Distinct descending and biomechanical influences on interlimb coordination in mice

Interlimb coordination, or gait, is a hallmark of locomotion, but has been challenging to study due to its partial dependence on speed and the difficulty of reliably evoking the full gait spectrum in genetically amenable quadrupeds such as mice. To address this, we developed a head-fixed locomotor paradigm that decouples the speed- and leg loading-related effects on gait by combining optogenetic stimulation in the cuneiform nucleus with head height and surface slope modulation. This approach revealed a largely speed-independent shift in homolateral phase preference from strict alternation to a quarter-of-phase more synchronized coordination upon a rearward redistribution of load. This load-related effect was observed regardless of hindlimb phase and aligned with changes in limb support patterns. These findings highlight how quadrupeds use biomechanical input to coordinate limbs across speeds and environments, and serve as an entry point to a behaviour-driven study of gait circuits.