Work over the last decade demonstrates that the myelin sheaths enwrapping axons, classically seen as static insulators, are highly dynamic and respond to axonal activity and experience. The phenomenon, called “myelin plasticity”, goes beyond postnatal stages into adulthood and is thought to fine-tune neuronal circuits to support adaptive behavior or functional recovery upon injury. I will discuss how non-conventional NMDA receptors containing GluN3A subunits, key modulators of juvenile synaptic plasticity in neurons, are repurposed in oligodendrocyte progenitor cells (OPCs) to control myelin plasticity.  I will describe: 1) transcriptomic and cell biology studies demonstrating that GluN3A expression correlates with OPC states linked to activity-sensing; 2) evidence from genetic models that GluN3A expression in OPCs is selectively required for OPC differentiation and myelin remodeling elicited by axonal stimulation, chronic exercise or complex motor training.  I will then show how GluN3A effects on activity-dependent oligodendrogenesis target task-related brain regions and control associated behavioral adaptations.  Our work identifies GluN3A-receptors as the first selective molecular mediator of myelin plasticity, and provides an entry point to develop strategies to engage myelin plasticity in specific brain circuits based on re-expressing GluN3A or modulating downstream activity-induced signaling pathways.