Grant: Project Grant

The motivational processes that guide value-based decisions are regulated in the brain by dopamine signaling and basal ganglia activity. Dysregulations in this circuitry have been identified in animal models of neurological and psychological disorders, but interpretations of these findings and attempts to leverage them to guide drug development efforts have been hampered by our limited understanding of the functions and computations of this circuitry. Drugs that target dopamine signaling and striatal activity are widely used (and abused) for a variety of reasons. A common side effect of these drugs is alterations in ingestive behaviour. Given that ingestive behaviour is primarily motivated by taste hedonics and the internal state of the animal, we believe we can elucidate general principles of striatal value encoding and circuit function by examining how taste and thirst influence striatal physiology and ingestive behaviour. We propose to use single-cell calcium imaging, fluorescence dopamine sensors, and chemogenetic manipulations of genetically-defined striatal cell populations to identify the causal relationships between distinct sources of value, ingestive decisions, and subregion-specific striatal neuron activity and dopamine signaling. This research will not only provide insight into the contributions of distinct striatal subregions to ingestive behaviour but also reveal how the two classes of projection neurons present throughout the striatum represent value for control of motivated behaviour. A better understanding of the functions of striatal subregions and associated value computations will undoubtedly improve researchers' ability to interpret striatal circuit dysregulations in disease models and aid rational drug development efforts.