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Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD
Name
nihms-1552758.pdf
Description
Accepted version
Size
2.7 MB
Format
Adobe PDF
Checksum (MD5)
b1bddcc9c6f7e245d6b09cda1711b4a0
Author(s)
Chen, Qian
Deister, Christopher A.
Gao, Xian
Guo, Baolin
Lynn-Jones, Taylor
Chen, Naiyan
Wells, Michael F.
Liu, Runpeng
Goard, Michael J.
Dimidschstein, Jordane
Date Issued
March 2020
Journal
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Citation
Chen, Qian et al. "Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD." Nature Neuroscience 23, 4 (March 2020): 520–532 © 2020 The Author(s)
Version
Author's final manuscript
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.
MIT Department
McGovern Institute for Brain Research at MIT
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
http://dx.doi.org/10.1038/S41593-020-0598-6
