皮质GABA能神经元功能异常导致感觉过度反应
2020-03-04   阅读:305   来源:自然

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》。

研究人员检查了ASD的Shank3B-/-小鼠模型新皮层中感官知觉的神经表征。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。
 
触须初级体感皮层(vS1)中的体内群体钙成像显示锥体神经元的自发性刺激激发,但中间神经元活性降低。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。
 
这些发现表明,皮质GABA能神经元功能异常在ASD的Shank3小鼠模型感觉高反应性中起关键作用,并确立了探索治疗干预的潜在细胞靶标。
 
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的使人衰弱的症状,但是尚未完全理解潜在的感觉异常的神经基础。
 
附:英文原文

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

Issue&Volume: 2020-03-02

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.

DOI: 10.1038/s41593-020-0598-6

编辑:小柯机器人

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