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：

---

自闭症中小脑连接的改变以及小脑介导的小鼠自闭症相关行为的拯救。


小脑异常，特别是右小腿 I (RCrusI) 的异常，在自闭症谱系障碍 (ASD) 中得到一致报道。尽管 RCrusI 在功能上与 ASD 相关回路相关，但 RCrusI 功能障碍对 ASD 的影响仍不清楚。在此，神经正常人类中 RCrusI 的神经调节导致与顶下小叶的功能连接发生改变，而患有自闭症谱系障碍 (ASD) 的儿童在该回路中表现出非典型的功能连接。非典型 RCrusI-顶下小叶结构连接在浦肯野神经元 (PN) TscI ASD 小鼠模型中也很明显。此外，化学遗传学介导的对小鼠 RCrusI PN 活性的抑制足以产生 ASD 相关的社交、重复和限制行为，而刺激 RCrusI PN 可以挽救 PN TscI ASD 小鼠模型的社交障碍。总之，这些研究揭示了 RCrusI 在 ASD 相关行为中的重要作用。此外，自闭症谱系障碍 (ASD) 小鼠模型中社交行为的拯救表明，可能有必要研究小脑神经调节在自闭症谱系障碍 (ASD) 中的治疗潜力。