SK2/3 CHANNELS COUPLE WITH T-TYPE CA2+ CHANNELS TO GATE SPINAL LOCOMOTOR RHYTHM GENERATION

Initiating locomotion requires central pattern generator (CPG) interneurons to transition from tonic firing to persistent sodium current (INaP)-dependent bursting. While INaP provides the rhythmogenic drive, the conductances gating this transition remain unclear. Here, we show that functional coupling between small-conductance calcium-activated potassium (SK2/3) channels and low-threshold T-type Ca2+ channels, notably Cav3.2, gates locomotor rhythm generation. Pharmacological or genetic disruption of this SK-T-type axis triggers intrinsic bursting in Hb9 interneurons, a genetically identified rhythmogenic population of the locomotor CPG, and initiates fictive locomotion, whereas SK activation silences ongoing rhythmic output. Immunohistochemical co-expression of SK2, SK3 and Cav3.2 in Hb9 interneurons provides an anatomical basis for this functional coupling. Simulation-based inference further shows that, beyond this gating mechanism, burst diversity is primarily determined by the balance between INaP and M-type potassium conductances. Together, these findings identify SK-T-type coupling as a tunable brake on CPG activation, defining a biophysical module that controls the initiation and termination of locomotor rhythmic activity, with potential relevance for rhythmogenic circuits beyond locomotion.