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Diurnal Rhythms in Learning, Motivated Behaviors, and Dopamine Dynamics

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Diurnal Rhythms in Learning, Motivated Behaviors, and Dopamine Dynamics
Stowe, Taylor
Diurnal rhythms exist throughout physiology and behaviors in a majority of organisms. These rhythms are essential for survival as they allow an organism to adapt to an environment. For instance, reward-seeking behaviors are higher during the dark cycle in rodents. Moreover, dysregulations within rhythms are common hallmarks of psychiatric disorders, like substance use disorders (SUDs). Gaining a better understanding of innate rhythms in behaviors associated with psychiatric disorders allows us to better characterize changes that lead to the neuropsychiatric state. This dissertation aimed to characterize diurnal rhythms in motivated behaviors and the underlying neurochemistry. First, we employed ex vivo fast scan cyclic voltammetry (FSCV) to determine diurnal rhythms in baseline dopamine (DA) dynamics. We also expanded on this study to examine diurnal rhythms in cholinergic interneuron (CIN) activity, a potent regulator of local DA release that may underlie fluctuations in DA dynamics. Collectively, these data support that diurnal rhythms exist in both baseline DA dynamics and CIN activity. We next utilized Pavlovian paradigms, Pavlovian conditioned approach (PCA) and Pavlovian instrumental transfer (PIT), to examine diurnal responses to reward-associated cues. We utilized these paradigms as DA mediates the behavioral responses, and little to no research has examined the potential diurnal rhythms in these responses to reward-associated cues. Our behavioral data demonstrated cue-directed behaviors were exclusive to rats midway through the dark cycle, which suggest there is heightened vulnerability to cues at this time. In contrast, rats midway through the light cycle primarily exhibited goal-directed behaviors. Thus, we wanted to determine if manipulating DA release during the light cycle in a PCA paradigm would induce cue-directed behaviors. With in vivo optogenetics, we stimulated DA neurons in the ventral tegmental area (VTA) during the presentation of the reward-associated cue and this led to cue-directed behaviors in rats at ZT 6. Overall, this dissertation revealed that there are potentially times within the day in which an individual has heightened vulnerability to reward-associated cues, which may be governed by rhythms in CIN activity modulating DA release.
Ferris, Mark J (committee chair)
McClung, Colleen A (committee member)
Jones, Sara R (committee member)
Raab-Grahm, Kim F (committee member)
2022-07-11T19:17:44Z (accessioned)
2022-07-11T19:17:44Z (available)
2022 (issued)
Physiology and Pharmacology (discipline)
http://hdl.handle.net/10339/101028 (uri)
en (iso)
Wake Forest University

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