Neuron to Oligodendrocyte Precursor Cell Synapses: Protagonists in Oligodendrocyte Development and Myelination, and Targets for Therapeutics.

Robert Brock,Daniela M. S. Moura,Laura A. Cocas,Emma J. Brennan

doi:10.3389/fnins.2021.779125

Abstract

The development of neuronal circuitry required for cognition, complex motor behaviors, and sensory integration requires myelination. The role of glial cells such as astrocytes and microglia in shaping synapses and circuits have been covered in other reviews in this journal and elsewhere. This review summarizes the role of another glial cell type, oligodendrocytes, in shaping synapse formation, neuronal circuit development, and myelination in both normal development and in demyelinating disease. Oligodendrocytes ensheath and insulate neuronal axons with myelin, and this facilitates fast conduction of electrical nerve impulses via saltatory conduction. Oligodendrocytes also proliferate during postnatal development, and defects in their maturation have been linked to abnormal myelination. Myelination also regulates the timing of activity in neural circuits and is important for maintaining the health of axons and providing nutritional support. Recent studies have shown that dysfunction in oligodendrocyte development and in myelination can contribute to defects in neuronal synapse formation and circuit development. We discuss glutamatergic and GABAergic receptors and voltage gated ion channel expression and function in oligodendrocyte development and myelination. We explain the role of excitatory and inhibitory neurotransmission on oligodendrocyte proliferation, migration, differentiation, and myelination. We then focus on how our understanding of the synaptic connectivity between neurons and OPCs can inform future therapeutics in demyelinating disease, and discuss gaps in the literature that would inform new therapies for remyelination.

Highlights

Myelination is critical for signal conduction within axons, and demyelination is an essential feature of traumatic brain injury and stroke, as well as degenerative diseases such as Alzheimer’s disease and multiple sclerosis
Application of GABA increases OPC process branching, number of myelin segments, and MBP expression in dorsal root ganglia neurons (DRG)-OPC co-cultures in the presence of GABAA inhibitors, suggesting that these effects are mediated through GABAB second messenger signals (Serrano-Regal et al, 2020b)
In this review we focused on the newest research that showed involvement of ion channels, neurotransmitter receptors, and an explanation of synaptic mechanisms relevant to the OPC-neuron synapse in the context of OPC development and myelination

Summary

Introduction

Myelination is critical for signal conduction within axons, and demyelination is an essential feature of traumatic brain injury and stroke, as well as degenerative diseases such as Alzheimer’s disease and multiple sclerosis. We address how neuron to OPC synapses can promote proliferation versus differentiation, the mechanisms behind the loss of functional synapses during development, and the developmental changes in receptor expression to update the current OPC review literature.

Results

Conclusion