The differential role of the subiculum > hypothalamic paths in diverse contextual fear responses to a live predator and physically harmful events

The subiculum > hypothalamic path has critical roles in expressing defensive responses in a wide range of threatening situations. This path is engaged during exposure to a natural predator or its context, social defeat, and contexts related to physically harmful events. Previous data have shown that the ventral and intermediate subiculum provide strong projections to a continuum formed by the anterior hypothalamic nucleus (AHN) and juxtadorsomedial part of the lateral hypothalamic area (LHAjd). By combining track tracing, chemogenetic, and calcium imaging experiments, we focused on differentiating how the subiculum > hypothalamic paths are involved in contextual fear responses to exposure to a live predator (i.e., a cat) or physically harmful events (i.e., footshock). Our tract-tracing experiments revealed a topographical projection from the ventral and intermediate subiculum to the AHN and the LHAjd, respectively. Chemogenetic silencing revealed that the subiculum > AHN path impaired contextual fear responses only to predator-related fear contexts. In contrast, the subiculum > LHAjd influenced contextual responses to predator and physically harmful events. In line with these observations, fiber photometry data revealed a differential role of the subicular cells projecting to the hypothalamus, where the ventral subicular cells respond only to predator-related contexts, whereas the intermediate subicular cells respond to both predator and physically harmful contexts. Therefore, subiculum > hypothalamic paths have a differential role in diverse contextual fear responses to different threatening events.