The role of central nervous system myelination in behaviour

1. Centre for Neuroregeneration, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh, EH16 4SB
2. Department of Neuroscience, Physiology and Pharmacology, University College London, Gower St, Bloomsbury, London WC1E 6BT

The white matter in our brain can adapt according to experience. Human brain imaging studies have documented changes in white matter volume and structural organization during development as well as the learning of a new skill in adulthood(1,2). There is mounting evidence that these changes may reflect underlying adaptations in myelin:  oligodendrocyte differentiation and myelination have been shown to play a key role in motor skill learning and cortical network function in vivo(3,4). Thus, it has been postulated that myelin may play a functional role in circuit development(5). However, the exact mechanisms by which this may occur at a cellular level remain largely unknown.

To dissect the role of myelin in circuit formation during development and learning, temporal analysis of multiple neuronal components is required in synchrony. Larval zebrafish, with their capacity for in-vivo imaging and well-mapped neural circuits, provide an excellent model to address this problem. Using in-vivo, single cell resolution imaging we will monitor the dynamics of myelination along reticulospinal neurons during the development of defined locomotor behaviours in larval zebrafish. Using transgenic reporters, we will monitor the onset and structural reorganization of myelin in relation to axonal, nodal and synaptic counterparts, during the refinement of behaviour. In parallel, we will employ models of enhanced and disrupted central nervous system myelination in established behavioural assays.

We hypothesise that structural organization of myelin is required for optimum development and fine-control of locomotor behaviour. We predict that these adaptations will occur in synchrony with synaptic modifications. Furthermore, disrupting myelinating capacity will alter the locomotor response of reticulospinal-mediated behaviours. Through this systems level approach, we aim to document the role of myelination in circuit development and behaviour further. Insights into this exciting field hold implications for our understanding of brain function and development, as well as our understanding of disorders of connectivity.

References

1. Schmithorst, V.J., Wilke, M., Dardzinski, B.J., Holland, S.K. (2002) Correlation of white matter diffusivity and anisotropy with age during childhood and adolescence: a cross-sectional diffusion-tensor MR imaging study. Radiology 222, 212–218.
2. Scholz, J., Klein, M.C., Behrens, T.E.J., Johansen-Berg, H. (2009). Training induces changes in white matter architecture. Nature Neuroscience 12 (11), 1370-1371. doi: 10.1038/nn.2412
3. McKenzie, I.A., Ohayon, D., Li, H., de Faria, J.P., Emery, B., Tohyama, J., Richardson, W.D. (2014). Motor skill learning requires active central myelination. Cell 346 (6207), 318-322. doi: 10.1126/science.1254960
4. Poggi G., Boretius, S., Mobius, W., Moschny, N., Baudewig, J., Ruhwedel, T., Hassouna, i., Wieser, G.L., Werner, H.B., Goebbels, S., Nave, K.A., Ehrenreich, H. (2016) Cortical network dysfunction caused by a subtle defect of myelination. GLIA 64, 2025-2040.
5. Fields, R.D. (2015). A new mechanism of nervous system plasticity: activity-dependent myelination. Nature Reviews Neuroscience 16, 756-767. doi:10.1038/nrn4023

Funded by: The Wellcome Trust