Persistent Nav1.1 and Nav1.6 currents drive spinal locomotor functions through nonlinear dynamics
Benoît Drouillas, Cécile Brocard, Sébastien Zanella, Rémi Bos, Frédéric Brocard
Abstract
Persistent sodium current ( I NaP ) in the spinal locomotor network promotes two distinct nonlinear firing patterns: a self-sustained spiking triggered by a brief excitation in bistable motoneurons and bursting oscillations in interneurons of the central pattern generator (CPG). Here, we identify the NaV channels responsible for I NaP and their role in motor behaviors. We report the axonal Nav1.6 as the main molecular player for I NaP in lumbar motoneurons. The inhibition of Nav1.6 , but not of Nav1.1 , in motoneurons impairs I NaP , bistability, postural tone, and locomotor performance. In interneurons of the rhythmogenic CPG region, both Nav1.6 and Nav1.1 equally mediate I NaP . Inhibition of both channels is required to abolish oscillatory bursting activities and the locomotor rhythm. Overall, Nav1.6 plays a significant role both in posture and locomotion by governing I NaP -dependent bistability in motoneurons and working in tandem with Nav1.1 to provide I NaP -dependent rhythmogenic properties of the CPG.