The roles of neuron-NG2 glia synapses in promoting oligodendrocyte development and remyelination

Abstract

NG2 immunopositive progenitor cells, also simply termed as NG2 glia and thought mainly to be oligodendrocyte precursor cells (OPCs), form synaptic connections with neurons in gray and white matters of brain. One of the most classical features of oligodendrocyte lineage cells is myelination, which will favor neuronal signaling transmission. Thus, is there a causal link between the specific synapses of neuron-NG2 glia and myelination? Building on this, here, we will discuss several relevant issues. First, in order to understand the synapses, it is necessary to integrate the definite inputs onto NG2 glia. We show that the synaptic activities and myelination are not synchronized, so the synapses are more likely to regulate early development of NG2 glia and prepare for myelination. Furthermore, several studies have suggested that the synapses also play a role in recovery of pathological conditions, such as multiple sclerosis (MS). Therefore, elucidating the activities of neuron-NG2 glia synapses will be beneficial for both physiological and pathological conditions.

The existence of neuron-NG2 glia synapses reveals that the neuronal activities projecting to NG2 glia is an elaborate regulation, and the signaling from neurons to NG2 glia is frequent in early stage. The neuron-NG2 glia synapses indirectly provide a basic condition to support myelination by extrasynaptic communication. The neuron-NG2 glia synapses also promote remyelination, and it occurs similar to physiological conditions.

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Abbreviations

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

CNS:

Central nervous system

DPL:

Day post lesion

EPSCs:

Excitatory postsynaptic currents

FSIs:

Fast-spiking interneurons

GABA:

γ-Aminobutyric acid

IPSCs:

Inhibitory postsynaptic currents

MNTB:

Medial nucleus of the trapezoid body

MS:

Multiple sclerosis

NFSIs:

Non-fast-spiking interneurons

NMDA:

N-methyl-D-aspartate

OL:

Oligodendrocyte

OPCs:

Oligodendrocyte precursor cells

PV:

Parvalbumin

SVZ:

Subventricular zone

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Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 31371147) and the Innovative Science Project of Chongqing for Graduate Students (No. CYB17136).

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Correspondence to Zhongxiang Yao.

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Highlights

1. Innervation of NG2 glia is similar to a neuron-neuron pattern.

2. The neuron-NG2 glia synapses support myelination indirectly by promoting development of NG2 glia.

3. The regulation pattern altered from synaptic to extrasynaptic communication in late stage.

4. Remyelination may be enhanced by activities of neuron-NG2 glia synapses.

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Li, R., Zhang, P., Zhang, M. et al. The roles of neuron-NG2 glia synapses in promoting oligodendrocyte development and remyelination. Cell Tissue Res 381, 43–53 (2020). https://doi.org/10.1007/s00441-020-03195-9

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Keywords

  • NG2 immunopositive progenitor cell (NG2 glia)
  • Neuron-NG2 glia synapse
  • Oligodendrocyte
  • Development
  • Remyelination
  • Multiple sclerosis (MS)