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Nat Neurosci. 2019 Aug;22(8):1223-1234. doi: 10.1038/s41593-019-0445-9. Epub 2019 Jul 22.

Anterior cingulate cortex dysfunction underlies social deficits in Shank3 mutant mice.

Author information

1
Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China.
2
Department of Anatomy and K.K. Leung Brain Research Center, Fourth Military Medical University, Xi'an, China.
3
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
4
Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
5
Interdisciplinary Institute of Neuroscience and Technology, Qiushi Academy for Advanced Studies, Zhejiang University, Hangzhou, China.
6
Brain Research Center, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China.
7
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
8
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. fengg@mit.edu.
9
Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China. wwt0657@fmmu.edu.cn.
10
Department of Neurobiology, School of Basic Medicine, Fourth Military Medical University, Xi'an, China. shengxi@fmmu.edu.cn.

Abstract

Social deficit is a core clinical feature of autism spectrum disorder (ASD) but the underlying neural mechanisms remain largely unclear. We demonstrate that structural and functional impairments occur in glutamatergic synapses in the pyramidal neurons of the anterior cingulate cortex (ACC) in mice with a mutation in Shank3, a high-confidence candidate ASD gene. Conditional knockout of Shank3 in the ACC was sufficient to generate excitatory synaptic dysfunction and social interaction deficits, whereas selective enhancement of ACC activity, restoration of SHANK3 expression in the ACC, or systemic administration of an α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-positive modulator improved social behavior in Shank3 mutant mice. Our findings provide direct evidence for the notion that the ACC has a role in the regulation of social behavior in mice and indicate that ACC dysfunction may be involved in social impairments in ASD.

PMID:
31332372
DOI:
10.1038/s41593-019-0445-9
[Indexed for MEDLINE]

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