Energy deficiency promotes rhythmic foraging behavior by activating neurons in paraventricular hypothalamic nucleus

BACKGROUND: Dysregulation of feeding behavior leads to a variety of pathological manifestations ranging from obesity to anorexia. The foraging behavior of animals affected by food deficiency is not fully understood. METHODS: Home-Cage system was used to monitor the behaviors. Immunohistochemical staining was used to monitor the trend of neuronal activity. Chemogenetic approach was used to modify neuronal activity. RESULTS: We described here a unique mouse model of foraging behavior and unveiled that food deprivation significantly increases the general activities of mice with a daily rhythmic pattern, particularly foraging behavior. The increased foraging behavior is potentiated by food cues (mouthfeel, odor, size, and shape) and energy deficit, rather than macronutrient protein, carbohydrate, and fat. Notably, energy deficiency increases nocturnal neuronal activity in paraventricular hypothalamic nucleus (PVH), accompanying a similar change in rhythmic foraging behavior. Activating neuronal activity in PVH enhances the amplitude of foraging behavior in mice. Conversely, inactivating neuronal activity in PVH decreases the amplitude of foraging behavior and impairs the rhythm of foraging behavior. DISCUSSION: These results illustrate that energy status and food cues regulate the rhythmic foraging behavior via PVH neuronal activity. Understanding foraging behavior provides insights into the underlying mechanism of eating-related disorders.