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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)520-532
Number of pages13
JournalNature Neuroscience
Volume23
Issue number4
DOIs
StatePublished - Apr 1 2020

ASJC Scopus subject areas

  • Neuroscience(all)

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    Chen, Q., Deister, C. A., Gao, X., Guo, B., Lynn-Jones, T., Chen, N., Wells, M. F., Liu, R., Goard, M. J., Dimidschstein, J., Feng, S., Shi, Y., Liao, W., Lu, Z., Fishell, G., Moore, C. I., & Feng, G. (2020). Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD. Nature Neuroscience, 23(4), 520-532. https://doi.org/10.1038/s41593-020-0598-6