Using zebrafish to study myelination and neural circuit function.

There is now compelling evidence that dynamic regulation of myelination represents a form of functional plasticity in the central nervous system. For example, learning and sensory experience can alter myelin in humans and animal models, and neuronal activity can regulate specific aspects of myelination. Because myelin is the principal regulator of conduction speed, and thus the timing of information arrival at pre-synaptic terminals, its regulation is well-placed to fine-tune synaptic communication and circuit function. However, we don’t know how myelin is formed or remodeled along axons within neural circuits in vivo, nor how dynamic regulation of myelination affects conduction, synaptic communication, or the activity of neurons underpinning circuit function. Here, using zebrafish, I propose to combine live-imaging and electrophysiology to determine how the formation and remodeling of myelin affects conduction within well-defined circuits. By combining optogenetics, functional imaging and gene-targetting, we will identify the mechanisms by which neuronal activity dynamically regulates myelination. Finally, to assess how (dys)regulation of myelination affects circuit function, we will assess synaptic communication by electrophysiology, and the activity of neuronal populations by large-scale functional imaging. This work will provide insights into a poorly understood, but fundamental, aspect of nervous system function, relevant to health and disease.