The myelination of axons by oligodendrocytes profoundly affects central nervous system function, but how this is regulated by neuronal activity in vivo is not known. Here we find that blocking synaptic vesicle release impairs CNS myelination by reducing the number of myelin sheaths made by individual oligodendrocytes during their short period of formation. We also find that stimulating neuronal activity increases myelin sheath formation by individual oligodendrocytes. These data show that neuronal activity regulates the myelinating capacity of single oligodendrocytes.

Myelinated axons with nodes of Ranvier are an evolutionary elaboration common to essentially all jawed vertebrates. Myelin made by Schwann cells in our peripheral nervous system and oligodendrocytes in our central nervous system has been long known to facilitate rapid energy efficient nerve impulse propagation. However, it is now also clear, particularly in the central nervous system, that myelin is not a simple static insulator but that it is dynamically regulated throughout development and life. New myelin sheaths can be made by newly differentiating oligodendrocytes, and mature myelin sheaths can be stimulated to grow again in the adult. Furthermore, numerous studies in models from fish to man indicate that neuronal activity can affect distinct stages of oligodendrocyte development and the process of myelination itself. This begs questions as to how these effects of activity are mediated at a cellular and molecular level and whether activity-driven adaptive myelination is a feature common to all myelinated axons, or indeed all oligodendrocytes, or is specific to cells or circuits with particular functions. Here we review the recent literature on this topic, elaborate on the key outstanding questions in the field, and look forward to future studies that incorporate investigations in systems from fish to man that will provide further insight into this fundamental aspect of nervous system plasticity.This article is part of a Special Issue entitled SI: Myelin Evolution.