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

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.

人类男性中MECP2基因的倍增将导致严重的自闭症症状.过表达人源MECP2基因,会使转基因小鼠(MECP2-TG)表现出类似自闭症的行为,但这种社交行为缺陷相关的神经环路机制尚不明确.本文在小鼠海马体CA1区植入微型荧光透镜,观察MECP2-TG小鼠和野生型小鼠的社交过程及相关的实时神经活动钙荧光信号,发现与社交行为紧密相关的神经活动在MECP2-TG小鼠中被削弱了.当使用CRISPR/Cas9技术,敲除成年MECP2-TG小鼠CA1区细胞中的过表达人源MECP2基因后,小鼠的社交障碍被缓解.这一数据提示了小鼠海马体中与社交行为相关的神经环路,并提出一种缓解成年自闭症患者社交障碍的潜在方法.