A POMC-originated circuit regulates stress-induced hypophagia, depression, and anhedonia

Chronic stress causes dysregulations of mood and energy homeostasis, but the neurocircuitry underlying these alterations remain to be fully elucidated. Here we demonstrate that chronic restraint stress in mice results in hyperactivity of pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus (POMC^ARH neurons) associated with decreased neural activities of dopamine neurons in the ventral tegmental area (DA^VTA neurons). We further revealed that POMC^ARH neurons project to the VTA and provide an inhibitory tone to DA^VTA neurons via both direct and indirect neurotransmissions. Finally, we show that photoinhibition of the POMC^ARH→VTA circuit in mice increases body weight and food intake, and reduces depression-like behaviors and anhedonia in mice exposed to chronic restraint stress. Thus, our results identified a novel neurocircuitry regulating feeding and mood in response to stress.