard MA . A study of and aspartate immunoreactivity in ology. Vol . IV : Intrinsic regulatory
flaccid and spastic paralysis pro - corticothalamic neurons of rats. In : system of the brain . Sect . I : The
duced by lesions of the cerebral Bentivoglio M. Spreatico R , eds. nervous system. Bethesda MD: .
cortex in primates. Prix Assoc Res Cellular thalamic mechanisms. American Physiological Society ,
Nerv Ment Dis 1934;13:158-210. Amsterdam : Elsevier, 1988:311- 1986:701-823.
101 Ga lambos R , Rose JE. Microelec - 320. 135. Hollander H . Projections from the
trode studies on medial geniculate 121. Giuffrida R , Rustioni A . Glutamate striate cortex to the diencephalon
body of the cat . Ill Response to and aspartate immunoreactivity in in the squirrel monkey ( Sai / mri sci
pure tone J Neurophvsiol 1952; corticospinal neurons of rat . J urcus ): a light microscopic radioau -
15:381-400. Comp Neurol 1989;288:154-164. tographic study following intracor -
102. Garey LJ . Visual system. In : Paxi - 122 Goldman PS, Nauta WJH . Colum - tical injection of lH leucine. J Comp
.
nos G ed . The human nervous sys - -
nar distribution of cortico cortical -
Neurol 1974;155:424 440.
tem . Ch . 28. New York : Academic fibres in the frontal association, 136. Holmes G, May WP On the exact
-
Press, 1990:945 977. limbic and motor cortex of the de - origin of the pyramidal tract in
103. Garey LJ , Jones EG, Powell TI *S. veloping Rhesus monkey . Brain man and other mammals. Brain
Interrelationships of striate and ex
trastriate cortex with the primary
- Res 1977;122:393-413
123. Goldman - Rakic PS. Circuitry of
-
1909;32: 1 43
137. Houser CR , Vaughn IE , Hendrv
SHC, Jones EG, Peters A . GABA 154 . Huerta MJ , Krubitzer LA, Kaas JH . 169. Jones EG, Coulter JD, Hendry
neurons in the cerebral cortex. In : Frontal eye field as defined by in - SHC. Intracortical connectivity of
Jones EG, Peters A , eds. Cerebral tracortical microstimulation in architectonic fields in the somatic
cortex. Vol. 2. New York: Plenum squirrel monkeys, owl monkeys sensory , motor and parietal cortex
-
Press, 1984:63 89. and macaque monkeys. II . Cortical of monkeys. I Comp Neurol
138. I lubel DH - The visual cortex of the connections. J Comp Neurol 1987; 1978; 181:291 - 348
139.
-
brain. Sci Am 1963;209:54 62.
Hubei DH, LeVay 5, Wiesel TN . 155.
-
265:332 361.
Ilinsky I A , Tourtellotte VVG, Kul -
170. Jones EG, Friedman DP. Projection
pattern of functional components
-
Mode of termination of retino tec- tas-llinsky K . Anatomical distinc- of thalamic ventrobasal complex
tal fibers in macaque monkey: an tions between the two basal gan - on monkey somatosensory cortex
J Neurophvsiol 1982;48:521 -544.
.-
autoradiographic studv. Brain Res glia afferent territories in the
140.
-
1975 96:25 40.
Hubei DH, Wiesel TN . Receptive
primate motor thalamus. Stereo-
tact Fund Neurosurg 1993,60: *
171 . Jones EG . Hendry SHC. Distribu -
tion of callosal fibers around the
fields of single neurons in the cat 's 62-69. hand representation in monkey so-
striate cortex. J Phvsiol ( Lend ) 156. Imig TJ , Adrian HO. Binaural matic sensory cortex. Neurosci Lett
1959;148:574 591.- columns in the primary field ( Al ) 1980;19:167 172. -
141. Hubei DH, Wiesel TN . Integrative of cat auditorv cortex. Brain Res 172. Jones EG, Leavit RY . Retrograde
action in the cat 's lateral geniculate 1977;138:241 -257. axonal transport and the demon -
body . I Phvsiol ( Lond ) 1961 ;155: 157. Imig TJ , Morel A . Tonotopic orga - stration of non -specific projections
142.
-
385 398.
Hubei DH , Wiesel TN . Receptive
nization of the ventral nucleus of
the medial geniculate body in the
to the cerebral cortex and striatum
from thalamic intralaminar nuclei
fields, binocular interaction and cat . J Neurophvsiol 1985;53:309- in the cat , rat and monkey. J Comp
functional architecture in the cat's 340. Neurol 1974,154:349- 378.
visual cortex . J Phvsiol ( Lond ) 158. .
Imig TJ , Ruggero MA Kitzes LM , 173. Jones EG , Porter R . What is area
143.
1962;160:106- 154.
Hubei DH, Wiesel TN . Shape and
Javel E, Brugge JF. Organization of
auditory cortex in the owl monkey 174 .
- .
3a ? Brain Res Rev 1980;2:1 43.
Jones F.G, Powell TPS. The ipsil it -
arrangement of columns in cat 's ( Aotus inrir utus ). J Comp Neurol eral cortical connexions of the so-
striate cortex. J Phvsiol ( Lond ) ^
1977;171:111-128. matic sensory areas in the cat
1963;165:559-568. 159. Jacobs Bl., Azmitia EC. Structure Brain Res 1968;9:71 -94.
144 Hubei DH , Wiesel TN . Receptive and function of the brain serotonin 175. Jones EG, Powell TPS. Connexions
fields of cells in striate cortex of system. Phvsiol Rev 1992:72: of the somatic sensory cortex of the
very young, visually inexperienced 165-229. rhesus monkey. I . Ipsilateral corti -
kittens. J Neurophvsiol 1963;26: 160. Jacobsen CF. Functions of frontal cal connexions. Brain 1969,92:
994-1002. association area in primates. Arch 477 502 .
145. Hubei DH, Wiesel TN . Receptive Neurol Psychiat 1935;33:558-569. 176. Jones EG, Powell TIN Connexions
fields and functional architecture 161 . Jasper HH . Unspecific thalamocor - of the somatic cortex of the rhesus
-
in two non striate visual areas ( 18 tical relations. In : Field J, ed . Hand - monkey . II Contralateral cortical
and 19) of the cat . J Neurophvsiol book of physiology. Vol II , Sect . I , connexions. Brain 1969;92:717-730.
1965;28:229-289. Ch . 53. Washington, DC: American 177. Jones EG, Powell T1*S. Connexions
146. Hubei DH , Wiesel TN . Cortical Physiological Society , 1960:1307- of the somatic sensory cortex of the
and callosal connections concerned 1326. rhesus monkey . II. Thalamic con -
with the vertical meridian of visual 162. Jerger JF. Observations on auditory nexions. Brain 1970,93:37-56.
fields in the cat . J Neurophvsiol behavior in lesions of the central 178. Jones EG, Powell TIN. Anatomical
1967;30:1561-1573. auditory pathways. AMA Arch organization of the somatosensory
147. Hubei DH , Wiesel TN . Receptive Otolaryngol 1960;71:797-806. cortex . In: Iggo A , ed . I land book of
fields and functional architecture 163. Jones EG . Some aspects of the or - sensory physiology. Vol. 2. Berlin :
of monkey striate cortex . 1 Physiol ganization of the thalamic reticular Springer- Verlag , 1973:579-620.
'
-
( Lond ) 1968;195:215 243. complex. J Comp Neurol 1975;162: 179. .
Jones EG Wise SP. Size, laminar
148. Hubei DH , Wiesel TN . Stereo- 285-308. and columnar distribution of effer -
scopic vision in macaque monkey. 164. Jones EG . Anatomy of cerebral cor - ent cells in the sensory- motor cor-
Nature 1970;225:41-42. tex : columnar input - output organi - tex of monkeys. J Comp Neurol
149. Hubei DH , Wiesel TN . Laminar
and columnar distribution of
zation . In : Schmitt FO, Worden FG,
Adelman G, Dennis SG , eds. The 180.
1977;175:391 438.-
Jones EG , WiseSP, Coulter JD. Dif -
-
geniculo cortical fibers in the organization of the cerebral cortex . ferential thalamic relationships of
Macaque monkey. J Comp Neurol Cambridge, MA : MIT Press, 1981 -
sensory motor and parietal cortical
1972;146:421-450 199-235. fields in monkey. J Comp Neurol
150. Hubei DH , Wiesel TN . Sequence 165. Jones EG . Connectivity of primate 1979;183:833-881
regularity and geometry of orien - -
sensory motor cortex. In: Jones EG, 181 . Jouvet M. Neurophysiology of the
tation columns in the monkey stri - Peters A , eds. Cerebral cortex. Vol. states of sleep. Phvsiol Rev 1967;
ate cortex. J Comp Neurol 1974; 5. New York : Plenum Press, 1986: 47:117-177.
158:267-294 -
113 183. 182. Jouvet M . Biogenic amines and the
151. Hubei DH , Wiesel TN. Uniformity 166. Jones EG . Ascending inputs to, and states of sleep. Science 1969; 16.3:
of monkey striate cortex: a parallel internal organization of , cortical -
32 41.
relationship between field size, motor areas. In : Motor areas of the 183 Jurgens J . The efferent and afferent
scatter and magnification factor. J cerebral cortex . CIBA Foundation connections of the supplementary
Comp Neurol 1974;158:295-306. symposium. Chichester: John motor area . Brain Res 1984;300:
152. Hubei DH , Wiesel TN , LeVay S. Wiley & Sons, 1987:132:21- 39 63-81 .
Plasticity of ocular dominance 167. Jones EG, Burton FI . Cytoarchitec - 184 . Kaes T. Die Grosshimrinde des
columns in monkey striate cortex . ture and somatic sensory connec- Menschen in ihren Masson und in
Phil Trans R Soc Lond ( Biol ) 1977; tivity of thalamic nuclei other than ihrem Fasergehalt . Vol. I. Jena:
-
278:377 409 .
153. Huerta ME, Krubit /er LA , Kaas 111
the ventrobasal complex in the cat .
J Comp Neurol 1974;154:395 432. -
Gustav Fischer, 1907.
185 Kandel ER . Disorders of thought
Frontal eye field as defined by in - 168. Jones EG, Coulter JD Burton II , schizophrenia In : Kandel FR ,
tracortical microstimulation in Porter R. Cells of origin and termi - Schwartz ) H , Jessell TM , eds. Prin -
squirrel monkeys, owl monkeys nal distribution of corticostriatal ciples of neural science. Ch. 55.
and macaque monkeys. I . Subcorti - -
fibers arising in the sensory motor New York: Elsevier, 1991:853 868
cal connections. J Comp Neurol cortex of monkeys. J Comp Neurol 186 Karol FA , Pandya DN The distrib -
1986;253:415-439. 1977;173:53-80. ution of the corpus callosum in the
rhesus monkev . Brain 1971;94 : 202. Krieg WJS. Connections of the 219. Lassek AM, Rasmussen GL. The
—
471 186 . cerebral cortex . I. The albino rat . C. human pyramidal tract: a fiber and
187. Kawamura S, Sprague JN, Niimi K . Extrinsic connections. ) Comp numerical analysis . Arch Neurol
Corticofugal projections from the Neurol 1947;86:267-394. Psychiatry 1939;42:872-876.
visual cortices to the thalamus in 203. Krieg WJS. Connections of the 220. Lassek AM, Rasmussen GL. A
the cat | Comp Neurol 1974;158: cerebral cortex . II. The macaque. E. comparative fiber and numerical
.339- 362. The postcentral gyrus. J Comp analysis of the pyramidal tract, j
188 Kelly IP, van Essen DC. Cell struc - Neurol 1954; 101: 101- 165. Comp Neurol 1940;72:417-428.
ture and function in the visual cor- 204 . Krnjevic K . Neurotransmitters in 221. Lawrence DG, Hopkins DA . The
tex of the cat . J Physiol ( Lond ) cerebral cortex . In: Jones EG, Peters development of motor control in
1974;238:515- 547 . A , eds. Cerebral cortex. Vol. 2. the rhesus monkey: evidence con-
189 Kemp |M , Powell FI’S. The cortico- New York: Plenum Press, 19K4 : cerning the role of corticomo-
striate projection in the monkev. 39-61. torneuronal connections. Brain
Brain 1970;93:525-546. 205. Kuffler SW . Discharge patterns 1976;99:235-254.
190. Kennard MA . Somatic functions. and functional organization of 222. Lawrence DG, Kuypers HGJM.
In: Bucy PC, ed. The precentral mammalian retina. J Neurophvsiol The functional organization of the
motor cortex . 2d ed. Ch. 9. Urbana . 1953;16:37-68. motor system in the monkey . 1
University of Illinois Press, 1949: 206. Kunzle II. Thalamic projections The effects of bilateral pyramidal
243- 276. from the precentral motor cortex in lesions. Brain 1988;91: 1- 14 .
191 . Kennard MA , Fulton JF. The local- Macaca fascicularis. Brain Res 1976; 223. Le Gros Clark WE. The structure
izing significance of spasticity, re- 105:253-267. and connections of the thalamus.
flex grasping and the signs of 207. Kunzle II. An autoradiographic Brain 1932;55:406-470.
Babmski and Rossolimo. Brain analysis of the efferent connections 224 . Le Gn>s Clark WE. The connec-
1933;56:213- 225. from premotor and adjacent pre- tions of the frontal lobes of the
192. Kennard MA . Viets HR , Fulton JF. frontal regions ( areas 6 and 9 ) in brain. Lancet 1948;1:353-356.
The syndrome of the premotor cor - Macaca fascicular is. Brain Bohav 225. Le Gros Clark WE, Boggon RH .
tex in man: impairment of skilKsJ Evol 1978;15: 185- 234. The thalamic connections of the
movement , forced grasping, spas- 208. Kunzle H , Akert K. Efferent con - parietal and frontal lobes ot the
ticity and vasomotor disturbances. nections ot cortical Area 8 ( frontal brain in the monkey . Phil Trans R
Brain 1934;57:89-84 eye field ) in Macaca fascicularis: a Sot Lond ( Biol ) 1935;224:313- 359.
193. Kennedy C, IX *s Rosiers Mil, reinvestigation using the autoradi- 226. Le Gros Clark WE. Powell TPS On
Sakurada O, et al. Metabolic map- ographic technique. ) Comp Neu- the thalamocortical connexions of
ping ot the primary visual system rol 1977; 173: 147- 164 the general sensory cortex ot
of the monkey by means of the au - 209 Kunzle H. Akert K , Wurtz RH. Macaca. Proc R Soc Lond ( Biol )
toradiographic |MC| dcoxvglucose Projections of area 8 ( frontal eye 1953; 141 :467-487.
technique. Proc Natl Acad Sci USA field ) to superior colliculus in the 227. LeVay S, I lubel D, Wiesel TN. The
1976;73:4230-4234 monkev : an autoradiographic pattern of ocular dominance
194 . Kerr FWL, I ippman Hll. The pri- study. Brain Res 1976;117:487-492 . columns in Macaque visual cortex
mate spinothalamic tract as 210. Kuo |- S, Carpenter MB. Organiza- revealed by reduced silver stain . |
demonstrated by anterolateral cor - tion of pallidothalamic projections Comp Neurol 1975;!59:559 576 .
dotomy and commissural myelot - in the rhesus monkev. J Comp 228 . LeVay S, Wiesel TN, Hubei Dll .
omy . Adv Neurol 1974 ;4 : 147- 158 Neurol 1973;151:201- 236. The development of ocular domi -
195 . Kievet J , Kuypers HGJM. Organi- 211. Kupfermann I . Localization of nance columns in normal visually
zation of the t ha I amocortical con - higher cognitive and affective deprived monkeys. J Comp Neurol
nexions to the frontal lobe in the functions: the association cortices. 1980;191:1- 51 .
rhesus monkev. Exp Brain Res In : Kandel FR , Schwartz JII, Jessell 229 Levin PM . The efferent fibers of the
1977;29:299- 322. TM, eds. Principles of neural sci- frontal lobe of the monkey ( Macaca
196. Kim R, Nakano K , J a vara man A , ence. Ch. 53. New York: Elsevier , .
mulatto ) J Comp Neurol 1936,*63:
Carpenter MB. Projections of the 1991:823-838. 369-419.
globus pallidus and adjacent struc- 212. Kuypers HGJM. Central cortical 230. Levin PM . Efferent fibers In. Bucy
tures: an autoradiographic study projections to motor and somato- IX. , ed . The precentral motor cor -
in the monkev . J Comp Neurol sensory cell groups. Brain 1980; tex . 2d ed . Ch. 5 . Urbana: Univer -
I 6 169 261 289 83: 161 - 184 . sity of Illinois Press, 1949:133-148.
197 Kisvarday ZF, Martin KAC, Fre- 213. Landis C, Zubi J , Mettler FA. The 231. Levin PM, Bradford FK. The exact
und TF, Maglbczy 7 , Whitteridge functions of the human frontal origin of the corticospinal tract in
D, Somogyi P Synaptic targets of lobe. J Psychol 1950;30: 123- 138. the monkev . I Comp Neurol 1938;
FIRP- filled layer ill pyramidal cells 214 Lassek AM. The human pyramidal 68: 411-422.
in the cat striate cortex . Exp Brain tract. II . A numerical investigation 232. Lewis DA, Campbell MJ, Foote SL,
Res 1986;64:541-552. of the Betz cells of the motor area . Goldstein M, Morrison JIL The dis-
198. Klcitman N. Sleep and wakeful - Arch Neurol Psychiatry 1940;44: tribution of tyrosine hydroxvlaso-
ness. Chicago: University of 718-724 . immunoreactive fibers in primate
Chicago Press, 1983. 215 Lassek AM. The human pyramidal neocortex is widespread but re-
199. Konishi M, Knudson EL A theory tract. IV . A study of the mature, gionally specific. | Neurosd 1987;
of neural auditory space. In: myelinated fibers of the pyramid . | 7:279- 290.
Woolsoy CN, ed. Cortical sensory Comp Neurol 1942;76:217-225. 233. Lewis DA, Campbell MJ, Foote SL,
organization. Vol. 3. Clifton, NJ: 216. Lassek AM. The pyramidal tract . Morrison JH. The monoaminergic
Humana Press, 1982:219- 229. The effect of pre- and postcentral innervation of the primate neocor-
200. Kornhuber Hll , Fredrickson JM, cortical lesions on the fiber compo- tex. Human Neurobiol 1986;5:
Figge U. Die korticale Projektion nents of the pyramids in monkey. | 181- 186 .
der vestibularen Affercnz Beim New Ment Dis 194205:721 729 234 . Lidov MS, Goldman- Rakic PS, Gal-
Rhesusatten Pfluegers Arch 1985; 217 Lassek AM . The pyramidal tract: lager DW , Geschwind Dll, Rakic
283:20. its status in medicine. Springfield, P. Distribution of major neuro-
201 Koskoff YD, Dennis W , Lazovik D, li e hartesc Thomas, 1951 transmitter receptors in the motor
Wheeler FT. The psychological of - 218. Lassek AM , Evans JP. The human and somatosensory cortex of the
feels of frontal lobotomy per - pyramidal tract. XII The effect of rhesus monkev . Neuroscience
formed for alleviation of pain . Proc hemispherectomies on the fiber 1989;32:609-627.
Assoc Res Nerv Ment Dis 1948; components of the pyramids. J 235 . Liedgren SRC , Milne AC , Rubin
27: 723- 753. Comp Neurol 1945;83:1i 3- 119. AM , Schwarz DWF, Tomlinsen
RD. Representation of vestibular tion following anterolateral cordot - le traitement de certaines psy -
afferents in somatosensory thala - omy: an experimental study in the choses. Paris: Masson , 1936.
mic nuclei of the squirrel monkey monkey. Brain 1960;83:718- 750. 263 Morest DK. The neuronal architec -
( Saimiri sciurcus ). | Neurophysiol 248. Merzenich MM , Brugge JF. Repre- ture of the medial geniculate body
1476;39:601-612. sentation of the cochlear partition of the cat . J Anal 1964 ;98:61 1 -6.38.
236. Lindslev DB. Attention , conscious- on the superior temporal plane of 264 . Morrison JH , Hof PR . The organi -
ness, sleep and wakefulness. In : the Macaque monkev. Brain Res zation of the cerebral cortex: from
Field J , ed . Handbook of physiol - 1973;50:275-296. molecules to circuits. In : Mag-
ogy . Vol. Ill , Sect . 1 . Washington, 249. Merzenich MM , Kaas JH , Sur M , istretti PJ , ed . Discussions in neu -
DC: American Physiological Soci - Lin CS. Double representation ot roscience. Vol . 9. Amsterdam : Else-
ety , I %0:1553-1393.
237. Lindvall O, Bjorklund A . General
the bixlv surface within cvtoarchi - .
vier 1992:11 - 79.
tectonic Areas 3b and 1 in “SI " in 265 Momizi G, Magoun HW . Brain
organization of cortical mono- the owl monkey ( Aotus trivigatu* ) I . stem reticular formation and acti -
amine systems. In : Descarries L, Comp Neurol 1978;181:41 - 74. vation of the EHG. Electroen -
Reader TR , Jasper HH, eds. 250. Merzenich MM , Knight PL, Roth cephalogr Clin Neurophvsiol 1949;
Monoamine innervation of cere- GL. Cochleotopic organization of -
1:455 473.
bral cortex. New York : Alan Liss, primarv auditory cortex in the cat 266 . Mountcastle VB. Modality and
1984:9-40. Brain Res 1973;63:343-346. topographic properties of single
238. Liu CN , Chambers WW . An exper - 251 . Merzenich MM , Knight PL, Roth neurons of cat 's somatic sensory
imental study of the corticospinal GL. Representation of cochlea cortex . | Neurophysiol 1957;20:
system in the monkey ( Macaca mu within the primary auditory cortex 408-434.
latta ): the spinal pathways and in the cat . | Neurophysiol 1975; 267. Mountcastle VB. Interhemispheric
preterminal distribution of degen - 38:231-249 . relations and cerebral dominance.
erating fibers following discrete le - -
252 . Mesulam M M, Geula C. Nucleus Baltimore: Johns Hopkins Univer -
sions of the pre- and postcentral basalis (Ch 4 ) and cortical choliner - sity Press, 1974 .
gvri and bulbar pyramid . J Comp gic innervation in the human 268. Mountcastle VB. Central nervous
Neurol 1964;123:257-284. brain: observations based on the mechanisms in mecanoreceptive
239. Lorente de No R . The structure of distribution of acetylcholinesterase sensibility. In: Darian -Smith I , ed
the cerebral cortex . In . Fulton |F, and choline acetyltransferase. J Handbt >ok of physiology. Vol . Ill
ed . Physiology of the nervous sys- Comp Neurol 1988;275:216-240. Sensory processes. Part 2, Sect. I
tem . 3rd ed . New York : Oxford 253. Mesulam M - M , Geula C. Overlap The nervous system . Bethesda ,
-
University Press, 1949:288 330. between acetylcholinesterase-rich MD. American Physiological Stxi -
240. Lund JS, Lund RD, Hendrickson -
and choline acetyltransferase posi - etv, 1984;789 878.
AH , Bunt AH, Fuchs AF. The origin tive ( cholinergic) axons in human 269. Mountcastle VB, l ynch JC, Geor -
of efferent pathways from the pri - cerebral cortex. Brain Res 1992; gopoulos A, Sakata II , Acuna C
mary visual cortex, area 17, of the 577:112-120. Posterior parietal association cor -
macaque monkey as shown by ret - 254 . Mesulam M - M , Mufson EJ , Levey tex of the monkey: command func-
rograde transport of horseradish Al , Wainer BH. Cholinergic inner- tions for operation within extra -
peroxidase. J Comp Neurol 1975; vation of the cortex by the basal personal space. J Neurophvsiol
164:287-303. forebrain : cytochemistry and corti - 1975;38:871-908.
241 . McCormick DA . Neurotransmitter cal connections of the septal area , 270. Mountcastle VB, Powell TPS. Cen -
actions in the thalamus and cere- diagonal band nuclei, nucleus tral nervous mechanisms subserv -
bral cortex and their role in neuro- basalis (substantia innominata ), ing position sense and kinesthesis .
modulation of thalamocortical ac - and hypothalamus in the rhesus Bull |ohns Hopkins Hosp 1959.
.
tivity Prog Neurobio! 1992#9: monkev. J Comp Neurol 1983; 105: 173 200 .
337-388. 214: 170-197. 271 . Mountcastle VB, Powell TPS.
242. Mamounas LA , Mullen CA, O'- 255. Mettler FA . Connections of the au - Neural mechanisms subserving cu -
Hearn H, Molliver ME. Dual sero - ditory cortex of the cat . J Comp taneous sensibility with special ref -
toninergic projections to forebrain Neurol 1932;55:139-183. erence to the role of afferent inhibi -
in the rat : morphologically distinct 256. Mettler FA . On the origin of the tion in sensory perception and
5- FIT axon terminals exhibit differ - fibers in the pyramid of the pri- discrimination . Bull Johns I lopkins
ential vulnerability to neurotoxic mate brain . Proc Soc Exp Biol Med Hosp 1959;105:201 - 232.
amphetamine derivatives. J Comp 1944;57:111-113. 272. Nauta WJH , Mehler WR Projec -
Neurol 1991;314:538-586. 257. Mettler FA . The non - pvramidal tions of the lentiform nucleus in
243 Martinez Millan L, Hollander IF motor projections from the frontal the monkey Brain Res 1966; 1 :3 -42.
Cortico-cortical projections from cerebral cortex. Proc Assix Res 273. Neff WD, Diamond IT. The neural
striate cortex of the squirrel mon - Nerv Ment Dis 1947;267: 162-199 basis of auditory discrimination
key ( Saimiri >durms ): a radioauto- 258. Mettler FA . Extracortical connec- In Harlow 111 , Woolsey CN , eds
graphic study . Brain Res 1975;3: tions of the primate frontal cere - Biological and biixhemical bases ol
405 417 bral cortex . IF Corticofugal connec- behavior. Madison : University of
.
244 Mash DC White WF, Mesulam M -
M . Distribution of muscarinic re-
tions. J Comp Neurol 1947;86:
119-154. 274
Wisconsin Press, 1958: 101 -126.
Niimi K , Katayama K , Kanaseki I ,
ceptor subtypes within architec- 259. Mettler FA . Selective partial abla - Morimoto K . Studies on the de-
tonic subregions of the primate tion of the frontal cortex: a correla - rivation of the centre median nu -
cerebral cortex. | Comp Neurol tive study of the effects on human cleus of Luys. Tokushima J Exp
-
1988;278:265 274 psychotic subjects. New York: Paul Med 1960;6:261 -268.
245. Masterton RB, Imig TJ . Neural B. I loeber, 1949. 275. Niimi K , Matsuoka H . Thalamo -
mechanisms for sound localiza - 260 Meyers RE. Function of corpus cal - cortical organization of the audi -
tion . Annu Rev Physiol 1984 ;46: losum in interocular transfer Brain tory system in the cat studied by
275-287. 1956;79:358-363. retrograde axonal transport of
246. Maveux K , Kandel HR Disorders 261. Molliver ME, Grzanna R , Lidow horseradish peroxidase. Adv Anat
of language: the aphasia . In : Kan - HGW , Morrison JII , Olschowka Fmbrvol Cell Biol 1979;57: 1 -56.
.
del HR , Schwartz |H Jessell TM , JA . Monoamine systems in the 276. Noback CR , Demarest R| The
eds. Principles of neural science. cerebral cortex. In : Chan - Palay J , human nervous system . 3rd ed.
Ch . 34. New York: Elsevier, 1991:
839-851 .
247. Mehler WR , Feferman ME Nauta .
Palay SL, eds. Cytochemical meth -
ods in neuroanatomy. New York:
Alan Liss, 1983:255-277.
-
New York! McGraw Hill, 1981.
277. Norgren R Gustatory afferents to
ventral forebrain . Brain Res 1974 ;
WJH. Ascending axon degenera - 262. Moniz E. Tentative operatoire dans 81 :285- 295.
278. Norgren R, Leonard CM. Ascend - 295. Patton HD, Ruch TC, Walker AE . tic mechanisms in cerebral cortex
ing central gustatory pathways. J Experimental hypogeusia from of cat . Neurophysiol 1956;19:
Comp Neurol 1973;150:217-238.
279. Norgren JR, Pfaffman C. The pon -
-
Horsley Clarke lesions of the thala -
mus in Macaca mulatto. J Neuro -
-
573 595.
311. Raczkowski D, Diamond IT, Winer
tine taste area in the rat . Brain Res -
physiol 1944;7:171 184 . J Jr. Organization of thalamocorti-
1975;91:99-117. 296. Penfield W . Vestibular sensation cal auditory system in the cat stud -
280. Norgren R , Wolf G. Projection of and the cerebral cortex . Ann Otol ied with horseradish peroxidase.
thalamic gustatory and lingual -
Rhinol 1957;66:691 698. -
Brain Res 1976;101:345 354.
areas in the rat . Brain Res 1975; 297. Penfield W , Boldrey E. Somatic 312. Ramon y Cajal S. Histologie du
92:123-129. motor and sensory representation Syst&me Nerveux de l' Homme et
281 . Nyby O, Jansen J . An experimental in the cerebral cortex of man as des Vertebres. ( Azoulay L, trans.)
investigation of the corticopontine studied by electrical stimulation . Paris: Maloine, 1909, 1911.
projection in Macaca mulatto . Norsk Brain 1937;60:389-443. ( Reprinted Consejo Superior de In-
Vidensk Akad Avh Mat - Naturv 298. Penfield W , Jasper HH . Epilepsy vestigaciones Cientificas, Instituto
1951;3:1-47. and the functional anatomy of the .
Ramon y Cajal, Madrid 1972.)
282. Ohuoha DC, Hyde TM, Kleinman human brain. Boston: Little Brown 313. Rezak M , Benevento LA . A com -
JE. The role of serotonin in schizo- & Company , 1954. parison of the organization of the
phrenia: an overview of the 299. Penfield VV, Rasmussen T. The projections of the dorsal lateral
nomenclature, distribution and al - cerebral cortex of man : a clinical geniculate nucleus, the inferior
teration of serotonin receptors in study of localization of function . pulvinar and adjacent lateral pulv -
the central nervous system. Psy - New York: MacMillan , 1950. inar to primary visual cortex ( area
chopha rmacology 1993;112:5-15. 300. Penfield W , Roberts L. Speech and 17) in the macaque monkey Brain
283. Oliver DL, Hall WC. The medial brain mechanisms. Princeton , NJ: Res 1979;167:19-40.
geniculate body of the tree shrew, Princeton University Press, 1959. 314 . Ricardo JA, Koh ET. Anatomical
Tufwia glis. II . Connections with the 301. Penfield W , Welch K . The supple- evidence of direct projections from
—
neocortex. J Comp Neurol 1978;
182:459 194.
284. Oscarsson O. Functional organiza -
tion of the spino- and cuneocere-
mentary motor area of the cerebral
cortex: a clinical and experimental
study . AMA Arch Neurol Psychia -
try 1951;66:289-317.
the nucleus of the solitary tract to
the hypothalamus, amygdala and
other forebrain structures in the
rat. Brain Res 1978;153:1-26.
bellar tracts. Phvsiol Rev 1965; 302. Percheron G. The thalamic terri - 315. Riley HA. An atlas of the basal
-
45:495 522. tory of cerebellar afferents and the ganglia , brain stem and spinal
285. Oscarsson O. Functional organiza - lateral region of the thalamus of cord. Baltimore: Williams &
tion of spinocerebellar paths. In: the macaque in stereotaxic ventric- Wilkins, 1943.
Iggo A , ed . Handbook of sensory ular coordinates. J Hirnforsch 316. Rinvik E. The corticothalamic pro-
physiology . Vol. 2. Berlin:
Springer-Verlag, 1973:339-380.
-
1977;18:375 400.
303. Perry F.K , Tomlinson BE, Blessed
jection from the pericruciate and
coronal gyri in the cat: an experi -
286. Oscarsson O, Rosen I . Short la - - G, Bergmann K , Gibson PH , Perry mental study with silver- impreg-
tency projections to the cat s cere- RH . Correlation of cholinergic ab - nation methods. Brain Res 1968;
bral cortex from skin and muscle normalities with senile plaques 10:79-119.
afferents in the contralateral fore- and mental test scores in senile de - -
317. Rispal Padel L, Massion J ,
limb. J Physiol ( Lond ) 1966;182: -
mentia . Br Med ) 1977;2:1457 1459. Grangetto A . Relations between
164-184 . 304. Petras JM. Some efferent connec- the ventrolateral thalamic nucleus
287. Otsuka R , Hassler R . liber Aufbau tions of the motor and somatosen - and motor cortex and their possi -
und Gliederung der corticalen sory cortex of simian primates and ble role in the central organization
Sehsphare bei der Katze. Arch Psy - felid , canid and procyonid carni - of motor control . Brain Res 1973;
-
chiatr Nervenk 1962;203:212 234. vores. Ann NY Acad Sci 1969; 60:1-20.
288. Ottersen OP, Storm - Mathisen J . 167:469-505. 318. Roberts TS, Akert K . Insular and
-
Glutamate and GABA -containing 305. Poggio GF, Mountcastle VB. A opercular cortex and its thalamic
neurons in the mouse and rat brain study of the functional contribu - projection in Macaca mulatto.
as demonstrated with a new im - tions of the lemniscal and Schweiz Arch Neurol Neurochir
munocytochemical technique. J spinothalamic systems to somatic Psychiatr 1963;92: 1 -43.
Comp Neurol 1984;229:374-392. sensibility. Bull Johns Hopkins 319. Robinson CJ , Burton H . Somatoto-
289. Pandya DN, Vignolo LA. Intra- Hosp 1960;106:266-316. pographic organization in the sec-
and interhemispheric projections 306. Pons TP, Garraghty PE, Cusik CG, ond somatosensory area of M. fas-
of the precentral, premotor and ar- Kaas JH . The somatotopic organi - cicularis. J Comp Neurol 1980;
cuate areas in the rhesus monkey. zation of area 2 in macaque mon- 192:43-67.
Brain Res 1971;26:217-233. keys. J Comp Neurol 1985; 320. Robinson CJ , Burton H. The orga-
290 Pandya DN , Seltzer B. The topog - 241:445-466. nization of somatosensory recep-
raphy of commissural fibers. Neu - 307. Powell TPS, Cowan WM . The in- tive fields in cortical area 7b,
rol Neurobiol 1986;17:47-73. terpretation of the degenerative retroinsular, postauditor)' and
291. Papez JW . Evolution of the medial changes in the intralaminar nuclei granular insular of M . fasacularis. J
geniculate body. J Comp Neurol of the thalamus. J Neurol Neuro - Comp Neurol 1980;192:69-92.
1936;64:41-61. surg Psvchiatrv 1967;30:140-153. 321. Robinson CJ , Burton H . Somatic
292. Parent A, Csonka C, Etienne P. 308. Powell TPS, Mountcastle VB. The submodality distribution within
The occurrence of large acetyl - cytoarchitecture of the postcentral the second somatosensory (SI I ), 7b,
-
cholinesterase containing neurons gyrus of the monkey Macaca mu - retroinsular, postauditory and
in human neostriatum as disclosed latto. Bull Johns Hopkins Hosp granular insular cortical areas of
in normal and Alzheimer-diseased 1959;105:18-131. M . fascicularis . J Comp Neurol
'
brains. Brain Res 1984;291:154-158. 309. Powell TPS, Mountcastle VB. Some 1980;192:93-108.
293. Parnavelas JG, McDonald JK . The aspects of the functional organiza - 322. Rockel AJ , Jones EG. The neuronal
cerebral cortex . In: Emson I *C, ed . tion of the cortex of the postcentral organization of the inferior collicu -
Chemical neuroanatomy. New gyrus of the monkey : a correlation lus of the adult cat . II . The pericen -
York: Raven Press, 1983:505-549. of findings obtained in a single tral nucleus. J Comp Neurol 1973;
294 . Partridge M . Prefrontal leucotomy: unit analysis with cytoarchitecture. 149:301-334.
a survey of 300 cases personally Bull Johns Hopkins Hosp 1959; 323. Roland PE. Brain activation. New
followed over 11 / 2-3 years. Ox- - .
105:133 162
ford : Blackwell Scientific Publica - 310. Purpura DP, Grundfest H . Nature
-
York: Wiley Liss, 1993.
324. Rose JE, Woolsey CN . Cortical con-
tions, 1950. of dendritic potentials and synap- nections and functional organiza-
tion of the thalamic auditory sys

tem of the cat . In : Harlow HF,
- tion of a novel dopamine receptor
( DO as a targets for neuroleptics.
nisms of visual localization and
discrimination . Am J Ophthalmol
Woolsev CN, eds. Biological and Nature 1990;347:146-151. -
1941;24:1255 1263.
biochemical bases of behavior. 341 . Sperryr RW . Cerebral organization 357. Tanji J , Wise SP. Submodality dis -
Madison: University of Wisconsin and behavior. Science 1961;133: tribution in sensorimotor cortex of
Press, 1938:127-150. 1749-1757. the unanesthetized monkey. J Neu -
325. Rose M . Cytoarchitektonik und 342. Sperry RW. Some general aspects rophysiol 1981;45:467-481 .
myeloarchitektonik der Grosshirn - of interhemispheric integration . In : 358. Thach WT, Jones EG. The cerebel -
rinde. In : Bumke O, Foerster O, Mountcastle VB, ed . Interhemi - lar dentatothalamic connection :
eds. Ilandbuch der Neurologie. spheric relations and cerebral terminal field , lamellae, rods and
Vol . 1 . Berlin: Springer- Verlag, dominance. Ch. 3. Baltimore: Johns somatotopy. Brain Res 1979;169:
1935:588-778. Hopkins University Press, 1962: 168- 172 .
326. Rosen I, Asanuma H. Peripheral 43-49. 359. Thompson JM , Woolsev CN, Tal -
afferents inputs to the forelimb 343. Sperry RW . Lateral specialization bot SA. Visual areas I and II of
area of the monkey motor cortex: in the surgically separated hemi - cerebral cortex of rabbit . J Neuro-
input -output relations. Exp Brain spheres. In . Schmitt FO, Worden physiol 1950;13:277-288.
Res 1972;14:257-273. FG, eds. The neurosciences, third 360. Tower SS. Pyramidal lesion in the
327. Rosenzweig MR . Cortical corre- study program Cambridge, MA : monkey . Brain 1940;63:36-90.
lates of auditory localization and -
MIT Press, 1974:5 19. 361 Tower SS. The pyramidal tract . In :
of related perceptual phenomena . I 344 . Steriade M , Biesold D. Brain Bucy l *C, ed . The precentral motor
Comp Phvsiol Psychol 1954;47: cholinergic systems. New York: cortex . 2d ed . Ch . 6. Urbana : Uni -
269-276. Oxford University Press, 1990. versity of Illinois Press, 1949:
328. Rossi GF, Brodal A . Corticofugal 345. Steriade M , McCarley RW . Brain - 149 172.-
fibers to the brain stem reticular stem control of wakefulness and 362 . Tracey DJ , Asanuma C, Jones EG ,
formation: an experimental study sleep. New York: Plenum Press, Porter R . Thalamic relay to motor
in the cat . J Anat 1956;90:42-62. 1990. cortex afferent pathways from
,
329. Russell 1R , Demyer W . The quanti - 346. Streit P. Glutamate and aspartate brain stem , cerebellum , and spinal
tative cortical origin of pyramidal as transmitter candidates for sys - cord in monkeys. J Neurophysiol
axons of Macaca rhesus. Neurology tems of the cerebral cortex . In : 1980,44:532-555.
1%1;11:96-108. Jones EG , Peters A, eds. Cerebral 363. Travis AM . Neurological deficien -
330. Rylander G . Personality analysis cortex. Vol . 2. New York : Plenum cies after ablation of the precentral
before and after frontal lobotomy. Press, 1984;119-143. motor area in Macaca mulatto. Brain
Proc Assoc Nerv Ment Dis 1948;
27:691-705.
.347. Strick PL . Anatomical analysis of
ventrolateral thalamic input to pri -
1955;78:155 173 - .
.364 Travis AM . Neurological deficien -
331 Scarff JE. Primary cortical centers mate motor cortex. J Neurophysiol cies following supplementary
for movement of upper and lower 1976;39:1020-1031. motor area lesions in Macaca mu -
limbs in man Arch Neurol Psychi - .348. Strick PL . Activity of ventrolateral . -
latto Brain 1955;78:174 198.
atry 1940;44:243-299 thalamic neurons during arm 365. Tusa RJ , Rosenquist AC, Palmer
332. Scarff JE. Unilateral prefrontal lo - movement . J Neurophysiol 1976; LA Retinotopic organization of
botomy for relief of intractable 39:1032-1044 areas 18 and 19 in the cat . J Comp
pain and termination of narcotic 349. Strick PL, Kim CC. Input to pri - Neurol 1979;185:657-678.
addiction. Surg Gynecol Obstet mate motor cortex from posterior 366 Van Tol HUM , Bunzow JR , Guan
1949;89:385-392. parietal cortex (area 5). I Demon - -
H C, et al . Cloning of the gene for a
333. Scheibel ME , Scheibe! AB The or- stration by retrograde transport . human dopamine D4 receptor with
ganization of the nucleus reticu - Brain Res 1978;157:325-330. high affinity for the antipsychotic
laris thalami: a Golgi study . Brain 350. Strick PL, Preston JB . Multiple rep- clozapine. Nature 1991;350: 610-
Res 1966;1 :43-62. resentation in the primate motor 614 .
334 Schwarz DWF, Fredrickson JM cortex. Brain Res 1978;154:366-370. 367. Verhaart WJC , Kennard MA . Cor -
Rhesus monkey vestibular cortex: 351 . Strick PL, Sterling P . Synaptic ter - ticofugal degeneration following
a binodal primary projection field . minations of afferents from the thermocoagulation of areas 4, 6,
Science 1971;171 :280-281. ventrolateral nucleus of the thala - and 4S in Macaca mulatto. J Anat
335. Scollo- Lavizzari JG, Akert K Corti - mus in the cat motor cortex: a light 1940;74:239-254.
cal area 8 and its thalamic projec- and electron microscope study. J 368. von Economo CF. The cytoarchi -
tion in Macaca mulatto. J Comp Comp Neurol 1974;153:77-106. tectonics of the human cerebral
Neurol 1 %3;121:259-267. 352. Sugar O, Amador LV , Griponis - cortex. London: Oxford Medical
336. Shinoda Y, Zarzecki P, Asanuma siotes B. Corticocortical connec - Publications, 1929.
H. Spinal branching of pyramidal tions of the walls of the superior 369. von Economo C, Horn L. Uber
tract neurons in the monkey. Exp temporal sulcus in the monkey Windungsrelief , Masse und
Brain Res 1979;34:59-72. ( Macaca mulatto ). J Neuropathol Rindenarchitektonik der Supra -
337. Sholl DA . The organization of the -
Exp Neurol 1950;9:179 185. temporalflache , ihre individuellen
cerebral cortex. New York: John 353. Sugar O, French JD, Chusid JG. und ihre Seitenunterschiede . Z
Wiley & Sons, 1956. Corticocortical connections of the Gesamte Neurol Psychiatry 1930;
338. Sidman RL. Cell proliferation , mi - superior surface of the temporal 130:678-757.
gration and interaction in the de- operculum in the monkey ( Macaca 370. Vogt BA , Pandya DN . Cortico-cor-
veloping mammalian central ner - mulatto ). J Neurophysiol 1948,11: tical connections of somatic sen -
vous system . In: Schmitt FO, ed .
The neurosciences. Second study 354 . Sur
-M Nelson RJ Kaas JII Repre-
175 184.
, , .
sory cortex (areas 3, 1, and 2 ) in the
rhesus monkey. J Comp Neurol
program. New York : Rockefeller sentations of the body surface in 1978;177:170-192
University Press, 1970:100-116. cortical areas 3b and I of squirrel 371 . Vogt C, Vogt O. Allgemeine Er -
339. Sillito AM . Functional considera - monkeys: comparisons with other gebnisse unserer I lirnforschung.
tion of the operation of GABAergic primates. J Comp Neurol 1982, Vierte Mitteilung: Die physiolo-
211:177- 192. gische Bedeutung der architek -
.
inhibitory processes in the visual
cortex. In: Jones EC , Peters A , eds.
Cerebral cortex. Vol. 2. New York:
355. Szentagothai J . The neuron net -
work of the cerebral cortex : a func-
tonischen Rindenreizungen J Psy -
chol Neurol 1919;25:279-462.
Plenum Press, 1984:91-117. tional interpretation . Proc R Soc 372. Walker AE. The primate thalamus.
.340. Sokoloff P, Giros B, Martres M - P, Lond ( Biol ) 1978;201:219-248. Chicago: University of Chicago
-
Bouthenet M L, Schwartz J -C . Mo- 356. Talbot SA, Marshall Wll. Physio- Press, 1938.
lecular cloning and characteriza - logical studies on neuronal mecha - 373. Walker AE, Fulton JF. Hemidecor -
tication in chimpanzee, baboon, the precentral gyrus of baboons and macaque monkeys. Brain Res
macaque, potto, cat and coati: a and monkeys. J Physiol (Lond) 1979;162:201-217.
study in encephalization. ) Nerv W3;228:2()3-219 . 403. Woolsey CN . Patterns of sensory
Ment Dis 1938;87:b77-7( X>. 389. Wiesendanger M. Recent develop- representation in the cerebral cor-
374 Walker AE, Weaver TA Jr. Ocular ments in studies of the supplemen - tex . Fed Proc 1947;6:437-141 .
movements from the occipital lobe tary motor area of primates. Rev 404 Woolsey CN. Organization of so-
in the monkey. J Neurophysiol Physiol Biochem Pharmacol 198b; matic sensory and motor areas of
the cerebral cortex. In: Harlow HF,
’
1940;3:353-357. 103:1 57
375. Walther JB, Rasmussen GL . De- 390. Wiesendanger M, Hummelsheim Woolsey CN, eds. Biological and
scending connections of auditory H, Bianchetti M, et al. Input and biochemical bases of behavior.
cortex and thalamus of the cat . Fed output organization of the supple- Madison: University of Wisconsin,
Prik 1960;19;29| . mentary motor area. In: Motor 1938:63-81.
37b Weinberger DR . Implications of areas of the cerebral cortex. CIBA 403 . Woolsey CN. Organization of cor -
normal brain development for the Foundation symposium. Chi- tical auditory system: a review and
pathogenesis of schizophrenia. chester: John Wiley & Sons, 1987: synthesis. In: Rasmussen GL. Win-
Arch Gen Psychiat 1987,44 : 660- 132:40-62. dle WF, eds. Neural mechanisms
bb9. .391. Wiesendanger M, Seguin JJ Kun- . of the auditor)' and vestibular sys-
377 Weinrich M, Wise SP. The premo- zle H. The supplementary motor tems. Springfield, lb: Charles C.
tor cortex in the monkey. | Neu- area: a control system for posture. Thomas, I9b0: lb3- I80.
rosci 1982;2: 1329-1345. Adv Behav Biol 1974;7:331 34b. 40b. Woolsey CN. Cortical motor map
378. Werner GW, Whitsel BL The . 392. Wilson Mb, Toyne M|. Retino-tec- of Manna mulatto after chronic sec -
topology ol the bi>dy representa - tal and corticotectal projections in tion of the medullary pyramid. In:
tion in somatosensory area I of pri -
mates . J Neurophysiol I9b8;3l
Macaca mulatto. Brain Res 1970;
—
243:395 10b. .
Zulch KJ, Creutzfeldt O, Galbraith
CC, eds. Cerebral localization.
856-869.
.
379 Werner C W, Whitsel BL. Func -
tional organization of the so-
393. Winer JA , Diamond IT, Racz-
kovvski D. Subdivisions of the au-
ditory cortex in the cat: the retro- 407.
Berlin: Springer- Verlag, 1973: 19-
31.
Woolsey CN, Fairman D. Con -
matosensory cortex . In: Iggo A , ed. grade transport of horseradish tralateral, ipsilateral and bilateral
I landkK >k of sensory physiology. peroxidase to the medial genicu- representation of cutaneous recep-
Vol 2. Berlin: Springer- Verlag, late body and posterior thalamic tors in somatic areas I and II of the
1973:621-7(H). nuclei, j Comp Neurol 1977;17b: cerebral cortex of pigs, sheep and
380. Wernicke C. The symptom-com-
.
-
387 118. other mammals. Surgery 194b,19:
plex of aphasia. In: Chuich A, ed. 394. Wise SP, Strick PL. Anatomical 684-702.
Diseases of the nervous system. and physiological organization of 408. Woolsey C’N, Sett la ge PII, Meyer
New York : Appleton, 1908: 265- the nonprimary motor cortex. DR, Sencer W , Hamuy TP, Travis
324.
381 White EL. Cortical circuits. Synap- .
395 Wise SP, Tanji J. Supplementary
—
Trends Neurosci 19S4;7:442 14b. AM. Patterns of localization in pre-
central and "supplementary"
tic organization in the cerebral cor- and precentral motor cortex: con- motor areas and their relation to
tex : structure, function, and theory . trast in responsiveness to periph - the concept of a premotor area.
Boston: Birkhaaser, 1989. eral input in the hindlimb area of Proc Asstv Nerv Ment Dis 1931;
382 Whitehouse PJ, Price DL, Clark the unanesthetized monkey . J 30:238-264.
AW, Coyle JT, Delong MR. Comp Neurol 1981;195:433-451. 409. Woolsey CN, Walzl EM. Topical
Alzheimer's disease: evidence for 39b. Witelson SF. The brain connection: projection of nerve fibers from
selective loss of cholinergic neu - the corpus callosum is larger in left local regions of the cochlea to the
rons in the nucleus basalis. Ann handers. Science 1985;229:665-668. cerebral cortex of the cat . Bull
Neurol 1981;10:122 12b. 397. Witelson SF I land and sex differ - lohns Hopkins Hosp I942;71:
.383. Whitlock DG, Perl FR . Thalamic ence in the isthmus and genu of 315-344 .
projections of spinothalamic path- the human corpus callosum: a 410. Woolsey CN, Walzl EM. Cortical
ways in monkey. F.xp Neurol postmortem morphological study. auditory area of Manna mulatto
1961;3:240-255. Brain 1989;! 12:799-835. and its relation to the second so-
384 Whitsel BL, IVtrucelli LM, Werner .
398. Witelson SF Goldsmith CH. The matic sensory area tSMIl ): determi -
C. Symmetry and connectivity in relationship of hand preference to nation by electrical excitation of
the map of the bix.lv surface in so- anatomy of the corpus callosum in auditory nerve fibers in the spiral
matosensory area II of primates. J men. Brain Res 1991;345:175- 182. osseous lamina and by click stimu-
Neurophvsiol 1%9;32:170- 183. .39 ). Witelson SF, Pollie W . I
* .eft hemi- lation. In: Woolsey CN, ed. Corti-
385 Wiesel TN, Hubei Dll Effects of sphere specialization for language cal sensory’ organization. Vol. 3.
visual deprivation on morphology in the newborn: neuroanatomical Clifton, Nj: Humana Press, 1982:
and physiology of cells in the cat 's evidence of asymmetry . Brain 231-256.
lateral geniculate txxlv . | Neuro- 1973;96:541-646. 411 Zangwill OL. Cerebral dominance
physiol 1963;26:978-993. .
400 Wong- Riley MTT. Changes in the and its relation to psychological
386 Wiesel TN, llubel Dll Ordered dorsal lateral geniculate nucleus of function. Springfield, IL: Charles
arrangement of orientation col - the squirrel monkey after unilat - C. Thomas, |9b9.
umns in monkeys lacking visual eral ablation of the visual cortex. | 412. Zarzecki P, Strick PL, Asanuma H.
.
experience J Comp Neurol 1974; Comp Neurol 1972;146:519-548. Input to primate motor cortex from
138: 307 318. 401 . Wong- Riley MTT. Demonstration posterior parietal cortex ( area 3 ). ||
387 Wiesel TN, Hubei Dll, Lam DMK . of geniculocortical and callosal identification by antidromic activa -
Autoradiographic demonstration projection neurons in the squirrel tion. Brain Res !978;157 131 338
of ocular -dominance columns in monkey by means of retrograde 413 . Zeki SM. lnterhemispheric connec -
the monkeys striate cortex by axonal transport of horseradish tions of prestriate cortex in mon-
means of transneuronal transport . peroxidase. Brain Res 1974;79: keys. Brain Res 1971;19:63-75.
Brain Res 1974;79:273-279. 267-272. 414 . Zilles. Cortex . In: Paxinos G, ed.
388. Wiesendanger M. Input from mus- 402. Wong- Rilev MTT. Columnar cor - The human nervous system. Ch.
cle and cutaneous nerves of the tico-cortical interconnections with- 22. New York: Academic Press,
hand and forearm to neurones tit in the visual system of the squirrel 1990:757-802.
Atlas of Brain and Brain Stem
Section I
Transverse sections of Brain Stem (A-l to A-13).
Section II
Frontal sections cut transverse to the longitudinal axis of the
diencephalon (A-14 to A-l8).
Section III
Frontal sections of diencephalon and basal ganglia (A- 19 to A-24).
Section IV
Sagittal sections of brain and brain stem (A-25 to A-32).
The following series of drawings of transverse sections of the brain stem

taken at critical levels are reproduced in colors that faithfully reveal the
definition of fiber tracts and cellular groupings characteristic of the original
preparations. These sections, stained with luxol fast blue and counter -
stained with cresyl violet (1334), appear particularly appropriate for labo-
ratory instruction since the student is presented with a complete picture of
cellular configurations in relationship with the myelinated fiber tracts in a
single microscopic slide. The outline drawing of the brain stem indicates
the levels and planes of section of the individual figures and should be
used as a key . The magnification of the figures is noted in the legends.
Illustrations used in Sections I, II and III were prepared by Miss Marjorie Stodgell, Med-
ical Artist, of the Hahnemann Medical College and Hospital of Philadelphia. Pho-
tographs used in Section IV were made from original Weigert preparations of the
late Professor Andrew T. Rasmussen of the University of Minnesota .
937
938 Section VII
Brain Stem Atlas

Posterior median sulcus
Fasciculus gracilis
Nucleus spinal tract of
trigeminal nerve v Fasciculus cuneatus
Central canal Spinal tract of trigeminal nerve

Si r.:'
- [
i i
Rubrospinal tract
Posterior spinocerebellar tract
' Anterior spinocerebellar tract
Spinal roots of
h Spinothalamic tracts
accessory nerve
i
Anterior horn cells
Vestibulospinal tract >
Anterior corticospinal tract Q
CO
Tectospinal tract o
S’
Q.
_
Q.
r
:
-
A 1. Transverse section of the caudal medulla near its junction with the cervical spinal cord x8 r
o
CA>
o
Fasciculus gracilis Nucleus gracilis
Fasciculus cuneatus
a
Nucleus cuneatus o3
Spinal tract of
trigeminal nerve
Nucleus spinal tract
of trigeminal nerve
Posterior spino -
cerebellar tract
Central canal
Rubrospinal tract
Anterior spino - Reticular formation

cerebellar tract
Anterior horn cells
Spinothalamic tracts first cervical
Vestibulospinal tract
Medial longitudinal
fasciculus Pyramid
A - 2. Transverse section of the medulla through the decussation of the corticospinal tracts x8
Fasciculus gracilis Nucleus gracilis
Fasciculus cuneatus
Nucleus cuneatus
Spinal tract of Accessory cuneate nucleus

trigeminal nerve
Nucleus spinal tract

Posterior spino - of trigeminal nerve
cerebellar tract
Dorsal nucleus
Nucleus ambiguus V of vagus
Hypoglossal
Internal arcuate fiber nucleus
Lateral reticular
Decussation of
medial lemniscus
- nucleus
>
Inferior olivary nucleus CO
Pyramid o
—
Q.
Arcuate nuclei 3
D
¥
er- .
co
:
3
of me decussation of me medial lemniscus showrng
me nuclei of 2
A -3 Transverse section of me medulla at the level
course of me internal arcuate fibers * 8
me posterior columns and the
Dorsal nucleus of vagus Hypoglossal nucleus 2
ro
Medial vestibular nucleus Inferior vestibular nucleus l

o
Solitary fasciculus and Accessory cuneate nucleus
nucleus
Nucleus spinal tract of
Inferior cerebellar trigeminal nerve
peduncle
Spinal tract of — f.
'
Vagus nerve
trigeminal nerve ^
Nucleus ambiguus
Medial longitudinal
fosciculus Lateral reticular nucleus
Olivocerebellar fibers ^ Dorsal accessory olivary

nucleus
Hypoglossal nerve
Arcuate nucleus Medial accessory olivary nucleus
Medial lemniscus Pyramid
A - 4. Transverse section of the medulla through the inferior olivary nuclear complex demonstrating cranial nerve
nuclei and the emergence of the hypoglossal root fibers x6.5
Nucleus prepositus hypoglossi Medial vestibular nucleus
Medial longitudinal Inferior vestibular nucleus

fasciculus
Dorsal cochlear
Inferior cerebellar nucleus
peduncle -
Solitary
fasciculus
Spinal tract and
nucleus of trigeminal Olivocerebellar
nerve fibers
Nerve IX
Nucleus reticularis
Nucleus ambiguus gigantocellularis
Anterior spinocerebellar Lateral reticular nucleus

tract
Medial lemniscus
Pyramid >
Q
O
T
Q
-.
..
3
0
-
Q.
A -5. Transverse section of the full development of the medulla showing the glossopharyngeal nerve, the vestibular <D
nuclei in the floor of the fourth ventricle, and the dorsal cochlear nuclei x6.5. r
§
Co
Fastigial nuclei
c
t
v
n
Emboliform nucleus
6
r
Dentate nucleus
<
Globose nucleus
Lateral vestibular
nucleus
Dorsal cochlear
nucleus — Inferior vestibular
nucleus
Inferior cerebellar
peduncle Medial vestibular nucleus
: ,T
/• Solitary fasciculus
Cochlear nerve
( rzm ) Spinal nucleus and
tract of trigeminal nerve
Ventral cochlear
nucleu s
Medial lemniscus

Glossopharyngeal
nerve
Pyramid
Middle cerebellar peduncle Arcuate nucleus

Pontine nuclei
A -6. Transverse section of the upper medulla near its junction with the pons The section is cut asymmetrically On
the left the cochlear division of the eighth nerve is seen The inferior cerebellar peduncle, well-developed on both
sides, can be seen entering the medullary core of the cerebellum on the right The Intrinsic nuclei of the cerebellum
are seen dorsal to the fourth ventricle K 4 5
Choroid p l e x u s Nodulus
D e n t a t e nucleus
Inferior Superior
cerebellar vestibular nucleus
peduncle
Central
Abducens t e g m e n t o l tract
nucleus
Spinal nucleus
Medial a n d tract of
longitudinal
trigeminal nerve
fasciculus
Facial —olivary
. Superior
nucleus
nucleus
Middle cerebellar >

peduncle Olivary peduncle a
co
o
Facial nerve Pontine nucleus
S
Q. ’
T r a p e z o i d body u
Medial lemniscus Q
SP
Abducens nerve
_
:
3
A - 7. Transverse section through the pons at the level of the abducens nuclei showing part of the course of the root o
fibers of N VI and VII The middle cerebellar peduncle, massive at this level, is seen entering the cerebellum x4 5
cn
Oral pontine reticular formation Medial longitudinal fasciculus g
:>
Anterior spinocerebellar Superior cerebellar peduncle

So’
tract c
3
Central Mesencephalic tract
tegmental tract of 3!
Motor
Principal sensory
nucleus Y
nucleus of V
Lateral Middle cerebellar

lemniscus peduncle
Reticulotegmental
nucleus
Medial lemniscus Trigeminal nerve
Corticospinal tract
Pontine nuclei
Trapezoid body and nuclei
A - 8. Transverse section of the upper pons at the level of the trigeminal nerve root The superior cerebellar peduncles
form well-defined fiber bundles on the lateral borders of the fourth ventricle *4 5
IV Ventricle Trochlear nerve decussation
Dorsal nucleus of raphe
of trigeminal nerve
Lateral lemniscus Locus ceruleus
Medial longitudinal
Superior cerebellar
fasciculus
peduncle
Spinothalamic tract
Central tegmental
fasciculus Superior central
nucleus
Medial lemniscus
Reticulotegmental
nucleus
Middle cerebellar
peduncle
Corticopontine tracts
Corticospinal tract
A - 9. Transverse section of the isthmus region of the brain stem Root fibers of the trochlear nerves can be seen
decussating in the superior medullary velum . x 4 5
g
00
Cerebral aqueduct Dorsal tegmental nucleus n
Medial longitudinal fasciculus Trochlear nucleus
Brachium of inferior colliculus Inferior colliculus
Lateral lemniscus Central tegmental tract
Decussation of sup.
cerebellar peduncle Medial lemniscus
Substantia nigra
Crus cerebri
Interpeduncular fossa Interpeduncular nucleus
A - 10. Transverse section of me caudal mesencephalon passing through me Inferior colliculus, me decussation of
the superior cerebellar peduncle, and me crus cerebri x4 5
Cerebral aqueduct Central gray
Superior colliculu Dorsal tegmental nuclei
Spinothalamic tracts Oculomotor nuclei

/•
Brachium of inf. colliculus Medial longitudinal fasciculus

v 4
y \
MV
"
Dorsal tegmental decussation
Medial lemniscus
Red nucleus
-
and occioito - oontine
Corticospinal and ‘
corticobulbar tracts
s*. , 1
*
| f Substantia nigra
Crus cerebri
Fibers of oculomotor nerve >

Frontopontine tibers 8
°
Q_ .
a-
Q.
r
cn
I
A - 11. Transverse section of the mesencephalon at the level of the superior colliculus x 4 5 g
c
-
<1
I
pu \ v \ nor
Nucleus o< .
s1. comm
p0
preiectol. Medio '

area qen > cu \ ote
body
"'
\ nlersli
nucleus
0
Medio '
Umniscos
ero'
'
Uo
qeniculole
nucleus
Subslool ' O
Crus cerebri
Oculomotor nuclei
4
cePr alorl and '00 *
d®ncepWJ
rri® meser
' '
|or>ctionof
at me
tton of me brain stem
,
a. 2. transverse
sec
Habenular nucleus
Third ventricle PuI vi n ar
Centromedian
nucleus Fasciculus
retrof lexu s
Lateral
geniculate Red nucleus
body
Subthalamic Optic tract

nucleus
>
Crus c e r e b r i Q
Substantia nigra CO
o
Interpeduncular Q.
r
fossa 7
Q.
r
cn
:
3
-
A 13. Transverse section of the caudal diencephalon at the level of the habenular nucleus and the fasciculus
retroflexus x 4 o
cr
952 Section VII
Outline of median sagittal surface of brain indicating level and plane of fronfal sections A - 14 to A - 18.
Corpus callosum Habenular nucleus
Choroid plexus of
lateral ventricle v . HI Ventricle Fornix (crus )
Caudate nucleus
Pulvinor
Medial
geniculate body
Ventral posterolateral
nucleus
Optic radiation
nucleus
Lateral geniculate body Red nucleus
Substantia nigra
Tegmental field - H
Crus cerebri
>
Ventral portion of pons Q•
-/ )
o
E?
Q.
I-
-r
CL
T
A - 14. Frontal section through the junction of the midbrain and the diencephalon at the level of the habenular Q.
nucleus x2.5 cn
<3
ai
Co
Fornix (crus) Gyrus cinguli E
Stria medulloris thalomi Corpus callosum
Caudate nucleus (body ) S

Stratum zonale
Thalamic nuclei :
Lateral dorsal —
Lateral posterior
Internal medullary
lamina and nuclei
Dorsal medial —
Centromedian V 7- tract
Mommillothalamic
Midline
Adhesio interthalamica
Internal capsule (massa intermedia)
Globus pallidus h ' Third ventricle
Putamen Js ' Hypothalamic nuclei.
Ansa lenticularis V /' . ' Posterior
i Ventromedial
Amygdaloid nuclei J Lateral
Tuberal
Tuber cinereum
Optic tract
Fornix (anterior column)
wn
*
cinereum and
and lentlform nucleus at me level of the tuber
-
A IS. Frontal section through the diencephalon
interthalamic adhesion. *3
Lateral ventricle Fornix (crus) Commissura fornicis Stria medullaris
Caudate nucleus
Stria terminalis
Internal capsule
(posterior limb)
^
Thalamic nuclei:
Anterior
Internal
_
Medullary laminae.
_____ _
Reticular nucleus
Dorsal medial
External — Midline
— iL
Ventral lateral (intermedius )
Third ventricle
Putamen
Hypothalamic nuclei:
Globus pallidus Dorsomedial
Ansa lenticularis Ventromedial
VI^
Anterior commissure
Amygdaloid nucleus
Optic tract
Infundibulum
A - 16. Frontal section through the diencephalon and lentiform nucleus at the level of the infundibulum and
interthalamic adhesion x 3
Body of fornix Choroid plexus of : c
g
-
Third ventricle
Stria medullaris / Lateral ventricle
n
Internal capsule 2g5c>>
-r Corpus callosum
o
3
Caudate nucleus (body )
Cortex of insula
Thalamic nuclei:
Claustrum - —_Anterior
Ventral anterior
External capsule Midline
Column of fornix
Lentiform nucleus:
Putamen
Globus pallidus _ Medullary laminae :
Medial
Lateral
Anterior commissure
Nucleus of stria terminalis ^ Anterior perforated substance

Hypothalamic nuclei :
Anterior cerebral artery
Anterior "
Paraventricular " Supraoptic recess ,II ventricle Optic chiasm
Supraoptic -
A - 17. Frontal section through the diencephalon and lentiform nucleus at the level of the optic chiasm and body of
the fornix x3
Cingulate gyrus Cingulum
Indusium griseum Corpus callosum
Column of fornix Anterior thalamic nucleus

Corona rodiata
Lateral ventricle
Arcuate fasciculus
Caudate nucleus ( body )
Internal capsule Reticular nucleus

( genu) of thalamus
Lentiform nucleus: Stria medullaris

Putamen
Globus pallidus Nucleus of stria
terminalis
External capsule
'
• : V Anterior commissure
V\
Claustrum V
A
'
- . -IS*.V‘ —*
-
Anterior perforated
substance
>
a
Anterior o
amygdaloid Column of fornix T
9.
area -
..
3
Q.
Optic ' Interventricular foramen S
chiasm 0.’
3
cn
3
A - 18 . Frontal section through the rostral diencephalon at the level of the optic chiasm and interventricular foramen x3 -o
'Vj
958 Section VII
Outline of median sagittal surface of brain indicating leveled plane of frontal sections A - 19 to A -24
Third ventricle Fornix (body )
Lateral ventricle Corpus callosum
Caudate nucleus
Subependymal stratum
Stria terminalis
Stria medullaris
Thalamic nuclei :
Lateral dorsal Thalamic medullary laminae:
Lateral posterior Internal
Dorsal medial
External
Centromedian
— Internal capsule
Globus pallidus — Zona incerta

I Subthalamic nucleus
Optic tract & Red nucleus
Crus cerebri
>
(fl
Substantia nigra Ventral tegmental decussation o

S
Q. ’
r
a
S
Q. ’
D
<2
CD
3
A - 19. Frontal section through midbrain and diencephalon at the level of red nucleus and posterior
thalamic nuclei x 2 5 o
cn
-o
c
Indusium griseum Septum pellucidum
Fornix ( body ) Stratum zonole £
Corpus callosum o
Caudate nucleus ( body ) c
n
Lateral ventricle
Corona
radiata
Internal capsule
Putamen
Thalamic nuclei:
Globus pallidus — Anterior
Third ventricle Medial
Thalamic fasciculus — Ventral lateral
Posterior hypothalamic area Zona incerto
Globus pallidus Lenticular fasciculus
Optic tract
Supramommillary commissure —77, ,
V
.
Subthalamic nucleus
Amygdaloid nucleus
Interpeduncular nucleus Choroid plexus, inferior horn
Crus cerebri -
j ‘
Tegmental field H
Interpeduncular
cistern
—rcr *'
'
* Substantia
fc
nigra
Fibers of oculomotor nerve

Corticospinal tract
—
A - 20 Frontal section through ventral pons, midbram. and diencephalon at the level ot the interpeduncular fossa
and posterior hypothalamus x3
Stria medulloris tholomi Fornix ( body )
Subependymal stratum
gpg Corona radiata
Caudate nucleus
. "- ! ,
( body )
Lo eral
Stria terminalis . ventricle
AW
Thalamic nuclei Internal capsule
Ventral anterior
Midline Third ventricle
Lenticular fasciculus
Globus pall id us
Subthalamic nucleus
Posterior hypothalamic Hypothalamic sulcus
nucleus
Mammillary nuclei
Optic tract
Amygdaloid nucleus Substantia nigra

>
Uncus Lateral ventricle
( inferior horn ) V
Dentate gyrus Fasciculus mammillaris princeps Q•.

_
Hippocampal fissure -
a
Ventral pons Parahippocampal gyrus SP
Q.
D
CO
A - 21. Frontal section tnrougn diencephalon at the level of the mammillary body x 3 O
3
V
T'
o
>
o
Lateral ventricle Corpus callosum NJ
vo
/ .. TV - - * ;'
>.
Corona radiata
5
Caudate nucleus ____ ' Vl-’
• /l:CV 5 Internal capsule
m
§
^
( anterior limb)
*
Lentiform nucleus
Putamen
:
Globus pa Nidus
- fc '
>
S'
r
Fornix (anterior column)
Anterior commissure
Ansa lenticularis
Substantia
innominata tract
Supraoptic nucleus HI Ventricle
Tuber cinereum
A - 22. Frontal section through rostral hypothalamus and lentiform nucleus at the level of
the tuber cinereum and
columns of the fornix. x3
Indusium griseum
Lateral ventricle (anterior horn ) Corpus callosum
Corona radiata
Caudate nucleus
Internal capsule
(anterior limb)
Lentiform nucleus:
Putamen
^
Globus pallidas External capsule
Lateral medullary lamina

Preoptic area
Anterior commissure
Lateral olfactory stria
Supraoptic recess Anterior perforated substance >

of third ventricle Q
CO
o
Q.
'
Supraoptic nucleus Middle cerebral artery c
J
Infundibulum Optic tract
Q.
to
3
A - 23. Frontal section through basal ganglia and anterior hypothalamus at the level of the infundibulum and anterior -5o
limb of fhe infernal capsule . 3 Co
*
Gyrus cinguli Anterior cerebral artery ~o
Corpus callosum Indusium griseum

2
)
Corona rodiata
Septum pellucidum \ I Lateral ventricle (anterior horn) o
mm Coudote nucleus
5
<
( head )
Arcuate fasciculus £.
• :
Internal capsule
Insular cortex ( anterior limb)
Extreme capsule j
Putamen
Claustrum
Nucleus accumbens
septi
External capsule
Rostrum of
corpus callosum
Inferior
occipito - frontal
fasciculus
Area subcallosa
Uncinate
fasciculus Gyrus orbitails
Anterior cerebral artery Gyrus rectus Olfactory / O

tract VHV
V
A 24 Frontal section through the rostral corpus striatum, area subcallosa, and the olfactory tract x3 5.
Atlas of Brain and Brain Stem 965
Third ventricle 26 28 30
\ 25 27 29 31 32
Habenula
Pineal
Lateral \
Superior colliculus
geniculate -V " "

\ \ s
/
\ y
body
/
J(
Inferior colliculus— v
Trochlear nerve -
Superior medullary
/
-
velum \
\
Cerebellar
peduncles
)
/
Lateral recess
of fourth
ventricle
Inferior cerebellar
peduncle
— hi
V .
Fasciculus and nucleus

cuneatus
<
Fasciculus gracilis —'

li!
25 27 29 31 32
Outline of dorsal surface of brain indicating level andean!oPsagittal sections A-25 to A 32

c
:
Septum pellucidum Fornix : V
Corpus callosum . ^ Anterior column a
Body
Genu Stria medullaris thalami
Rostrum Dorsal medial nucleus
Anterior commissure .
- Third ventricle
Habenulor commissure
Supraoptic reces Pineal body
Optic chiasm — Cerebral aqueduct
Infundibulum ^
Mammillary body - Oculomotor nucleus
Cerebellum
Superior cerebellar
peduncle ( decussation ) Fastigial nucleus
^ Fourth ventricle
Ventral portion of pon & - Facial nerve

Basilar artery Medial lemniscus
Nucleus gracilis
Pyramid —'
Pyramidal decussatioi Fasciculus gracilis
A - 25. Sagittal section through the ventricular system and brain stem at the level of the pineal body x!5
Lateral ventricle Choroid Stria medullaris thalami
( anterior horn ) plexus
Thalamic nuclei -
Anterior
Dorsal medial
Corpus callosum ( splenium )
Central gray substance
Area subcallosa Superior colliculus
Fornix (anterior column) Inferior colliculus
Optic chiasm Trochlear nerve
Hypothalamus
Superior medullary velum
Mammillothalamic fasciculus
Red nucleus Medial lemniscus
Superior cerebellar peduncle Facial nerve
Transverse pontine fibers Stria medullaris of >
' fourth ventricle
Longitudinal pontine fibers
Nucleus and tractus
solitarius
°
Inferior olivary nucleus Q
-
.
. Reticular formation Q
Pyramid ( corticospinal tract )
Nucleus gracilis -T
Lateral corticospinal tract 9.
CO
Posterior funiculus :
Anterior gray column ( cervical cord ) 3
O
o
A - 26. Sagittal section through brain stem at the level of the nucleus gracilis and emergence of the trochlear nerve xl .3 -
" si
o
o
00
Choroid Thalamic nuclei: CO

Caudate nucleus CD
( head )
Anterior
Dorsal medial
ao
Lateral dorsal
Fornix ( body )
Anterior Habenula
commissure
— -v
Superior colliculus
Trochlear nerve
Fornix ( anterior column >/ Superior cerebellar

peduncle
Lenticular fasciculus
Central tegmental
Oculomotor nerve tract
Dentate nucleus
Substantia nigra
Medial lemniscus Facial nerve
Corticospinal tract
Nucleus cuneatus
Pyramid
tc — Fasciculus cuneatus
A - 27 . Sagittal section through the brain stem at the level of the nucleus cuneatus and habenula , xl 3
Stria medullaris Thalamic nuclei :
Inferior thalamic peduncle \ Ventral anterior
Lateral ventricle> Anterior
( anterior horn ) Dorsal medial
Lateral dorsal
Fornix:
Body
Caudate nucleus Crus
( head ) ~
^
Mammillothalamic fasciculus
Lenticular fasciculus ( H
Optic chiasnn Superior colliculus
Forel ' s field H Central gray

Red nucleus Trochlear nerve
Oculomotor nerv
Medial lemniscus
Ventral portion of pons . Lateral lemniscus >
Mesencephalic -
root of N. 3T 9.
Abducens nucleus 9.
*<: Fasciculus solitarius Q
..
Corticospinal tract Nucleus ambiguus S
Inferior olivary nucleus 9.
r
’
Spinal nucleus N. 3C c/>
:
r
A - 28 . Sagittal section through the brain stem at the level of the nucleus ambiguus. lateral lemniscus, and fasciculus
retroflexus. xl . 3 .
$
5
o
Caudate nucleus ( heod ) Stria terminals

Lateral ventricle Choroid plexus :
Thalamic nuclei :
Ventral anterior
Lateral dorsal
Dorsal medial
Anterior Centromedian
commissure Posterior (pulvinar)
Mammillothalamic tract Fasciculus retroflexus
Internal medullary lamina Brachium of
superior colliculus
Optic nerve
Red nucleus
Supraoptic nucleus"'" Trochlear nerve
Lenticular fasciculus Lateral lemniscus
Subthalamic nucleus
Substantia nigra
Frontopontine tract
r
—— Superior cerebellar
peduncle
Facial nerve
Medial lemniscus
Lateral lemniscus i — Facial nucleus
Lateral vestibular nucleus •
Fasciculus solitarius
Superior olivary nucleus Nucleus ambiguus
r Inferior cerebellar peduncle Nucleus cuneatus
-
A 29. Sagittal section through the brain stem at the level of the facial, subthalamic and centromedian nuclei xl 3
Internol capsule (genu ) Stria terminalis
Lateral ventricle I .
Caudate nucleus,
Thalamic nuclei 1
Ventral lateral
Corpus callosum x / Ventral posteromedial
(genu) L /^ / Dorsal medial
Anterior
commissure
^
i
*L / Lateral dorsal
/
Centromedian
Posterior ( pulvinar )
Nucleus accumbens
septi Medial lemniscus
Anterior perforated substance
Ansa lenticularis
Optic troct
Ifil ’
^^
-S /
'
Brachium of -
Superior colliculus
„ Inferior colliculus
Lenticular fasciculus/
Thalamic fasciculus'
V
/
.— Trochlear nerve
Anterior >
spinocerebellar tract
-
Subthalamic nucleuy' ''
Substantia nigra /
Crus cerebri
_
Principal sensory
nucleus of N/S-
Dentate nucleus
a
~
Q.
r Trigeminal nerve
Q
S
-
’
Facial nerve " nferior cerebellar peduncle
-t
, and r
A - 30. Sagittal section through the brain stem at the level of the trigeminal nerve, brachia of the colliculi
thalamic nuclei , xl . 5 .
5
ro
Lenticular fasciculus a
Stria medullaris
Internal capsule (posterior limb ) Thalamic nuclei :
Ansa Ventral lateral
Caudate nucleus ( head
Dorsal medial
/ Centromedian
Lentiform nucleus : 1
Globus pallidus
/ Posterior ( pulvinar )
Putamen
Medial lemniscus
Olfactory trigone
Thalamic fasciculus
Optic tract.
Subthalamic nucleus
— Medial geniculate body
Crus cerebri
Fibers of trigeminal nerve —

Principal sensory nucleus of N. H'' Dentate nucleus
A -31. Sagittal section through upper prom stem at the level of the trigeminal nerve and the medial geniculate body xl 3
Internal capsule
Lentiform nucleus : I Caudate nucleus ( body )
Globus pallidus Stria terminalis
Putamen
callosum
Dentate gyrus
Lateral
medullary Calcarine
lamina cortex
Anterior ^
commissure
Middle cerebral ,
artery
Amygdaloid nucleus
Hippocampus
>
Uncus 8
°5
Optic Tract Q.
Lateral geniculate body Q
Lateral ventricle ( inferior horn ) Middle cerebellar peduncle

S
’
Q.
Flocculus
-
A 32. Sagittal section of the brain at the level of the flocculus lateral geniculate boay. ana inferior horn of the lateral ventricle x 65
,
o
co
Figure/Table Credits
FIGURES Figure 2.17 from Mettler FA . Neu - icine, and Dr . Brian C. Pate, Profes -
Figure 1.1 from Mettler FA . Neu - roanatomy 2d ed . St. Louis: C.V. sor at the Faculty of Medicine of
roanatomv 2d ed. St. Louis: C.V. Mosby Co., 1948. the University of British Columbia .
Mosby to., 194«. Figure 2.18 from Mettler FA. Neu - Figure 2.41 images were kindly
Figure 1.2 from Mettler FA . Neu - roanatomy 2d ed . St . Louis: C.V. provided by Dr. Donald B. Caine,
roanatomy 2d ed . St. Louis: C.V. Mosby Co., 144«. Division of Neurology , Depart -
Mosby Co., 1948. Figure 2.19 from Mettler FA. Neu - ment of Medicine, University of
Figure 1.3 from Mettler FA. Neu - roanatomv 2d ed . St . Louis: C.V. British Columbia , and Dr . Brian C.
roanatomy 2d ed . St. Louis: C.V. Mosby Co., 1948. Pate, Professor at the Faculty of
Mosby Co., 144«. Figure 2.20 from Mettler FA . Neu - Medicine of the University of
Figure 1.4 from Mettler FA. Neu - roanatomy 2d ed. St. Louis: C.V. British Columbia .
roanatomv 2d ed . St. Louis: C.V. Mosby Co., 1948. Figure 2.42 images were kindly
Mosby Co., 144«. Figure 2.26 from Mettler FA . Neu - provided by Dr. Donald B. Caine,
Figure 1.5 from Mettler FA. Neu - roanatomy 2d ed . St. Louis: C.V. Division of Neurology, Depart -
roanatomy 2d ed . St . Louis: C.V. Mosby Co., 1948. ment of Medicine, University of
Mosbv Co., 144«. Figure 2.30 from Mettler FA . Neu - British Columbia, and Dr. Brian C.
Figure 1.8 from Mettler FA. Neu - roanatomy 2d ed . St. Louis: C.V. Pate, Professor at the Faculty of
roanatomv 2d ed St . Louis: C.V. Mosby Co., 1948. Medicine of the University of
Mosbv Co., 144«. Figure 2.31 from Mettler FA. Neu - British Columbia .
Figure 1.14 from Fenstermacher roanatomy 2d ed . St. Louis: C.V. Figure 3.2 A from Davis CL De . -
JD, Rail DP. Physiology and phar- Mosby Co., 1948. scription of a human embryo hav -
macology of cerebrospinal fluid . Figure 2.32 from Mettler FA . Neu - ing 20 paired somites. Contrib Em -
In: Fenstermacher JD, ed. Pharma - roanatomy 2d ed . St. Louis: C.V. bryol 1923;15:1-51 .
cology of the cerebral circulation . Mosby Co., 1948. Figure 3.2B from Ingalls NW . A
Vol. I . Oxford: Pergamon Press, Figure 2.33 from Mettler FA. Neu - human embryo at the beginning of
1973:35-79. roanatomy 2d ed . St. Louis: C.V. segmentation with special refer-
Figure 1.16 modified from Weindl Mosby Co., 1948. ence to the vascular system. Con -
A , Sofroniew MV. Relation of neu - Figure 2.34 from Hanaway J , Scott trib Embrvol 1920;11:61-90.
ropeptides to mammalian circurn - WR , Strother CM. Atlas of the Figure 3.3C from Payne F. General
ventricular organs. In: Martin JB, human brain and the orbit for com - description of a 7-somite human
Reichlin S, Bick KL, eds. Advances puted tomography. St . Louis: War- embryo. Contrib Embrvol 1424;16:
in biochemical psychopharmacol- ren H. Green , Inc., 1980. 115-124.
ogy. Vol 2«. Neurosecretion and Figure 2.35 from Hanaway J , Scott Figure 3.4 from Sauer FC. Mitosis
brain peptides. New York: Raven W' R , Strother CM . Atlas of the in the neural tube . J Comp Neurol
- .
Press, 1981 303 320 human brain and the orbit for com - 1935;62:377-405.
^
Figure 2.2 from Mettler FA. Neu -
roanatomv 2d ed . St. Louis: C. V.
puted tomography. St. Louis: War
ren H. Green , Inc., 1980.
- Figure 3.5 from Keibel F, Mall FP.
Manual of Human Embryology,
.
Mosby Co, 14 1« .
Figure 2.36 from Hanaway J , Scott
WR , Strother CM . Atlas of the
Vol II , Ch . XIV. Philadelphia: J . P.
Lippincott, 1912: 1 - 144.
roanatomv 2d ed . St. Louis: C.V. human brain and the orbit for com - Figure 3.10 from Hochstetter F.
Mosby Co., 144«. puted tomography. St. Louis: War- Beitrage zur Entwicklungs-
Figure 2.5 from Mettler FA . Neu - ren 11. Green, Inc., 1980. geschichte des menschlichen
roanatomv 2d ed. St. Louis: C. V. Figure 2.37 images were kindly Gehirns. Vol . I . Vienna and
Mosby Co., 194«. provided by Drs. Denis Melan <;on Leipzig: F. Deutcke, 1919.
Figure 2.6 from Mettler FA. Neu - and Donatella Tampieri , Montreal Figure 3.11 from Hochstetter F.
roanatomv 2d ed . St. Louis: C.V . Neurological Institute, McGill Uni - Beitrage zur Entwicklungs-
Mosbv Co., 144«. versity . geschichte des menschlichen
Figure 2.7 from Mettler FA. Neu - Figure 2.38 images were kindly Gehirns. Vol . I Vienna: F. Deutcke,
roanatomv 2d ed . St . Louis: C. V . provided by Drs. Denis Melant;on 1919.
Mosby Co., 144«. and Donatella Tampieri , Montreal Figure 3.14 from Prentiss CW,
Figure 2.9 from Truex RC, Kellner Neurological Institute, McGill Uni - Arey LB. A laboratory manual and
CE. Detailed atlas of the head and versity. textbook of embryology. Ch . XII .
neck. New York: Oxford Univer- Figure 2.39 images were kindly Philadelphia : W.B. Saunders Com -
sity Press, 194«. provided by Drs. Denis Melancon pany, 1920:321-352.
Figure 2.10 from Mettler FA . Neu - and Donatella Tampieri, Montreal Figure 3.15 from Hamilton WJ ,
roanatomv 2d ed . St. Louis: C. V. Neurological Institute, McGill Uni- Boyd JD, Mossman HW'. Human
Mosby Co., 144«. versity . embryology. Prenatal development
Figure 2.11 from Mettler FA. Neu - Figure 2.40 images were kindly of form and function . Ch . XII . Balti -
roanatomv 2d ed . St . Louis: C. V. provided by Dr . David Li, Division more: Williams & Wilkins,
Mosbv Co., 194«. of Neurology, Department of Med - 1962:315-388.
975
976 Figure /Table Credits
Figure 3.17 from Keibcl I , Mall FI’. brain. Arch Neurol 1967a;16: Sandford Palay, Harvard Medical
Manual of Human Embryology,
Vol. II , Ch. XIV . Philadelphia: J . P.
-
404 409.
School , Boston , MA.
Figure 5.17 courtesy of Dr. C.
Lippincott, 1912:1 -144 . roanatomy . St . Louis: C.V . Mosby Sotelo, Laboratoire d ’ Histologie
Figure 3.19 modified from Tuch -
'
Co., 1948. Normale et Pathologique du Sys-
man- Duplessis II , Auronx M , Figure 4.26 modified from teme Nerveux , Paris; from Sotelo
I laegel P. Illustrated human em - Schwartz P, Fink L. Morphologic C, Palay SL. The fine structure of
bryology . Vol . 3. Nervous system und Entstehung der geburstrauma - the lateral vestibular nucleus in the
and endocrine glands ( translated tischen Blutungenim Gehirn und rat . I . Neurons and neuroglial cells.
from French ). New York : Springer- Schadel des Neugeborenen . 7. J Cell Biol 1968;36:151-179.
Verlag, 1474 . Kinder heilk 1926;40:427-474. Figure 5.18 from the work of A . F.
Figure 4.1 based on Bolton B. The Figure 4.27 modified from Sadikot , and A . Parent , Neurobiol-
blood supply of the human spinal Schlesinger B. Venous drainage of ogy Research Center, Laval Uni-
cord . ) Neurol Psychiatry 1939; the brain , with special reference to versity , Quebec, Canada .
2:137-14b; Suh Til , Alexander L . galenic system. Brain 1939;62: Figure 5.19 from the work of L - N
Vascular system of the human 274-291. Hazrati, A. Charara , and A. Parent,
spinal cord . Arch Neurol Psychia - Figure 4.28 from Hassler O. Deep Neurobiology Research Center,
try 1939;41:654-677; and Ziilch K ) . cerebral venous system in man: a Laval University , Quebec, Canada .
Mangeldurchblutung an der microangiographic study on this Figure 5.21 from Copenhaver WM ,
Grenzzone zweier Gefassgebiete areas of drainage and its anasto- Bunge RP, Bunge MB. Bailey's text -
als Ursache bisher ungeklarter moses with the superficial cerebral book of histology. 16 th eel . Balti -
Ruckenmarksschadigungen . Dtsch veins. Neurology 1966a;16: more: Williams & Wilkins, 1471 .
7. Nervenheilk 1954;172:81 -101. 505-511 . Figure 5.22 from Bunge RP. Glial
Figure 4.3 courtesy of Drs. Daniel Figure 4.29 modified from cells and the central myelin sheath .
Hottenstein and Keith Himes, Holy Schlesinger B. Venous drainage of Physiol Rev 1468;48:197-251.
Spirit I lospital, Camp Hill , PA. the brain, with special reference to Figure 5.23 courtesy of H .J . Ralston
Figure 4.4 from Truex RC, Kellner galenic system. Brain I 934;62: 111, University of California School
CF . Detailed atlas of the head and 274-241 . of Medicine, San Francisco.
neck . New York: Oxford Univer- Figure 4.30 from Hassler O. Deep Figure 5.24 courtesy of Drs. M B.
sity Press. 1448. cerebral venous system in man: a Bunge and R . P. Bunge, Washing-
Figure 4.9 from Taverns|M , Wood microangiographic study on this ton University School of Medicine,
EH . Diagnostic neuroradiology. 2d areas of drainage and its anasto- St. Louis.
ed . Baltimore: Williams & Wilkins, moses with the superficial cerebral Figure 5.26 courtesy of Dr . R . P.
1976. veins. Neurology 1966a;16:505-511. Bunge.
Figure 4.10 courtesy of Dr. Harry Figure 5.4 from the work of L. N. Figure 5.27 courtesy of Dr. J .
A Kaplan Hazrati and A. Parent, Neurobiol- Rhodin, School of Medicine, Uni-
Figure 4.12 courtesy of Dr. Harry ogy Research Center, Laval Uni - versity of South Florida , Tampa.
A Kaplan.
Figure 4.13 modified from Aitken
versity, Quebec, Canada .
Figure 5.5 courtesy of Drs. Y.
Figure 5.29 modified from Stan
daert FG, Dretchen KL . Cyclic
-
I IF. A report on the circulation of Soltesz and M . Deschenes, Neuro- nucleotides and neuromuscular
the lobar ganglia made to Dr. biology Research Center, Laval transmission . Fed Proc 1979;38:
James B. Ayer ( with a postscript by University, Quebec, Canada . 2183-2142.
|B Ayer, MD ). Boston Med Surg J Figure 5.6 courtesy of Dr . J -J Figure 5.30 courtesy of Dr. J . Fran -
1909;160(Suppl):18. Soghomonian, Neurobiology Re- cis Hartmann , Presbvterian-St.
Figure 4.14 based on Alexander L . search Center, Laval University, Luke' s I lospital, Chicago.
The vascular supply of the stri- Quebec, Canada. Figure 5.31 courtesy of Dr. Ray C.
opnllidtim Proc Assoc Res Nerv Figure 5.7 based on Bodian D. The I lendrikson, Albany College of
Ment Dis 1442;21:77-132. generalized vertebrate neuron . Sci- Medicine of Union University , Al -
Figure 4.15 courtesy of Drs. Daniel ence 1962;137:323-326. bany, NY.
.
I lottenstein and Keith I limes Holy Figure 5.8 courtesy of the late Dr . Figure 5.32 based on Greengard P.
.
Spirit 1 lospital Camp Hill, PA.
Figure 4.16 courtesy of Drs. Daniel
Clement Fox, Wayne State Univer-
sity .
Cyclic nucleotides, phosphorylated
proteins and neuronal structure.
Hottenstein and Keith Himes, Holy Figure 5.9 courtesy of the late Dr. New York : Raven Press, 1478;
Spirit Hospital, Camp Hill , PA. Clement Fox, Wayne State Univer- Greengard P. Cyclic nucleotides,
Figure 4.17 courtesy of Dr. Abbas sity . phosphorylated proteins and the
F. Sadikot , Montreal Neurological Figure 5.11 from Barr ML, Bertram nervous system . Fed Proc 1979;
Institute, McGill University . l.F, Lindsay HA. The morphology 38:2208-2217.
Figure 4.19 from Hassler O. Ve- of the nerve cell nucleus according Figure 5.34 based on Kandel E.
nous anatomy of human hind - to sex. Anat Rec 1950;107:283-297. Cellular insights into behavior and
brain. Arch Neurol 1967a ;16: Figure 5.13 courtesy of H .J . Ralston learning. In: The Harvey Lectures,
404-409. III , University of California School series 73. New York: Academic
Figure 4.20 based on Stopford JSB. of Medicine, San Francisco. Press, 1974:19-92; Greengard P.
The arteries of the pons and Figure 5.14 courtesy of Drs. Sand - Possible role for cyclic nucleotides
medulla oblongata . Part I . J Anat ford L. Palay and Victoria Chan- and phosphorylated membrane
Physiol 1915;50:131-164; and Stop- Palay, Harvard Medical School; proteins in postsynaptic actions of
ford JSB. The arteries of the pons from Cerebellar cortex: cytology neurotransmitters. Nature 1976;
and medulla oblongata. Part II. | and organization . Berlin: Springer- 260:101-108.
Anat Physiol 1916;51:255-280. Verlag, 1974. Figure 5.35 from Young JZ. The
Figure 4.21 from I iassler O. Ve- Figure 5.15 courtesy of Drs. Alan functional repair of nervous tissue.
nous anatomy of human hind - Peters, Henry de Webster, and Physiol Rev 1942;23:318-374.
Figure / Table Credits 977
Figure 5.38 based on Ramon v Figure 7.1 modified from Tuch - Paris: Maloine, 1909, 1911.
Cajal, S.. Histologie du Systeme mann - Duplessis II , Auronx M , ( Reprinted , Consejo Superior de
Nerveux de 1' Homme et des I laegel P. Illustrated human em - Investigaciones Cientificas, Insti -
Vertebra's. ( Azoulay L, trans. ) bryology. Vol. .3: Nervous system tute Ramon y Cajal, Madrid, 1972. )
Paris: Maloine, 1909, 1911 and endocrine glands ( translated Figure 7.11 after Barker D. The in -
( Reprinted, Consejo Superior de from French ) New York: Springer- nervation of the muscle-spindle. QJ
Investigaciones Cientificas, Insti - Verlag, 1974. Microscop Sci 1948;89:143-186.
tuto Ramon v Cajal, Madrid , 1972 ). Figure 7.2 from Ramon y Cajal S. Figure 7.12 courtesy of Dr. W . R .
Figure 5.39 from Young JZ . Factors Histologie du Svsteme Nerveux de Kennedy, University of Minnesota ,
influencing the regeneration of l'Homme et des Vertebres. Minneapolis, MN .
nerves. AdvSurg 1949;1:165-220. ( Azoulay L, trans.) Paris: Maloine, Figure 7.13 courtesy of Dr . W . R .
Figure 5.41 based on Weiss P, His- 1909, 1911 . ( Reprinted , Consejo Su - Kennedy, University of Minnesota,
coe 1111. Experiments on the mech - perior de Investigaciones Cientifi- Minneapolis, MN .
anism of nerve growth. I Exp Zool cas , Institute Ramon v Cajal , Figure 7.14 courtesy of Dr. W . R .
1948;107:315-396; Young JZ. Fac- Madrid , 1972. ) Kennedy, University of Minnesota ,
tors influencing the regeneration of Figure 7.4 A based on De Castro F. Minneapolis, MN .
nerves. Adv Surg 1949;1:165-220. Contribution a la connaissance de Figure 7.15 modified from
Figure 5.42 courtesv of Dr. P.J . Be- l'innervation du pancreas. Y a t -il Schoultz TW , Swell JE . The fine
dard , Neurobiologv Research Cen - des conducteurs specifiques pour structure of the Golgi tendon
ter, Laval University, Quebec, les ilots de Langerhans, pour les organ. J Neurocytol 1972;1:1 -26.
Canada . acini glandulaires et pour les vais- Figure 7.16 from Schoultz TW ,
Figure 6.1 trom Bodian D. The neu - seaux. Trav Lab Rech Biol Univ Swett JE . The fine structure of the
rosciences. In: Quarton GC , ed . A Madrid 1923;21:423-457. Golgi tendon organ . J Neurocytol
studv program. New York: Rocke- Figure 7.4 B based on Smirnow A. 1972;1 :1-26.
feller University Press, 1967:6-24. Uber die sensiblen Nervenendi- Figure 7.17 modified from Robert -
Figure 6.3 from Penfield W. Cytol - gungen ini Herzen bei Amphibien son |D. The ultrastructure of a rep-
ogy and cellular pathology of the und Saiigetieren. Anat An / tilian myoneural junction. J Bio-
nervous system. New York: Paul B. 1895;10:737-749. plus Biochem Cvtol I 956;2:
Hoeber, 1932. Figure 7.4C based on Larsell O, 381-394; Robertson JD. Electron
Figure 6.5 courtesy of Dr. James E. Dow RS. Innervation of the human microscopy of the motor end - plate
Vaughn, City of Hope Medical lung. Am J Anat 1933;52:414-438. and the neuromuscular spindle.
Center , Duarte, CA.
Figure 6.8 courtesy of Dr. James E.
Figure 7.4 D based on Carpenter
EW . Nerve endings of sensory type
-
Am J Phys Med 1960;39:1 43; and
Couteaux R , Morphological and
Vaughn , City of Hope Medical in the muscular coat of the stomach cytochemical observations on the
Center , Duarte, CA. and small intestine. J Comp Neurol postsvnaptic membrane at motor
Figure 6.9 courtesv of Dr. R . P.
Bunge; from Copenhaver WM ,
1918;29:553-560.
Figure 7.5 modified from Cauna N .
-
end plate , and ganglionic synapses.
Exp Cell Res 1958;5:294-322.
Bunge KP, Bunge MB, et al . Bai- The effects of aging on the receptor Figure 7.18 from Larsell O, Dow
-
ley's textbook of histology 16th ed . organs of the human dermis. In: RS. Innervation of the human lung.
Baltimore: Williams & Wilkins ,
1971 .
Montagna W , ed . Advances in biol-
ogy of skin . Vol. 6. Aging. New
-
Am J Anat 1933;52:414 438 .
Figure 8.2 from Carmel PW , Stein,
Figure 6.12 based on Ramon y York: Pergamon Press, 1963:63 69. BM . J Comp Neurol ] 9h9;135:
Cajal S. Histologie du Svsteme Figure 7.6 from Merkel F. 145-166.
Neveux de l’Homme et des Tastzellen und Tastkdrperchen bei- Figure 8.3 after Ramon y Cajal S.
Vertebres. ( Azoulav L, trans.) den Hausthieren und beim Men- Histologie du Systeme Nerveux de
Paris: Maloine , 1909, 1911 . schen. Arch Mikrosk Anat Entwick l ' Homme et des Vertebres. ( Trans-
( Reprinted ,Consejo Superior de Mech 1975;11:636-652. lated by L . Azoulay ), Paris: Mal -
Investigaciones Cientificas, Insti - Figure 7.7 based on Ralston HJ III, oine, 1909, 1911 . ( Reprinted , Con -
tute Ramon v Cajal , Madrid , 1972. ) Miller MR , Kasahara M . Nerve sejo Superior de Investigaciones
Figure 6.14 courtesy of Dr. Virginia endings in human fasciae, tendons, Cientificas, Institute Ramon y
Tennyson , College of Physicians ligaments, periosteum , and joint Cajal, Madrid , 1972.)
and Surgeons, Columbia Univer- synovial membrane. Anat Rec Figure 8.4 from Truex RC. Mor -
sity, New York. I 960;136:137-148. phological alterations in the
Figure 6.15 from Brightman MW , Figure 7.9 A based on Dogiel AS. Gasserian ganglion cells and their
Palay SL. The fine structure of Die Nervenendkorperchen ( End - association with senescence in
ependyma in the brain of the rat . J kolben . W . Krause ) in der Cornea man . Am J Pathol 1940;16:255-268.
Cell Biology 196.3, 19:415-4.39. und Conjunctiva Bulbi des Men - Figure 8.5 from Carmel PW , Stein
Figure 6.16 from Page RB, Rosen - schen . Arch Mikrosk Anat En - BM . Cell changes in sensory gan -
stein JM , Dovev BJ , et al . Ependy - twickl-Gesch 1891;37:602-619. glia following proximal and distal
mal changes in experimental hy
drocephalus. Anat Rec 1979; 194:
- Figure 7.9 B from Ruffini A. Sur un
nouvel organe nerveux terminal et
nerve section in the monkey. J
Comp Neurol 1969;135:145-166.
67-82. sur la presence des corpuscules Figure 8.7 from Copenhaver WM .
Figure 6.19 courtesv of Dr. Virginia
Tennyson, College of Physicians
-
Golgi Mazzoni dans le conjonctif
sous-cutane de la pulpe des doigts
Bailey's textbook of histology. 15th
ed . Baltimore: Williams & Wilkins,
and Surgeons, Columbia Univer- de I ' homme. Arch Ital Biol 1964.
sity , New York. 1894;21:249-265. Figure 8.8 modified from Hay -
Figure 6.20 courtesy of Dr . R . Figure 7.10 based on from Ramon maker W , Wood hall B . Peripheral
Marchand , Neurobiology Research y Cajal S. Histologie du Systeme nerve injuries: principles of diag-
Center , Laval University, Quebec, Nerveux de l' Homme et des nosis. Philadelphia: W . B. Saunders,
Canada . Vertebres. ( Azoulay L, trans.) 1945.
Figure 8.9 modified from Hay - nization of the brachial spinal cord Kuypers HGJM . Pericentral corti -
maker W , Wood hall B. Peripheral of the cat. II . The motoneuron cal projections to motor and sen-
nerve injuries: principles of diag- plexus. Brain Res 1967;4:16-32. sory nuclei. Science 1958;128:
nosis. Philadelphia: W .B. Saunders, Figure 10.26 based on Cummings 662-663.
1945.
Figure 8.10 modified from Hay -
JF, Petras JM . The origin of Spin
ocerebellar pathways. I . The nu -
- Figure 13.6 from Mettler FA . Neu -
roanatom v St . Louis: C.V. Mosby
*
maker W , Woodhall B. Peripheral cleus cervicalis centralis of the cra - Co., 1948.
nerve injuries: principles of diag- nial cervical spinal core. J Comp Figure 13.11 from Rivera -
nosis. Philadelphia: W .B. Saunders, Neurol 1977; 173:655-692. Dominguez M , Agate FJ Jr, Noback
1945. Figure 10.28 from Jessell TM , CR . Scanning electron microscopy
Figure 8.16 after I laymaker W . Iversen LL. Opiate analgesics in - of the spiral organ of Corti of the
Bing's local diagnosis in neurologi- hibit substance P release from rat adult rhesus monkey . Brain Res
cal diseases. St . Louis: C. V. Mosby, trigeminal nucleus. Nature 1977; 1973;65:159-164.
1956. 268:549-551; and courtesy of Pro- Figure 13.12 from Rose JE, Galam -
Figure 8.17 after Haymaker W . fessor Stephen Hunt, Cambridge bos R , Hughes JR . Organization of
Bing's local diagnosis in neurologi- University . frequency sensitive neurons in the
cal diseases. St . Louis: C. V . Mosby, Figure 12.18 based on Kalia M , cochlear complex of the cat . In:
1956. Mesulam M - M . Brain stem projec- Rasmussen GL, Windle WF, eds.
Figure 8.18 after Haymaker W . tions of sensory' and motor compo- Neural mechanisms of the audi-
Bing's local diagnosis in neurologi - nents of the vagus complex in the tory and vestibular systems.
cal diseases. St. Louis: C.V. Mosby , cat . I . The cervical vagus and no- Springfield , IL: Charles C. Thomas,
1956. dose ganglion . J Comp Neurol I960;116-136 .
Figure 9.4 adapted from Furness -
1980;193:435 465; Loewy AD, Bur-
ton H . Nuclei of the solitary tract:
Figure 13.12 from Carpenter MB.
Core text of neuroanatomy. Balti -
JB, Costa M . Types of nerves in the
enteric nervous system. Neuro - efferent projections to the lower more: Williams & Wilkins, 1991.
science 1980;5:1-20. brain stem and spinal cord of the Figure 13.14 modified from Ras-
Figure 9.6 A after Ramon y Cajal S. cat . J Comp Neurol 1978;181: mussen GL. Efferent fibers of the
Histologic du Systeme Nerveux de 421 ^150; and Beckstead RM , Nor- cochlear nerve and cochlear nu -
PHomme et des Vertebres. gren R. An autoradiographic ex- cleus. In: Rasmussen GL, Windle
( Azoulay L, Trans.) Paris: Maloine, amination of the central distribu - WF, eds. Neural mechanisms of the
1909, 1911. ( Reprinted, Consejo Su - tion of the trigeminal, facial, auditory and vestibular systems.
perior de Investigaciones Cientifi - glossopharyngeal and vagal nerves Ch . 8. Springfield , IL: Charles C.
cas, Institute Ramon y Cajal , in the monkey . J Comp Neurol Thomas, 1960:105-115.
Madrid , 1972. ) 1979;184:455-472. Figure 13.15 from Carpenter MB,
Figure 9.6 B after Ranson SW , Figure 12.20 based on Ramon y Chang L, Pereira AB, Hersh LB,
Billingsley PR . The superior cervi- Cajal S. Histologic du Systeme Bruce G , Wu JY. Vestibular and
cal ganglion and the cervical por- Nerveux de l ' Homme et des cochlear efferent neurons in the
tion of the sympathetic trunk . J Vertebres. ( Azoulay L, trans.), monkey identified by immunocy-
Comp Neurol 1918;29:313 358.- Paris: Maloine, 1909, 1911. tochemical methods. Brain Res
Figure 9.7 courtesy of Dr . Torbjorn ( Reprinted , Consejo Superior de 1987;408:275-280.
Malmfors, Karolinska Institutet , Investigaciones Cientificas, Insti- Figure 13.16 from Stein BM , Car -
Sweden . tuto Ramon y Cajal, Madrid , 1972.) penter MB. Central projections of
Figure 9.8 courtesy of Dr. Michael Figure 12.21 reproduced from portions of the vestibular ganglia
D. Gershon, College of Physicians Kalia M , Mesulam M - M . Brain innervating specific part of the
and Surgeons, Columbia Univer- stem projections of sensory and labyrinth in the rhesus monkey .
sity, New York . motor components of the vagus Am J Anat 1967;120:281-318.
Figure 9.10 modified from White complex in the cat. I . The cervical Figure 13.17 from Stein BM, Car-
JC, Okelberry AM , Whitelaw GP. vagus and nodose ganglion . J penter MB. Central projections of
Vasomotor tonus of the denervated Comp Neurol 1980;193:435-465. portions of the vestibular ganglia
artery. Arch Neurol and Psychiatry Figure 12.22 from Kalia M , Mesu - innervating specific part of the
1936;36:1251-1276 . lam M - M . Brain stem projections of labyrinth in the rhesus monkey .
Figure 10.20 adapted from Cull - sensory and motor components of Am J Anat 1967;120:281-318.
heim S, Kellerth J -O. Morphologi- the vagus complex in the cat . 1. The Figure 13.21 from Carpenter MB,
cal study of the axons and recur- cervical vagus and nodose gan - Chang L, Pereira AB, Hersh LB,
rent axon collaterals of cat sciatic a glion . J Comp Neurol 1980;193: Bruce G, Wu JY. Vestibular and
motoneurons after intracellular 435-465. cochlear efferent neurons in the
staining with horseradish peroxi- Figure 12.23 reproduced from monkey identified by immunocv -
dase. J Comp Neurol 1978;178: Kalia M , Mesulam M - M . Brain tochemical methods. Brain Res
537-558; and Cullheim S, Kellerth stem projections of sensory and 1987;408:275-280.
J -O, Conradi S. Evidence for direct motor components of the vagus Figure 13.25 from Carpenter MB,
synaptic interconnections between complex in the cat. I . The cervical Carleton SC. Comparison of
cat spinal gamma - motoneurons via vagus and nodose ganglion . J vestibular and abducens projec-
the recurrent axon collaterals: A Comp Neurol 1980;193:435-465. tions to the medial rectus subdivi-
morphological study using intra - Figure 12.24 modified from Loewy sion of the oculomotor complex in
cellular injection of horseradish AD, McKellarS. The neuroanatom- the monkey . Brain Res 1983;274:
peroxidase. Brain Res 1977;132: ical basis of central cardiovascular 144 149.
1-10. control. Fed Proc 1980;39: 2495- Figure 13.29 from Carpenter MB.
Figure 10.21 based on Sterling P, 2503. Core text of neuroanatomy. Balti -
Kuypers HGJM . Anatomical orga- Figure 12.27 modified from more: Williams & Wilkins, 1991 .
Figure /Table Credits 979
Figure 13.31 modified from Ramon Figure 15.6 courtesy of the late Dr schliclien Diencephalon: Abhand -
y Cajal S. Histologic du Systeme C.A. Fox, School of Medicine, lungen der kbnighl preuss.
Nerveux de 1' Homme et des Wayne State University. Akademie der Wissenschaften
Vertebres. ( Azoulav L, Trans.) Figure 15.7 courtesy of Dr. P. De 1910;92.
I’aris: Maloine, 1909, 1911. Camilli , Department of Cell Biol - Figure 16.11 modified from Mal -
( Reprinted , Consejo Superior de ogy, School of Medicine, Yale Uni - one EF. Uber die Kerne des men -
Investigations Cientificas, Insti- versity .
tuto Ramon y Cajal, Madrid , 1972. ) Figure 15.8 from Boegman RJ , Par-
schlichen Diencephalon : Abhand
lungen der kdnighl preuss.
-
Figure 13.35 courtesy of Drs. ent A , Flawkes R . Zonation in the Akademie der Wissenschaften
Jacqueline McGinty and Floyd rat cerebellar cortex: patches of 1910;92.
Bloom , Salk Institute, La Jolla , CA . high acetylcholinesterase activity Figure 16.15 from Roberts TS,
Figure 14.10 from Carpenter MB, in the granular layer are congruent Akert K . Insular and opercular cor -
Pierson RJ. Pretectal region and the with Purkinje cell compartments. tex and its thalamic projection in
pupillary light reflex: an anatomi- Brain Res 1988;448:237-251. Macaca mulatta Schweiz Arch
cal analysis in the monkey. J Comp Figure 15.9 courtesy of Dr. D. B. Neurol Neurochir Psychiat 1963;
-
Neurol 1973;149:271 300. Newman, Uniformed Service Uni-
Figure 14.11 from Carpenter MB, versity , Bethesda , MD.
-
92:1 13.
Figure 16.16 modified from
Pierson RJ . Pretectal region and the Figure 15.11 courtesy of the late Sadikot AF, Parent A, Francois C.
pupillary light reflex: an anatomi - Dr. C.A. Fox, School of Medicine,
cal analysis in the monkey. J Comp Wayne State University.
Efferent connections of the centro
median and parafascicular thala -
-
Neurol 1973;149:271-300. Figure 15.12 based on Eccles JC, Ito mic nuclei in primates. A PHA -L
Figure 14.14 based on Warwick R . M , Szentagothai J . The cerebellum studv of subcortical projections. J
Representation of the extraocular as a neuronal machine . New York: Comp Neurol 1992;315:137-159.
muscles in the oculomotor nuclei Springer-Verlag, 1967. Figure 16.18 modified from
of the monkey. J Comp Neurol Figure 15.13 courtesy of Dr. R.C. Hazrati L- N , Parent A. Contralat -
-
1953;98:449 504; and Warwick R. Henrikson, Albany Medical Col-
The identity of the posterocentral lege, Albany , NY.
eral pallidothalamic and palli -
dotegmcntal projections in pri -
nucleus of Panegrossi . J Comp Figure 15.14 modified from Eccles mates: an anterograde and
Neurol 1953;99:599-612. JC, Ito M, Szentagothai J . The cere- retrograde labeling study. Brain
Figure 14.15 from Carpenter MB, Ix’llum as a neuronal machine. Res 1991;567:212-223.
Peter P. Accessory oculomotor nu - New York: Springer- Verlag, 1967. Figure 16.19 based on Jones EC, .
clei in the monkey. J Hirnforsch Figure 15.15 from Jakob A. Das Friedman DP. Projection pattern of
1970 / 71;12:405-418. Kleinhirn . In: von Mollendorff W , functional components of thalamic
Figure 14.16 from Carpenter MB, ed . Handbuch der mikroskopishen ventrobasal complex on monkey
Pierson RJ . Pretectal region and the Anatomic des Menschcn . Vol. IV . somatosensory cortex. | Neuro-
pupillary light reflex: an anatomi- Berlin: Julius Springer, 1928: physiol 1982;48:521-544.
cal analysis in the monkey. J Comp 674-916. Figure 16.20 based on Jones EG,
Neurol 1973;149:271-300. Figure 15.16 based on I’alay SL, Friedman DP. Projection pattern of
Figure 14.17 from Carpenter MB, Chan-Palay V. Cerebellar cortex: functional components of thalamic
Harbison JW, Peter P. Accessory cytology and organization. Berlin : ventrobasal complex on monkey
oculomotor nuclei in the monkey. Springer-Verlag, 1974 . somatosensory cortex . J Neuro-
Projections and effects of discrete Figure 15.17 from Mettler FA. Neu
lesions. I Comp Neurol 1970;140: roanatomy. St . Louis: C.V. Mosbv,
- physiol 1982;48:521-544.
Figure 16.21 from Beckstead RM ,
131-154. 1948. Morse JR, Norgren R . The nucleus
Figure 14.18 after Ramon y Cajal S. Figure 15.20 based on Snider RS. of the solitary tract in the monkey:
Histologie du Systeme Nerveux de Recent contributions to the projections to the thalamus and
1’ Homme et des Vertebres. anatomy and physiology of the brain stem nuclei. J Comp Neurol
( Azoulay L, trans.), Paris: Maloine, cerebellum . Arch Neurol Psychia - 1980;190:259-282.
1909, 1911 . ( Reprinted , Consejo Su - try 1950;64:196-219. Figure 16.22 modified from Jones
perior de Investigaciones Cientifi- Figure 15.23 from Batton RR III , Ja - EG, Powell TPS. An analysis of the
cas, Instituto Ramon y Cajal, yaraman A, Ruggiero D, Carpenter posterior group of thalamic nuclei
Madrid , 1972.) MB. Fastigial efferent projections on the basis its afferent connec-
Figure 15.3 modified from Ramon in the monkey: an autoradi- tions. | Comp Neurol 1971;143:
y Cajal S. Histologie du Systeme ographic study. J Comp Neurol 185-216.
Nerveux de 1' Homme et des 1977;174:281-306. Figure 16.23 based on Morest DK .
Vertebres. ( Azoulav L, trans.), Figure 15.25 modified from Brodal The laminar structure of the medial
Paris: Maloine, 1909, 1911. A , Pompeiano O, Walberg F. The geniculate body of the cat . J Anat
( Reprinted , Consejo Superior de vestibular nuclei and their connec- 1%5;99:143 159 ,
Investigaciones Cientificas, Insti - tions, anatomy and functional cor- Figure 16.25 from Hickey TL,
tuto Ramon y Cajal , Madrid , 1972.) relations. Springfield , IL: Charles Guillery RW. Variability of laminar
Figure 15.5 based on Eccles JC, Ito C. Thomas, 1962. patterns in the human lateral
M , Szentagothai J . The cerebellum Figure 16.1 from Mettler FA. Neu - geniculate nucleus. J Comp Neurol
as a neuronal machine. New York:
Springer-Verlag, 1967; and Gray Co., 1948.
-
roanatom v St . Louis: C. V . Mosbv 1979;183:221-246.
Figure 16.26 from Kaas ) H ,
EG. The granule cells, mossy Figure 16.8 from Carpenter MB. Guillery RW, Allman JM . Some
synapses and Purkinje spine Core text of neuroanatomy. Balti - principles of organization in the
synapses of the cerebellum: light more: Williams & Wilkins, 1978. dorsal lateral geniculate nucleus.
and electron microscopic observa- Figure 16.10 modified from Mal - Brain Behav Evol 1972;6:253-299 ,
tions. J Anat 1961;95:345-356. one EF. Uber die Kerne des men- Figure 16.27 modified from Kaas
JH, Guillery RW , Allman JM. Some study. J Comp Neurol 1991;312: Georges Pelletier, Molecular En-
principles of organization in the 1- 18 . docrinology Laboratory, CHUL,
dorsal lateral geniculate nucleus. Figure 16.40 modified from Dowl- Quebec, Canada.
Brain Behav Evol 1972;6:253-299. ing JE, Boycott BB. Organization of Figure 17.14 based on Nauta WJH .
Figure 16.28 based on Hoyt WF, the primate retina : electron mi- Hippocampal projections and re-
Luis O. V' isual fiber anatomy in the croscopy . Proc R Soc Lond ( Biol) lated neural pathways to the mid -
infragcniculate pathway of the pri - 1966;166:80- 111; and Noback CR, brain in the cat . Brain 1958;8l:
mate. Arch Opthalmol 1962;68: Laemle LK . Structural and func- 319-340.
94- 106; and Noback CR, Laemle tional aspects of the visual path- Figure 17.17 modified from Rais-
LK . Structural and functional as- ways of primates. In: Noback CR, man G. Neural connections of hy-
pects of the visual pathways of pri - Montagna W, eds. Advances in pri- pothalamus. Br Med Bull 1966;
mates. In: Noback CR, Montagna matology • Vol. 1: The primate 22:197- 201.
W, eds. Advances in primatology. brain. Ch. 3. New York: Appleton- Figure 17.19 from Page RB, Berg-
Vol. I : The primate brain. Ch. 3. Century-Crofts, 1970: 55—81 . land RM . The neurohypophyseal
New York: Appleton-Centurv - Figure 16.42 from Mettler FA . Neu- capillary bed. I . Anatomy and arte-
Crofts, 1970:55-81. roanatomy . St . Louis: C. V . Mosbv rial supply. Am J Anat 1977;
'
Figure 16.29 based on Malpcli JG, Co., 1948 . 148:345-357.
Baker FH. The representation of Figure 16.43 modified from Hay- Figure 17.20 modified from Schally
the visual field in the lateral genic- maker W . Bing' s local diagnosis in AV , Kastin AJ, Arimura A . Hypo-
ulate nucleus of the Macaca mu- neurological diseases. St . Louis: thalamic hormones: The link be-
latta . I Comp Neurol 1975;161: C. V . Mosby Company, 1956:57-62 tween brain and body . Am Sri
569- 594 . and 105- 112. 1977;65:7122-719.
Figure 16.30 modified from Szen- Figure 17.2 based on I ,e Gros Clark Figure 17.21 from Hdkfelt T, Jo-
tagothai j . Glomerular synapses, WF, Beattie J, Riddoch C, Dolt hansson O, Fuxe K, Goldstein M,
complex synaptic arrangements, NM, eds . The hypothalamus. Edin- Park D. Immunohistochemical
and their operational significance. burgh: Oliver and Boyd , 1938. studies on the localization and dis-
In: Schmitt FO, ed. The neuro- Figure 17.3 based on Le Gros Clark tribution of monoamine neuron
sciences. Second study program . WE, Beattie J , Riddoch G, Dott systems in the rat brain. I . Tyrosine
Ch. 40. New York: Rockefeller Uni- NM, eds. The hypothalamus. Edin- hydroxylase in the mes- and dien-
versity Press, 1970:427-443. burgh: Oliver and Boyd, 1938. cephalon. Med Biol 1976;54: 427-
Figure 16.31 courtesy of Drs. M . Figure 17.5 modified from Parent 453.
Deschenes and D. Pinault , Neuro- A , Descarries L, Beaudet A . Orga - Figure 17.22 from Gorski RA , Gor-
biology Research Center, Laval nization of ascending serotonin don |H, Shrvne JE, Southam AM.
University, Quebec, Canada. systems in the adult rat brain . A ra- Evidence for a morphological sex
Figure 16.32 modified from dioautographic study after intra - difference within the medial pre-
Sadikot AF, Parent A , Francois C. ventricular administration of optic area of the rat brain. Brain
Efferent connections of the centro- Pill 5-hydroxytryptamine. Neuro- Res 1978;148:333-346.
median and para fascicular thala - science 1981;6: 115- 138. Figure 18.2 based on Nauta WJH.
mic nuclei in primates. A PHA-L Figure 17.6 courtesy of S. Bovetto, Hippocampal projections and re-
study of subcortical projections. I C. Rouillard, and D. Richard of the lated neural pathways to the mid-
Comp Neurol 1992;315: 137- 159. Neurobiology Research Center and brain in the cat . Brain 1958;8 l :
Figure 16.33 modified from Smith Physiology Department, Laval 319-340.
Y , Parent A , Seguela P, Descarries University , Quebec, Canada. Figure 18.4 from the work of P- Y
L. Distribution of GABA-im- Figure 17.7 from Silverman AJ , Cote, P. Levitt, and A . Parent, Neu-
munoreactive neurons in the basal Pickard GE. The hypothalamus. In: robiologv Research Center, Laval
ganglia of the squirrel monkey Emson PC, ed. Chemical neu- University , Quebec, Canada, and
( Snimiri Scinmts ) . J Comp Neurol roanatomy. New York: Raven Robert Johnson Wood School of
1987;259:50-65. Press, 1983:295-336. Medicine, Piscataway, NJ.
Figure 16.34 modified from Smith Figure 17.8 from Pickard GE, Sil- Figure 18.5 after Ramon y Cajal S.
Y , Parent A , Seguela P, Descarries verman A -J . Direct retinal projec- Histologie du Systeme Nerveux de
L. Distribution of GABA -im- tion to the hypothalamus, piriform I'Homme et des Vertebres.
munoreactive neurons in the basal cortex, and accessory optic nuclei ( Azoulay L, trans. ) Paris: Maloine,
ganglia of the squirrel monkey in the golden hamster as demon- 1909, 1911 . ( Reprinted Consejo Su-
( Saimiri Scinrms ). | Comp Neurol strated by a sensitive anterograde perior de Investigaciones Cientifi-
1987;259:50-65. horseradish peroxidase technique. cas, Instituto Ramon y Cajal,
Figure 16.35 courtesy of Dr . J .- J . J Comp Neurol 1981 ; 196: 155— 172. Madrid, 1972.)
Soghomonian, Neurobiology Re- Figure 17.9 from Millhouse OE. A Figure 18.8 based on Valverde F.
search Center, Laval University, Golgi anatomy of the rodent hy - Studies on the piriform lobe. Cam-
Quebec, Canada. pothalamus. In: Morgane P, bridge: Harvard University Press,
Figure 16.36 modified from Lavoie Panksepp J , eds. Handbook of the 1965.
B, Parent A . Serotoninergic inner- hypothalamus. Vol . I: Anatomy of Figure 18.9 based on Potter H,
vation of the thalamus in the pri- the hypothalamus. New York : Nauta WJH . A note on the problem
'
mate: an immunohistochemical Marcel Dekker, 1979:221- 265. of olfactory associations of the or-
study. Comp Neurol 1991;312: Figure 17.10 from Silverman AJ,
| bitofrontal cortex in the monkey.
l i s. Pickard GE. The hypothalamus. In: Neuroscience 1979;4:361- 369.
Figure 16.37 modified from Lavoie Emson PC, ed. Chemical neu- Figure 18.10 modified from Krieg
B, Parent A . Serotoninergic inner - roanatomy. New York: Raven WJS. Functional neuroanatomy .
vation of the thalamus in the pri - Press, 1983:295-336. New York: Blakiston Company,
mate: an immunohistochemical Figure 17.11 courtesy of Dr . 1953:658.
Figure /Table Credits 981
Figure 18.11 from Mettler FA. Neu - process in the expression of striatal 154- 164, with permission of the au -
roanatomy. 2d ed . St. Louis: C.V. functions. Trends Neurosci 1990; thors and Alan R . Liss, Inc., New
Mosby, 1948. 13:277-280. York .
Figure 18.15 The assistance of Dr. Figure 19.46 based on DeLong MR , Figure 20.7 from Houser CR,
J . B. Angevine of the University of Georgopoulos AP, Crutcher MD. Vaughn IE, Hendry SHC , Jones '
Arizona , College of Medicine, and Cortico-basal ganglia relations and EG , Peters A. GABA neurons in the
Dr. R .S. Nowakowski, University coding of motor performance. Exp cerebral cortex. In: Jones EG, Peters
of Mississippi Medical Center, is
acknowledged for delimiting the
Brain ResSuppI 1983;7:30 40.-
Figure 19.47 based on Albin RL,
A , eds. Cerebral cortex. Vol. 2.
New York : Plenum Press, 1984:
cytoarchitectonic boundaries. Young AB, Penney ) B. The func- 63-89; and courtesy of Dr. Carolyn
Figure 18.16 based on Lorente de tional anatomy of basal ganglia R . Houser, Brain Research Insti-
No, R . 1934. Studies on the struc- disorders. Trends Neurosci 1989; tute, UCLA , Los Angeles, CA .
ture of the cerebral cortex. II . Con - 12:366-375; Alexander GE , DeLong Figure 20.9 based on Morrison JH ,
tinuation of the study of the am - MR , Strick PL. Parallel organiza - Hot PR . The organization of the
nionic system . J Psychol Neurol tion of functionally segregated cir- cerebral cortex: from molecules to
46:113-177; and Peele I' L . The neu - cuits linking basal ganglia and cor- circuits. In : Magistretti PJ , ed . Dis-
roanatomical basis for clinical neu - tex. Ann Rev Neurosci 1986;9: cussions in neuroscience. Vol . 9.
rology . New York: McGraw I till , 357-381; DeLong MR . Primate Amsterdam: Elsevier, 1992:11 79. -
1961. models of movement disorders of Figure 20.10 after Brodmann K .

the basal ganglia . Trends Neurosci
Figure 18.21 modified from
Sadikot A, Parent A . The mono- - .
1990;13:281 285; and C uridi J ,
Vergleichende Lokalisation lehre
der Grosshirnrinde in ihren
aminergic innervation of the amyg
dala in the squirrel monkey: an im -
- Luquin MR, Herrero MT, Obeso Prinzipien dargestellt auf Grund
des Zellenbaues. Leipzig: |. A.
JA . The subthalamic nucleus: a
munohistochemical study . Neuro- possible target for stereotaxic Barth, 1909.
science 1990;36:431-447. surgery in Parkinson's disease. Figure 20.12 after von Economo
Figure 18.22 modified from Des- Mov Disord 1993;8:421-429. CF. The cytoarchitectonics of the
jardins C, Parent A. Distribution of Figure 20.1 after Brodmann K . Ver - human cerebral cortex . London :
somatostatin immunoreactivity in gleichende Lokalisation lehre der Oxford Medical Publications, 1929.
the forebrain of the squirrel mon - Grosshirnrinde in ihren Prinzipien Figure 20.13 after von Economo
key. Basal ganglia and amygdala .
Neuroscience 1992;47:115-133.
dargestellt auf Grund des Zellen
baues. Leipzig: J .A. Barth, 1909.
- CF. The cytoarchitectonics of the
human cerebral cortex. London:
Figure 18.24 modified from Sutin ) , Figure 20.2 based on Ramon y Oxford Medical Publications, 1929.
McBride RL . Anatomical analysis Cajal S. Histologie du Systeme Figure 20.14 after Campbell AW .
of neuronal connectivity. In: Myers Nerveux de THomme et des Histological studies on the local -
RD, ed . Methods in psychobiology . Vertebres. ( Azoulay L, trans.) ization of cerebral function . New
Vol . 3. New York: Academic Press, Paris: Maloine, 1909, 1911 . York: Cambridge University Press,
1977:1-26. ( Reprinted Consejo Superior de In - 1905.
Figure 18.25 modified from Parent vestigaciones Cientificas, Institute Figure 20.15 after Campbell AW
A , Csonka C, Etienne P. The occur - Ramon y Cajal, Madrid , 1972. ); and Histological studies on the local -
rence of large acetylcholinesterase- Lorente de No R . The structure of ization of cerebral function . New
containing neurons in human the cerebral cortex. In : Fulton JF, York: Cambridge University Press,
neostriatum as disclosed in normal
and Alzheimer-diseased brains.
ed . Physiology of the nervous sys
tem . 3rd ed. New York: Oxford
- 1905.
Figure 20.16 based on Powell TPS,
-
Brain Res 1984;291:154 158 .
Figure 19.9 from DiFiglia M , Pasik
-
University Press, 1949:288 330.
Figure 20.3 redrawn from Jones
Mountcastle VB. The cytoarchitec
ture of the postcentral gyrus of the
-
P, Pasik T. A Golgi study of neu - EG. Connectivity of primate sen - monkey Macaca mulatta. Bull
ronal types in the neostriatum of sory - motor cortex. In: Jones EG , Johns Hopkins Hosp 1959; 1()5:
monkeys. Brain Res 1976;!14: Peters A , eds. Cerebral cortex. Vol . 18-131; and Powell LI’S, Mount -
245-256. 5. New York: Plenum Press, 1986: castle VB. Some aspects of the
Figure 19.10 courtesy of the late 113-183. functional organization of the cor-
Dr. C. A. Fox, Wayne State Univer- Figure 20.4 based on Lorente de tex of the postcentral gyrus of the
sity, Detroit , Ml . NcS R . The structure of the cerebral monkey: a correlation of findings
Figure 19.17 courtesy of Prof . Ann
M . Graybiel, Massachusetts Insti -
cortex. In: Fulton JF, ed . Physiol
ogy of the nervous system . 3rd ed .
- obtained in a single unit analysis
with cytoarchitecture. Bull Johns
tute of Technology, Amherst, MA . New York: Oxford University Hopkins Hosp 1959;105:133-62.
Figure 19.24 and 19.25 based on Press, 1949:288-330. Figure 20.17 based on , and re-
the work of B. Lavoie and A. Par
ent , Neurobiologv Research Center,
- Figure 20.5 courtesy of Dr . Marc
Colonnier, Neurobiologv Research
drawn from , Jones EG, Friedman
DP. Projection pattern of functional
Laval University, Quebec, Canada . Center, Laval University, Quebec, components of thalamic ven
trobasal complex on monkey so-
-
Figure 19.26, 19.27, 19.28, and 19.29 Canada , and Elsevier Publishing
based on the work of LN Hazrati
and A. Parent, Neurobiology Re-
Company, Amsterdam . matosensory cortex . J Neurophvs -
Figure 20.6 courtesy of Dr . R . Giuf - iol 1982;48:521-544.
search Center, Laval University, frida , Istituto di Fisiologia Umana, Figure 20.18 after Penfield W , Ras-
Quebec, Canada . Catania , Italy, and Dr. A . Rustioni , mussen T. The cerebral cortex of
Figure 19.35 from Mettler FA . Neu - University of North Carolina , and man: a clinical study of localization
roanatomv. St. Louis: C.V. Mosby, from Giuffrida R , Rustioni A. Glu - of function . New York: MacMillan ,
1948. tamate and aspartate immunoreac- 1950.
Figure 19.45 based on Chevalier G, tivity in corticospinal neurons of Figure 20.19 after Woolsey CN. Or-
Deniau JM . Disinhibition as a basic rat . J Comp Neurol 1989;288: ganization of somatic sensory and
motor areas of the cerebral cortex. Hubei and Allan R . Liss, Inc., New Brugge ) F. Representation of the
In : Harlow HF, Woolsey CN , eds. York; from LeVay S, Wiesel TN , cochlear partition on the superior
Biological and biochemical bases of Hubei DH . The development of oc- temporal plane of the Macaque
behavior. Madison: University of ular dominance columns in normal monkey. Brain Res 1973;50:
Wisconsin, 1958:63-81. visually deprived monkeys. J 275-296.; and Imig TJ , Ruggero
Figure 20.20 after Robinson C) , Comp Neurol 1980;191:1-51 . MA , Kitzes LM , Javel E, Brugge
Burton H . The organization of so- Figure 20.26 after Hubei DH, JF. Organization of auditory cor-
matosensory receptive fields in Wiesel TN . Uniformity of monkey tex in the owl monkey ( Aotus
cortical area 7b, retroinsular . striate cortex: a parallel relation - trivirgalus ). I Comp Neurol 1977;
postauditory and granular insular ship between field size, scatter and 171:111-128.
of M . fasciculari* . J Comp Neurol magnification factor. J Comp Neu - Figure 20.32 after Foerster O.
1980;192:69-92. rol 1974;158:295-306; and Hubei Svmptomatologie der Erkrankun -
Figure 20.22 after Hubei DH , DH , Wiesel TN , LeVay S. Plasticity gen des Grosshirns. Motorische
Wiesel TN . Receptive fields, binoc- of ocular dominance columns in Felder und Bahnen . In: Bumke O,
ular interaction and functional ar- monkey striate cortex. Phil Trans R Foerster O, eds. Handbuch der
chitecture in the cat's visual cortex.
J Physiol ( Lond ) 1962;160:106-154.
-
Soc Lond ( Biol ) 1977;278:377 109. Neurologie. Vol. 6. Berlin: Julius
Figures 20.27 and 20.8 courtesy of Springer, 1936:1-357.
Figure 20.23 after Hubei DH . The Dr. Louis Sokoloff , National Insti- Figure 20.33 after Travis AM . Neu -
visual cortex of the brain. Sci Am tute of Mental Health, N.I. H . rological deficiencies after ablation
1963;209:54-62. Figure 20.29 after Woolsey CN . Or- of the precentral motor area in
Figure 20.24 courtesy of Dr . Louis ganization of cortical auditory sys- Macaco Mulatto . Brain 1955;78:
Sokoloff , Laboratory of Cerebral tem: a review and synthesis. In : 155-173.
Metabolism, National Institute of Rasmussen CL, Wincile WF, eds.
.
Mental Health Bethesda, MD; and Neural mechanisms of the audi- TABLES
from Kennedy C, Des Rosiers Mil , tory and vestibular systems.
Springfield , IL: Charles C. Thomas, Table 7.1 from Horch KW Tuckett
,
Sakurada O, el al . Metabolic map-
1960:165-180; and Merzenich MM , RP Burgess PR. A key to the classi-
,
ping of the primary visual system
of the monkey by means of the au - Knight PL, Roth GL. Representa - fication of cutaneous mechanore-
.
tion of cochlea within the primary ceptors J Invest
Dermatol 1977;
toradiographic |' 4C| deoxyglucose
technique. Proc Natl Acad Sci USA auditory cortex in the cat. ) Neu - 69:75-82.
1976;73:4230-4234. rophysiol |975;38: 231- 249.
Figure 20.25 courtesy of Dr. David Figure 20.30 after Merzenich MM ,
Index
Page numbers in italics indicate figures; those followed by t indicate tables.
Abdominal aorta plexus, characteristics

301
. storage granules, functions, 308 -
ventral anterior nucleus, 652 653
transmission inactivation, 308 vestibular nuclei, 489
Abdominal superficial reflexes, spinal Adrenergic receptors, types, 310 -
visceral , 293, 303 304
innervation. 273 Adrenergic transmission, autonomic Afferent neurons, function , 144
Abducens nerve nervous system, 307-310 Agnosia
amino acid transport , 499 Adrenocorticotrophic hormones, 735 definition, 924
lesions, 499 Afferent fibers types, 924
neuron types, 498-499 abducens nucleus, 499 Agonist, definition , 617
root fibers, transverse section , 496 amygdaloid , medial nuclear group, 645 Akinetic mutism, 556
Abducens nucleus cerebellar cortex, 596 Alar plate, 73
afferent input, 499 cerebellar nuclei ventromedial portions, 81
lesions, 499-500 corticonuclear fibers, 604 Alexia , definition , 924
transverse section , 470 extracerebellar fibers, 604-605 Alvear path, dentate gyrus, 765
Accessory cuneate nucleus, 371 nucleocortical fibers, 604 Alveus
anatomic and functional features, cerebellum , 618 characteristics, 763
428 olivocerebellar fibers, 608-610 inward laminae, 763
Accessory oculomotor nuclei pontocerebellar fibers, 610-611 Alzheimer's disease
interstitial nucleus, 544 precerebellar nuclei , 611 amygdala destruction, 786
nucleus ot Darkschewitsch, 545 reticulocerebellar fibers, 610 basal nucleus, 788
posterior commissure nuclei , 545 spinocerebellar tracts, 607-608 basal nucleus of Meynert , 881
Accessory olfactory bulb, characteristics, vestibulocerebellar fibers, 606-607 microglia , 218
-
756 757 cerebral cortex, 869 olfactory deficits and degenerative
Accommoda t ion -con vergence reaction, dentate nucleus, 605 changes, 759
process, 548 facial nerve, 496-497 Amiculum olivae, 433
Acetylcholine, ( see also Cholinergic globus pallidus Amine precursor uptake and
neurons) other types, 832 decarboxylation cells, amine
autonomic nervous system , 306 striatopallidal fibers, 831 retention , 68
cerebral cortex, 880-882 > ubthalamopallidal fibers, 831-832 Amino acids
enteric neurons, 302 golgi tendon organ , 252 in amygdala , 776
hippocampus, 769 hypothalamus, 716-719 aspartate, spinal cord , 355-356
motoneuron effects, 77 schematic, 727 excitatory
muscle contraction, 257 intralaminar nuclei, 649 cerebral cortex, 873
in primate amygdala, 776, 778 lamina I , 339 thalamus, 679
receptors, types, 307 lamina 11, 340 glutamate
spinal cord transmitter, 352-353 lamina III , 341 cerebral cortex, 973
storage in motor end plates, 255 -
lamina IV , 341 342 hippocampal formation, 768
synaptic excitation , 177 lower motor neurons, 402 neurotransmitter, 161
thalamus, 673-675 medullary reticular formation , 435 regulation , astrocytes, 207
Acetylcholinesterase* oculomotor complex, 545-547 spinal cord, 355
cholinergic neurons, 353 -
olfactory bulb, 752 753 subthalamic nucleus, 840
function , 307 primary glycine, 356
inhibitor)’ drugs, 307 topographic organization, 351 transport, diencephalon , 837
myasthenia gravis, 258 zone of Lissauer, 351 -352 -
y Aminobutyric acid
presence in thalamus, 673-674 raphe nuclei, 821-822 basal ganglia core structures, 805
ACh, (see Acetylcholine) red nucleus, 550 cerebral cortex, 873-875
AChE, see Acetylcholinesterase ( x ) striatum , 798 enteric neurons, 302
Achilles tendon reflex, spinal amygdalostrial, 822 hippocampus receptors, 769
innervation , 273 corticostriatal, 811-814 inhibitory transmitter in spinal cord ,
Acoustic reflex, mechanisms, 482-483 -
nigrostriatal, 815 818, 821 356
Acoustic striae, types, 480 thalamostriatal, 814-815 neocortex, receptors, 875
Acoustic tubercle, 476 substantia nigra striatofugal neurons, 828
Acousticofacial reflex, secondary corticonigral, 563 subthalamic nucleus, 840
auditory fiber regulation , 497 pallidonigral, 562 thalamus, 675, 676 -677
ACTH, ( see Adrenocorticotrophic pedunculonigral, 563 Amygdala , 774
hormones) -
raphe nigral, 563 amygdalocortical connections,
Action potential striatonigral , 560-562 782-783
definition , 132 subthalamonigral, 562 camera lucida drawing, in monkey
purpose, 133 subthalamic nucleus, 835, 839, central nucleus, dopaminergic
single, climbing fiber, 597 841-842 projections, 782
Adenohypophysis, tumors, 737 superior colliculus, 535-536 cytochemical features
Adrenergic blocking agent , definition . thalamus, 695 acetylcholine, 776, 778
310 trigeminal nerve, mesencephalic amino acids, 775-776
Adrenergic fibers, overactivity , 311 nucleus, 506 monoamines, 776
Adrenergic neurons types, in visceral structures, 240 neuroactive peptides, 778-779
characteristics, 458 vagus nerve, 443 other substances, 779-780
983
984 Index
—
Amygdala continual
fiber bundles, 775
frontal cortex and , connections, 786
spinomedullary transition , 423
structures, 42
syringomyelia , 411
aneurysms, 110
anterior and posterior, 99
dura mater, 6
functional considerations, 783-786 Anterior median nucleus, 543 hypophysial portal system , 728
hippocampus and , relationship, 781 Anterior neuropore, 66 intercostal, occlusion , %
hvpothalamus and , relationship, Anterior nuclear group, 647 lenticulostriate, 107
781 -782 thalamus medial striate, characteristics, 104
intrinsic connections, 780 functions, 643-644 meningeal, 119-120
monoaminergic fibers and terminals . illustration , 649 occipital, internal, 107
777 nuclei classifications, 642 ophthalmic, dura mater, 6
nuclear organization , 773, 775 Anterograde axonal transport paramedian, 116
role in emotion , 786 fast and slow components, 182 pericallosal, 105
subcortical connections features, 190 posterolateral, 111
basal forebrain, 780 Anterograde degeneration , axon and posteromedial, 111
olfactory system , 780 .
myelin 184-186 quadrigeminal, 118
striatum , 780-781 Anterograde double-labeling technique radicular, characteristics, 95
thalamus and , relationship, 781 example, 139 spinal, anterior and posterior, 94-95,
tliberal region and optic chiasm, in neuronal imaging, / 58 114
cat, 785 substantia nigra , 566 temporo-occipital , 107
Amygdalocortical connections, Anterograde transport thalamogeniculate, 111
structures, 782-783 axons, 182 thalamoperforating, 111
Amygdaloid afferent fibers, medial components 190 . vertebral
nuclear group, 645 substances transported , / 83 branches, 113
Amygdaloid nuclear complex, 37 Antipsychotic drugs, schizophrenia , 879 characteristics 98.
autonomic and visceral functions, Aphasia Artery of Adamkiewicz, 95
785-786 characteristics. 924-925 Ascending fiber systems
bilateral lesions, 783 types, 924-925 locus coeruleus, 513
brain stem input , 782 Apraxia spinopontine, 383
characteristics, 42 characteristics, 925 spinoreticular, 382
fiber projections, hypothalamus, 717 types, 925 926- spinovestibular, 383
food and water intake, 785 APUD cells, ( sec Amine precursor Ascending spinal tracts
frontal section, 796 uptake and decarboxylation cells) function , 368
illustration , 761 Arachnoid spinotectal, 378
olfactory inputs, 756
stimulation , endocrine responses,
characteristics 9 . spinothalamic
anterior, 373-374
granulations
784-785 characteristics, 11 lateral, 375, 376
transverse section, 774 illustration, / 3 Aspartate, presence in spinal cord ,
Amygdaloslriatal fibers, characteristics, villi, 11 355-356
822 Arbor vitae, 53 Association fibers
Amyotrophic lateral sclerosis Archicerebellum cerebral cortex, 918-919
fasciculations, 289 characteristics 584 . interconnection to cortical regions,
spinal cord pathology, 409 lesions, 621 39
Anal reflex , spinal innervation, 273 Archipallium , 748 long and short groups, 39 40
Anastomoses, cerebral veins, 123 Arcuate fasciculus, characteristics, 40-41 Associative memory , 923
Aneurysms Arcuate fibers, internal , 428 Astereognosis, definition, 920
cerebral, 93 Arcuate nucleus Astrocytes
anterior communicating artery, / / 0 characteristics, 430, 713 Bergman, 82
characteristics, 109 dopamine presence, 725 biochemical markers
saccular cerebral, cerebral arterial somatostatin-14 localization , 721 glial fibrillary acidic protein , 206
circle occurrence, 102 Area postrema , 445 glutamine synthetase, 206
Angiograms characteristics, 23, 432 biogenic amine regulation , 207
cerebral, 102 Areflexia , definition , 403 -
bliKKi brain barrier formation,
limitations, 109 -
Argyll Kobertson pupil , 548 208-209
vessel imaging, 109 Argyrophilia , 134 characteristics, 203-204
principles, 54 Arterial vasocorona , 96 classes, 598
Anisocoria , 548 Arteries distribution and appearance, gray and
Anisomorphic gliosis, definition , 209 anterolateral, 111 white matter of spinal cord , 201
Anosmia , 758 anteromedial , 111 fibrous, 202 , 203
Ansa cervicalis, 275 basilar, 116 characteristics, 204
Ansa lenticularis branches, 113 in rat optic nerve, 205
characteristics, 832-833 brain functions, homeostasis, 206
fiber organization , 830 lateral surface, 101 GABA regulation , 207
nucleus, 843 medial surface, 101 glutamate regulation, 207
Ansa peeluncularis, 644 callosomarginal, 104-105 illustration, 200
Antagonist, definition, 617 carotid , internal , characteristics, 98 immunoreactivity for glial acidic
Anterior commissure central fibrillary protein, 227
characteristics, 41 characteristics, 103 injury reactions, 209-210
development , 89 groups, 111 intermediate filament 206.
frontal section , 37, 796 cerebellar , characteristics, 118-119 lamellar, 598
horizontal section, 35, 36 cerebral, 99 neuronal development , 208
hypothalamus, 712 cortical branches, 103 oligodendrocytes and , comparison,
structure's, 759, 759-760 .
middle 106-107 211
Anterior gray horn , characteristics, 328 posterior, 107, 109 plasticity , 208
Anterior horn cells radiopaque imaging , 103-104 potassium concentration regulation ,
activation , .363 choroidal , anterior and posterior, 112 -
206 207
amyotrophic lateral sclerosis, 409 circumferential , long and short , 116 protoplasmic, 203
injury, 402 communicating characteristics, 204-205
Index 985
reaction to hepatic encephalopathy . preganglionic regulation , 303 synapses, 173

209 structures, 302 unmyelinated , action potential, 168
reactive, 210 ganglia , structure, .304-306 Axoplasmic transport
.
smooth 598, 600 general arrangement , 294 anterograde, 181
transmitter receptors, 207-208 innervation overview, 183
Astrocytomas, definition , 210-211 -
eye, 316 317 purpose, 181
Asymmetric synapses, 174 salivary glands, 316-317 retrograde, 181-182
.
Asynergia definition , 620 urinary bladder, 377, 318-319 Axosomatic synapses, 172
Ataxia , definition , 620-621 neuroactive peptides, 310-311
Athetosis, 568 neuronal classifications, 293 Babinski 's sign , ( see Sign ol Babinski )
characteristics, 848-849 norepinephrine varicosities, .308 Ballism , 568
pathologic changes, 850 -
organization , tract tracing techniques, characteristics, 849
Auditory areas Band of Gennari, 893
cerebral cortex, 886 parasympathetic Bands of Baillarger, 865
actual and potential sites, 907 cranial region, 301-302 Basal forebrain
characteristics, 905-908 function, 262 amygdala and , relationship, 780
Auditory cortex preganglionic fibers, 301-302 substantia innominata, 774
functional architecture, 906-907 sacral region , 302 choline acetyltransferase
primary, cholinergic and sympathetic system and , immunoreactivity, 784
monoaminergic innervation , 877 antagonistic effects, 315-316 cholinergic neurons, 715
unilateral lesions, 908 visceral structures, 372 structures, 715, 786-788
Auditory fibers pseudorabies virus studies, 298-299 transverse section, 747, 787
primary , 478, 479 sympathetic Basal ganglia
secondary cervical ganglia, 300 -
y aminobutyric acid immunoreactive
480
.
acousticofacial reflex regulation function , 262
neural reflex arcs, 295
neurons, 805
arterial supply , 105
groups, 480 parasympathetic system and , associative circuits, 853
tonotopic localization , 478 -
antagonistic effects, 315 316 blood supply , 106
Auditory radiation , 33
Auditory system
postganglionic fibers, 307, 311, 373
preganglionic fibers, 373
-
caudate nucleus, 41 42
muscarinic cholinergic receptor
cochlea projections, 294 binding sites, 811
in monkey , 477
-
characteristics, 474 475 spinal ganglia , 300
topographic organization, 299-300
-
PHA L anterograde labeled
elements, 816
radial section , 476, 477 visceral structures, 312 circuitry schematic, 854
structures, 477 vomeronasal organ , 757 claustrum, 41
cochlear duct , 476 Autoradiographic tracing method cerebral cortex projections, 846
cochlear nerve examples, 141 characteristics, 798, 846
-
characteristics, 461 462 principles, 138 direct and indirect pathways, 852-853,
destruction , 484 Axial lines, human body, 270 H 54
-
nuclei, 475 476 , 478 Axillary nerve, muscle innervation , diseases, 568
fibers 281 animal models, 851-854
primary, 478, 479 Axodendritic synapses, 172 dyskinesias, ( see Dyskinesias )
secondary, groups, 480 cerebral cortex dopaminergic innervation , 819
tonotopic localization, 478 human , 176 -
frontal section , serotonin
lesions, 484 monkey, 177 im mu noreactive fibers, 820
Augmenting response, characteristics
693
. Axolemma , 165 functional considerations,
disinhibition of functions, 846-848
Axons
Autaptic synapses, 559 action potential, 132-133 globus pallidus, 41, 706
Autoimmune diseases, molecules definition , 132 afferent fibers, 652-653, 831
necessary for, 258 .
purpose 133 characteristics, 41
Autonomic cells, characteristics, 304 axoplasm , 149 development , 829, 831
Autonomic ganglia axoplasmic transport divisions, in primates, 795
classifications, 296 anterograde, 181-182 , 183 efferent fibers, 832-834, 836,
description, 295 definition , 181 836-838
neuroactive peptides, functions, 311 retrograde, 181-182 immunohistochemica ) features .
nicotinic receptors, 306 breakup, during nerve degeneration , 829
-
structure, 304 306 184-185 intrinsic organization , 831
Autonomic nervous system characteristics, 132 output organization , 836
afferent fibers, visceral structures, connective tissue sheaths -
topography, 828 829
303-304 endoneurium, 169 horizontal section, 683, 801
body functions, 319 epineurium , 169, 171 internal capsule and , 86
central pathways, 314-315 perineurium , 169, 171 nomenclature, 795, 797, 798
chemical anatomy corticostriatal, terminals, 813 output nuclei , entry into thalamus,
adrenergic transmission , 307-310 cutaneous, properties, 244-245 -
672 673
cholinergic transmission , 306-307 elongation , role of astrocytes, 208 placement in brain , 642
Dale's principle, 310-311 function, 132 putamen , 41 , 706, 774
coord i nation fusimotor, types, 247 characteristics, 41, 801
bodv temperature regulation , myelin sheath, 163, 764 frontal section of brain , 796
733-734 action potential, 168 illustration , 800
overview, 732-733 molecular organization, 167-168 muscarinic cholinergic receptor
definition , 293 nodes of Ranvier, 168 binding sites, 811
denervation sensitization , 311-314 Schmidt - Lantermann clefts, 168 sagittal section , 800
enteric sheath of Schwann, 168-169 sensorimotor circuits, 853
characteristics, 302-303 structural organization, 165-167 somatostatin immunoreactivity , 810
function, 262 noradrenergic, enteric system , 309 striatum
neurons, 302 regeneration, 188 y - aminobutyric acid concentrations
,
.
noradrenergic axon , 309 spinal nerve ventral root, 264 sir
986 Index
—
Basal ganglia continued Bowel, spinal cord transection effects. macrophages, (see Brain
amygdala and , relationship, 780 781 - 407 macrophages)
caudate nucleus, 798-799 Brachial plexus medial surface
characteristics, 112, 798 development, cervical enlargement , 327 dissection , 40
illustration , 799 formation, 276 limbic lobe, 36
intrinsic organization, 801-802 embryologic origins, 277 medulla , (see Medulla )
neuronal types, 802 , 802-804 injuries meninges, 3
putamen , 801 -
Duchenne Erb syndrome, 283 midbrain, (see Midbrain )
subthalamic region , (see Subthalamic Klumpke syndrome, 283 occipital lobe, components, 34
region ) structures, 275-277, 277 olfactory structures, 749
telencephalic subcortical nuclear Brain parietal lobe, parts, 32
masses, 795 adrenergic receptors, in primates, 878 peripheral nervous system,
transverse section , 774 anterior commissure components, 25
asymmetric, 643 characteristics, 41 rostral aspect, frontal view, 29
inferior thalamic peduncle fibers. development, 89 sagittal view , 4
644 frontal section, 37, 79b cerebrospinal fluid circulation, 12
optic chiasm level, 640 horizontal section, 35, 36 sensory receptors, function , 235
ventral striatopallidal complex structures, 759, 759-760 subdivisions, 25, 78-79
chemical anatomy , 845 arteries superior surface, 28
circuitry , sagittal view, 844 lateral surface, 101 temporal lobe, components, 34
connections, 844-845 medial surface, 101 topographic relationships, 27
functions, 845-846 barriers ventricular system, 78-79
ventral pallidum , 844
ventral striatum , 844-845
-
blood brain, 16-19, 20 , 208-209
blood -CSF, 16-17, 20, 20 , 21
Brain macrophages, resident, (see also
Microglia )
Basal nucleus of Meynert , involvement interrelationships, 20 neuronal shaping, 217- 218
in Alzheimer's disease, 881 blood flow measurements, 93 types, 217
Basal plate, neuroblasts, 73 blixxi supply Brain -derived neurotrophic factor.
Basement membrane, 18 carotid artery, internal, 98 193
Basilar artery , 116 vertebral artery , 98-99 Brain stem
branches, 113 capillaries amygdaloid nuclear group, 782
occlusion , 116-117 dopamine impermeability, 21 arteries, medial surface, 101
Basilar membrane, 476 general circulation capillaries and , corticobulbar pathways, 453
Basket cells, cerebellar cortex comparison, 17 corticoreticular fibers, 452
characteristics, 587 structure, 17 cranial nerves and , 44
neurotransmitter, 588 central nervous system, (see Central descending spinal tracts
transverse section, 586 nervous system ) .
fastigiospinal fibers 397
Bell's palsy , etiology, 498 circumventricular organs, midsagittal medial longitudinal fasciculus,
Belt projection , 906 view', 22 -
396 397
Bergmann cells, characteristics, 598 cranial nerves, 31 reticulospinal , 394 , 394-396
Biceps tendon reflex, spinal innervation, developmental stages, 77-79 rubrospinal, 389-390 . 391
273 dissection , relationship of internal .
tectospinal, 389, 389 391
-
Bilirubin , unconjugated , blood brain structures, 642 vestibulospinal, 391-392, 392, 394
barrier permeability, 19 edema, signs and symptoms, 19 -20 development , 87
Binasal hemianopsia , 690 fetus, lateral view, 89 fourth ventricle
Bitxhemical markers, astrocytes, 206 forebrain, (see Forebrain ) eminences, 432-433
Biocytin, neuronal morphology studies, frontal lobe periventricular gray matter, 511
138 convolutions, 31 structures, 48
Biogenic amines, ( see also Monoamines ) in monkey , 753 transverse section, 431
imaging methods, 160 frontal section vagal nuclei, 444
pineal gland , 638 gonadectomy, 736 lateral surface, 46
Bipolar neurons, characteristics, 144 striatum , 799 longitudinal axis, 774
Bitemporal hemianopsia, 690 structures, 796-797 lower portion , lesions, 556
Bladder , { see Urinary bladder ) thalamic nuclear groups, 796 medial forebrain bundle
Blinking agents, adrenergic, 310 functions, 25 afferent fibers, 716
Blood plasma gliomas, 210-211 efferent fibers, 719-720
cerebrospinal fluid , 15-16 gray matter removal, lateral view, 39 medial lemniscus, posterior white
-
filtration , 15 16
BIIXKI vessels, cerebral, 18
hypothalamus, 706
imaging techniques
column formation and course
369
.
-
Blood brain barrier computerized tomography, 55, medulla , (see Medulla )
components, 17 56 57 midbrain , ( see Midbrain )
dopamine impermeability 18 . magnetic resonance imaging, 55, 57, midsagittal view, 47 , 48
formation , role of astrocytes, 208- 209
in newborns, 18-19
-
58 61, 60
positron emitting tomography,
noradrenergic fibers, 596
parts, 25, 47
-
purpose, 16 17 -
60 64, 62 peripheral ganglia , 441
-
regions without, 18 19 -
x ray, 54 pons, ( see Pons )
schematic, 20 inferior surface, 10 , 38 posterior surface, 6, 45 , 423
-
Blood CSF barrier
permeability, 17
structures, 755
insula , characteristics, 34
epithalamus and pulvinar
placement, 634
purpose, 16, 20 intracellular fluid compartment , 19 raphe nuclei , 455
schematic, 20 ischemic necrosis, astrocytic reaction, reticular formation
Bodian method , neuronal morphology 209 hypothalamus, 717
studies, 134 lateral surface, 27 -
neurotransmitter presence, 556 557
Body movement, postcentral gyrus, 890. auditory' region, 907 projections to cerebellum, 610
89! gyri and sulci, 883 stimulation , 396
Ikxly temperature, regulation , 733-734 insula , 34 rixif plate, 47
Border/one infarction, 103 locus coeruleus, 457 sagittal section , 635, 722 - 723
Botulinum toxin , 257 ascending and descending structures, 45
Boutons, terminal, types, 156 noradrenergic axons, 514 subdivisions, 23
Index 987
transverse section , mesencephalon nigrostriatal fibers, 816 Purkinje, 82, 597

and diencephalon junction , 636
upper portion, lesions, 556
-
PHA L anterograde labeled elements,
816
characteristics, 588-589
dendrites, 146
venous drainage, 118 Causalgia , definition , 282 dendritic arborizations, 589
Broca 's aphasia , characteristics, 925 Cavenous sinus nucleus, 149, 152
Broca 's speech area , 32 characteristics, 120-121 transverse section , 586
Brodmann’s area , unilateral lesions of venous connections and related pyramidal, 866
auditory cortex, 908 structures, 122 characteristics, 865
Brown -Sequard syndrome, 377 Cavernous sinus, oblique coronal dendritic pattern , 146
spinal cord degenerative pattern , section, 100 excitatory role in neocortex, 873
408 Celiac plexus, characteristics, 300-301 hippocampal formation , 763
Bulbocavernous reflex , spinal
-
spinal cord hemisection , 407 408 Cell adhesion molecules, 72
Cells
length, 146
Renshaw
innervation, 273 anterior horn characteristics, 344
activation , 363 types, 345
Calamus scriptorius, 48 amyotrophic lateral sclerosis, 409 satellite
Calcar avis, 44 injury, 402 development, 265-266
Calcarine cortex, frontal section , 894 spinomedullary transition, 423 origins, 202
Calcitonin gene- related peptide, spinal structures, 42 perineuronal, 211 , 211
cord laminae, 358 syringomyelia , 411 Schwann , 75
Calmodulin , characteristics, 180 autonomic, characteristics, 304 behavior, after anatomic severance,
CAM, ( sec Cell adhesion molecules) basket 290
cAMP, ( see Cyclic adenosine characteristics, 587 cross section, 170
monophosphate) neurotransmitter, 588 nuclear division , 186
Canal, central, embryonic and adult transverse section, 586 role in degeneration and
human spinal cord , 329 Bergmann , characteristics, 598 regeneration of neurons, 185-186
Cannon 's law of denervation, precepts, capsule, autonomic ganglia , 305-306 sensory receptors, classifications, 236
313 choroid epithelium, phosphatase simple, functional characteristics, 898
Capillaries activity 22S stellate, 5%, 866
brain chromatolytic, lumbar spinal ganglia . characteristics, 585, 587, 865
dopamine impermeability, 21 267 striate cortex , in cat , 870
endothelial cells, 21 cuboidal epithelial , choroid plexus, transverse section , 586
general circulation capillaries and , 16, 226 tufted , 750
comparison , 17 dopaminergic nigral, examples, 192 Central arteries
structure, 17 endothelial, blood -brain barrier , 21 characteristics, 103
characteristics, 18 ependyma groups, 111
morphologic and enzymatic characteristics, 218 Central canal , embryonic and adult
properties, 18 cytoplasm structures, 223 -
human spinal cord , 329, 329 330
Capsule cells, autonomic ganglia , embryonic and adult human spinal Central cervical nucleus, cervical spinal
305-306 cord , 329 segments, in dog, 350
Carotid artery, internal features, 221 Central chromatolysis
branches, 98 origins, 202 in monkey neurons, 187
segments, 98 tanycytes, 223-224 principles, 186
Carotid sinus nerve, 450 fusiform, 866 Central nervous system
Carotid sinus reflex, 451 characteristics, 865 blood supply
Carpal tunnel syndrome, etiology , 282 ganglion basilar artery , 113
Catecholamines dorsal root , / 53, 349 carotid artery, internal , 98
cell groups retinal , 688-687, 895 , 8% central arteries, 109, 111
hypothalamus, principal locations, -
spinal, 75 76 cerebral arterial circle, 99, 102-103
725 sympathetic, 305, 306 cerebral arteries, 103-109
-
noradrenergic, 457 458 gitter , 217 cerebral veins, 122-127
definition , 160 glial choroidal arteries, 112
projections characteristics, 73 overview, 93-94
characteristics, 399 macroglia , 201 radicular arteries, 95-%
descending, 448 microglia , 201, 214-216 spinal arteries, 94-95
pontine cell group, 400 golgi epithelial spinal veins, 96-98
Cauda equina , 325 cerebral cortex, 600 vertebral artery, 98-99, 113
development , 74 characteristics, 598 brain , (see Brain )
sagittal view, 8 granule components, 25, 26
Caudal anesthesia , purpose, 7 cerebellar cortex, 592 determination and differentiation , 65
Caudal central nucleus, 543 characteristics, 750 development
Caudal medulla, ceil groups and tracts, illustration , 751 cerebellum , 81 -82
441 .
interfascicular, characteristics 211 congenital abnormalities, 90-91
Caudal midbrain Merkel, 241 early stages, 67
inferior colliculi, 527, 530-531 mitral, olfactory bulb, 750 glial cells, 73
parabigeminal area , 531 neural crest, spinal ganglia creation , 76 mesencephalon, 83
pretectal region, 540-541 neurilemma , origins, 202 metencephalon , 81 82-
tegmental and interpeduncular nuclei,
531-534
neuroepithelial, sensory nerve cells . neural crest , 67-69
neural tube, 69
241
trochlear nerve, 531 neuroglia , histogenesis, 71 neural tube formation , 65-67
Caudal pons olfactory bulb, 749 -
telencephalon, 85 86
dorsal, 469, 473 peri glomerular extracellular space, 200
ventral, 470 characteristics, 750 potassium concentration regulation ,
Caudate nucleus, 774 illustration, 751 206
- -
characteristics, 41 42, 798 799 progenitor intima pia , 12, 14
head , 800 differentiation into type-2 ionic channels, 214
muscarinic cholinergic receptor astrocytes, induction factors, 203 mvelination , oligodendrocytes,
binding sites, 811 oligodendrocyte development , 203 -
212 214
988 Index
—
Central nervous system continued
nerve fibers , size and appearance,
Cerebel loret icu la r fibers, characteristics,
435
Cerebral arterial circle
base of brain , 104
histologic staining, / 36 Cerebellum formation and branches, 100
neuroglia , (see Neuroglia ) afferent fibers, 6 / 8 structures, 99, 102-103
neurons cuneocerebellar, 380- 381 Cerebral arteries
axons distributed in , 143 olivocerebellar, 608-610 anterior
categories, 144 other types, 381 anomalies, 105-106
components. 131 pontocerebellar, 610-611 branches, 103- 106
intercellular and intracellular prccerebellar nuclei, 611 middle
communication, 132 reticulocerebellar, 610 branches, 107
nerve growth factor, 193 spinocerebellar, 378, 379 , 380, characteristics, 106- 107
regenerative processes, 189- 190 , 1 9 1 607-608 occlusions, 107
nodal regions, / 64 vestibulocerebellar, 606 607 posterior, 99
pi I regulation , 214 anterior lobe', lesions, 621 -622 characteristics, 107, 109
resident macrophages, 217 archicerebellum, 584 occlusion, 109
serotoninergic receptors, subtypes , arteries Cerebral blood flow
680 characteristics, 118- 119 blockage, 93
spinal cord, (seeSpinal cord ) types, 116 flow amounts, 93
subdivisions, 26 blood supply , arteries, 101 , 118-119 Cerebral cortex
vascular lesions, 93 comparator role, 617 association fibers, 918-919
Central sulci , functions , 923 cortical inhibition , 550 axodendritic synapse, 17 b
Central tegmental tract , 469 development, 81 , 81 -82 cell types, 144
ascending projections, bundle type's, efferent fibers, 6 / 8 chemical anatomy
555 cerebellovestibular projections, y -aminobu lyric acid , 873-873
impulse transport , 617 614-615 cholinergic innervation , 880-882
Centrobasal nucleus, 342. fastigial nucleus, 614 excitatory amino acids, 873
Centromedian nucleus superior cerebellar peduncle, 612-613 neuroactive peptides, 875-876
afferent fibers , 649 fissures, 53, 584 daustrum projections, 846
characteristics, 648, 649 function, 583, 617 columnar organization , 871 -872
input , 695 glomerular complex , 593, 594 595 consciousness, 355
Cen t romed la n - pa ra fascicula r nuclear horizontal section, 603 cortical areas, 882-883, 884 - 885 886
,
complex, 648 inferior surface, 53 cortical cells and fibers , 864-865,

liber projection, 650 information processing, 622 866
formation, 648 lateral zone, 617 cortical layers , 865-866
input , 694-695 learning and , relationship , 622 cortical neurons, interrelation ,
thalamic afferents to striatum, 814 lesions 869-871
transverse* sections, 6 74 archicerebellar, 621 corticopontocerebellar pathway, 474
Centromedian - paralascicular- neocerebellar, 620-621 cytoarchitectonic areas, 871 , 882
subparafascicular complex , output lobules, 584 development , 86-87
organization , 655 motor skills, 622-623 divisions, 763
Centrosomes, characteristics, 154 , 156 neocerebellum, 585 dyskinesia development, 852
Cerebellar cortex nuclei emotion , subjective aspects, 746- 747
cell types , / 44 corpus medullare, 600-601 fibers
circuit organization, 596-597 corticonuclear fibers, 604 afferent , 869
connections dentate , 601 -602, 602 association , 918-919
corticonuclear fibers, 604 emboliform, 602-603 commissural , 918
extracerebellar inputs, 604-605
nucleocortical fibers, 604
fastigial, 603-604
globose, 603
-
5 HT, 878
functions
cortical inputs interposed, 6 / 3 cerebral dominance, 919-920
climbing fibers , 593-595 neurotransmitters, 601 integrated cortical functions,
monoaminergic and cholinergic relay, 617 923-926
inputs, 595- 596 vestibular fibers, 489 interhemispheric transfer, 920-922
mossy fibers, 592-593 paleocerebellum, 584-585 prefrontal cortex , 926-928
interneurons, 82 paravermal zone, 617 sleep, 922-923
layers, 586 pathways interneurons, 872
granular, 589-590, 592 input and output , 607, 620 monoamines
molecular, 585, 587-588 neuronal types, 380 dopaminergic innervation , 878-880
purkinje cell , 588-589, 598 peduncles, (see Cerebellar peduncles ) noradrenergic innervation , 877-878
neuroglia cells, 599 posterior lobe, vermal parts, 53 serotoninergic innervation, 878
sagittal and transverse planes, cell posterior spinocerebellar tract , 378, motor areas
and fiber arrangements, 586 -587 379 eye fields, 915-916
sections, folium of rhesus monkey, posterior surface, 30 inputs, 915
585 posteroinferior surface, 52 primary, 909-913
somatotopic localization , 606 regional organization , 583-585 supplementary , 913-915
Cerebellar peduncles sagittal section, 54 neocortex , layers, 867-868
brain stem projection, 600 sensory inputs, 368 nonpyramidal corticofugal fibers
inferior somatotopic localization, 605-606 corticopontine, 916-917
characteristics, 606 structures, 52- 54, 583 corticoreticular, 916
fiber organization , 437 superior surface, 52 corticothalamic, 917
in medulla , 463 transverse section, 473 projection neurons, 867
structure’s, 437 veins, characteristics, 119 sensory areas
superior, 509 vermal zone, 616-617 auditory, 905-908 , 906 - 907
characteristics, 612-613 Weigert -stained section , 603 gustatory , 908
fiber organization, 510 Cerebral aneurysms, 93 primary , 886-887, 893
Cerebellomedullary cistern , 10 characteristics, 109 secondary, 887
Cerebellopontine angle, 462 limitations, 109 somesthetic
formation . 469 Cerebral angiography , cerebral vessel primary , 887-888, 888
lateral view , 472 imaging, 109 secondary, 892
Index 989
vestibular representation, ‘NW 9( N peptides, 23 Choroid point , 112

visual peripheral endocrine functions, 15 Choroidal arteries
primary, 892-893, 8%, 899 production sites, 14 anterior and posterior, 112
secondary, 904-905 subarachnoid space, 9 structures supplied by , 112
-
six layered cellular structure, 864 waste removal, 15 Choroidal fissure, 85
somatotopic localization, body parts . water content , 16 Chromatin , neuron nucleoproteins 151 .
890 Cerebrovascular accident, (see Stroke) Chromatolysis, 154
structure, 864 Cerebrum Chromatolytic cells, lumbar spinal
visual sensory areas, primary, visual aneurysms, 102-103, 109 ganglia, 267
deprivation, 902-904 arterial circle, (see Cerebral arterial Chromophilic substances, neurons, 152
Cerebral dominance, differences in circle ) Ciliary neurotrophic factor, 193
-
hemispheric functions, 919 920 arteries, (see Cerebral arteries ) progenitor cell differentiation , 203
Cerebral hemispheres hemispheres, (see Cerebral Cingulate cortex , anterior, stimulation ,
anterior commissure hemispheres ) somatic effects, 747
characteristics, 41 lobes, 28 Cingulum , 33
development, 89 veins, (see Cerebral veins ) characteristics, 41 , 918
.
frontal section , 37 796 Cervical enlargement illustration, 40
horizontal section , 35 characteristics, 327 Circadian rhythms, 639
structures, 759.759-760 section through, 187 Circle of Willis, ( see Cerebral arterial
central branches Cerv ical flexure, 74 circle )
central arteries, 109- 112 Cervical ganglia , related fibers . 500 CircumferentiaI arteries
.
choroidal arteries 112 Cervical plexus, structures, 275 blood supply to midbrain , 114 , 118
cortical branches, anterior cerebral Cervical segments obstruction , 117
artery. 103-106 cell groups , 346 C i rcu m ven t ricu la r orga ns
crus cerebri, horizontal section , 35 nuclei components, 21
.
development 87, 88 central, 350 median eminence, 23
inferior surface, parts, 38 lateral, 377 purpose, 23
internal structures and internal spinal cord vascular casts, 729
capsule, horizontal section , 35 characteristics, 330, 331 333, 334 / ona interna and externa, 720
lateral aspects, 40 crush injury , 372 373 in nonmammalian vertebrates, 23
lateral surface, 28, 31 Cervical spinal nerves, cutaneous schematic, 22
dissection , 39
—.
frontal lobe, 31 32
occipital lobe , 34
parietal lobe, 32 34
innervation , 274
CltAT, (sec Choline acetyltransferase )
Chemical messengers, putative, criteria
tor neurotransmitter, 159
serotoninergic innervation , 711
Cisterns, subarachnoid , 10, II
Claustrum, 41
cerebral cortex projections, 846
primary somesthetic area , 888.891 Chemical synapses, advantages, 175 characteristics, 798, 846
temporal lobe, 34 Chemical transmission, neurons, Claw hand , definition, 282
lateral ventricles receptors, 177-178, 180 Climbing libers
anterior horn , 42 Chemoeleetric transduction , sensory characteristics, 593-595
inferior horn , 42 receptors, 237 Purkinje cells, 5^7
lateral and superior views, 43 t hemoreceptors, function , 238 Clonus, definition, 405
posterior horn , 44 C holecystokinin, spinal cord laminae . CMTt . ( stv Centromedian -
structures, 42-45 33* parafascicular nuclear complex )
left, medial surface dissection, 40 Choline acetyltransferase, 295 .
CM - IM -sl 'f ( sec Centromedian -
longitudinal fissure, 25 immunoreactive fibers -
pa ra fascicula r subpa rafascicula r
medial surface, 29 medulla , 460 complex )
limbic lobe, 36 thalamus, 674 CNTF, ( see Ciliary neurotrophic factor )
structures, 34-36 Cholinergic fibers, overactivity, 311 Coccygeal ligament, characteristics, 7
posterior view, Ml Cholinergic neurons, (sec also Cochlea , 907
superior surface, 33
white matter
Acetylcholine )
genomic regulatory mechanisms, 180 in monkey 477 . —
characteristics, 474 475
association fibers, 39-41 globus pallidus, 829 radial section , 476 , 477
astrocytes, distribution and identification, 458 structures, 477
appearance, 201 medial habenular nucleus, 637-638 Cochlear duct , 476
commissural fibers, 41 substantia innominata , 715 Cochlear nerve
internal arrangement , 331 Chorea characteristics, 461-462
projection fibers, 38 characteristics, 849 destruction , 484
spinal cord, 3,30 I luntington 's, biochemical changes . nuclei, 475-476, 478
Cerebral veins 851 Cogwheel phenomenon , definition , 849
deep, 125-127 pathologic changes, 850-851 Colchicine, purpose, 147
angiographic appearance, 125 / 26 types, 849 Collateral eminence. 42
superficial and , connections Choroid epithelium Collateral fibers, characteristics, 435
between , 126 , 127 cells, phosphatase activity, 225 Collateral trigone, 42
drainage patterns, 123 illustration, 224 Colliculi
illustration , 123 Choroid plexus facialis, 498
.
superficial 122-123, / 24 cerebrospinal fluid , 14, 228 inferior, 649
deep and , connections between , characteristics, 16 superior, 649
126.127 development , frontal section , 84 Coma , sleep and , comparison, 556
Cerebral vesicle, development , 87 formation, 44, 223, 224 Combined system disease
Cerebrospinal fluid frontal section, 84 -
blood plasma filtration, 1 ^-16 function, 224 spinal degenerative pattern , 410
buovancy, 15 illustration, 223 Commissural fibers, (scco/sn Anterior
characteristics, 14 purpose, 17 commissure; Posterior commissure)
choroid plexus, 16 rabbit cerebral cortex , 9|g
molecular substance barrier, 228 dual secretory-absorptive role, 225 corpus callosum , 33
circulation , in brain and spinal cord , illustration, 226 characteristics, 89
12 schematic, 22 frontal section , 43
composition and pressure, 14 villi, 22 .
function 35, 920-921
990 Index
—
CommissuraI fibers coniinued
genus, 774
Corpuscle of Meissner, ( see Meissner's
corpuscles)
infratentorial, 440
medulla , 47-48, 437
lesions, 921 Corpuscles of Golgi - Mazzoni midsagittal view , 439
morphology, 921 -922 characteristics, 247 midbrain, 49
parts, 41 illustration, from finger tip, 246 peripheral ganglia , 441
structures, 34 Cortical inputs pons, 49
structures, 41 climbing fibers, 593-595 root fiber origins, 532
Commissural nucleus, 443 monoaminergic and cholinergic, schematic, 31
Commissures 595-5% Cranial outflow, preganglionic fibers, 2%
anterior mossy fibers, 592-593 Cranial region, ganglia, 301
characteristics, 41 Cortical surface, meninges and , Cranium , base, 121
development, 89 relationship, 13 Cremasteric superficial reflex, spinal
frontal section, 37, 796 Cortical zone, medial, 604 innervation , 273
gray, 328 Corticobulbar fibers Cribiform plate, fractures, effect on
horizontal section, 35, 36 characteristics, 451, 474 smell, 758
hypothalamus, 712, 723 pathways, 453 Crista ampullaris, 484
structures, 759, 759-760 unilateral lesions, 454 Crus cerebri, 33, 45, 47, 49, 527
fomical, 767 spinal trigeminal nucleus, 502 projections, 49-50
posterior Corticofugal fibers structures, 572
gray, 328 -
accommodation convergence CSF, ( see Cerebrospinal fluid )
lesions. 541-542 reaction , 548 CT, ( see Computerized tomography )
structure's, 541-542 inhibitory effects, 452 Cuboidal epithelial cells, choroid plexus,
transverse section, 540 , 545 internal capsule, 685 16, 226
Common peroneal nerve nonpyramidal Cuneate nucleus, accessory , 371
muscle innervation , 287 corticopontine fibers, 916-917 anatomic and functional features, 428
section ot , 287 corticoreticular fibers, 916 Cuneate tubercle, 46
Communicating arteries, anterior and corticothalamic fibers, 917 Cuneocerebellar fibers, characteristics,
posterior, 99 origins, 909 428, 606
aneurysm, 110 Corticohypothalamic fibers, Cuneocerebellar tract , schematic, 379
Communicating hydrocephalus, characteristics, 718 Cuneus, 29
definition , 15 Corticomedial nuclear group, Cupula , 484
Computerized tomography characteristics, 773 Cutaneous axons, properties, 244 - 245
brain imaging, 55 Corticonigral fibers, characteristics, 563 Cutaneous fields, innervation
operation principles, 55 .
Corticonuclear fibers, characteristics 604 peripheral nerve, 271
planes, 56 Cortico-olivary fibers, origins, 433 segmental, 270
schematic and illustration , 56-57 Corticopontine fibers Cutaneous nerves
tomographic planes, 56 cerebellum , 618 antebrachial and brachial branches,
Conductance, definition, 132 -
characteristics, 474, 916 917 283
Conduction aphasia , characteristics, 925 Corticoreticular fibers femoral
Conduction deafness, 484 brain stem , 452 lateral, 285-286
Conduction velocity, 171 reticular formation, 555 posterior, 287
Cones, characteristics, 685 characteristics, 435, 916 Cutaneous receptive fields, 235
Confluens of sinuses, structures, 120 Corticorubral fibers, precentral and Cutaneous receptors
Congenital dermal sinus, 91 premotor cortex, 550 mechanical stimuli sensitivity,
Conjugate horizontal gaze Corticospinal decussation classification criteria , 242-243
characteristics, 493 characteristics, 422 peritrichal endings, 241
lesions that affect , 494
Connective tissue sheaths
-
illustration, 424 425
Corticospinal fibers, characteristics, 474
Cutaneous sensibility
effect of dorsal root sectioning, 406
characteristics, 267-268 Corticospinal neurons, characteristics, elemental qualities, 236
peripheral nerve fibers 185 Cutaneous somatotopic representation,
endoneurium, 169 Corticospinal system body surface, 658
epineurium , 171 decussation, 383-384, 385 Cyclic adenosine monophosphate,
perineurium , 169, 171 lateral and anterior sections, 384, 384 , synaptic transmission, 179
Consciousness, cerebral cortex 386 Cytokeratins, neurofilaments, 148
influences, 555 structures, 383
Conus medullaris, 74, 325 Corticospinal tract Dale's principle, precepts, 310
characteristics, 327 effect of lesions, 388 Decerebrate rigidity, characteristics,
sagittal view , 8 primary motor area , 910 493-494
syndrome, 407 Corticostriatal axons, terminals, 813 Decussations
Copied deoxyribonucleic acid , in situ Corticostriatal fibers medial lemniscus, 427 428-
hybridization and , 141 -
characteristics, 811 814 supraoptic, 722-723
Corneal reflex, secondary trigeminal origins, 814 Deglutition , (sec Swallowing )
fibers, 508 Corticotectal fibers, characteristics, 536 -
Dejerine Roussy syndrome, 692
Cornu ammonis, 765 Corticothalamic fibers, 633 Dementia, characteristics, 786
Corona radiata , 33 , 40 characteristics, 917-918 Dendrites
characteristics, 683 excitatory action , methods to mediate, action potential, 133-134
illustration, 689 679 expansion illustration , 155
Corpus callosum, 33 Cotranslational modification , proteins . Purkinje cells, 14
characteristics, 89 159 Dendritic zone, definition , 132
frontal section , 43 Cranial fossae Denervation , Cannon 's law, 313
function, 35, 920-921 anterior, 3 Dentate gyrus
genus, 774 middle, 3 characteristics, 763
lesions, 921 posterior, 3 illustration , 755, 767 , 764
morphology, 921-922 Cranial nerves intrinsic connections, 765-766
parts, 41 emergence and entrance, in brain three layers, 765
structures, 34 stem, 44 Dentate nucleus
Corpus medullare, characteristics, frontal view, 29 afferent fibers, 605
-
600 601 inferior view, 10 characteristics, 601-602
Index 991
dissections, 602 Dopaminergic neurons, hypothalamus, Dysmetrin, definition, 620

efferent fibers, 609.612, 618 73 / Dystonia, 568
Denticulate ligaments, characteristics, 9 Dopaminergic nigral cells, examples of ,
2-Deoxyglucose IV EAA, ( see Excitatory amino acids)
neuronal metabolism , 142 Dorsal accessory olivary nucleus, 433 Edinger - Westphal nucleus, 543
PET scans, 61 Dorsal cochlear nucleus, cell divisions, EEC, ( see Electroencephalogram )
Dermatomes 476 Effectors
function , 268 Dorsal longitudinal fasciculus, 532 somatic, 255-257
mapping, 270 characteristics, 717 motor end plates, 255, 256, 257, 295
peripheral nerve innervation Dorsal motor nucleus, vagus nerve, 446 visceral, 259
anterior, 271 Dorsal nucleus of Clarke, 334 Efferent fibers
posterior, 272 anatomic and functional features, 428 central nucleus of inferior colliculus .
Descending spinal tracts, brain stem -
characteristics, 349 350 531
fastigiospinal fibers, 397 dorsal root fiber termination, 352 cerebellum, 618
medial longitudinal fasciculus, Dorsal rami superior cerebellar peduncle,
-
3% 397
reticulospinal, 394 , 394-396
divisions, 267
muscle innervation , 274
612 613
cochlear, 482-484
rubrospinal, 389 390, 391 Dorsal raphe nuclei in cat, 483
tectospinal, .389, 389, 391 circumventricular organ innervation . dentate nucleus, 609
vestibulospinal, 391 392, 392 , 394 711 descending rubral, 550
Determination, central nervous system , -
serotonin containing neurons, 517 external pallidal segment, 838
65 Dorsal roots facial nerve, 4%
Diabetes insipidus, causes, 734 ganglion cells fastigial nucleus, 614, 615
Diaphragm, movements, spinal cytoplasm, 153 globus pallidus, 836
innervation , 273
Diaphragma sellae, characteristics, 3
major branches and collaterals
349
. lenticular fasciculus, 833, 833
pallidohabenular fibers, 8.34
Diencephalon nerve fibers, 268 pallidonigral fibers, 834, 836
amino acid transport, 837 spinal cord pallidotegmental fibers, 836 837
development , 83-85 arrangement , 348 pallidothalamic fibers, 834
epithalamus, 50 degenerated image, 350 subthalamic fasciculus, 837-838
frontal section, 84 lesions, 403, 405-406 -
thalamic fasciculus, 833 834
hypothalamus, (see Hypothalamus) termination sites, 352 hypothalamus
lateral view, 46 spinal nerve, 327 descending projections, 721-722
midsagittal view, 47.48 characteristics, 262-263 hvpothalamocortical fibers, 722
pathways, 554-555 schematic, 326 medial forebrain bundle, 719-720,
limbic, 724, 745 Dorsal tegmental decussation, 389 724
posterior surface, 45 , 51 Dorsal tegmental nucleus, supraoptic decussations, 722-723
regional organization, 633 characteristics, 531-532 locus coeruleus, 513
-
structures, 50 51 Dorsal thalamus, characteristics, 633 mammillary , 720-721
subthalamus, structures, 51 52- Duchenne- Erb syndrome, medullary reticular formation,
thalamus, (see Thalamus ) characteristics, 283 435 436
transverse section, 637 Dura mater parietal cortex, 917
habenular nuclei and mammillary arteries, 119-120 pars com pacta and pars reticulata ,
bodies, 646 base view, 5 comparison , 817
inferior thalamic peduncle fibers, blood supply, 6 striatum, striatopallidal, 822, 823,
I> 44
optic chiasm level, 640
components, 3
innermost layer
-
825 826
substantia nigra
thalamic and hypothalamic nuclei , spinal dura , 6 nigrostriatal fibers, 564- 566
646 subdural space, 6 nigrotectal and nigrotegmental
zones, 84 posterior surface, 4 fibers, 567-568
Differentiation , central nervous system . venous sinuses, 120-122 nigrothalamic fibers, 566-567
65 Dural sinus subthalamic nucleus, 842-843
Diplopia extracranial veins and , relationship, superior colliculus, 538-539
definition , 49*J 117, 121-122 ventral nuclei
trochlear nerve lesion , 531 venous anterior, 654
Directly -gated transmission , 178 characteristics, 120 lateral , 656-657
Disconnection syndrome, types, 921 sagittal view, 121 ventral striatum, 845
Discriminative sensibility, 377 Dvnorphin immunoreactivity, 358 vestibular, labyrinth hair cells and ,
Disinhibition, basal ganglia functions, Dysdiadochokinesis, definition, 620 relationship, 491
846-848 Dyskinesias Efferent neurons, visceral
l 3ominance cells, ocular, striate cortex, athetosis, 848-849 intermedinlateral nucleus, .347
900-902 ballism , 849 sacral autonomic nuclei, 347
Dopamine chorea, 849 Efferent vestibular system
arcuate nucleus, 725 choreiform , drug therapy, 851 characteristics, 491 492
basal ganglia neural mechanisms, 849-851 labyrinth hair cells and , relationship,
effect on direct and indirect Parkinson's disease 491
pathways, 852-853 causes, 18 Electrical synapse, definition, 175
innervation , 819 characteristics, 850 Electroencephalogram, brain stem
blood - brain barrier impermeability , experimental animal models, reticular formation , procedures,
18 852-853 554
cerebral cortex innervation , 878-880 initial symptoms, 849 Electron microscopy , neuronal cytology .
effect on striatal neurons, 817 motor disturbances, 853-854 137
PET visualization, 64 neural mechanisms, 850 Emboliform nucleus, characteristics,
receptor subtypes, 565 neuropathologic features, 568 602-603
synthesis, in nigrostriatal fibers, treatments, 569 Embryonic disk , schematic, 66
815 sterotaxic surgery effects, 314-315 Embryonic neural crest, spinal ganglia
visualiza tion , i m munocytochemica I subthalamic, animal models, 851-852 development , 265
methods, 140 tremor, 848 Emissaries, dural sinus, 121 - 122
992 Index
Emotion Extrafusal muscle fibers Foramen of Magendie, 48

amygdala influences, 786 Golgi tendon organ and muscle cerebrospinal fluid transportation, 14
subjective aspects, role of cerebral spindle, anatomic and functional Foramina of Luschka , 48
cortex , 746-747 relationships, 3b I cerebrospinal fluid transportation , 14
Emotional behavior, control, innervation by spinal nerve ventral Forearm
hypothalamus, 738 nx »ts, 263 innervation, 281
En grappe endings, 257 Extraocular muscles peripheral nerves, 276
En plaque endings, 257 localization in oculomotor nuclear Forebrain, ( see also Brain )
Encapsulated endings complex, 543 basal, ( see Basal forebrain )
end bulbs, characteristics, 243 origin of root fibers to, 532 frontal sections, enkephalin -
Meissner's corpuscles Eye immunoreactive axons terminals
characteristics, 243 autonomic innervation , 316-317 and cell bodies, 806
illustration, 243 movement serotoninergic innervation, 533
pacinian corpuscles, characteristics, horizontal and vertical, 500 Forel's field H, (see Prerubral field )
243, 246-247 secondary vestibular fibers, 492 Formalin fixation , neuronal
Encephalopathy, hepatic, protoplasmic Eye fields, cerebral cortex, 915-916 morphology, 134
astrocyte reaction, 209 Fornix, b47
End bulbs Facial colliculus, 46 columns, frontal section of brain , 796
characteristics, 243 Facial nerve fiber projections
Krause, from conjunctiva , 246 functional components, 495 divisions, 717
End feet , 204
Endocytosis, 177
-
lesions, 497 198
motor nuclei, 495
efferent , 766
illustration , 755, 759
Endoneurium , 268 -
afferent fiber source, 496 497 pillar of, 722
characteristics, 169 muscle innervations, 495 Fossae
-
Endothelial cells, blood brain barrier, 21 overview, 495 dural blood supply, 120
Enkephalin fibers, 459 parasympathetic fibers, group interpeduncular, 49
lamina 1 and II, 357 division , 497 posterior, 5
Enteric system Facial palsies, central types, 498 rhomboid, 48
function , 262 Falx cerebelli, 52 Fourth ventricle
neurons, 302 characteristics, 3 choroid plexus, 226
noradrenergic axon , 309 sagittal view, 4 -
eminences, 432 433
preganglionic regulation, 303 Falx cerebri periventricular gray matter, 511
structure, 302 characteristics, 3 structures, 48
Entorhinal area sagittal view, 4 transverse section of medulla
characteristics, 768 Familial dysautonomia, characteristics, through , 431
illustration, 7b4 315 vagal nuclei, 444
Ependyma Fasciculi Fovea centralis, definition, 685
cells amyotrophic lateral sclerosis, 409 Fractured somatotopy, 605
characteristics, 218 cuneatus, 330, 368 Free nerve endings
cytoplasm structures, 223 definition, 289 afferent , 240
embryonic and adult human spinal dorsal longitudinal, characteristics, 717 characteristics, 239-240
cord , 329 .
gracilis 330, 368 in skin and hair follicle, 239
features, 221
origins, 202
interfascicularis, 371
lower motor neurons, 404
-
Freeze etch apparatus, 137
FRH , ( S<Y Follicle-stimulating- releasing
illustration, 219-220 proprii , 401 factor )
scanning electron micrographs, 222 retroflexus, 634 Frontal cortex, amygdala and ,
Epidural space, 7 solitarus, 443-444 connections, 786
Epidural venogram, 97 Fast excitatory synaptic potential, Frontal lobe
Epineurium presynaptic fiber stimulation, 307 convolutions, 31
characteristics, 169, 171 Fastigial nucleus functional divisions, 926-927
peripheral nerve fibers, 267 afferent fibers, 605 Frontal lobotomy
Epipial layer , characteristics, 8 characteristics, 603-604 function, 927
Epithalamus, 45 efferent fibers, 614, 615 intellectual damage, 927
characteristics, 633 Fastigiospinal fibers, characteristics, 397 origins, 927
habenula , characteristics, 635 Fastigium , 48 Funiculi
illustration , 634 Femoral nerve spinal cord
pineal gland injury, 285 posterior, 425
characteristics, 638-639 muscle innervation , 285 white matter, 328
development , 83 Fibrillary gliosis, definition , 209 spinospinal , 401
secretions, 638-639 Fibrillation , definition , 289, 404 Fusiform cells, 866
structure, 638 Fibroblast growth factor, 193 characteristics, 865
structures, 50 Filum terminate, 325 Fusiform layer, dorsal cochlear nucleus .
EPSP, (MV Fast excitatory synaptic characteristics, 327 476
potential) Fimbria , 42
Equilibrium, governing mechanisms, Fissures, cerebellum, 53, 584 , 584 GABA, (see •y- Aminobutyric acid )
493 FITC, ( see Fluorescein isothiocyanate ) Ganglia
Estradiol, effect on sexual behavior, 737 Flexor muscle spasms, spinal cord autonomic, 295
Excitatory amino acids recovery, 406-407 structure, 304-306
cerebral cortex, 873 Flexor reflex afferents, 609 basal
thalamus, 679 Flocculonodular lobe, 82 associative circuits, 853
Exteroceptive impulses, trigeminal Fluorescein isothiocyanate, antibody circuitry schematic, 854
nerve, 500 visualization, 140 disinhibition of functions, 846-848
Exteroceptors, function, 237 Folium , dorsal surface, 598 dopaminergic innervation , 819
Extracellular space Follicle-stimulating - releasing factor, horizontal section , 683 , 801
central nervous system , 200 hypothalamus, 732 nomenclature, 795, 798
potassium concentration , 206 Food intake, control, hypothalamus, optic chiasm level, 640
Extracranial veins, dural sinuses and , -
737 738 output nuclei, entry into thalamus,
relationship, / 17, 121-122 Foramen cecum posterior, 463 672-673
Index 993
placement in brain, 642 lesions, in baboon, 666 spinal cord , 355

sensorimotor circuits, #53 parvicellular layers, 664 subthalamic nucleus, 84( 1
820
-
serotonin immunoreactive fibers . retinae, representation of visual
field , 667
Glutamic acid decarboxylase expression,
in reticular nucleus, 678
somatostatin immunoreactivity, 810 retinal ganglion cell terminations . Glutamine synthetase, astrocyte marker,
thalamic peduncle fibers, inferior, 668 206
644 retinal surface, topographic Gluteal nerves, muscle innervation, 287
.
transverse section , 640 643, 644 , representation , 664-665 Gluteal superficial reflex , spinal
774 right visual hemifield , 669 innervation , 273
cervical, 299 serotonin - immu noreactive fibers , Glycine, inhibitory transmitter in spinal
related fibers, 300 682 cord , 356
ciliary, 301 medial, 662-663 Golgi apparatus, characteristics, 156
dorsal root, major branches and
collaterals, 349
seroton in -i mmu noreacti ve fibers
6#2
. Golgi epithelial cells
cerebral cortex , 600
geniculate, lesions, 498 thalamus, medial nucleus, 662-663 characteristics, 598
inferior, nerve X , 447 Geniculocalarine fibers, striate cortex , Golgi technique
otic, 301 894 advantages, 137
peripheral, brain stem and cranial Geniculocalcarine tract , characteristics, neuronal morphology studies, 134, 137
nerves, 447 687-690 Golgi tendon organ
prevertebral, 296, 290 Genital corpuscles, 243 afferent fibers , 252, 363
pterygopalatine, 301 Germinal / one anatomic and functional relationships,
spinal neural tube histogenesis, 69 to extrafusal muscle fibers, 367
related nerves, 300-301
schematic, 326
stellate, 299
.oscillatory movements in, 70
Cerstmann 's syndrome
characteristics, 926
axonal branches and collagen
bundles, relationship, 253
capsule, 251
submandibular, 301 definition , 920 illustration, 252
sympathetic GFAP, (see Glial fibrillary acidic protein ) Gonadotropic hormones, regulation, 735
amine production, 67-68 Gitter cells Gracilis tubercle, 46
-
preganglionic fibers, 299 300 characteristics, 217 Grafting experiments, peripheral nerve
terminal, 296 formation stages, 276, 217 fibers, 192-193
trigeminal , divisions, 501 Glial acidic fibrillary protein , Granule cells
vestibular, 475 i m mu noreacti vity, astrocy tic cerebellar cortex, 592
characteristics, 485 processes, 227 characteristics, 730
labyrinth innervation , 485 Glial cells illustration , 757
Ganglion cells characteristics, 73 Gray horns, spinal cord
retinal macroglia, (sec Macroglia ) anterior, 328
characteristics, 686-687 microglia, (see Microglia ) activation , 363
receptive fields, #95, 8% Glial fibrillary acidic protein, cell groups in cervical spinal
spinal, processes, 75-76 intermediate filament, 206 segment , 346
Gap junction channels, definition , 175 Glial membrane, 223 motor neuron groupings, 345-346
Gate control theory of pain , principles
360
. Gliomas, astrocytes and , 210 motor nuclei, in cervical segment ,
Gliosomes, 204 344
Gating Globose nucleus, characteristics, 603 posterior, 328, .347-349
definition , 178 Globus pallidus, 706 cutaneous input , 336
role of thalamus, 693 afferent fibers Gray matter
Gaze paralysis, lateral, 494 striatopallidal, 831 astroevtes, distribution and
etiology , 500 subt hala mopa11 id a 1, 831-832 appearance, 201
Gene expression, role in neuronal ventral anterior thalamic nuclei, cytoarchitectural lamination
protein synthesis, 157 652-653 lamina 1, 339
General efferent fibers, 80 characteristics, 41 lamina II , 340-341
General somatic afferent fibers, 80, 437, development , 829, 831 lamina III , 341
458-440.450 divisions, in primates, 795 lamina IV , 341-342
intermediate nerve, 497 efferent libers, #36 .
lamina IX 343-344
General somatic efferent fibers, 80, 437, -
ansa lenticularis, 832 833 lamina V , 342
-
458 140
General somatic sense,
pallidonigral , 834, 836
pallidotegmental , 836-837
lamina VI , 342
lamina VII, 342-343
glossopharyngeal nerve, 450 pallidothalamic, 834 lamina VIII , 343
General visceral afferent fibers, 80, 437, subthalamic fasciculus, 837-838 internal arrangement , 337
-
458 140.450
General visceral efferent fibers, 437,
thalamic fasciculus, 833-834
immunohistochemical features, #29
spinal cord , characteristics, 329, 330
Gray ramus communicans, 3tK )
-
458 140.450
facial nerve, 495
intrinsic organization, 831
output organization, #36
Great cerebral vein ( Galen ), 122
intermediate nerve, 497 topography, laminae, 828-829 Growth cones, 71
Geniculate bodies Glomeruli direction of , influences, 72
lateral, 50 complex formation , 593, 594 595 Growth hormones
secondary visual area , 905 sympathetic ganglion cell control, role of hypothalamus, 737
medial, 50 dendrites, 306 hypothalamic releasing factors,
auditory area , 905-906 lateral geniculate nucleus, 669 729-730
Geniculate ganglia , lesions, effect on Glossopharyngeal nerve Growth promoting factors, neurons, 193
taste, 498 characteristics, 449-451 Guamanian syndrome, characteristics,
Geniculate nuclei effect on swallowing, 451 -
62 63
lateral functional components, 450 Gustatory areas, cerebral cortex , 886
cellular lamination , 664 lesions, 451 characteristics, 908
components, 663-664 Glutamate Gustatory nucleus, 444
-
cross section, 665
glomeruli , neuronal arrangements,
cerebral cortex, 973
hippocampal formation, 768
Gvri
angular , 34
670 neurotransmitter, 161 brain, 27-28
laminae. 669 regulation , astrocytes, 207 lateral view , 885
994 Index
—
Gyri continued
definition , 28
fiber projection , hypothalamus,
716-717
Hypothalamus
afferent connections
frontal lobe, 29, 31
hippocampal, 36, 761
formation, ( see Hippocampal
formation ) 716-717
-
h i ppoca m po hy pot ha la mic fibers,
medial forebrain bundle, 716, 719

limbic lobe, 36
occipital lobe, 34
orbital, 29
.
fundamental layers, 763
C ABA receptors, 769
illustration, 755
schematic, 727
amygdala and , relationship, 781-782
parahippocampal, transverse section. localized lesions, 770 anterior commissure, 723
760 memory functions, 770-771 anterior region
postcentral morphologic plasticity, 773 preoptic, 710-711
activation, by cutaneous stimuli Histochemical techniques, supraoptic, 711-713
and joint movement , 888 neurotransmitters, 140-141 arcuate nucleus, somatosatin - 14
characteristics, 887 Histologic techniques, neuronal localization, 727
neuronal activation, 889-890 morphology studies, 134-137 autonomic nervous system regulation,
somatotopic localization , body examples, 135 314
parts, 890 Homeostasis blood supply , 113
stimulation, effects, 891 definition , 706 dopaminergic neurons, 731
thalamic projections, 887-888 enteric system , 302 efferent connections
ventral posterior nucleus role of neuroglia , 199-200 descending projections, 721-722
projection , 659 Homonymous hemianopsia, 690 dorsal longitudinal fasciculus, 720
temporal lobe, 29, 34 Homonyous quadrantanopia , definition , hypothalamocortical fibers, 722
Gyrus rectus, 32 8% main categories, 728
Homotypical cortex mammillary fibers, 720-721
I labenula , characteristics, 635 characteristics, 886 medial forebrain bundle, 719-720,
Habenular nuclei definition, 882 724
characteristics, 634 Hormone-releasing factors, pathways, 726
transverse section, 646 cerebrospinal fluid transportation . -
supraoptic decussations, 722 723
I lair follicles 15 external structures, 707
characteristics, 241 1 lormones fiber connections, 727
nerves and nerve endings, 239 cerebrospinal regulation , 15 functions
l lead gonadotropic, regulation , 711, 735 -
anterior pituitary control, 734 735
cutaneous fields, 274 -
hypothalamic releasing, 162 body temperature regulation ,
movements, spinal innervation , 273 neurohypophyseal, ( sec 733
I tearing, unilateral loss, 484 Neurohypophyseal hormones) control of growth, 737
Hemianopsia , types, 690-691 pituitary , 730 emotional behavior, 738
I temiparesis, contralateral, causes, Horner's syndrome, 316 food intake, 737-738
116-117 causes, 548 -
reproduction control, 735 737
Hemiplegia characteristics, 283 water balance maintenance, 734
alternating definition , 406 hormone release, 735
inferior , 114, 442 Horseradish peroxidase method hypophysial portal system , structures,
middle , 499 principles, 138 728-729
superior, 118, 548-549 retrograde transport studies, 182 hypophysiotrophic agents. 729
definition , 389 HRP, ( see Horseradish peroxidase types, 729-730, 732
motor function recovery , 405 method ) input to mesencephalon , pathways .
Hepatic encephalopathy, protoplasmic Huntington's disease 314
astrocyte reaction, 209 characteristics, 209-210 lateral surface, 710
I ierpes zoster, dermatome mapping . role of astrocytes, 209-210 lesions, 734
270 Hydrocephalus lesions, effect on thalamus, 638
Herring bodies, 161 causes, 15 mammillary region , nuclei, 715
I lindbrain , (see Brain stem ) communicating, 15 medial and periventricular areas,
I lip, segmental innervation, 280 Hyperacusis, definition, 498 710
Hippocampal formation , 42, 85 I typerkinetic disorders median eminences, 706-707
anatomic circuitry, 766 characteristics, 848 mediolateral divisions, 709-710
chemical anatomy , 768-769 pathophysiologic mechanisms, neurosecretory, 162
dentate gyrus 852 nuclei
characteristics, 763 1 iyperphagia , definition , 737 illustration , 707
illustration, 755, 767 , 764 Hyperpolarizing potential, 133 paraventricular, 772, 776
intrinsic connections, 765-766 Hypertonicity, 404 sexual dimorphism, 737
three layers, 765 Hypoglossal eminence, 46, 432 supraoptic, 772
extrinsic connections, 766-768 Hypoglossal nerve posterior
functional considerations, 769-773 characteristics, 438, 440, 442 -
functions, 733 734
illustration, 759, 764 lesions, 442 lesions, 734
layers, 76 perihypoglossal nuclei, 442 releasing factors, 730
neuronal activity , 768 Hypokinetic disorders role in homeostasis, 706
Papez's theory , 773 characteristics, 848 rostrocaudal regions, 51
pyramidal layer, 763
sagittal section , 767
pathophysiologic mechanisms
852
. sagittal section, 709
sleep and , relationship, 738
subicular cortex Hypophysectoniy, 732 structures, 51
efferent fibers, 767 Hypophysial portal system supraopticohypophysial tract ,
hippocampus and , 763-765 artery supply , 728 characteristics, 723-724
thalamic projections, 768 schematic, 728 sympathetic responses, 733
topographic organization, 760-763 I lypophvsiotrophic agents, transverse section , 774
transverse section, 747, 760 hypothalamus, types, 729-730, 732 infundibular region, 708
Hippocampus Hypophysis, 29 mammillary region , 708
amygdala and , relationship, 781 Hyporeflexia , definition , 288 supraoptic region, 708
basket cells, 764 Hypothalamic sulcus, 84 tuberal region
bilateral damage, 770 H ypothalamocorticaI fibers, overview, 719
CA - 1 sector pyramidal neurons, 772 characteristics, 722 structures, 713
Index 995
tuberohypophysial tract, Inhibitory factors, nerve regeneration , Ischemia , definition, 93

characteristics, 724-725, 728
ventromedial nucleus, lesions, effect
193
Inhibitor)' transmitters, spinal cord
Ischemic necrosis, astrocytic reaction
209
.
on aggressive behavior, 738 -
7 aminobulyric acid , 356 -
Isotopes, positron emitting, half - life, 61
visceral reflexes, 315 glycine, 356 Isthmus, transition to midbrain , 527
Hypotonia, definition, 288, 403, 620 Initial glomerulus, 265 Isthmus rhombencephali , regions,
Insula , 30 509-510
Imaging techniques characteristics, 34
angiogram, 54 definition , 28 Jaw- jerk reflex, 509
computerized tomography, 55 Intention tremor, definition , 620 Juxtarestiform body , 437
brain imaging, 55 Intercostal arteries, occlusion , %
operation principles, 55 Interfascicular cells, characteristics, 211 Karvosomes, 151
-
schematic and illustration , 56 57 Interhemispheric transfer, effect of Kernicterus, characteristics, 19
tomographic planes, 56 hemispheric separation, 921 Kernig’s sign , 286
magnetic resonance imaging Interleukin - 1 Kinesin , 182
frontal sections, 59 nerve growth factor production , 218 Kinesthesia , effects of posterior white
horizontal sections, 58 neuronal shaping, 218 column lesions, 371
operation principles, 55, 57 Intermediate filaments, astrocyte Kinesthetic sense, definition, 238
parasagittal sections, 60 reactions, 206, 209 Klumpke syndrome, characteristics, 283
positron emitting tomography Intermediate gray zone, structures Kluver - Bucy syndrome, characteristics,
brain imaging, 93 dorsal nucleus of Clarke, 349-350 783
imaging examples, 62 intermediomedial nucleus, 350 Knife-clasp phenomenon , definition , 407
microglia , 218 Intermediate nerve, characteristics, 497 Kolliker- Fuse nucleus, 511
neurotransmitter presence in brain , Internal arcuate fibers, 428 Korsakoff 's syndrome, characteristics,
63-64 Internal capsule, 33 773
operation principles, 60-61 basal ganglia and , 86
scanning electron microscopy, blood supply, iff 6 Labyrinth
ependymal cells, 222 characteristics, 112 amino acid transport , 488
x - ray, 54 composition, 683 equilibrium , 493
ImmunocytochemicaI methods corticofugal fibers, 685 hair cells, vestibular efferent fibers
neuronal imaging examples, 158 horizontal section, 683.801 and , relationship, 491
principles, 140 parts, 38 structures, 484
Impulse transmission, central nervous placement in brain , 642 vestibular ganglia , 485, 485
system to viscera, 2% posterior limb, structures, 683-684 vestibular nuclei, 485-486
In situ hybridization, principles, 141 retrolenticular portion , 684-685 Labyrinthine, anatomic orientation, 475
Inclusion bodies, characteristics, right portion , 684 Lacrimal reflex , 508
-
156 157 sagittal section, 800 Lamina affixa , 50
Induction factors thalamocortical fibers, 685 Lamina I
ciliary neurotrophic factor, progenitor Internal mesaxon, 167 afferent fibers, 339
cell differentiation , 203 Intemeurons, ( see also Neurons ) characteristics, 339
platelet -derived growth factor, .
anterior nuclei 642 enkephalin fibers, 357
progenitor cell differentiation , 203 cerebral cortex, 82, 872 nociceptor input , 339
Indusium griseum , 761 function, 144 substance P localization , 357
Infarction , definition , 93 Renshaw cells, 344 Lamina II
Inferior cerebellar peduncle
fiber arrangement, 437 types, 144
-
striatal cholinergic, 808 809 afferent fibers, 340
enkephalin fibers, 357
medulla , 463 Intemudear ophthalmoplegia GABA receptors, 356
structures, 437 causes, 500 glutamate receptors, 356
Inferior colliculi characteristics, 493 horseradish peroxidase studies .
fiber organization, 530 Interoceptors, function, 238 340
neurons, 481 Interossei, paralysis, 282 neuronal classification, 340
nuclei Interpeduncular nucleus, structures, 533 substance P localization , 357
central, 527 Interposed nuclei Lamina III
external, 530 cerebellum, 613 afferent fibers, 341
pericentral, 530 projections, 612-613 characteristics, 341
rostral part , 532 Interstitial nucleus of Cajal neuronal types, 341
sagittal section, 529 degeneration from lesion in , 546 Lamina IV
-
tonotopic organization , 530 531 nucleus of Darkschewitsch and , afferent fibers, 341-342
neuron types, 341
transverse section relationship, 547
midbrain of 3- month infant, 529 Interthalamic adhesion, 50 Lamina IX
through adult midbrain , 528 Intima pia -
Inferior frontal gyrus, parts, 31 characteristics, 8 motor neuron types, 343
Inferior horn , structures, 42 purpose, 12, 14 Lamina terminalis, 67
Inferior olivary complex , 80 Intrafusal muscle fibers Limina V
characteristics, 432-434 illustration, 247-248 characteristics, .342
gray band of cells, 433 size variations, 247 neuron types, .342
-
medullo pontine junction , 462 spinal nerve innervation, 263 .
Lamina VI centrobasal nucleus, 342
transverse section of medulla Intralaminar nuclear group Lamina VIII , characteristics, 343
through, 43 / caudal, 648 Laminin , nerve regeneration , 193
Inferior olive, 29 connections and functional I AMP, ( sec Limbic system -associated
Inferior salivatory nucleus, 451 organization , 648-651 membrane protein )
Information processing, cerebellum , 622 cortical projections, 650 Lateral cervical nucleus
Infratentorial dura , 3 rostral, 647 characteristics, 377
innervation 6. thalamostriatal projections, 649-650 illustration, 377
Infundibulum , 706 thalamus, 654 Lateral geniculate body , secondary
stalk, vascular casts, 729 Ionic channels, expression in visual area , cell projections, 905
stem, 707 oligodendrocytes, 214 Literal geniculate neurons, receptive
transverse section, 708 Iron , in ventral pallidum , 845 .
fields 895, 8%
996 Index
Literal geniculate nucleus

cellular lamination , 664
-
Limbic system associated membrane
protein, 746, 747
immunoreactivity fc» r glial acidic
fibrillary protein, 227
components, 663 664 Limen insula , 30, 34 inducing factors, 203
-
cross section , 665 Lipochrome, 156 intermediate filament, 206
glomeruli Lobotomy, frontal ionic channels, 206-207
neuronal arrangements, 670 function , 927 lamellar, 598
synaptic organization , 671 intellectual damage, 927 neuronal development, 208
laminae, 669 origins, 927 oligodendrocytes and , comparison,
lesions, illustration , in baboon, 666 Lock-in syndrome, 117 211
neurons, receptive fields, 689-690 Locus coeruleus -
pathologic conditions, 209 210
parvicellular layers, 664 ascending and descending plasticity, 208
retinal ganglion cell terminations, 668 norad renergic axons, 514 potassium concentration regulation ,
retinal surface brain stem innervation , 514 206-207
ti » pogra ph ic represen tation, cell types, 51 / , 513 protoplasmic, 203, 204-205, 209
664-665 characteristics, 457, 513 .
reactive 210
visual field representation, 667 neurons, norepinephrine, 399, 512 smooth, 598, 600
-
serotonm immunoreactive fibers, 682 noradrenergic input -
transmitter receptors, 207 208
visual hemifield , right , 669 cerebellum , 611 oligodendrocytes
Lateral lemniscus hypothalamus, 769 astrocytes and, comparison , 211
nuclei, 481, 509 Longitudinal fasciculus discovery, 211
pathways, 481 medial, head position regulation, 397 electrical properties, 214
Lateral medullary syndrome superior, characteristics, 918-919 illustration , 202
characteristics, 463 Longitudinal fissure, 25 ionic channels, 214
dorsolateral structures, 463 Longitudinal striae, 33 myelin sheath formation, 272, 214
Lateral nuclear group -
Long term potentiation , definition , 771 spinal cord, 211
serotoninergic innervation, 680 Lower extremity . -
types 211 212
thalamus movements, spinal innervation, 273 Macula, 484
components, 651-652 segmental innervation , 280 afferent fibers, 484-485
nuclei types, 639 Lower motor neurons Macula lutea, characteristics, 685
Lateral reticular nucleus,
cytoarchitectural parts, 434
effect of lesions, 289 glycoprotein )
-
MAG, (MV Myelin associated
Lateral tegmental system , formation , fasciculations, 404 Magnetic resonance imaging

399-400 LSD, ( see Lysergic acid diethylamide) brain imaging, 55, 57, 60
Literal ventricles Lumbar cistern frontal sections, 59
anterior horn . 42 cerebrospinal fluid pressure, 15 horizontal sections, 58
inferior horn , 42 characteristics, 10 multiple sclerotic patient , 61
lateral and superior views, 43 diagrammatic representation , 8 operation principles, 55, 57
posterior horn , 44 Lumbar enlargement , characteristics . parasagittal sections, 60
Lateral vestibular nucleus, reflex activity 327 Mammillary bodies, 85, 649, 706
of spinal cord , 394 Lumbar plexus frontal section, 37
-
L Dopa anterior division, 285 transverse section, 646
blood - brain barrier passage, 2 / , 64 development , lumbar enlargement, Mammillary fibers, hypothalamus,
Parkinson's disease, 18, 569 327 720-721
Learning, cerebellum and , relationship . illustration , 284 Mammillary peduncle, 533
622 pi >sterior division , 285 Mammillary region , hypothalamus
Lenticular fasciculus Lumbar segments efferent fibers, 720 721
characteristics, 833 spinal cord , 334 , 335, 337 nuclei, 715
fiber organization, 830 crush injury , section , 388 substantia innominata , 715
.
illustration 833 transverse section , 347 transverse section , 70S
Lesions Lumbosacral plexus Mammillotegmental tract , 721
cerebellum illustration, 284 Mammillothalamic tract , 647, 649 ,
anterior lobe, 621 -622 lower extremity innervation, 283 722-723
archicerebellar, 621 Luteinizing hormone- releasing hormone Mandibular branch , trigeminal ganglia .
neixerebellar, 620-621 hypothalamus, 732 501
corticospinal tract , 388-389 organum vasculosum laminae MAO, ( see Monoamine oxidase)
posterior white columns, 371 terminal is, 23 -
MAPs, ( see Microtubule associated
visual pathway , 69/1 release by neuropeptide Y, 732 proteins )
LGB, (s< r Lateral geniculate btxlv ) Lysergic acid diethylamide Marchi technique, neuronal morphology
LGN , (sir Lateral geniculate nucleus) characteristics, 516 studies, 134
I HR!I , (sir Luteinizing hormone- effect on serotoninergic system , 557 Marginal layer, 69
releasing hormone ) Mass reflex , definition , 407
Ligaments Macroglia Maxillary branch, trigeminal ganglia ,
coccygeal, characteristics, 7 astrocytes 501
denticulate, 9 Bergman , 82 Mochanoelectric transduction, sensory
Limb bud , upper extremity, biochemical markers, 205-206 receptors, 237
developmental stages, 269 biogenic amine regulation, 207 Mechanoreceptors, function, 2.38
Limbic lobe -
blood brain barrier formation , Medial accessory olivary nucleus, 433
characteristics, 36 20B 2( H) Medial forebrain bundle
schematic, 745 characteristics, 203-204 hvpothalamus, afferent projections,
structures, 36. 744 classes, 598 716
Limbic pathways distribution and appearance, 201 illustration , 724. 745
diencephalon , 724 .
fibrous, 202 203, 204, 205 Medial geniculate body , auditory area
telencephalon , 724 GABA regulation, 207 -
of cerebral cortex, 905 906
Limbic system glial fibrillary acidic protein , 206 Medial geniculate nucleus
diencephalon , 745 glutamate regulation , 207 -
serotonin immunoreactive fibers, 682
limbic lobe, structures, 744 glutamine synthetase, 206 ventral nucleus
major interconnections, 746 homeostasis, 206 fibrodendritic laminations, 662
telencephalon , 745 illustration , 200 laminar organization , 663
Index 997
Medial lemniscus midolivary region , transverse section , inferior view, 10

ascending fibers, 436 432 pia mater, characteristics, 8-9
-
decussation. 427 128
transverse section, 426
midsagittal section , microangiogram ,
116
posterior view , 6
spinal cord coverings, 9
fiber organization, in brain , 658 noradrenergic cells, 457 subarachnoid and perivascular
pons, dorsal part , 509 olivocerebellar and pontocerebellar spaces, 13
posterior white column formation and fibers, transverse section, 619 Meningitis, acute bacterial
course, 369. 370 raphe nuclei, 515 detection using cerebrospinal fluid , 14
upper medulla , 462 respiratory regulation , 446 pencillin treatment, 19
Medial longitudinal fasciculi, 469 reticular formation Meningocele, characteristics, 91
ascending and descending fibers, 490 afferent fibers, 435 Meningomyelocele, associated
internuclear ophthalmoplegia, 493 cytoarchitecture, 434 complications, 91
lesions, 493
Medial nuclear group
amygdaloid afferent fibers, 645
lesions, 645
divisions, 436
——
efferent fibers, 435 436
major subdivisions, 434 435
nuclear masses, 435
Merkel cell, characteristics, 241
characteristics, 503-504
illustration, 506
parvicellular portion, 645
thalamus
nuclei types, 639
regions, 644
spinomedullarv transition
—
corticospinal decussation , 422 423,
425
medial lemniscus decussation,
sensory neuron presentation, 508
Mesencephalon , ( see Midbrain )
Messenger ribonucleic acid
methods for detecting, 141
Medial tegmental region , midbrain , -
427 428 neuronal protein synthesis, 157
744-745
Median eminence
purpose, 23
overview, 421
—
posterior column nuclei, 425 427
trigeminal tract, 428-432
Metabotropic receptors, 178
Metencephalon
caudal, 80
in rat , zona interna and externa , 720
vascular casts, in monkey , 729
Median fissure, anterior, 325
Median nerve
injury, 282
—
spinoreticular fibers, 381
structures, 47 48
transverse section, 424
fourth ventricle, caudal, 431
inferior olivary complex, 431
developmental stages, 81 -82
1 - Methy -4- phenyl -4- 1 ,2,5,6,-
tet ra hyd ropy rid i ne
Guamanian syndrome, 64
Parkinsonism , 852
lesion , sensory loss, 282 medial lemniscus decussation , 426 MGB, ( see Medial geniculate body )
muscle innervation, 281 -282 1 -month infant , 427, 449 M - l , (MV Primary motor cortex )
Median septum , posterior, 325 pons, caudal border, 462 Microfilaments, characteristics, 148
Median sulcus, posterior, 325 upper portion, 450 Microglia , ( seealso Brain macrophages )
Mediodorsal nucleus, (sec Medial vestibulospinal tract , 490 -
nuclear group ) Weigert-stained section, 603 illustration, 215 , 216
thalamus, characteristics, 694 zones, 552 imaging studies, 218
Medulla Medulla oblongata , 27 neuronal shaping, 217-218
anterior aspect, 422 Medullary lamina origins, 201
arteries, 115, 115 external, thalamus, 640 pathologic processes, 218
ascending tracts. 436-437 internal, 639 role in Alzheimer's disease, 218
blood supply , 113

.
basic features, transverse section 438 .
Medullary pyramid, 33, 45 47
vascular lesion, transverse section
Microtubule-associated proteins, types,
147
microangiogram , 114 through cervical enlargement , 387 Microtubules, characteristics, 147
caudal, cell groups and tracts, 441 Medullary syndrome, lateral Micturition
characteristics, 79 causes, 116 innervation
chemical anatomy characteristics, 430, 463 autonomic, 318
acetylcholine, 457 dorsolateral structures, 463 sympathetic, 318
-
catecholamines, 457 457 Medullary - pontine junction vesical capacity and frequency, 319
neuroactive peptides, 458-461 characteristics, 462 Midbrain
neuromediators, 454-455 overview , 461 anterior aspect, 422
-
serotonin , 455 457 transverse section , 461 autonomic pathways, 314
bliH »d supply
chol i ne a cetv 11ransferase Meissner's corpuscles
immunoreactivity , transverse characteristics, 243 arteries, 117
section, 460 dermal papilla , 24 / microangiogram , 114
corticobulbar fibers illustration , 243 caudal
corticoreticular, 452 Melanin , presence in substantia nigra . inferior colliculi, 527, 530-531
pathways, 453 157 parabigeminal area , 531
sensory relay nuclei, 451-452 Melatonin pretectal region , 540-541
cranial nerves inhibitory effects, 84 tegmental and interpeduncular
glossopharyngeal, 449 451 pineal gland synthesis, 638 -
nuclei, 531 534
hypoglossal, 438, 440, 442 Membrane proteins, in neurons, types, trochlear nerve, 531
—
midsagittal view , 439
overview, 437 438
159
Memory
cranial nerves, 49
crus cerebri, structures, 572
— ——
spinal accessory, 442
vagus, 442 446, 448 449
descending tracts, 436 437
development , 80
regulation by hippocampus, 770-771
role of vasopressin and oxytocin , 732
Meningeal layer, dura mater, 3
Meninges
development, 83
divisions, 527
hypothalamic input , pathways, 314
isthmic transition, 527
horizontal section, 445 arachnoid , characteristics, 9 medial tegmental region , 744-745
horseradish peroxidase studies, cortical surface and, relationship, 13 midsagittal section, microangiogram .
-
446 447
—
inferior olivary complex , 80, 432 434
-
dura mater
-
arteries, 119 120
base view, 5
116
oculomotor nerve, nuclear complex ,
542 544, 544
gray band of cells, 433
-
transverse section of medulla
through , 431
—
medullo pontine junction, 461 463
blood supply , 6
characteristics, 3
components, 3
innermost layer, 6
posterior commissure, structure's,
541 -542
pupillary reflexes, types, 547-548
reticular formation
lateral medullary syndrome, 116 posterior surface, 4 caudal transeetions, 553
lesions, 463 venous sinuses, 120-122 cytoarchitectonic divisions, 552
998 Index
—
M id bra in conl inued
functional considerations, 552-553
somatotopic organization, 911 , 911
body parts, 890
Muscle atrophy, causes, 404
Muscle end plate, neuromuscular
inhibitory and facilitatory regions, supplementarv , characteristics, transmission , 175
stimulation, 554 913-915 Muscle spasms, flexor, spinal cord
neuronal systems
.
ascending 554-556
Motor deficits, causes, 402
Motor end plates
recovery. 406 407
Muscle tone
-
descending, 553 extraocular muscles, 257 cerebellar influence, 621-622
rostral skeletal muscle fibers, 256 pontine reticular formation effects,
oculomotor nerve, 542- 547 smooth muscle fibers. 256 493
posterior commissure, 541-542 striated muscle, 295 Muscle tonus, reflex regulation ,
pretectal region, 540-541 structural features, 255 neuromuscular spindles, 251
pupillary reflexes, 547-549 Motor nerve terminal, neuromuscular Musculocutaneous nerve, muscle
superior colliculi, 535-540 transmission , 175 innervation, 281
.
transverse section 528 , 534-535, Motor neurons Myasthenia gravis, characteristics, 258
.549 .
« 345-346 Mvelencephalon , (set* Medulla )
structures, 49 acetylcholine use, 353 Myelin sheath
substantia nigra , (str Substantia nigra ) anterior gray horn , 345-346 basic protein, 167-168
tegmentum , ( sec Midbrain muscle innervation , 346 breakup, during nerve degeneration .
tegmentum)
thalamic junction, 633-635, 636
axons, trajectories, 345
function , 144
184 185 -
central, oligodendrocytes and ,
transection , inferior view, 32 lower relationship, 124
transverse section fasdculations, 404 cross section, 170
level of oculomotor nerve, 534 lesions. 289 formation
posterior commissure, 545 segmental input , 402 jelly - roll theory , 166, 167
Midbrain periaqueductal gray , muscle fiber innervation, 257 molecular organization, 167-168
characteristics, 533 recurrent inhibition , 344 neuroglia function , 201
Midbrain tegmentum somatic, involvment in bladder oligodendrocytes, 212-214
lesions, 551-552 function , 318 stages, 167
red nucleus spinal cord, 154 structural organization, 165-167
cerebellum, 618 upper nodes of Ranvier, 168
-
connections, 550 551 lesions, 404 -
Schmidt Lantermann clefts, 168
cytoarchitecture, 549-550 paralysis, 405 -
Myelin associated glycoprotein, role in
fiber organization, 391 Motor nuclei myelination , 167
functional considerations, 551 cranial nerves Myotactic reflex, 361
illustration , 649 skeletal muscle innervation , 452 methods to elicit , 363
lesions, 551-552 supranuclear innervation, 452-453 Myotomes. innervation
neurons, 391 trigeminal nerve, 507 segmental, 273
neurotransmitters, 551 Motor skills, cerebellum influences, ventral root , 268
.
rubrospinal tract 391 622-623
topography, 549 Motor unit -
Nauta Gygax method, neuronal
Middle alternating hemiplegia , 49M functional components, 257 -
morphology studies, 137 140
MIDDLE cerebellar peduncle, 49 myasthenia gravis, 258 Neck , cutaneous fields, 274
Midline nuclear group -- -
MPTP, ( set 1 - Methyl -4- phenvl 4 1 ,2,5,6, N eocerebe!I u m
cell groups, 647 tetrahydropvridine ) characteristics, 585
characteristics, 645, 647 MRI , ( see Magnetic resonance imaging) lesions
Midolivary region, medulla , transverse rnRNA, (set* Messenger ribonucleic acid ) characteristics, 620
section , 432 Multiple sclerosis tremors, 620
M - lI , ( xv Supplementary motor cortex ) characteristics, 15, 412 Neocortex
Mitochondria , 155 detection using cerebrospinal fluid , 15 -
y aminobutyric and regulation ,
characteristics, 154 -
spin echo MRI imaging, 61 receptors 875 .
Mitral cells, olfactory bulb, 750 Multipolar neurons, characteristics, 146 layers
Mixed nerve Muscarinic receptors, presence in spinal granular, 867-868
branches, 267 cord , 353 molecular, 867
lesions, 402 Muscle multiform , 868-869
Ml.F, (sir Medial longitudinal fasciculi ) « motor neuron innervation , 346 pyramidal, 867-868, 874
Mnemonic reactions, 923 extraocular Neopallium, 748
Molecular layer localization in oculomotor nuclear Nerve cell body , ( see Soma )
cerebellar cortex, 585, 587-588 complex , 543 Nerve compression, effect on spinal
dorsal cochlear nucleus, 476 root liber origins, 532 roots 288.
Monoamine oxidase, intraneuronal progressive atrophy , 291 .
Nerv e constriction , consequences of
.
enzyme 308 skeletal 191
Monoaminergic systems, spinal cord afferent fibers, 348 Nerve endings
catecholaminergic projections . efferent fibers, 348 afferent , visceral structures, 240
-
394 4tX)
sorotoninergic projections, 399
motor cranial nerve nuclei
innervation, 452
encapsulated
end bulbs 243 .
Monoamines, ( seealso Biogenic amines) motor end plates, 256 Meissner's corpuscles, 243, 243
amygdala 776 . smooth pacinian corpuscles, 243, 246-247
neuronal activity, 307-308 efferent axon, 295-296 free, in skin and hair follicle, 239
spinal cord innervation , 353 innervation , 295 unencapsulated , in deep somatic
thalamus, 679-680, 682 motor end plates, 256 tissues of humans, 242
Mossy fibers norepinephrine effects, 310 Nerve fibers
characteristics, 592-593 paralysis, 313 degeneration
granular layer, 593 urinary bladder , 318 anterograde, 184-186
synaptic excitatory action, 597 stretch receptors, 890 axons, 184
transverse section, 586 striated myelin sheath, 184
Motor cortex innervation , 295 myelinated
primary motor end plate, 295 conducta nee speed , 171
-
electrical stimulation, 910 911 .
trunk , segmental innervation 278 size variations, 171
Index 999
peripheral tibial, muscle innervation , 286 Neuroepithelial cells, sensory nerve

classification table, 173 trigeminal cells, 241
connective tissue sheaths, 169, 171 exteroceptive and proprioceptive Neurofilaments, characteristics, 147-148
severed portion , transverse section . impulse's, 500-501 Neuroglia , ( sir also Glial cells)
189 supratentorial dura innervation , 6 astrocytes
regeneration, stages, 19 J trochlear, characteristics, 531 characteristics, 203-204
three types, 172 ulnar, 277 fibrous, 202 , 205
unmyelinated , characteristics, 171 muscle innervation , 282 protoplasmic, 203
Nerv e growth factor vagus biochemical investigations, 199
nerve regenerative ability, 193 -
characteristics, 442 443 cell lineage, 200-203
production, effect of interleukins- 1 dorsal motor nucleus, 446 cerebellar cortex, 599
and -6, 218 infratentorial dura innervation , 6 function, 199
purpose, 72 lesions, 449 general features, 200
Nerve section, regeneration, 290 vestibulocochlear, cochlea and related macroglia, ( see Macroglia )
Nerves nerve and nuclei, 474-478 microglia , ( see Microglia )
abducens Nervous system myelin sheath formation, 201
neuron types, 498-499 central , (see Central nervous system ) oligodendrocytes
root fibers, transverse section , 496 peripheral, ( see Peripheral nervous astrocytes and , comparison , 211
accessory, spinal, 442 system ) discovery, 211
auricular, great , 275 Neural connections, composition stages . illustration, 202
axillary , 277 72 structures, 597-598, 600
muscle innervation, 281 Neural crest Neuroglia cells, histogenesis, 71
--
cochlear, 461 462 cell differentiation , 76 Neurohypophyseal hormones
nuclei, 475 476 , 478 characteristics, 67 oxytocin
common peroneal, muscle derivatives, 67 effect on memory, 732
innervation , 287 embryonic, spinal ganglia function , 162
cranial, (see Cranial nerves ) development , 265 medulla , 460
root fiber origins, 532 Neural crest cells, spinal ganglia production, 712
cutaneous creation , 76 spinal cord laminae, 359
femoral Neural fold , 66 vasopressin
lateral, 285-286 Neural groove, 66 function , 162
posterior, 287 Neural induction , 65 medulla , 460
medial branches, 277, 283 Neural plate, 66 memory, 732
facial Neural tube production , 712
functional components, 495 dividing cells of germinal zone, 70 spinal cord laminae, 359
overview, 495 formation , 65-67 Neurohypophysis, 23, 707
root fibers, transverse section, histogenesis, 69 Neurokeratin network, 168
496 Neurilemma cells, origins, 202 Neurolemma sheath , 169
glossopharyngeal Neurite growth inhibitory proteins, Neuromediators
characteristics, 449-451 function, 193 pain control, 456
effect on swallowing, 451 Neuroactive peptides types, in medulla , 454
lesions, 451 autonomic ganglia , functions, 311 Neuromuscular spindles
gluteal, 287 autonomic nervous system, 310-311 characteristics, 247
greater occipital, 274 calcitonin gene- related , spinal cord intercostal, 248
hypoglossal, 438, 440, 442 laminae, 358 fusiform axons, 250
injury , types, 289 -
cerebral cortex, 875 876 sensory nerve endings, 249
intermediate, 497 choleeytokinin, spinal cord laminae. intrafusal and extrafusal fibers, 247
long thoracic, 276 358 proprioceptive impulses, 254
median , muscle innervation, 281 list , 162-163 Neuron doctrine, principles, 131
mixed , characteristics, 267 locus coeruleus, 513 Neuronal systems, reticular
musculocutaneous, 277 medulla , 454 ascending, 554-556
muscle innervation, 281 opioid peptides, 458-459 descending, 553-554
obturator, muscle innervation , 285 -
oxytocin , 460 461 Neurons, ( see also Interneurons )
occipital, lesser, 275 substance P, 460 abducens nerve, 498
oculomotor vasopressin, 460-461 adrenergic, 458
nuclear complex , 542-544, 544 , neuropeptide Y, 358 arborization pattern, 146
-
545 547 in amygdala , 778 -
auditory pathway, 481 482
root fiber pathway , 544 cerebral cortex, 876 axons, 143
transverse section, 534 luteinizing hormone release, 732 myelin , 165-168
pectoral, medial and lateral , 276 spinal cord laminae, 358 overview, 162 163-
peripheral , dermatome and cutaneous opioid , presence in spinal cord , 357-358 catecholaminergic, noradrenergic cell
innerv ation , 271-272 oxytocin, spinal cord laminae, 359 group, 457-458
phrenic, 275 purpose, 161 cerebellum pathway, 380
.
radial 277
muscle innervation, 281
somatostatin
in amygdala , 778-779
cholinergic, 458
globus pallidus, 829
scapular, dorsal, 276 immunoreactivity in basal ganglia . immunohistochemical studies, 353
-
sciatic, cross section, drawing, 269 810 medial habenular nucleus, 637-638
spinal spinal cord laminae, 358-359 substantia innominata , 715
dorsal roots, 262 subcoeruleus, 513 classification , chemospecificity, 306
general organization, 262 thalamus, 675.678 claustral , receptive field properties,
splanchnic, 300 thyrotropin releasing hormone, spinal 846
suboccipital, 274 cord laminae, 359 cochlear efferent , 483
subscapular, 276 vasopressin , spinal cord laminae, components, 131
supraclavicular, 275 *59 cortical
suprascapular, 276 Neuroblasts, differentiation into dendritic and axonal branchings,
terminal , olfactory system , 757 neurons, 69 866
Neuroectoderm, capillary production.
thoracodorsal, 276
^
third , lesions, 548 - 549
18
interrelations, in cerebral cortex,
869-871
1000 Index
Neurons vnlinueJ
corticospinal, characteristics, 385
sensory, 145
impulse site, 142
- basal ganglia core structures, 805
y aminobutyric acid , 160
cytoplasm , 149 trigeminal ganglion, 266 cerebral cortex , 873-875

cytoskeleton serotoninergic, 158 enteric neurons, 302
centrosomes, 154 , 156 effects of LSD, 516 hippocampus receptors, 769
chromophilic substances, 151- 154 -
medulla , 455 456 inhibitory transmitter in spinal
Golgi apparatus, 156 raphe nuclei , 515, 517 cord , 356
illustration, 151 soma, ( see Soma ) neocortex, receptors, 875
inclusion bodies, 156-157 spinal striatofugal neurons, 828
microfilaments, 147- 148 immunocytochemical staining, in subthalamic nucleus, 840
microtubules, 147 monkey, 354 thalamus, 675, 676-677
mitochondria , 154 posterior horn, 347-349 aspartate
neurofilaments, 147-148 somatic efferent, .345-347 cerebral cortex, 873, 874
nucleolus, 15(4-151 visceral efferent , 347 presence in spinal cord , 355-356
peroxisomes, 154 spinothalamic tracts, 373 biogenic amines, 160
polymerization, 148 stapedius reflex , 497 pineal gland , 638
Da le’s pri nci pie, 31(4 striatal, 802 cerebellar nuclei, 601
degeneration aspiny, 803, 807-808 chemical synapses, 176
anterograde, 184-186 effect of dopamine, 817 enteric neurons, 302
retrograde, 186 neurotransmitter use, 826 glutamate, 161
dendrites, 143 spiny , 802-803, 803-804 , 821 cerebral cortex, 873, 874 , 973
development substantia nigra , 208, 557 hippocampal formation, 768
astrocytes, 2(18 sympathetic, 145 neurotransmitter, 161
resident brain macrophage description, 293 presence in spinal cord, 355
-
presence, 217 218 illustration , 305 regulation , astrocytes, 207
differentiation stages, 69 synapses subthalamic nucleus, 840
dopaminergic, 158 chemical, 175-176 ion channel gating, 178
hypothalamus, 731 electrical, 174-175 neuronal communication, 133
luberohvpophvsial tract, 724-725 overview, 172 173 - PET scan, 663-664
enteric, 302 receptors, 177-178, 180 putative chemical messengers,
description, 293 ultrastructural classifications, classification criteria , 159
ganglia, differentiation, 75 -
173 174 receptor localization, 141
growth vesicle recycling, 176-177 visualization methods, 141
peripheral and central grafting thalamic, gating functions, 693 red nucleus, 551
experiments, 192 193 types, 144 ventral striatopallidal complex , 845
promoting and inhibiting factors . unipolar, histologic staining, 135 visualization
193 varying lengths, 146 histochcmical techniques, 140- 141
histogenesis, 71 visceral efferent , 492 i mm unocytochemica1 techniques,
histologic staining, 135 types, 347 140 141
Neurulation , stage's, 65-66
hypothalamic, 397
internal pallidal , terminal boutons
842
.
Neuropeptide Y
amygdala, 778
cerebral cortex, 876
.
NC F, ( see Nerve growth factor )
Nicotinic receptors, 306
intracellular and intercellular luteinizing hormone release, 732 Nigrostriatal dopaminergic system , PET
communication, 133 spinal cord laminae, 358 visualization, 64
lamina II , 340 Neuropeptides, solitary nuclear Nigrostriatal fibers
lamina III , 341 complex , 445 characteristics, 815-818, 821
lamina IV , .341 .342 Neurophysins, supraopticohypophysial feedback loop, 565
lamina IX . .343 tract, 723 substantia nigra , 564-566
lateral geniculate, receptive fields, Neuropil, 329 termination locations, 565
895. 8^6
locus coemleus, 512
Neurosecretion, concept development
712
. Nigrotectal fibers
origins, 567
metabolic activity , visualization Neurosecretory neurons, 723 terminations, 568
methods , 141 , 144 Neurotendinous organs Nigrotegmental fibers, origins, 568
morphology, histologic study characteristics, 251 Nigrothalamic fibers, characteristics,
-
techniques, 134 137
motor, ( see Motor neurons )
.
C olgi tendon organ
afferent fibers, 252, 363
5ht>-567
Nissl bodies
multipolar anatomic and functional characteristics, 152
characteristics, 146 relationships, 361 retrograde degeneration , 186
histologic staining, 135 axonal branches and collagen .
Nitric oxide synthase 588
neurosecretory, 161 - 162, 723
nucleus, characteristics, 149- 150
bundles, relationship, 253
capsule, 251
- -
NMDA, (s*v N methyl D aspartate)
- --
-
N methyl D aspartate, conductance in
olfactory, 750 illustration , 252 hippocampal formation, 769
pallidal , dendrites of , 831 Neurotoxins, effect on motor neurons, NO synthase, (set* Nitric oxide synthase )
parasympathetic, 14 5 257, 257 Nocioceptors
description, 293 Neurotransmitters fiber types, 359
ptwtganglionic, characteristics, 296 acetylcholine, 160, 353 function , 139
preganglionic, characteristics, 2^6 autonomic nervous system . lamina 1 input , 339
proteins 106 Node of Ranvier
synthesis, 157, 159 -
cerebral cortex, 880 882 characteristics, 165, 168
type's, 157 enteric neurons, 302 illustration , 165
pyramidal, 140 hippocampus, 769 Nodulus, 53
glutamic acid decarboxvlase- motoneuron effects, 77 Nonpvramidal corticofugal fibers
immunoreactive terminals, 875 muscle contraction, 257 corticopontine fibers, 916-917
in hippocampus, afferent input , 772 in primate amygdala , 776, 778 corticoreticular fibers, 91 n
red nucleus, 391 receptor types, 307 corticothalamic libers, 917
regeneration , 18<v- 189 spinal cord transmitter, 352 -353 Noradrenaline
resting, ( see Resting neuron ) storage in motor endplates, 255 axons
reticular nucleus, 671 , 672 thalamus, 673-675 ascending and desc ending, 514
Index 1001
enteric system , 309 Nystagmus spinal cord, 211

fibers, thalamic innervation, 679-680 characteristics, 621 types, 211-212
postganglionic sympathetic nerve definition, 492 Olivary complex, inferior
release, 307 afferent input , 608
Norepinephrine Obturator nerve, muscle innervation , characteristics, 432-434
chemical transmission , 306 285 climbing fibers, 594
content in terminals, 308 Occipital eye center, 916 gray band of cells, 433
effects on smooth muscle, 310 Occipital lobe, components, 34 Olivary eminences, 45
synthesis, 638 Ocular dominance columns Olivary nucleus, inferior
Notochord, 65 primary visual sensory areas, 900-902 afferent input , 609-610
Nuclear membrane, soma , 149 , 150 .
striate cortex, 901 -902 904 climbing fibers, 608
Nuclei Oculomotor nerve Olivocerebellar fibers
hypothalamic accessory oculomotor nuclei, 544-545 cerebellum , 605, 618
illustration, 707 nuclear complex, 542-544 characteristics, 608-609
paraventricular and supraoptic, 712 afferent connections, 545-547 Olivocochlear bundle, fiber origins, 482
tuberal region , 713 extraocular muscle locations, 543 Opercular portions, 28
intermediate gray zone sagittal section, 544 Ophthalmic artery, dura mater, 6
central cervical, 350-351 visceral nuclei, 543-544 Ophthalmic branch , trigeminal ganglia ,
intermediomedial, 350 root fiber pathway, 544 501
posterior gray horn transverse section , 534 Opiate receptors, pain mechanisms, 361
posteromarginal, 348 Odor discrimination, ( see Smell ) Opioid peptides
proper sensory, 348-349 OKR , ( see Optokinetic eye movement in medulla , 458-459
thalamus response) nociceptive transmission , 361
-
anterior, 642 644 , 649 Olfaction , overview, 756 presence in spinal cord , 357-358
classification , 641 -
Olfacto frontal connections, in primate Opioids, endogenous
intralaminar, 647-648 brain 753. pain mechanisms, 360
lateral, 651-652 Olfactoria fila , 748 pain regulation, 358
medial, 644-645 Olfactory area , cerebral cortex , 886 Optic chiasm , 45
midline, 645, 647 Olfactory bulb lesions, 690
overview, 640-642 accessory, characteristics, 756-757 Optic nerves, characteristics, 687
ventral, 652-660 afferent fibers, 752-753 Optic radiations, 33, 38, 40, 43
visceral efferent neurons anterior olfactory nucleus, 753 Optic tract
intermediolateral, 347 cells, 749 characteristics, 687
sacral autonomic, 347 functional organization , 752 nucleus, 540
Nudeocortical projections, interconnections, 752 Optokinetic eye movement response,
characteristics, 604 intemeuron types, 75(1 622
-
Nucleolus, characteristics, 150 151 mitral cells, 750 Orbitofrontal cortex, lateroposterior
Nucleus, neurons, characteristics, striae, 754 quadrant , olfactory information ,
149-150 structures, 750 75b
Nucleus ambiguus Olfactory glomeruli Organ of Corti, 476
-
caudal parts, 448 149

Neuroanatomy - Carpenter 9E (1996)

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Neuroanatomy - Carpenter 9E (1996)

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Andre Parent, Ph.D.

Williams & Wilkins

Printed in the United States of America

First Edition 194.1

Parent , Andre, 1944-

Francois Rabelais, 1554

Franqois Rabelais, 1554

1 Meninges and Cerebrospinal Fluid 3

2 Regional Anatomy of the Brain 25

3 Development of the Nervous System 65

4 Blood Supply of the Central Nervous System 93

Section II Neurohistology and Neurocytology

Section III Peripheral Nervous System

8 Spinal Nerves and Peripheral Innervation 262

9 Autonomic Nervous System 293

Section IV Spinal Cord

11 Spinal Cord: Fiber Tracts 368

Section V Brainstem and Cerebellum

18 Limbic System 744

19 Basal Ganglia 795

20 Cerebral Cortex 864

Section VII Atlas of the Human Brain

Regional Anatomy , Development,

Foramen magnum level

halx cerebri Anterior cranial

Internal carotid Optic chiasm

NN 2E and T7TTT Sulcus for inf . cerebral veins

Atlas Vertebral artery

Dura mater Trunk of fourth

Spinal ganglia Ventral root

Pia and dorsal

Pia Mater 29 ). The epipial layer is formed by a mesh-

Denticulate ligament \ / Subarachnoid space

Cerebral subarachnoid spaces Olfactory bulb and tract

Optic n. ond central

Cerebral subarachnoid space

Pontine cistern Cerebellomedullary cistern

Spinal subarachnoid space

Dura mater Superior sagittal sinus Arachnoid

tribution of the number of ions and nonelec- -

BRAIN CAPILLARY GENERAL CAPILLARY

Foot process of Intercellular

CEREBRAL AND SPINAL ARTERIAL BLOOD

BLOOD- BRAIN- BARRIER BLOOD- CSF- BARRIER

Intracellular fluid Cerebrospinal fluid

VENOUS BLOOD OF DURAL

Lateral intercellular space Fenestrated capillary

Subfornical organ Subcommissural organ

Median eminence postrema

References 18. Gomez DG , Chambers AA ,

brospinal fluid by the ventricular

MAJOR COMPONENTS EMBRYONIC SUBDIVISIONS ADULT CAVITIES ^I J

Spinal cord Neural tube Spinal cord Central canal

in adults, as well as the corresponding ventricular compartments

Central sulcus Postcentral sulcus

Sup. frontal sulcus

Figure 2.3. Lateral surface of the brain

Longitudinal cerebral fissure

the cerebral cortex in humans is highly con - Lateral Surface