Neuronal activity is established as a driver of oligodendrocyte (OL) differentiation and myelination. The concept of activity-dependent myelin plasticity, and its role in cognition and disease, is gaining support. Methods capable of resolving changes in the morphology of individual myelinating OL would advance our understanding of myelin plasticity and injury, thus we adapted a labelling approach involving Semliki Forest Virus (SFV) vectors to resolve and quantify the 3-D structure of OL processes and internodes in cerebellar slice cultures. We first demonstrate the utility of the approach by studying changes in OL morphology after complement-mediated injury. SFV vectors injected into cerebellar white matter labelled transitional OL (TOL), whose characteristic mixture of myelinating and non-myelinating processes exhibited significant degeneration after complement injury. The method was also capable of resolving finer changes in morphology related to neuronal activity. Prolonged suppression of neuronal activity, which reduced myelination, selectively decreased the length of putative internodes, and the proportion of process branches that supported them, while leaving other features of process morphology unaltered. Overall this work provides novel information on the morphology of TOL, and their response to conditions that alter circuit function or induce demyelination.
Bibliographical noteFunding Information:
This work was supported by a fellowship to D.F. from the Birmingham Science City Research Alliance funded by the Higher Education Funding Council for England (HEFCE), a grant from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (CIG 294051), and the University of Birmingham’s Wellcome Trust Institutional Strategic Support Fund (2014 round). S.M.R. was supported by funding from the Engineering and Physical Sciences Research Council through a studentship from the Physical Sciences of Imaging in the Biomedical Sciences Doctoral Training Centre (EP/F50053X/1). We thank Dr Zubair Ahmed (Institute of Inflammation and Ageing, University of Birmingham) for his useful comments on the manuscript, and Professor Pranab Das (University of Birmingham) for discussions and advice on complement-mediated injury.
© 2021, The Author(s).