USE DEPENDENT MODULATION OF SYNAPTIC PLASTICITY FOLLOWING SPINAL CORD INJURY

University Of California Los Angeles, Los Angeles CA

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Abstract

Both humans and animals can regain the ability to stand or step after a complete spinal cord transection injury. The ability to execute these tasks depends upon specific training regimens, illustrating the importance of motor learning in the spinal cord. A thoracic spinal cord transection in both cats and rats leads to a persistent increase in the inhibitory capacity within the lumbar portion of the spinal cord, and step training returns the inhibitory capacity towards normal levels. However, the degree of plasticity and reorganization of inhibitory and excitatory synapses upon motoneurons, the final common pathway in motor control, is not known. The central hypothesis of this proposal is that complete spinal cord transection results in a selective proliferation of inhibitory synapses upon lumbar flexor and extensor motoneurons, while subsequent repetitive step training selectively decreases the number and capacity of inhibitory synapses within these motor pools. We will use a step-training paradigm and retrograde labeling techniques to study quantitatively the synaptology of soleus and tibialis anterior motoneurons in the electron microscope. We will also use electron microscopic immunogold techniques to study quantitatively the number and ratios of GABAergic and glycinergic terminals forming synaptic contacts with soleus and tibialis anterior motoneurons. The proposed studies will provide fundamental and critical data to assist in our understanding of cellular mechanisms of neural plasticity after spinal cord injury and locomotor training. The proposed studies can therefore contribute significantly in developing strategies designed to improve motor recovery after spinal cord injury.