Corticotropin-releasing hormone signaling from prefrontal cortex to lateral septum suppresses interaction with familiar mice

Social preference, the decision to interact with one member of the same species over another, is critical to optimize social interactions. Thus, adult rodents favor interacting with novel conspecifics over familiar ones, but whether this social preference stems from neural circuits facilitating interactions with novel individuals or suppressing interactions with familiar ones remains unknown. Here, we identify neurons in the infra-limbic area (ILA) of the mouse prefrontal cortex that express the neuropeptide corticotropin-releasing hormone (CRH) and project to the dorsal region of the rostral lateral septum (rLS). We show how release of CRH during familiar encounters disinhibits rLS neurons, thereby suppressing social interactions with familiar mice and contributing to social novelty preference. We further demonstrate how the maturation of CRH expression in ILA during the first 2 post-natal weeks enables the developmental shift from a preference for littermates in juveniles to a preference for novel mice in adults. [Display omitted] •Release of CRH from PFC to LS suppresses social interaction with familiar mice•Suppression of social interaction with familiar mice supports social novelty preference•Maturation of this circuit induces a shift in social preference in young mice Corticotropin-releasing hormone release from the infra-limbic area of the prefrontal cortex to the lateral septum suppresses social interaction with familiar but not novel mice to support the social novelty preference exhibited by adult mice. The maturation of this circuit during the first two post-natal weeks enables the developmental shift from a preference for littermates in juveniles to a preference for novel mice in adults.