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 (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied 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 GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.

许多受脆性 X 综合征 (FXS) 和自闭症谱系障碍影响的人都有感觉处理缺陷，例如对听觉、触觉和视觉刺激过敏。与人类的 FXS 一样，啮齿动物中Fmr1的缺失也会导致感觉、行为和认知缺陷。然而，感觉障碍，尤其是视力障碍的神经机制仍不清楚。视觉处理缺陷是否源于输入的损坏、初级感觉皮层的感知受损或高级皮层的整合改变，目前尚不清楚，并且没有有效的治疗方法。在这项研究中，我们使用基因敲除小鼠模型 ( Fmr1 ^KO )、体内成像和行为测量来表明Fmr1损害初级视觉皮层 (V1) 的信号处理。具体而言，Fmr1 ^KO小鼠对低强度刺激的反应增强，但对高强度刺激的反应正常。这种异常伴随着 V1 微电路中局部网络连接性的增强和 V1 神经元树突复杂性的增加。这些影响通过 GABA _A受体激活剂的急性应用得到改善，这增强了抑制性神经元的活性，或者通过在幼年和年轻成年小鼠的敲除 V1 神经元中重新引入Fmr1基因表达。总体而言，V1 在Fmr1 ^KO的视觉异常中起重要作用小鼠，并且有可能挽救发达的 FXS 和自闭症患者的感觉障碍。