Integrating Reproductive States and Social Cues in the Control of Sociosexual Behaviors (scRNAseq data)

Female sociosexual behaviors, essential for survival and reproduction, are modulated by ovarian hormones and triggered in the context of appropriate social cues. Here we identify primary estrous-sensitive Cacna1h-expressing medial prefrontal cortex (mPFCCacna1h+) neurons that integrate hormonal states with recognition of potential mates to orchestrate these complex cognitive behaviors. Bidirectional manipulation of mPFCCacna1h+ neurons shifts opposite-sex-directed social behaviors between estrus and diestrus females via anterior hypothalamic outputs. In males, these neurons serve opposite functions compared to estrus females. Miniscope imaging reveals mixed-representation of self-estrous states and social target sex in distinct mPFCCacna1h+ subpopulations, with biased-encoding of opposite-sex cues in estrus females and males. Mechanistically, ovarian hormone-induced Cacna1h upregulation enhances T-type rebound excitation after oxytocin inhibition, driving estrus-specific activity changes and the sexually dimorphic function of mPFCCacna1h+ neurons. These findings uncover a prefrontal circuit that integrates internal hormonal states and target-sex information to exert sexually bivalent top-down control over adaptive social behaviors. To characterize the molecular features of mPFC neurons responsive to estrous cycle and sex, the mPFC tissues were extracted from two estrous female mice, two diestrous female mice, and two male mice, and the cells were isolated for 10x Genomics scRNAseq analyzing.