Sparse interaction between oligodendrocyte precursor cells (NG2⁺cells) and nodes of Ranvier in the central nervous system

Abstract

Regeneration of propagating action potentials at nodes of Ranvier allows nerve impulses to be conducted over long distances. Proper nodal function is believed to rely on intimate associations among axons, myelinating oligodendrocytes, and perinodal astrocytes. Studies in the optic nerve, corpus callosum, and spinal cord suggest that NG2+ cells are also key constituents of CNS nodes and that these glia may influence conduction efficacy and formation of axon collaterals. However, the prevalence of NG2+ cell processes at CNS nodes of Ranvier has not been rigorously quantified. Here we used a transgenic mouse expressing membrane-targeted EGFP to visualize the fine processes of NG2+ cells and to quantify the spatial relationship between NG2+ cells and nodes of Ranvier in four distinct CNS white matter tracts. NG2+ cell processes came within close spatial proximity to a small percentage of nodes of Ranvier and approximately half of these spatial interactions were estimated to occur by chance. The majority of NG2+ cell process tips were not found in close proximity to nodes and gray matter NG2+ cells in regions of low nodal density were as morphologically complex as their white matter counterparts, indicating that attraction to nodes does not critically influence the elaboration of NG2+ cell processes. Finally, there was no difference in nodal density between small regions devoid of NG2+ cell processes and those containing numerous NG2+ cells processes, demonstrating that the function of CNS nodes of Ranvier does not require ongoing interaction with NG2+ cells.Significance StatementEffective propagation of action potentials along neuronal axons is dependent upon periodic regeneration of depolarization at nodes of Ranvier. The position, structural integrity, and function of nodes of Ranvier is believed to be regulated, in part, by intimate physical interactions between nearby glial cells and nodes. Clarifying whether oligodendrocyte precursor cells are obligate members of this nodal support system is critical for defining whether these cells contribute to pathologies in which nodal structure is compromised.

Clusters of neuronal neurofascin prefigure the position of a subset of nodes of Ranvier along individual central nervous system axons in vivo

“…Only 6% (4/62) of all clusters analyzed disappeared over a 2-day period along unmyelinated axon domains ( Figure 2 C). It has been reported that processes of oligodendrocyte precursor cells (OPCs) can associate with nodes and pre-nodal clusters to varying extents ( Biase et al., 2017 ; Serwanski et al., 2017 ; Thetiot et al., 2020 ). To test if OPC processes associate with Nfasca clusters where they could be held in position, we analyzed their co-localization in full transgenic olig1:mScarlet-CAAX, which have all OPC processes labeled.…”

Clusters of neuronal Neurofascin prefigure node of Ranvier position along single axons

“…2C). It has been reported that processes of oligodendrocyte precursor cells (OPCs) can associate with nodes and pre-nodal clusters to varying extents (Biase et al, 2017; Thetiot et al, 2020). In order to test if OPC processes preferably associate with Nfasca clusters where they could hold them in position, we analysed their association with OPC processes labelled in full transgenic Tg(olig1:mScarlet-CAAX) lines.…”