Neuronal Activity Promotes Oligodendrogenesis and Adaptive Myelination in the Mammalian Brain

Abstract

Myelination of the central nervous system requires the generation of functionally mature oligodendrocytes from oligodendrocyte precursor cells (OPCs). Electrically active neurons may influence OPC function and selectively instruct myelination of an active neural circuit. In this work, we use optogenetic stimulation of the premotor cortex in awake, behaving mice to demonstrate that neuronal activity elicits a mitogenic response of neural progenitor cells and OPCs, promotes oligodendrogenesis, and increases myelination within the deep layers of the premotor cortex and subcortical white matter. We further show that this neuronal activity–regulated oligodendrogenesis and myelination is associated with improved motor function of the corresponding limb. Oligodendrogenesis and myelination appear necessary for the observed functional improvement, as epigenetic blockade of oligodendrocyte differentiation and myelin changes prevents the activity-regulated behavioral improvement.

Myelination and mTOR

“…However, also apposition of new myelin lamella to already existing internodes might be involved in this process. This is suggested by the observed thicker myelin sheaths upon optogenetic stimulation of the premotor cortex, concomitant with improved motor function of the corresponding limb (Bechler & Ffrench‐Constant, 2014; Gibson et al, 2014). …”

“…Based on (a) the metabolic challenge endured by myelinating cells during development (Forbes & Gallo, 2017; McKenzie et al, 2014); (b) the requirement of a regular supply of myelin components in adult life (in homeostasis and during adaptive myelination) (Bechler & Ffrench‐Constant, 2014; Gibson et al, 2014); and (c) the central role of remyelination after injury and in disease (Cole, Early, & Lyons, 2017), signaling pathways central to cell metabolism are likely to occupy strategically relevant positions in the regulation of myelination in health and disease. Among such pathways, we will focus in this review mainly on the role of mTOR and closely associated signaling components.…”

“…Following up on pioneering work (Barres & Raff, 1994; Demerens et al, 1996), electrical axonal activity and release of synaptic vesicles have been proposed recently as a major axonal signal modulating oligodendrogenesis, regulating the numbers and lengths of internodes generated, guiding the selection of axons to be myelinated, and adjusting the growth of myelin sheaths (Gibson et al, 2014; Hines, Ravanelli, Schwindt, Scott, & Appel, 2015; Koudelka et al, 2016; Mensch et al, 2015; Wake et al, 2015; Wake, Lee, & Fields, 2011). The molecular players underlying such activity‐dependent myelination are not univocally defined.…”

Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training

“…9 Observed changes in white matter following training may instead reflect increased myelination elicited simply by neural activation underlying the complex motor behavior required to engage in physical exercise. 40 For example, we observed the majority of change in white matter architecture following training in the corpus callosum (Supplementary Table 3). Activity-dependent growth in callosal white matter has been documented following motor learning.…”

Computationale Neuroanatomie und Mikrostrukturbildgebung mit der Magnetresonanztomographie

“…5), und es steht in Beziehung zur Nervenleitgeschwindigkeit [16]. Weiterhin wird die G-Ratio durch plastische Prozesse durch Training [55] und durch demyelinisierende Krankheiten wie multiple Sklerose beeinflusst [56]. Das 2-Kompartiment-Modell von Stikov et al [57] zur Schätzung der G-Ratio kombiniert MT-und Diffusionsbildgebungs(DWI)-Daten.…”