Sexually dimorphic dopaminergic circuits determine sex preference

Science. 2025 Jan 10;387(6730):eadq7001. doi: 10.1126/science.adq7001. Epub 2025 Jan 10.

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 (VTADA) neurons. In males, VTADA 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 VTADA-NAc projection determines sociosexual preferences. These findings define VTADA neurons as a key node for social decision-making and reveal the sexually dimorphic DA circuit mechanisms underlying sociosexual preference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism
  • Dopaminergic Neurons* / physiology
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiology
  • Nucleus Accumbens* / physiology
  • Preoptic Area* / physiology
  • Sex Characteristics*
  • Social Behavior*
  • Social Interaction*
  • Ventral Tegmental Area* / physiology

Substances

  • Dopamine