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

More information is available at Theses and Dissertations at University of Maryland Libraries.

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    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.
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    INTERACTIONS BETWEEN SEROTONIN AND BEHAVIORAL SENSITIVITY TO ACUTE ALCOHOL EXPOSURE IN CRAYFISH
    (2021) Ho, Tawen; Herberholz, Jens; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Social isolation has been found to correlate with an increase in alcohol consumption in humans. However, neurobehavioral and neurocellular mechanisms underlying interactions between alcohol and social isolation have been understudied. Prior work has shown that socially isolated crayfish exhibit lower behavioral and neural sensitivity to acute ethanol (EtOH) exposure than communally-housed conspecifics. Here we report an important role of the serotonergic system in mediating this socially-dependent effect. We found that depletion of serotonin (5-HT) from serotonergic neurons reduced behavioral sensitivity to EtOH, but the effect was more pronounced in communally housed animals. In addition, antagonizing 5-HT2β receptors also reduced EtOH sensitivity, and more strongly in group-housed animals, suggesting a possible down-regulation of 5-HT2β receptors in isolates. Pre-treatment with a selective serotonin reuptake inhibitor (fluoxetine) produced opposite modulatory effects, affirming the role of 5-HT in shaping the interactions between social experience and EtOH sensitivity. Thus, we show here, for the first time, that behavioral sensitivity to acute EtOH (i.e., intoxication) in crayfish is partially mediated by 5-HT, and our results suggest specific 5-HT receptor subtypes as possible targets for these interactions. This work might have relevance for studying the neurochemical mechanisms underlying the interplay between social history and alcohol sensitivity in other organisms. However, due to large variability in the experimental data and differences in sample sizes across conditions, the results should be considered preliminary, and future work will be aimed at increasing sample sizes and replication of results.