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.

包含MECP2的基因组片段的重复导致男性出现严重的自闭症症状。过度表达人类MECP2基因的转基因小鼠表现出类似自闭症的行为。MECP2转基因 ( MECP2 -TG ) 小鼠社会缺陷背后的神经回路仍然未知。为了在体内观察MECP2 -TG小鼠的神经活动，我们通过在MECP2 -TG和野生型 (WT) 小鼠的海马 CA1 区植入显微内窥镜进行钙成像。我们确定了其活动与社交互动密切相关的神经元，哪些活动模式在MECP2中受到损害-TG 小鼠。引人注目的是，我们通过在成年期间使用 CRISPR/Cas9 方法删除人类MECP2转基因，挽救了 CA1 中的社会相关神经活动和MECP2 -TG小鼠的社会缺陷。我们的数据指向负责社交互动的神经回路，并为成年期自闭症提供了潜在的治疗目标。