Understanding how sensory feedback can be used to facilitate locomotion is vital for designing effective locomotor rehabilitation strategies for spinal cord injury. Here we describe an in vitro spinal cord-hindlimb preparation (SCHP) that can be used to answer clinically relevant questions about the interaction of sensory feedback and spinal locomotor circuitry. The SCHP, composed of the exposed rodent spinal cord with hindlimbs intact, combines the neural accessibility and manipulability of classic in vitro isolated cord preparations with intact sensory feedback and many of the behavioral analysis techniques used in the clinic, such as kinematics, treadmill walking, and electromyography. Using the SCHP, we demonstrate the importance of task-appropriate limb loading and posture for establishing intact rat-like kinematic trajectories and muscle activation patterns. We also show that applying stepping-like movements to the limbs, similar to those applied during physical therapist-assisted or robot-guided body weight–support treadmill training, can reinforce weak neurochemically induced locomotion or even initiate locomotion in the presence of subthreshold neurochemical concentrations. Finally, we present the first intracellular recordings from spinal interneurons during unrestrained hindlimb locomotion, demonstrating the capacity of the SCHP for directly assessing neural function during locomotion and in response to mechanosensory perturbations. As shown here, the SCHP allows for simultaneous behavioral and neuronal measurements, enabling us to relate behavioral outcomes to underlying neural mechanisms. In the future, the SCHP promises to advance our understanding of the neural mechanisms underlying therapeutic interventions and to provide a tractable platform for testing neural interfaces, rehabilitation techniques, and neurochemical agents.
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