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.
Highlights
NG2 glia, known as oligodendrocyte precursor cells (OPCs), play an important role in proliferation and give rise to myelinating oligodendrocytes during early brain development
Consistent with previous studies, we confirmed that Pdgfrα is a cellspecific marker for NG2 glia and immunohistochemistry from Pdgfrα-creERTM;ChR2(H134R)-eYFP mice showed a 94.69 ± 0.89% (n = 1524 cells from 12 mice) colocalization between YFP-labeled cells and NG2 antibody and a 100% (n = 746 cells from 7 mice) colocalization between YFP-labeled cells and Olig[2] (Oligodendrocyte lineage cell marker)
There was a 6.93 ± 1.62% (n = 284 cells from 3 mice) colocalization between YFP-labeled cells and mature oligodendrocyte marker CC1, they were not colocalized with the neuronal marker NeuN nor with the astrocytic marker GFAP in the hippocampus, suggesting that Pdgfrα-creERTM;ChR2(H134R)-eYFP mouse strain is specific for the oligodendrocyte lineage and mostly labels NG2 glia (Fig. 1a and Supplementary Fig. 1)
Summary
NG2 glia, 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. Whether this synaptic interaction is bidirectional or unidirectional, or its physiological relevance has not yet been clarified. 1234567890():,; NG2 glia, known as oligodendrocyte precursor cells (OPCs), were first identified in the 1980s and displayed self-renewal functionality as multipotent stem cells by providing myelinating oligodendrocytes during early brain development[1,2,3]. Further behavioral studies suggest that NG2 glia activation induces anxiety-like behavior in a chronic social defeat stress (CSDS) mouse model
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