Substantial data on the neural mechanism of locomotion over the last 20 years have demonstrated convincingly the capability of the spinal cord in a variety of vertebrates, including mammals, to control the kinetic and kinematic details necessary to execute full weight supporting locomotion. In spite of these accomplishments, rehabilitative strategies after severe neural impairment are yet to take advantage of the capacity of the spinal cord to generate locomotor activity. Rather, patients with severe spinal cord injury are usually informed of the futility of assuming any degree of success in recovery of significant mobility following such an injury. This view is inconsistent with the current neurophysiological concepts which demonstrate a remarkable ability of the mammalian lumbar spinal cord to integrate and execute complex motor patterns and even """"""""learn"""""""", in the absence of supraspinal input. The present proposal is designed to quantify the level of automaticity of hindlimb stepping that can be attributed to the lumbar spinal cord of adult cats and to determine which specific control features are absent or deficient in spinally controlled locomotion. Experiments are designed also to develop strategies to maximize motor recovery of the spinal cord using rehabilitation interventions based on sound neurophysiological and neurobiological concepts. These interventions include chronic training of spinal cats to walk on a treadmill combined with the temporal modulation of cutaneous input at selected points in the step cycle, and/or combined enhanced loading of the hindlimbs. Finally acute and chronic pharmacological interventions using selected agonists and antagonists of monoaminergic, glutamergic, glycernergic and NMDA systems will be used to optimize locomotor patterns. Electromyographic signals from flexors and extensors of the hip, knee and ankle, angle of the hip, knee and ankle and muscle force (medial gastrocnemius) in cats will be used as measures of neural output and the mechanical consequences. Waveforms (EMG amplitude modulation) of flexor and extensor muscles of the hip, knee and ankle will be defined in each cat during normal quadripedal and bipedal locomotion and during bipedal stepping after acute and chronic spinalization. From these data the capability of central and peripheral pathways to control specific kinetic, kinematic and neurophysiological events in locomotion will be determined. The pharmacologic effects on locomotion will be compared in chronic spinal cats after they are trained to stand and after they are trained to step. These studies will provide strong clues of which neuromodulating and neurotransmitting systems that have motor effects exhibit plasticity in response to spinalization and/or repetive use. These data could provide a neurophysiological rationale for the development of more efficacious medical rehabilitative programs for neurally impaired patients.
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