Theses and Dissertations from UMD
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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM
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Item INTERACTIONS OF SOCIAL EXPERIENCE, ALCOHOL SENSITIVITY, AND THE SEROTONERGIC SYSTEM(2024) Ho, Ta-wen; Herberholz, Jens; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Social isolation has been shown to correlate with increased alcohol consumption in various animal species. In humans, a decreased sensitivity to acute alcohol is correlated with future alcohol dependence and addiction. A plausible explanation for this correlation is that alcohol sensitivity decreases after isolation; however, our understanding of the mechanistic interaction between social isolation and sensitivity to acute alcohol is still in its infancy. The serotonergic system is one promising candidate that could be involved in this interaction because of its wide range of behavioral and physiological effects, especially those related to social experiences. In my dissertation, I investigated the roles of the serotonergic (5-HT) system with three separate aims: In the first aim, I measured the effects of several 5-HT agents (neurotoxin, reuptake blocker, and receptor agonist/antagonists) in freely-behaving crayfish that were communally housed (COMs) or individually isolated (ISOs) prior to ethanol (EtOH) exposure. I found that 5-HT is important in regulating the social differences in EtOH sensitivity, and 5-HT2βPRO receptors emerged as candidates to produce this interaction between 5-HT and EtOH. My results from this aim suggest that these receptors are downregulated in isolated crayfish, leading to reduced behavioral EtOH sensitivity. The second aim employed single-cell neurophysiology and pharmacology in the lateral giant (LG) circuit of reduced ex vivo crayfish preparations to investigate the cellular-molecular mechanisms that underlie the interaction between 5-HT and specific EtOH receptor targets. I found that the LG neurons are stimulated by EtOH, and social differences in EtOH sensitivity between COMs and ISOs are paralleled at the level of these single neurons. Specifically, my results suggest that social isolation causes downregulation of 5-HT2βPRO receptors and 5-HT1αPRO receptors on the LG neurons and upregulation of these receptors subtypes in GABAergic neurons that send feed-forward inhibition onto the LG neurons. In my third aim, I developed a wearable, miniature, cyclic voltammetry device that is capable of detecting (injected) monoamine neurotransmitters (including 5-HT) in freely-behaving crayfish. With improved sensor sensitivity in the future, this will allow measurements of 5-HT release patterns in crayfish with different social histories, including during EtOH exposure. Together, the results from my dissertation will inform work in other model systems and improve our understanding of the interactions between social experience, the 5-HT system, and alcohol use.Item Physiological Effects of Alcohol on Crayfish Escape Circuitry(2016) Swierzbinski, Matthew Edward; Herberholz, Jens; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Alcohol is one of the oldest and most widely used drugs on the planet, but the cellular mechanisms by which it affects neural function are still poorly understood. Unlike other drugs of abuse, alcohol has no specific receptor in the nervous system, but is believed to operate through GABAergic and serotonergic neurotransmitter systems. Invertebrate models offer circuits of reduced numerical complexity and involve the same cell types and neurotransmitter systems as vertebrate circuits. The well-understood neural circuits controlling crayfish escape behavior offer neurons that are modulated by GABAergic inhibition, thus making tail-flip circuitry an effective circuit model to study the cellular mechanisms of acute alcohol exposure. Crayfish are capable of two stereotyped, reflexive escape behaviors known as tail-flips that are controlled by two different pairs of giant interneurons, the lateral giants (LG) and the medial giants (MG). The LG circuit has been an established model in the neuroscience field for more than 60 years and is almost completely mapped out. In contrast, the MG is still poorly understood, but has important behavioral implications in social behavior and value-based decision making. In this dissertation, I show that both crayfish tail-flip circuitry are physiologically sensitive to relevant alcohol concentrations and that this sensitivity is observable on the single cell level. I also show that this ethyl alcohol (EtOH) sensitivity in the LG can be changed by altering the crayfish’s recent social experience and by removing descending inputs to the LG. While the MG exhibits similar physiological sensitivity, its inhibitory properties have never been studied before this research. Through the use of electrophysiological and pharmacological techniques, I show that the MG exhibits many similar inhibitory properties as the LG that appear to be the result of GABA-mediated chloride currents. Finally, I present evidence that the EtOH-induced changes in the MG are blocked through pre-treatment of the potent GABAA receptor agonist, muscimol, which underlines the role of GABA in EtOH’s effects on crayfish tail-flip circuitry. The work presented here opens the way for crayfish tail-flip circuitry to be used as an effective model for EtOH’s acute effects on aggression and value-based decision making.