Abstract：
The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also non-motor 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.
摘要：
小脑与其他大脑区域紧密相连，子服务不仅电机，而且非电机功能。导致小脑功能障碍的基因突变与精神疾病有关，但是在这种情况下还没有系统地研究小脑输出。这里,我们展示了来自野生型小鼠和Nlgn3R451C突变小鼠的小脑核（CN）的50,168个靶神经元的三维分布，自闭症小鼠模型。我们从36个靶核得出的结果表明，从CN到丘脑的投影，中脑和脑干受Nlgn3R451C突变的不同影响。重要的是,Nlgn3R451C突变改变了CN→透明带（ZI）途径的神经支配能力，和从CN接受输入的ZI中神经元亚群的化学遗传抑制挽救了Nlgn3R451C小鼠的社会缺陷。我们的研究强调了小脑输出在自闭症发病机理中的潜在作用，并为该疾病提供了潜在的新治疗策略。
