Neuroscience and Neurobiology Commons^™

Stromal Interaction Molecule (Stim) Proteins In Microglia And The Impact On Store-Operated Calcium Entry (Soce) And Spinal Cord Injury Recovery, Norah G. Hill

College of Arts & Sciences Senior Theses

In spinal cord injury (SCI), worsening functional outcomes are largely because of secondary injury processes and prolonged chronic inflammation. A major contributor of secondary injury is overload of intracellular calcium, causing neuronal overexcitation and persistent inflammatory responses. One of the primary mediators of calcium entry into the cell is store-operated calcium entry (SOCE). In SOCE, sensors detecting calcium depletion from the endoplasmic reticulum stores are called STIM proteins (1-2). When calcium is low in the cell, STIM proteins will activate Orai channels to open, allowing for the influx of calcium into the cell. The purpose of this study was to …

The Influence Of Valence On Action Control: A Comparison Of Simon Effects In The Extrinsic Affective Simon Task (East) And The Spatial Simon Task, Yaara Aleissa

College of Arts & Sciences Senior Theses

People adjust their thoughts and actions in response to a changing environment every day and emotions may influence these actions. Understanding how emotion impacts action control in situations where emotion is central to the action (task-relevant) compared to when it is present in the environment as distracting information (task-irrelevant) is essential. Currently it is unclear when emotion most significantly modulates action control. This study seeks to compare how valence (positive versus negative emotion) impacts action control performance when valence is task-relevant and task-irrelevant by using two modified versions of the Simon conflict task.

The Simon task is a paradigm to …

Expanding Access To Noninvasive Spinal Neuromodulation For Pediatric Spinal Cord Injury Rehabilitation: A Comparative Device Study, Alice E C Palmer

College of Arts & Sciences Senior Theses

Paralysis following spinal cord injury (SCI) has traditionally been considered permanent due to the disruption of supraspinal input to spinal motor circuits. However, growing evidence suggests that spinal networks below the level of injury retain intrinsic motor-generating capabilities through central pattern generators. Transcutaneous spinal cord stimulation (scTS) is a noninvasive neuromodulation technique that delivers electrical stimulation through the skin to reactivate these spinal networks. Although prior studies demonstrate that scTS delivered through research-grade devices is safe and effective in adults and children with chronic SCI, clinical translation remains limited by lack of FDA-approved systems, high costs, and restricted access to …

Using A Toxic Aging Coin To Assess Hexavalent Chromium Neurotoxicity: Impact Of Cr(Vi) On The Blood-Brain Barrier, Liam Buchanan

College of Arts & Sciences Senior Theses

The US population faces simultaneous public health threats from both aging and environmental pollutants. Chief among these is hexavalent chromium [Cr(VI)], whose toxic effects in peripheral tissues are well-established but its effects on the brain are still understudied. Following previous results indicating hippocampal metals dyshomeostasis after Cr(VI) exposure, we aim to assess Cr(VI)’s impact on the blood-brain barrier (BBB), a key structure for brain protection. We exposed young, middle-aged, and geriatric rats of both sexes to low levels of Cr(VI) in their drinking water for 90 days, after which we used immunofluorescence and confocal microscopy to analyze tissues for evidence …

Hsp90 Inhibitor In Reducing Integrated Stress Response In An Experimental Mouse Model Of Spinal Cord Injury, Yousef Abozaid, Aditya Sarkar, Lukasz P. Slomnicki, Michal Hetman

The Cardinal Edge

Spinal cord injury (SCI) initiates a complex cascade of molecular events, including protein misfolding and neuroinflammation, contributing to neural damage and impaired functional recovery. Heat Shock Protein 90 (HSP90), a critical molecular chaperone involved in cellular stress responses, emerges as a promising therapeutic target to mitigate secondary damage after SCI. This study was designed to validate the in-vivo effects of different doses of HSP90 inhibitor, HSP990-i, administered acutely after moderate T9 SCI mouse model. The level of HSP70 protein level is measured through western blot from the injury epicenter. Adult mice underwent experimental contusive SCI at the T9 level, followed …

Hallucinogens For Mood And Anxiety Disorders: A Critical Review Of Psychedelic-Assisted Therapies, Georgia Chlebek

The Cardinal Edge

In quite a few people worldwide, there are several mental disorders that prevent the brain from operating in the “proper” way, depression, anxiety, and post-traumatic stress disorder (PTSD) being among the most common. Luckily, there are several medications that are produced and used to treat these disorders, but some medications are hard to access, and others simply don’t help the patient. Firstly, these medications take time to study and prove safe for public use, though in some cases time is not readily available. In other cases, these medications are going through shortages and becoming increasingly difficult for patients to access …

Disrupted Nuclear Function And Nucleocytoplasmic Transport In Parkinson’S Disease, Ichiro M. Matoba

The Cardinal Edge

No abstract provided.

Mindreading And Embodiment: Beyond Mirror Neurons., Sanad Al Khatib

College of Arts & Sciences Senior Theses

This paper examines the question: how do we figure out what other people are thinking and why they act as they do, or put differently, how is it that we can read minds in daily life? For decades, the dominant view held that we explain and predict other people’s behavior by attributing to them mental states such as beliefs, desires, and intentions, represented symbolically in the brain. The embodied simulation model challenges this view, proposing that understanding others primarily relies on mirror neurons that activate both when we perform an action and when we observe someone else performing it. This …

Examing Fear Conditioning/Extinction And The Role Of The Amygdala In Human Neuroimaging., Olivia Cook

Electronic Theses and Dissertations

Fear plays a crucial role in survival but can lead to psychological disorders when dysregulated. Fears can be innate due to evolutionary relevance or learned through associative processes, where predictive accuracy of threat is pivotal. Disruptions in fear neurocircuitry contribute to anxiety disorders, characterized by heightened activation and impaired learning. Fear conditioning and extinction paradigms based on classical Pavlovian conditioning have been used to study mechanisms underlying fear learning. Using this experimental model, fear networks in rodents have been described in detail with clear distinction between conditioning and extinction neural functioning. Yet, there is no consensus on the neurobiological processes …

Integration And Modulation Of Visual Signals In Dorsal Thalamus., James Whitley

Electronic Theses and Dissertations

The visual thalamus is influenced by a diverse array of cortical and subcortical inputs that shape how information is transmitted to cortex. Using a variety of anatomical, optogenetic, and in vitro physiological techniques I investigated the differential impacts of modulation and integration of first and higher-order thalamic nuclei, while relying on influential concepts on the general organization of thalamic nuclei. In the first data chapter, I determined how GABAergic pretectum (PT) projections to the dorsal lateral geniculate nucleus (dLGN) and visual thalamic reticular nucleus (vTRN) can influence retinogeniculate signal transfer. We found that the PT provides over 75% of the …

Genetic Identification Of A Rapidly-Adapting Low-Threshold Mechanoreceptor Innervating Fungiform Papillae., Thomas Alexander Myers Ii

Electronic Theses and Dissertations

Mechanosensory innervation of the oral cavity enables us to detect the texture and location of the foods we consume. Our goal was to find a genetic identifier for a mechanoreceptive subtype. Toward this goal, we examined neurons expressing the neurotrophin receptor TrkC, parvalbumin (Pvalb), and the glutamate transporter Vglut3. Because different papilla types contribute to food detection in different ways, we examined the innervation patterns of these neuron subtypes. We found that Pvalb+ and Vglut3+ neurons were fungiform papilla specific, where TrkC innervated both papilla types. We examined the anatomy of the three genetic populations, finding that the Pvalb+ neurons …

Sensory And Motor Tectothalamic Circuits: Two Sides Of The Same Coin., Nazratan Naeem

Electronic Theses and Dissertations

Integration of sensorimotor information in the visual system has always been an intriguing topic to scientists, yet the subcortical sensory and motor circuits that are essential components of this process have remained elusive. In these studies, we used a blend of classical and contemporary techniques such as viral tracing, immunohistochemistry, optogenetics in-vitro whole cell electrophysiology, and electron microscopy in mice to characterize sensory and motor circuits of the superior colliculus (SC), a conserved visuomotor structure with connections with a wide variety of brain structures, including the thalamus. We focused on two SC cell types: visually responsive widefield vertical (WFV) cells …

Odor Concentration Matters: How Odor Concentration Guides Consummatory Behavior And Formation Of Odor-Taste Associations In Rats, Dinna N. Ferreira

College of Arts & Sciences Senior Theses

Taste concentration is a key determinant of palatability. For example, higher concentrations of sucrose, a sweet taste, are typically preferred to lower ones, whereas the opposite is true for citric acid, a sour taste. Yet taste is not the only determinant of food preference. Flavor arises from the integration of taste and olfactory cues, and repeated exposure to odor-taste combinations can lead odors to acquire the hedonic value of their associated taste. However, the contribution of odor concentration, independent of taste, in guiding consummatory behavior is not well understood.

To address this, we conducted two experiments using a two-bottle brief-access …

Anterior Cingulate Cortex Connectivity And The Role In Neuroticism: A Diffusion-Weighted-Imaging-Based Investigation Of Limbic And Prefrontal Circuits., Jake Cox Ii

College of Arts & Sciences Senior Theses

Neuroticism is a trait which has been shown to significantly predict psychopathology. Investigating its neurobiological underpinnings may uncover a brain-based relationship that allows clinicians to conceptualize a shared predispositional factor across multiple psychopathologies, implicating treatment protocols. Inter-connectivity network and structural variation has been shown to be implicated in neuroticism, more specifically the frontoparietal network, default mode network, salience networks, and limbic networks. These networks tackle executive, salience, and emotional information, respectively. The anterior cingulate cortex (ACC) is a brain region nested between and functionally related to various networks stated above that are implicated in neuroticism. As such, it was hypothesized …

Minimizing Secondary Spinal Cord Injuries With Hypertonic Saline., Francisco A. Cortez-Thomas

Master of Engineering Theses

Spinal cord injury (SCI) disrupts white matter, causing periaxonal swelling, axonal degeneration, and impaired function. To examine vascular edema’s role, we developed a 3Dprinted dual-compartment imaging chamber to mimic and manipulate interstitial and vascular fluid dynamics in real time. We hypothesized that hypertonic saline (HTS) in the "vascular" chamber would osmotically shift fluid from the periaxonal space and preserve myelinated fibers after SCI. Using two-photon excitation microscopy, we imaged myelin and axons ex vivo in Thy1^YFP+ transgenic mice following C5 contusive SCI and assessed three clinically relevant HTS concentrations versus normal saline for their effectiveness in mitigating periaxonal swelling …

Defining The Peripheral Plasticity Of Nociceptive Afferents Following Spinal Cord Injury And Physical Therapy Intervention., Morgan Julianna Forston

Electronic Theses and Dissertations

The focus of this dissertation is to explore the peripheral plasticity of nociceptive afferents following spinal cord injury (SCI) and whether it is exacerbated or induced when physical therapy-based muscle stretching, a therapy we have shown to be detrimental to locomotor recovery in rodents, is implemented post-SCI. Chapter I provides a brief introduction on sensory afferents with particular emphasis on nociceptive afferents and their multifaceted role within the peripheral and central nervous systems. Chapter II describes SCI epidemiology and common sensory related complications that occur in patients as well and pharmaco- and physical therapies that are employed post-SCI. Chapter III …

Increased Neuroinflammation And Compromised Blood Brain Barrier In A Mouse Model Of Autism, Amani S. Ikram, Rekha Jagadapillai, Idil Tuncali, Gregory N. Barnes, Evelyne Gozal

The Cardinal Edge

No abstract provided.

Low Concentrations Of Hexavalent Chromium In Drinking Water Induce Alzheimer’S Disease Neuropathology: Using A Toxic Aging Coin Approach To Assess Hexavalent Chromium Neurotoxicity, Liam Buchanan, Samuel Vielee, Spencer Roof, Haiyan Lu, Jamie L Young, Idoia Meaza Isusi, Aggie Williams, Joseph Kouokam, Sandra Wise, Luping Guo, Jun Cai, John Wise, John P. Wise Jr.

The Cardinal Edge

Introduction: We are currently facing an aging crisis, as 20% of the U.S. population will be geriatric (65+) by 2030. This growing geriatric population will result in increasing prevalence of age-related diseases, coinciding with increasingly prevalent environmental pollution. Environmental pollution is a ubiquitous health threat that affects people at all ages and contributes to aging pathology. However, geriatric individuals are likely more susceptible to the negative health effects from environmental pollution. The distinct effects of environmental pollutants across age groups are currently understudied. We use a Toxic Aging Coin approach to investigate: 1) how age impacts toxicity (heads), …

Emotional Content In Working Memory Processes: An Fmri Study., Manal Zafar

Electronic Theses and Dissertations

Working memory (WM) is a dynamic system that processes and manipulates both goal-relevant and goal-irrelevant information, integral to higher-level cognition and executive control (Fujii, 2001; Nyberg & Erikkson, 2016). The processing and manipulation of representations is modulated by the affective nature of the information (Pessoa, 2009) such that negative information can either impair or enhance WM processing. WM impairments are seen commonly across clinical disorders such as depression, anxiety, PTSD and schizophrenia (Levens & Gotlib, 2010; Joorman et a., 2011; Brodziak et al., 2015). Specifically, negative information is known to have differential processing in WM compared to neutral and positive …

Epidural Stimulation For Urogenital Dysfunction In The Spinal Cord Injured Rat., Natasha Lorraine Wilkins

Electronic Theses and Dissertations

Spinal cord injury (SCI) is a devastating, life changing event that greatly impacts quality of life. SCI can have body-wide, multi-system consequences including dysfunction within the urogenital system. Challenges with the urinary system include urinary incontinence, urine retention, and detrusor-sphincter dyssynergia all of which require maintenance through the regular use of catheters. Sexual dysfunction in men, who comprise nearly 80% of the SCI population, includes erectile dysfunction, anejaculation, retrograde ejaculation, poor expulsive force during ejaculation, and poor sperm quality. The treatment for sexual function in SCI men is focused more on fertility through the collection of sperm for insemination procedures …

Establishing A Mouse Model Of Cerebral/Cortical Visual Impairment., Dana K. Oakes

Electronic Theses and Dissertations

Cerebral/cortical visual impairment (CVI) is a disorder most often caused by perinatal hypoxic injury to the developing brain. CVI is the leading cause of childhood visual impairment in developed nations, encompassing deficits in many aspects of vision including visual acuity, contrast sensitivity, and object recognition. The pathophysiology of CVI is not well understood because no animal model currently exists to study this disorder. Because there is no animal model, the pathophysiology of CVI is poorly understood. Here, we developed a murine early postnatal hypoxic model of CVI by exposing mice to 9.5% O₂ at postnatal day (P)3 for a …

Sdf-1Α Mediates Primary Tumor Escape In Glioblastoma Through Activation Of Mesenchymal Transitions., Charles T. Froman-Glover

College of Arts & Sciences Senior Theses

Glioblastoma (GBM), a highly aggressive primary brain tumor originating in glial cells, poses a significant challenge due to its rapid growth and invasive nature within healthy brain tissue.

Current treatments involve surgical resection, chemotherapy, and radiation. These treatments alone are not enough to cure this disease, and a better understanding the mechanics of the tumor micro-environment is imperative to furthering the field of cancer research. This research focuses on understanding the tumor microenvironment's impact, specifically investigating the role of stromal cell-derived factor 1 (SDF-1) mechanics on GBM aggressiveness. SDF-1 is known to facilitate disease progression by facilitating chemotaxis toward the …

Assessing The Role Of Stim1 And Stim2 In Microglial Response To Spinal Cord Injury., Sarayu Alli

College of Arts & Sciences Senior Theses

Microglia, immune cells of the central nervous system, constantly survey their environment for damage. Once damage is detected, they are activated into become reactive, resulting in morphological changes, such as larger cell bodies, and functional changes, such as releasing inflammatory mediators. The switch from surveying to reactive occurs because the microglia received signals that sense danger in the environment. The release of Ca2+ from intracellular stores is involved in store-operated calcium entry (SOCE), a signaling pathway. Recent studies have shown that calcium release from the intracellular stores is a factor of microglial activation. SOCE is specific to monitoring low calcium …

Exploring Resilience With Neuroimaging: Moderators Of The Impacts Of Childhood Traumatic Stress On Fear Processing., Karisa June Hunt

Electronic Theses and Dissertations

Childhood trauma is an alarming public health crisis, and the field of trauma research is relatively underdeveloped given population rates of childhood trauma and post-trauma pathology. Even less studied than the impacts of trauma are the impacts of resilience, and the protective factors that foster it. It is widely acknowledged that an investigation of trauma is incomplete without an investigation of its impacts on fear processing. Understanding the neural underpinnings of resilience to childhood trauma during fear conditioning is vital to the development of therapeutic interventions able to moderate its devastating impacts. The present study investigated the complex neurobiological interplay …

Using A Toxic Aging Coin To Assess Hexavalent Chromium-Induced Neurotoxicity., Samuel Thomas Vielee

Electronic Theses and Dissertations

We are facing an aging crisis, with 20% of the U.S. population projected to be geriatric (65+) by 2030 and live another 40+ years. Age-related diseases accompany a growing geriatric population, emphasizing the need to understand their etiology. Environmental pollutants compound this crisis by: 1) geriatrics are more susceptible, exacerbating age-related diseases and comorbidities, and 2) they accelerate biological aging, inducing age-related diseases at younger ages. We address this crisis using a ‘toxic aging coin’ approach; heads examines how age impacts toxicity, tails examines how chemicals accelerate aging. This thesis applies the heads side for Cr(VI)-induced neurotoxicity across ages. We …

The Neural Sequalae Of Subjectively Experiencing Autobiographical Memories From The Remote Past And Recent Present Using Fmri, Ava G. Peruski, Nim Singh, Brendan E. Depue

The Cardinal Edge

Autobiographical memory is central to one's sense of self and continuity from past to present. Despite this, there is little research on the neural correlates underlying individual subjective experience of autobiographical memory and how that is related to brain phenomena (i.e., activity, communication). The purpose of this study was to help minimize this gap. We recruited twenty healthy adult participants, who were asked to generate memory cues (1-3 word descriptions) for locations and objects from their early and recent life. After 24 hours, participants were shown these cues then asked to recall the appropriate memory while in an fMRI scanner. …

All-Cause And Opioid-Related Mortality Compared Between Traumatic Spinal Cord Injury And The Us General Population, Jaden Whitehead, Beatrice Ugiliweneza

The Cardinal Edge

Individuals with spinal cord injury (SCI) are susceptible to the misuse of opioids due to the introduction of these substances for pain management. There are very few studies examining the relationship between unintentional deaths caused by opioid usage following spinal cord injury. The objective of this study was to evaluate the trend of opioid-related mortality of individuals with spinal cord injury (SCI) over the years and compare these findings to the mortality rates due to opioid misuse in the general population. In this study, we used data provided by the National Spinal Cord Injury Model Systems (NSCIMS) for SCI 1999-2016 …

Novel Insights Into Oligodendrocyte Biology From Developmental Myelination Studies In Autophagy Deficient Mice And Analysis Of Oligodendrocyte Translatome Response To Contusive Spinal Cord Injury., Michael David Forston

Electronic Theses and Dissertations

Loss of myelin causes severe neurological disorders and functional deficits in white matter injuries (WMI) such as traumatic spinal cord injury (SCI). This dissertation is focused on autophagy in OL development and the OL translatome after SCI. Chapter I describes the history of myelin, OL development, and their involvement in neurodegenerative diseases and SCI. The proteostasis network, in particular autophagy, and its contributions to white matter pathology is discussed. It concludes examining advantages and disadvantages of unbiased omics tools, like RiboTag, to study transcriptional/translational landscapes after SCI. Chapter II focuses on autophagy in OPC/OL differentiation, survival, and proper myelination in …

Connectivity Of Amygdala Somatostatin-Expressing Neurons And Their Role In Taste-Guided Behavior., Jane Jeruto Bartonjo

Electronic Theses and Dissertations

The nucleus of solitary tract (NST) and parabrachial nucleus (PBN) represent the first and second central synapses of ascending gustatory information. Neural processing in these nuclei is influenced by descending input from forebrain regions such as the central nucleus of the amygdala (CeA). In mice, we have shown that somatostatin (Sst) expressing neurons of CeA that project to NST and PBN are largely distinct cell populations and optogenetic inhibition of the CeA/Sst-to-NST subpopulation increases the intake of high concentrations of quinine with no apparent effect on sucrose intake. Synaptic connectivity of these cells is needed to understand the possible mechanisms …

Immobilization And Its Effects On Functional Recovery After Spinal Cord Injury., William H. Gregory

College of Arts & Sciences Senior Theses

Recovery, or rather the failure to recover, is a perplexing issue of spinal cord injury that is currently being investigated. This issue becomes more puzzling when investigating models in which spinal cord injury (SCI) is studied. There appears to be greater functional recovery experienced by animals within these models after injury as compared to patients in the clinical setting. While many things could contribute to this disparity, one difference that stands out when comparing the basic research model and clinical experience of SCI is the inactivity and limb disuse after the injury. This same level of immobility is rarely accounted …