Striatal circuits for the control of movement - probing the “relative activity” model

When we go about our daily routines, we constantly have to make conscious and unconscious decisions about what actions we want to take next. However, how our brains decide which actions to perform and which potentially inappropriate actions to suppress in any given situation is still one of the central unresolved questions in neuroscience. What is clear is that a specific brain region, the striatum, is essential for the control of goal-oriented movements. The striatum is made up of two major types of neurons which through different projections can oppositely affect the activity of central movement processing centers in the brain. The main hypothesis of this proposal is that before movement onset, both cell types compete over the control of these central movement processing centers. If the activity of the first class of cells dominates in the striatum, movements are imitated. If on the other hand, activity of the second class of cells dominates, movements are suppressed. To test this hypothesis, I will record brain activity from the striatum of mice that are trained to initiate and suppress specific movements and then correlate brain activity with movement initiation. In a second part, I will then use state-of-the-art genetic and optical techniques to gain control over the activity of both cell types and try to use targeted manipulations of neuronal activity patterns to bias movement decisions. In combination, these experiments will provide a comprehensive description, including correlational and causal evidence, for how the two different cell classes in the striatum control movement initiation and lay the necessary groundwork to tackle malfunctions of this process in human patients, specifically with Parkinson’s disease, in the future.