After spinal cord injury (SCI) above the lumbar level, the lower limbs will be paralyzed due to the loss of descending commands from the brain. However, after SCI the interneuronal network in lumbar spinal cord can still sustain locomotor function such as air-stepping. Chronic SCI cats can also stand or walk for a short time on a treadmill after training. Patients with incomplete SCI can regain over ground mobility after extensive treadmill training. All of these observations indicate that the interneuronal network in lumbar spinal cord can carry out locomotion after SCI, if it can be activated properly. Therefore, we propose in this project to electrically activate the lumbar interneuronal locomotor network in cats to restore walking function after SCI. Previous studies have shown that the lumbar interneuronal locomotor network can be activated with only a few electrodes to elicit complex, coordinated, multi-joint movements. Such movements require many electrodes when traditional peripheral neuromuscular stimulation is used: Other advantages of spinal cord stimulation include: (1). electrodes in spinal canal experience relatively small movements, and thus exhibit less breakage, than the intramuscular electrodes; (2). the lumbar interneuronal locomotor network can activate muscles in a physiological recruitment order, which is more resistant to fatigue. Muscle fatigue is a major problem in the peripheral neuromuscular stimulation. In this project we will identify the effective stimulation locations and develop the control strategy to restore walking function in SCI cats, using extra- spinal electrical stimulation of the lumbar spinal cord in combination with intra-spinal stimulation. The extra- spinal electrode is less invasive to the spinal cord than the intra-spinal electrode, but the intra-spinal electrode is more effective than the extra-spinal electrode to activate the neural component deep in the lumbar spinal cord. The success of this study in cat will suggest how human studies could be pursued. The long-term goal of this project is to develop a new neuroprosthesis for locomotion based on lumbar spinal cord stimulation. The proposed studies will not only improve our understanding of locomotion control in lumbar spinal cord but also benefit SCI patients. ? ?