Neuronal Activity Promotes Node‐Like Cluster Assembly Prior to Myelination and Remyelination in the Central Nervous System

In recent years, myelination has been recognized as a key process in neural plasticity and network refinement, in addition to its role in axonal conduction and neuronal metabolic support. The fast saltatory conduction along myelinated fibers relies on the nodes of Ranvier. Node-like clusters can form prior to myelin deposition in development and repair and can regulate axonal conduction, myelin deposition initiation, as well as contribute to the formation of mature nodes of Ranvier. In this study, we show that node-like cluster assembly is modulated by neuronal activity and could thus be an intermediate step in activity-induced (re)myelination. We further identify the regulation of Nav1.1 expression, which we show to be required for node-like cluster formation, as part of the molecular mechanism implicated in the activity-dependent regulation of node-like cluster assembly. This process may serve in shaping neuronal networks and myelin patterns during development, plasticity and repair.