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Visualization and correction of social abnormalities-associated neural ensembles in adult MECP2 duplication mice

Science Bulletin 2020年第14期65卷 1192-1202,M0004页

作者： Le Sun Ruiguo Chen Long Li Bo Yuan Kun Song Na Pan Tian-Lin Cheng Shiyang Chang Kunzhang Lin Xiaobin He Qian Wu Fuqiang Xu Zilong Qiu Xiaoqun Wang State Key Laboratory of Brain and Cognitive Science CAS 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 Neuroscience CAS 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 Science University of Chinese Academy of SciencesBeijing 100049China The College of Life Science Hebei Normal UniversityShijiazhuang 050016China State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics Wuhan Institute of Physics and MathematicsCAS Center for Excellence in Brain Science and Intelligence TechnologyChinese Academy of SciencesWuhan 430071China Advanced Innovation Center for Human Brain Protection Beijing Institute for Brain DisordersCapital Medical UniversityBeijing 100069China

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.

关键词： MECP2 CRISPR/Cas9 in vivo calcium imaging Social activity Autism

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