Manipulating Neuronal Activity in the Developing Zebrafish Spinal Cord to Investigate Adaptive Myelination

In the central nervous system, oligodendrocyte-lineage cells and myelination can adapt to physiological brain activity. Since myelin can in turn regulate neuronal function, such "adaptive" myelination has been proposed as a form of nervous system plasticity, implicated in learning and cognition. The molecular and cellular mechanisms underlying adaptive myelination and its functional consequences remain to be fully defined, partly because it remains challenging to manipulate activity and monitor myelination over time in vivo at single-cell resolution, in a model that would also allow examination of the functional output of individual neurons and circuits. Here, we describe a workflow to manipulate neuronal activity and to assess oligodendrocyte-lineage cell dynamics and myelination in larval zebrafish, a vertebrate animal model that is ideal for live imaging and amenable to genetic discovery, and that has well-characterized neuronal circuits with myelinated axons.