Persistent Nav1.6 current drives spinal locomotor functions through nonlinear dynamics

Abstract

SummaryPersistent sodium current (INaP) 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 identified the NaV channels responsible forINaPand their role in motor behaviors. We report the axonalNav1.6as the main molecular player forINaPin lumbar motoneurons. The motoneuronal inhibition ofNav1.6, but not ofNav1.1, impairsINaP, bistability, postural tone and locomotor performance. In interneurons of the CPG region,Nav1.6withNav1.1equally mediateINaPand the inhibition of both channels is required to abolish oscillatory bursting activities and the locomotor rhythm. Overall,Nav1.6plays a significant role both in posture and locomotion by governingINaP-dependent bistability in motoneurons and working in tandem withNav1.1to provideINaP-dependent rhythmogenic properties of the CPG.