Hypothalamic CRH neurons gate rapid social appraisal of conspecifics

Abstract

Successful navigation of the social environment requires rapid evaluation of conspecifics to distinguish safe from threatening encounters. While the corticotropin-releasing hormone neurons in the paraventricular nucleus of the hypothalamus (CRHPVN) are well known for orchestrating endocrine stress responses, their role in real-time social appraisal is unknown. Here, using fibre photometry and optogenetics during ethologically relevant social interactions, we show that CRHPVN neurons exhibit a rapid, transient increase in activity that precedes sniffing, an investigative behaviour through which mice gather social information. This transient signal scales with social context: it is heightened during interactions with unfamiliar and aggressive conspecifics and significantly reduced toward familiar partners. Inhibiting these neurons selectively diminished anogenital sniffing, demonstrating their necessity for optimal social evaluation. Strikingly, across repeated exposures to the same conspecific, behavioural investigation declined while CRHPVN activity remained robust, revealing a dissociation between neuronal and behavioural habituation. This persistence suggests that CRHPVN neurons encode stable neural representation of threat during social encounters. Together, our findings identify CRHPVN neurons as a fast, integrative node linking endocrine stress control to rapid social decision-making.