Download Hypothalamus - aHuman Project

Lecture outline
• Structural organisation of hypothalamus
Hypothalamus
– Localisation + nuclei
– Input/output pathways
• Physiological function of hypothalamus
[email protected]
Overview of anatomy
anterior
chiasmatic
Overview of anatomy
tuberal
posterior
medial view
Overview of physiological functions
coronal view
Third ventricle
Mamillo-thalamic tract
Dorsal hypothalamic area
Dorsomedial nucleus
Fornix
Lateral
hyothalamic
area Supraoptic nucleus
Medial
forebrain
bundle
Amygdala
Amygdala
Lateral
tuberal
nucleus
Median eminence
Arcuate
nucleus
Optic
tract
Ventromedial nucleus
1
Overview of physiological functions
Overview of physiological functions
• Maintenance of milieu interne
• Maintenance of milieu interne
• Behaviour
• Behaviour
• Memory
• Memory
¾ Regulation of energy metabolism (food intake, metabolic
rate, temperature regulation, growth)
¾ Regulation of energy metabolism (food intake, metabolic
rate, temperature regulation, growth)
¾ Reproductive function (including milk production, social
interactions)
¾ Reproductive function (including milk production, social
interactions)
¾ Biological clock, sleep-wake cycles
¾ Biological clock (sleep-wake cycles)
¾ Control of blood flow (cardiac output, blood osmolarity
and renal clearance, thirst regulation)
¾ Control of blood flow (cardiac output, blood osmolarity
and renal clearance, thirst regulation)
Overview of physiological functions
Overview of physiological functions
• Detection of (changes in)
¾Regulation of the autonomic nervous system
¾ Blood osmolarity
¾ Blood nutrient levels
¾Release of hormones
Hypothalamic neurons can release hormones
(neuro-endocrine)
¾ Blood hormone levels
¾ Body temperature
ÍDirectly and indirectly
Overview of connections
• Input from
¾ Retina (retinohypothalamic tract – terminates in SCN)
¾ Olfactory receptors (medial forebrain bundle)
¾ Cutaneous receptors
¾ Higher (limbic) system (hippocampal formation: fornix – to
mammillary bodies; amygdala: stria terminalis – to medial
hypothalamus)
¾ Viscera
Overview of connections
• Output to
¾ Thalamus (via mammillothalamic tract (Papez circuit: cingulate
gyrus – hippocampal formation – mammillary bodies – anterior thalamic
nucleus – cingulate gyrus))
(also mammillotegmental tract to midbrain tegmentum)
¾ Amygdala (from medial hypothalamus)
¾ Midbrain PAG (from medial hypothalamus) (aggression, rage,
flight)
¾ Frontal and parietal lobes, habenular nucleus, midbrain…
¾ Blood stream (pituitary)
2
Overview of basic functions
• Feed-back system
Overview of basic functions
• Feed-back system
• Feed-forward system
– Hypothalamus corrects
deviations from a given
set-point:
– Hypothalamus corrects
deviations from a given
set-point:
– Hypothalamus can override feed-back under
special conditions
• measures current value
• compares current value
with supposed value
• makes adjustments to
achieve supposed value
• measures current value
• compares current value
with supposed value
• makes adjustments to
achieve supposed value
• Stress responses
• Fever (body T set point is
changed to higher T)
– helps maintain body
homeostasis
– helps maintain body
homeostasis
Overview of basic functions
• Feed-back system
• Feed-forward system
– Hypothalamus corrects
deviations from a given
set-point:
– Hypothalamus can override feed-back under
special conditions
• measures current value
• compares current value
with supposed value
• makes adjustments to
achieve supposed value
• Stress responses
• Fever (body T set point is
changed to higher T)
– helps maintain body
homeostasis
• Anticipation
• Look at neuroendocrine functions of
hypothalamus
• Look at regulation of non-endocrine
functions (ANS) of hypothalamus
– Hypothalamus adjusts
its output to meet future
needs
• Insulin secretion prior to
food intake
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
3
Neuroendocrine hypothalamus
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
• Via anterior pituitary
Hypothalamus
R
I
Anterior
Pituitary
Neuroendocrine hypothalamus
Hypothalamus
R
I
Anterior
Pituitary
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
(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
• Via anterior pituitary
Hypothalamus
R
I
Anterior
Pituitary
Rel./Inhib.
hormone:
(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
Rel./Inhib.
hormone:
GnRH
gonadotrope
FSH+LH
CRH
corticotrope
ACTH
TRH
thyrotrope
TSH
GHRH
somatotrope
Sost
DA
gonads
Hypothalamus
R
Anterior
Pituitary
Ant. Pit.
target cell:
GnRH
gonadotrope
FSH+LH
CRH
corticotrope
ACTH
TRH
thyrotrope
TSH
GH
GHRH
somatotrope
GH
somatotrope
GH
Sost
somatotrope
GH
lactotrope
prolactin
DA
lactotrope
prolactin
thyroid
I
gonads
thyroid
4
Rel./Inhib.
hormone:
Ant. Pit.
target cell:
Hormone:
target:
release
from:
Rel./Inhib.
hormone:
GnRH
gonadotrope
FSH+LH
gonads
arcuate
CRH
corticotrope
ACTH
adrenal
gland
TRH
thyrotrope
TSH
thyroid
GHRH
somatotrope
GH
Sost
somatotrope
GH
many cells
(bones)
DA
lactotrope
prolactin
mammary
glands
Neuroendocrine hypothalamus
• Via anterior pituitary
– Hypothalamic parvocellular
neurons release releasing or
inhibiting
hormones into
Hypothalamus
hypothalamo-pituitary portal
veins
– Hypothalmo-pituitary portal
veins carry these hormones to
anterior pituitary
– Anterior pituitary has cells
median to the different
responding
eminence
releasing
or inhibiting
hormones
– Responsive cells release
or
posterior
stop releasing hormones
in
pituitary
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
– Hypothalamohypophyseal tract
(axons of
neuroendocrine
magnocellular neurons)
Neuroendocrine hypothalamus
Ant. Pit.
target cell:
Hormone:
target:
GnRH
gonadotrope
FSH+LH
gonads
paraventricular
(PVN)
CRH
corticotrope
ACTH
adrenal
gland
TRH
thyrotrope
TSH
thyroid
arcuate
GHRH
somatotrope
GH
somatotrope
GH
many cells
(bones)
lactotrope
prolactin
anterior
Sost
HT
arcuate
DA
mammary
glands
Neuroendocrine hypothalamus
• Via anterior pituitary
– Hypothalamic parvocellular
neurons release releasing or
inhibiting
hormones into
Hypothalamus
hypothalamo-pituitary portal
veins
– Hypothalmo-pituitary portal
veins carry these hormones to
anterior pituitary
– Anterior pituitary has cells
median to the different
responding
eminence
releasing
or inhibiting
hormones
– Responsive cells release
or
posterior
stop releasing hormones
in
pituitary
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
– Hypothalamohypophyseal tract
(axons of
neuroendocrine
magnocellular neurons)
Neuroendocrine hypothalamus
Release
from:
Hormones
released:
Hormone
targets:
Release
from:
Hormones
released:
Hormone
targets:
paraventricular
(PVN)
+
supraoptic
(SON)
ADH
kidneys
ADH
kidneys
oxytocin
mammary gland
+ uterus
paraventricular
(PVN)
+
supraoptic
(SON)
oxytocin
mammary gland
+ uterus
bonding (autism?)
bonding (autism?)
5
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
¾How 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
osmosensitive
¾Firing rate of ADH-releasing neurons integrates central
and peripheral information and their own osmosensitivity
ADH-release
¾How 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
¾How can a cell be intrinsically osmosensitive?
stretch-activated
¾Change in osmolarity will
cause cell swelling or
shrinking, resulting in
increased or decreased
stretch of plasma
membrane
extracellular
matrix
cytoskeleton
¾Stretch of plasma
membrane can gate ion
channels
Lumpkin & Caterina
Nature 445, 858-865 (2007)
ADH-release
¾Which is (are) the candidate ion channel(s)
involved in osmosensing?
tethered
indirectly gated
cytoskeleton
extracellular
matrix
mechanosensitive
protein
ADH-release
¾Which is (are) the candidate ion channel(s)
involved in osmosensing?
Transient Receptor Potential channels
of the Vanilloid family (TRPV channels)
(non-selective cation channels)
¾TRPV1
¾opens in response to
hypertonic stimulus
¾TRPV4
¾opens in response to
hypotonic stimulus
¾TRPV1
¾opens in response to
hypertonic stimulus
¾TRPV4
¾opens in response to
hypotonic stimulus
6
TRPV1
ADH-release
cell volume
(cell shrinking)
¾Which is (are) the candidate ion channel(s)
involved in osmosensing?
(TRPV1-/-)
Transient Receptor Potential channels
of the Vanilloid family (TRPV channels)
(non-selective cation channels)
¾TRPV1
¾opens in response to
hypertonic stimulus
membrane
membrane
conductance
conductance
N-terminal variant
¾TRPV4
Sharif Naeini et al. Nat. Neurosci. 9:
9, 93 - 98 (2006)
¾opens in response to
hypotonic stimulus
indirect effect
TRPV1
TRPV1
Impaired ADH release in TRPV1 knock-out mice
in response to hypertonic solution
Action potential firing rate in
response to hypertonic solution
(TRPV1-/-)
Sharif Naeini et al. Nat. Neurosci. 9: 93 - 98 (2006)
Sharif Naeini et al. Nat. Neurosci. 9: 93 - 98 (2006)
AVP = ADH
TRPV4
TRPV4 channels
open in response
to cell swelling
(indirect effect)
in expression systems
Liedtke & Friedman PNAS;100:13698-13703 (2003)
+/+ = 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.
ADH-release
¾How 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
¾Firing rate of ADH-releasing neurons depends on central
and peripheral inputs as well as their intrinsic
osmosensitivity
7
ADH-release
ADH-release
¾How does it all come together?
¾How 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
¾Firing rate of ADH-releasing neurons depends on central
and peripheral inputs as well as their intrinsic
osmosensitivity
• 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
¾Firing rate of ADH-releasing neurons depends on central
and peripheral inputs (baroreceptors!) as well as their
intrinsic osmosensitivity
Diabetes insipidus
Summary of neuroendocrine hypothalamus
• Arcuate
– Central DI
• failure to secrete
ADH, resulting in
excess urine output
and dehydration
• following pituitary stalk
damage (accident)
• Brattleboro rat
produces no ADH
GnRH (FSH, LH); GHRH (GH);
DA (prolactin)
¾ Reproduction; growth
• PVN
CRH (ACTH); TRH (TSH); ADH;
oxytocin
¾ Steroid hormone production, energy metabolism, water
retention; social behaviours, reproduction
• Ant. HT
Sost (GH)
¾ Growth
• SON
ADH; oxytocin
¾ water retention; social behaviours, reproduction
Summary of neuroendocrine hypothalamus
• Arcuate
Non-endocrine control via the hypothalamus
GnRH (FSH, LH); GHRH (GH);
DA (prolactin)
¾ reproduction; energy metabolism
• PVN
CRH (ACTH); TRH (TSH); ADH;
oxytocin
¾ behaviours, energy metabolism, water retention (blood flow),
reproduction
• Ant. HT
Sost (GH)
¾ energy metabolism
• SON
ADH; oxytocin
¾ water retention (blood flow), behaviours, reproduction
8
Non-endocrine control via the hypothalamus
Non-endocrine control via the hypothalamus
• Food and drink intake
• Food and drink intake
• Thermoregulation
• Thermoregulation
• Circadian rhythms
• Circadian rhythms
¾Parasympathetic and
sympathetic control
¾Parasympathetic and
sympathetic control
Food intake
Non-endocrine control via the hypothalamus
• Food and drink intake
• Thermoregulation
• Circadian rhythms
¾ANS control
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
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
– Receptors for leptin (adipose tissue) and insulin
¾Separate lecture on food intake
¾Separate lecture on food intake
9
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
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
– Receptors for leptin (adipose tissue) and insulin
¾Separate lecture on food intake
¾Separate 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)
other cirumventricular organs also contribute
¾More 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
10
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
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
also receive peripheral temperature information
(TRPM8, TRPV3, TRPV4)
(TRPM8, TRPV3, TRPV4)
Thermoregulation
•
What is the central temperature sensor?
Thermoregulation
•
What is the central temperature sensor?
2 current models:
2 current models:
1. Heat directly opens ion channel that then
depolarises neuron – AP firing
1. Heat directly opens ion channel that then
depolarises neuron – AP firing
2. Heat indirectly promotes depolarisation of
neuron – AP firing
2. Heat indirectly promotes depolarisation of
neuron – AP firing
Thermoregulation
TRPV1
Thermoregulation
TRPV1
– peripheral or central administration of TRPV1 agonist capsaicin
induces hypothermia
– 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)
– administration of TRPV1 antagonists induces hyperthermia
(increased metabolism and reduced heat loss from body
surface)
– TRPV1 is expressed in anterior hypothalamus
– 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!
◄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!
¾ thought to be mediated by visceral TRPV1 channels that are
tonically active
¾ thought to be mediated by visceral TRPV1 channels that are
tonically active
11
Thermoregulation
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)
•
What is the central temperature sensor?
still unclear
– 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!
¾ thought to be mediated by visceral TRPV1 channels that are
tonically active
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)
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
• Posterior hypothalamic area
– Lesions cause hypothermia
– Lesions cause hypothermia
• Dilation or contraction of cutaneous circulation and
control of sweat glands
also receive peripheral temperature information
(TRPM8, TRPV3, TRPV4)
• Dilation or contraction of cutaneous circulation and
control of sweat glands
also receive cutaneous temperature information
(TRPA1?, TRPM8, TRPV3, TRPV4)
12
Circadian rhythms
Circadian rhythms
• Suprachiasmatic nucleus
– Sleep-wake cycle, feeding,
temperature control, hormone
release…..
– direct input from lightsensitive 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
13
Summary non-endocrine hypothalamus
Summary non-endocrine hypothalamus
• Anterior HT
ANS regulation;
endogenous T sensor;
osmoregulation (energy
metabolism, blood flow)
• Anterior HT
ANS regulation;
endogenous T sensor;
osmoregulation (energy
metabolism, blood flow)
• SCN
circadian rhythms
• SCN
biological clock
• Arcuate nucleus
food intake
• Arcuate nucleus
food intake
• Ventromedial nucleus
“satiety” centre
• Ventromedial nucleus
“satiety” centre
• Lateral hypothalamus
“hunger” centre
• Lateral hypothalamus
“hunger” centre
• Posterior HT
ANS regulation
(T sensor)
• Posterior HT
ANS regulation
(T sensor)
• Mammillary bodies
memory (behaviours?)
• Mammillary bodies
memory (behaviours?)
Aggression and the hypothalamus
• Neuronal subpopulations of ventromedial hypothalamus cause
aggressive behaviour (Lin et al. (2011) Nature 470:221-226)
energy
metabolism
“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
Sex and the hypothalamus
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
14
Sexual dimorphism of hypothalamus
Sexual dimorphism of hypothalamus
Sexually dimorphic nucleus of preoptic area: Interstitial nucleus III
Sexually dimorphic nucleus of preoptic area: Interstitial nucleus III
and also other hypothalamic regions
and also other hypothalamic regions
VERY controversial data
VERY controversial data
/ woman
/ woman
15