The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.

中文翻译：

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自闭症小鼠模型中小脑核的异常输出和社交缺陷的靶向拯救。


小脑与其他大脑区域密切相关，不仅服务于运动功能，还服务于非运动功能。导致小脑功能障碍的基因突变与精神疾病有关，但尚未在此背景下系统地研究小脑输出。在这里，我们展示了来自野生型小鼠和 Nlgn3R451C 突变小鼠（一种自闭症小鼠模型）的小脑核 （CN） 的 50,168 个靶神经元的三维分布。我们从 36 个靶核得出的结果表明，从 CN 到丘脑、中脑和脑干的投射受到 Nlgn3R451C 突变的不同影响。重要的是，Nlgn3R451C 突变改变了 CN→zona incerta （ZI） 通路的神经支配能力，并且 ZI 中接收来自 CN 输入的神经元亚群的化学遗传学抑制挽救了 Nlgn3R451C 小鼠的社交缺陷。我们的研究强调了小脑输出在自闭症发病机制中的潜在作用，并为这种疾病提供了潜在的新治疗策略。