Using intracortical electrical stimulation mapping in rats, we have demonstrated that a dynamic relationship exists between the motor cortex (MI) and the muscles. Following peripheral nerve injury the affected part of MI subsumes a new muscle relationship, which appears as an expansion of adjacent MI representations. Novel representation patterns are evident in adult MI if the nerve section is performed either on the day of birth or in adults. Shift in representation occur within hours of nerve transection, and require only that a motor nerve be damaged. The proposed studies will determine the adequate stimulus that will produce reorganization, the sites where shifts occur, and mechanisms within the cortex that contribute to a dynamic cortical architecture. The central hypotheses to be tested in the present proposal are: (1) Alterations in the activity if peripheral nerves induces rapid reorganization of MI representations. Since motor nerve injury disrupts activity in motor and sensory pathways and involves structural damage, it is first important to distinguish which of these features shift MI organization. We will use stimulation techniques to monitor the form of change that occurs in MI over time after manipulations that alter activity in sensory of motor nerves or after sensory nerve damage. (2) Shifts in organization occur within MI. Two approaches will be used to examine sites of reorganization. Biochemical markers will be used as a potential means to mark locations that change in response nerve damage and to identify mechanisms that control MI organization (see 3 below). Electrical stimulation techniques will be used to test each relay from the motor nucleus back to MI for evidence of shifts in organization after nerve injury. (3) Changes in the strength of inhibitory connections reorganizes MI. We will begin to examine the mechanisms that underlie MI reorganization. Recent experiments suggest that the amount of intracortical inhibition is regulated by peripheral nerve activity. Electrophysiological and receptor binding and In Situ hybridization techniques will be used to examine the hypothesis that the change in the strength of inhibition in MI is responsible for shifts in MI representation pattern. Our recent experiments have revealed such a substrate in cortex. These experiments should provide a link between factors that regulate transmitter expression and functional architecture of MI cortex. The results of these studies may provide important new information concerning the mechanisms of recovery of function after nerve injury and the role of MI in motor skill acquisition. The results may suggest pharmacological or rehabilitative strategies for enhancing or suppressing cortical responses to damage of the motor system.
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