Traumatic Brain Injury Induces Cerebrovascular Dysfunction: Consequences For Ischemia And Cerebral Hypoperfusion, Bailey J. Whitehead

Graduate Theses, Dissertations, and Problem Reports

Traumatic brain injury (TBI) is a significant health concern across the United States as well as the broader globe, affecting millions of individuals on an annual basis. While most recover from their TBI and resume their lives normally, some subsets of TBI survivors continue to experience impairments and increased risk for future diseases like cardiovascular disease, stroke, and aging related disease like Alzheimer’s Disease or VCID.

TBI remains a fundamentally difficult neurological injury to pin down mechanistically, due to the variability in severity, timing, and age of patient, among other factors. One significant factor in the pathology has consistently been …

Structural And Functional Consequences Of Pde6 Prenylation In Rod And Cone Photoreceptors, Faezeh Moakedi

Graduate Theses, Dissertations, and Problem Reports

Phosphodiesterase-6 (PDE6) serves as a pivotal component in the phototransduction pathways of both cone and rod photoreceptors. In cones, PDE6 consists of tetrameric subunits: inhibitory (γ') and catalytic (α'). The catalytic subunit, PDE6α', contains a C-terminal prenylation motif. Deletion of this motif is associated with achromatopsia (ACHM), a form of color blindness. The mechanisms underlying the disease and the roles of PDE6 lipidation in vision remain elusive. Meanwhile, rod PDE6 is composed of α and β catalytic subunits and γ inhibitory subunits, with alterations in the C-terminal "prenylation motif" of PDE6β linked to retinitis pigmentosa (RP) pathology. In this comprehensive …

Spiking Neural Network That Maps From Generalized Coordinates To Cartesian Coordinates, Chloe K. Guie

Graduate Theses, Dissertations, and Problem Reports

In this thesis, I look to understand how insects compute task-level quantities by integrating range-fractionated sensory signals to create a sparse-spatial coding of Cartesian positions. I created biologically plausible 2-D and 3-D models of one species of the stick insect (Carausius morosus) leg and encoded the foot position through a spiking neural network. This model used spiking afferents from three angles of an insect leg which are integrated by one non-spiking interneuron. This model contains many dendritic compartments and one somatic compartment that encode the foot’s position relative to the body. The Functional Subnetwork Approach (FSA) was used …

Multimodal Neuron Classification Based On Morphology And Electrophysiology, Aqib Ahmad

Graduate Theses, Dissertations, and Problem Reports

Categorizing neurons into different types to understand neural circuits and ultimately brain function is a major challenge in neuroscience. While electrical properties are critical in defining a neuron, its morphology is equally important. Advancements in single-cell analysis methods have allowed neuroscientists to simultaneously capture multiple data modalities from a neuron. We propose a method to classify neurons using both morphological structure and electrophysiology. Current approaches are based on a limited analysis of morphological features. We propose to use a new graph neural network to learn representations that more comprehensively account for the complexity of the shape of neuronal structures. In …

Computational Mechanisms Of Face Perception, Jinge Wang

Graduate Theses, Dissertations, and Problem Reports

The intertwined history of artificial intelligence and neuroscience has significantly impacted their development, with AI arising from and evolving alongside neuroscience. The remarkable performance of deep learning has inspired neuroscientists to investigate and utilize artificial neural networks as computational models to address biological issues. Studying the brain and its operational mechanisms can greatly enhance our understanding of neural networks, which has crucial implications for developing efficient AI algorithms. Many of the advanced perceptual and cognitive skills of biological systems are now possible to achieve through artificial intelligence systems, which is transforming our knowledge of brain function. Thus, the need for …

Effects Of Development On Hpa Function Following Pubertal Stress, Brittany D. Elliott

Graduate Theses, Dissertations, and Problem Reports

For women, two of the greatest risk factors for affective disorders are adversity experienced during puberty and later becoming pregnant. We have created a translationally relevant mouse model where we address these complex risk factors. Previously, we discovered that pregnant mice (dams) that experienced chronic variable stress (CVS) during puberty display a blunted hypothalamic-pituitary-adrenal (HPA) response when exposed to an acute stressor. Interestingly, this alteration only first becomes apparent during pregnancy, which is a sensitive period for these effects due to normative neuroendocrine changes. Further investigation of the mechanisms underlying this dysfunction revealed altered gene expression in the paraventricular nucleus …

Artificial Light At Night Disrupts Pain Behavior And Cerebrovascular Structure In Mice, Jacob Raymond Bumgarner

Graduate Theses, Dissertations, and Problem Reports

Artificial Light at Night Disrupts Pain Behavior and Cerebrovascular Structure in Mice

Jacob R. Bumgarner

Circadian rhythms are intrinsic biological processes that fluctuate in function with a period of approximately 24 hours. These rhythms are precisely synchronized to the 24- hour day of the Earth by external rhythmic signaling cues. Solar light-dark cycles are the most potent environmental signaling cue for terrestrial organisms to align internal rhythms with the external day. Proper alignment and synchrony of internal circadian rhythms with external environmental rhythms are essential for health and optimal biological function.

The modern human environment on Earth is no longer …

Sense And Sensitivity: Spatial Structure Of Conspecific Signals During Social Interaction, Keshav Ramachandra

Graduate Theses, Dissertations, and Problem Reports

Organisms rely on sensory systems to gather information about their environment. Localizing the source of a signal is key in guiding the behavior of the animal successfully. Localization mechanisms must cope with the challenges of representing the spatial information of weak, noisy signals. In this dissertation, I investigate the spatial dynamics of natural stimuli and explore how the electrosensory system of weakly electric fish encodes these realistic spatial signals. To do so In Chapter 2, I develop a model that examines the strength of the signal as it reaches the sensory array and simulates the responses of the receptors. The …

Spatial Processing Of Conspecific Signals In Weakly Electric Fish: From Sensory Image To Neural Population Coding, Oak Everette Milam

Graduate Theses, Dissertations, and Problem Reports

In this dissertation, I examine how an animal’s nervous system encodes spatially realistic conspecific signals in their environment and how the encoding mechanisms support behavioral sensitivity. I begin by modeling changes in the electrosensory signals exchanged by weakly electric fish in a social context. During this behavior, I estimate how the spatial structure of conspecific stimuli influences sensory responses at the electroreceptive periphery. I then quantify how space is represented in the hindbrain, specifically in the primary sensory area called the electrosensory lateral line lobe. I show that behavioral sensitivity is influenced by the heterogeneous properties of the pyramidal cell …

Cue Reactivity In Electronic Cigarette Users With Sign-Tracking Or Goal-Tracking Behaviors, Polina Krom

Graduate Theses, Dissertations, and Problem Reports

Polina Krom

Cue reactivity is an important predictor of addiction course and relapse. However, cue reactivity is only observed after an addiction develops. As such, it is unclear to what degree cue reactivity represents a state stemming from the addiction process versus a trait-like propensity towards developing cue-reward associations. Work in animal models has pointed to important individual differences in trait-like inclination to attribute incentive salience to reward-predictive cues that is associated with addiction-relevant behavioral and neurobiological features. These individual differences manifest as sign-tracking (ST) and goal-tracking (GT) behaviors during Pavlovian conditioning. Little research has attempted to translate ST and …

An Investigation Into The Mechanism Of Proteasome Dysfunction In Neurodegenerative Disease And The Biological Impact Of Proteasome Hyperactivation In C. Elegans, Raymond T. Anderson

Graduate Theses, Dissertations, and Problem Reports

Aging is an inevitable process that occurs as humans grow older. It is characterized by the chronological accumulation of cellular damage over time leading to functional decline as an organism grows older. Several processes are thought to contribute to the aging phenomenon, but one of the most prolific of these is the disruption of protein homeostasis (proteostasis). The collapse of proteostasis can lead to accelerated aging and the development of age-related diseases including devastating neurodegenerative diseases (NDs) like Alzheimer and Parkinson disease. Virtually all NDs are characterized by the buildup of proteins in and around neurons resulting in neuronal death …

A Combinatorial 5-Htr Expression Pattern Within The Ventral Projection Neurons Of The D. Melanogaster Olfactory Circuit., Mohd Freezely Ezzani Bin Mazri

Graduate Theses, Dissertations, and Problem Reports

Neuromodulation allows neurons within a circuit to respond to stimuli from the environment according to the correct ecological value, context, and internal state of the animal. Serotonin (5-HT) is a neuromodulator that can generate different outcomes based on its target’s serotonin receptor (5-HTR) expression by affecting secondary messenger cascades. Within the Drosophila olfactory system, ventral projections neurons (vPN) express all five insect 5-HTR that project into two olfactory processing regions, the antennal lobe (AL) and the lateral horn (LH). The significance of this 5-HTR expression is unknown. In this study, I theorized the patterns of 5-HTR expression of vPNs. I …

Exploiting Modulation Of The Blood-Brain And Blood-Tumor Barrier Permeability By Translational Focused Ultrasound For Therapeutic Delivery To Cns Metastases, Tasneem A. Arsiwala

Graduate Theses, Dissertations, and Problem Reports

Transcranial low-intensity focused ultrasound is a unique technology to modulate the integrity of tight endothelial junctions and transiently increase BBB/BTB permeability to enhance therapeutic delivery. Despite promising early studies, present literature lacks agreement on key experimental conditions, which restricts our knowledge and the technique's widespread translation. This dissertation first provides a critical review of the current gaps in knowledge regarding the universal use of LiFUS in preclinical and clinical use. We then identify key parameters for translational and predictable opening of the BBB using a 3T MRI coupled with a clinical device. Our investigation highlights that passive permeability of the …

Mechanistic Insight Into Chronic Stress-Induced Cerebrovascular Dysfunction, Emily Nicole Burrage

Graduate Theses, Dissertations, and Problem Reports

Despite decades of research psychological stress remains a prevalent problem in society, often diminishing quality of life and increasing the risk of developing dementia. The brain plays a central role in the response to stress and as it is unable to store energy substrates, the brain relies heavily on dynamically regulated blood flow. Therefore, it is important that there is a tight coupling between neural activity and cerebral blood flow to meet metabolic demands and maintain critical brain function. It has been established that chronic psychological stress has detrimental effects on cerebrovascular function, potentially through increased superoxide anion production through …

Examining Development And Function Of Pretectal Visual Neural Circuits In Gs Homeobox 1 Mutant Zebrafish, Alexandra Rose Schmidt

Graduate Theses, Dissertations, and Problem Reports

Brain development requires a coordinated genetic code to regulate initial cell identity determination, migration, and connectivity, to establish function of neural circuits. Independent neural circuits underlie our ability to produce both complex and innate behavioral responses to sensory stimuli that are often conserved across vertebrate organisms. Sensory processing disruptions are associated with several neurodevelopmental disorders (NDDs). Therefore, gene mutations altering neurodevelopment can lead to changes influencing structure and function of individual neural circuits, causing behavioral deviations in sensory responsiveness. Crucial gene networks that define functional properties of sensory domains are often explored using non-mammalian vertebrate models, such as the zebrafish. …

Biomechanically Inspired Assistive Technology To Restore Movement Of The Upper Limbs After Stroke, Ariel Thomas

Graduate Theses, Dissertations, and Problem Reports

A stroke often damages the neural structures responsible for movement. Stroke is a heterogeneous disease, affecting each survivor differently. There are common motor features of a stroke, but even these features vary across time as an individual proceeds through different stages of recovery. The different ways in which stroke motor impairment can present itself are often overlooked, but these differences are fundamental to the understanding of the disease and its recovery. When motor assessments are capable of acquiring information necessary to parse out a detailed profile of each stroke case, this will lead to an improved neuromechanical understanding of the …

Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls

Graduate Theses, Dissertations, and Problem Reports

This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …

Investigating The Role Of Attention And Memory In Visual Exploration, Jacob E. Suffridge

Graduate Theses, Dissertations, and Problem Reports

This research investigates the role that attention and memory plays in visual exploration through a comprehensive analysis of eye movement and behavioral data, alongside incorporation of a computational saliency model. The purpose of this project is to quantify differences in visual attention over repeated viewings of natural scene images by employing a free viewing task that contains a memory component. In Chapter 2, we explore the task’s behavioral data showing that participants generally memorize our images well before we investigate the effect of numerous object and individual feature inclusion. In Chapter 3, we develop four primary methods to quantify visual …

Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor

Graduate Theses, Dissertations, and Problem Reports

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …

Describing A Putative Corollary Discharge Circuit In Drosophila, Kaitlyn Nicole Boone

Graduate Theses, Dissertations, and Problem Reports

Corollary discharge (CD) circuits provide critical information about movement and behavior to provide context to sensory processing. However, to date, there has not been a comprehensive study of CD circuits at a single-cell level. In this thesis, I aimed to resolve the connectivity of ascending histaminergic neurons, consisting of two pairs, the mesothoracic pair (MsAHNs) and metathoracic pair (MtAHNs) at a single-cell level and characterize contexts of activation. Using transgenic techniques, connectomics and transcriptomics, we identify neural populations receiving input from the AHNs and neural populations with significant output to the AHNs. We explored where the AHNs predominantly receive synaptic …

Manipulating The Perineuronal Net In The Deep Cerebellar Nucleus, Deidre E. O'Dell

Graduate Theses, Dissertations, and Problem Reports

Perineuronal nets (PNN) are a type of specialized extracellular matrix in the central nervous system. The PNN forms during postnatal development but the ontogeny of the PNN has yet to be elucidated. Studying the PNN in the rat brain may allow us to further understand the PNN’s role in development, learning, and memory. The PNN is fully developed in the deep cerebellar nuclei (DCN) of rats by post-natal day 18. By using enzymatic digestion of the PNN with chondroitinase ABC (ChABC), we studied how digestion of the PNN affects cerebellar-dependent eyeblink conditioning (EBC) and performed electrophysiological recordings from DCN neurons. …

Using Zebrafish To Elucidate The Expression And Gene Regulatory Network Of The Genomic Screen Homeobox Transcription Factors And Bring Innovative Science Learning Experiences To West Virginia, Rebecca Ann Coltogirone

Graduate Theses, Dissertations, and Problem Reports

Central nervous system (CNS) development requires a code of regionally expressed transcription factors that impart initial neuronal cell identity, connectivity, and function. The absence of a transcription factor code would eliminate the neurodevelopmental logic producing diverse cell types in the CNS. Furthermore, early disruptions in transcription factor expression can affect later connectivity and function of neuronal circuits mediating sensory processing, defects in which are often observed as comorbid with various neurodevelopmental disorders (NDDs). Characterizing transcription factor expression and function is therefore an essential step in discerning the molecular mechanisms underlying human NDDs. genomic screen homeobox 1 and 2 (gsx1 …

The Receptor Basis Of Serotonergic Modulation In An Olfactory Network, Tyler Ryan Sizemore

Graduate Theses, Dissertations, and Problem Reports

Neuromodulation is a nearly ubiquitous process that endows the nervous system with the capacity to alter neural function at every level (synaptic, circuit, network, etc.) without necessarily adding new neurons. Through the actions of neuromodulators, the existing neural circuitry can be adaptively tuned to achieve flexible network output and similarly dynamic behavioral output. However, despite their near ubiquity in all sensory modalities, the mechanisms underlying neuromodulation of sensory processing remain poorly understood. In this dissertation, I address three main questions regarding the mechanisms of one modulator (serotonin) within one sensory modality (olfaction). I begin by establishing a "functional atlas" of …

Mitochondrial Aspects Of Neuronal Pathology In Triple-Transgenic Alzheimer’S Disease Mice, John Zachary Cavendish

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a fatal, progressive neurodegenerative disease afflicting millions of people in the United States alone and is the only one of the top leading causes of morbidity and mortality with no effective disease-modifying therapies. It is the most common form of dementia, affecting one in three people over the age of 85. While the hallmarks of the disease include accumulation of beta-amyloid-based extracellular plaques and hyperphosphorylated tau-based intracellular neurofibrillary tangles, treatment strategies centered on removing or mitigating these components of AD have all failed in humans. Mitochondrial dysfunction has been increasingly recognized as an early and consistent …

Cerebrovascular Dysfunction And Degeneration In Alzheimer’S Disease Pathophysiology, Dominic Dimitri Quintana

Graduate Theses, Dissertations, and Problem Reports

Alzheimer’s disease (AD) is a terminal illness and the most common form of dementia, which disproportionately affects the aged population. The pathophysiology of AD is characterized by neurodegeneration that slowly progresses, affecting regions of the brain that are involved in learning, memory, language, and executive function. In patients with the disease, early symptoms include non-disruptive forgetfulness that evolves into the inability to form new memories and ultimately the loss of autonomy at late stages. Histopathological hallmarks in the brain from patients with AD is the presence of amyloid-β (Aβ)-plaques and neurofibrillary tangles (NFT) deposited in the parenchyma. Since the discovery …

The Interplay Of Progestins, Matrix Metalloproteinases, And The Aging Brain, Keyana Nicole Porter

Graduate Theses, Dissertations, and Problem Reports

Progestins are synthetic hormones that are designed to mimic the biological actions of progesterone. They, however, possess other pharmacological actions and properties, in addition to their progestational activities. Medroxyprogesterone Acetate (MPA) is a progestin used globally in the hormonal contraceptive, Depo Provera®, by women in their reproductive prime and is a major compound found in hormone therapy (HT) formulations used by menopausal women. MPA is used by approximately 1 in 5 adolescents and adult women in the United States who are sexually active. Globally, nearly 48 million women utilize injectable contraceptives to prevent pregnancy, with most users utilizing MPA as …

A Flight Sensory-Motor To Olfactory Histamine Circuit Mediates Olfactory Processing Of Ecologically And Behaviorally Natural Stimuli, Samual P. Bradley

Graduate Theses, Dissertations, and Problem Reports

Environmental pressures have conferred species specific behavioral and morphological traits to optimize reproductive success. To optimally interact with their environment, nervous systems have evolved motor-to-sensory circuits that mediate the processing of its own reafference. Moth flight behavioral patterns to odor sources are stereotyped, presumably to optimize the likelihood of interacting with the odor source. In the moth Manduca sexta wing beating causes oscillatory flow of air over the antenna; because of this, odorant-antennal interactions are oscillatory in nature. Electroantennogram recordings on antennae show that the biophysical properties of their spiking activity can effectively track odors presented at the wing beat …

Neuroimaging Of Real-World Audio-Visual Sensory Integration In High-Functioning Autism, Paula J. Webster

Graduate Theses, Dissertations, and Problem Reports

Sensory processing differences are a prevalent aspect of autism spectrum disorder (ASD) that may contribute to core deficits of ASD such as repetitive behaviors as well as comorbidities including anxiety disorders. The ability to integrate information among our senses is required to comprehend the world around us and is crucial for the development of language, motor skills, and social communication. Prior studies have shown that individuals with autism differ from individuals without autism when presented with simple, non-natural audio-visual stimuli such as basic shapes accompanied by pure tones. Because the human brain processes non-natural and natural stimuli differently, more recent …

Automated And Standardized Tools For Realistic, Generic Musculoskeletal Model Development, Trevor Rees Moon

Graduate Theses, Dissertations, and Problem Reports

Human movement is an instinctive yet challenging task that involves complex interactions between the neuromusculoskeletal system and its interaction with the surrounding environment. One key obstacle in the understanding of human locomotion is the availability and validity of experimental data or computational models. Corresponding measurements describing the relationships of the nervous and musculoskeletal systems and their dynamics are highly variable. Likewise, computational models and musculoskeletal models in particular are vitally dependent on these measurements to define model behavior and mechanics. These measurements are often sparse and disparate due to unsystematic data collection containing variable methodologies and reporting conventions. To date, …

The Wiring Logic Of Identified Serotonergic Neurons Across Olfactory Networks In Drosophila, Kaylynn E. Coates

Graduate Theses, Dissertations, and Problem Reports

Serotonin is a ubiquitous neuromodulator that confers flexibility in networks to modulate a wide array of behavioral and physiological processes. However, due to the complexity and heterogeneity of serotonergic systems, it has been challenging to determine the patterns of connectivity as well as the physiological contexts that influence individual serotonin neurons. In this dissertation, I use two serotonergic neurons which innervate the Drosophila olfactory system, the CSDns, as a model to explore these broad questions comprehensively using anatomical approaches. I first show that the CSDns have distinct connectivity relationships with populations of antennal lobe principal olfactory neurons and that their …