Dysfunction of NG2 glial cells affects neuronal plasticity and behavior. Issue 6 (18th February 2023)

• Record Type: Journal Article
• Authors: Timmermann, Aline; Tascio, Dario; Jabs, Ronald; Boehlen, Anne; Domingos, Catia; Skubal, Magdalena; Huang, Wenhui; Kirchhoff, Frank; Henneberger, Christian; Bilkei‐Gorzo, Andras; Seifert, Gerald; Steinhäuser, Christian
• Is Part Of: Glia. Volume 71:Issue 6(2023)
• Page Start: 1481
• Page End: 1501
• Publication Date: 2023-02-18
• Subjects: Kir4.1 -- myelination -- neuronal plasticity -- neuron–glia signaling -- NG2 glia; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.24352
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: NG2 glia represents a distinct type of macroglial cells in the CNS and is unique among glia because they receive synaptic input from neurons. They are abundantly present in white and gray matter. While the majority of white matter NG2 glia differentiates into oligodendrocytes, the physiological impact of gray matter NG2 glia and their synaptic input are still ill defined. Here, we asked whether dysfunctional NG2 glia affect neuronal signaling and behavior. We generated mice with inducible deletion of the K + channel Kir4.1 in NG2 glia and performed comparative electrophysiological, immunohistochemical, molecular and behavioral analyses. Kir4.1 was deleted at postnatal day 23–26 (recombination efficiency about 75%) and mice were investigated 3–8 weeks later. Notably, these mice with dysfunctional NG2 glia demonstrated improved spatial memory as revealed by testing new object location recognition while working and social memory remained unaffected. Focussing on the hippocampus, we found that loss of Kir4.1 potentiated synaptic depolarizations of NG2 glia and stimulated the expression of myelin basic protein while proliferation and differentiation of hippocampal NG2 glia remained largely unaffected. Mice with targeted deletion of the K + channel in NG2 glia showed impaired long‐term potentiation at CA3‐CA1 synapses, which could be fully rescued by extracellular application of a TrkB receptor agonist. Our data demonstrate that proper NG2 glia function is important for normal brain function and behavior. Main Points: GPCs in the adult human white and gray matter are transcriptionally distinct. GM and WM hGPCs differentially express WNT, NOTCH, BMP and TGFβ pathway genes. The expression of BMP antagonists is significantly higher in WM hGPCs. hGPCs in the GM are larger and more complex than in the WM.