A hypothalamic-vagal pathway mediates stress-induced feeding suppression and gastric dysfunction.

Acute stress alters feeding behavior and is associated with gastrointestinal dysfunction. Although the hypothalamic paraventricular nucleus (PVN) is traditionally considered to mediate stress responses through neuroendocrine pathways, whether it coordinates stress-related behavioral responses through neural circuits remains unclear. Here, we identify PVN neurons expressing neuropeptide Y receptor Y1 (NPY1R) as a population rapidly activated by diverse acute stressors. Selective activation of PVN NPY1R neurons projecting to the dorsal vagal complex (DVC) suppresses feeding, whereas inhibition of this pathway reverses stress-induced hypophagia. Further investigation reveals that PVN NPY1R neurons form direct synaptic connections with choline acetyltransferase (ChAT)-positive neurons in the DVC, and inhibition of DVC ChAT neurons partially restores stress-induced feeding suppression. Moreover, activation of the PVN NPY1R-DVC pathway induces gastrointestinal dysmotility, whereas inhibition of this pathway rescues stress-induced impairment of gastric emptying. Together, our findings reveal a hypothalamic-brainstem circuit linking acute stress to feeding suppression and gastric dysfunction.