Sequential activation of lateral hypothalamic neuronal populations during feeding and their assembly by gamma oscillations

Abstract

Neural circuits supporting innate behaviors, such as feeding, exploration, and social interaction, intermingle in the lateral hypothalamus (LH). Although previous studies have shown that individual LH neurons change their firing relative to the baseline during one or more behaviors, the firing rate dynamics of LH populations within behavioral episodes as well as the coordination of behavior-related LH populations remain largely unknown. Here, using unsupervised graph-based clustering of LH neurons firing rate dynamics in freely behaving male mice, we identified distinct populations of cells whose activity corresponds to feeding, specific times during feeding bouts or to other innate behaviors – social interaction and novel object exploration. Feeding-related cells fired together with a higher probability during slow and fast gamma oscillations (30-60 and 60-90 Hz) than during non-rhythmic epochs. In contrast, the co-firing of neurons signaling other behaviors than feeding was overall similar between slow gamma and non-rhythmic epochs but increased during fast gamma oscillations. These results reveal a neural organization of ethological hierarchies in the LH and point to behavior-specific motivational systems, dysfunction of which may contribute to mental disorders.

Significance Statement The LH is pivotal for the regulation of innate behaviors yet the organization of LH neuronal populations at fine temporal resolution within behavioral episodes remains unknown. Such knowledge would be crucial for understanding the contribution of the LH to different innate behaviors. Here, we identified distinct groups of LH cells active at specific times within feeding bouts, and additionally, populations more continuously active during feeding, exploration or social interaction. Cells from feeding-related populations coalesce during LH slow gamma oscillations, while fast gamma also promotes assembly across multiple behavioral populations. Our findings suggest that appetitive behaviors and phases of consummatory acts are supported by distinct LH populations. Dysfunction of their interaction and plasticity during network oscillations may contribute to eating disorders.