Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD.,Nature Neuroscience

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Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD.
Nature Neuroscience ( IF 21.2 ) Pub Date : 2020-03-02 , DOI: 10.1038/s41593-020-0598-6
Qian Chen ₁ , Christopher A Deister ₂ , Xian Gao _{1,

3} , Baolin Guo _{3,

4} , Taylor Lynn-Jones ₁ , Naiyan Chen ₁ , Michael F Wells ₃ , Runpeng Liu ₁ , Michael J Goard _{5,

6} , Jordane Dimidschstein _{3,

7} , Shijing Feng ₈ , Yiwu Shi ₉ , Weiping Liao ₉ , Zhonghua Lu ₈ , Gord Fishell _{3,

7} , Christopher I Moore ₂ , Guoping Feng _{1,

3}

Affiliation

McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Department of Neuroscience, Brown University, Providence, RI, USA.
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, USA.
Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA, USA.
NYU Neuroscience Institute, New York University Langone Medical Center, New York, NY, USA.
Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, The Brain Cognition and Brain Disease Institute, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou, China.

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.

中文翻译：

在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。

在自闭症谱系障碍（ASD）的个体中，对感觉输入的过度反应是一种常见且使人衰弱的症状，但是尚未完全理解潜在的感觉异常的神经基础。在这里，我们检查了ASD的Shank3B-/-小鼠模型新皮层中感觉知觉的神经表征。雄性和雌性Shank3B-/-小鼠在触须运动检测任务中对相对较弱的触觉刺激更为敏感。触角初生体感皮层（vS1）中的体内人群钙成像显示，锥体神经元的自发和刺激诱发的放电增加，但中间神经元的活性降低。在vS1抑制性中间神经元中Shank3的优先缺失会导致锥体神经元活动亢进并增加触须运动检测任务中的刺激敏感性。

更新日期：2020-03-02

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