Long-Distance Descending Spinal Neurons Ensure Quadrupedal Locomotor Stability

Locomotion is an essential animal behavior used for translocation. The spinal cord acts as key executing center, but how it coordinates many body parts located across distance remains poorly under- stood. Here we employed mouse genetic and viral approaches to reveal organizational principles of long-projecting spinal circuits and their role in quadrupedal locomotion. Using neurotransmitter identity, developmental origin, and projection pat- terns as criteria, we uncover that spinal segments controlling forelimbs and hindlimbs are bidirection- ally connected by symmetrically organized direct synaptic pathways that encompass multiple geneti- cally tractable neuronal subpopulations. We demon- strate that selective ablation of descending spinal neurons linking cervical to lumbar segments impairs coherent locomotion, by reducing postural stability and speed during exploratory locomotion, as well as perturbing interlimb coordination during rein- forced high-speed stepping. Together, our results implicate a highly organized long-distance projection system of spinal origin in the control of postural body stabilization and reliability during quadrupedal loco- motion.