1 research outputs found
L-Type Ca2+ Channels of NG2 Glia Determine Proliferation and NMDA Receptor-Dependent Plasticity
NG2 (nerve/glial antigen 2) glia are uniformly distributed in the gray and white matter
of the central nervous system (CNS). They are the major proliferating cells in the brain
and can differentiate into oligodendrocytes. NG2 glia do not only receive synaptic input
from excitatory and inhibitory neurons, but also secrete growth factors and cytokines,
modulating CNS homeostasis. They express several receptors and ion channels that
play a role in rapidly responding upon synaptic signals and generating fast feedback,
potentially regulating their own properties. Ca2+ influx via voltage-gated Ca2+ channels
(VGCCs) induces an intracellular Ca2+ rise initiating a series of cellular activities. We
confirmed that NG2 glia express L-type VGCCs in the white and gray matter during CNS
development, particularly in the early postnatal stage. However, the function of L-type
VGCCs in NG2 glia remains elusive. Therefore, we deleted L-type VGCC subtypes
Cav1.2 and Cav1.3 genes conditionally in NG2 glia by crossbreeding NG2-CreERT2
knock-in mice to floxed Cav1.2 and flexed Cav1.3 transgenic mice. Our results showed
that ablation of Cav1.2 and Cav1.3 strongly inhibited the proliferation of cortical NG2
glia, while differentiation in white and gray matter was not affected. As a consequence,
no difference on myelination could be detected in various brain regions. In addition, we
observed morphological alterations of the nodes of Ranvier induced by VGCC-deficient
NG2 glia, i.e., shortened paired paranodes in the corpus callosum. Furthermore, deletion
of Cav1.2 and Cav1.3 largely eliminated N-methyl-D-aspartate (NMDA)-dependent
long-term depression (LTD) and potentiation in the hippocampus while the synaptic
input to NG2 glia from axons remained unaltered. We conclude that L-type VGCCs
of NG2 glia are essential for cell proliferation and proper structural organization of nodes
of Ranvier, but not for differentiation and myelin compaction. In addition, L-type VGCCs
of NG2 glia contribute to the regulation of long-term neuronal plasticity