NG2 glia-derived GABA release tunes inhibitory synapses and contributes to stress-induced anxiety

Xiao Zhang, Yao Liu, Xiaoqi Hong, Xia Li, Charles K. Meshul, Cynthia Moore, Yabing Yang, Yanfei Han, Wei-Guang Li, Xin Qi, Huifang Lou, Shumin Duan, Tian-Le Xu and Xiaoping Tong ()
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Xiao Zhang: Shanghai Jiao Tong University
Yao Liu: Shanghai Jiao Tong University
Xiaoqi Hong: Shanghai Jiao Tong University
Xia Li: Institute of Special Environmental Medicine, Co-innovation Center of Neuroregeneration, Nantong University
Charles K. Meshul: Research Services, VA Medical Center
Cynthia Moore: Research Services, VA Medical Center
Yabing Yang: Shanghai Jiao Tong University
Yanfei Han: Shanghai Jiao Tong University School of Medicine
Wei-Guang Li: Shanghai Jiao Tong University
Xin Qi: Shanghai Jiao Tong University
Huifang Lou: Zhejiang University School of Medicine
Shumin Duan: Zhejiang University School of Medicine
Tian-Le Xu: Shanghai Jiao Tong University
Xiaoping Tong: Shanghai Jiao Tong University

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract NG2 glia, also known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development. In contrast to other glial cell types, the most intriguing aspect of NG2 glia is their ability to directly sense synaptic inputs from neurons. However, whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. Here, we report that NG2 glia form synaptic complexes with hippocampal interneurons and that selective photostimulation of NG2 glia (expressing channelrhodopsin-2) functionally drives GABA release and enhances inhibitory synaptic transmission onto proximal interneurons in a microcircuit. The mechanism involves GAD67 biosynthesis and VAMP-2 containing vesicular exocytosis. Further, behavioral assays demonstrate that NG2 glia photoactivation triggers anxiety-like behavior in vivo and contributes to chronic social defeat stress.

Date: 2021
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DOI: 10.1038/s41467-021-25956-y

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