It takes two to tango: M-current swings with the persistent sodium current to set the speed of locomotion

Summary The central pattern generator (CPG) for locomotion is set of pacemaker neurons endowed with inherent bursting driven by the persistent sodium current ( I NaP ). How they proceed to regulate the locomotor rhythm remained unknown. Here, in neonatal rodents, we identified a persistent potassium current, critical in regulating pacemakers and locomotion speed. This current recapitulates features of the M-current ( I M ); a subthreshold non-inactivating outward current blocked by XE991 and enhanced by ICA73. Immunostaining and mutant mice highlight an important role of axonal Kv7.2 channels in mediating I M . Pharmacological modulation of I M regulates the emergence and the frequency regime of both pacemaker and CPG activities, and controls the speed of locomotion. Computational models captured these results and show howed an interplay between I M and I NaP that endows the locomotor CPG with rhythmogenic properties. Overall, this study provides fundamental insights into how I M and I NaP work in tandem to set the speed of locomotion.