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 MINIMALLY INVASIVE NEUROCHEMICAL SENSING SYSTEMS FOR IN VITRO AND IN VIVO INVESTIGATION OF SEROTONERGIC MODULATION(2023) Han, Jinjing; Ghodssi, Reza; Electrical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Serotonin (5-hydroxytryptamine, 5-HT) plays a crucial role as a monoamine neurotransmitter, regulating various behavioral and physiological functions in the brain and peripheral systems. Its effects encompass emotions, behaviors, gastrointestinal motility, hemostasis, and cardiovascular function. Dysregulation of the serotonergic system and imbalances in 5-HT levels have been associated with psychiatric disorders, underscoring its potential as a biomarker for conditions like anxiety disorders, depression, Alzheimer's disease, and impulsive aggressiveness. However, the precise mechanisms by which 5-HT modulates these physiological conditions and behavioral processes remain unknown, necessitating the use of sensing tools to monitor 5-HT dynamics in specific locations. Traditional techniques such as high-performance liquid chromatography (HPLC) and enzyme-linked immunosorbent assay (ELISA) have been employed to measure 5-HT concentrations in biological samples. However, these offline methods only provide information at the end of an experiment and lack spatial and temporal resolution. Due to the rapid extracellular release and uptake of 5-HT, there is a clear need for detection techniques with high spatiotemporal resolution to investigate serotonergic modulations.This dissertation focuses on the development of minimally invasive neurochemical sensing systems to address challenges related to real-time 5-HT sensing and facilitate in vitro and in vivo investigation of serotonergic modulation. Two sensing systems were developed. For in vitro 5-HT sensing, surface-modified microelectrodes with single carbon fiber were developed and integrated with a portable potentiostat for point-of-care (POC) applications. These microelectrodes were tested for detecting in vitro cell-secreted 5-HT and 5-HT in homogenized crayfish nerve cord samples. The portable system exhibited a sensitivity of 74 nM/µM with a limit of detection (LOD) of 140 nM. Moreover, it was tested for detecting 5-HT in artificial urine, showcasing its application as a POC device for early diagnosis of 5-HT syndrome from urine tests. For in vivo 5-HT sensing, surface-modified microelectrodes with multiple carbon fibers were developed to enhance mechanical robustness specifically for in vivo applications. After integration with a miniature PCB, the device was able to co-detect dopamine (DA) and 5-HT at sub-micromolar concentrations with wireless communication. The integrated untethered implantable system demonstrated its capabilities for in vivo simultaneous monitoring of DA and 5-HT in freely moving crayfish during injection events. Overall, these developed systems offer electrochemical 5-HT sensing solutions for both in vitro and in vivo applications, providing reliable tools to obtain real-time 5-HT dynamics information with high spatial resolution. This capability significantly enhances our ability to investigate precise 5-HT signaling and mechanism underlying serotonergic modulation in the disorder development and behavioral processes.Item SEROTONIN SENSOR-INTEGRATED IN VITRO SYSTEMS AS RESEARCH TOOLS TO ADDRESS THE GUT BRAIN AXIS(2022) Chapin, Ashley Augustiny; Ghodssi, Reza; Bentley, William E; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The gut-brain-axis (GBA) is a bi-directional communication system between the gastrointestinal (GI) enteric nervous system and the central nervous system, capable of complex crosstalk between the gut and the brain to maintain GI homeostasis and influence mood and higher cognitive functions. Under healthy conditions, this communication is beneficial for regulating immune function, proper peristaltic motion, and hormone release related to hunger and feeding behaviors. However, GBA communication can cause co-morbid occurrence of both GI and neural disorders. For instance, chronic inflammatory conditions of the gut, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), often present with symptoms of depression and anxiety. Clinical studies, animal models, and molecular research techniques have implicated serotonin (5-HT) as a key signaling molecule to both regulate GI functions and stimulate enteric nerves. These studies are limited by the inability to study sub-mucosal 5-HT on the basolateral side of the epithelium, wheremost of the 5-HT is released and acts on nerves endings. The ability to measure 5-HT release patterns in this area, at native spatial and temporal scales, within an in vitro culture of the gut epithelium, would allow researchers to distinguish 5-HT release patterns stimulated by different GI luminal conditions associated with health and disease, to better understand how these stimuli affect the brain. In this dissertation, electrochemical sensors are fabricated within two types of in vitro platforms to measure 5-HT at physiological scales (sub-micromolar concentrations). The goal of this design is to facilitate the direct detection of 5-HT released from cells cultured in the platform to improve both spatial and temporal access to basolaterally-secreted molecules and provide continuous, automated measurements over experimental time scales. 5-HT sensors fabricated on both porous and smooth cell culture substrates are demonstrated, achieving sensitivities of ~1 – 10 μA/μM and limits of detection of ~100 nM. Electrochemical characterization allow understanding of 5-HT adsorption kinetics, which was modeled to track and predict sensor fouling over continuous measurements. These sensor-integrated substrates were packaged in 3D printed structures, which allowed rapid fabrication of custom designs and were shown to be biocompatible and support growth of RIN14B cells, a model 5-HT-secreting cell line. Finally, cell-secreted 5-HT was detected at ~100 – 500 nM, corresponding to ~4 pmol 5-HT / 105 cells. Ultimately, slow adsorption kinetics prevented direct detection of 5-HT from cells cultured directly on top of the sensors, but the thorough characterization of the platform demonstrated here lays significant groundwork for future optimization of the sensing protocol.Item Characterization and Control of Aggression and Reproduction in the Male Clouded Leopard (Neofelis nebulosa)(2012) DeCaluwe, Heather Burton; Ottinger, Mary Ann; Animal Sciences; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Clouded leopards are a striking and elusive cat species whose secretive nature has made it difficult to gather information on population statistics and behavior in the wild, where the population is in decline. While captive populations are intended as a hedge against extinction, breeding clouded leopards ex situ has been a challenge, primarily due to extreme male aggression toward females. Despite the importance of aggression in this species, there has as yet been no systematic study characterizing the basis of aggressive episodes. Two mechanisms seem to underlie the aggressive behavior in clouded leopards: degree of anxiety and circulating testosterone levels. Three studies were conducted to characterize mechanisms modulating aggression in male clouded leopards. In Study 1, sixteen adult male clouded leopards were categorized as `anxious' or `calm' using a keeper questionnaire and fecal endocrine (androgen and glucocorticoid) profiles; these measures were correlated with behavior rates and frequencies before, during, and after a series of behavioral reaction tests aimed at assessing an individual's response to stress-inducing situations. In Study 2, the behavioral and endocrine responses to the same tests were compared in the same clouded leopards following three treatments: 1) an anxiety-reducing psychotropic drug (clomipramine, n = 4); 2) a gonadotropin releasing hormone agonist (deslorelin, n = 5), or 3) no treatment (n = 4). In Study 3, the long-term effects of the drug treatments on spermatogenesis and hormone concentrations were compared in clouded leopards (n = 2/treatment) and domestic cats (n = 5/treatment), a model for non-domestic felid reproduction. Studies revealed important findings about the basis of aggressive behavior in male clouded leopards. First, two of the behavioral reaction tests - `mirror image stimulation' and `unfamiliar people' - were effective tools for evaluating temperament and eliciting a behavioral response. Second, treatment with both clomipramine and deslorelin reduced anxious and aggressive behaviors (e.g. `tail flicking' and `growling') indicating multiple physiological mechanisms likely modulate aggression in this species. Finally, deslorelin temporarily suppressed hormone concentrations and reproductive function, while clomipramine had no clear effect on either. Ultimately, this information provides important tools for improving male-female pairing success and the overall management of captive clouded leopards.