Nucleus Accumbens Processing of Reward-predictive Cues

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The nucleus accumbens (NAc)is an important contributor to the neural circuitry responsible for the engagement of goal-directed behavior (such as drug seeking) in response to environmental stimuli that predict reward availability. The research proposed here is an investigation of the physiological mechanisms by which the NAc processes stimuli and influences the probability that a stimulus will result in goal-directed behavior. The firing of NAc neurons can be divided into three broad categories: cue-evoked discharges, operant-related increases or decreases in firing, and reward-related firing changes. The information contained by these patterns will be determined by changing the information contained by the cue (for instance, where to go to get the reward) and examining whether and how the neural responses consequently change. The relationship between locomotor behavior and NAc neuron firing will be explicitly examined, particularly as it relates to cues that drive goal-directed behavior. In addition, the degree to which NAc neurons encode the reward predicted by cues will be examined. Although a great deal of behavioral pharmacology and anatomy research suggests that the roles of the NAc core, shell and rostral pole in behavior are different, few electrophysiological studies have identified differences in how neurons in these regions respond during behavioral tasks known to be controlled or influenced by the NAc.Therefore, a second goal of this project is to determine how NAc firing patterns are distributed among the subregions of the NAc. A third major goal of this work is to establish the role of the dopaminergic projection to the NAc in modulating neural firing during natural reward-seeking behavior. Microinjection of dopamine antagonists within the NAc intended to alter specific firing patterns will be used to establish a causal link between neural activity and reward-seeking behavior. These experiments will lead to a more complete understanding of how NAc neurons, and dopamine released within the NAc, contribute to the processes underlying natural reward. Such an understanding is essential for the determination of the neural mechanisms of drug reward.