Psyc417 Hypothamalus
Last updated: 1/9/2025
Questions
What is the arcuate nucleus?
Notes
Craniopharyngamia is a tumor between the pituitary gland and the hypothalamus. Pituitary adenoma is a benign tumor that can cause hyperphagia.
Ventromedial hypothalamus is considered the satiety center and rats with ventromedial hypothalamus lesions are hyperphagic and obese. Lateral hypothalamus is considered the hunger center and rats with lateral hypothalamus starved to death. There is not ONE hunger or satiety center, but multiple.
Rats that were obese before VMH lesions did not overeat and they started to lose weight slightly after lesion. Rats that are lean and then get the VMH lesion instantly become obese.
Lateral hypothalamus lesions lead to aphagia and adipsia. These rats recover first by eating wet and palatable foods, then they can regulate food intake and body weight on wet palatable foods, then they eat dry foods, and finally they are able to drink water and survive. Animals with LH lesion that are starved will instead gain body weight of getting anorexia.
The LH has to do with body set-point. If animal is lean it will gain weight, if else it will starve.
There is no specific area as a feeding center this is because aspects of feeding syndromes can be mimicked by knife cuts that damage tracts passing through the hypothalamus. Also, 6-hydroxydopamine, is a neurotoxic that specifically kills dopamine neurons. This mimics LH syndrome. Deleting noradrenergic axons originating in the hindbrain mimics VMH syndrome. Other neurotransmitter mediates eating such as serotonin, cannabinoid, optiods.
Homeostatic food intake involves coordination between GI and adiposity signals, DVC and the hypothalamus.
Hypothalamic Signals
There are orexigenic signals which include neuropeptide (NPY), agouti-related protein (AgRP), melanin concentraing hormone (MCH). These increase food intake and decrease energy expenditure.
There are instead anorexigenic signals which include pro-opiomelanocortin (POMC), melanocyte-stumlating hormones (MSH), cocain and amphetamine regulated transcript (CARD). This decreases food intake and increases energy expenditure.
Having a low body-fat signal means you have low leptin which biases orexigenic and inhibits anorectic signals. Vice versa for high body fat.
Melanocortin system is an important system.
POMC is expressed in the arcuate nucleus (ARC) of hypothalamus & cNST. POMC gets cleaved into melanocyte stimulating hormone.
MC3R (Melanocortin 3-receptor) and MC4R manage homeostasis. MC4 receptor is important and it cares about Beta, thean alpha, than gamma version of MSH. It is inhibited by AgRP.
Proprotein convertase 1/3 (PC 1/3) cleaves POMC into aphra and beta-MSH which are MC4R agonist. MC4R genetic mutation is the number one obesity causing mutation.
AgRP neurons also express NPY and GABA.
Neonatal ablation has little effect, but sudden loss of AgRP neurons in adulthood causes self-starvation. This anorexia can be reversed by administration of GABA agonist.
AgRP is an endogenous MC4R antagonist
NPY interacts with GPCYR. It is synthesized in neurononal cell bodies, often in GABAergic neurons, particularly in the hypothalamic arcuate nucleus (ARC). It is found in the hypothalamus, hippocampus, amygdala, and nucleus accumens. It has multiple functions such as overeating, anxiety, and decreased sensitivity to pain.
NPY/AgRP and POMC/CART neurons are pimary sensor of alterations in energy stores.
Paraventricular nucleus (PVN ) of the hypothalamus and lateral hypothalamus. Melanin concentrating hormore neuons receive information from ARC and conts the brainstem, by sending information to the dorsol vagal complex. It causes increase in food intake.
Leptin stimulates POMC and CART. Stimulating melanocortin pathway will allow people to lose weight. A way to combat obesity is to create an MC4R agonist (which would be an anorexigenic signal).
There is a weightloss drug that combats genetic obesity by creating MC4R agonist. It targets definiteicies of POMC, PCSK1(which codes for PC1/3) and leptin receptor deficiency.
AgRP neurons project to paraventricular nucleus of hypothalamus, LH, amygdala... POMC neurons projects to the PVN, LH, and PBN
Optogenetic method creates light-sensitive ion channel which lights up the neurons.
AgRP can have a quick timulation and it will cause its effect, but actional of POMC neurons takes a long time to have its effect.
Hypocretin/Orexin neurons were thought to be the same as the neurons that express MCH but they are a different population of neurons. Their activity increases during fasting and reduces once food is consumed. They activate the orexin receptor within the hypothealamus to increase food intake. The actactivation of these neurons promotes food intake but increases energy expenditure. Leptin increases physical activity.
Knocking out orexin renders hypohagia and narcoepsy because it decreases their NEAT. They still become obese because they have decreased movement even if they eat less.
Orexin neurons project to multiple brain areas including feeding and reward regions such as ventral tegmental area (VTA) and nucleus accumebns (NAc). While you are awake there is high level of orexin activity, when you are sleep, there is none.
Orexin neurons are involved in arousal and motivation, any salient signal (such are getting a reward, escaping a stressor, or a sexual opporunity) will boost orexin signals. A cue that leads to a stronger reward will take longer to go extinct compared to a weaker signal.
Feeding behavior is relatively fixed during childhood. For the 5 month dutch famine when children were undernutritioned they didn't have many symptoms early in life but they had difficulty focusing their attention.
Folate is required for DNA synthesis