A transient hypothalamic CRH signal coordinates social investigation in mice

Successful navigation of the social environment depends on the ability to rapidly evaluate conspecifics and adjust behaviour accordingly. Encounters with unfamiliar individuals are particularly challenging because they introduce uncertainty about how the interactions may unfold. Such social encounters can lead to beneficial or detrimental outcomes, making rapid assessment critical for survival; yet the neural mechanisms underlying this process remain poorly understood. Corticotropin-releasing hormone synthesizing neurons in the paraventricular nucleus of the hypothalamus (CRHPVN), traditionally viewed as the canonical endocrine controllers of the stress response, have been implicated in processing behaviourally relevant environmental and social information, including the investigation of stressed conspecifics. However, their role in rapidly evaluating conspecifics during social encounters remains unclear. Here, using fibre photometry and optogenetics during ethologically relevant social encounters, we show that CRHPVN neurons exhibit a rapid, transient increase in activity that precedes investigative behaviour. This signal scales with social context, is elevated during exposure to unfamiliar relative to familiar conspecifics, persists across novel environments, and generalizes across unfamiliar strains. In contrast, interactions with juvenile conspecifics and inanimate objects do not elicit this differential activity, indicating that CRHPVN recruitment is not driven solely by novelty. Critically, temporally specific inhibition of CRHPVN neurons during this brief activity window produces lasting changes in behaviour beyond the period of inhibition, including the reduction of appropriate social investigation, indicating that this transient activity is necessary for gating subsequent social behaviour. Together, these findings identify CRHPVN neurons as a rapid integrative node linking hypothalamic function to social evaluation.