Chavez, A. R. | Search bioRxiv

bioRxiv2026

Premyelinating Oligodendrocyte Survival Governs CNS Remyelination

Myelinating oligodendrocytes are produced throughout life by the constitutive differentiation of oligodendrocyte precursor cells (OPCs). However, the rate of oligodendrocyte generation changes with age and after a demyelinating injury. Here, we report that variation in premyelinating oligodendrocyte (preOL) survival modulates the rate of oligodendrocyte production. PreOL survival increased to drive the regeneration of oligodendrocytes after demyelination and decreased in middle-aged mice to contribute to age-related decline in oligodendrocyte production. Furthermore, we demonstrate that treatment with a GPR17 antagonist, Myro-02, increases oligodendrocyte replacement by promoting preOL survival after demyelination. Together, our findings demonstrate that increased survival of preOLs governs the regeneration of oligodendrocytes following demyelinating injury and suggest that modulating preOL survival may be an alternative therapeutic avenue to promote oligodendrocyte regeneration.

neuroscience↗

bioRxiv2021

Motor Learning Drives Dynamic Patterns of Intermittent Myelination onBehaviorally-Activated Axons

Myelin plasticity occurs when newly-formed and pre-existing oligodendrocytes remodel existing patterns of myelination. Recent studies show these processes occur in response to changes in neuronal activity and are required for learning and memory. However, the link between behaviorally-relevant neuronal activity and circuit-specific changes in myelination remains unknown. Using longitudinal, in vivo two-photon imaging and targeted labeling of learning-activated neurons, we explore how the pattern of intermittent myelination is altered on individual cortical axons during learning of a dexterous reach task. We show that behavior-induced plasticity is targeted to learning-activated axons and occurs in a staged response across cortical layers in primary motor cortex. During learning, myelin sheaths retract, lengthening nodes of Ranvier. Following learning, addition of new sheaths increases the number of continuous stretches of myelination. Computational modeling suggests these changes initially slow and subsequently increase conduction speed. Finally, we show that both the magnitude and timing of nodal and myelin dynamics correlate with behavioral improvement during learning. Thus, learning-activated, circuit-specific changes to myelination may fundamentally alter how information is transferred in neural circuits during learning.

neuroscience↗