Neural mechanism of the sexually dimorphic winner effect in mice

The "winner effect," where prior victories increase the likelihood of future wins, profoundly shapes social hierarchy dynamics and competitive motivation. Although human literature suggests a less pronounced winner effect in females, the neural mechanisms underlying these sex differences remain unclear. Here, we show that, compared with male mice, female mice take longer to form social hierarchies and exhibit a weaker winner effect. The dorsomedial prefrontal cortex (dmPFC), crucial for social dominance in males, plays a similar role in female mice. However, female mice exhibit reduced long-term potentiation (LTP) at the mediodorsal thalamus (MDT)-to-dmPFC synapses. In vitro recordings revealed that female mice have heightened excitability of dmPFC parvalbumin interneurons (PV-INs). Modulation of dmPFC PV-IN activity regulates LTP and the winner effect in a sexually dimorphic manner. This work identifies dmPFC PV-INs as a target for enhancing the winner effect, establishing a circuit-level framework for sex differences in competitive behaviors.