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

• Published in: Nature communications Vol. 12; no. 1; pp. 5740 - 18
• Main Authors: Zhang, Xiao, Liu, Yao, Hong, Xiaoqi, Li, Xia, Meshul, Charles K, Moore, Cynthia, Yang, Yabing, Han, Yanfei, Li, Wei-Guang, Qi, Xin, Lou, Huifang, Duan, Shumin, Xu, Tian-Le, Tong, Xiaoping
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 30.09.2021; Nature Publishing Group UK; Nature Portfolio
• Subjects: Animals; Antigens; Anxiety; Anxiety - etiology; Anxiety - pathology; Anxiety - psychology; Biosynthesis; Cell Differentiation; Cell proliferation; Disease Models, Animal; Exocytosis; gamma-Aminobutyric Acid - metabolism; Glial cells; Glial stem cells; Glutamate Decarboxylase - biosynthesis; Hippocampus; Hippocampus - cytology; Hippocampus - pathology; Humans; Interneurons; Interneurons - pathology; Male; Mice; Mice, Transgenic; Neuronal-glial interactions; Neurons; Oligodendrocyte Precursor Cells - metabolism; Oligodendrocytes; Patch-Clamp Techniques; Photoactivation; Social Defeat; Social interactions; Stress, Psychological - complications; Stress, Psychological - pathology; Stress, Psychological - psychology; Synapses; Synapses - pathology; Synaptic transmission; Synaptic Transmission - physiology; Synaptogenesis; Vesicle-Associated Membrane Protein 2 - metabolism; γ-Aminobutyric acid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-25956-y

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.