ANTERIOR HYPOTHALAMIC NUCLEUS DRIVES DISTINCT ANTAGONISTIC BEHAVIOURS THROUGH CELL-TYPE-SPECIFIC REGULATION IN MICE

In nature, animals rely on a dynamic control of approach and avoidance behaviours to navigate interactions with prey and predators. The anterior hypothalamic nucleus (AHN), a key region in the medial hypothalamic defense system, contains a complex circuitry between inhibitory and excitatory cells. While the AHN has been identified to mediate anxiety-associated defensive responses, the roles of each cell-type in achieving the dynamic control of innate adaptive behaviours have not been systematically examined. Here, we used fiber photometry and optogenetic manipulations to demonstrate that the AHN drives distinct antagonistic behaviours through cell-type-specific regulation. Through fiber photometry, we found that both glutamatergic and GABAergic AHN neurons dynamically respond to a predator and distinct stages of prey encounter. Furthermore, optogenetic stimulation studies revealed that activation of glutamatergic AHN neurons is aversive and evokes escape responses in environments across a continuum of valences. On the other hand, we found that activation of GABAergic AHN neurons is appetitive and evokes investigatory and hunting behaviours in the presence of a predator and prey, respectively. Interestingly, we also identified robust object chasing behaviours upon stimulation of GABAergic AHN neurons. Moreover, optogenetic inhibition studies suggest GABAergic AHN neurons are necessary for hunting behaviours. Lastly, our work shows preliminary insight into the cell-type specific role of the AHN in mediating context-associated approach and avoidance behaviours. Taken together, our study identifies a cell-type specific mechanism by which the anterior hypothalamic nucleus drives approach and avoidance behaviours, critical to hunting and escape.