PROJECT SUMMARY / ABSTRACT The striatum is the main input region of the basal ganglia, receiving and integrating massive amounts of sensory, motor and cognitive information in order to output, through activation of the direct and indirect pathways, appropriate actions in response to particular external stimuli and contexts. Imbalances in the activity of the striatum have been implicated in movement disorders like Parkinson’s disease and disorders of action selection and learning like addiction and obsessive compulsive disorder. This range of diseases are characterized by distinct behavioral deficits ranging from immediate action selection to learning-related adaptive responses. However, it is still unknown how simultaneous output of the two main pathways of the striatum support immediate action selection and how these dynamics evolve across learning to support adaptive decision making and action selection. The purpose of this proposal is to determine how activity in direct and indirect pathways evolves on timescales ranging from 100s of ms to days to support learning and performance of appropriate, instrumental actions. Literature evidence suggests that the anterior and posterior regions of the dorsomedial striatum (aDMS and pDMS) are a locus for the performance and acquisition, respectively, of goal-directed actions. We have designed three different aims in which we will address how simultaneous activation of the direct and indirect pathways in the aDMS and pDMS leads to proper performance and acquisition of instrumental behaviors. The first aim will test how simultaneous dynamics of the direct and indirect pathways in the aDMS support context-dependent immediate action selection by performing high-resolution 2-photon recordings of the calcium dynamics on both pathways while mice perform a context-dependent instrumental task. We will inject D1-cre and Adora2a-cre mice with two AAV-viral vectors containing the calcium indicator GCaMP7f, a proxy for neural activity, and the static cre-dependent label td-Tomato to acquire cell type specificity. The second aim will test how the dynamics of the direct and indirect pathways evolve during instrumental learning to allow for the proper acquisition of instrumental behaviors. To answer this question, we will employ the same imaging approach mentioned above with longitudinal recording to access the same population of pDMS cells across days, mice will be imaged as they learn new contingencies. Lastly, our third aim will test the individual contributions of each pathway to the acquisition of contralateral versus ipsilateral instrumental action selection by optically inhibiting each pathway during key task events across days of training. This will be done by selectively expressing cre-dependent inhibitory opsins in the pDMS of D1-cre and Adora2a-cre mice. Overall, results from the proposed studies will provide fundamental understanding about how these circuits normally function, which is a key step towards und...