Activity-dependent white matter plasticity in circuit function and repair

The ability of the central nervous system (CNS) to respond to an ever-changing environment is essential to our survival. Studies of neural circuit plasticity focus almost exclusively on functional and structural changes in neuronal synapses. Recently myelin plasticity has emerged as a potential modulator of temporal precision in neuronal networks. Unlike synaptic plasticity, however, the mechanisms of activity-dependent myelin changes remain unclear. From my preliminary findings I hypothesise that myelin plasticity is driven by activity-dependent mechanisms, akin to synaptic plasticity, and underlies the regenerative potential of myelin. This research proposal will use the visual system, and an innovative approach combining electrophysiology, pharmacogenetics, imaging, transgenic animals, and in vivo models of remyelination, to test the hypothesis by answering the following fundamental questions: 1. Is myelin plasticity bidirectionally regulated by neuronal activity? 2. What are the mechanisms underlying myelin plasticity in adults? 3. Does myelin plasticity mediate the myelin regeneration essential for functional recovery following demyelination? This proposal has the potential to transform our understanding of myelin plasticity and regeneration, offering insights that may drive novel therapeutic strategies for diseases like multiple sclerosis. This project will significantly expand our understanding of activity-dependent structural plasticity in the brain beyond synapses to oligodendrocytes and myelin.