Persistent Nav1.1 and Nav1.6 currents drive spinal locomotor functions through nonlinear dynamics

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.

Keywords: CP: Neuroscience; CPG; Nav1.1; Nav1.6; bistability; interneuron; locomotion; motoneuron; pacemakers; posture; spinal cord.