美国德克萨斯大学西南医学中心Peter T. Tsai研究组在研究中取得进展。他们的最新研究提出小脑-前额叶皮层回路对自闭症相关行为的调控。相关论文于2020年7月13日发表于《自然-神经科学》。
在这项研究中，他们证明了小鼠小脑与内侧前额叶皮层（mPFC）之间的功能连接，显示了mPFC介导小脑调节的社交和重复/不灵活行为，并显示了在多个自闭症谱系障碍（ASD）相关基因小鼠模型以及ASD个体中这些区域之间的连通性受到破坏。
他们从小脑皮质区域右小腿1（Rcrus1）和后蚓部（vermis）之间划出一条回路，这条回路通过小脑核和腹膜丘脑，并在mPFC中达到顶点。此回路的调制引起社交缺陷和重复行为，而激活Rcrus1和后vermis的Purkinje细胞（PCs），分别改善了雄性PC-Tsc1突变小鼠的社交偏好障碍和重复/不灵活行为。这些数据增加了这些回路为治疗ASD提供神经调节靶标的可能性。
据悉，小脑功能障碍已在ASD中得到证实。然而，小脑对与ASD相关行为的贡献所依据的回路仍然未知。
附：英文原文
Title: Regulation of autism-relevant behaviors by cerebellar–prefrontal cortical circuits
Author: Elyza Kelly, Fantao Meng, Hirofumi Fujita, Felipe Morgado, Yasaman Kazemi, Laura C. Rice, Chongyu Ren, Christine Ochoa Escamilla, Jennifer M. Gibson, Sanaz Sajadi, Robert J. Pendry, Tommy Tan, Jacob Ellegood, M. Albert Basson, Randy D. Blakely, Scott V. Dindot, Christelle Golzio, Maureen K. Hahn, Nicholas Katsanis, Diane M. Robins, Jill L. Silverman, Karun K. Singh, Rachel Wevrick, Margot J. Taylor, Christopher Hammill, Evdokia Anagnostou, Brad E. Pfeiffer, Catherine J. Stoodley, Jason P. Lerch, Sascha du Lac, Peter T. Tsai
Issue&Volume: 2020-07-13
Abstract: Cerebellar dysfunction has been demonstrated in autism spectrum disorders (ASDs); however, the circuits underlying cerebellar contributions to ASD-relevant behaviors remain unknown. In this study, we demonstrated functional connectivity between the cerebellum and the medial prefrontal cortex (mPFC) in mice; showed that the mPFC mediates cerebellum-regulated social and repetitive/inflexible behaviors; and showed disruptions in connectivity between these regions in multiple mouse models of ASD-linked genes and in individuals with ASD. We delineated a circuit from cerebellar cortical areas Right crus 1 (Rcrus1) and posterior vermis through the cerebellar nuclei and ventromedial thalamus and culminating in the mPFC. Modulation of this circuit induced social deficits and repetitive behaviors, whereas activation of Purkinje cells (PCs) in Rcrus1 and posterior vermis improved social preference impairments and repetitive/inflexible behaviors, respectively, in male PC-Tsc1 mutant mice. These data raise the possibility that these circuits might provide neuromodulatory targets for the treatment of ASD.
DOI: 10.1038/s41593-020-0665-z
Source: https://www.nature.com/articles/s41593-020-0665-z
Nature Neuroscience：《自然—神经科学》，创刊于1998年。隶属于施普林格·自然出版集团，最新IF：28.771
官方网址：https://www.nature.com/neuro/
投稿链接：https://mts-nn.nature.com/cgi-bin/main.plex
本期文章：《自然—神经科学》：Online/在线发表
