Sexually dimorphic dopaminergic circuits determine sex preference.

Wei, Anqi; Zhao, Anran; Zheng, Chaowen; Dong, Nan; Cheng, Xu; Duan, Xueting; Zhong, Shuaijie; Liu, Xiaoying et al. · Science · 2025

basic_science · Level V

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Abstract

Sociosexual preference is critical for reproduction and survival. However, neural mechanisms encoding social decisions on sex preference remain unclear. In this study, we show that both male and female mice exhibit female preference but shift to male preference when facing survival threats; their preference is mediated by the dimorphic changes in the excitability of ventral tegmental area dopaminergic (VTA<sup>DA</sup>) neurons. In males, VTA<sup>DA</sup> projections to the nucleus accumbens (NAc) mediate female preference, and those to the medial preoptic area mediate male preference. In females, firing-pattern (phasic-like versus tonic-like) alteration of the VTA<sup>DA</sup>-NAc projection determines sociosexual preferences. These findings define VTA<sup>DA</sup> neurons as a key node for social decision-making and reveal the sexually dimorphic DA circuit mechanisms underlying sociosexual preference.

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