A ROLE OF PREFRONTAL CORTICAL INPUTS ONTO LATERAL HYPOTHALAMUS IN ANXIETY-RELATED BEHAVIOR IN HEALTH AND IN ACTIVITY-BASED ANOREXIA NERVOSA MODEL

Adaptive behavior requires the integration of cognitive appraisal with subcortical motivational circuits. The prefrontal cortex (PFC) is central to higher-order processing of environmental contingencies, yet how prefrontal signals influence hypothalamic control of anxiety-related behavior remains poorly defined.
In this study, we examined functional connectivity between the PFC and the lateral hypothalamus (LH) in the context of anxiety-related behavioral regulation. Using fiber photometry in freely behaving mice, we characterized activity patterns within PFC neurons projecting to the LH and their relationship to behavioral state. We used several classic tests for anxiety-related behavior, as well as the activity-based anorexia model, a pre-clinical model for anorexia nervosa.
Our results indicate that prefrontal input to the LH is engaged during anxiogenic conditions and is linked to behavioral outcomes associated with anxiety. Further, activity of prefrontal inputs in LH increased during interaction with food in a pre-clinical anorexia nervosa disease model. These findings suggest that PFC–LH pathways provide a route by which cognitive and contextual information can influence hypothalamic processing of emotional state. This work advances our understanding of how cortical–subcortical interactions contribute to adaptive behavioral regulation under challenging environmental conditions. We gratefully acknowledge support by the ERC consolidator grant HypFeedNet (to TK), DFG RTG1960 (to RF), DFG CRC1451 (to TK and AP), EXC2030-CECAD to T.K.