The Persistent Sodium Current Generates Pacemaker Activities in the Central Pattern Generator for Locomotion and Regulates the Locomotor Rhythm.

Rhythm generation in neuronal networks relies on synaptic interactions and pacemaker properties. Little is known about the contribution of the latter mechanisms to the integrated network activity underlying locomotion in mammals. We tested the hypothesis that the persistent sodium current (INaP ) is critical in generating locomotion in neonatal rodents using both slice and isolated spinal cord preparations. After removing extracellular calcium,75%of interneurons in the area of the central pattern generator (CPG) for locomotion exhibited bursting properties and INaP was concomitantly upregulated. Putative CPG interneurons such as commissural and Hb9 interneurons also expressed INaP-dependent (riluzole-sensitive) bursting properties. Most bursting cells exhibited a pacemaker-like behavior (i.e., burst frequency increased with depolarizing currents). Veratridine upregulated INaP , induced riluzole-sensitive bursting properties, and slowed down the locomotor rhythm. This study provides evidence that INaP generates pacemaker activities in CPG interneurons and contributes to the regulation of the locomotor activity. [ABSTRACT FROM AUTHOR]