Contributions of M- and Persistent Sodium Currents in Regulating Locomotor Rhythms: A Computational Modeling Study

Physiological experiments have demonstrated that M-current ([Formula: see text]) and persistent sodium current ([Formula: see text]) expressed in rhythm-generating neurons play a key role in the generation and regulation of locomotor rhythms. However, the intrinsic mechanisms by which these two ionic currents control the locomotor rhythms are poorly understood. Here, a computational model is constructed to investigate the roles of [Formula: see text] and [Formula: see text] in regulating locomotor rhythms and explain the underlying ionic mechanisms. The simulation results show that decreasing [Formula: see text] or increasing [Formula: see text] facilitates the generation of the bursting activity; during the bursting activity, the burst frequency of the model has a positive dependence on [Formula: see text], and the flexion-extension as well as left-right coordination are not affected by varying [Formula: see text]. These results accurately reproduce the experimental results. In addition, the results also show that the dependence of burst frequency-[Formula: see text] is similar to that of burst frequency-[Formula: see text], but with distinct regulation mechanisms, i.e. [Formula: see text] regulates the burst frequency by affecting the burst and interburst durations, whereas [Formula: see text] regulates the burst frequency via manipulating the interburst duration. Finally, a dynamical analysis is given to reveal the intrinsic neural mechanisms of [Formula: see text] and [Formula: see text] in regulating the burst properties. Our study provides new insights into how outward and inward currents work in tandem to set the speed of locomotion, and provides testable predictions for biological experimental studies.