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

Dysfunction of cortical GABAergic neurons leads to sensory hyper-reactivity in a Shank3 mouse model of ASD. 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. Nature Neuroscience, March, 2020.

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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.

@article{chen_dysfunction_2020,
	title = {Dysfunction of cortical {GABAergic} neurons leads to sensory hyper-reactivity in a {Shank3} mouse model of {ASD}},
	issn = {1097-6256, 1546-1726},
	url = {http://www.nature.com/articles/s41593-020-0598-6},
	doi = {10.1038/s41593-020-0598-6},
	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.},
	language = {en},
	urldate = {2020-03-06},
	journal = {Nature Neuroscience},
	author = {Chen, Qian and Deister, Christopher A. and Gao, Xian and Guo, Baolin and Lynn-Jones, Taylor and Chen, Naiyan and Wells, Michael F. and Liu, Runpeng and Goard, Michael J. and Dimidschstein, Jordane and Feng, Shijing and Shi, Yiwu and Liao, Weiping and Lu, Zhonghua and Fishell, Gord and Moore, Christopher I. and Feng, Guoping},
	month = mar,
	year = {2020}
}

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