One of the most reliable consequences of survivable brain damage is that animals undergo major behavioral changes as they attempt to compensate for their impairments. Knowing how these behavioral changes interact with injury-induced brain changes may be critical for understanding neural and behavioral adaptation to brain damage. This research will investigate the possibility that the partial denervation that occurs in a connected region after focal cortical injury promotes some types of learning and the neuronal changes underlying this learning. The ability of rats with unilateral damage to the forelimb region of the sensorimotor cortex (SMC) to acquire skilled motor tasks with the non-impaired forelimb has recently been found to be enhanced in comparison to their intact counterparts. It is hypothesized that the enhancement of motor learning results because mild lesion-induced degenerative events facilitate the neuronal changes underlying this learning in the primary motor cortex opposite the lesion. Because these lesions cause the rats to rely on this limb, this provides a unique model system to investigate neural mechanisms underlying the development of behavioral compensation. The specific goals are to: (1) further investigate the SMC lesion-induced enhancement of motor learning with the non-impaired forelimb, including its dependency on innate forelimb preferences and preinjury training, (2) test the hypothesis that the enhanced learning is linked to lesion-induced neuroplastic changes in the motor cortex, (3) determine the dependency of the enhanced learning and associated neuroplastic changes on lesion-induced denervation and lesion-induced behavioral changes, (4) determine whether there is a sensitive post-injury time window for these effects and (5) assess their implications for functional outcome. These studies will use sensitive behavioral measures in combination with quantitative light and electron microscopic measures of changes in immediate early gene expression, dendritic cytoskeletal restructuring and changes in synaptic connections in the motor cortex. The results or these studies are expected to be of major relevance to rehabilitation efforts.
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