Behavioral functions of cotransmission in cost/benefit choices

About This Grant

Project Summary To survive in dynamic environments animals must choose appropriate actions to pursue rewards and avoid threats. While foraging, successful animals will leverage their past experiences to select, moment to moment, the action most likely to maximize reward while minimizing risk. This fundamental process of “action selection” is believed to require basal ganglia (BG) circuits in all vertebrates. Influencing the process of action selection, midbrain dopamine neurons (mDAs) project to the BG. Canonically, a primary function of nucleus accumbens projecting mDAs is to reinforce previously performed actions that have resulted in positive outcomes and discourage those that resulted in negative outcomes. As such, mDAs are crucial for learning action values and controlling adaptive behavior. Recently, DA released in the posterior “tail” of the striatum (TS) has been shown to exhibit wholly different responses to environmental stimuli. DA release in TS shows little or no change to reward, but instead increases in response to highly salient and/or threatening stimuli. It is now clear that different striatal subregions are innervated by distinct populations of mDA neurons which may imbue different plasticity and behavioral functions to BG subcircuits, for example reward vs threat learning. In preliminary studies, we have found a unique population of entopeduncular neurons (EPSst+) lie directly downstream of the TS. These neurons are peculiar in that cotransmit both GABA and glutamate and project directly to the lateral habenula (LHb) a region important for learning and predicting aversive stimuli. We hypothesize that the specialized circuitry linking TS, EP, and LHb is critical for rapid behavioral adaptation following aversive stimuli. We will test circuit function using a task that requires an animal to suppress its escape response to a threatening stimulus to obtain a reward. These studies will reveal new BG circuit architectures that are required for an animal to appropriately respond in a dynamic environment with changing costs and benefits of its actions.