Dissociating Reward Prediction from Action Selection: Distinct Roles for Nucleus Accumbens Inputs

Our everyday behavior is energized by the desire to maximize beneficial, rewarding outcomes while minimizing harmful ones. Brain circuitry has evolved to strengthen associations between rewards and the cues that predict their availability as well as to direct our behavior to approach and consume rewards. In today’s society, not all rewards are beneficial and cues that predict food and drugs can hold powerful sway over our behavior – leading to obesity and drug addiction. The mesolimbic system – consisting of the neurotransmitter dopamine, other inputs to and the outputs of the nucleus accumbens – is highly responsive to reward-predictive cues. However, it remains unclear whether signaling in the mesolimbic system reflects the associative strength between cues and their outcomes or underlies approach behavior. I developed two Go/NoGo paradigms to dissociate the roles of several components of the mesolimbic system in reward-directed behavior. The Go/NoGo paradigms were paired with real-time physiological recordings of dopamine release, or pharmacological manipulations of several neurochemicals, within the nucleus accumbens. I found that brief, high concentration ‘spikes’ in dopamine signaling within the nucleus accumbens reflect the associative strength between cues and reward. Cues that predicted reward availability, regardless of approach behavior, increased dopamine release within the nucleus accumbens. Pharmacological manipulations of the nucleus accumbens revealed that blockade of dopamine and glutamate NMDA receptors and activation of GABA receptors reduced goal-directed behavior. Blockade of glutamate AMPA receptors, though, resulted in a marked increase in approach behavior, even when it was inappropriate. Given the pervasive temptation to approach and consume various goods in our society, these studies elucidate roles for components of the mesolimbic system in reward-related behavior and behavioral inhibition. These data call for increased focus on microcircuits within the nucleus accumbens in order to direct treatment options for a variety of clinical conditions characterized by impaired impulse control such as compulsive gambling, over-eating, and drug addiction.