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 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 SEX DIFFERENCES IN THE FOREBRAIN DOPAMINERGIC CIRCUIT(2022) Manion, Matthew Timothy Coon; Glasper, Erica R; Wang, Kuan Hong; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Several psychiatric disorders exhibit different incidence rates in men and women and areassociated with dysfunctions in forebrain dopaminergic circuits. Although anatomical and functional sex differences in the brain have been studied, little is known about sex differences in the forebrain dopaminergic circuits associated with behavioral dysfunction. We hypothesized that known sex differences in forebrain dopamine circuit-associated behaviors would be the result of sex differences in forebrain dopamine circuit anatomy. As a first step to address this hypothesis, we combined a mouse transgenic driver line (tyrosine hydroxylase promoter-driven Cre recombinase) with virally encoded fluorescent reporters (FLEX-tdTomato and SynaptophysinGFP) to compare the density of midbrain dopaminergic axon projections and terminal boutons in dopamine projection target regions. Using this technique, we analyzed projections from the ventral tegmental area (VTA) to prefrontal cortex and basolateral amygdala (BLA) in male and female adult mice. Multiple analyses at 10x and 25x magnification revealed higher bouton density in BLA in males compared to females. To determine if this anatomical difference is mediated by gonadal steroid hormones, subjects were treated with a drug used to reduce gonadal steroid hormone production in clinical populations, leuprolide acetate (Lupron), before anatomical measures. Leuprolide administration resulted in a reduction in circulating testosterone, but did not show an effect on dopamine circuit anatomy. The finding of an anatomical sex difference in the forebrain dopamine circuit provides a structural foundation for further investigation of how sex differences in brain circuits may underlie behavioral dysfunction that play roles in psychiatric illnesses.Item Neural Mechanisms of Approach and Avoidance(2017) Gentry, Ronny; Roesch, Matthew R; Psychology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Using environmental cues to acquire good things and avoid harmful things is critical for survival. Rewards and punishments both drive behavior through reinforcement learning mechanisms and sometimes occur together in the environment, but it remains unclear how these signals are encoded within the brain and if signals for positive and negative reinforcement are encoded similarly. The dopaminergic system and, more broadly, the corticomesolimbic circuit are known to be involved in the processing of positive and negative reinforcement. Here, I investigated neural correlates of decision-making and associated behavioral patterns within two key corticomesolimbic regions: the ventromedial prefrontal cortex (vmPFC), which is thought to generate contextually appropriate responses, and the nucleus accumbens (NAc), which is thought to use dopamine (DA) prediction error signals to motivate behavior. The goal of this work was to uncover the underlying brain mechanisms encoding positive and negative reinforcement signals and to explore individual differences in neural and behavioral patterns that arise during learning and performance. To achieve this, I recorded from single neurons within vmPFC and measured DA release within NAc core during two behavioral tasks examining distinct aspects of learning: initial Pavlovian responses, as well as more complex combined positive and negative reinforcement. I found that, within the vmPFC, cell firing was modulated more often and more robustly by cues predicting reward than by cues preceding avoidable shock; overall, we found very few cells that responded to shock cues, and responses to shock avoidance and reward cues were not colocalized within the same cells. Alternatively, I found that DA release within the NAc increased to both reward and shock avoidance cues compared to neutral cues, and these changes occurred within the same microdomain of the NAc. Additionally, we uncovered intriguing individual differences in NAc DA release and behavioral responses during both our combined approach avoidance and autoshaping tasks and, in the final chapter, shifted these responses by manipulating task parameters and inhibiting VTA-NAc DA neurons. Together, these results help further our understanding of how differences in vmPFC activity and accumbal DA release influence cue-driven learning and behavioral performance across various contexts.