Experience-dependent Compensation and Brain Plasticity

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The acquisition of new motor skills critically depends on experience and practice. Experience-dependent motor skill learning represents a central mechanism by which individuals with a brain lesion overcome loss of motor function. Most individuals with a brain lesion are required to learn some kind of compensatory movement strategies over time that substitute for lost motor capacity. My NSERC-funded work showed that compensatory movement strategies are clearly recognizable and distinguishable from original, intact movements, and they closely reflect anatomical rearrangements of the underlying neuronal pathways. Notably, we found a considerable variation in the use of compensatory strategies among individuals. Individual variation in compensation appears to be influenced by intrinsic factors such as age, sex and stress, but is also determined by environmental conditions, the type of experience and training. Thus, I hypothesize that intrinsic factors such as age, sex, stress, and extrinsic factors, such as environmental conditions and experiences, contribute in important ways to compensation and brain plasticity. I propose that individual variations in compensatory strategies can be used as a model to study the fundamental mechanisms of brain plasticity. My research is directed toward using compensation as a model to study how intrinsic factors and experiences interact with the fundamental neuronal and molecular mechanisms of brain plasticity.* In the proposed research, we will identify compensatory strategies and its neuronal and molecular basis in laboratory rats and human subjects (1) to investigate how motor learning and compensatory strategies in skilled movements adapt to task-specific demands in relation to physiological, genetic and epigenetic variables; (2) to identify strategies in motor skill acquisition and compensation as a function of age, sex and stress response; (3) to determine how environmental experiences can facilitate or impede motor learning and compensation; and (4) to examine if experience in previous generations generates heritable patterns of compensation and brain plasticity. Using innovative technologies in rats and human subjects, we will identify activity-dependent physiological, genetic and epigenetic regulators of motor learning, compensation and brain plasticity. We now have modern, in vivo, high-resolution tools available to pursue novel longitudinal studies of dynamic brain plasticity and behaviour. I predict that compensation can be used as a superb model to study the influences of "nature versus nurture" on brain plasticity.* The novel, multidisciplinary research approach to the study of compensation proposed here will significantly advance the understanding of neurobiological mechanisms and experience-dependent regulation of brain plasticity. Because compensation in the lesion brain is mediated by the same neural mechanisms as those that contribute to development and aging, the study of compensation leads to insights into nervous system function on a more general level. Thus, understanding the neural basis of compensation represents a problem that is central to basic neuroscience. This research will also ultimately have an impact on current technology trends; for example, my laboratory has already started to generate new technologies to quantify molecular regulators of brain plasticity using bioengineered portable health devices.