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

Abstract

JX conceived the study; MN performed the experiments and analyzed data; RW, DG and JF assisted the experiments and data analysis; AH contributed to experimental design; JX and SM supervised the study; MN and JX wrote the manuscript. Scholarship and the University of Melbourne STRAPA Scholarship to M.N. Confocal Microscopy was performed at the Biological Optical Microscopy Platform, The University of Melbourne (www.microscopy.unimelb.edu.au). AbstractNeuronal 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 preexisting 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.

Oligodendroglial Epigenetics, from Lineage Specification to Activity-Dependent Myelination

“…This includes myelin ensheathment, compaction around the axon, and internode sizes. This is not limited to developmental myelination as myelin is constantly remodeled in adult CNS, especially during learning and when facing depressive or social isolation experiences [24,25,[176][177][178][179][180][181] (Table 4). [168] hMeDIP: hydroxymethylated DNA immunoprecipitation, RRHP: reduced representation 5-hydroxymethylcytosine profiling, Seq: sequencing.…”