QUESTIONS on Neuroscience Lecture 21 Motivation

Regarding the two hypothalamus areas discussed and lesions:

1) Are the MC4 receptors inhibiting the active state of the lateral hypothalamic neuron? If I understand your
question, MC4 activation will inhibit the activity of the LHA neuron. 2) Why do we need two types of medial hyp.
neurons for its regulation? Why questions are always hard because they become a little philosophical. You need a
mechanism for stimulating behaviour for energy intake lets face it, we are in a relatively rare time and place
where all you have to do is wander down to the shopsor just to your fridge, to get a decent meal. It has been
dangerous to get food. It requires effort and so we need a pathway linked into the energy storage system to
promote the behaviour. But I think the drive to eat is very powerful and extends past the need for energy
enjoyment, culture, etc. So to stop that you also need a mechanism for inhibiting the behaviour, not just removing
the drive. That then is my rationale for having two opposing systems regulating food intake. What do you think?
Here is my line of thought leading to these questions:
ad1) arcuate nucleus/VMH lesion -> overweight.
Lateral hyp. lesion -> underweight.
why?
intrinsically, the lateral hyp. lesion must enable the stimulation of food intake, because without its signal, the
organism doesn't eat. If it intrinsically stimulates food intake, why would the POMC reduce food intake by activating
it? Does stimulation of the receptors actually decrease neuronal activity? Yes is the short answer.
You also need to consider that brain pathways are rarely singular and point to point. Lets say we have a group of
cortical neurons that are the food intake behaviour neurons. These probably receive input from many sources
mood pathways, temperature pathways, energy balance pathways etc. These probably tick along providing mostly
sub-threshold inputs lets for arguments sake say there are 3 inputs each at baseline providing of the input
required for activation of the behaviour. Now we have reduced energy stores and need to eat. The energy pathway
doubles its activity so now we have 2/4 + + - threshold and activation. Lets say you are hot and the temperature
pathway is turned off. Now you need more drive from the other pathways to take you to threshold. Similarly
activation of the POMC pathway reduces the LHA input and takes the circuit further away from threshold.
Then the AgRP would act as inhibition of stimulation of inhibition and thus activate the neuron? Yes
ad2) If it's intrinsically active, why do we need two kinds of neurons then and not just one that inhibits it? Or is it
more that one starts food intake and the other one stops it, so if we have no signaling we wouldn't start eating, but
if we did we also couldn't stop? I think above answers this.
3) How is the metabolic rate reduced without major impact on other systems which functions would also be
lowered? How long can this reduction be held up before this would be adjusted again (if the food intake stays low
for a long time before it increases again) Reduced metabolic rate does affect everything. People who diet feel more
slow and tired when the metabolic rate is lowered. I am not sure though whether metabolic rate would bounce back
after time I suspect not as it would place the body in more severe energy crisis.

Regarding the endocannabinoid system:

1) Taking cannabis stimulates food intake, here we block the receptor instead - but why would that have the same
psychotropic effects as cannabis then? Not the same cannabis tends to be associated with euphoria antagonists
are depressive. The point I was making was that the antagonists induced unacceptable changes in mental state.
2) Decreasing metabolism leads to less energy burning -> so why is body weight reduced (long-term) by
administering this drug, even though metabolism is also decreased as a consequence? The decreased body weight
we observed over the longer term was due to increased brown fat activity and that futile energy burning cycle.

Regarding the reward system:

1) How does the ventral tegmental area stand in relation to food intake is it stimulated by serotonine in response?
Where does the area output to for the motivation for eating to take place or, to formulate it differently, in which
brain area does motivation ultimately come to be? I think the first part is not clear, but most brain regions receive a
serotonergic input and I suspect the VTA is no different. You would quickly search the literature to find that one out.
We consider motivated behaviours are being cortical for feeding/drinking the anterior cingulate is likely important.
2) How is the action of food intake reinforced? Same as drug addiction stimulation of the dopaminergic pathway.
3) Can it be reversed? Big question occupying many research teams.
4) Why are some people more susceptible to it? Big question occupying many research teams.
5) Would the same people also be more susceptible to other drugs and if not, why not? Big question occupying
many research teams, but apparently so. Why is a really interesting question. Why is one persons stress anothers
mere annoyance? We have some ideas and are working on it, but it is difficult.