Palmer, Dakota2023-11-282023-11-282023-06https://hdl.handle.net/11299/258640University of Minnesota Ph.D. dissertation. June 2023. Major: Neuroscience. Advisor: Jocelyn Richard. 1 computer file (PDF); vi, 52 pages.Sensory cues associated with reward allow us to predict future outcomes and modify behavior accordingly. However, reward-predictive cues acquire motivating and reinforcing properties which enable them to capture attention and powerfully bias behavior in favor of reward pursuit. Drug-predictive cues, for example, can trigger potent cravings and sustain compulsive drug seeking. The impact of such cues contributes to chronic risk of relapse in addiction, a significant challenge to long-term patient outcomes. The ventral pallidum (VP) and ventral tegmental area (VTA) are two key nodes in brain reward circuitry implicated in addiction and necessary for the performance of cue-driven behavior. Evidence suggests that VP neurons projecting to the VTA (VP→VTA) promote cue-induced reinstatement of drug-seeking, but the mechanisms by which these neurons do so are undefined. In addition, the role of these neurons in the pursuit of non-drug reward is not known. In the current study, we used in vivo fiber photometry and optogenetics to record from and manipulate VP→VTA in rats performing a discriminative stimulus task (DS task) with sucrose reward to determine the fundamental role these neurons play in invigoration and reinforcement by reward and associated discriminative cues. We find that VP→VTA neurons are selectively active during reward consumption, that optogenetic stimulation of these neurons paired with reward consumption biases choice, and that VP→VTA optogenetic stimulation is reinforcing. Critically, we found no significant encoding of cue-elicited reward-seeking vigor and acute optogenetic stimulation of these neurons paired with cue onset did not enhance the probability or vigor of reward-seeking. Our results suggest that VP→VTA neurons are active during the consumption of natural reward and that this activity reinforces seeking behavior.enThesis or Dissertation