Characterization of Na+ currents regulating intrinsic excitability of optic tectal neurons

Developing neurons adapt their intrinsic excitability to maintain stable output despite changing synaptic input. The mechanisms behind this process remain unclear. In this study, we examined Xenopus optic tectal neurons and found that the expressions of Nav1.1 and Nav1.6 voltage-gated Na+ channels are regulated during changes in intrinsic excitability, both during development and becsuse of changes in visual experience. Using whole-cell electrophysiology, we demonstrate the existence of distinct, fast, persistent, and resurgent Na+ currents in the tectum, and show that these Na+ currents are co-regulated with changes in Nav channel expression. Using antisense RNA to suppress the expression of specific Nav subunits, we found that up-regulation of Nav1.6 expression, but not Nav1.1, was necessary for experience-dependent increases in Na+ currents and intrinsic excitability. Furthermore, this regulation was also necessary for normal development of sensory guided behaviors. These data suggest that the regulation of Na+ currents through the modulation of Nav1.6 expression, and to a lesser extent Nav1.1, plays a crucial role in controlling the intrinsic excitability of tectal neurons and guiding normal development of the tectal circuitry.