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Integrating Reproductive States and Social Cues in the control of Sociosexual Behaviors

ABSTRACT: Female sociosexual behaviors, essential for survival and reproduction, are adaptively modulated by ovarian hormones and triggered in the context of appropriate external social cues. Here we identify primary estrous-sensitive Cacna1h-expressing medial prefrontal (mPFCCacna1h+) neurons that integrate hormonal states with recognition of potential mates to orchestrate these complex cognitive behaviors. Bidirectional manipulation of mPFCCacna1h+ neurons drives opposite-sex-directed behavioral shifts 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 social cues in estrus females and males. Mechanistically, ovarian hormone-driven upregulation of Cacna1h-encoded T-type calcium channels underlies estrus-specific activity changes and sexual-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.

ORGANISM(S): Mus musculus

PROVIDER: GSE283376 | GEO | 2025/05/20

REPOSITORIES: GEO

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

Project description: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.

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