State-dependent rhythmogenesis and frequency control in a half-center locomotor CPG

The spinal locomotor central pattern generator (CPG) generates rhythmic activity with alternating flexion and extension phases. This rhythmic pattern is likely to result from inhibitory interactions between neural populations representing flexor and extensor half-centers. However, it is unclear whether the flexor-extensor CPG has a quasi-symmetric organization with both half-centers critically involved in rhythm generation, features an asymmetric organization with flexor-driven rhythmogenesis, or comprises a pair of intrinsically rhythmic half-centers. There are experimental data that support each of the above concepts but appear to be inconsistent with the others. In this theoretical/modeling study, we present and analyze a CPG model architecture that can operate in different regimes consistent with the above three concepts depending on conditions, which are defined by external excitatory drives to CPG half-centers. We show that control of frequency and phase durations within each regime depends on network dynamics, defined by the regime-dependent expression of the half-centers' intrinsic rhythmic capabilities and the operating phase transition mechanisms (escape vs. release). Our study suggests state dependency in locomotor CPG operation and proposes explanations for seemingly contradictory experimental data. NEW & NOTEWORTHY Our theoretical/modeling study focuses on the analysis of locomotor central pattern generators (CPGs) composed of conditionally bursting half-centers coupled with reciprocal inhibition and receiving independent external drives. We show that this CPG framework can operate in several regimes consistent with seemingly contradictory experimental data. In each regime, we study how intrinsic dynamics and phase-switching mechanisms control oscillation frequency and phase durations. Our results provide insights into the organization of spinal circuits controlling locomotion.