Functional relevance remains the least understood aspect of neural plasticity in spite of numerous studies. In order to address questions of function, the rodent corticospinal tract (CST), which forms anomalous projections in response to neonatal cortical or spinal cord lesions, provides an excellent model for study. The precise somatotopic distribution of the normal CST reflects its participation in the control of discrete limb movements. Anatomical studies are proposed to determine if the anomalous CST demonstrates a similar orderly distribution pattern. These studies, which will use retrograde fluorescent tracing techniques, also address questions concerning mechanisms of formation specifically concerning whether anomalous CST axons form as collaterals of normal CST axons. Movements evoked by intracorticl microstimulation at low current thresholds are found to be mediated via CST fibers as evidence by study after medullary pyramidotomy. Experiments are proposed to examine cortically-evoked movements in order to test the functional efficacy of the anomalous CST. In light of recent reports suggesting that the noradrenergic system may influence neuronal growth and plasticity, experiments are designed to examine possible effects on the anomalous CST. The distribution of CST axons, as measured by anterograde tracing methods, and their functional state, as determined by measuring current thresholds need to evoke movements by cortical stimulation, will be examined after the neonatal administration of the neurotoxin 6-OHDA. This drug destroys cortical noradrenergic fibers; its effects will be determined by measuring cortical noradrenalin levels using high performance liquid chromography (HPLC). The late developmental sequence of the rodent CST is advantageous to the study of axonal growth and regeneration. Partial spinal cord lesions in newborn rats causes the formation of anomalous CST fibers which grow around the lesion. Cortical stimulation and anatomical tracing techniques will be used to assess the functional state of these axons.
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