The cerebellum, a primary brain structure involved in the control of sensorimotor tasks, also contributes to higher cognitive functions including reward, emotion and social interaction. Although the regulation of these behaviors has been largely ascribed to the monoaminergic system in limbic regions, the contribution of cerebellar dopamine signaling in the modulation of these functions remains largely unknown. By combining cell-type-specific transcriptomics, histological analyses, three-dimensional imaging and patch-clamp recordings, we demonstrate that cerebellar dopamine D2 receptors (D2Rs) in mice are preferentially expressed in Purkinje cells (PCs) and regulate synaptic efficacy onto PCs. Moreover, we found that changes in D2R levels in PCs of male mice during adulthood alter sociability and preference for social novelty without affecting motor functions. Altogether, these findings demonstrate novel roles for D2R in PC function and causally link cerebellar D2R levels of expression to social behaviors.

小脑是参与控制感觉运动任务的主要大脑结构，也有助于更高的认知功能，包括奖励、情感和社交互动。尽管这些行为的调节在很大程度上归因于边缘区域的单胺能系统，但小脑多巴胺信号传导在这些功能调节中的作用仍然很大程度上未知。通过结合细胞类型特异性转录组学、组织学分析、三维成像和膜片钳记录，我们证明小鼠中的小脑多巴胺 D2 受体 (D2R) 优先在浦肯野细胞 (PC) 中表达并调节突触对 PC 的功效。而且，我们发现成年雄性小鼠 PC 中 D2R 水平的变化会改变社交能力和对社交新奇事物的偏好，而不会影响运动功能。总而言之，这些发现证明了 D2R 在 PC 功能中的新作用，并将小脑 D2R 表达水平与社会行为联系起来。