Activity-dependent alteration of early myelin ensheathment in a developing sensory circuit

This work was funded by a chaire de recherche from the Fonds de recherche du Québec – Santé (FRQS Grant 31036) to E. S. R., the Montreal Neurological Institute – University of Cambridge Collaboration Grant to R. T. K. and E. S. R., the European Union's Horizon 2020 Research and Innovation Programme (Grant Agreement No 771411) through the European Research Council (ERC) to R. T. K., the Wellcome Trust [203151/Z/16/Z] and the UKRI Medical Research Council [MC_PC_17230] to R. T. K., the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant to P. W. W., the NSERC Canada Graduate Scholarship – Master's and McGill University Integrated Program in Neuroscience Studentships to Z. C. and V. J. L., and the Douglas Avrith Award to Z. C. Publisher Copyright: © 2021 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLCMyelination 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.Peer reviewe