Cellular and Molecular Mechanisms of Motor Skill Learning

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The capacity to learn new motor sequences is fundamental to adaptive motor behaviour in human and animal life. This type of procedural ability builds through the integration of initially distinct movements into one particular behavioural unit. The execution of those actions depends on our knowledge of the environment, in encoding action-outcome relations, and on the capacity to execute the actions efficiently. In the process of optimizing the action, there is an initial stage of rapid increment in performance, which is followed by slow increment as performance reaches asymptotic levels. This process of optimization of the action may change the nature of the action, and after extensive practice the action may become automatic or habitual, instead of goal directed. The search for the neuronal substrates regulating motor learning has been the focus of a large body of animal and human studies in the past decade. However, little is known as to how skilled movement is encoded in the brain at the cellular and molecular levels. The major goal of my research program is to understand the organization and functions of the cellular and molecular substrates that regulates the different phases of motor learning during the acquisition of a new motor task in rodents. A particular attention will be paid to the differences that might exist between the plasticity induced in the striatopallidal indirect or striatonigral direct pathway neurons in regards to their inputs and respective places in the basal ganglia circuitry. We will first characterize motor learning-induced structural plasticity particularly in the striatum structures in mice. We will then investigate the intracellular mechanisms that integrate dopamine and glutamate signal at the corticostriatal synapses during the learning of motor tasks. Understanding the relationship between molecular processes and adaptive behaviour is an important but daunting goal of neuroscience research. Our data will identify the functional sub-regions of the striatum that are necessary for specific forms of learning and action control and establish a heuristic model of the intracellular signalling pathways of the corticostriatal synapse that are involved in the short and long-term acquisition of a complex motor skill.