Synaptic Control of Dopamine as a Driver of Reward Learning

Abstract

Ventral tegmental area dopamine (VTADA) neurons fire in a manner consistent with Reward Prediction Error, with better-than-expected and worse-than-expected outcomes correlating with bursts and pauses, respectively. Burst and pause firing dynamics are believed to be responsible for driving associative learning, yet interrogating this causality, and understanding how these firing patterns are synaptically created within endogenous neural circuits, has been technically difficult. Utilizing a novel tool, DART (drug acutely restricted by tethering), paired with a multiplexed cue-reward associative learning task and in vivo neural recordings, I explore which classes of endogenous synaptic inputs to VTADA neurons create their canonical firing dynamics, and their role in the associated reward learning behaviors. My key finding is that antagonizing GABAA receptors on VTADA neurons decreases the pauses in firing these cells exhibit, but also accelerates extinction learning in response to unexpected reward omission. In the same mice, the manipulation had no impact on conditioning to a novel cue-reward pairing, indicating that positive-valence learning was unperturbed. This dissertation work provides critical insight into the neural circuitry underlying adaptive behaviors by creating a new framework for understanding conditioning and extinction as anti-correlated behaviors, and by establishing a novel role for direct inhibitory GABAA signaling to VTADA cells in conditioned conviction.