Spinal cord injury affects upwards of 230,000 people and can cost between $487,150 and $2,185,667 per person. Interneuronal networks within the L1-L2 region of the spinal cord are intrinsically capable of coordinating the activation of multiple functional muscle groups as is required in locomotion. By tapping into this network using intraspinal microstimulation within the spinal cord, simple, natural, and adaptable control of locomotion may be achievable. In order to identify the key regions and timing of activation, we will simultaneously record the extracellular activity at an array of sites within the L1-L2 region during stepping to create a spatiotemporal population map. Recent advances in neuronal ensemble recording make it possible to look at the spatial and temporal properties of neuronal networks in vivo. We will record from the L1-L2 region of the spinal cord using high-density-multielectrode arrays during locomotion, and will correlate the spatiotemporal profile with electromyographic (EMG) data, videography, and ankle position/force measurements. Locomotion will be studied in acute decerebrate rats by stimulation of the mesencephalic Iocmotor region and in rats that have been chronically implanted with a multielectrode array for recording and stimulation on a treadmill. Using principal component analysis and independent component analysis, we will characterize the overall neural activity and identify neurons that are highly correlated with specific phases of the step cycle or rate of stepping. Then we will determine the dynamic interdependence of these sets using directed coherence to determine which sites are appropriate targets. The efficacy of these sequences will be explored by electrically stimulating the implanted multielectrodes in spinal transected rats. To do this, a 96- channel multielectrode stimulation system capable of outputting a spatially and temporally patterned stimulus is being developed. The results of these studies could lead towards the development of models for activation of the lumbar circuits in humans and could be used in combination with treadmill training, pharmacological intervention, functional nerve stimulation strategies, and other neural repair therapies, for the restoration of locomotion. ? ?