Faith Bonneson

Our motivation to act in the world is strongly influenced by available rewards we can pursue in the environment and our perception of their attainability. While previous studies have investigated brain circuits that facilitate behavioral flexibility by regulating learning and motivation, details about their interactions, and how they are relevant to decision making and psychiatric disorders remains incomplete. Here, we set out to understand how learning about costs (learning from losses) and benefits (learning from gains) are supported by opponent basal ganglia pathways. It has been previously demonstrated that D2 dopamine receptors in striatal medium spiny neurons accumulate evidence for costs and restrain behaviors, a process critically refined by dopamine. The intracellular cascade initiated by the D2 receptor utilizes an orphan G-protein coupled receptor 6 (GPCR6), with unknown cellular function and behavioral consequences. We utilized mice lacking GPR6 (GPR6-KO mice) to study how learning from costs within the D2 pathway affects behavior. We designed a two-lever probabilistic trial and error task where mice had to dynamically adjust their choices to changing reward probabilities. We have thus far characterized this task in wild type animals and demonstrate bidirectional cost-benefit learning across different reward rates. We plan to extend these analyses to GPCR6-KO mice as a behavioral assessment of whether these mice (and heterozygous littermates) display deficits in cost-benefit learning, in addition to measurement of dopamine release during task performance.