Dysfunction of grey matter NG2 glial cells affects neuronal plasticity and behavior

Timmermann, A.; Jabs, R.; Boehlen, A.; Domingos, C.; Skubal, M.; Huang, W.; Kirchhoff, F.; Henneberger, C.; Bilkei-Gorzo, A.; Seifert, G.; Steinhauser, C. W.

doi:10.1101/2021.08.20.457086

bioRxiv · 10.1101/2021.08.20.457086

Dysfunction of grey matter NG2 glial cells affects neuronal plasticity and behavior

Timmermann, A.·Jabs, R.·Boehlen, A.·Domingos, C.·Skubal, M.·Huang, W.·Kirchhoff, F.·Henneberger, C.·Bilkei-Gorzo, A.·Seifert, G.·Steinhauser, C. W.

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Abstract

NG2 glia represent a distinct type of macroglial cells in the CNS and are unique among glia because they receive synaptic input from neurons. They are abundantly present in white and grey matter. While the majority of white matter NG2 glia differentiates into oligodendrocytes, the physiological impact of grey matter NG2 glia and their synaptic input are ill defined yet. 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. Focussing on the hippocampus, we found that loss of the Kir4.1 potentiated synaptic depolarizations of NG2 glia and enhanced the expression of myelin basic protein. Notably, while mice with targeted deletion of the K+ channel in NG2 glia showed impaired long term potentiation at CA3-CA1 synapses, they demonstrated improved spatial memory as revealed by testing new object location recognition. Our data demonstrate that proper NG2 glia function is critical for normal brain function and behavior.

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Timmermann, A., Jabs, R., Boehlen, A., Domingos, C., Skubal, M., Huang, W., Kirchhoff, F., Henneberger, C., Bilkei-Gorzo, A., Seifert, G., Steinhauser, C. W.. 2021-08-20. Dysfunction of grey matter NG2 glial cells affects neuronal plasticity and behavior. https://doi.org/10.1101/2021.08.20.457086

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