2. Academic Validation
  3. Integrating reproductive states and social cues in the control of sociosexual behaviors

Integrating reproductive states and social cues in the control of sociosexual behaviors

  • Cell. 2025 Jun 26;188(13):3530-3549.e24. doi: 10.1016/j.cell.2025.04.035.
Yuping Wang 1,  Xinli Song 1,  Xiangmao Chen 2,  Ying Zhou 1,  Jihao Ma 1,  Fang Zhang 1,  Liqiang Wei 1,  Guoxu Qi 1,  Nakul Yadav 3,  Benjie Miao 1,  Yiming Yan 1,  Guohua Yuan 1,  Da Mi 1,  Priyamvada Rajasethupathy 3,  Ines Ibañez-Tallon 3,  Xiaoxuan Jia 1,  Nathaniel Heintz 4,  Kun Li 5
Affiliations

Affiliations

  • 1 IDG/McGovern Institute for Brain Research at Tsinghua, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China.
  • 2 Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 3 The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
  • 4 The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: heintz@rockefeller.edu.
  • 5 IDG/McGovern Institute for Brain Research at Tsinghua, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address: kli@mail.tsinghua.edu.cn.
PMID: 40398420 DOI: 10.1016/j.cell.2025.04.035
Abstract

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 with 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.

Keywords

Cacna1h; T-type calcium channels; anterior hypothalamic nucleus; estrous states; mPFC; mixed selectivity; oxytocin; prefrontal cortex; sex differences; sociosexual behavior.

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