The role of the ventral tegmental area in motivated behavior

Duke University, Durham NC

Investigators

Abstract

Summary The ventral tegmental area (VTA) is a midbrain region that has long been implicated in the learning and expression of motivated behavior. It contains dopamine (DA) neurons that give rise to the mesolimbic dopamine pathway, as well as GABAergic (GABA) projection neurons that target multiple midbrain and brainstem regions. According to the reward prediction error (RPE) hypothesis, phasic activity of VTA DA neurons encode a reward prediction error, whereas GABA neurons encode reward prediction, which is used to compute reward prediction error. However, recent work has begun to challenge this hypothesis, by showing precise encoding of action parameters by VTA DA and GABA neurons. It remains unclear how the role of VTA in performance may be reconciled with a role in learning and reinforcement. The overall aim of this proposal is to elucidate the function of the VTA circuits using a highly integrative approach that combines multiple levels of analysis, from single neurons to behavior. We will use bidirectional optogenetics, in vivo electrophysiology and photometry, and quantitative behavioral measures with unprecedented temporal and spatial resolution, to elucidate the contribution of the VTA circuit to the learning and performance of motivated behaviors. This proposal will test the hypothesis that the VTA GABA projection neurons provide continuous descending commands for steering of the head and body, and that the output of the DA neurons is used to adjust the gain in the limbic basal ganglia responsible for generating such commands critical for approach and retreat in all motivated behaviors. We will record and perturb neural activity from VTA DA and GABA neurons using a number of behavioral tasks in head-fixed as well as freely moving mice. Using the latest DA sensors, we will also record DA signaling in multiple striatal regions that receive VTA projections. Finally, we will develop a computational model of the VTA circuit, focusing on interactions between VTA DA and GABA neurons and their collective contributions to behavioral output. Results from proposed experiments can lead to a new and unified model of adaptive performance and learning in motivated behaviors.