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...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 adulthood.Our data points to the neural circuitry responsible for social interactions and provides potential therapeutic targets for autism in adulthood.展开更多
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)+2 种基金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).
文摘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 adulthood.Our data points to the neural circuitry responsible for social interactions and provides potential therapeutic targets for autism in adulthood.
