Oligodendrocyte precursor cells (OPCs) are produced throughout life and are required for motor learning, but their role in this process is unclear. Within 2–3 hours of beginning a motor-learning task, mice lacking the transcription factor MYRF (myelin regulator factor) showed reduced levels of new oligodendrocytes and impaired learning. Wild-type mice trained in this task exhibited accelerated differentiation of OPCs, suggesting that OPC differentiation contributes to motor learning in this task.