Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning

Abstract

SummaryWe identified a novel marker of newly-forming oligodendrocytes – the ecto-enzyme Enpp6 – and used this to track oligodendrocyte differentiation in adult mice as they learned a motor skill (running on a wheel with unevenly spaced rungs). Production of Enpp6 - expressing immature oligodendrocytes was accelerated within just 2.5 hours exposure to the complex wheel in subcortical white matter and within 4 hours in motor cortex. Conditional deletion of Myelin regulatory factor (Myrf) in oligodendrocyte precursors blocked formation of new Enpp6+ oligodendrocytes and impaired learning within the same ~2-3 hour time frame. This very early requirement for oligodendrocytes suggests a direct and active role in learning, closely linked to synaptic strengthening. Running performance of normal mice continued to improve over the following week accompanied by secondary waves of oligodendrocyte precursor proliferation and differentiation. We conclude that new oligodendrocytes contribute to both early and late stages of motor skill learning.

On Myelinated Axon Plasticity and Neuronal Circuit Formation and Function

“…Using a novel marker of newly differentiating 246 oligodendrocytes, Xiao et al showed that when control mice learn to run in a complex wheel, G1-247 paused OPCs rapidly transition into newly differentiating oligodendrocytes without proliferation, 248 specifically in task-relevant regions, e.g. within 2.5h in the subcortical WM (Xiao et al, 2016). Over the 249 course of the training week, the OPC population did exhibit an increase in proliferation, which 250 generated a later secondary wave of oligodendrocyte differentiation, in line with the previously noted 251 days-long timeline of differentiation following OPC division.…”

Oligodendroglia: metabolic supporters of neurons

“…Multiple studies have shown that myelin deposition is not static, but far more dynamic than initially thought, with adaptive changes in myelin driven by changes in neuronal activity (myelin plasticity) (6,(20)(21)(22)(23)(24)(25). These changes, e.g., induced by optogenetic stimulation or stimulated through learning of complex motor skills, promote oligodendrogenesis and the deposition of new myelin sheaths along the axons.…”

BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions

“…The developing and adult mouse central nervous system (CNS) both contain an abundant population of oligodendrocyte progenitor cells that continuously generate oligodendrocytes (7) and provide a source for reforming myelin after injury (8). Both oligodendrocyte progenitor cell proliferation and differentiation can increase within active neuronal circuits, and there is evidence that adult-born oligodendrocytes are actively engaged in forming new myelin sheaths in mice (9)(10)(11). For example, in adult mice, learning a new motor task is associated with changes in white matter structure (12).…”