The transcriptome of playfulness is sex-biased in the juvenile rat medial amygdala: a role for inhibitory neurons

Social play is a well-conserved, dynamic behavior known to be sexually differentiated. In most species, males play more than females, a sex difference largely driven by the medial amygdala (MeA) yet the full mechanism establishing this bias is unknown. Here, we explore “the transcriptome of playfulnessâ€� in both sexes for the first time, demonstrating that the transcriptomic profile in the juvenile rat MeA associated with playfulness is markedly distinct in males and females. Parallel single-cell RNA-sequencing experiments from newborn rats suggest that inhibitory neurons drive this sex difference. Furthermore, we show that inhibitory neurons comprise the majority of play-active cells in the juvenile MeA, with males having more play-active cells than females, of which a greater proportion are GABAergic. Through integrative bioinformatic analyses, we further explore the expression, function, and cell-type specificity of key play-associated gene modules, providing valuable insight into the sex-biased mechanisms underlying this fundamental social behavior.社交玩耍是一种高度保守且具有动态性的行为，且存在性别分化特征。在多数物种中，雄性的玩耍行为频次高于雌性，这一性别差异主要由内侧杏仁核（medial amygdala, MeA）调控，但阐明该偏向形成的完整分子机制仍是未解之谜。本研究首次针对雌雄两性开展了“玩耍行为相关转录组”的系统性探索，结果显示：幼年大鼠内侧杏仁核中与玩耍行为相关的转录组谱在雌雄个体间存在显著差异。针对新生大鼠开展的并行单细胞RNA测序（single-cell RNA-sequencing, scRNA-seq）实验结果提示，抑制性神经元是该性别差异的核心驱动因素。此外，本研究证实幼年大鼠内侧杏仁核内的玩耍激活细胞绝大多数为抑制性神经元；雄性个体的玩耍激活细胞数量多于雌性，且其中γ-氨基丁酸能（GABAergic）神经元的占比更高。通过整合生物信息学分析，本研究进一步解析了核心玩耍相关基因模块的表达模式、功能特性及细胞类型特异性，为阐明这一基础社交行为背后的性别偏向调控机制提供了关键见解。