BACKGROUND Studies in humans and nonhuman primates have identified a region of the dentate nucleus of the cerebellum, or the lateral cerebellar nucleus (LCN) in rodents, activated during performance of cognitive tasks involving complex spatial and sequential planning. Whether such a subdivision exists in rodents is not known. Dopamine and its receptors, which are implicated in cognitive function, are present in the cerebellar nuclei, but their function is unknown. METHODS Using viral and genetic strategies in mice, we examined cellular phenotypes of dopamine D1 receptor-positive (D1R+) cells in the LCN with whole-cell patch clamp recordings, messenger RNA profiling, and immunohistochemistry to examine D1R expression in mouse LCN and human dentate nucleus of the cerebellum. We used chemogenetics to inhibit D1R+ neurons and examined behaviors including spatial navigation, social recognition memory, prepulse inhibition of the acoustic startle reflex, response inhibition, and working memory to test the necessity of these neurons in these behaviors. RESULTS We identified a population of D1R+ neurons that are localized to an anatomically distinct region of the LCN. We also observed D1R+ neurons in human dentate nucleus of the cerebellum, which suggests an evolutionarily conserved population of dopamine-receptive neurons in this region. The genetic, electrophysiological, and anatomical profile of mouse D1R neurons is consistent with a heterogeneous population of gamma-aminobutyric acidergic, and to a lesser extent glutamatergic, cell types. Selective inhibition of D1R+ LCN neurons impairs spatial navigation memory, response inhibition, working memory, and prepulse inhibition of the acoustic startle reflex. CONCLUSIONS Collectively, these data demonstrate a functional link between genetically distinct neurons in the LCN and cognitive behaviors.

中文翻译：

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小脑外侧核中的多巴胺 D1 受体阳性神经元有助于认知行为

背景对人类和非人类灵长类动物的研究已经确定了啮齿类动物的小脑齿状核或外侧小脑核 (LCN) 的一个区域，在执行涉及复杂空间和顺序规划的认知任务期间被激活。尚不清楚啮齿动物中是否存在这种细分。与认知功能有关的多巴胺及其受体存在于小脑核中，但其功能尚不清楚。方法 在小鼠中使用病毒和遗传策略，我们通过全细胞膜片钳记录、信使 RNA 分析和免疫组织化学检查 LCN 中多巴胺 D1 受体阳性 (D1R+) 细胞的细胞表型，以检查小鼠 LCN 和人类齿状突中的 D1R 表达小脑的核。我们使用化学遗传学来抑制 D1R+ 神经元，并检查了包括空间导航、社会识别记忆、声惊反射的前脉冲抑制、反应抑制和工作记忆在内的行为，以测试这些神经元在这些行为中的必要性。结果我们确定了一群 D1R+ 神经元，它们位于 LCN 的解剖学上不同的区域。我们还在人类小脑齿状核中观察到 D1R+ 神经元，这表明该区域存在进化上保守的多巴胺受体神经元群。小鼠 D1R 神经元的遗传、电生理和解剖学特征与异质性的 γ-氨基丁酸能细胞类型一致，谷氨酸能细胞类型在较小程度上是一致的。选择性抑制 D1R+ LCN 神经元会损害空间导航记忆，反应抑制、工作记忆和听觉惊跳反射的前脉冲抑制。结论 总的来说，这些数据证明了 LCN 中基因不同的神经元与认知行为之间的功能联系。