Visualization and correction of social abnormalities-associated neural ensembles in adult MECP2 duplication mice
成年MECP2倍增小鼠中社交障碍相关神经集合的实时成像及功能挽救作者机构:State Key Laboratory of Brain and Cognitive ScienceCAS Center for Excellence in Brain Science and Intelligence TechnologyInstitute of Brain-Intelligence Technology(Shanghai)Institute for Stem Cell and RegenerationInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Institute of NeuroscienceCAS Key Laboratory of Primate NeurobiologyState Key Laboratory of NeuroscienceCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesShanghai 200031China The College of Life ScienceUniversity of Chinese Academy of SciencesBeijing 100049China The College of Life ScienceHebei Normal UniversityShijiazhuang 050016China State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsWuhan Institute of Physics and MathematicsCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesWuhan 430071China Advanced Innovation Center for Human Brain ProtectionBeijing Institute for Brain DisordersCapital Medical UniversityBeijing 100069China
出 版 物:《Science Bulletin》 (科学通报(英文版))
年 卷 期:2020年第65卷第14期
页 面:1192-1202,M0004页
核心收录:
学科分类:1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
基 金:This work was supported by the National Basic Research Program of China(2017YFA0103303) Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32010100,XDB02050400,XDB02050005,XDA16020601) National Basic Research Program of China(2017YFA0102601,2019YFA0110100) National Natural Science Foundation of China(NSFC)(91732301,31671072,31771140,81891001,91432111,81527901,31400977,31625013) Grants of Beijing Brain Initiative of Beijing Municipal Science&Technology Commission(Z181100001518004)
主 题:MECP2 CRISPR/Cas9 In vivo calcium imaging Social activity Autism
摘 要:Duplications of MECP2-containing genomic segments led to severe autistic symptoms in male. Transgenic mice overexpressing the human MECP2 gene exhibit autistic-like behaviors. Neural circuits underlying social defects in MECP2 transgenic(MECP2-TG) mice remain unknown. To observe neural activity of MECP2-TG mice in vivo, we performed calcium imaging by implantation of microendoscope in the hippocampal CA1 regions of MECP2-TG and wild type(WT) mice. We identified neurons whose activities were tightly associated with social interaction, which activity patterns were compromised in MECP2-TG mice. Strikingly, we rescued the social-related neural activity in CA1 and social defects in MECP2-TG mice by deleting the human MECP2 transgene using the CRISPR/Cas9 method during *** data points to the neural circuitry responsible for social interactions and provides potential therapeutic targets for autism in adulthood.