Coordination, execution and learning of skilled movements strongly depend on motor cortex function, which, in turn, depends on the modulatory action of different neurotransmitters. In particular, dopaminergic inputs to the motor cortex have been associated with synaptic plasticity, changes in cortical excitability and modulation of cortical motor maps. The integrity of dopaminergic terminals is required for the acquisition of novel motor tasks, but not for the performance of already learned ones. Despite evidence pointing to the importance of dopamine in the learning of novel motor skills, technical limitations have impeded solving several key questions. For instance, what are the exact behavioral conditions leading to dopamine release in the motor cortex during skill learning? Are dopamine fibers in the motor cortex synchronously activated affecting large cortical areas? Is dopamine necessary and/or sufficient for cortical motor learning? I will address these questions by combining my expertise in the field of dopamine signaling with the use of novel optical techniques recently developed by the European host institution and thereby dissect the role of dopamine with never-before-reached level of spatio-temporal accuracy. Specifically I aim to use in vivo two-photon imaging and optogenetic manipulations of genetically targeted dopamine axon terminals in the mouse motor cortex in combination with quantitative behavioral testing and characterize their role in the learning of novel motor skills. By recording and manipulating dopamine axon activity in the motor cortex I will test the hypothesis that dopamine acts as a necessary global signal of reward prediction error at the motor cortex level. This project will provide novel insights in the exact contribution of dopaminergic neurotransmission to motor learning and to cortical microcircuit plasticity and will further our knowledge on the basic neuronal mechanisms governing our behavior.
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