lecture 18

Question 1

Do sympathetic neurons (and parasympathetic?) function autonomously?

Answer 1

• no, they require input in order to fire

Question 2

What is the hierarchical control of the autonomic nervous system?

Answer 2

• End organs provide feedback about their state (e.g. brain and oxygen supply via blood)
• spinal visceral sensory neurons (e.g. cranial nerves IX and X)
• feedback inputs on nucleus of solitary tract (in the medulla)
• from here many pathways:
  1. loops within the medulla that come straight back out to the end organ (preganglionic neurons in brainstem/spinal cord, primary motor neurons in autonomic ganglia, end organ) (e.g. baroreceptor reflex)
  2. parabrachial nucleus (to cortex) (we won’t focus on it)
  3. inputs onto hypothalamus
  4. inputs onto autonomic centres in brainstem reticular formation
• information gets processed in the cortex before descending down through the autonomic nervous system as well
• hypothalamus: the conductor, regulates patterns of autonomic innervation; e.g. after a meal ensures you still have adequate blood perfusion outside of the gut
• amygdala: plays an important role in memory and fear related changes to autonomic nervous system activity

Question 3

How is the hypothalamus central to conducting the autonomic (and other) response?

Answer 3

Hypothalamus receives:

1. contextual information: cerebral cortex, amygdala, hippocampal formation
2. sensory inputs: visceral and somatic sensory pathways, chemosensory and humoral signals

Hypothalamus compares input to biological set points and coordinates the visceral motor, somatic motor, neuroendocrine and behavioural responses

Question 4

How much glycogen can we store?

Answer 4

• a limited amount

Question 5

How do we store energy?

Answer 5

• as glycogen and as triglycerides

Question 6

Where do triglycerides get stored?

Answer 6

• in adipose tissue

Question 7

How much triglyceride can we store in adipose tissue?

Answer 7

• work on the assumption that there is almost a limitless ability to store triglycerides in adipose tissue

Question 8

Does the body attempt to maintain a level of adiposity and weight?

Answer 8

• yes
• if you starve a rat for a period of time it will maintain its body weight but eventually this will be overcome and it will lose weight (when re-fed it will come back to normal)
• similarly in periods of forced feeding it will maintain weight for a period of time but eventually begin to put on weight

Question 9

What is being monitored in the body’s attempt to maintain a level of adiposity and weight?

Answer 9

• evidence suggests that it is body fat

- the lipostatic hypothesis

Question 10

What is key to detecting body fat?

Answer 10

• hypothalamus:
• paroventricular nucleus (PVN)
• lateral hypothalamic area
• arcuate nucleus

Question 11

What hypothalamic lesions can affect weight?

Answer 11

• lesions of lateral hypothalamus lead to lateral hypothalamic syndrome (too lean)
• lesions of the ventromedial hypothalamus lead to ventromedial hypothalamic syndrome –> obese rats

Question 12

What is balanced in the maintenance of body weight/fat? How?

Answer 12

• food intake and energy expenditure
• there are key nuclei, and key neurons within those nuclei that are very important for the regulation of feeding behaviour
• energy expenditure can be adjusted in the body through brown adipose tissue – sympathetic innervation of brown adipose tissue causes it to burn energy and release heat, thereby wasting energy. Possible to do this because it is usually stored in the periphery (between scapulae is main store)

Question 13

What is in the arcuate nucleus?

Answer 13

• two types of neurons that are key in this whole process
• AgRP/NPY neuron make neuropeptide Y, release of this will increase food intake and decrease energy expenditure
• Other neurons make POMC (pro-opiomelanocorpin): a large peptide, opiates, an important one of these is alpha-MSH (melanocyte stimulating hormone), inhibits food intake, more expenditure
• often go to the same second order neurons to regulate behaviour

Question 14

What does alpha-MSH act on?

Answer 14

• one target is the MC4 receptor in neurons in the lateral hypothalamic area
• inhibits feeding behaviour by activating receptor

Question 15

What does AgRP act on?

Answer 15

functional antagonist of alpha-MSH
comes along and binds to same receptor to prevent it from doing its drop
therefore activates feeding behaviour

Question 16

To where do the arcuate POMC neurons project?

Answer 16

• lateral hypothalamic area to inhibit feeding behaviour
• paraventricular nucleus: the PVN stimulates the release of ACTH and thyrotropin from anterior pituitary, thereby mobilising energy stores; they also activate brain stem neurons and preganglionic neurons of sympathetic ANS to affect brown fat

Question 17

To where to the AgRP/NPY neurons project?

Answer 17

• lateral hypothalamic area: stimulate feeding behaviour

- PVN: inhibit secretion of hypophysiotropic hormones controlling ACTH and TSH

Question 18

What was is something interesting about some neurons in the lateral hypothalamic area?

Answer 18

• some neurons function in both food intake and energy expenditure
• perhaps regulatory neurons

Question 19

For what is the lateral hypothalamus critical?

Answer 19

• regulation of food intake

- and other homeostatic behavious associated with body weight regulation

Question 20

What inputs doe LHA neurons receive from the arcuate nucleus?

Answer 20

• both stimulatory and inhibitory inputs from leptin-sensitive neurons of arcuate nucleus

Question 21

What two main groups of neurons in LHA appear to be involved in food intake?

Answer 21

• Orexin containing – arousal

- Melanin-concentrating hormone containing

Question 22

What is leptin?

Answer 22

• a hormone that is made by and released from adipose tissue
• increased adiposity leads to increased levels of leptin
• a large peptide that is able to affect the neurons of the arcuate nucleus because of the fact that it has a leaky blood-brain barrier (circumventricular organ)
• inhibits activity of feeding intake neurons and stimulates activity of feeding inhibition neurons

Question 23

What molecules affect the activity of the arcuate neurons?

Answer 23

• insulin
• leptin
• some free floating nutrients

Question 24

What experiment was performed using ob/ob mouse and normal mouse?

Answer 24

• very obese mouse was joined via a skin graft to a normal mouse
• they share a blood supply etc
• genetically identical so no transplant response
• parabiosis experiment showed that ob/ob mouse could come back to normal with something in the blood of the normal mouse
• something in the adipose tissue of the ob/ob mouse caused a loss of leptin
• leptin

Question 25

Why do we still have obesity in people despite normal (or even high) levels of leptin?

Answer 25

• with obesity comes leptin resistance

Question 26

What is leptin’s role in food intake?

Answer 26

• the hormone leptin is produced by adipose tissue and acts as a signal to decrease food intake
• • leptin deficiency leads to obesity
• leptin acts via the arcuate nucleus in the basal hypothalamus
• leptin stimulates neurons containing the peptide alpha-melanocyte-stimulating hormone (alpha-MSH) which acts via specific receptors (MC3/4) in the lateral hypothalamus to decrease food intake
• leptin also inhibits another population of neurons in the arcuate nucleus that contain the peptide neuropeptide Y (NPY) which also acts via specific receptors in the lateral hypothalamus to stimulate food intake
• net effect = decrease food intake

Question 27

What do we use to measure adiposity?

Answer 27

leptin

Question 28

What short term mechanisms are in place to regulate food intake/energy expenditure balance?

Answer 28

Food intake triggers satiety signals

• gastric distension (vagus nerve to hindbrain)
• cholecystokinin (vagus nerve to hindbrain)
• insulin (directly to basal hypothalamus)
• • increase insulin in concert with increased glucose is a powerful satiety signal

Multiple factors stimulate food intake
- one of these is decreased blood glucose

Question 29

Why do we eat?

Answer 29

• for energy

- because we like it

Question 30

What is another affect of food intake?

Answer 30

• stimulates dopaminergic neurons in the ventral tegmental area
• widespread influence on frontal cortex
• reward pathway
• hedonic/pleasurable activity

Question 31

Why are substances such as cocaine, heroin and nicotine addictive?

Answer 31

• act on the dopaminergic neurons to prevent reuptake of dopamine therefore extending its affects and activating reward pathway

Question 32

What is the CB1 receptor?

Answer 32

• receptor that binds the active ingredient from marijuana
• marijuana is a very strong driver of food intake –> munchies
• due to this receptor
• why do we have a receptor system for a drug that comes from a weed?
• we also have antagonists - endocanabinoids
• really it’s just hijacking a system that is important for food intake
• if you give the natural antagonist of CB1 to a rat on a high fat diet it will not gain as much weight - potentially it has a role in food intake as well as energy expenditure
• didn’t develop resistance like it would with leptin
• agonists also have influences on perception and awareness and so on which is why it is not used to treat obesity (yet)

Question 33

How is homeostasis maintained?

Answer 33

• by a combination of reflex and motivated behaviours

Question 34

How is energy balance regulated?

Answer 34

• by a number of factors acting over both the long and short term
• leptin: measure of adiposity
• gastric distension and CCK: satiety factors
• insulin: regulator of glucose levels

Question 35

What are critical neurons in the basal hypothalamus that regulate food intake?

Answer 35

in the arcuate nucleus

• alpha-MSH containing neurons inhibit food intake
• NPY containing neurons stimulate food intake
• these affect food intake via projections to the lateral hypothalamus

Question 36

What does energy balance regulation also affect?

Answer 36

• reward and mood pathways in the CNS