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Regulation of autism-relevant behaviors by cerebellar-prefrontal cortical circuits.
Nature Neuroscience ( IF 25.0 ) Pub Date : 2020-07-13 , DOI: 10.1038/s41593-020-0665-z
Elyza Kelly 1, 2 , Fantao Meng 1 , Hirofumi Fujita 3 , Felipe Morgado 4, 5 , Yasaman Kazemi 1 , Laura C Rice 6 , Chongyu Ren 1 , Christine Ochoa Escamilla 1 , Jennifer M Gibson 1, 2 , Sanaz Sajadi 1 , Robert J Pendry 2 , Tommy Tan 1 , Jacob Ellegood 5 , M Albert Basson 7 , Randy D Blakely 8 , Scott V Dindot 9 , Christelle Golzio 10 , Maureen K Hahn 8 , Nicholas Katsanis 11 , Diane M Robins 12 , Jill L Silverman 13 , Karun K Singh 14 , Rachel Wevrick 15 , Margot J Taylor 16 , Christopher Hammill 5 , Evdokia Anagnostou 17 , Brad E Pfeiffer 2 , Catherine J Stoodley 6 , Jason P Lerch 4, 5, 18 , Sascha du Lac 3 , Peter T Tsai 1, 2, 19
Affiliation  

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.



中文翻译:

小脑前额叶皮层回路对自闭症相关行为的调节。

小脑功能障碍已在自闭症谱系障碍(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。在这项研究中,我们证明了小鼠小脑与内侧前额叶皮层(mPFC)之间的功能连接;表明,mPFC介导小脑调节的社交和重复/不灵活的行为;并显示了在多个ASD相关基因小鼠模型中以及ASD个体中这些区域之间的连通性受到破坏。我们从小脑皮质区域右小腿1(Rcrus1)和后ver通过小脑核和腹膜丘脑绘制了一个回路,并在mPFC中达到顶点。这种电路的调制会引起社会缺陷和重复行为,Tsc1突变小鼠。这些数据增加了这些电路可能提供神经调节靶标治疗ASD的可能性。

更新日期:2020-07-13
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