Ventral hippocampal NPY interneurons regulate circadian feeding in mice

Feeding behavior is tightly regulated by circadian rhythms, and disruption of this coordination promotes mistimed eating and metabolic dysfunction. Here, using mouse models, we identify a noncanonical role of neuropeptide Y-expressing interneurons (NPY-INs) in the ventral hippocampus (vHPC) in circadian feeding control. vHPC NPY-INs exhibit robust diurnal activity fluctuations that are lost under chronic circadian disruption. Functionally, these neurons regulate feeding across the day-night cycle by engaging distinct transmitters: NPY signaling predominates during the light phase, whereas gamma-aminobutyric acid (GABA) signaling dominates during the dark phase. Furthermore, vHPC NPY-INs receive monosynaptic glutamatergic and GABAergic inputs from the medial preoptic area (MPOA), which confer circadian plasticity, and project to the ventral subiculum (vSub), where NPY₁R and NPY₂R signaling mediates feeding behavior. Together, these findings identify the vHPC NPY-INs as a critical hub linking circadian regulation and energy balance, offering new insight into neural mechanisms underlying mistimed feeding and metabolic disorders.