Remodeling of pre-existing myelinated axons and oligodendrocytes is stimulated by environmental enrichment in the young adult brain

Neuronal activity influences oligodendrocyte production and myelination during brain development. While it is known that the myelinating process continues across the lifespan, the extent to which neuronal activity influences oligodendrocyte production and myelin acquisition during adulthood is not fully understood. Here, we find that using environmental enrichment (EE) to physiologically upregulate neuronal activity for 6-weeks during young adulthood in C57Bl/6 mice results in increased axon diameter in the corpus callosum, with a corresponding increased thickness of pre-existing myelin sheaths. Furthermore, EE uniformly promotes the differentiation of pre-existing oligodendroglia in both corpus callosum and cerebral somatosensory cortex, while differentially altering new OPC production in these regions. Together, results of this study suggest that neuronal activity induced by EE exerts a pronounced influence on adult myelination, promoting the remodeling of pre-existing myelinated axons and accelerating the differentiation of pre-existing oligodendroglia. Importantly, we show that these effects are independent of the addition of new myelin or contributions by newly-generated oligodendroglia. This impact on pre-existing oligodendroglia and pre-existing myelin sheaths is a previously undescribed form of adaptive myelination that potentially contributes to neuronal circuit maturation in the young adult central nervous system.