A population of Insula neurons encodes for social preference only after acute social isolation in mice.

The Insula functions as a multisensory relay involved in socio-emotional processing with projections to sensory, cognitive, emotional, and motivational regions. Notably, the interhemispheric projection from the Insula to the contralateral Insula is a robust yet underexplored connection. Using viral-based tracing neuroanatomy, ex vivo and in vivo electrophysiology, in vivo fiber photometry along with targeted circuit manipulation, we elucidated the nature and role of Insula Ins communication in social and anxiety processing in mice. In this study, we 1) characterized the anatomical and molecular profile of the Insula Ins neurons, 2) demonstrated that stimulation of this neuronal subpopulation induces excitation in the Insula interhemispheric circuit, 3) revealed that Insula Ins neurons are essential for social discrimination after 24 h of isolation in male mice. In conclusion, our findings highlight Insula Ins neurons as a distinct class of neurons within the insula and offer new insights into the neuronal mechanisms underlying social behavior.