Restoration of FMRP expression in adult V1 neurons rescues visual deficits in a mouse model of fragile X syndrome

• 作者: Chaojuan Yang Yonglu Tian Feng Su Yangzhen Wang Mengna Liu Hongyi Wang Yaxuan Cui Peijiang Yuan Xiangning Li Anan Li Hui Gong Qingming Luo Desheng Zhu Peng Cao Yunbo Liu Xunli Wang Min-hua Luo Fuqiang Xu Wei Xiong Liecheng Wang Xiang-yao Li Chen Zhang
• 来源期刊: 蛋白质与细胞
• 年，卷（期）: 2022,（3）
• 所属期刊栏目: RESEARCH ARTICLES
• 页码范围: 203-219
• 页数: 17页
• 语种: 英文

摘要

Many people affected by fragile X syndrome(FXS)and autism spectrum disorders have sensory processing deficits,such as hypersensitivity to auditory,tactile,and visual stimuli.Like FXS in humans,loss of Fmr1 in rodents also cause sensory,behavioral,and cognitive deficits.However,the neural mechanisms underlying sensory impairment,especially vision impairment,remain unclear.It remains elusive whether the visual processing deficits originate from corrupted inputs,impaired perception in the primary sensory cortex,or altered integration in the higher cortex,and there is no effective treatment.In this study,we used a genetic knockout mouse model(Fmr1KO),in vivo imaging,and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex(V1).Specifically,Fmr1KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli.This abnormality was accom-panied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons.These effects were ameliorated by the acute application of GABAA receptor activators,which enhanced the activity of inhibitory neurons,or by rein-troducing Fmr1 gene expression in knockout V1 neu-rons in both juvenile and young-adult mice.Overall,V1 plays an important role in the visual abnormalities of Fmr1KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.