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.