UC San Diego

Movement is fundamentally essential for our survival in an ever-changing environment. Movement is controlled by the coordinated activity of several interconnected brain regions. Motor regions of the cortex, basal ganglia and thalamus form a major circuit involved in movement control. The striatum, the input nucleus of the basal ganglia, receives and integrates major excitatory inputs from the motor cortex and the thalamus. I aim to understand how striatal neuronal activity is influenced by these upstream inputs during a motor task that requires training, and whether one of the two inputs has a greater influence on striatal activity and potentially, on movement execution. I combined two-photon calcium imaging of striatal activity via GRIN lens with pharmacological inhibition of the activity in primary (M1) and secondary motor cortex (M2) and the parafascicular nucleus (PF), at early, middle and late stages of motor learning. After M2 inactivation, striatal activity was not significantly altered in beginners, but it was decreased or abolished in expert and master mice. After PF inactivation, striatal activity was absent across all learning stages. In preliminary experiments, M1 inactivation led to complete striatal activity abolishment during early learning. Strong performance deficits were observed after PF inactivation at all stages of learning. M1 inactivation led to significant alterations in beginners’ but not in experts’ performance. M2 inactivation led to no significant alterations. These results give insight about the contribution of upstream inputs to striatal activity during motor learning and uncover the role of striatum in the execution of a learned task.