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
Oligodendrocyte progenitor cells (OPCs) are immature cells in the central nervous system (CNS) that can rapidly respond to changes within their environment by modulating their proliferation, motility and differentiation. OPCs differentiate into myelinating oligodendrocytes throughout life, and both cell types have been implicated in maintaining and modulating neuronal function to affect motor performance, cognition and emotional state. However, questions remain about the mechanisms employed by OPCs and oligodendrocytes to regulate circuit function, including whether OPCs can only influence circuits through their generation of new oligodendrocytes, or can play other regulatory roles within the CNS. In this review, we detail the molecular and cellular mechanisms that allow OPCs, newborn oligodendrocytes and pre-existing oligodendrocytes to regulate circuit function and ultimately influence behavioral outcomes.
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.
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.
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