RORβ Spinal Interneurons Gate Sensory Transmission during Locomotion to Secure a Fluid Walking Gait

Animals depend on sensory feedback from mechanosensory afferents for the dynamic control of movement. This sensory feedback needs to be selectively modulated in a task- and context-dependent manner. Here, we show that inhibitory interneurons (INs) expressing the RORβ orphan nuclear receptor gate sensory feedback to the spinal motor system during walking and are required for the production of a fluid locomotor rhythm. Genetic manipulations that abrogate inhibitory RORβ IN function result in an ataxic gait characterized by exaggerated flexion movements and marked alterations to the step cycle. Inactivation of RORβ in inhibitory neurons leads to reduced presynaptic inhibition and changes to sensory-evoked reflexes, arguing that the RORβ inhibitory INs function to suppress the sensory transmission pathways that activate flexor motor reflexes and interfere with the ongoing locomotor program. Video Abstract [Figure presented] Koch et al. identify an inhibitory spinal circuit that is required for fluid rhythmic stepping movements. Inhibitory RORβ⁺ neurons in the spinal cord selectively gate proprioceptive transmission during locomotion by a presynaptic mechanism.