Author ORCID Identifier

https://orcid.org/0000-0002-5247-8036

Date of Award

Spring 5-9-2025

Document Type

Thesis (Ph.D.)

Department or Program

Psychological & Brain Sciences

First Advisor

Kyle Smith

Abstract

Sign-tracking, a conditioned response in which animals are physically attracted to reward-predictive cues due to motivational value attribution, is known to be persistent but can be flexible under some circumstances. For example, during an omission paradigm, in which vigorous responses must be withheld to avoid reward cancellation, animals can quickly restructure their responses. However, sign-tracking does not cease entirely, and cue attraction persists. This dissertation explores the behavioral and neural mechanisms underlying the simultaneous persistence and flexibility of sign-tracking during omission procedures. First, a novel method for behavioral analysis is introduced to accurately depict sign-tracking animals in dynamic tasks such as omission, as current automated measures were found to be insufficient and sometimes inaccurate. Next, a set of pharmacological experiments were conducted in which acetylcholine receptors in the nucleus accumbens core were found to have opposing roles in sign-tracking flexibility and response restructuring during omission. These results may indicate acetylcholine as a regulator of motivation when circumstances change. Finally, using fiber photometry, dopamine transmission underlying separable motivational and reinforcement mechanisms during omission were uncovered. This revealed a unique framework of the two reward processes in which both motivation and reinforcement can coexist within distinct phasic dopamine signals, and challenges current models of reward processes. Altogether, these results characterize sign-tracking in a new light as a dynamic and rich behavior that can provide a critical and unique window to study reward processing in the brain. These results will be particularly relevant to understanding the neural underpinnings of excessive motivation in disorders such as addiction.

Original Citation

Townsend, E.S. & Smith, K.S. (2025). Behavioral microanalyses refine sign-tracking characterization and uncover different response dynamics during omission and extinction learning. Learning and Memory, 32(3). doi: 10.1101/lm.054065.124

Townsend, E.S., Amaya, K.A., Smedley, E.B., Smith, K.S. (2023). Nucleus accumbens core acetylcholine receptors modulate the balance of flexible and inflexible cue-directed motivation. Sci Rep 13, 13375. doi: 10.1038/s41598-023-40439-4.

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