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.

The low density lipoprotein-receptor related protein 1 (LRP1) is a large endocytic cell surface receptor that is known to interact with a variety of ligands, intracellular adaptor proteins and other cell surface receptors to regulate cellular behaviours ranging from proliferation to cell fate specification, migration, axon guidance, and lipid metabolism. A number of studies have demonstrated that LRP1 is expressed in the brain, yet it is unclear which central nervous system cell types express LRP1 during development and in adulthood. Herein we undertake a detailed study of LRP1 expression within the mouse brain and spinal cord, examining a number of developmental stages ranging from embryonic day 13.5 to postnatal day 60. We report that LRP1 expression in the brain peaks during postnatal development. On a cellular level, LRP1 is expressed by radial glia, neuroblasts, microglia, oligodendrocyte progenitor cells (OPCs), astrocytes and neurons, with the exception of parvalbumin+ interneurons in the cortex. Most cell populations exhibit stable expression of LRP1 throughout development; however, the proportion of OPCs that express LRP1 increases significantly from ~69% at E15.5 to ~99% in adulthood. We also report that LRP1 expression is rapidly lost as OPCs differentiate, and is absent from all oligodendrocytes, including newborn oligodendrocytes. While LRP1 function has been primarily examined in mature neurons, these expression data suggest it plays a more critical role in glial cell regulation–where expression levels are much higher.

Primary cilia are small microtubule‐based organelles capable of transducing signals from growth factor receptors embedded in the cilia membrane. Developmentally, oligodendrocyte progenitor cells (OPCs) express genes associated with primary cilia assembly, disassembly, and signaling, however, the importance of primary cilia for adult myelination has not been explored. We show that OPCs are ciliated in vitro and in vivo, and that they disassemble their primary cilia as they progress through the cell cycle. OPC primary cilia are also disassembled as OPCs differentiate into oligodendrocytes. When kinesin family member 3a (Kif3a), a gene critical for primary cilium assembly, was conditionally deleted from adult OPCs in vivo (Pdgfrα‐CreER™:: Kif3a fl/fl transgenic mice), OPCs failed to assemble primary cilia. Kif3a‐deletion was also associated with reduced OPC proliferation and oligodendrogenesis in the corpus callosum and motor cortex and a progressive impairment of fine motor coordination.

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