Neuronal mechanisms of myelination and myelin remodeling in the zebrafish

Centre for Neuroregeneration, University of Edinburgh

In our nervous systems neurons communicate with one another rapidly and must often send signals with precise timings within circuits. Subsequently many axons are myelinated to speed up signal propagation via saltatory conduction. However, recent research has also unveiled that myelin is required for much more than just electrical insulation, with increasing evidence suggesting that myelin is a plastic structure which is responsive to experience and is involved in the regulation of learning and behaviours. It is clear that neuronal activity can influence the generation of oligodendrocytes and initial formation of myelin sheaths – yet the specific signalling mechanisms underpinning activity-mediated myelination and myelin plasticity are still under investigation. Recent work has demonstrated the use of zebrafish to follow the myelination of individual axons during development. This project aims to use zebrafish to further investigate the role of neuronal activity in initial myelination, observe whether individual neurons can remodel their myelination profiles beyond initial sheath formation, and determine whether neuronal activity affects the remodelling and/or maintenance of myelin. We will use transgenic manipulations to either increase neuronal activity (using the TRP channel system) or decrease synaptic vesicle release (using neurotoxins such as tetanus (TeNT) or botulinum toxin (BoNT)), coupled with a battery of fluorescent reporters to follow individual myelinated axons over time.

Funded by: Medical Research Council