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Myelination allows for the regulation of conduction velocity, affecting the precise timing of neuronal inputs important for the development and function of brain circuits. In turn, myelination may be altered by changes in experience, neuronal activity, and vesicular release, but the links between sensory experience, corresponding neuronal activity, and resulting alterations in myelination require further investigation. We thus studied the development of myelination in the Xenopus laevis tadpole, a classic model for studies of visual system development and function because it is translucent and visually responsive throughout the formation of its retinotectal system. We begin with a systematic characterization of the timecourse of early myelin ensheathment in the Xenopus retinotectal system using immunohistochemistry of myelin basic protein (MBP) along with third harmonic generation (THG) microscopy, a label-free structural imaging technique. Based on the mid-larval developmental progression of MBP expression in Xenopus, we identified an appropriate developmental window in which to assess the effects of early temporally patterned visual experience on myelin ensheathment. We used calcium imaging of axon terminals in vivo to characterize the responses of retinal ganglion cells over a range of stroboscopic stimulation frequencies. Strobe frequencies that reliably elicited robust versus dampened calcium responses were then presented to animals for 7 d, and differences in the amount of early myelin ensheathment at the optic chiasm were subsequently quantified. This study provides evidence that it is not just the presence but also to the specific temporal properties of sensory stimuli that are important for myelin plasticity.

Funder: Montreal Neurological Institute – University of Cambridge Collaboration, Funder: Natural Sciences and Engineering Research Council of Canada; Id: http://dx.doi.org/10.13039/501100000038, Myelination allows for the regulation of conduction velocity, affecting the precise timing of neuronal inputs important for the development and function of brain circuits. In turn, myelination may be altered by changes in experience, neuronal activity, and vesicular release, but the links between sensory experience, corresponding neuronal activity, and resulting alterations in myelination require further investigation. We thus studied the development of myelination in the Xenopus laevis tadpole, a classic model for studies of visual system development and function because it is translucent and visually responsive throughout the formation of its retinotectal system. We begin with a systematic characterization of the timecourse of early myelin ensheathment in the Xenopus retinotectal system using immunohistochemistry of myelin basic protein (MBP) along with third harmonic generation (THG) microscopy, a label‐free structural imaging technique. Based on the mid‐larval developmental progression of MBP expression in Xenopus, we identified an appropriate developmental window in which to assess the effects of early temporally patterned visual experience on myelin ensheathment. We used calcium imaging of axon terminals in vivo to characterize the responses of retinal ganglion cells over a range of stroboscopic stimulation frequencies. Strobe frequencies that reliably elicited robust versus dampened calcium responses were then presented to animals for 7 d, and differences in the amount of early myelin ensheathment at the optic chiasm were subsequently quantified. This study provides evidence that it is not just the presence but also to the specific temporal properties of sensory stimuli that are important for myelin plasticity.

Precise timing of neuronal inputs is crucial for brain circuit function and development, where it contributes critically to experience-dependent plasticity. Myelination therefore provides an important adaptation mechanism for vertebrate circuits. Despite its importance to circuit activity, the interplay between neuronal activity and myelination has yet to be fully elucidated. In recent years, significant attention has been devoted to uncovering and explaining the phenomenon of white matter (WM) plasticity. Here, we summarize some of the critical evidence for modulation of the WM by neuronal activity, ranging from human diffusion tensor imaging (DTI) studies to experiments in animal models. These experiments reveal activity-dependent changes in the differentiation and proliferation of the oligodendrocyte lineage, and in the critical properties of the myelin sheaths. We discuss the implications of such changes for synaptic function and plasticity, and present the underlying mechanisms of neuron–glia communication, with a focus on glutamatergic signaling and the axomyelinic synapse. Finally, we examine evidence that myelin plasticity may be subject to critical periods. Taken together, the present review aims to provide insights into myelination in the context of brain circuit formation and function, emphasizing the bidirectional interplay between neurons and myelinating glial cells to better inform future investigations of nervous system plasticity.

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