Chemical Control of the Brain

and Behaviour

Copyright: UTS, Neuroscience, Bear et al., Porth et al., LWW

Andreassi, Erlbaum
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Objectives
Bear et al., - Chapter 15

After this session you should be able to:

 Describe and label the functional areas of the hypothalamus
 List the relevant hormones and describe the secretory functions of the
hypothalamus
 Discuss the 2 main divisions of the autonomic system
 The sympathetic nervous system
 The parasympathetic system
 Describe the neurotransmitters in autonomic system
 Describe how the diffuse modulatory systems of the brain exert control
 The locus coerulus
 The raphe nuclei
 The Substantia Nigra/Ventral Tegmental Areaa
 The basal forebrain complex
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Introduction
Organisation of synaptic connections are important to
brain function & control

Point-to-point connections
 Restricts synaptic communication to specific, appropriate
areas (a)
 Requires site-specific neurotransmitters with rapid, brief
action for normal function

Brain areas with expanded influence (Space and time )

 The secretory hypothalamus influences functions
throughout the brain and body
 Via hormones secreted into the blood (b)
 Via the Autonomic Nervous System (ANS) (c)

 The Diffuse modulatory systems of the CNS (d)

 Regulate diverse functions including mood and
arousal

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The Limbic System

 A region of cerebral grey matter that acts as a link between higher cognitive
functions, vegetative functions and more primitive emotional responses.
 The hypothalamus is a major part of the Limbic system which is vital to
neuroendocrine control of motivational drives and emotional behaviour.
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The Hypothalamus
Location
 Hypothalamus is inferior to the thalamus
forming the walls of the 3rd ventricle.
 It is connected to the pituitary gland by a
stalk, the infundibulum

Differences between thalamus and

hypothalamus

Functions are quite different

 Thalamic defect
 Causes lack of feeling, blind spot,
discrete sensory or motor deficits
 Hypothalamic defect
 Causes fatal disruption to body
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Hypothalamic Structure
Three functional zones in the hypothalamus
 Lateral, Medial, and Periventricular

The periventricular zone receives input from the other zones, the brain stem and
telencephalon. Contains a complex mix of neurons with varied functions:
 Suprachiasmatic nucleus (SCN) - Circadian rhythms
 Periventricular cells  ANS innervation and control of viscera
 Periventricular neurosecretory cells  secrete hormones into the blood stream

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Hypothalamic Function
 Mainly concerned with effects of the periventricular neurosecretory neurons
that has axons which extend down the pituitary stalk
 The pituitary is the “mouthpiece” i.e. how the Hypothalamus communicates
with the body

 The hypothalamus integrates somatic and visceral responses in accordance

with the needs of the brain and environmental stimuli / change.

 The hypothalamus is crucial to homeostasis regulating physiology via

neuroendocrine secretions, in response to changes in the external
environment
 Body Temperature, Blood pressure, Blood composition & pH to cope with
environmental change

 Tiny changes and/or damage can cause dramatic or fatal disruption to a wide
variety of physiological functions

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The Pituitary
Axons of Hypothalamic magnocellular
neurosecretory cells extend into the pituitary
stalk and into the post pituitary.
 The post pituitary is really part of the brain

 The magnocellular neurons secrete 2

neurohormones into the blood
 Oxytocin
 Lactation, suppress hypothalamic
function
 Vasopressin /Antidiuretic Hormone
 Regulates blood volume and salt
concentration

 These are stored in the post pituitary and

released into circulation when needed

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The Kidneys & the Brain
The hypothalamus is crucial in control of fluid balance,
and maintenance of blood volume
 However there is a vital driving force from the
kidney to achieve the control

When blood volume OR blood pressure drops the

responses are 2-fold:
1. Renin is produced in the kidney which sets off
renin-angiotensin cascade. This produces
Angiotensin II, a vasoconstrictor that increases BP.

2. Telencephalon subfornical cells detect change,

and stimulate the Hypothalamus to secrete ADH.
 ADH stimulates facultative reabsorption of
H2O in the kidney DCT, thus increasing blood
vol and BP
 Activate lateral hypothalamic cells to
stimulate thirst and drinking behaviour
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Hypothalamus & Pituitary
 The Anterior Pituitary is controlled by
parvocellular neurosecretory cells of
the hypothalamic periventricular area

 These cells do not have extending

axons, but secrete hypophysiotropic
hormones into a portal circulation
originating in the floor of the 3rd
ventricle

 Releasing / tropic hormones travel to

the Ant Pituitary receptors and activate
cells to secrete or STOP secreting
hormones into circulation
 Examples are ACTH, TSH, GH, FSH

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The Stress Response
 Periventricular hypothalamus secretes
Corticotropin- releasing Hormone (CRH)
into the portal circulation in response to
stress.

 Within approx 15 secs ACTH released into

circulation.

 ACTH stimulates Cortisol release from

adrenal cortex to mobilise energy and
enable us to cope with stress

 Cortisol is a steroid and is lipophilic, it can

readily cross the blood brain barrier

 Negative feedback due to plasma cortisol

levels controls the process
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Hypothalamus & the ANS
The Hypothalamic periventricular zone also controls the Autonomic nervous
system (ANS)

 The ANS is an extensive network of neurons widely distributed inside the

body cavity. Its activities are automatic - no conscious control and highly co-
ordinated with parallel actions by the 2 divisions.

Divisions of autonomic nervous system (ANS)

 Sympathetic division
 Increased heart rate and blood pressure, depressed digestive function, mobilized
glucose reserves

 Parasympathetic division
 Slower heart rate, fall in blood pressure, increased digestive functions, stop
sweating

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ANS vs Somatic Motor
 The somatic motor system has a single function - innervating and
controlling skeletal muscle fibres (voluntary action)

 The ANS controls every other tissue and organ in the body (involuntary
action)
Cell bodies of somatic
lower motor neurons lie
in the CNS

Cell bodies of ANS lower

neurons lie outside the
CNS in ganglia

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Autonomic Nervous System

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Autonomic Nervous System
The divisions act in parallel but use distinct pathways with different stricture and different
neurotransmitters
 Sympathetic - preganglionic axons emerge from thoracolumbar outflow (mid 1/3 of spinal cord)
 Parasympathetic - preganglionic axons emerge from the brain stem and sacral spinal cord,
craniosacral outflow
 Thus the 2 systems complement each other anatomically

Sympathetic preganglionic neurons lie within the intermediolateral gray matter of the
spinal cord.
 Send axons thru ventral roots & synapse on neurons in the ganglia of the sympathetic chain next
to the spinal column or within collateral ganglia in the abdominal cavity

Parasympathetic preganglionic neurons sit within the brain stem nuclei and the sacral
spinal cord
 Axons tend to travel in cranial nerves as well as nerves of the sacral spinal cord, thus travel
farther than sympathetic axons
 i.e. parasympathetic ganglia are typically located next to, on, or in the target organs

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Autonomic Nervous System
1. Innervates
 Secretory glands - sweat, saliva, tears, mucous
 Heart and blood vessels -controls BP and flow
 Bronchi of lungs -meets O2 demands
2. Regulates
 Digestive and metabolic functions of liver, GIT, pancreas
 Functions of the kidney, urinary bladder, large intestine and rectum
3. Essential
 For sexual responses of genitalia and reproductive organs
4. Interacts
 With the immune system

Physiological influences are generally in opposition but reciprocal i.e. some activity in both e.g.

Crisis: High Sympathetic activity -fright, fight, flight

Low parasympathetic activity
Rest: High Parasympathetic activity - feed and breed, digestion, growth, immune response,
reproduction
Low sympathetic activity
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The Enteric Division
Considered the “little brain“ of the ANS, since it has a great deal of independence,
controls many physiological processes and has approximately the same number of
neurons as entire spinal cord

Location:
 Lining of oesophagus, stomach, intestines, pancreas, and gallbladder

Composition:
 Two complicated networks- myenteric (Auerbach's) plexus and submucous
(Meissner's) plexus

Function:
 Control physiological processes involved in transport, enzyme secretion and
digestion of food

Inputs:
 From brain via axons of the sympathetic and parasympathetic divisions

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Control of the ANS
Connections for Autonomic control
 Hypothalamic Periventricular zone connections to brain stem
and spinal cord nuclei
 Nucleus of solitary tract in the brain stem

Function of solitary nucleus

 Important centre for autonomic control of vegetative functions
 Integrates sensory information from internal organs (including
taste information from the tongue) and coordinates output as
appropriate
 No conscious control

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Neurotransmitters
The ANS is outside the blood brain barrier (BBB) so there is direct access for drugs

Study of the ANS: Better understanding of drug mechanisms influencing synaptic

transmission (vs. CNS)

1. Preganglionic Neurotransmitters
 Primary neurotransmitter is Acetylcholine (ACH) for both Sympathetic and
parasympathetic ANS peripheral neurons
 ACH: Binds to nicotinic receptor (nAChR), evokes fast EPSP, excitatory effect

 Ganglionic ACH can do more than neuromuscular ACH and also bind to
muscarinic receptor (mACHR), which are Metabotropic (G-protein coupled)

 Ganglionic ACH: Activates mACHR, slow EPSPs and IPSPs (inhibitory effect)
 Preganglionic terminals: Small EPSPs
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Preganglionic Neurotrans
 Small EPSPs last for several minutes

 Due to Neuropeptide Y (NPY) and vasoactive intestinal

polypeptide (VIP) that interact with G-protein-coupled receptors
 NPY and VIP have a modulatory effect - make postsynaptic neurons more
responsive to fast nicotinic effects

 Need more than one Action Potential to stimulate the release of

NPY and VIP

 The number of APs is variable and thus the pattern of firing in the
relevant preganglionic neurons is important in determining the
type of postganglionic activity evoked
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Postganglionic Neurotrans
Postganglionic neurons stimulate autonomic motor activity
 e.g. glandular secretion, Contraction and relaxation of sphincters

2. Postganglionic Neurotransmitters
 Parasympathetic: Release Acetylcholine (ACh)
 Local effect  Acts only through mAChRs
 Sympathetic: Release Nor Adrenalin (NA) / Nor epinephrine (NE)
 Far-reaching effect  circulates in blood enabling wide spread
 Can predict effects of drugs that interact with cholinergic / noradrenergic
systems

Parasympathomimetic:
 Mimic or promote muscarinic actions of ACh or inhibit actions of NE
Sympathomimetic:
 Mimic or promote NE actions or inhibit muscarinic actions of Ach
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Diffuse Modulatory Systems
 Collection of neurons (neurohormonal systems) with widespread pattern of axons
 Regulate/Modulate impact of postsynaptic activity  vital to motor control,
modulation of mood, memory, motivation and metabolism

Anatomy and Functions

The Four systems are:
 Noradrenergic (Locus Coeruleus)
 Serotonergic (Raphe Nuclei)
 Dopaminergic (Substantia Nigra and Ventral tegmental Area)
 Cholinergic (Basal Forebrain and Brain Stem Complexes)

Common principles:
 Small set of neurons at core
 Arise from brain stem
 One neuron influences many others
 Synapses release transmitter molecules into extracellular fluid, this diffuse to
many neurons (not confined to synaptic cleft)
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Diffuse Modulatory Systems
Focus on systems that use one of the following neurotransmitters
 Noradrenalin (NA / NE), Serotonin (5-HT), Dopamine (DA),
Acetylcholine (Ach)
 All of these activate specific metabotropic (G-
proteincoupled) receptors

These G-protein-coupled receptors mediate the effects of the

neurotransmitters

Functions of the diffuse modulatory systems depend on

 How electrically active they are
 How much neurotransmitter is available for release
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Noradrenergic System
 The NA Locus Coeruleus is a tiny
“blue spot” in the Pons
 Bilateral structure, axons fan out
to approx “every part of the brain”
 One of its neurons can make 250,000
synapses
 VERY diffuse

 Path: Axons innervate cerebral cortex,

thalamus, hypothalamus, olfactory bulb,
cerebellum, midbrain, spinal cord

 Function  Involved in regulation of attention, arousal, sleep-wake cycles,

learning and memory, anxiety and pain, mood, brain metabolism
 Activation of LC neurons: New, unexpected, nonpainful sensory stimuli

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Serotonergic System
 Nine Raphe nuclei
 Lie on either side of the midline
of the brain stem each project to
different brain regions

 Serotonin containing neurons

 Path  Innervate many of the same

areas as noradrenergic system

 Function  Together with noradrenergic system, comprise the ascending

reticular activating system
 Raphe system particularly involved in sleep/wake cycles as well as mood

 Activation of RN neurons  novel, unexpected, nonpainful sensory stimuli

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Dopaminergic System
Dopamine is a crucial CNS neurotransmitter

 Substantia Nigra
 Arises in the midbrain, projects to the
striatum
 Facilitates the initiation of voluntary
movements ( NB Parkinson’s Disease)

 Ventral tegmental area

 Innervates circumscribed region of
telecephalon (include frontal cortex & parts of the Limbic system)
 Mesocorticolimbic dopamine system
 Dopaminergic projection from midbrain

 Involved in psychiatric disorders; reward and reinforcement of behaviour

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Cholinergic System
Basal forebrain complex
 Scattered Cholinergic neurons
in several related nuclei
 Core of telencephalon, medial and
ventral to basal ganglia
 Best known - medial and septal nuclei
innervate hippocampus and
basal nucleus of Meynert

Function: Unknown, participates in learning

and memory (possibly Alzheimer’s?)

Pontomesencephalotegmental complex
 Releases Ach  acts on dorsal thalamus
 Function  Regulates excitability of thalamic sensory relay nuclei

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Drugs and the DMS
 Psychoactive drugs: Act on CNS, interfere with Chemical synaptic
transmission

 Many drugs of abuse act on modulatory systems, particularly the

noradrenergic, dopaminergic and serotonergic systems

Hallucinogens
 Lysergic acid diethylamide (LSD), Psilocybe mushrooms, and peyote cactus
close to structure of serotonin

Stimulants
 Cocaine and amphetamine affect dopaminergic and noradrenergic systems
 Sympathomimetics

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Drugs and the DMS
 Stimulants block Catecholamine reuptake
 Cocaine targets DA reuptake.
 Amphetamine blocks NE and DA reuptake and stimulates DA
release

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Conclusion
 Three components of nervous system characterised
by the great reach of their influences:
 Secretory hypothalamus (all over the body)
 Autonomic nervous system (all over the body)
 Diffuse modulatory systems (all over the brain)

 Detailed level
 Each system performs different functions

 General level
 All work to maintain brain homeostasis.

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