BASIC EMBRYOLOGY

NEUROANATOMY &
NEUROPHYSIOLOGY
Maria Lina D.Renales,M.D.
Fellow, Phil. Neurological
Association
 Introduction

The human brain is the most

complex and sophisticated
system to be found on planet
earth that we will never
succeed in understanding it
fully..
Brain- the control center
and the organ of thought
This makes humans superior to other
mammals.
outline
¼ General Divisions
¼Embryology
¼Histology
¼Physiology
¼Neurotransmitters
¼Gross anatomy
MainDivisions
Nervous System

Central Nervous Peripheral Nervous

System System

Brain Spinal Cord

EMBRYOLOGY - FROM THEZYGOTE
TO THE NEWBORN
 CNS/PNS COMES FROM
ECTODERM

• The CNS/PNS is the earliest to be formed (3rd fetal

week)and the last to be completed post natally (40
years old).
• Ectodermal cells that fail to follow the neural
program of differentiation give rise to the epidermis
of the skin.
2 major factors in cell differentiation

• ¼INDUCING FACTORS -signalling molecules

provided by other cells- non-neural cells in
mesoderm such as bone morphogenic protein
subclass transforming growth factorBeta.
• ¼COMPETENCE FACTORS -molecules activated or
induced inside the cells by the inducing factors
which depends on the precise repertoire of
receptors, transductionmolecules and transcription
factors expressed by the cell
Rostrocaudal axis growth of Neural
Tube
¼The neural tissue induced by follistatin,
noggin and chord appears to express
genes that are characteristic of forebrain
but not of posterior tissues.
¼Additional signalling pathways are required
for induction of posterior neural tissue which
later gives rise to midbrain, hindbrain and
spinal cord. The hindbrain & spinal cord
development is patterned homeobox
genes regulating body plan in vertebrates
and Drosophila (fly). Mouse & humans
have 4 Hox genes.
Neuronal fate is decided by a process of signalling
between adjacent cells in the pro neural region

¼2 cell surface proteins encoded by neurogenic

genes: (1) delta, as ligand and
(2) notch as receptor
¼Cells with low level of notch signalling become
neurons. Notch signalling is regulated by other
proteins like the numb protein which inhibits notch
signalling. During the division of neural progenitor
cells, one of two daughter cells receives the
numb protein which in turn are destined to be
neurons.
Secreted Factors direct differentiation of
neural crest cells into Neurons & Glia

¼ Bone Morphogenic proteins

¼Basic helix-loop-helix
transcription factors
¼Glial growth factors - platelet
derived growth factor(PDGF)
and ciliary neurotrophic
factor (CNTF)
 Neuron differentiation
• ¼birthday neuron -a dividing precursor
undergoes its final round of cell division and
gives rise to its post mitotic neutron
• ¼Layering of neurons in the cortex is
established in aninside first, outside last
manner
• ¼Progenitor cells in the cortex divide in an
asymmetric manner
The Neurotransmitter phenotype of a neutron is
controlled by signals from the neuronal target

¼Example: Sympathetic
neurons secreting
norepinephrine stopped
secreting norepinephrine
once their axons come in
contact with sweat glands
and start secreting
acetylcholine.
Survival of a Neuron is also regulated by
signals from the neuronal target

• ¼The size of muscle targets critical for

the survival of spinal motorneurons
• ¼Electrical activity in theneurons is
required for appropriate responses for
neurotrophic factors, thereby permitting
the extent to which neuronal
population attain its eventual number.
Neurotrophins
¼ NGF - nerve growth factor -
interacts with trek
¼BDNF - brain derived
neurotrophic factor- interacts
with trkB
¼Neurotrophin 3-activates trkC
¼Neurothrophin 4/5- interacts
with trkB
Deprivation of neurotrophic factors activates
a cell death program in neurons

¼ caspaces -executors of
cell death program
¼apoptosis activating
factor
Molecules of different families interact to
guide axons to their destinations

• ¼example: retinal axons: tyrosine

kinases, ephrin A2 and ephrin A5-
required for formation of
retinotopic map in the optic
tectum
 Secretory
1 Phase fertilization, Secretory
Stage 1
Phase

2 Stage 2 morula, Blastula

3 blastocyst
blastocyst Hatching (zona
4 Stage 3
pellucida lost)
5 Late Secretory, blastocyst (free
floating)
6 Stage 4 Adplantation
7 Stage 5

8
implantation
13 Stage 6
Chorionic Cavity

14

Day Stage Event

15

16 Stage 7
Stage 8 neural neurogenesis, neural
groove and folds are first seen

19

20 Stage 9
Musculoskeletal
• somitogenesis, first somites form and continue to
be added in sequence caudally (1 - 3 somite pairs).
• neural the three main divisions of the brain, which
are not cerebral vesicles, can be distinguished
while the neural groove is still completely open
• Neural Crest mesencephalic neural crest is
visible[1]
• Day 21 heart cardiogenesis, week 3 begins as
paired heart tubes
 Day 22
Stage 10
• Neural Crest differentiation at spinal cord level from
day 22 until day 26
• neural folds begin to fuse near the junction between
brain and spinal cord, when Neural Crest cells are
arising mainly from the neural ectoderm
• Neural Crest trigeminal, facial, and postotic ganglia
components visible[1]
• Neural Crest migration of vagal level neural crest cells
begins (7-10 somite stage)
• neural rostral neural tube forms 3 primary brain
vesicles (week 4) respiratory Week 4 - laryngotracheal
groove forms on floor foregut.
Day 23
Stage 10
•heart begins to beat in Humans
by day 22-23, first functioning
embryonic organ formed.
23

24

25
Day 24
Stage 11
• thyroid - thyroid median endodermal
thickening in the floor of pharynx
• neural rostral (or cephalic) neuropore closes
within a few hours; closure is bidirectional, it
takes place from the dorsal and terminal lips
and may occur in two areas simultaneously.
The two lips, however, behave differently.
• ventricular Optic ventricle appears and the
neural groove/tube space is initially filled
with amniotic fluid.[2]
Day 25
Stage 12
• pituitary Week 4 hypophysial pouch, Rathke's pouch,
diverticulum from roof
• liver septum transversum forming liver stroma and hepatic
diverticulum forming hepatic trabeculae
• neural caudal neuropore takes a day to close (closure is
approximately at future somitic pair 31/sacral vertebra 2)
• neural secondary neurulation begins
• ventricular onset of the ventricular system and separates the
ependymal from the amniotic fluid
• neural crest cardiac crest, neural crest from rhombomeres 6 and
7 that migrates to pharyngeal arch 3 and from there the truncus
arteriosus
• neural crest vagal neural crest enter the foregut (20-25 somite
stage)
 Day 28
Stage 13
•neural the neural tube is normally completely closed,
ventricular system now separated from amniotic fluid.
Neural crest at spinal level is segregating, and spinal
ganglia are in series with the somites. Spinal cord
ventral roots beginning to develop.[4]
• telencephalon cavity appears
• Neural - Vascular Development - hindbrain is supplied
by two parallel neural arteries (or channels) that obtain
their blood supply from carotid-vertebrobasilar
anastomoses given by the pharyngeal arch arteries;
trigeminal artery, the otic artery, hypoglossal artery,
and the proatlantal artery.[5]
• liver epithelial cord proliferation enmeshing stromal
capillaries
• smell Crest comes from the nasal plates
• integumentary 4 weeks - simple ectoderm epithelium
over mesenchyme integumentary 1-3 months
ectoderm- germinative (basal) cell repeated division of
generates stratified epithelium; mesoderm-
differentiates into connective tissue and blood vessels
• vision Optic vesicle lies close to the surface ectoderm.
The surface ectoderm overlying the optic vesicle, in
response to this contact, has thickened to form the lens
placode.
• Diaphragm - pleuroperitoneal fold (PPF) first
discernible in human embryos (CRL 6mm).
 Day 29
• pituitary Week 5 elongation, contacts
infundibulum, diverticulum of diencephalon
• heart Week 5 septation starts, atrial and ventricular
• respiratory Week 5 left and right lung buds push into
the pericardioperitoneal
• canals (primordia of pleural cavity)
• Respiratory Week 5 to 17 lung histology -
pseudoglandular
• hearing Week 5 cochlear part of otic vesicle elongates
(humans 2.5 turns)
 Day 32
Stage 14
•Placodes sensory placodes, lens pit, otocyst, nasal placode, primary/
secondary vesicles, fourth ventricle of brain
• Template:Somite continued segmentation of paraxial mesoderm (somite pairs), heart
prominence
• head 1st, 2nd and 3rd pharyngeal arch, forebrain, site of lens placode, site of otic
placode, stomodeum
• Body - heart, liver, umbilical cord, mesonephric ridge visible externally as
• bulges.
• limb upper and lower limb buds growing.
• Abdominal Wall mesoderm of the primary body wall coalesced in the ventral midline
to create the abdominal cavity.
• neural first appearance of the future cerebral hemispheres. Cerebellar plate
• differentiated to an intermediate layer, and future rhombic lip identifiable
• Neural - Vascular Development - basilar
artery forms from the consolidation of the
neural arteries.
• ventricular Subarachnoid space initially as
irregular spaces on the ventral surface of
the spinal cord.
• liver hepatic gland and its vascular
channels enlarge, hematopoietic function
appears
• vision lens placode is indented by the lens
pit.
 Day 35

• neural cranial nerves (except olfactory and optic) are

identifiable in more advanced embryos
• Neural - Vascular Development - vertebral arteries
form from transverse anastomoses between cervical
intersegmental arteries, beginning with the proatlantal
artery and proceeding downward to the 6th
intersegmental artery,
• vision lens pit is closed. The lens vesicle and optic cup
lie close to the surface ectoderm and appear to press
against the surface.
• vision 35 to 37 days retinal pigment present
Day 36
• pituitary Week 6 - connecting stalk between pouch
and oral cavity degenerates parathyroid Week 6 -
diverticulum elongate, hollow then solid, dorsal cell
proliferation
• thymus Week 6 - diverticulum elongate, hollow then
solid, ventral cell proliferation adrenal Week 6 - fetal
cortex forms from mesothelium adjacent to dorsal
mesentery, medulla neural crest cells from adjacent
sympathetic ganglia
• respiratory Week 6 - descent of heart and lungs into
thorax. Pleuroperitoneal foramen closes
• tongue Week 6 - gustatory papilla, caudal midline
near the foramen caecum (week 6 to 7 - nerve fibers
approach the lingual epithelium)
Day 37
Stage 16
• Neural first parasympathetic ganglia,
submandibular and ciliary, are identifiable[13]
Neural - Vascular Development - development of
the middle cerebral artery is first identified as
small buds originating proximal to the anterior
cerebral artery on the anterior division of the
primitive internal carotid artery.
• limb upper limb bud nerves median nerve, radial
nerve and ulnar nerve entered into hand plate,
myoblasts spindle shaped and oriented parallel to
limb bud axis.
• musculoskeletal
• Sternum right and left sternal bars are present.[23] (figs. 7-17
and 7-22)
• Abdominal Wall segregation of the myoblasts into four distinct
muscle groups with unidirectional orientation of myoblasts.
Myoblast migrated over half of the distance to the ventral
midline, abdominal wall thickest where the muscles migrated
and the outermost layer of connective tissue comprises
approximately half of the total thickness of the abdominal wall.
Rectus muscle completely separated after migrating over half
the distance to the midline.[9]
• neural
• rhombencephalon migration for olivary and arcuate nuclei
begins.
• choroid plexus of the fourth ventricle present.
• stria medullaris thalami reaches the habenular nuclei.
• habenular commissure begins to develop.
• accessory olivary nucleus appears[24]
• Neural - Vascular Development - middle cerebral artery
becomes more prominent, the plexi fuse into a single artery
and further branches pierce the cerebral hemisphere.[5]
Day 50
Stage 20

•Head scalp vascular plexus visible

•limb upper limbs begin to rotate
ventrally
•neural amygdaloid body has at least
four individual nuclei
 Day 53
Stage 21
• neural cortical plate appears in the area of future insula[25]
• Neural - Vascular Development - formation of the anterior
communicating artery.[5] limb upper and lower limbs rotate
• Intraembryonic Coelom pericardioperitoneal canals close
• Abdominal Wall Myoblasts have reached the ventral midline
and myotubes were present and oriented uniformly within all
muscle groups. The rectus abdominis formed distinct
bundles of muscle. Connective tissue layers comprised the
majority of the thickness of the abdominal wall, outermost
layer of connective tissue accounted for the majority of this
thickness.[9]
Day 54
Stage 22
• neural neocortical fibres project to epithalamus,
to dorsal thalamus, and to mesencephalon
• limb fingers and toes lengthen
• smell Stage 22 to early fetal period - migratory
streams of neurons from the subventricular
zone of the olfactory bulb towards the future
claustrum[6]
second & third trimester
Overview of BrainDevelopment
Week 3 embryo
Neural Plate
Development of the neural plate region at the Week 3 embryonic disc stage.
Dorsal view of the embryonic disc from the amniotic cavity side showing the
ectoderm with the central region developing into the neural plate.
The neural plate extends from buccopharyngeal membrane to primitive node
and forms above the notochord and paraxial mesoderm.The
neuroectodermal cells form a broad brain plate and narrower spinal cord
region.
Three specific regions medial to lateral can also be identified: midline region
floor plate,
neural plate, edge of neural plate neural crest
• blue - neural plate region
• white and black midline strip - primitive streak ending in primitive node
• white - ectoderm forming the epithelium of the skin
• upper circular region - buccopharyngeal membrane
• lower circular region - cloacal membrane
embryo at 4weeks
Overview of the brain
 Postnatal brain development: Structural imaging of dynamic neurodevelopmental
processes
Terry L. Jernigan†,‡,§,*, William F. C. Baaré‡,§, Joan Stiles†, and Kathrine Skak
Madsen‡,§ †Department of Cognitive Science and Center for Human Development,
University of California,

San Diego, CA, USA

The visual appearance of the brain on MR images changes appreciably over the first 2–3 years
of life, mirroring an orderly pattern of myelination in white matter regions.

At that time, we conducted MR morphometry studies comparing brain morphology in children

and adults. Surprisingly, these showed that estimates of gray matter volumes, both in the
cerebral cortex and in subcortical nuclei, were considerably larger in school-aged children than
in young adults (Jernigan and Tallal, 1990; Jernigan et al., 1991). This suggested that tissue
alterations related to brain maturation might be much more protracted during childhood than
was generally supposed, and that some of these alterations might be regressive; that is, they
might involve tissue loss.

What is clear is that dynamic biological changes in the tissues continue throughout
childhood and adolescence.
Estimated volumes of brain structures in normal volunteers are plotted against
age.
histology
The finer details
The blood –brain barrier
THE NEURON
¼ Cell body - contains nucleus
¼ Nucleus – contains DNA
¼ Dendrites – cell body (receives
information)
¼ Receptors – receive information
using a chemical signal.
¼ Axons – sends information
¼ Axon hillock – junction between
cell body and axon
**Lowest threshold for action
potential**
 THE NEURON
¼ Terminal (buttons or boutons) –
swelling on the surface (see slide)
- Inside buttons are synaptic vesicles,
packaging of neurotransmitter
¼ Myelin sheath – insulation for axons
- comprised of glial cells
A. In CNS it’s Oligodendrocytes
B.In PNS it’s Schwann cells
¼ Nodes of Ranvier – spaces between
myelinating cells along the axon
Neurohistology: types of neurons
Sensory neurons =
Pseudounipolar, myelinated

Special senses = Bipolar

(smell is unmyelinated-slow,
hearing is myelinated-fast)

Motor neurons = Multipolar

 Neuroglial Cells
• Neuroglial cells—usually referred to simply as glial cells or glia—are quite
different from nerve cells. The major distinction is that glia do not participate directly
in synaptic interactions and electrical signaling, although their supportive functions
help define synaptic contacts and maintain the signaling abilities of neurons. Glia are
more numerous than nerve cells in the brain, outnumbering them by a ratio of
perhaps 3 to 1. Although glial cells also have complex processes extending from their
cell bodies, they are generally smaller than neurons, and they lack axons and
dendrites (Figure 1.4). The term glia (from the Greek word meaning “glue”) reflects
the nineteenth-century presumption that these cells held the nervous system together
in some way. The word has survived, despite the lack of any evidence that binding
nerve cells together is among the many functions of glial cells. Glial roles that are
well-established include maintaining the ionic milieu of nerve cells, modulating the
rate of nerve signal propagation, modulating synaptic action by controlling the uptake
of neurotransmitters, providing a scaffold for some aspects of neural development,
and aiding in (or preventing, in some instances) recovery from neural injury.
There are three types of glial cells in the mature central nervous system:
astrocytes, oligodendrocytes, and microglial cells.

Astrocytes, which are restricted to the brain and spinal cord, have elaborate local
processes that give these cells a starlike appearance (hence the prefix “astro”). The
major function of astrocytes is to maintain, in a variety of ways, an appropriate
chemical environment for neuronal signaling.

Oligodendrocytes, which are also restricted to the central nervous system, lay down a
laminated, lipid-rich wrapping called myelin around some, but not all, axons. Myelin
has important effects on the speed of action potential conduction (see Chapter 3).
In the peripheral nervous system, the cells that elaborate myelin are called Schwann
cells.

As the name implies, microglial cells are smaller cells derived from hematopoietic
stem cells (although some may be derived directly from neural stem cells). They share
many properties with tissue macrophages, and are primarily scavenger cells that
remove cellular debris from sites of injury or normal cell turnover. Indeed, some
neurobiologists prefer to categorize microglia as a type of macrophage. Following
brain damage, the number of microglia at the site of injury increases dramatically.
Some of these cells proliferate from microglia resident in the brain, while others come
from macrophages that migrate to the injured area from the circulation.
CELL MEMBRANES OF NEURON
Cell membranes cover all cells
- Two layers of fat molecules
- Tucked inside are channels made up
of protein molecules
- Protein molecules
a.Serve as receptors for NT’s
b.Serve as channels for ions (Ca++,
Na+, K+, and Cl-)
c.Location along neuron differs in
the type of channel protein
d. Membranes are dynamic and
alive
2 types of receptors
1.Ionotropic Receptors - fast acting
ion channel/receptor complex
same only a few
Neurotransmitter activate
them
2.Metabotropic Receptors-slower
acting ion channel and receptor
are different and most
neurotransmitters activate them
Neurofilaments
Cytoskeletons (Neurofilaments) inside
cell provide structural support
- Microfilaments
- Microtubules – Fairly large,
play important role in
transport
a.Send vesicles to the buttons
where they are filled with NT.
Acts like a conveyor belt.
Intracellularorganelles
Organelles within the cell
a. Mitochondria – Convert
glucose into energy we can
use: ATP
(energy source for cell)
b. Endoplasmic Reticulum –
Synthesis of fat molecules
and protein molecules
Synapse
Synapse - the junction between cells
(neurons).
synaptic cleft -space between cells
a.synapse is made of 3 parts:
1.Presynaptic cell– sending side of
synapse
2.Postsynaptic – receiving side of neuron
3.Synaptic Cleft
b.Purpose: promote chemical-
electrical signal
c. Types of Synapses:
(1)axodendritic, (2)axosomatic
(3)axoaxonic, (4) dendrodendritic
The neuron-physiology
Chemical Milieu of Cellular Spaces when the
neuron is “at rest”
Intracellular space & extra cellular space
(inside of cell membrane & outside of cell
membrane)
a.Cl- = Chloride (more outside than inside)
b.Na+ = Sodium (more outside than inside)
c.A- = Anions (more inside than outside)
d.K+ = Potassium (more inside than outside)
The neuron-physiology
Forces that maintain the chemical
balance
i.Concentration gradient –lesser
concentration
ii.Electrostatic pressure – attraction
toward opposite charges
iii.Na & K pumps – Throws out sodium
and takes in potassium to keep cell
balanced
Theneuron-physiology
Four states of neuronal electrical charge
(potentials)
a. Resting Membrane Potential
-70 mV (transient state, constantly
affected
by forces that increase or decrease charge)
b. Excitatory Post-Synaptic Potential or EPSP–
Charge across the membrane becomes less
negative
-depolarization of the neuron (i.e. decrease
negative charge from –70mV to –65mV)
-Leads to an action potential
Theneuron-physiology
c. Inhibitory Postsynaptic Potential or IPSP
Charge across the membrane becomes
more negative
- hyperpolarization of neurons (i.e.
increase in negative
charge from –70mV to –90 mV)
- Reduces the likelihood of an action
potential
d.Action Potential or AP
• Charge across the membrane becomes
less negative
•- depolarization of neurons (i.e.
decrease in negative charge from
–65mV to +55 mV)
-charge for the AP begins at Axon
Hillock
-significant shift in ions
Neurotransmitters
¼ 80 plus chemical substances
that provide communication
between cells. Some of these
are actually NTs and others
are neuromodulators (i.e.
they augment the activity of
the NT)
Amino Acid neurotransmitters
Glutamate GABA
¼Uses both ¼Uses ionotropic
ionotropic and receptors
metabotropic
receptors
¼ Most prevalent NT in
¼NT of the cerebral the CNS
cortex
¼Inhibitory effect
¼Excitatory effect

Seizure disorders are the caused by overactive Glutamate

and/or under active GABA.
Monoamine neurotransmitters

C atecholamines Indolamines
Dopamine
Serotonin
Norepinephrine

Epinephrine

They use both reuptake and enzymes

(e.g. MAO) to terminate action
NeurotransmitterAcetylcholine
¼ Two Receptors:
nicotinic receptor – uses ionotropic
receptor
muscarinic receptor – uses metabotropic
receptor

Degradation is through enzyme only:

acetylcholinesterase
Neuropeptides
¼ Long chains of amino acids
¼Numerous categories (see
appendix VII)
¼ One category is the
ENDORPHINS
¼ Enkephalins
¼ Beta-endorphin
Solublegases
¼Nitric Oxide – involved
in learning and memory
Neurotransmitters
Neurotransmitters have 7 actions
1. Synthesized
2. Stored
3. Enzymatically destroyed if not stored
4. Exocytosis
5. Termination of release via binding
with autorecptors
6. Binding of NT to receptors
7. NT is inactivated

Drugs are developed that address these

actions as an AGONIST (mimic the NT ) or
ANTAGONIST (block the NT)
Drugsthatblock reuptake of neurotransmitters

¼SSRIs (Selective
Serotonin Reuptake
Inhibitors)
¼ Cocaine
- highly addictive, both
physiologically and
psychologically
Tolerance and dependence
¼ Tolerance – state of decreased sensitivity to the
drug as a result of exposure to it.
functional tolerance (number of
binding sites is reduced – also called “down
regulation” of receptors)
note:opposite phenomenon: up-
regulation
¼ Physical Dependence – caused by withdrawal
symptoms (not the reason that people continue to
take most drugs)
¼ Psycholological Dependence (now called
positive-incentive theory of addiction)
GROSSANATOMY
ORGANIZATION OF
PARTS
Definitions
¼Nerve: collection of axons outside
CNS
¼Tract: collection of axons inside
CNS
¼Nucleus: collection of cell
bodies inside CNS
¼Ganglion: collection of cell bodies
outside CNS
Peripheral Nervoussystem
 Subdivisionsof the PNS
¼Sensory (afferent): receptors from
somatic or visceral organs to CNS
¼ Motor (efferent): from CNS to muscle
¼ Autonomic nervous system : afferent
and efferent from visceral organs
classified as parasympathetic and
sympathetic
Ganglia
¼ ganglia are composed mainly of somata
and dendritic structures which are
bundled or connected.
¼ Ganglia often interconnect with other
ganglia to form a complex system of
ganglia known as a plexus.
¼ Ganglia provide relay points and
intermediary connections between
different neurological structures in the
body, such as the peripheral and central
nervous systems.
Peripheralnerves
¼During ontogeny and phylogeny, somites
develop alongside the neuraxis up to the
midbrain where nerves are sent out.
¼ Each pair of sdomites receive a pair os
spinal nerves and spinal arteries.
¼The spinal cord innervates 30 somites: 8
cervical, 12 thoracic, 5 lumbar and 5
sacral.The brainstem innervates 10
starting with CN IIIthrough XII.
Peripheral nerve
Dermatomal Innervation -back
Dermatomal Innervation-front
Mnemonic fordermatomal distribution

¼ C2, C3, C4 – hooded cape distribution

¼ C5, C6, C7 – superior aspect of arm
¼ C7, C8, T1, T2 – inferior aspect of arm
¼ T4 – nipple level
¼ T10 – umbilicus
¼ L1 – groin
¼ L5 – large toe
¼ S1 – small toe
¼ S2, S3 - genitalia
Central nervoussystem
Brain and SpinalCord
The brain and spinal cord
are protected by a series of
membranes termed
meninges
Dura mater-outer (thick)
layer
Arachnoid-middle layer
Overlies the
arachnoid space (CSF)
Blood vessels run
through the arachnoid layer
Pia mater- inner layer
Overlies every detail
of the outer brain
Cerebrospinal fluid
¼ The brain floats in a pool of cerebrospinal fluid
(CSF) which reduces its net weight from 1400 g
--> 80g
¼ CSF is also contained within four
brain ventricles
¼ CSF is produced by the choroid plexus of each
ventricle
¼ The brain ventricles are an access point for
drug studies
¼ The brain ventricles can expand when brain
cells are lost (as in alcoholism or certain
diseases)
SPINALCORD
¼Divisions:
dorsal and ventral
¼Functional types of neurons: afferent
and efferent
1.All afferent systems except vision originates
in nodules of neurons called sensory ganglia
located outside the CNS on a CrN os SN
2.Efferent systems consists of somatic and
autonomic lower motoneurons lies within the
CNS but their axons exit into the PNS.
White matter tracts afferent and efferent
White Matter Tracts of the SpinalCord
Lamination of Axons of Spinothalamic Tract
3partsof the wholebrain
¼Cerebrum – brain’s higher
mental functions
¼Limbic System – primitive
unconscious area of the brain
including emotions
¼Brainstem and Cerebellum –
regulate bodily function and
movement
Organization of the Brainstem
¼Longitudinal
Layers
¼Transverse
1.tectum- roof
Subdivisions 2.tegmentum –
1. Mesenceph tracts and nuclei
alon 3.basis – bottom
2. Pons pyramidal and
3. Medulla corticopontine
tracts
Organization of the Brainstem
Generalized cross section of the
brainstem
Medulla
Pons
Pons at the level of the V nerve
Midbrain
The Reflex Arc –sensory receptor, dorsal root
ganglion, internuncial neuron, motor neuron,
effector organ
The Tegmental gray matter consists of CrN nuclei,
supplementary motor nuclei and reticular
formation.
¼ Cranialnerve (CrN) nuclei are scattered in
the tegmentum.
¼Supplementary motor nuclei occupy the
ventral half of the tegmentum:
¼ Midbrain contains substantia nigra and red
nucleus
¼ Pons constain pontine nuclei
¼ Medulla contains inferior olivary nuclei

¼Reticular formation- mixture of

perikarya, axons & dendrites
 Functions of Reticular Formation
¼ I Rostral Half – ponto-mesencephalic –
sends ascending pathways to thalamus
and cortex known as ascending feticular
activating system which mediates waking
state and consciousness
¼ II. Caudal half – mediates vital reflexes
related to breathing, feeding, homeostasis,
BP and PR, alimentation and elimination,
posture, and eye movements
¼ Pontine RF is necessary for sleep regulation
 Brainstemwhitematter
¼Transmits short, medium and long
ascending and descending pathways
¼ 1. medial longitudinal fasciculus connects
vestibular nuclei with III, IV, VI and spinal
cord
¼ 2. Lemnisci – relay to thalamic nuclei
¼ 3. Pyramidal and corticopontine tracts
¼ 4. Cerebellar pathways – afferent and
efferent tracts forming the cerebellar
peduncles
Diencephalon
TheCerebellum
 Cerebellum
¼ . VERMIS = Medial zone or (part of)
Spinocerebellum
¼ 2. PARAVERMIS = Intermediate zone or (part
of) Spinocerebellum
¼ 3. CEREBELLAR HEMISPHERES = Lateral
zone or Cerebrocerebellum (or
Pontocerebellum)
¼ 4. FLOCCULONODULAR LOBE =
Vestibulocerebellum
Cerebellumfunctions
¼ . VERMIS = axial motor fxn; balance (Fastigial
nuc) Spinocerebellum
¼ 2. PARAVERMIS = distal motor
fxn/execution (Globose & Emboliform)
Spinocerebellum
¼ 3. CEREBELLAR HEMISPHERES = motor
planning (Dentate)
Cerebrocerebellum
¼ 4. FLOCCULONODULAR LOBE = eye mvmt &
balance; vestibulo-ocular
reflex. Vestibulocerebellum
 Cerebellarcells
¼ Granule cell (only excitatory CELL) endings
(Parallel Fibers) go to Molecular layer but not out
of Cerebellar Ctx. Stellate, Basket, & Golgi cells
(inhibitory) do not project out of Cerebellar Ctx
either.
¼ Purkinje cell (only ones that project out of ctx)
inhibitory fibers from Cerebellar Ctx to Cerebellar
Deep Nuclei. Climbing fibers from Inf Olivary
Nuc via Inf Cerebell Ped.
¼ Cerebellar Deep Nuclei receive excitatory
afferents from Climbing fibers and Mossy fibers
(collaterals on their way to the Granule layer).
Cerebellarpeduncles
• ¼ . Sup Cerebellar Ped
(cerebellum to cerebral ctx =
dentatothalamic tract, VSCT)
• ¼ 2. Middle Cerebellar Ped

(cerebral ctx to cerebellum =

pontocerebellar fibers)

• ¼ 3. Inf Cerebellar Ped (spine to

cerebellum = DSCT, CCT, OCT,
vestibulocereb…JRB)
Cerebellum asModulator
¼The sensory system, the cerebellum,
basal motor nuclei, thalamic
somatomotor nuclei and motor cortex
function by modulating each other.
¼To modulate means to control thr force,
velocity, distance, amplitude and
trajectory of volitional movements and the
required sequence of activation of the
muscles.
Motor circuits modulatedby cerebellum
Diencephalon
¼ 4 subdivisions of nuclear zones which form
roof, walls and floor of IIIventricle:
¼1. Epithalamus
¼2. Thalamus dorsalis
¼3. Thalamus Ventralis (subthalamus)- basal
motor
¼4. Hypothalamus- controls homeostatic
and autonomic functions and emotional
expression
Diencephalon showing Thalamus
 ¼ Ant+MD/DM (Papez
Thalamus limbic emotion)
¼ VA/VL (GP+SN—EPS
motor)
¼ VPL (sensory--body)
¼ VPM (sensory--head)
¼ LGN (vision, Light)
¼ MGN (hearing)
¼ Pulvinar (sensory
association)
¼ Intralaminar CM (diffuse
to cerebral ctx, ends in
layer I for cortical excit)
¼ Reticular (GABA-ergic to
thal)
MRI Picture showing Diencephalon
Epithalamus
¼1. pineal body
¼2. habenula
¼3. membranous roof
plate of III ventricle
 Thalamus
¼Almost everything (except smell) that
enters or exits the cortex must submit to
thalamic modulation. Thalamic lesions
can impair mental, motor and sensory
functions
¼ 5 nuclei (1) sensory nuclei; (2)
somatomotor; (3) midline and intralaminar
nuclei (for consciousness); (4) association
nuclei; (5) limbic nuclei
The 12 Cranial nerves
Cranial nerve nucleiin brainstem
 Basal Ganglia- 5parts
¼Caudate – control of eye movements,
behavior and memory
¼Putamen- motor control
¼Globus pallidus- motor control
¼Subthalamic nucleus- motor control;
destruction results in hemiballismus
¼Substantia nigra- where dopamine is
produced
Limbic System –4 parts
• ¼ Amygdala –interprets taste; fight or
flight; alerting areas for fear, anger and
sadness
• ¼ Hypothalamus –registers and controls
temperature, libido, hunger, aggression,and
endocrine andautonomic systems
• ¼ Thalamus –modulates levels of awareness
and attention; relay organfor sensory cortex
• ¼ Hippocampus –lays down memories;
storage of memories as it connects to cortex
Amygdala
¼ In women, the amygdala is larger
than men. Which of the following
stereotypes might be explained by
this anatomic difference?
¼ (A) Women live longer than men.
¼(B) Women are more thoughtful
about emotions than men.
¼ (C) Women worry more than men.
¼ (D) Women seek more college
degrees than men.
Cerebralhemispheres
¼Frontal lobe – seat of conscious
ideas, plans, language and
movement
¼Parietal lobe – contains body
maps that responds to sensory
information
¼Temporal lobe – encodes long
term memories, process sound
input and language
¼Occipital lobe- receives stimuli
from the eyes and translates
them to perceptions
CorpusCallosum
¼A band of white matter
tissue or fiber tracts that
connect the right and left
cerebral hemispheres
Corpus
C allosum
6-Layered Neocortex
¼ Layer I (Molecular)
¼ Layer II (External Granular)—cortico-cortical
fibers in.

¼ Layer III (External Pyramidal)—cortico-cortical

fibers out.

¼ Layer IV (Internal Granular)—thalamocortical

fibers in (VPL, VPM, LGN).

¼ Layer V (Internal Pyramidal)—CS/CB, &

corticostriatal fibers out.
(Betz giant pyramidal cells)

¼ Layer VI (Multiform)—corticothalamic fibers out.

CORTICOSPINAL TRACT
Area 4 (primary motor ctx)
Area 6 (premotorctx)
Area 3,1,2 (primary sensory ctx)
corona radiata

post limb of Internal Capsule

crus cerebri (cerebral peduncles)
pontine CS fibers
pyramids (decussation)
lateral CS tract (85-90% crossed)
ventral/med CS tract (10-15%uncrossed)
Motor nerves Muscles
Corticospinal tract or Pyramidaltract
ANTEROLATERAL SYSTEM
(SPINOTHALAMIC TRACTS
Area 3,1,2(primarysensory ctx)

VPL ofthalamus

Ant &Lat Spinothalamic Tracts (ALS)

Lissauer’s tract - (lamina I)

(dorsolateral fasciculus of spinal cord)
Substantia gelatinosa (lamina II)
Ventral/Ant White Commissure
Sensory nerve receptors
Spinothalamic tract
What’s wrong with
his gait?

Where isthe
lesion?
Clinical correlations
¼ Cerebral hemisphere lesions cause
contralateral motor and sensory
signs.

¼Cerebellar hemisphere lesions

causeipsilateral motor signs
What is the problem in the eye
movement? Where is the lesion?
Which side is
abormal?

Where is the lesion?

What is the difference in the 2 faces?
CN VII
Summaryof Clinical syndromesat variouslevels of the
motor system
¼ Lower motor neurons – paralysis of
individual muscles
¼ Upper motorneurons –contralateral
paralysis of groups –hemiplegic,
quadriplegic, paraplegic, triplegic
¼ Basal motor nuclei – rigidity, bradykinesia,
postural instability, involuntary movements
that is unilateral or bilateral
¼ Cerebellum – ataxia, hypotonia, tremor
during movement ipsilateral to lesion
Imaging the
brain and spinal
cord
Through the eyes of
Radiology
SkullX-ray AP
SkullX-ray - Lateral
CTand MRIat base ofbrain
CTand MRIatmidbrain
CTand MRIat cerebralcortex
References
¼ Kandel et al, Principlles of Neural Science
4th edition,McGraw Hill,2000
¼Biller,Gruener, and Brazis, DeMyer’s The
Neurologic Examination, McGraw Hill, 2011.
Chap. 2 (review of Clinical Neuroanatomy.
¼ Clinical
Radiology
¼Internet (Neuroanatomy powerpoint
presentation)