Hypothalamus Input/output pathways Physiological function of - - PDF document

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Hypothalamus

maike.glitsch@dpag.ox.ac.uk

Lecture outline

• Structural organisation of hypothalamus

– Localisation + nuclei – Input/output pathways

• Physiological function of hypothalamus

Overview of anatomy

chiasmatic tuberal

posterior anterior

medial view

Amygdala

Mamillo-thalamic tract Dorsal hypothalamic area

Lateral hyothalamic area Supraoptic nucleus

Optic tract Ventromedial nucleus Arcuate nucleus Median eminence

Lateral tuberal nucleus

Fornix Dorsomedial nucleus

Amygdala

Medial forebrain bundle Third ventricle

Overview of anatomy

coronal view

Overview of physiological functions

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Overview of physiological functions

• Maintenance of milieu interne
• Behaviour
• Memory

Regulation of energy metabolism (food intake, metabolic rate, temperature regulation, growth) Reproductive function (including milk production, social interactions) Biological clock, sleep-wake cycles Control of blood flow (cardiac output, blood osmolarity and renal clearance, thirst regulation)

Overview of physiological functions

• Maintenance of milieu interne
• Behaviour
• Memory

Regulation of energy metabolism (food intake, metabolic rate, temperature regulation, growth) Reproductive function (including milk production, social interactions) Biological clock (sleep-wake cycles) Control of blood flow (cardiac output, blood osmolarity and renal clearance, thirst regulation)

Overview of physiological functions

Regulation of the autonomic nervous system Release of hormones

Hypothalamic neurons can release hormones (neuro-endocrine)

Overview of physiological functions

• Detection of (changes in)

Blood osmolarity Blood nutrient levels Blood hormone levels Body temperature Directly and indirectly

Overview of connections

• Input from

Retina (retinohypothalamic tract – terminates in SCN) Olfactory receptors (medial forebrain bundle) Cutaneous receptors Higher (limbic) system (hippocampal formation: fornix – to mammillary bodies; amygdala: stria terminalis – to medial hypothalamus) Viscera

Overview of connections

• Output to

Thalamus (via mammillothalamic tract (Papez circuit: cingulate

gyrus – hippocampal formation – mammillary bodies – anterior thalamic nucleus – cingulate gyrus)) (also mammillotegmental tract to midbrain tegmentum)

Amygdala (from medial hypothalamus) Midbrain PAG (from medial hypothalamus) (aggression, rage,

flight)

Frontal and parietal lobes, habenular nucleus, midbrain… Blood stream (pituitary)

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Overview of basic functions

• Feed-back system

– Hypothalamus corrects deviations from a given set-point:

• measures current value
• compares current value

with supposed value

• makes adjustments to

achieve supposed value

– helps maintain body homeostasis

Overview of basic functions

• Feed-back system

– Hypothalamus corrects deviations from a given set-point:

• measures current value
• compares current value

with supposed value

• makes adjustments to

achieve supposed value

– helps maintain body homeostasis

• Feed-forward system

– Hypothalamus can over- ride feed-back under special conditions

• Stress responses
• Fever (body T set point is

changed to higher T)

Overview of basic functions

• Feed-back system

– Hypothalamus corrects deviations from a given set-point:

• measures current value
• compares current value

with supposed value

• makes adjustments to

achieve supposed value

– helps maintain body homeostasis

• Feed-forward system

– Hypothalamus can over- ride feed-back under special conditions

• Stress responses
• Fever (body T set point is

changed to higher T)

• Anticipation

– Hypothalamus adjusts its output to meet future needs

• Insulin secretion prior to

food intake

• Look at neuroendocrine functions of

hypothalamus

• Look at regulation of non-endocrine

functions (ANS) of hypothalamus

Neuroendocrine hypothalamus

• Hypothalamic neurons can act as neuroendocrine

cells

• Neurotransmitter = (neuro)hormone is released

directly into blood stream

• Site of hormone release is pituitary gland
• 2 principal pathways for eliciting hormone release:

– Via the anterior pituitary (adenohypophysis)

• 2-tiers process

– Via the posterior pituitary (neurohypophysis)

• 1-step process

Neuroendocrine hypothalamus

• Via anterior pituitary

(adenohypophysis) – Hypothalamic parvocellular neurons release releasing or inhibiting hormones into hypothalamo-pituitary portal veins – Hypothalmo-pituitary portal veins carry these hormones to anterior pituitary – Anterior pituitary has cells responding to the different releasing or inhibiting hormones – Responsive cells release or stop releasing hormones in response to binding of hypothalamic releasing or inhibiting hormones into systemic circulation

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Neuroendocrine hypothalamus

• Via anterior pituitary

(adenohypophysis) – Hypothalamic parvocellular neurons secrete releasing or inhibiting hormones into hypothalamo-pituitary portal veins – Hypothalmo-pituitary portal veins carry these hormones to anterior pituitary – Anterior pituitary has cells responding to the different releasing or inhibiting hormones – Responsive cells release or stop releasing hormones in response to binding of hypothalamic releasing or inhibiting hormones into systemic circulation

R I Anterior Pituitary Hypothalamus

Neuroendocrine hypothalamus

• Via anterior pituitary

(adenohypophysis) – Hypothalamic parvocellular neurons secrete releasing or inhibiting hormones into hypothalamo-pituitary portal veins – Hypothalamo-pituitary portal veins carry these hormones to anterior pituitary – Anterior pituitary has cells responding to the different releasing or inhibiting hormones – Responsive cells release or stop releasing hormones in response to binding of hypothalamic releasing or inhibiting hormones into systemic circulation

R I Anterior Pituitary Hypothalamus

Neuroendocrine hypothalamus

• Via anterior pituitary

(adenohypophysis) – Hypothalamic parvocellular neurons secrete releasing or inhibiting hormones into hypothalamo-pituitary portal veins – Hypothalamo-pituitary portal veins carry these hormones to anterior pituitary – Anterior pituitary has cells responding to the different releasing or inhibiting hormones – Responsive cells release or stop releasing hormones in response to binding of hypothalamic releasing or inhibiting hormones into systemic circulation

R I Anterior Pituitary Hypothalamus

Neuroendocrine hypothalamus

• Via anterior pituitary

(adenohypophysis) – Hypothalamic parvocellular neurons secrete releasing or inhibiting hormones into hypothalamo-pituitary portal veins – Hypothalamo-pituitary portal veins carry these hormones to anterior pituitary – Anterior pituitary has cells responding to the different releasing or inhibiting hormones – Responsive cells secrete or stop secreting hormones in response to binding of hypothalamic releasing or inhibiting hormones into systemic circulation

R I Anterior Pituitary Hypothalamus

GnRH gonadotrope FSH+LH gonads CRH corticotrope ACTH TRH thyrotrope TSH thyroid GHRH somatotrope GH Sost somatotrope GH DA lactotrope prolactin

Rel./Inhib. hormone:

GnRH gonadotrope FSH+LH gonads CRH corticotrope ACTH TRH thyrotrope TSH thyroid GHRH somatotrope GH Sost somatotrope GH DA lactotrope prolactin

Rel./Inhib. hormone:

• Ant. Pit.

target cell:

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GnRH gonadotrope FSH+LH gonads CRH corticotrope ACTH TRH thyrotrope TSH thyroid GHRH somatotrope GH Sost somatotrope GH DA lactotrope prolactin adrenal gland mammary glands many cells (bones)

Rel./Inhib. hormone:

• Ant. Pit.

target cell: Hormone: target:

GnRH gonadotrope FSH+LH gonads CRH corticotrope ACTH TRH thyrotrope TSH thyroid GHRH somatotrope GH Sost somatotrope GH DA lactotrope prolactin adrenal gland mammary glands

arcuate arcuate para- ventri- cular (PVN) arcuate anterior HT

many cells (bones)

release from: Rel./Inhib. hormone:

• Ant. Pit.

target cell: Hormone: target:

Neuroendocrine hypothalamus

• Via anterior pituitary

– Hypothalamic parvocellular neurons release releasing or inhibiting hormones into hypothalamo-pituitary portal veins – Hypothalmo-pituitary portal veins carry these hormones to anterior pituitary – Anterior pituitary has cells responding to the different releasing or inhibiting hormones – Responsive cells release or stop releasing hormones in response to binding of hypothalamic releasing or inhibiting hormones into systemic circulation

• Via posterior pituitary

(neurohypophysis) – Hypothalamic magnocellular neurons release hormones directly into systemic veins that drain into the systemic circulation – Hypothalamo- hypophyseal tract (axons of neuroendocrine magnocellular neurons) Hypothalamus median eminence posterior pituitary

Neuroendocrine hypothalamus

• Via anterior pituitary

– Hypothalamic parvocellular neurons release releasing or inhibiting hormones into hypothalamo-pituitary portal veins – Hypothalmo-pituitary portal veins carry these hormones to anterior pituitary – Anterior pituitary has cells responding to the different releasing or inhibiting hormones – Responsive cells release or stop releasing hormones in response to binding of hypothalamic releasing or inhibiting hormones into systemic circulation

• Via posterior pituitary

(neurohypophysis) – Hypothalamic magnocellular neurons release hormones directly into systemic veins that drain into the systemic circulation – Hypothalamo- hypophyseal tract (axons of neuroendocrine magnocellular neurons) Hypothalamus median eminence posterior pituitary

Neuroendocrine hypothalamus

ADH kidneys

• xytocin

mammary gland + uterus bonding (autism?)

paraventricular (PVN) + supraoptic (SON) Hormones released: Hormone targets: Release from:

Neuroendocrine hypothalamus

ADH kidneys

• xytocin

mammary gland + uterus bonding (autism?)

paraventricular (PVN) + supraoptic (SON) Hormones released: Hormone targets: Release from:

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ADH-release

• ADH promotes water retention in kidneys
• release is modified when blood osmolarity

changes by more than ~ 1% from set point (~ 280 mOsm/kg)

– Hypotonic conditions inhibit ADH release – Hypertonic conditions stimulate ADH release

ADH-release

How do cells in supra-optic and paraventricular nuclei know that blood osmolarity has changed?

• Osmosensitive neurons
• Intrinsically osmosensitive neurons in OVLT, SFO

and NTS

• ADH releasing neurons are intrinsically
• smosensitive

Firing rate of ADH-releasing neurons integrates central and peripheral information and their own osmosensitivity

ADH-release

How do cells in supra-optic and paraventricular nuclei know that blood osmolarity has changed?

• Osmosensitive neurons
• Intrinsically osmosensitive neurons in OVLT, SFO

and NTS that directly project to the supraoptic and paraventricular nuclei

Circumventricular organ: brain structure that is devoid of blood brain barrier

How can a cell be intrinsically osmosensitive?

Change in osmolarity will cause cell swelling or shrinking, resulting in increased or decreased stretch of plasma membrane Stretch of plasma membrane can gate ion channels

stretch-activated tethered indirectly gated

Lumpkin & Caterina Nature 445, 858-865 (2007)

cytoskeleton cytoskeleton extracellular matrix extracellular matrix mechano- sensitive protein

ADH-release

TRPV1

• pens in response to

hypertonic stimulus

TRPV4

• pens in response to

hypotonic stimulus

Which is (are) the candidate ion channel(s) involved in osmosensing?

ADH-release

TRPV1

• pens in response to

hypertonic stimulus

TRPV4

• pens in response to

hypotonic stimulus

Which is (are) the candidate ion channel(s) involved in osmosensing?

Transient Receptor Potential channels

• f the Vanilloid family (TRPV channels)

(non-selective cation channels)

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ADH-release

TRPV1

• pens in response to

hypertonic stimulus

TRPV4

• pens in response to

hypotonic stimulus

Which is (are) the candidate ion channel(s) involved in osmosensing?

N-terminal variant indirect effect

Transient Receptor Potential channels

• f the Vanilloid family (TRPV channels)

(non-selective cation channels) cell volume (cell shrinking)

Sharif Naeini et al. Nat. Neurosci. 9, 93 - 98 (2006)

membrane conductance

(TRPV1-/-)

Sharif Naeini et al. Nat. Neurosci. 9: 93 - 98 (2006)

membrane conductance

TRPV1

(TRPV1-/-)

Sharif Naeini et al. Nat. Neurosci. 9: 93 - 98 (2006)

Action potential firing rate in response to hypertonic solution

TRPV1

Sharif Naeini et al. Nat. Neurosci. 9: 93 - 98 (2006)

Impaired ADH release in TRPV1 knock-out mice in response to hypertonic solution

TRPV1

AVP = ADH Liedtke & Friedman PNAS;100:13698-13703 (2003)

TRPV4

+/+ = wild type

• /- = TRPV4 knock-out

TRPV4 knock-out mice drink significantly more when infused with ADH-analogue dDAVP (i.e. when water retention is increased, which should result in decreased water intake) than wildtype mice.

TRPV4 channels

• pen in response

to cell swelling (indirect effect) in expression systems

ADH-release

How does it all come together?

• Increased blood osmolarity causes osmosensitive OVLT

neurons to shrink

• TRPV1 channels open, leading to depolarisation and eventually

firing of OVLT neurons (graded response)

• OVLT neurons make monosynaptic glutamatergic contacts with

supra-optic nuclei neurons

• This promotes firing of ADH-releasing neurons and hence ADH

release

• ADH releasing neurons are intrinsically osmosensitive

Firing rate of ADH-releasing neurons depends on central and peripheral inputs as well as their intrinsic

• smosensitivity

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ADH-release

How does it all come together?

• Increased blood osmolarity causes osmosensitive (OVLT)

neurons to shrink

• TRPV1 channels open, leading to depolarisation and eventually

firing of (OVLT) neurons (graded response)

• (OVLT) neurons make monosynaptic glutamatergic contacts

with supra-optic nuclei neurons

• This promotes firing of ADH-releasing neurons and hence ADH

release

• ADH releasing neurons are intrinsically osmosensitive

Firing rate of ADH-releasing neurons depends on central and peripheral inputs as well as their intrinsic

• smosensitivity

ADH-release

How does it all come together?

• Increased blood osmolarity causes osmosensitive (OVLT)

neurons to shrink

• TRPV1 channels open, leading to depolarisation and eventually

firing of (OVLT) neurons (graded response)

• (OVLT) neurons make monosynaptic glutamatergic contacts

with supra-optic nuclei neurons

• This promotes firing of ADH-releasing neurons and hence ADH

release

• ADH releasing neurons are intrinsically osmosensitive

Firing rate of ADH-releasing neurons depends on central and peripheral inputs (baroreceptors!) as well as their intrinsic osmosensitivity – Central DI

• failure to secrete

ADH, resulting in excess urine output and dehydration

• following pituitary stalk

damage (accident)

• Brattleboro rat

produces no ADH

Diabetes insipidus Summary of neuroendocrine hypothalamus

• Arcuate

GnRH (FSH, LH); GHRH (GH); DA (prolactin)

Reproduction; growth

• PVN

CRH (ACTH); TRH (TSH); ADH;

• xytocin

Steroid hormone production, energy metabolism, water retention; social behaviours, reproduction

• Ant. HT

Sost (GH)

Growth

• SON

ADH; oxytocin

water retention; social behaviours, reproduction

Summary of neuroendocrine hypothalamus

• Arcuate

GnRH (FSH, LH); GHRH (GH); DA (prolactin)

reproduction; energy metabolism

• PVN

CRH (ACTH); TRH (TSH); ADH;

• xytocin

behaviours, energy metabolism, water retention (blood flow), reproduction

• Ant. HT

Sost (GH)

energy metabolism

• SON

ADH; oxytocin

water retention (blood flow), behaviours, reproduction

Non-endocrine control via the hypothalamus

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Non-endocrine control via the hypothalamus

• Food and drink intake
• Thermoregulation
• Circadian rhythms

Parasympathetic and sympathetic control

Non-endocrine control via the hypothalamus

• Food and drink intake
• Thermoregulation
• Circadian rhythms

Parasympathetic and sympathetic control

Non-endocrine control via the hypothalamus

• Food and drink intake
• Thermoregulation
• Circadian rhythms

ANS control

Food intake Food intake

• Lateral hypothalamic area

– “Feeding centre” (bilateral lesions: aphagia) – Receives olfactory input via medial forebrain bundle

• Ventromedial nucleus

– “Satiety centre” (bilateral lesions: hyperphagia) – Receptors for glucose and free fatty acids

• Arcuate nucleus

– Receptors for leptin (adipose tissue) and insulin

Separate lecture on food intake

Food intake

• Lateral hypothalamic area

– “Feeding centre” (bilateral lesions: aphagia) – Receives olfactory input via medial forebrain bundle

• Ventromedial nucleus

– “Satiety centre” (bilateral lesions: hyperphagia) – Receptors for glucose and free fatty acids

• Arcuate nucleus

– Receptors for leptin (adipose tissue) and insulin

Separate lecture on food intake

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Food intake

• Lateral hypothalamic area

– “Feeding centre” (bilateral lesions: aphagia) – Receives olfactory input via medial forebrain bundle

• Ventromedial nucleus

– “Satiety centre” (bilateral lesions: hyperphagia) – Receptors for glucose and free fatty acids

• Arcuate nucleus

– Receptors for leptin (adipose tissue) and insulin

Separate lecture on food intake

Food intake

• Lateral hypothalamic area

– “Feeding centre” (bilateral lesions: aphagia) – Receives olfactory input via medial forebrain bundle

• Ventromedial nucleus

– “Satiety centre” (bilateral lesions: hyperphagia) – Receptors for glucose and free fatty acids

• Arcuate nucleus

– Receptors for leptin (adipose tissue) and insulin

Separate lecture on food intake

Drink intake/Thirst Drink intake/Thirst

• Subfornical organ

– contains osmosensitive neurons – projects to PVN, SON and POA – stimulation of drinking behaviour (thirst)

• ther cirumventricular organs also contribute

More in separate lecture

Thermoregulation Thermoregulation

• Alert consciousness and normal patterned motor

activities only when CNS temperature ~ 36 - 39°C

• Hypothalamus can stimulate thermogenesis

– shivering, piloerection, skin vasoconstriction – behaviours that increase body temperature (or minimise heat loss)

• Hypothalamus can stimulate heat loss

– sweating, skin vasodilation – behaviours that promote body temperature cooling

• Controlled elevation of body temperature (fever)

reduces pathogen viability and boosts immune system function

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Thermoregulation

• Anterior hypothalamus (POA)

– Lesions cause hyperthermia – Endogenous temperature sensors (warm-sensitive neurons)

• T set-point can be changed by pyrogens, causing

elevated core temperature (PGE2 acting on EP3 receptors)

• Posterior hypothalamic area

– Lesions cause hypothermia – Involved in sympathetic activation

• Dilation or contraction of cutaneous circulation and

control of sweat glands receive peripheral temperature information

(TRPM8, TRPV3, TRPV4)

Thermoregulation

• Anterior hypothalamus (POA)

– Lesions cause hyperthermia – Endogenous temperature sensors (warm-sensitive neurons)

• T set-point can be changed by pyrogens, causing

elevated core temperature (PGE2 acting on EP3 receptors)

• Posterior hypothalamic area

– Lesions cause hypothermia – Involved in sympathetic activation

• Dilation or contraction of cutaneous circulation and

control of sweat glands also receive peripheral temperature information

(TRPM8, TRPV3, TRPV4)

• What is the central temperature sensor?

2 current models:

• 1. Heat directly opens ion channel that then

depolarises neuron – AP firing

• 2. Heat indirectly promotes depolarisation of

neuron – AP firing

Thermoregulation

• What is the central temperature sensor?

2 current models:

• 1. Heat directly opens ion channel that then

depolarises neuron – AP firing

• 2. Heat indirectly promotes depolarisation of

neuron – AP firing

Thermoregulation

TRPV1

– peripheral or central administration of TRPV1 agonist capsaicin induces hypothermia – administration of TRPV1 antagonists induces hyperthermia (increased metabolism and reduced heat loss from body surface) – TRPV1 is expressed in anterior hypothalamus ◄However: TRPV1 knock-out mice have no obvious deficit in body temperature control and TRPV1 channels in anterior hypothalamus are not activated by normal body temperature: TRPV1 is unlikely to be the hypothalamic thermosensor! thought to be mediated by visceral TRPV1 channels that are tonically active

Thermoregulation

TRPV1

– peripheral or central administration of TRPV1 agonist capsaicin induces hypothermia – administration of TRPV1 antagonists induces hyperthermia (increased metabolism and reduced heat loss from body surface) – TRPV1 is expressed in anterior hypothalamus ◄However: TRPV1 knock-out mice have no obvious deficit in body temperature control and TRPV1 channels in anterior hypothalamus are not activated by normal body temperature: TRPV1 is unlikely to be the hypothalamic thermosensor! thought to be mediated by visceral TRPV1 channels that are tonically active

Thermoregulation

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TRPV1

– peripheral or central administration of TRPV1 agonist capsaicin induces hypothermia – administration of TRPV1 antagonists induces hyperthermia (increased metabolism and reduced heat loss from body surface) – TRPV1 is expressed in anterior hypothalamus ◄However: TRPV1 knock-out mice no obvious deficit in body temperature control; TRPV1 channels in anterior hypothalamus not activated by normal body temperature: TRPV1 unlikely to be hypothalamic thermosensor! thought to be mediated by visceral TRPV1 channels that are tonically active

Thermoregulation

• What is the central temperature sensor?

still unclear

Thermoregulation Thermoregulation

• Anterior hypothalamus (POA)

– Lesions cause hyperthermia – Endogenous temperature sensors (warm-sensitive neurons)

• T set-point can be changed by pyrogens, causing

elevated core temperature (PGE2 acting on EP3 receptors)

• Posterior hypothalamic area

– Lesions cause hypothermia – Involved in sympathetic activation

• Dilation or contraction of cutaneous circulation and

control of sweat glands also receive peripheral temperature information

(TRPM8, TRPV3, TRPV4)

Thermoregulation

• Anterior hypothalamus (POA)

– Lesions cause hyperthermia – Endogenous temperature sensors (warm-sensitive neurons)

• T set-point can be changed by pyrogens, causing

elevated core temperature (PGE2 acting on EP3 receptors)

• Posterior hypothalamic area

– Lesions cause hypothermia

• Dilation or contraction of cutaneous circulation and

control of sweat glands also receive peripheral temperature information

(TRPM8, TRPV3, TRPV4)

Thermoregulation

• Anterior hypothalamus (POA)

– Lesions cause hyperthermia – Endogenous temperature sensors (warm-sensitive neurons)

• T set-point can be changed by pyrogens, causing

elevated core temperature (PGE2 acting on EP3 receptors)

• Posterior hypothalamic area

– Lesions cause hypothermia

• Dilation or contraction of cutaneous circulation and

control of sweat glands also receive peripheral temperature information

(TRPM8, TRPV3, TRPV4)

Thermoregulation

• Anterior hypothalamus (POA)

– Lesions cause hyperthermia – Endogenous temperature sensors (warm-sensitive neurons)

• T set-point can be changed by pyrogens, causing

elevated core temperature (PGE2 acting on EP3 receptors)

• Posterior hypothalamic area

– Lesions cause hypothermia

• Dilation or contraction of cutaneous circulation and

control of sweat glands also receive cutaneous temperature information

(TRPA1?, TRPM8, TRPV3, TRPV4)

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Circadian rhythms Circadian rhythms

• Suprachiasmatic nucleus

– Sleep-wake cycle, feeding, temperature control, hormone release….. – direct input from light- sensitive ganglion cells in retina (melanopsin) (retinohypothalamic tract) – phototransduction cascade similar to invertebrate one

• TRPC channels (originally

cloned from drosophila photoreceptors)

• Separate lecture

Mammillary bodies Mammillary bodies

• Role in memory: Korsakoff’s syndrome

» alcohol-induced Vitamine B1 deficiency: damage to mammillary bodies (but also thalamus) » Symptoms: anterograde and retrograde amnesia, confabulation

• Contain several nuclei with distinct connections
• Head direction cells (lateral nuclei)

» fire selectively when animal faces specific direction in horizontal plane; navigation

• Memory formation (medial nuclei)

» connected with hippocampus via fornix and fire at theta frequency (4-8Hz), which elicits long term potentiation in hippocampus

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Summary non-endocrine hypothalamus

• Anterior HT

ANS regulation; endogenous T sensor;

• smoregulation (energy

metabolism, blood flow)

• SCN

circadian rhythms

• Arcuate nucleus

food intake

• Ventromedial nucleus

“satiety” centre

• Lateral hypothalamus

“hunger” centre

• Posterior HT

ANS regulation (T sensor)

• Mammillary bodies

memory (behaviours?)

Summary non-endocrine hypothalamus

• Anterior HT

ANS regulation; endogenous T sensor;

• smoregulation (energy

metabolism, blood flow)

• SCN

biological clock

• Arcuate nucleus

food intake

• Ventromedial nucleus

“satiety” centre

• Lateral hypothalamus

“hunger” centre

• Posterior HT

ANS regulation (T sensor)

• Mammillary bodies

memory (behaviours?)

energy metabolism

Aggression and the hypothalamus

• Neuronal subpopulations of ventromedial hypothalamus cause

aggressive behaviour (Lin et al. (2011) Nature 470:221-226)

“sexually experienced” male C57BL/6N mouse under investigation Some cells are active during number of different behaviours whereas others (cell 4) are only active during one particular behaviour “sexually experienced” male C57BL/6N mouse under investigation Some cells are active during number of different behaviours whereas others (cell 4) are only active during one particular behaviour Went on to selectively initiate behaviours by activating certain neurons and showed that neurons activated during an attack are inhibited during mating

Sex and the hypothalamus

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Sexual dimorphism of hypothalamus

Sexually dimorphic nucleus of preoptic area: Interstitial nucleus III and also other hypothalamic regions

VERY controversial data

/ woman

Sexual dimorphism of hypothalamus

Sexually dimorphic nucleus of preoptic area: Interstitial nucleus III and also other hypothalamic regions

VERY controversial data

/ woman