Human and animal studies have shown that exposure to ethanol during development results in permanent morphological changes in the cerebellum and in motor and other behavioral deficits. It has been demonstrated in the rat that a period of """"""""motor learning,"""""""" as opposed to simple motor activity, results in morphological increases in synapse numbers, vasculature and glial cell processes in the cerebellar cortex and improved performance in challenging motor tasks. The proposed project will behaviorally assess the therapeutic effects of exposure to a program of motor training upon the behavioral symptoms of cerebellar (and other probable brain) dysfunction observed in adult rats following a period of postnatal alcohol exposure. This period of exposure corresponds to third trimester fetal alcohol exposure in humans. A parallel study using independent groups of rats will assess the rehabilitative effects of motor training upon cerebellar cortical morphology, in particular the synaptic complement per Purkinje cell (the sole output of the cerebellum) and related changes in non-neural tissue, in the paramedian lobule and the floccular-parafloccular region. Behavioral tests will involve locomotion on a rotating rod, climbing of ropes and a parallel bar walking test, performance upon all of which has been shown to be sensitive to alcohol exposure during brain development, motor training, or both. Morphological assessment will involve the use of state-of-the-art stereological methods, including the optical dissector, to determine cell loss following alcohol exposure, the double dissector to assess synapse number, and appropriate methods for vasculature and glia. These unbiased stereological methods have been shown capable of detecting differences that earlier morphometric methods failed to detect The overall goals of this study are l) to obtain the most accurate possible view of the effects of postnatal alcohol exposure upon cerebellar organization and behavioral performance and their relationship and 2) to obtain a similarly accurate view of the effects of the program of motor skill intervention training upon these same measures. The long-range goal is to assess the potential therapeutic value of intervention programs in human offspring suffering from alcohol-related brain defects.
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