Motivation

Question 1

What is the integrated response to bring the parameter back to its optimal value generally broken into?

Answer 1

1. Humoral response: hypothalamic neurons respond to sensory signals by stimulating or inhibiting the release of pituitary hormones into the bloodstream
2. Visceromotor response: neurons in the hypothalamus respond to sensory signals by adjusting the balance of sympathetic and parasympathetic outputs of the autonomic nervous system (ANS)
3. Somatic motor response: Hypothalamic neurons (particularly within the lateral hypothalamus) response to sensory signals by inciting an appropriate somatic motor behavioural response

Question 2

what is prandial state?

Answer 2

-The body’s energy stores being replenished during and immediately after consuming a meal, blood is filled with nutrients
-during this time, energy is stored in 2 forms: glycogen and triglycerides

Question 3

describe the energy stored in glycogen form

Answer 3

-glycogen reserves have a finites capacity, they are found mainly in the liver and skeletal muscle

Question 4

describe the energy store in triglyceride reserves

Answer 4

-found in adipose (fat) tissue, and they have virtually unlimited capacity

Question 5

what is anabolism?

Answer 5

-the assembly of macromolecules such as glycogen and triglycerides from simple precursors is called anabolism (aka anabolic metabolism)

Question 6

what is the postabsorptive state?

Answer 6

-the fasting condition between meals
-stored glycogen and triglycerides are broken down to provide the body with a continuous supply of the molecules used as fuel for cellular metabolism (glucose for all cells, and fatty acids and ketones for all cells other than neurons)

Question 7

what is catabolism?

Answer 7

-the process of breaking down complex macromolecules is called catabolism or catabolic metabolism, its the opposite of anabolism

Question 8

when is the system in proper balance? and what happens when the intake and storage of energy consistently exceeds usage or fails to meet the body’s demands

Answer 8

-when energy reserves are replenished at the same average rate that they are expended
-if the intake and storage of energy consistently exceed the usage, the amount of body fat, or adiposity, increases, eventually resulting in obesity
-if the intake of energy consistently fails to meet the body’s demands, loss of fat tissue occurs, eventually resulting in starvation

Question 9

what is lipostatic hypothesis?

Answer 9

-the idea that the brain monitors the amount of body fat and acts to “defend” this energy store against perturbation

Question 10

what gene is responsible for encoding the hormone telling the brain that fat reserves are normal? and how was this demonstrated?

Answer 10

-a gene called ob
-demonstrated by mice who lack both copies of the ob gene (aka ob/ob mice) overate
-to test this a parabiosis experiment was performed. when ob/ob animals were parabiosed with normal mice, their feeding behaviour and obesity were greatly reduced, as if missing hormone had been replaced)

(parabiosis is a long term anatomical and physiological union of two animals, as in Siamese twins. fusion can also be achieved surgically, thereby resulting in parabiosed animals sharing a common blood supply)

Question 11

what is leptin?

Answer 11

-a hormone, the protein encoded by the ob gene

Question 12

what does treating ob/ob mice with leptin do?

Answer 12

-completely reverses the obesity and the eating disorder

Question 13

where is leptin released from and what does it do?

Answer 13

-released from adipocytes (fat cells), regulates body mass by acting directly on neurons of the hypothalamus that decrease appetite and increase energy expenditure

Question 14

what lesions of hypothalamus cause anorexia and obesity?

Answer 14

-anorexia –> bilateral lesions of the lateral hypothalamus – severely diminished appetite for food –>lateral hypothalamic syndrome

-obesity –> bilateral lesions of the ventromedial hypothalamus –> overeating –> ventromedial hypothalamic syndrome

Question 15

what happens when leptin molecules circulate in the bloodstream?

Answer 15

• Circulating leptin molecules, released into the bloodstream by fat cells, activate leptin receptors on neurons of the arcuate nucleus of the hypothalamus, which lies near the base of the third ventricle.
• The arcuate neurons that are activated by a rise in blood leptin levels contain peptide neurotransmitters called alpha-MSH and CART, the levels of these peptides in the brain vary in proportion to the level of leptin in the blood.

Question 16

describe the alphabet soup of naming peptides

Answer 16

-peptides are often named by their first discovered function, and these names can lead to confusion when other roles are recognised. Therefore, neuropeptides are usually referred to simply by their abbreviations. e.g., alpha-MSH stands for alpha-melanocyte-stimulating hormone, and CART stands for cocaine- and amphetamine-regulated transcript. like other neurotransmitters, the functional role of these molecules depends on the circuits in which they participate

Question 17

what happens when there is excessive adiposity, high leptin levels and activation of the alpha-MSH/CART neurons of the arcuate nucleus?

Answer 17

-Humoral response –> increased secretion of TSH (thyroid-stimulating hormone) and ACTH (adrenocorticotropic hormone) –>these pituitary hormones act on the thyroid and adrenal glands and have the effect of raising the metabolic rate of cells throughout the body
-Visceromotor response –> increases tone of sympathetic division of the ANS, which raises metabolic rate, in part by raising body temperature
-Somatic motor response –> decreases feeding behaviour

-the alpha-MSH/CART neurons of the arcuate nucleus project their axons directly to the regions of the nervous system that orchestrate this coordinated response

Question 18

how is humoral, visceromotor and somatic response activated?

Answer 18

-alpha-MSH/CART neurons trigger the humoral response by activating neurons in the paraventricular nucleus of the hypothalamus, which in turn causes the release the hypophysiotropic hormones that regulate the secretion of TSH and ACTH from the anterior pituitary.
-the paraventricular nucleus also controls the activity of the sympathetic division of the ANS with direct axonal projections to neurons in the lower brain stem and to preganglionic neuron in the spinal cord. Additionally, there is also a direct path for arcuate control of the sympathetic response: The alpha-MSH and CART neurons themselves project axons directly down to the intermediolateral gray matter of the spinal cord.
-finally, feeding behaviour is inhibited via connections of the arcuate nucleus neurons with cells in the lateral hypothalamus

Question 19

what does the injection of alpha-MSH and CART into the brain do?

Answer 19

-Mimics the response to elevated leptin levels. Thus, these are said to be anorectic peptides; they diminish appetite
-the injection of drugs that block the actions of these peptides increases feeding behaviour.
-these findings suggest that alpha-MSH and CART normally participate in the regulation of energy balance, in part by acting as the brain’s own appetite suppressants

Question 20

what does a fall in leptin levels cause?

Answer 20

-turning off the responses mediated by alpha-MSH/CART neurons
-stimulated another type of arcuate nucleus neuron, these neurons contain their own mix of peptides: NPY (neuropeptide Y) and AgRP (agouti-related peptide)

Question 21

describe the connections and consequence of NPY/AgRP neurons activation

Answer 21

-NPY/AgRP neurons of arcuate nucleus also have connections with the paraventricular nucleus and lateral hypothalamus.
-the effects of these neuropeptides on energy balance are the opposite of the effects caused by alpha-MSH/CART neurons
-NPY and AgRP inhibit the secretion of TSH and ACTH, they activate the parasympathetic division of the ANS, and they stimulate feeding behaviour –> they are there referred to as orexigenic peptides

Question 22

describe the relationship of AgRP and alpha-MSH

Answer 22

-antagonistic neurotransmitters
-both peptides bind to the MC4 receptor on postsynaptic neurons in the hypothalamus
-alpha-MSH activated the receptors and AgRP inhibits it
-activation of MC4 receptors on lateral hypothalamic neurons inhibits feeding; inhibiting the receptors stimulates feeding

Question 23

What is the role MCH (melanin-concentrating hormone) in terms of lateral hypothalamus?

Answer 23

-one group of neurons in the lateral hypothalamus that receives direct input from the leptin-sensitive cells of the arcuate nucleus has yet another peptide neurotransmitter called MCH
-these cells have extremely widespread connections in the brain, including monosynaptic innervation of most of the cerebral cortex –> the cortex is involved in organising and initiating goal-directed behaviours, such as raiding the fridge.
-the MCH system is in a strategic position to inform the cortex of leptin levels in the blood and therefore could contribute significantly to motivating the search for food
-supporting this idea, the injection of MCH into the brain stimulates feeding behaviour. Moreover, mutant mice that lack this peptide exhibit reduced feeding behaviour, have elevated metabolic rate and are lean

Question 24

what is the role of lateral hypothalamic neurons containing peptide orexin?

Answer 24

-this is a second population of lateral hypothalamus neurons with widespread cortical connections (MCH is the other one)
-these cells receive direct inputs from the arcuate nucleus.
-orexin is an orexigenic peptide (stimulates feeding behaviour)

Question 25

describe what happens when with MCH and orexin when leptins levels on blood fall

Answer 25

-levels of both MCH and orexin rise in brain
-these 2 peptides are complementary, not redundant
- e.g., orexin promotes meal initiation, whereas MCH prolongs consumption

Question 26

describe orexin and its relationship with sleep

Answer 26

-orexin aka hypocretin, plays very important role in regulation of wakefulness
-gene mutations that disable orexin (hypocretin) signalling not only lead to weight loss but also to excessive daytime sleepiness
-insomnia and obesity often comorbid

Question 27

summarise hypothalamic response to blood leptin levels.

Answer 27

leptin levels rise when body fat is increase, they fall when body fat is decrease

-a rise in leptin levels stimulate the release of alpha-MSH and CART from arcuate nucleus neurons. These anorectic peptides act on the brain, in part by activating the MC4 receptor, to inhibit feeding behaviour and increase metabolism
-a fall in leptin levels stimulates the release of NPY and AgRP from arcuate hypothalamic area. These orexigenic peptides act on the brain to stimulate feeding behaviour and decrease metabolism

Question 28

how is the regulatory process of the drive to eat and not eat regulated?

Answer 28

-drive to eat, increased by orexigenic signals generated in response to a period of fasting
-inhibited by satiety signals that occur when we eat and begin the process of digestion (i.e., the prandial period.)
-these satiety signals both terminate the meal and inhibit the feeding for some time afterwards
-During this postabsorptive (fasting) period, the satiety signals slowly dissipate, and the orexigenic signals build, until the drive to eat again takes over

Question 29

What is the cephalic phase?

Answer 29

First phase
-The sight and smell of food triggers a number of physiological processes that anticipate the arrival of food. The parasympathetic and enteric divisions of the ANS are activated, causing the secretion of saliva into your mouth and digestive juices into your stomach.

Question 30

What is the gastric phase?

Answer 30

Second phase
-These responses of the cephalic phase grow much more intense, when you start chewing, swallowing, and filling your stomach with food

Question 31

What is the substrate phase?

Answer 31

third phase
-As your stomach fills and the partially digested food move into your intestines, nutrients begin to be absorbed into your bloodstream

Question 32

what is ghrelin?

Answer 32

-peptide
-highly concentrated in the stomach and is released into the bloodstream when the stomach is empty
-your growling stomach releases ghrelin (“ghrrrrrrelin).
-intravenous administration of ghrelin strongly stimulates appetite and food consumption by activating the NPY/AgRP - containing neuron of the arcuate nucleus (same neurons activated by a drop in leptin in the bloodstream

Question 33

Describe gastric distention

Answer 33

-stretching of stomach wall is powerful satiety signal –> wall is richly innervated by mechanosensory axons, most of these ascend to the brain via vagus nerve (cranial nerve X (10))
-the vagal sensory axons activate neurons in the nucleus of the solitary tract in the medulla –> these signals inhibit feeding behaviour

Question 34

describe cholecystokinin (CCK) in relation to eating behaviour

Answer 34

-administration of CCK inhibits meal frequency and size.
-Present in some of the cells that line the intestines and some of the neurons of the enteric nervous system
-released in response to stimulation by certain types of food, especially fatty ones.
-major action of CCK as a satiety peptide is exerted on the vagal sensory axons
-CCK acts synergistically with gastric distension to inhibit feeding behaviour
-CCK is also contained within selected populations of neurons with CNS

Question 35

Describe the role of insulin

Answer 35

-releases into the bloodstream by the beta cells of the pancreas
-Although glucose is always readily transported into neurons, glucose transport into the other cells of the body requires insulin –> important for anabolic metabolism when glucose is transported into liver, skeletal muscle, and adipose cells for storage as well as catabolic metabolism when the glucose liberated from storage sites is taken up as fuel by the other cells of the body –> thus, level of glucose in blood is tightly regulated by level of insulin.
- Blood glucose levels are elevated when insulin levels are reduced; blood glucose levels fall when insulin levels rise

Question 36

Describe the release and inhibition of insulin

Answer 36

-during the cephalic phase, when you’re anticipating food, the parasympathetic nervous system innervation of the pancreas (delivered by the vagus nerve) stimulates the beta cells to release insulin. in response, blood glucose levels fall slightly, and this change, detected by the neurons of the brain, increases your drive to eat (in part, part activation of the NPY/AgRP neurons of the acruate nucleus)
-During the gastric phase, when food enters your stomach, insulin secretation is stimulated further by gastrointestinal hormones, such as CCK
-insulin release is maximal when the food is finally absorbed in the intestines and blood glucose levels rise, during the substrate phase.
-primary stimulus for inuslin release is increases blood glucose levels
-the rise in insulin, coupled with the elevated blood glucose levels, is a satiety signal and causes you to stop eating

Question 37

how does insulin act to inhibit feeding behaviour compared to other satiety signals

Answer 37

-other satiety signal communicate with brain mainly via vagus nerve
-bloodborne insulin acts to inhibit feeding behaviour by acting directly on the arcuate and ventromedial nuclei of the hypothalamus
-it appears that insulin acts in much the same way as leptin to regulate feeding behaviours

Question 38

what is the drive reduction of wanting food?

Answer 38

We eat because we are hungry and we want food, i.e., satisfying a craving

Question 39

Describe electrical self-stimulation

Answer 39

-where animals repeatedly deliver electrical stimulation by way of the lever. Sometimes they would shun food and water for this stimulation since it gave them positive feelings
-appeared to provide a reward that reinforced the habit of pressing the lever

Question 40

What areas of the brain were found to be most effective sites for self-stimulation and what does it mean? and give evidence

Answer 40

-most effective sites were along the trajectory of dopaminergic axons arising in the ventral tegmental area, projecting through the lateral hypothalamus to several forebrain regions
-drugs that block dopamine receptors reduced self-stimulation, suggesting that the animals were working to stimulate the release of dopamine in the brain –> this idea was further supported when researchers discovered that animals will press a lever to receive an injection of amphetamine, a drug that releases dopamine in the brain

Question 41

where does most of the dopamine projections for the brain come from?

Answer 41

from the ventral tegmental areas to the forebrain

Question 42

how does an animal act with food when it is dopamine deprived? and when there is stimulation of dopamine axons

Answer 42

-acts as if it likes food but does not want food
-lacks the motivation to seek food, even though it may seem enjoyable when available
-stimulation of the dopamine axons in the lateral hypothalamus of normal rats appears to produce a craving for food without increasing the food’s hedonic impact. (some highly addictive drugs, cocaine, amphetamine for example, act directly on the dopamine synapses on brain

Question 43

describe reward prediction

Answer 43

-events that are “better than expected” cause dopamine neurons to come to life, those that are “worse than expected” cause them to be inhibited, and those that occur “as expected” cause no change in firing, even if these events still provide hedonic reward.
-behaviours that cause expected or better-than-expected outcomes are repeated; those with outcomes that are worse than expected are not.

Question 44

describe the type of learning that is related to dopamine and eating

Answer 44

-smelling or seeing food can predict meals, this type of learning is integral to the body’s “cephalic” preparation for ingestion of a meal. Dopamine is intimately involved in the mechanism behind this learning.
-synaptic connections that are active during and shortly before the rise in dopamine are persistently changed to store this memory
-while this type of learning is beneficial under normal circumstances, it is hijacked during exposure to addictive drugs, often with devastating consequences. They act on the central dopaminergic system in brain

Question 45

describe serotonin and its role eating and mood.

Answer 45

-Measurements of serotonin in the hypothalamus reveal that levels are low during the postabsorptive period, rise in anticipation of food, and spike during a meal, especially in response to carbohydrates
-serotonin is derived from the dietary amino acid tryptophan, and tryptophan levels in the blood vary with the amount of carbohydrate in the diet
-the rise in blood tryptophan and brain serotonin is one likely explanation for the mood-elevating effects of carbs
-this effect of carbs on mood is particularly evident during periods of stress, possibly explaining the food-seeking behaviour –> drugs that elevate serotonin levels in the brain are powerful appetite suppressants (e.g., dexfenfluramine), but have side effects
-abnormalities in brain serotonin regulation are believed to be one factor that contributes to eating disorders
-defining characteristics of anorexia nervosa is a compulsion to maintain body weight at an abnormally low level
- while bulimia nervosa is characterised by frequent eating binges, often compensated for by forced vomiting
-these eating disorder commonly accompanied by depression which is linked to lowered levels of serotonin levels

Question 46

what are the 2 different physiological signals that stimulate drinking behaviour?

Answer 46

-one way is the decrease in blood volume, or hypovolemia
- the other is an increase in the concentration of dissolved substances (solutes) in the blood, or hypertonicity
-these 2 stimuli trigger thirst by different mechanisms

Question 47

describe thirst trigger by hypovolemia

Answer 47

-is called volumetric thirst
-decreased blood volume also releases vasopressin in posterior pituitary by the magnocellular neurosecretory cells
-vasopressin (aka antidiuretic hormone (ADH)) acts directly on the kidneys to increase water retention and inhibit urine production
-The release of vasopressin associated with volumetric thirst is triggered by two types of stimuli –> First, a rise in blood levels of angiotensin II occurs in response
to reduced blood flow to the kidneys. The circulating angiotensin II acts on the neurons of the subfornical organ in the telencephalon, which in turn directly stimulate the magnocellular neurosecretory cells of the hypothalamus to release vasopressin –> Second, mechanoreceptors walls of the major blood vessels and heart signal the loss of blood pressure that accompanies a loss of blood volume. These signals make their way to the hypothalamus via the vagus nerve and the nucleus of the solitary tract.
- In addition to this humoral response, reduced blood volume (1) stimulates the sympathetic division of the ANS, which helps correct the drop in blood pressure by constricting arterioles, and (2) powerfully motivates animals to seek and consume water. lateral hypothalamus has been implicated in inciting the behavioural response, but this is poorly understood.

Question 48

describe thirst trigger by hypertonicity

Answer 48

Hypertonicity is sensed by neurons in yet another specialized region of the telencephalon lacking a blood–brain barrier, the vascular organ of the lamina terminalis (OVLT). When the blood becomes hypertonic, water leaves cells by the process of osmosis. This loss of water is transduced by the OVLT neurons into a change in action potential firing frequency.
- The OVLT neurons (1) directly excite the magnocellular neurosecretory cells that secrete vasopressin, and (2) stimulate osmometric thirst, the motivation to drink water when dehydrated. Lesions of the OVLT completely prevent the behavioural and humoral responses to dehydration (but not the responses to loss of blood volume).

Question 49

describe what occurs as a result of a loss of vasopressin-secreting neurons

Answer 49

-The motivation to drink and the secretion of vasopressin from the hypothalamus (and the retention of water by the kidneys) normally go hand in hand. However, selective loss of the vasopressin-secreting neurons of the hypothalamus produces a curious condition called diabetes insipidus, in which the body works against the brain. As a consequence of the loss of vasopressin, the kidneys pass too much water from the blood to the urine. The resulting dehydration stimulates the strong motivation to drink water; however, the water absorbed from the intestines passes quickly through the kidneys into the urine. Thus, diabetes insipidus is characterized by extreme thirst coupled with frequent excretion of a large amount of pale, watery
urine. This condition can be treated by replacing the missing vasopressin.

Question 50

what is the humans body temperature

Answer 50

-37 degrees and deviations from this temperature interfere will cellular functions
- neurons that change their firing rate in response to small changes in temperature are found throughout the CNS

Question 51

what is the most important neurons for temperature homeostasis and describe its role

Answer 51

-Most important neurons for temperature homeostasis found clustered in the anterior hypothalamus. These cells transduce small changes in blood temperature into changes in their firing rate. Humoral and visceromotor responses are subsequently initiated by neurons in the medial preoptic area of the hypothalamus; somatic motor (behavioural) responses are initiated by the neurons of the lateral hypothalamic area. Lesions in these different regions can selectively abolish different components of the integrated response.
-A fall in temperature is detected by cold-sensitive neurons of the anterior hypothalamus. In response, TSH is released by the anterior pituitary. TSH stimulates
the release of the hormone thyroxin from the thyroid gland, which causes a widespread increase in cellular metabolism. The visceromotor response is constricted blood vessels in the skin and piloerection (goose bumps). An involuntary somatic motor response is shivering (to generate heat in the muscles), and, of course, the other somatic response is to seek warmth. A rise in temperature is detected by warm-sensitive neurons of the anterior hypothalamus. In response, metabolism is slowed by reducing TSH release, blood is shunted toward the body periphery to dissipate heat, and behaviour is initiated to seek shade. In some mammals, an involuntary motor response is panting—in humans, it is sweating—which helps cool the body