近日，美国麻省理工学院Guoping Feng、布朗大学Christopher I. Moore等研究人员合作发现，在自闭症谱系障碍（ASD）的Shank3小鼠模型中，皮质GABA能神经元功能异常导致感觉过度反应。这一研究成果于3月2日在线发表于《自然—神经科学》。
Title: Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD
Author: Qian Chen, Christopher A. Deister, Xian Gao, Baolin Guo, Taylor Lynn-Jones, Naiyan Chen, Michael F. Wells, Runpeng Liu, Michael J. Goard, Jordane Dimidschstein, Shijing Feng, Yiwu Shi, Weiping Liao, Zhonghua Lu, Gord Fishell, Christopher I. Moore, Guoping Feng
Abstract: Hyper-reactivity to sensory input is a common and debilitating symptom in individuals with autism spectrum disorders (ASD), but the neural basis underlying sensory abnormality is not completely understood. Here we examined the neural representations of sensory perception in the neocortex of a Shank3B/ mouse model of ASD. Male and female Shank3B/ mice were more sensitive to relatively weak tactile stimulation in a vibrissa motion detection task. In vivo population calcium imaging in vibrissa primary somatosensory cortex (vS1) revealed increased spontaneous and stimulus-evoked firing in pyramidal neurons but reduced activity in interneurons. Preferential deletion of Shank3 in vS1 inhibitory interneurons led to pyramidal neuron hyperactivity and increased stimulus sensitivity in the vibrissa motion detection task. These findings provide evidence that cortical GABAergic interneuron dysfunction plays a key role in sensory hyper-reactivity in a Shank3 mouse model of ASD and identify a potential cellular target for exploring therapeutic interventions.