Hypothalamic Control

Question 1

1. Hypothalamus and pituitary are in the x
2. The hypothalamus contains x
   a) It is crucial to the control of x, x , x, and x and x responses.
   b) That control always involves x, i.e. processing chemical and neural signals from the body to monitor how well things are working and to detect disturbances.
   c) Some control systems maintain x — keeping some aspect of x (e.g. osmolality) roughly constant despite disturbances. Other control systems x, e.g. in circadian rhythms
3. The hypothalamus exerts its influence x and x
   a) x within the hypothalamus send x to each other and to other parts of the brain.
   b) The hypothalamus also x which it transports down x to the x of the x, where they are released into the blood.
   c) And the hypothalamus makes x that travel through capillaries (the hypophyseal portal system) to the x, where they trigger the release into the blood of other hormones, made in the pituitary

Answer 1

1. Hypothalamus and pituitary are in the diencephalon
2. The hypothalamus contains control centers for many biological systems
   a) It is crucial to the control of feeding, plasma osmolality, body temperature, and sexual and stress responses.
   b) That control always involves negative feedback, i.e. processing chemical and neural signals from the body to monitor how well things are working and to detect disturbances.
   c) Some control systems maintain homeostasis — keeping some aspect of the internal environment (e.g. osmolality) roughly constant despite disturbances. Other control systems vary things through
   time, e.g. in circadian rhythms
3. The hypothalamus exerts its influence neurally and hormonally
   a) Nuclei within the hypothalamus send neural signals to each other and to other parts of the brain.
   b) The hypothalamus also synthesizes hormones which it transports down axons to the posterior lobe of the pituitary, where they are released into the blood.
   c) And the hypothalamus makes releasing hormones that travel through capillaries (the hypophyseal portal system) to the anterior pituitary, where they trigger the release into the blood of other hormones, made in the pituitary

Question 1

Hypothalamic control of feeding

1. Feeding is tightly controlled
   a) Mice fed solutions with different concentrations of nutrients adjust their eating to x e.g. if the nutrient concentration is halved, they eat twice as much.
   b) The x is crucial to this control, e.g. mice with lesions in the x overeat and become obese; those with lesions in the x get thin.
   c) These areas are in turn controlled by two groups of neurons in the x of the hypothalamus: x cells drive feeding, while x neurons inhibit feeding
2. In the x state, x neurons
   encourage feeding
   a) These are neurons in the x nucleus of the hypothalamus which release x), x, and (in the case of some cells) also x
   3.Arc-NPY projects mainly to x
   a) Signals from Arc-NPY cells inhibit neurons in the x of the hypothalamus (), a x or x center, i.e. a center that quells your appetite for food.
   b) Arc-NPY signals excite neurons in the x, a x center.
3. Arc-NPY inhibits x’s action on the x
   a) High activity in the PVN would excite the x, but Arc-NPY inhibits x, so the x receives x
   b) i.e. Arc-NPY acts via PVN to decrease x.
4. The result is reduced x and therefore more x
   a) High sympathetic activity would x, but Arc-NPY x, i.e. Arc-NPY disinhibits fx
5. LH releases x, which drives x and inhibits x
   a) Projections from LH release x at their x, inhibiting x and stimulating x , though the mechanisms by which x affects feeding are not understood in any detail.

Answer 1

1. Feeding is tightly controlled
   a) Mice fed solutions with different concentrations of nutrients adjust their eating to keep their caloric intake consistent, e.g. if the nutrient concentration is halved, they eat twice as much.
   b) The hypothalamus is crucial to this control, e.g. mice with lesions in the ventromedial hypothalamus overeat and become obese; those with lesions in the lateral hypothalamus get thin.
   c) These areas are in turn controlled by two groups of neurons in the arcuate nucleus of the hypothalamus: arcuate NPY cells drive feeding, while arcuate POMC neurons inhibit feeding
2. In the fasting state, arcuate NPY neurons
   encourage feeding
   a) These are neurons in the arcuate nucleus of the hypothalamus which release neuropeptide Y (NPY), GABA, and (in the case of some cells) also agouti-related peptide (AgRP)
   3.Arc-NPY projects mainly to other hypothalamic areas
   a) Signals from Arc-NPY cells inhibit neurons in the paraventricular nucleus of the hypothalamus (PVN), a satiety or anorexigenic center, i.e. a center that quells your appetite for food.
   b) Arc-NPY signals excite neurons in the lateral hypothalamus (LH), a feeding center.
3. Arc-NPY inhibits PVN’s action on the sympathetic nervous system
   a) High activity in the PVN would excite the sympathetic system, but Arc-NPY inhibits PVN, so the sympathetic system receives very little excitation from there,
   b) i.e. Arc-NPY acts via PVN to decrease sympathetic activity.
4. The result is reduced sympathetic action and therefore more feeding
   a) High sympathetic activity would inhibit feeding, but Arc-NPY inhibits those sympathetic actions, i.e. Arc-NPY disinhibits feeding behavior
5. LH releases orexin, which drives feeding and inhibits PVN
   a) Projections from LH release orexin at their synapses, inhibiting PVN and stimulating feeding behavior, though the mechanisms by which orexin affects feeding are not understood in any detail.

Question 2

1. In the x state, x inhibit feeding
   a) These are another group of neurons in the x, containing not NPY or AgRP but x
   b) They cleave x to make x, which they release at their x
2. Arc-POMC neurons project mainly to x
   a) α-MSH is released from the synapses of x cells and excites neurons in the x and the x
   b) It inhibits neurons in the x
3. One result is increased activity in the x
   a) x and x excite the sympathetic nervous system.
   b) Activity in x inhibits the x, but x inhibits DMH, so the net result is that x, i.e. x
4. x inhibits feeding
5. Arc-POMC is excited by x and inhibited by x

Answer 2

1. In the postprandial state, arcuate POMC neurons inhibit feeding
   a) These are another group of neurons in the arcuate nucleus, containing not NPY or AgRP but pro-opiomelanocortin (POMC).
   b) They cleave POMC to make α-melanocyte stimulating hormone (α-MSH), which they release at their synapses
2. Arc-POMC neurons project mainly to other hypothalamic nuclei
   a) α-MSH is released from the synapses of POMC cells and excites neurons in the PVN and the ventromedial hypothalamus (VMH).
   b) It inhibits neurons in the dorsomedial hypothalamus (DMH
3. One result is increased activity in the sympathetic nervous system
   a) PVN and VMH excite the sympathetic nervous system.
   b) Activity in DMH inhibits the sympathetic system, but Arc-POMC inhibits DMH, so the net result is that sympathetic activity is disinhibited, i.e. increased
4. sympathetic activity inhibits feeding
5. Arc-POMC is excited by sympathetic activity and inhibited by Arc-NPY

Question 3

1. x and x centers receive feedback
   a)Control of feeding, like most control systems in the body, works based on x, i.e. on signals that tell the control center how close the system is to some goal state, or set point.
   b) In feeding, the set point x. Rats with x don’t get fatter and fatter for ever, but level off at a new set point above their original weight; and rats with LH lesions level off at a new, low set point.
2. The hypothalamus infers body weight from **
   a) ** is a protein released into the blood mainly by X, so the more X you have, the more circulating **.
   b) Some cells in the body have X for **, including especially cells in X and X centers of the hypothalamus.
   c) Mutations in the genes that produce ** or the ** receptor
   cause X
3. ** inhibits the feeding centers X and X, and excites X
   A) ** also excites X and X,
   and inhibits X

Answer 3

1. Hypothalamic feeding and anorexigenic centers receive feedback
   a)Control of feeding, like most control systems in the body, works based on negative feedback, i.e. on signals that tell the control center how close the system is to some goal state, or set point.
   b) In feeding, the set point defines a target body weight. Rats with VMH lesions don’t get fatter and fatter for ever, but level off at a new set point above their original weight; and rats with LH lesions level off at a new, low set point.
2. The hypothalamus infers body weight from leptin levels
   a) Leptin is a protein released into the blood mainly by fat cells, so the more fat you have, the more circulating leptin.
   b) Some cells in the body have membrane receptors for leptin, including especially cells in the feeding and anorexigenic centers of
   the hypothalamus.
   c) Mutations in the genes that produce leptin or the leptin receptor
   cause obesity in mice and humans
3. Leptin inhibits the feeding centers Arc-NPY and LH, and excites PVN
   b) Leptin also excites Arc-POMC and VMH,
   and inhibits DMH

Question 4

1. How does your brain know when to end a meal?
   a) Not from leptin, because **: you don’t lay on much new fat during a single meal. The control system needs faster sources of feedback.
   b) One of these faster signals is **:: it **:: as you eat, and its rising level excites **:: and inhibits **::, inhibiting **::
   c) Other mechanisms involve **:: and **:: that measure **:: and **::, and respond by **::that act on the **::
2. In the postprandial state, **::
   inhibit feeding
   a) Sensors in the wall of the small intestine detect **:: and **:: and **::, leading to the release of **:: **::and **::
   b) These hormones act via the **:: to excite **::, **::, and **:: and to inhibit **::. They also excite the **::, which excites **:: via the **::
3. in fasting, **:: released from the stomach encourages **::
   a) **::, the hunger hormone, is released into the blood by **:: when **::; stretching the stomach **::
   b) **:: acts directly on **:: and **:: (exciting them) and on **:: (inhibiting it)

Answer 4

1. How does your brain know when to end a meal?
   a) Not from leptin, because it is too slow: you don’t lay on much new fat during a single meal. The control system needs faster sources of feedback.
   b) One of these faster signals is blood glucose: it increases as you eat, and its rising level excites Arc-POMC and inhibits LH, inhibiting further feeding.
   c) Other mechanisms involve sensors in the walls of the stomach and intestines that measure nutrients and stretch, and respond by releasing hormones that act on the hypothalamus
2. In the postprandial state, gut hormones
   inhibit feeding
   a) Sensors in the wall of the small intestine detect stretch and sugar and protein, leading to the release of cholecystokinin (CCK), peptide YY (PYY), and glucagon-like peptide 1 (GLP-1).
   b) These hormones act via the blood to excite Arc-POMC, PVN, and VMH and to inhibit DMH. They also excite the vagus nerve, which excites VMH via the nucleus tractus solitarius, NTS
3. in fasting, ghrelin released from the stomach encourages feeding
   a) Ghrelin, the hunger hormone, is released into the blood by cells in the stomach wall when the stomach is empty; stretching the stomach stops ghrelin release.
   b) Ghrelin acts directly on Arc-NPY and LH (exciting them) and on PVN (inhibiting it)

Question 5

Drug treatments for obesity

1. Many drugs suppress **, but **,, e.g. amphetamines and fenfluramine (an anti-obesity drug withdrawn in 1997 because of cardiovascular side effects).
2. Rimonabant, which blocks **,, can lead to **,, but causes **,, **,, and **,.
3. **, rarely helps, because **,
4. **, and **, agonists have been tested, without much success. A **, agonist called **, may be better.

Answer 5

1. Many drugs suppress appetite, but they are dangerous, e.g. amphetamines and fenfluramine (an anti-obesity drug withdrawn in 1997 because of cardiovascular side effects).
2. Rimonabant, which blocks CB1 endocannabinoid receptors, can lead to moderate weight loss, but causes nausea, major depression, and suicide.
3. Leptin rarely helps, because fewer than 1% of humans with morbid obesity are leptin-deficient.
4. CCK and PYY agonists have been tested, without much success. A GLP-1 agonist called liraglutide may be better.