Visualization and correction of social abnormalities-associated neural ensembles in adult MECP2 duplication mice
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摘要:
Duplications ofMECP2-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 MECP2TG mice.Strikingly,we rescued the social-related neural activity in CA1 and social defects in MECP2TG 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.