UCSF

Food intake is a homeostatic process that requires careful regulation. Appetite drives eating while sensory feedback slows it down. The brain needs to balance these two competing states to avoid obesity or anorexia. Here, I contribute to our understanding of how this process happens by evaluating how key appetite neurons encode and use sensory information to guide behavior. First, I found that agouti-related peptide (AgRP) expressing “hunger” neurons are inhibited in real time by taste cues, and that these neurons use this information to time the end of a meal. Next, I evaluated how key inputs to these neurons respond to different feeding-related sensory information, starting with a known inhibitory input from the dorsomedial hypothalamus (DMH). I found that leptin receptor-expressing neurons therein (DMHLepR) exhibit a variety of activity patterns during feeding, but the robustly activated neurons are specifically tuned to food ingestion, gastrointestinal information, and taste. Following these experiments, I next evaluated how DMHLepR neurons respond to humoral signals. Here I found that DMHLepR neurons activated by food ingestion are inhibited by peripheral serotonin and activated by cholecystokinin injection, amongst a variety of combinations of response types. Finally, I evaluated to what extent a major glutamatergic input to AgRP neurons responds to food: pituitary adenylate cyclase activating peptide expressing neurons in the paraventricular nucleus of the hypothalamus (PVHPACAP). Through this pilot study, I found that PVHPACAP neurons can be activated or inhibited during food ingestion, but the inhibited responses are more tuned to food. Together, this work contributes to our understanding of how sensory information is represented in the brain to slow appetite, identifying potential therapeutic targets for maladaptive eating disorders.