Male mice and female mice employ different circuit-based decision-making mechanisms.

On Jan 10, Professor Wang Changhe's team from Xi'an Jiaotong University (XJTU) published a paper in Science titled "Sexually dimorphic dopaminergic circuits determine sex preference". The study revealed that under normal physiological conditions, male and female mice exhibit a preference for female social interactions. However, under survival-threatening conditions, their preference shifts to male interactions.

The midbrain dopamine (DA) reward system is the central mechanism underlying this behavioral decision. However, male and female mice employ different circuit-based decision-making mechanisms, exhibiting sexual dimorphism.

In males, the reward circuit involving dopaminergic neurons (VTA^DA) in the ventral tegmental area projecting to the nucleus accumbens (NAc), driven by intrinsic reproductive needs, mediates their preference for female social interactions. Conversely, the defense circuit, where DA neurons project to the medial preoptic area (mPOA) in response to external survival threats, mediates their preference for male interactions. The competition and balance between these two circuits determine their ultimate gender selection decision.

In females, the VTA^DA-NAc reward circuit mediates both male and female social preferences. The firing modes of DA neurons within this circuit – tonic firing promotes male preference and phasic firing mediates female preference – dictate their social gender preference.

The researchers used social interaction experiments, fiber photometry, and neural circuit tracing to confirm that various sensory signals (e.g., olfactory, visual, and auditory) could alter gender preferences under survival threats. Optogenetic and chemogenetic experiments also demonstrated that manipulating these circuits could reverse the gender preference in mice.

This study identifies VTA^DA neurons as the critical hub of social decision-making and unveils a novel sexually dimorphic dopaminergic circuit mechanism underlying social gender preference. It establishes a new neural circuit framework for decision-making in social behavior, offering a paradigm for understanding how intrinsic physiological needs and external survival environments collaboratively regulate instinctive behaviors through neural circuit integration. Furthermore, it offers a fresh perspective on the emotional and behavioral differences between males and females, while providing theoretical support for addressing gender-specific differences in treating related neurological disorders.

The journal Science provided a special recommendation for this study and simultaneously published a perspective article, "Stress drives a switch in sex preference", highlighting its key insights.