Individual neuronal subtypes exhibit diversity in CNS myelination mediated by synaptic vesicle release

1. Centre for Neuroregeneration, MS Society Centre for Translational Research, Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh EH16 4SB, UK.
2. Department of Developmental Biology, Stanford University, Stanford CA 94305, USA.
3. MRC Centre for Developmental Neurobiology, New Hunt’s House, King's College London, Guy’s Hospital Campus. London SE1 1UL, UK

Regulation of myelination by oligodendrocytes in the CNS has important consequences for higher-order nervous system function and there is growing consensus that neuronal activity regulates CNS myelination (e.g. 1,2) through local axon-oligodendrocyte synaptic-vesicle-release mediated signalling (3,4). Recent analyses have indicated that myelination along axons of distinct neuronal subtypes can differ (5), but it is not known whether regulation of myelination by activity is common to all neuronal subtypes or only some. This limits insight into how specific neurons regulate their own conduction. Here, we use a novel fluorescent fusion protein reporter to study myelination along the axons of distinct neuronal subtypes over time in zebrafish. We find that the axons of reticulospinal and commissural primary ascending (CoPA) neurons are among the first myelinated in the zebrafish CNS. To investigate how activity regulates myelination by different neuronal subtypes, we express tetanus toxin (TeNT) in individual reticulospinal or CoPA neurons to prevent synaptic vesicle release. We find that the axons of individual tetanus toxin expressing reticulospinal neurons have fewer myelin sheaths than controls and that their myelin sheaths are 50% shorter than controls. In stark contrast, myelination along tetanus-toxin-expressing CoPA neuron axons is entirely normal. These results indicate that while some neuronal subtypes modulate myelination by synaptic vesicle release to a striking degree in vivo, others do not. These data have implications for our understanding of how different neurons regulate myelination and thus their own function within specific neuronal circuits.

References

1. McKenzie, I.A., Ohayon, D., Li, H., de Faria, J.P., Emery, B., Tohyama, K., and Richardson, W.D. (2014). Motor skill learning requires active central myelination. Science 346, 318–322.
2. Gibson, E.M., Purger, D., Mount, C.W., Goldstein, A.K., Lin, G.L., Wood, L.S., Inema, I., Miller, S.E., Bieri, G., Zuchero, J.B., et al. (2014). Neuronal activity promotes oligodendrogenesis and adaptive myelination in the mammalian brain. Science 344, 1252304.
3. Mensch, S., Baraban, M., Almeida, R., Czopka, T., Ausborn, J., El Manira, A., and Lyons, D.A. (2015). Synaptic vesicle release regulates myelin sheath number of individual oligodendrocytes in vivo. Nat. Neurosci. 18, 628–630.
4. Hines, J.H., Ravanelli, A.M., Schwindt, R., Scott, E.K., and Appel, B. (2015). Neuronal activity biases axon selection for myelination in vivo. Nat. Neurosci. 18, 683–689.
5. Tomassy, G.S., Berger, D.R., Chen, H.-H., Kasthuri, N., Hayworth, K.J., Vercelli, A., Seung, H.S., Lichtman, J.W., and Arlotta, P. (2014). Distinct profiles of myelin distribution along single axons of pyramidal neurons in the neocortex. Science 344, 319–324.

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