4 Hypothalamus I & II Flashcards
Big picture: what’s the role of the hypothalamus?
- controls homeostasis
- integrates endocrine, autonomic and somatomotor systems
- also involved w/ affective behavior
define: diencephalon
the thalamus, subthalamus, hypothalamus and epithalamus
define: infudibulum
“funnel” = pituitary stalk
tuber cinerum
“Grey swelling” is region on ventral surface of brain that extends from the optic chiasm to the mammilary bodies
median eminence
part of the tuber cinerum that is raised and forms the infundibulum; contains 1° capillary network of the hypophysial portal system
True or False: The neurons of the hypothalamus are nice and neatly ordered?
False, unlike the neat rows of neurons in the hippocampus, the neuronal organization of the hypothalamus is highly heterogeneous.
Describe”the”information”integrated”and”affected”by”the”hypothalamus”(e.g.,”sensory,” affective,”motor;”control”of”temperature,”osmolarity”and”salt”balance,”circadian”rhythms,” reproduction,”stress,”arousal).
??
Describe the anatomical landmarks of the brain that demarcate the hypothalamus.
- just dorsal to pituitary
- just ventral to thalamus from which it is separated by the hypothalamic sulcus
- makes up floor and lateral walls of 3rd ventricle
- continuous with the pre-optic area anteriorly and the mammillary bodies posteriorly
- medial and rostral to the subthalamic region
Describe”the”MAJOR”afferents (5) of”the”hypothalamus”and”the”type”of”
information”these”tracts”carry.”
- mfb* (median forebrain): carry sensory, motor, limbic and autonomic info from the cortex, striatum and septum
- retinohypothalamic: carry sensory/circadian info from the retina
- dlf* (dorsal longitudinal fasiculus): carry motor, sensory and autonomic info from the brainstem and spinal cord
- stria-terminalis*: carries limbic info from amygdala
- fornix: carries info from hippocampus (memory?)
*also contain efferents from hypothalamus
Describe”the”MAJOR”efferents (6) of”the”hypothalamus”and”the”type”of”
information”these”tracts”carry.”
- mfb: carry limbic, autonomic and motor info to median forebrain
- tuberoinfundibular tract: endocrine signals to adenohypophysis
- supraopticohypophysial: endocrine signals to neurohypophysis
- dlf: motor, autonomic, etc. to brainstem and spinal cord
- mammillothalamic: limbic info
- stria terminalis: limbic info to amygdala
Describe”the”nuclei”and”hormones”that”provide”input”to”the”posterior”pituitary.
SO (supraoptic) and PVN (paraventricular) nuclei of hypothalamus project their axons to the neurohypophysis via the supraopticohypophyseal tract.
- -signal with AVP (arginine vasopressin) and oxytocin–two related nonapeptides
- -cell bodies in both the SO and PVN make both hormones; each nuclei has 50/50 breakdown of AVP- and oxytocin-producing neurons
What does AVP do?
acts on the kidney to promote water reabsorption
Lesions of the ant. hypothalamus that disrupt input to the SO and PVN nuclei lead to ?
diabetes insipidus – abnormal production of lots of dilute pee
When is oxytocin released?
released in response to: sexual stim, uterine dilation, nursing and, sometimes stress
What does oxytocin do?
-stimulates uterine contraction
-stimulates milk secretion
Along with AVP, oxytocin is also involved with:
-maternal instincts, pair bonding, love, empathy, trust, eye contact
-aggressive behaviors, too
-oxytocin deficit in autism may be?
Prairie vs. Montaine voles
Have different expression of AVP and oxytocin receptors:
- prairie voles express these receptors in their nucleus acumbens (part of the mesolimbic reward system); they are monogamous and males show aggression towards other males etc.
- montaine voles express these in other areas like the lateral septum and the amydala and do not show these parental, partner-preference, mating for life behaviors
Tuberoinfundibular tract definition
the name for the collection of axons from periventricular regions of the hypothalamus (paraventricular, arcuate and ventromedial nuclei and the preoptic area) that secrete releasing/inhibitory factors into the anterior pituitary via a vascular connection
Describe”the”HPG”axis.
[photo]
Describe how gonadal steroids and other environmental factors influence GnRH neurons.
Kisspeptin neurons integrate information from estrogen, progestins, androgens and other hormones (e.g. leptin, glucocorticoids ) (i.e. they have a high amt of receptors for these hormones) and then serve as presynaptic afferents that innervate GnRH neurons in the hypothalamus.
- -The secrete kisspeptin which then acts thru G-prot coupled receptors on the GnRH neurons.
- -It therefore serves as a master regulator of the HPG axis.
- -These kisspeptide cells are responsible for the onset of puberty and regulation of cycling in adults.
Describe the difference between activational and organizational effects of steroids.
Organizational effects: permanent effects on hormone on the structure/function of brain regions; leads to sexual dymorphism (e.g. ∆s in size of SDN-POA); will continue to have their effect in the absence of that hormone later
Activational effects: transient effects of hormones involved with normal cyclicity in females sex-specific behavior and ∆s in the HPG axis necessary for parturition
–also involves w/ PMS, PMDD, enhanced sz susceptibility in catamenial epilepsy
Name the nucleus that is the master regulator of circadian rhythms and describe how loops of transcription factor expression control the “clock”.
Peripheral clocks exists all over the body, but the SCN in the master clock.
- -In the SCN (suprachiasmatic nucleus), transcription factors (clock, BMAL1, Crypton and Period) encode proteins that regulate each other’s and other downstream proteins’ expression in such a way that you get 24hr periodicity.
- -the stability of these prots is regulated by casein kinase which is mutated in FASPS (familial advanced sleep phase syndrome)
What are two sexually dimorphic regions of the forebrain/hypothalamus?
VMN (ventromedial nucleus of the hypothalamus) and POA (pre-optic area)
What is the human equivalent of the SDN-POA?
INAH3 (the interstitial nucleus of the anterior hypothalamus 3)
Name the molecule that signals peripheral energy stores from white adipose tissue.
leptin
What are the anorexogenic peptides and what do they do?
leptin, POMC, α-MSH; they suppress feeding and stimulate energy expenditure
What are orexogenic peptides and what do they do?
NPY, orexin and AgRP (agouti-related protein); these increase feeding and suppress energy expenditure
Describe the effect of leptin on the opposing orexigenic and anorexigenic neuronal circuits
in the arcuate nucleus.
[photo]
when there is decreased food:
1. leptin falls
2. this activates NPY/AgRP neurons and inhibits POMC neurons in the arcuate nucleus
3a. More NPY and AgRP is released; both increase food intake; AgRP also blocks binding of α-MSH to melanocortin receptors which decreases the melanocortin anorexia pathways
3b. α-MSH expression and release is directly decreasd
Describe the routes by which peripheral information about energy state gets to the hypothalamus.
Info from GI and Pancreas:
- -insulin: from pancreatic ß-cells
- -ghrelin: acute signal to increase food intake, decr, energy usage and incr adiposisity
- -CCK transmits info about stomach filling; via vagus to the nucleus of the solitary tract
From White fat: leptin signals via JAK/STAT on long form leptin receptors
these get into CNS:
- -in areas where BBB in breached (E.g. posterior pituitary and area postrema)
- -via active transport
- -via hypothalamic neurons that project directly into the blood stream
What gene codes for leptin?
The ob gene
What is the primary evolutionary role of leptin?
To get us to maintain adequate fat stores when there is enough food around, NOT to diminish energy intake under high food or high already-have-a-lot-stored-up situations.
What gene encodes from the leptin receptor?
db
Describe the routes by which hypothalamic control of energy homeostasis reaches
peripheral structures.
Signaling mostly from the arcuate nucleus via POMC and NPY/AgRP neurons (??)
Define”the”genetic”deficit”in”ob/ob”and”db/db”mice.”
ob/ob mice cannot make leptin while db/db mice cannot make the leptin receptor; both exhibit:
- obesity
- hyperphagia
- low metab rate
- hypothyroid
- hypothalamic infertility
- decr. growth
- decr. immune f(X)
Describe the dysregulation in leptin homeostasis in obese individuals and why clinical trials with leptin have had such a low success rate.
- leptin levels are paradoxically very elevated in obese individuals, so it appears they have become resistant to its effects;
- only 1-2% of obese individuals are obese 2° to a defects in the genes of leptin and/or its receptor, so clinical trials w/ leptin were not effective for most subjects
Describe the relationship between CRF, stress, eating of high fat foods, and reward
- stress incr. CRF (Corticotropin releasing factor) –> incr ACTH from ant. pituitary –> cortisol release –> ∆s energy homeostasis and incr intake of high-fat foods
- *CRF also involved in anxiety
- *this path whacked in people w/ anorexia nervosa
**reward??
Describe the pathophysiology in hypothalamic function that occurs in anorexia.
HPA axis becomes dysregulated and produces too much CRF and cortisol
–HPG also affected: amenorrhea etc.
Describe the location of orexin neurons in the hypothalamus
orexin neurons are located in the LHA (lateral hypothalamic region of the hypothalamus
What is the role of orexin neurons in arousal and the pathophysiological basis for narcolepsy?
- -orexin neurons are a very small group of neurons (only ~6700 in whole brain), but are highly branched and innervate widespread areas of the brain; plays central role in arousal
a) their signals coordinate vigilance, energy homeostasis (e.g. they activate brown fat cells), reward and emotion
b) they promote transition between sleep and wakeful state - -Narcolepsy is a neurodegenerative disease in which >90% of orexin neurons (again, found in the LHA) are lost.
What is the proposed mechanism of drugs like modafinil?
- -stimulates orexin signaling and other stimulatory pathways;
- -may also augment dopamine (DA) levels in the mesolimbic reward system (i.e. NAc, nucleus acumbens) which means we know that increased DA in the NAc = addiction
Describe”the”importance”of”the”discovery”of”brown”fat”in”adults”and”its”relationship”to”
thermoregulation”and”energy”homeostasis”in”women”versus”men.”
Brown adipose tissue (BAT) burns calories to generate heat
- stimulated to do so by orexin
a) normothermia –> GABAergic neurons in POA inhibit a multisynaptic pathway that controls heat generation in BAT
b) hypothermia –> sensory info from skin –>activates other GABAergic neurons that suppress the aforementioned tonic inhibition allowing BAT activation –> heat generation
SEX: two times more in women than men; hypothesized that women, who have less muscle mass on avg than men, use this extra BAT to generate heat
