Dopamine signaling of expected outcomes within the striatum

University Of Maryland Baltimore, Baltimore MD

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): Rewards are not procured and consumed in a vacuum. Rather, organisms learn to optimize behaviors through associations formed between relevant environmental stimuli and actions that consistently predict rewards. Numerous psychiatric conditions, including addiction, lead to aberrant decision-making in which people continue to respond to previously rewarded cues despite now adverse or undesirable consequences. As such, understanding the neural circuitry of such maladaptive learning processes is critical to developing successful therapeutic approaches. A diverse network of neural substrates, including regions of the ventral (VS) and dorsal striatum (DS) and their dopaminergic input from the midbrain, have been heavily implicated in reward learning. Here, we aim to test the hypothesis that cue-evoked dopamine signaling within the ventral and dorsal striatum has access to information about changes in the value of an expected outcome. Behaviorally, we can test this hypothesis by utilizing a reinforcer devaluation paradigm to establish what is known about the current value of a predicted outcome. Importantly, we know that conditioned responding in this behavioral paradigm is dependent on activity of the orbitofrontal cortex, and sensitive to cocaine induced dysfunction. Here, we will use fast-scan cyclic voltammetry and pharmacological manipulations (of the orbitofrontal cortex) in an outcome devaluation procedure, to provide novel characterization of striatal dopamine signaling. Furthermore, we will examine how prior cocaine experience alters striatal dopamine signaling within this task. Taken together, these studies will significantly advance our understanding of dopamine signaling of expected value, and more clearly define its role in reinforcement learning. PUBLIC HEALTH RELEVANCE: Numerous psychiatric conditions, including drug addiction, are associated with cognitive deficits that impair the ability to represent and use expected outcomes to guide appropriate responding, potentially reflecting modifications within learning circuits that mediate these behaviors. In an effort to understand these cognitive deficits, we must first understand the biological mechanisms that mediate them. This proposal seeks to provide a novel characterization of the role of dopamine in learning and processing of expected outcomes, particularly involving changes following chronic cocaine exposure, in an effort to provide key information for the development of therapeutic treatments for psychiatric conditions in humans.