Research in the last three decades has made enormous progress in demonstrating and elucidating plasticity in the central nervous system of ~adult animals~. Two important types of proof of this plasticity arise from studies of damage to the brain and from studies using manipulations of behavioral experience. Studies of the effects of brain damage have shown that regions connected to the site of damage undergo reactive neuronal growth and reorganization. Studies manipulating behavioral experience have shown that regions involved in those behaviors also undergo neuronal changes. The emphasis of the present proposal is that these two types of plasticity may be interactive following brain damage. It is obvious that brain damage can produce behavioral changes. Based on abundant evidence that changes in behavioral experience can lead to central neuronal structural changes, it seems reasonable that these behavioral changes may influence and interact with plastic neuronal responses that occur after brain damage. Recent research has revealed a novel examples of neural plasticity following brain damage which seems o be mediated by behavioral changes. Unilateral lesions to the forelimb representation area of the sensorimotor cortex (Flsmc) in adult rats leads to impairments in the use of the forelimb contrlateral to the damage. Animals appear to compensate for these impairments, in part, by developing an over-reliance on the forelimb ipsilateral to the damage (the non-impaired forelimb). Examination of neurons and synapses within the forelimb motor cortex opposite the damage and the non-impaired forelimb revealed a marked dendritic growth and synaptogenesis. This neural plasticity appears to be mediated by the post lesion changes in the use of forelimbs and to be facilitated by the presence of a lesion in the opposite cortex. The processes underlying this behaviorally mediated neural plasticity are not understood and are potentially very important for ongoing attempts to understand brain adaptation to brain injury and to identify processes which can be manipulated to facilitate functional recovery. The proposed studies will (1) characterize structural (neuronal and glial) and connectional plasticity of the motor cortex and cerebellum following unilateral Flsmc lesions using quantitative electron microscopy, immunocytochemistry and anatomical tract tracing methods (2) relate these changes to behavioral changes using sensitive behavioral measures and behavioral manipulations, and (3) manipulate, and perhaps facilitate, adaptive neuronal and behavioral changes using complex motor skills training as """"""""therapy"""""""" after the lesions. These studies may be of relevance to post-injury rehabilitation and neurolgical disorders in humans.
