The Functional Neurocircuitry of Sign-tracking Behavior

Abstract

Cues that are paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the attribution of incentive salience. When previously neutral cues are imbued with incentive salience, they become attractive, “wanted” stimuli capable of motivating behavior. Pavlovian conditioned approach procedures are commonly used to investigate the attribution of incentive salience in rodents. During Pavlovian conditioned approach training, two conditioned responses develop: sign-tracking (behavior directed towards a reward-related cue) and goal-tracking (behavior directed towards the site of reward delivery). Goal-trackers and sign-trackers both use the reward-related cue as a predictor of reward delivery; however, only sign-trackers attribute it with incentive salience and are more vulnerable to addiction-like behaviors, such as cue-induced reinstatement of drug-seeking. Currently, it is known that sign-tracking behavior is dependent on dopamine in the nucleus accumbens, a central hub in the ‘motive circuit,’ an array of mesocorticolimbic brain regions that process incentive stimuli. However, the role of other signaling pathways and the contribution of afferent brain regions within the motive circuit to sign-tracking behavior is poorly understood. In this dissertation, I demonstrate that the ventral hippocampus is a part of the motive circuit, regulating sign-tracking behavior and dopamine signaling in the nucleus accumbens. In addition, I show that the motive circuit can be manipulated environmentally and pharmacologically using prolonged stress and subanesthetic ketamine, respectively, to decrease sign-tracking behavior. Taken together, the results of this dissertation advance our understanding of the functional neurocircuitry of sign-tracking behavior and how it is influenced by environmental and pharmacological manipulations of the motive circuit.