The Functionality of the Regenerated Corticospinal Tract

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DESCRIPTION (provided by applicant): The goal of this project is to assess the function of sprouting axons resulting from the overexpression of neurotrophic factors (NT-3, BDNF, and GDNF) using adenoviral transduction of motoneurons, a gene therapy approach to the treatment of spinal cord injury. The functionality assessment is to be accomplished using comparative electrophysiology techniques of cortical stimulation of motor areas housing corticospinal neurons and then make extracellular recordings of motor evoked potentials (MEPs) from a peripheral nerve of the hind limb, the sciatic nerve. To begin to test synaptic function imaging studies will be done using confocal microscopy to evaluate the colocalization of molecular markers, BDA and synaptophysin, indicative of functional synapses within the CST. To test the behavioral consequences of a potential gain of function associated with the axon sprouting, tests of limb aiming and limb placement, for which the CST is responsible in rat, will be conducted. The ultimate goal of the investigation is to assess any gain of function in the motor system following the overexpression of neurotrophic factors delivered by adenovirus.