Aberrant outputs of cerebellar nuclei and targeted rescue of social deficits in an autism mouse model  

作　　者：Xin-Yu Cai Xin-Tai Wang Jing-Wen Guo Fang-Xiao Xu Kuang-Yi Ma Zhao-Xiang Wang Yue Zhao Wei Xie Martijn Schonewille Chris De Zeeuw Wei Chen Ying Shen 

机构地区：[1]Center for Brain Health,The Fourth Affiliated Hospital of School of Medicine,and International School of Medicine,International Institutes of Medicine,Zhejiang University,Yiwu 322000,China [2]Department of Physiology and Department of Psychiatry,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [3]Institute of Life Sciences,College of Life and Environmental Sciences,Hangzhou Normal University,Hangzhou 311121,China [4]Zhejiang Lab,Hangzhou 311500,China [5]The Key Laboratory of Developmental Genes and Human Disease of the Ministry of Education,School of Life Science and Technology,Southeast University,Nanjing 210096,China [6]Department of Neuroscience,Erasmus University Medical Center,3000 CA Rotterdam,The Netherlands [7]The Netherlands Institute for Neuroscience,Royal Dutch Academy of Arts&Science,1105 BA Amsterdam,The Netherlands [8]Key Laboratory of Medical Neurobiology of Zhejiang Province,Zhejiang University School of Medicine,Hangzhou 310058,China

出　　处：《Protein & Cell》2024年第12期872-888,共17页蛋白质与细胞(英文版)

基　　金：supported by grants from the STI2030-Major Projects (2021ZD0204000);Key Strategic Science and Technology Cooperation Project (2023YFE0206800) of the Ministry of Science and Technology of China;the National Natural Science Foundation of China (81625006, 31820103005, 32000692);Zhejiang Province Natural Science Foundation of China (LZ24C090003 and LY21C090003);the Science and Technology Programme of Hangzhou Municipaility (20190101A10);the Key Realm R&D Program of Guangdong Province (2019B030335001);the Netherlands Organization for Scientific Research (NWO-ALW 824.02.001);the Dutch Organization for Medical Sciences (Zon MW 91120067);Medical Neuro-Delta (MD 01092019-31082023);INTENSE LSH-NWO (TTW/00798883);ERC-adv (GA-294775);ERC-POC (737619 and 768914)

摘　　要：The cerebellum is heavily connected with other brain regions,sub-serving not only motor but also nonmotor 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.

关 键 词：CEREBELLUM THALAMUS MIDBRAIN large-scale tracing AUTISM 

分 类 号：R749.94[医药卫生—神经病学与精神病学] R-332[医药卫生—临床医学]