Mechanisms Mediating Cue-Induced Ethanol Seeking in Drosophila

Nunez, Kavin Milciades

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Year:: 2021
Contributor:: Nunez, Kavin Milciades (creator); Kaun, Karla (Advisor); De la Monte, Suzanne (Reader); Moore, Christopher (Reader); O'Connor-Giles, Kate (Reader); Certel, Sarah (Reader); Brown University. Department of Molecular Pharmacology, Physiology and Biotechnology (sponsor)
Genre:: theses
Subject:: Drosophila melanogaster; Alcohol; behavioral neuroscience; Alcoholism; Hunger; Alcohol Use Disorder; Ethanol
Extent:: xxii, 283 p.

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Abstract:: Ethanol is a naturally occurring organic compound that has had a profound impact on behavior and society. In the natural environment it directs an animal towards essential resources, but at pharmacological concentrations proves to be detrimental to health. Studying ethanol-induced behaviors and circuits in different model systems can be beneficial to understanding the progression of alcohol use disorders. Drosophila melanogaster are a genetically tractable model system that conserves the acute and more maladaptive ethanol-induced behaviors. Using this model system, we can parse out the complexities underlying ethanol-induced behavior and dissect out circuits that are mediating these effects. I initially describe methods that measure the acute behavioral effects of ethanol intoxication, focusing on ethanol induced-locomotion and the implementation of the fly Group Activity Monitor (flyGrAM). Subsequently, I transition to understanding longer-term effects by characterizing a cue-induced ethanol seeking paradigm following olfactory conditioning. Our study highlights that fruit flies display both acute and persistent memories for ethanol-conditioned odor cues, and that a combination of parameters that determine the intoxication state of the fly influence the retention and expression of memories associated with intoxication. Building off this initial characterization, I sought to ask how hunger affects circuits important for ethanol-related behaviors in order to understand how stress impacts ethanol-memory processing and retrieval circuitry. Using a combination of behavior, immunohistochemistry, and in-vivo 2-photon calcium imaging I was able to identify a hunger-responsive neuron that modulates ethanol memory processing and retrieval. This octopaminergic ventral unpaired median ascending 3 (VUMa3) neuron responds to hunger by increasing its baseline calcium activity as a function of food-deprivation over the course of 18-24 hours, and specifically responding to the conditioned stimulus 24 hours after conditioning and only when the fly is hungry. These findings suggest that hunger activates a parallel circuit that drives learned preference, providing an anatomical framework through which internal state influences acquisition and expression of memory for ethanol-associated cues. Finally, I discuss the implications of my findings on both the ethanol and neuroscience research communities with regards to other animal models, and considering the overall influence internal state has on behavior.
Notes:: Thesis (Ph. D.)--Brown University, 2021

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Nunez, Kavin Milciades, "Mechanisms Mediating Cue-Induced Ethanol Seeking in Drosophila" (2021). Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:6ejws4rv/

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Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations

Theses and Dissertations for the Molecular Pharmacology, Physiology, and Biotechnology department.
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