Hand Use and Neuronal Plasticity After Dorsal Rhizotomy

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DESCRIPTION (provided by applicant): Injuries of the cervical dorsal roots in humans and other primates can severely impair hand function - particularly the performance of manipulative tasks that depend on sensory feedback. Such injuries are relatively common following accidents and trauma in humans, and are typically difficult to repair surgically. Some recovery of function has been demonstrated that has been linked to reorganization within the sensory neocortex and subcortical structures. This application is a systematic examination of behavioral, physiological and structural changes that occur following damage to the sensory neurons that supply feedback from the hand to the brain. Although reorganization has been demonstrated, we still know relatively little about the neural basis for it, where it occurs, and how such changes mediate behavioral recovery or compensation. Without this knowledge we cannot target realistic therapeutic strategies to the appropriate regions. We will use a unique model that allows us to select and block sensory input from a discrete part of the non-human primate hand- namely the index finger and thumb and surrounding regions. We will use physiological and anatomical analyses to determine changes in the somatosensory neuronal circuitry and correlate these results with the behavioral deficit and recovery of manual dexterity over a period of several months. The specific aims are inter-dependent, and can be summarized by the following questions. 1. How does the spontaneous recovery of precision grip relate to the extent of the dorsal root section? Over a period of several months we evaluate the ability to perform a precision grip task. We will then correlate this function with the size of the lesion to provide an indication of the sensory feedback required for some recovery of hand function. 2. Do subcortical somatosensory neuron populations contribute to cortical reactivation and recovery of hand function? We will evaluate electrophysiological changes at different levels of the neuraxis to identify where functional reorganization is concentrated. This information will identify regions where therapy could be targeted. 3. Do primary afferents that 'sprout' into the spinal dorsal horn and cuneate nucleus during the post-lesion months form functional synapses on cuneothalamic and spinothalamic cells? This question arises from the results of a preliminary study. We will use neuroanatomical and ultrastructural techniques to directly identify functional synapses and to reconstruct changes in the primary afferent circuitry that occur following the dorsal root lesion. The proposed studies will contribute important new insight into the central neural mechanisms responsible for the behavioral adaptations that are observed during the months following a well defined dorsal root injury. In addition they will provide insight into the mechanisms of adult neuronal dorsal root avulsion injuries in humans which are debilitating. A better understanding of the post-lesion reorganization of the somatosensory pathways is needed if patients with avulsed spinal dorsal roots are to be treated more effectively.