Does neuronal activity modulate action potential conduction along myelinated axons in developing neural circuits?

A new form of brain plasticity, activity-driven modification of axons, has recently been proposed. This is based on many studies indicating brain activity can influence myelinated axon anatomy. Because these anatomical features influence conduction of electrical impulses (action potentials), the premise is that brain activity must influence AP conduction. Yet, the hypothesis that activity-driven modifications to myelinated axons represents a fundamental form of brain plasticity remains untested. To test this hypothesis, I will use the developing zebrafish larva in which activity-driven changes to myelinated axons are known to occur, and which are ideally suited to high-resolution structural and functional analysis in vivo, repeatedly at single-cell resolution. My key goals are 1) manipulate neuronal activity using various methods to determine how anatomical features such as axon domains, axon diameter, and myelin sheaths are collectively modulated and how they affect action potential conduction over developmental days along single axons of distinct neuron types. 2) Manipulate myelin’s ability to respond to neuronal activity to determine the effect activity-dependent myelination has on other anatomical features of the axon and AP conduction. I aim to address an outstanding question in neurobiology and redefine the field’s understanding of the relationship between myelinated axon form and function.