UNIT XI: Neuroscience II, W3

PHYSIOLOGY OF THE HYPOTHALAMUS

Prof. Laiche Djouhri, PhD
Department of Basic Medical
Sciences
College of Medicine H

Email: ldjouhri@qu.edu.qa
 Objectives
 Outline the functions of hypothalamus

 Outline the behavioral functions of the

hypothalamus

 Describe some of the basic disorders

associated with hypothalamic
dysfunctions.
 Outline the functions of brain
neurotransmitters
Chapter 59
Behavioral and Motivational Mechanisms of the
Brain—The Limbic System and the Hypothalamus
Chapter 72
Dietary Balances: Regulation of Feedings…
2
 The Hypothalamus
 Anatomically, it is part of diencephalon, but
functionally, it is part of the limbic system

 Is a small portion of brain (~4 cm3, or ~ 0.3%

brain volume, ~4g).

 Is a collection of nuclei and associated

fibers.

 It is essential for life and acts mainly through

3 systems:
• Autonomic nervous system
• Endocrine system
• Limbic system
Hypothalamus is a Central Element of Limbic System
 From a physiological point of view,
it is one of the central elements of
the limbic system

 One of the most important of the

control pathways of the limbic
system.

 It is “the brain of the brain”!

 It controls most of the vegetative
and endocrine functions of the body
and many aspects of emotional
behavior.
 There is hardly a tissue that is not
influenced by hypothalamus
 Much of the limbic system output is coordinated
by hypothalamus into behavioral & endocrine
responses.
 The Hypothalamic Nuclei

❼
PPASS

❽
❾ ❷
❿
❸
⓫

 Influence sympathetic
 Influence parasympathetic ❺ ❹ responses
responses ❻
Above tuber cinereum
Putative Functions of Different Hypothalamic Nuclei
❶ Thirst, hunger & emotions Anterior Posterior
❼
(reword) BP & HR (PSNS)
BP & HR (SNS)
❷ Heat production (e.g. shivering)
❸ Feeding reflexes (e.g., swallowing)
❹
❹ Food intake/appetite control
❺ Satiety ❽
❷
❻ Food intake & appetite.
❼ Release of oxytocin & (ADH) ❾
❽ Sleep ❶
❾ Heat loss (e.g., sweating) ❿
❿ Release of oxytocin & (ADH)
⓫ Biological clock ⓫ ❺

⓬Periventricular nucleus(not ❻ ❸
shown, fear & punishment)

 Sexual drive: several nuclei

What are the Functions of the Hypothalamus?
Behavioral Functions Endocrine Vegetative
 Feeding regulation: Functions Functions
(Lateral &  Site of synthesis  Cardiovascular
Ventromedial nuclei) and release of regulation
 Reward/pleasure posterior pituitary  Body
(Lateral H) hormones temperature
 Fear & punishment  Secretion of regulation
reactions hypothalamic  Body water
(Periventricular nucleus) releasing or regulation
 Sexual drive (various inhibitory
parts) hormones
Hypothalamic Functions: Feeding Regulation-1
 There are 2 H. centers
for feeding regulation:
1. Feeding center in
the lateral
hypothalamic area

2. Satiety center in the

ventromedial nucleus 1 2

What happens when areas in these centers are stimulated or destroyed by lesions ?
Hypothalamic Functions: Feeding Regulation-2
Feeding center in lateral hypothalamic area
A. Stimulated B. Destroyed

 Desire for food search  Loss of appetite & desire for

 Intense desire to drink food and drink
 Extreme hunger  Sometimes lethal starvation
 Great appetite  Extreme passivity, with loss of
most drives
Hypothalamic Functions: Feeding Regulation-3
Satiety center in the ventromedial nucleus
A. Stimulated B. Destroyed

 Loss of appetite  Voracious appetite

 Complete loss of desire  Animal can not be satiated
for food  Tremendous obesity
 Cessation of eating  Hyperactivity, often frequent
bouts of extreme rage upon slightest
provocation.
Feedback Mechanisms for Control of Food Intake
 The hypothalamus Paraventricular nuclei
receives:
 Neural signals from GIT
Dorsomedial
about stomach filling: inhibit
nuclei
food intake (-)
 Signals from GIT hormones (e.g.
CCK, PYY & insulin): suppress
further feeding (-)
 Signals from hormones released  Cross talk
by adipose tissue (e.g. Leptin): between
inhibit food intake (-) neurons
 Signals from the Ghrelin
hormone (from stomach): Fig. 72-2
stimulate appetite (+) POMC= pro-opiomelanocortin
CART = cocaine-amphetamine-regulated transcript
 Arcuate nuclei are the sites where these Fig. 72-1 (α-MSH) = α–melanocyte-stimulating hormone
hormones converge to regulate food intake AGRP = agouti-related protein
Summary of Hypothalamic Feeding Regulation
 Hypothalamic regulation of food intake:
1. Involves several nuclei including paraventricular, dorsomedial & arcuate
2. Depends on interactions of two area:

Feeding center: Satiety center

 In lateral hypothalamus
 It is tonically activated.
 Its stimulation »»» increase eating.
 Its destruction »»» fatal anorexia.
 In ventromedial nucleus
 Its stimulation causes cessation of
eating.
 It acts by inhibiting the activity of the
feeding center.
 Its destruction »»» hyperphagia &
obesity.

 Mammillary bodies are also involved in control of GI tract activity e.g.

feeding reflexes (licking the lips & swallowing)
 Lesions of paraventricular nuclei often cause excessive eating
 Lesions of dorsomedial nuclei usually depress eating behavior
Hypothalamic Functions: Fear & Sexual Drive
 Fear and punishment
reaction:
 Most potent area is
the periventricular
nuclei
 Sexual drive (most
anterior & most 2
posterior hypothalamic 1
Lateral
hypothalamus
parts and several other
Ventromedial
areas)
 Lesions in these areas may result in opposite effects such as no fear and
decreased libido (sex drive)
Hypothalamic Functions: Rage Behavior
 Strong stimulation of periventricular zone & lateral hypothalamus causes the animal to:

 Develop a defense posture

 Extend its claws & lift its tail
 Hiss, spit, growl & piloerection
 Wide-open eyes & dilated pupils
 Immediate savage attack upon slightest
provocation
 This pattern of behavior is called rage

 In normal animal, rage behavior is inhibited by signals from the

ventromedial nucleus of the hypothalamus & other limbic areas
Hypothalamic Functions: Reward/Pleasure-1
 Dopamine plays a key role in  These structures form neuronal
substrate for reward
reward  Lateral hypothalamus is a major
 Dopaminergic neurons from VTA potent reward area (believed !)
(midbrain) project to the reward
structures ( see diagram)
 VTA receives direct or indirect
feedback from prefrontal cortex
 All these structures communicate
with hypothalamus to initiate
responses to reward

 The reward & punishment centers

control our bodily activities & our drives
 Almost every behavior is related in  Tranquilizers (used in psychotic states)
some way to reward or punishment. inhibit both the reward & punishment centers
Hypothalamic Functions: Reward/Pleasure-2
 Major potent reward centers include lateral hypothalamus (multifunctional)
 Weak stimuli result in a sense of reward (placidity & tameness)
 Strong stimuli cause a sense of punishment.

 Less potent reward centers

include:
• Septum
• Amygdala,
• Certain areas of thalamus
• Certain basal nuclei

 A rat will self deliver up to 5000 stimulations per hour, and will reject food
even when starving, in preference for pleasure derived from self stimulation.
Hypothalamic Functions: Circadian Rhythms
 Suprachiasmatic nucleus (SCN) serves as a
“master biological clock”
 It controls physiological & behavioral
circadian rhythms, including sleep-wake
cycle, hormonal secretion &
thermoregulation
 Intrinsic activity of SCN is regulated by:
• Light input from retina
(retinohypothalamic tract)
• Secretion of melatonin from pineal
gland (high at night & low during the day )
 SCN sends projections through
hypothalamic nuclei that influence
endocrine secretion, eating, temperature
regulation & pineal gland
Endocrine Functions of the Hypothalamus-1
Paraventricular N.
CRH Supraoptic nucleus

TRH

GHRH

Vasopressin
Oxytocin

GRH

TRH

GRH
Endocrine Functions of the Hypothalamus-2

 The pituitary
hormones
are controlled
by either
neuronal or
hormonal
signals from
hypothalamus
Hypothalamic Functions: Temperature Regulation
A. Responses to Heat B. Responses to cold
Pre-optic area & Anterior N activates Posterior N. activates heat generating
heat losing mechanisms: mechanisms:

 Hyperthermia (lesions in PO & anterior area)  Poikilothermia (lesions in PN)

 Hypothalamic Dysfunctions
Hypothalamic diseases/lesions can
cause opposite effects to those caused
by stimulation:
 Insomnia (lesions in VLPO)
 Hypersomnia (lesions in posterior area)
 Weight loss (lesions in lateral n)
 Obesity (VMN)
ADH Syndrome of Inappropriate
ADH (SIADH)  Hyperthermia (lesions in anterior area)
 ADH  Poikilothermia (lesions in posterior area)
Symptoms: Symptoms:  Visual defects or even blindness
 Polyurea  20 L/day  Too much water in (lesions of the optic chiasm)
 Hypothalmic hamartoma (benign
(normal  1.5 L/d): blood & low urine
 Polydipsia (excessive output tumor causing seizures of laughing
thirst/drinking)  Mental status episodes, associated with irritability and
changes & coma aggression)
Functions of Some Brain Neurotransmitters
 ❶ Cholinergic system (Acetylcholine)
 ❷ Noradrenergic system (Noradrenaline)
 ❸ Dopaminergic system (Dopamine)
 ❹ Serotoninergic system (Serotonin)
❺ Glutamatergic system (Glutamate)
❻ GABAergic system (GABA)
 For the first 4 neurotransmitters refer to the
previous lecture on the Limbic System
 ❺ The Glutaminergic System
 Glutamate is the most
commonly found NT in the
brain (king of NTs, ~50%
neurons).
 Can cause excitotoxicity:
is converted in astrocytes
into glutamine (not toxic)
and passed onto
glutaminergic neurons
Glutamatergic neurons are found throughout the CNS, but high levels in
the cerebral cortex, limbic system, brain stem & spinal cord
❺ Functions & Disorders of Glutamatergic System

 Memantine (Namenda), an NMDA receptor

antagonist, slows down the symptoms of
Alzheimer`s disease.
❻ Functions & Disorders of GABAergic System

 GABA is the main inhibitory NT in CNS.

 GABAergic inhibition is seen at all CNS levels
GABA interneurons are abundant in the brain, with ~ 50% of inhibitory
synapses in the brain being GABAergic.
Depressant drugs (alcohol, barbiturates) work by increasing GABA activity
 The Fabulous GABA Receptors
 There are 3 types: Multiple binding sites
GABA A , GABA B & GABA C
 GABA A & GABA B receptors are widely
distributed in CNS.
 GABA C receptors (in retina only)
 GABA B are metabotropic (increase K+
conductance and decrease Ca+2 influx).
 GABA A & GABA C receptors
(ionotropic) have multiple binding sites
for CNS depressants
 The channel is a Cl- channel

 Activation of GABA receptors causes

IPSPs resulting in synaptic inhibition 26
 Unit XI

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