Myelin Maintenance and Addition Regulate Synaptic Plasticity in the Adult Mouse Cortex

Abstract

ABSTRACT Myelin has the capacity to affect synapse number or plasticity across the lifespan. We report that disrupting oligodendrocyte (OL) and myelin maintenance from P57 ( Plp‐CreER T2 :: Myrf fl/fl mice) induces myelin loss and impairs action potential conduction and gross motor performance. By studying sparsely labeled layer V pyramidal neurons in the primary motor cortex of P57 + 60 mice, we determined that apical and basal dendritic spine densities were normal; however, more were large, stable mushroom spines that generated larger amplitude miniature excitatory postsynaptic currents. When we instead prevented OL and myelin addition from P57 ( Pdgfrα‐CreER:: Myrf fl/fl mice), action potential conduction velocity, gross motor performance, and spine densities were normal; however, basal dendritic spine morphology was changed. Without adult myelination, the basal dendrites of P57 + 60 mice retained the morphological characteristics of dendrites in P57 + 0 mice, which have a higher proportion of thin, plastic spines. These data indicate that existing myelin imposes limits on the proportion of spines that become mushroom spines, allowing neurons to remain plastic, while adult myelination is required for spine stabilization within the basal but not apical dendritic compartment. These data show that myelin regulates synaptic plasticity within the motor circuit and offer a potential mechanism by which myelination can influence motor skill learning and/or recall.

The authors' abstract, as published at the source. Glia, 2026 · DOI ↗