Highlights d Altering neuronal activity reversibly modifies node of Ranvier length d Neuronal activity alters periaxonal space width in the adult mouse brain d Nodal and periaxonal plasticities synergistically modulate action potential speed d The level of skill acquisition with learning correlates with action potential speed

Neuronal activity is a potent extrinsic regulator of oligodendrocyte generation and central nervous system myelination. Clinically, repetitive transcranial magnetic stimulation (rTMS) is delivered to noninvasively modulate neuronal activity; however, the ability of rTMS to facilitate adaptive myelination has not been explored. By performing cre‐lox lineage tracing, to follow the fate of oligodendrocyte progenitor cells in the adult mouse brain, we determined that low intensity rTMS (LI‐rTMS), administered as an intermittent theta burst stimulation, but not as a continuous theta burst or 10 Hz stimulation, increased the number of newborn oligodendrocytes in the adult mouse cortex. LI‐rTMS did not alter oligodendrogenesis per se, but instead increased cell survival and enhanced myelination. These data suggest that LI‐rTMS can be used to noninvasively promote myelin addition to the brain, which has potential implications for the treatment of demyelinating diseases such as multiple sclerosis.

Myelination of central nervous system axons increases action potential conduction velocity and increases the speed of information transfer. However, it is unclear whether myelination optimizes action potential conduction to achieve synchronicity and facilitate information processing within cortical and associative circuits. Here we show that myelin sheaths 25 remain plastic in the adult mouse and undergo subtle structural modifications to influence action potential conduction. Repetitive transcranial magnetic stimulation and spatial learning, two stimuli that modify neuronal activity, alter the length of the nodes of Ranvier and the size of the periaxonal space within active brain regions. This change in the axon-glial configuration, which is independent of oligodendrogenesis, tunes conduction velocity to increase the synchronicity of 30 action potential conduction. One Sentence Summary:The activity-dependent modulation of nodes of Ranvier and the periaxonal space allows central conduction to be tuned to achieve synchronicity.