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

Abstract

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.

Keywords: Autism; CRISPR/Cas9; In vivo calcium imaging; MECP2; Social activity.