Date of Award

Fall 2025

Document Type

Open Access Thesis

Department

Psychology

First Advisor

Peter Vento

Abstract

Maladaptive decision-making, such as persistent reward seeking despite negative consequences, is a hallmark of substance use disorder (SUD) and related psychiatric conditions. These behaviors are thought to arise from impairments in aversive learning and disrupted neural signaling that normally supports behavioral inhibition. The prelimbic cortex (PL) plays a critical role in encoding cue–outcome associations and exerting top-down control over behavior, while the rostromedial tegmental nucleus (RMTg) serves as a GABAergic inhibitor of midbrain dopamine neurons in response to aversive stimuli. Although both structures have been implicated in reward and avoidance processes, little is known about how direct PL-RMTg projections contribute to discriminating cues that predict rewarding versus aversive outcomes.

This study examined how inhibiting the PL and its projections to the RMTg influences cue-guided decision making in a mixed-valence discrimination task incorporating reward-, neutral-, and aversion-predictive cues. Using pharmacological inactivation (baclofen/muscimol) and chemogenetic inhibition (Gi DREADDs), we tested three related hypotheses: (1) that global inactivation of the PL would produce indiscriminate responding across cues, (2) that chemogenetic inhibition of PL neurons would replicate this behavioral pattern, and (3) that pathway-specific inhibition of PL- RMTg terminals would increase responding on reward and neutral trials and particularly on aversive trials through disinhibition of downstream dopaminergic targets. Pharmacological inactivation of the PL produced a trend toward increased responding during neutral and aversive trials, suggesting reduced cue discrimination. In contrast, chemogenetic inhibition of the PL or PL-RMTg pathway did not significantly alter responding across cue types, despite verified viral expression and behavioral validation.

Although findings did not reach statistical significance, they suggest that PLRMTg signaling may be selectively recruited under conditions requiring strong behavioral inhibition or conflict. Future studies employing temporally precise optogenetic techniques and larger cohorts will further clarify how this pathway contributes to aversive learning and adaptive behavioral control.

Rights

© 2025, Emma Lane Carlson

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