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Nouvelle publication à P3M parue dans Cell Reports 

Publié le 06/09/2023

Nouvelle publication à P3M parue dans Cell Reports

B. Drouillas; C. Brocard; S. Zanella; R. Bos; F. Brocard

Highlights

● Nav1.6 mediates INaP and self-sustained spiking activity in bistable motoneurons

● Silencing Nav1.6 in spinal motoneurons alters posture and locomotor performance

● Nav1.6 works with Nav1.1 to mediate INaP and bursting pacemakers within locomotor CPG

● The Nav1.1-Nav1.6 partnership generates the locomotor rhythm

eTOC Blurb

Drouillas et al. show how Nav1.1 and Nav1.6 channels regulate spinal locomotor activity. Nav1.6, by mediating persistent sodium current (INaP) in bistable motoneurons,produces postural tone and amplifies locomotor outputs. Together with Nav1.1, it drives the locomotor rhythm by mediating INaP-dependent bursting activities in interneurons of the central pattern generator.

Abstract: Persistent 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 identify the NaV channels responsible for INaP and their role in motor behaviors. We report the axonal Nav1.6 as the main molecular player for INaP in lumbar motoneurons. The inhibition of Nav1.6, but not of Nav1.1, in motoneurons impairs INaP, bistability, postural tone, and locomotor performance. In interneurons of the rhythmogenic CPG region, both Nav1.6 and Nav1.1 equally mediate INaP. 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 INaP-dependent bistability in motoneurons and working in tandem with Nav1.1 to provide INaP-dependent rhythmogenic properties of the CPG.

Persistent Nav1.1 and Nav1.6 currents drive spinal locomotor functions through nonlinear dynamics. Drouillas B, Brocard C, Zanella S, Bos R, Brocard F. Cell Reports. 2023