Cerebellar abnormalities, particularly in Right Crus I (RCrusI), are consistently reported in autism spectrum disorders (ASD). Although RCrusI is functionally connected with ASD-implicated circuits, the contribution of RCrusI dysfunction to ASD remains unclear. Here neuromodulation of RCrusI in neurotypical humans resulted in altered functional connectivity with the inferior parietal lobule, and children with ASD showed atypical functional connectivity in this circuit. Atypical RCrusI–inferior parietal lobule structural connectivity was also evident in the Purkinje neuron (PN) TscI ASD mouse model. Additionally, chemogenetically mediated inhibition of RCrusI PN activity in mice was sufficient to generate ASD-related social, repetitive, and restricted behaviors, while stimulation of RCrusI PNs rescued social impairment in the PN TscI ASD mouse model. Together, these studies reveal important roles for RCrusI in ASD-related behaviors. Further, the rescue of social behaviors in an ASD mouse model suggests that investigation of the therapeutic potential of cerebellar neuromodulation in ASD may be warranted.

中文翻译：

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自闭症中的小脑连接性改变以及小脑介导的小鼠自闭症相关行为的抢救

在自闭症谱系障碍（ASD）中，一直有小脑异常的报道，尤其是在Right Crus I（RCrusI）中。尽管RCrusI在功能上与涉及ASD的电路相连，但RCrusI功能障碍对ASD的贡献仍不清楚。在此，典型神经元人类中RCrusI的神经调节导致与顶下小叶的功能连通性改变，患有ASD的儿童在该回路中表现出非典型的功能连通性。浦肯野神经元（PN）TscI中也显示出非典型的RCrusI-下壁小叶结构连通性ASD鼠标模型。此外，化学上介导的小鼠RCrusI PN活性抑制足以产生ASD相关的社交，重复和受限行为，而RCrusI PNs的刺激挽救了PN TscI ASD小鼠模型中的社交障碍。这些研究共同揭示了RCrusI在ASD相关行为中的重要作用。此外，在ASD小鼠模型中社交行为的挽救表明，可能需要对小脑神经调节在ASD中的治疗潜力进行研究。