UMD Theses and Dissertations
Permanent URI for this collectionhttp://hdl.handle.net/1903/3
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Item Reactivation of plasticity in the adult visual cortex by control of neuronal excitability(2023) Borrell, Andrew; Quinlan, elizabeth; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Amblyopia is a highly prevalent form of monocular vision loss that impacts between 1-4% of the worldwide population. Amblyopia is characterized by decreased visual acuity in a single eye and is highly refractory to treatment past a “critical period” of heightened plasticity during early adolescence (>5 years of age). The time course of this critical period is due to the developmental regulation of experience-dependent synaptic plasticity in the primary visual cortex (V1). During early development, visual experience drives activity-dependent changes in NMDA-R subunit composition, refines the convergence of binocular inputs, and promotes the maturation of inhibitory circuits in V1. The transient conditions in V1 that permit the refinement of cortical circuits during the critical period also render V1 vulnerable to the detrimental impacts of amblyopia.The expression of critical period plasticity requires visual experience: dark-rearing delays the onset and closure of the critical period and prevents the experience- dependent change in NMDA-R subunit composition. It is now understood that visual experience in adulthood is also important for the expression of plasticity: sensory deprivation via prolonged dark exposure (DE) rejuvenates the V1 circuit to a juvenile-like state via a homeostatic increase in spontaneous excitatory in V1. Subsequent visual experience during light reintroduction (LRx) enables the expression of critical period plasticity and the functional rewiring of thalamocortical inputs to V1. Here I asked how the homeostatic increase in spontaneous activity induced during DE is regulated by visual experience immediately following LRx (LRxi), and during one day of subsequent day of LRx (LRxs). I demonstrate that the homeostatic increases in spontaneous excitatory neuron activity is maintained during LRxi and is accompanied by increased evoked excitatory neuron activity. These increases in averaged spontaneous and evoked activity returned to baseline by LRxs. Next, I asked whether decreased spontaneous activity following one day of LRx was necessary for the reactivation of critical period plasticity. Using the mouse model of ocular dominance plasticity (ODP) and cell-type specific expression of inhibitory chemogenetic Gi-DREADD receptors in fast spiking Parvalbumin-expressing interneurons, I demonstrated that prolonged disinhibition of spontaneous V1 activity during LRx occludes the reactivation of ODP, but not the reactivation of the plasticity of acuity. These results demonstrate the differing contribution of cortical mechanisms to ocular dominance versus acuity in the regulation of the critical period plasticity, and the necessity of the decrease in average spontaneous activity for the re-expression ODP.Item Cortical Contributions to a Combined Appetitive-Aversive Social Outcome Task.(2021) Schneider, Kevin N; Roesch, Matthew R; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Learning through the emotional states of others is a critical skill for navigating our complex social environments, which is why it is a focal point of investigation in social neuroscience. Significant advances have been made in recent years, highlighting cortical brain regions where the transfer and processing of socially-derived affective information may be taking place. Among these regions are the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), known for their roles in attention and valuation during decision-making tasks, respectively. However, social decision-making studies have typically focused on either reward or punishment as the outcome valence, making it difficult to determine the social specificity of neural contributions observed. Using a social task that manipulates reward and shock within the same experiment, I recorded single-unit activity from ACC and OFC in rats. I found that during the task, ACC activity shared responses for reward and shock outcomes, suggesting it encoded socially-derived information in the service of attention. OFC neurons showed responses to self and vicarious reward outcomes, consistent with previous work in primates. Interestingly, OFC also encoded the positive value of the rats’ approach to their conspecific following foot-shock delivery, which leads to stress relief and a reduced fear response. Thus, in this task, ACC and OFC encoded other-related outcome information with respect to the self, in accordance with their nonsocial functions, suggesting that during social decision-making tasks, internal state goals are prioritized when outcomes to the self are at stake.Item ARABIDOPSIS THALIANA GLUTAMATE RECEPTOR-LIKE 3.7 UNDERLIES ROOT MORPHOLOGY AND SIGNALING VIA MEMBRANE POTENTIAL HOMEOSTASIS(2021) Barbosa-Caro, Juan Camilo; Feijó, José A; Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Plants perceive highly variable environments and biotic interactions through membrane receptors like the GLutamate Receptor-like (GLR) family, related to the ionotropic Glutamate Receptors that underlie information transmission in neurons. GLRs underpin information transduction and morphological adaptations in plants. However, mechanistic understanding is scarce. In Arabidopsis thaliana roots, we investigated how GLRs underlie amino acid-induced electric and Ca2+ excitability. We also assessed the contribution of GLR3.7 in root hair elongation. We present GLRs as mediators of a local, glutamate-induced electric and Ca2+ response in roots, with the same initiation kinetics of wound-induced Slow Wave Potentials (SWP). We identify GLR3.7 as mediator of root hair elongation through maintenance of membrane depolarization at the growing cell apex. These results propose a parallel between glutamate-triggered signals and SWP initial phase as local and chemically induced, and posit GLR3.7 as a possible contributor to Ca2+ homeostasis in root hair apical growth.Item LOCAL AND TOP-DOWN REGULATION OF OLFACTORY BULB CIRCUITS(2020) Hu, Ruilong; Araneda, Ricardo C; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)The olfactory bulb (OB) is the first place in the brain where chemosensory processing occurs. The neurophysiological mechanisms underlying these processes are mostly driven by inhibition, which is implemented by a large population of local inhibitory neurons, and among them, the granule cell (GCs) is the most prominent type. Local inhibitory interneurons sculpt the coding of output neurons, affecting odor detection, discrimination, and learning. Therefore, the regulation of inhibitory circuits is critical to OB function and fine-tuning OB output. Specifically, inhibitory tone in the OB can be regulated by the dynamic interactions between cell-intrinsic factors affecting neuronal excitability and extrinsic top-down modulation associated with an animal’s behavioral state. Here, I provide new evidence for intrinsic mechanisms governing inhibitory interneuron excitability in the OB and how modulation by noradrenaline works in concert with these intrinsic mechanisms to affect circuit function. This work highlights circuit- and cell-specific differences in noradrenergic modulation with regards to short- and long-term plasticity within OB circuits.Item INTRACELLULAR REGULATION OF ATRIAL EXCITATION CONTRACTION COUPLING IN NORMAL AND ARRHYTHMOGENIC HEARTS(2017) Garber, Libet; Lederer, Jonathan W; Bioengineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Atrial fibrillation (AF) is the most common arrhythmia with a prevalence of 1-2% of the US population and it is the most important single risk factor for an ischemic stroke. Despite decades of research, successful termination of the arrhythmia remains difficult. The challenge is in part due to our incomplete understanding of atrial myocyte Ca2+ signaling and underlying disease mechanisms. In the atria, like all cardiac tissue, the conducted action potential (AP) underlies triggering of the [Ca2+]i transient, which is responsible for activating contraction. The process that links electrical activity to Ca2+ signaling and contraction is known as excitation-contraction coupling (ECC). The objective of this dissertation is to understand the mechanism of excitation contraction coupling in atrial myocytes. To achieve this goal, we (1) developed tools to specifically study atrial cell biology, (2) we studied the role of altered Ca2+ buffering on ionic membrane currents and Ca2+ signaling, (3) we investigated the role that reactive oxygen species (ROS) plays in altered Ca2+ signaling and the morphology of the AP and (4) we measured intracellular sodium concentration ([Na+]i ) and studied Na+ and Ca2+ signaling in a transgenic murine model of AF. This work includes mathematical modeling of atrial cell electrical and Ca2+ signaling to define our quantitative understanding of the processes involved. Our results indicate that increased Ca2+ buffering plays a major role in speeding the inactivation of the L type Ca2+ current (ICa,L ). This work also shows that low concentrations of H2O2 for a brief period increases atrial Ca2+ spark rate, changes spark characteristics and decreases the duration of the AP. We quantified for the first time the [Na+]i in murine atrial cells both at rest and during field stimulation in control and transgenic mice. Our results indicate that [Na+]i is significantly lower in atrial myocytes in comparison to their ventricular counterparts, which reveal important differences in how [Na+]i is regulated in atrial cells. Moreover, our work demonstrates that [Na+]i and [Ca2+]i homeostasis are profoundly affected during AF. The results further our understanding of mechanisms that modulate excitation-contraction coupling in atrial myocytes in normal and pathophysiological conditions.Item Structural and semantic selectivity in the electrophysiology of sentence comprehension(2008-11-21) Stroud, Clare Margaret Anne; Phillips, Colin; Linguistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation is concerned with whether the sentence processor can compute plausible relations among a cluster of neighboring open class words without taking into account the relationships between these words as dictated by the structure of the sentence. It has been widely assumed that compositional semantics is built on top of syntactic structures (Heim & Kratzer, 1998; Pollard & Sag, 1994). This view has been challenged by recent electrophysiological findings (Kim and Osterhout, 2005; Kuperberg, 2007; van Herten et al., 2005, 2006) that appear to show that semantic composition can proceed independently of syntactic structure. This dissertation investigates whether the evidence for independent semantic composition is as strong and widespread as has been previously claimed. Recent studies have shown that sentences containing a semantically anomalous interpretation but an unambiguous, grammatical structure (e.g., The meal was devouring) elicit a P600 response, the component classically elicited by syntactic anomalies, rather than an N400, the component typically elicited by semantic anomalies (Kim and Osterhout, 2005). This has been interpreted as evidence that the processor analyzed meal as a good theme for devour, even though this interpretation is not supported by the sentential structure. This led to the claim that semantic composition can proceed independently of syntactic structure. Two event-related potentials (ERP) studies investigated whether the processor exploits prior structural biases and commitments to restrict semantic interpretations to those that are compatible with that expected structure. A further ERP study and a review of relevant studies reveal that in the majority of studies the P600 is not modulated by manipulations of thematic fit or semantic association between the open class words. We argue that a large number of studies that have been taken as evidence for an independent semantic processing stream can be explained as violations of the verb's requirement that its subject be agentive. A small number of studies in verb-final languages cannot be explained in this way, and may be evidence of independent semantic composition, although further experimental work is needed. We conclude that the evidence for independent semantic composition is not as extensive as was previously thought.Item BILAYER LIPID MEMBRANE (BLM) INTEGRATION INTO MICROFLUIDIC PLATFORMS WITH APPLICATION TOWARD BLM-BASED BIOSENSORS(2007-04-27) Hromada, Jr., Louis Paul; DeVoe, Donald L; Mechanical Engineering; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)Bilayer Lipid Membranes (BLMs) have been widely used as an experimental tool to investigate fundamental cellular membrane physics and ion channel formation and transduction. Traditional BLM experimentation is usually performed in a macro-sized electrophysiology rig, which suffers from several well-known issues. First, BLMs have short lifetimes (typically on the order of tens of minutes to a few hours) and the laborious, irreproducible membrane formation process must be repeatedly applied for long-term testing. Second, stray capacitance inherent to traditional test rigs limits the temporal response leading, for example, to poor resolution in determining fast ion channel translocation events. Lastly, BLM testing is done within a single site format thus limiting throughput and increasing data collection time. To mitigate the above drawbacks, BLM technology and microfluidic platforms can be integrated to advance the state-of-the-art of BLM-based biosensor technology. Realization of BLM-based microfluidic biosensors can offer significant improvement towards sensor response characteristics (e.g. lower noise floor, increased time response). In addition, microfluidic biosensing chips can be fabricated with multiple BLM test sites that allow for parallel testing thus increasing data collection efficiency. Other benefits that microfluidics offer are: small reagent sensing volumes, disposable packaging, mass manufacturability, device portability for field studies, and lower device cost. Novel polymer microfluidic platforms capable of both in-situ and ex-situ BLM formation are described in this work. The platforms have been demonstrated for the controlled delivery of trans-membrane proteins to the BLM sites, and monitoring of translocation events through these ion channels using integrated thin film Ag/AgCl electrodes. The detailed design, fabrication, and characterization of various micro-fabricated BLM platforms is presented in this dissertation.Item Lexical Structure and the Nature of Linguistic Representations(2006-08-09) Fiorentino, Robert D.; Poeppel, David; Linguistics; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)This dissertation addresses a foundational debate regarding the role of structure and abstraction in linguistic representation, focusing on representations at the lexical level. Under one set of views, positing abstract morphologically-structured representations, words are decomposable into morpheme-level basic units; however, alternative views now challenge the need for abstract structured representation in lexical representation, claiming non-morphological whole-word storage and processing either across-the-board or depending on factors like transparency/productivity/surface form. Our cross-method/cross-linguistic results regarding morphological-level decomposition argue for initial, automatic decomposition, regardless of factors like semantic transparency, surface formal overlap, word frequency, and productivity, contrary to alternative views of the lexicon positing non-decomposition for some or all complex words. Using simultaneous lexical decision and time-sensitive brain activity measurements from magnetoencephalography (MEG), we demonstrate effects of initial, automatic access to morphemic constituents of compounds, regardless of whole-word frequency, lexicalization and length, both in the psychophysical measure (response time) and in the MEG component indexing initial lexical activation (M350), which we also utilize to test distinctions in lexical representation among ambiguous words in a further experiment. Two masked priming studies further demonstrate automatic decomposition of compounds into morphemic constituents, showing equivalent facilitation regardless of semantic transparency. A fragment-priming study with spoken Japanese compounds argues that compounds indeed activate morphemic candidates, even when the surface form of a spoken compound fragment segmentally-mismatches its potential underlying morpheme completion due to a morpho-phonological alternation (rendaku), whereas simplex words do not facilitate segment-mismatching continuations, supporting morphological structure-based prediction regardless of surface-form overlap. A masked priming study on productive and non-productive Japanese de-adjectival nominal derivations shows priming of constituents regardless of productivity, and provides evidence that affixes have independent morphological-level representations. The results together argue that the morpheme, not the word, is the basic unit of lexical processing, supporting a view of lexical representations in which there are abstract morphemes, and revealing immediate, automatic decomposition regardless of semantic transparency, morphological productivity, and surface formal overlap, counter to views in which some/all complex words are treated as unanalyzed wholes. Instead, we conclude that morphologically-complex words are decomposed into abstract morphemic units immediately and automatically by rule, not by exception.