Recovery of hindlimb motor function after complete mid-thoracic spinal cord transection is highly dependent on routinely practiced motor skills. Development of use-dependent therapeutic procedures to facilitate recovery of motor function following injury has advanced to testing stages with human patients, but little is known about the adaptations in the spinal cord that can account for this recovery. In the present study, behavioral, physiological and biochemical adaptations that occur as a result of the hindlimbs of neonatal transected rats acquiring the ability to step or stand will be examined. Motion analysis and electromyograms will be used to quantify the activation of motor pools. We will test whether improvements in stepping and standing are associated with a loss of glycinergic and GABAergic inhibition in spinal pathways. Biochemical adaptations in the glycinergic and GABAergic systems that occur in lumbar spinal cord and/or dorsal root immunohistochemistry. Because limitations in flexion and/or extension of the hindlimb can limit the ability to step or to stand, the identification of specific biochemical changes associated with flexor and extensor neural pathways would represent an important advance toward understanding the neural substrates of motor recovery following spinal cord injury. To address this issue dorsal root ganglion neurons and motor neurons of extensor and flexor pathways will be identified using retrograde labeling of the soleus and tibialis anterior, respectively. Therefore, we will be able to identify changes in GABAergic and glycinergic properties of pathways associated with primarily flexion versus extension in transected rats that have acquired skills that require the use of flexors and extensors in different ways, i.e. standing versus stepping. Results from the proposed studies will provide a better understanding of how spinal neural pathways that control posture and locomotion are influenced by use-dependent mechanisms. These results will provide a framework around which strategies for pharmacologically modulating these tasks can be developed.
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