Adolescence is a developmental period in which the mesolimbic dopaminergic "reward" circuitry of the brain, including the nucleus accumbens (NAc), undergoes significant plasticity. Dopamine D1 receptors (D1rs) in the NAc are critical for social behavior, but how these receptors are regulated during adolescence is not well understood. In this report, we demonstrate that microglia and complement-mediated phagocytic activity shapes NAc development by eliminating D1rs in male, but not female rats, during adolescence. Moreover, immune-mediated elimination of D1rs is required for natural developmental changes in male social play behavior. These data demonstrate for the first time that microglia and complement-mediated immune signaling (i) participate in adolescent brain development in a sex-specific manner, and (ii) are causally implicated in developmental changes in behavior. These data have broad implications for understanding the adolescent critical period of development, the molecular mechanisms underlying social behavior, and sex differences in brain structure and function.

中文翻译：

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小胶质细胞多巴胺受体的消除决定了青春期大鼠的性别特异性伏隔核发育和社会行为。


青春期是一个发育时期，其中大脑的中边缘多巴胺能“奖励”回路，包括伏隔核（NAc），经历了显着的可塑性。 NAc 中的多巴胺 D1 受体 (D1rs) 对于社会行为至关重要，但这些受体在青春期如何受到调节尚不清楚。在本报告中，我们证明小胶质细胞和补体介导的吞噬细胞活性通过消除青春期雄性大鼠而非雌性大鼠中的 D1rs 来影响 NAc 的发育。此外，免疫介导的 D1rs 消除是男性社交游戏行为自然发育变化所必需的。这些数据首次证明，小胶质细胞和补体介导的免疫信号（i）以性别特异性方式参与青少年大脑发育，并且（ii）与行为的发育变化存在因果关系。这些数据对于理解青少年发育关键期、社会行为背后的分子机制以及大脑结构和功能的性别差异具有广泛的意义。