Neuroscience and Neurobiology Commons^™

Perivascular Waste Metabolites Clearance In Central Nervous System (Cns), Yiming Cheng

Dissertations

Efficient clearance of interstitial waste metabolites is essential for normal brain homeostasis. Such effective clearance is hampered by the lack of a lymphatic system in the brain, and the cerebrospinal fluid (CSF) is unable to clear large size waste metabolites in the brain. Here, a novel idea that brain arterial endothelium and smooth muscle cells reactivity regulates the clearance of these water-insoluble large size waste metabolites through the perivascular dynamic exchange, and that low dose ethanol promotes this perivascular clearance is proposed.

In Aim 1, the biodistribution of a large size waste metabolite (Amyloid-β protein mimic) in rat perivascular space …

Cerebro-Vascular Disruption Mediated Initiation And Propagation Of Traumatic Brain Injury In A Fluid Percussion Injury Model, Xiaotang Ma

Dissertations

Traumatic brain injury (TBI) is a major health problem for over 3.17 million people in the US. There is no FDA-approved drug for the treatment because the injury mechanisms have not been clearly identified. The knowledge gap is addressed here by the lateral fluid percussion injury (FPI) rat model, through the understanding of layer-structured mechanisms from physical vascular rupture to acute necrosis, as well as biochemical changes in perivascular space as secondary events.

Firstly, the cerebrovascular hemorrhage and related infarct volume are investigated as the primary events in moderate FPI, which is found to be increased with injury severity in …

Sexual Dimorphism In A Mouse Model Of Dry Eye Disease, Neal Mecum

Electronic Theses and Dissertations

Dry eye can result from multiple causes, including a reduction in the quantity or altered composition of tears. The lacrimal gland is the major supplier of the aqueous tear components, including water, electrolytes, and proteins. Reduced output from the lacrimal glands results in aqueous tear deficiency, a specific subclass of dry eye disease (DED) marked by inadequate tear volume. The prevalence of DED is 1.5-2 times greater in women than men, yet a comprehensive comparison of dry eye symptoms in male and female animals in an animal model of DED has not been performed. We excised the lacrimal gland to …

Cognitively Normal Women With Alzheimer’S Disease Proteinopathy Show Relative Preservation Of Memory But Not Of Hippocampal Volume, Jessica Z.K. Caldwell, Jeffrey L. Cummings, Sarah J. Banks, Sebastian Palmqvist, Oskar Hansson

School of Medicine Faculty Publications

Background: We examined interactive effects of sex, diagnosis, and cerebrospinal fluid (CSF) amyloid beta/phosphorylated tau ratio (Aβ/P-tau) on verbal memory and hippocampal volumes. Methods: We assessed 682 participants (350 women) from BioFINDER (250 cognitively normal [CN]; and 432 symptomatic: 186 subjective cognitive decline [SCD], 246 mild cognitive impairment [MCI]). General linear models evaluated effects of Alzheimer’s disease (AD) proteinopathy (CSF Aß/p-tau ratio), diagnosis, and sex on verbal memory (ADAS-cog 10-word recall), semantic fluency (animal naming fluency), visuospatial skills (cube copy), processing speed/attention functions (Symbol Digit Modalities Test and Trail Making Part A), and hippocampal volumes. Results: Amyloid-positive (Aβ/P-tau+) CN women …

Towards A Unified Disease Mechanism For Trna Synthetase-Mediated Peripheral Neuropathy, Emily L. Spaulding

Electronic Theses and Dissertations

Charcot-Marie-Tooth disease (CMT) is a debilitating inherited peripheral neuropathy resulting in progressive distal muscle atrophy and loss of sensation. CMT is genetically heterogeneous, with mutations in over 80 different genes leading to demyelinating or axonal forms. There are genetically similar subgroups, including the largest protein family implicated in the disease, the tRNA synthetases (ARSs). ARSs are responsible for aminoacylation of tRNAs during translation and are therefore ubiquitously expressed and essential proteins. Dominant mutations in at least five ARSs cause axonal forms of CMT. How mutations in ARSs cause CMT is unclear, however, the similar clinical presentation of patients suggests shared …

Nanomedicine-Driven Neuropathic Pain Relief In Rat Model Is Associated With Macrophage Polarity And Mast Cell Activation, Muzamil Saleem

Electronic Theses and Dissertations

We explored the immune neuropathology underlying multi-day relief from neuropathic pain in a rat model initiated at the sciatic nerve by using a nanoemulsion-based nanomedicine as a biological probe. The nanomedicine is theranostic: both therapeutic (containing celecoxib drug) and diagnostic (containing near-infrared fluorescent (NIRF) dye) and is small enough to be phagocytosed by circulating monocytes. A model of neuropathic pain is initiated by tying four 1mm spaced knots around the sciatic nerve with chromic gut suture, which results in neuroinflammation, and a resultant pain-like behavior manifests. We show that pain-like behavior reaches a plateau of maximum hypersensitivity 8 days post-surgery, …

Characterization Of The Effect Of Exercise Dose And Integrative Nonpharmacological Therapies In The Treatment Of Chronic Pain, Anna M. Polaski

Electronic Theses and Dissertations

Chronic pain includes debilitating conditions affecting large populations of people throughout the world. These diseases are further complicated by comorbid psychological disorders which make chronic pain conditions difficult to treat. Nonpharmacological treatment options have more recently become an important mainstay of effective therapies and are currently being used to supplement or replace traditional pharmacological treatment methods. Exercise-based therapies in particular are of interest due to their demonstrated success in reducing pain symptoms as well as improving psychological outcomes. Dose is an important factor in being able to effectively prescribe treatments in the context of specific exercise interventions and specific pain …

Role Of Astrocyte-Derived Extracellular Vesicles In Neuroinflammation Mediated By Drug Abuse, Ke Liao

Theses & Dissertations

Neuronal damage and neuroinflammation is a hallmark feature of HIV-associated neurological disorders (HANDs). Opioids abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Extracellular vesicles (EVs) are essential conduits in HIV and drug abuse-mediated synaptodendritic injury and neuroinflammation. Findings from our group have demonstrated that astrocyte-derived EV (ADEV)-miRNA-29b mediates HIV Tat and morphine-induced neuronal injury, thus underscoring the importance of such interactions in NeuroHIV.

Besides, HIV Tat and morphine-mediated synaptodendritic injury via ADEVs, we are also interested in whether ADEVs contributes to neuroinflammation. Microglia are critical players in …

Roles Of Autism Gene Arid1b In Murine Brain Development And Behavior, Amanda L. Smith

Theses & Dissertations

Autism spectrum disorder (ASD) and intellectual disability (ID) are highly prevalent neurodevelopmental disorders characterized by social and communication deficits, stereotyped behaviors, cognitive dysfunction, and deficits in adaptive behaviors. The pathogenesis underlying these disorders remains unknown, and thus no pharmacologic or genetic therapies are currently available. Recent progress in the field has shown that haploinsufficiency of the AT-rich interactive domain-containing 1B (ARID1B) gene is a genetic cause of ASD and ID. Our lab recently developed an Arid1b knockout mouse model to better study its role in the pathogenesis of these disorders. One theory regarding the cause of neurodevelopmental disorders …

Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen

Theses & Dissertations

Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …

Genetic Taster Status As A Mediator Of Neural Activity And Swallowing Mechanics In Healthy Adults, Angela M. Dietsch, Ross M. Westemeyer, William G. Pearson Jr., Douglas H. Schultz

Center for Brain, Biology, and Behavior: Faculty and Staff Publications

As part of a larger study examining relationships between taste properties and swallowing, we assessed the influence of genetic taster status (GTS) on measures of brain activity and swallowing physiology during taste stimulation in healthy men and women. Twenty-one participants underwent videofluoroscopic swallowing study (VFSS) and functional magnetic resonance imaging (fMRI) during trials of high-intensity taste stimuli. The precisely formulated mixtures included sour, sweet-sour, lemon, and orange taste profiles and unflavored controls. Swallowing physiology was characterized via computational analysis of swallowing mechanics plus other kinematic and temporal measures, all extracted from VFSS recordings. Whole-brain analysis of fMRI data assessed blood …

Dynamics And Control In Spiking Neural Networks, Fuqiang Huang

McKelvey School of Engineering Theses & Dissertations

In the brain, neurons (brain cells) produce electrical impulses, or spikes, that are thought to be the substrate of information processing and computation. Through enigmatic processes, these spikes are ultimately decoded into perceptions and actions. The nature of this encoding and decoding is one of the most pervasive questions in theoretical neuroscience. In other words, what are the specific functions enacted by neural circuits, through their biophysics and dynamics? This thesis examines the dynamics of neural networks from the perspective of control theory and engineering. The pivotal concept is that of the normative synthesis of neural circuits, wherein neural dynamics …

A Microfluidic Platform To Investigate The Mechanism By Which Gdnf Overexpression In Schwann Cells Causes Neuronal Axon Entrapment, Ze Zhong Wang

McKelvey School of Engineering Theses & Dissertations

Twenty million Americans suffer from peripheral nerve injury (PNI) caused by trauma and medical disorders, with approximately $150 billion spent in annual health-care dollars in the United States. Even with proper surgical reconstruction, less than 50% of the patients achieve satisfactory functional recovery. The gold standard surgical repair for long gaps (>3cm) is the autologous nerve graft, despite its disadvantages such as donor site morbidity, risk of infection, and increased cost. Alternative methods, such as acellular nerve grafts (ANA), are ineffective for large lesion gaps because of the lack of cells and regeneration factors. Recent efforts have been focused …

Genomic Contributors To Individual Differences In Reward-Related Neural Activity, Lindsay Jane Michalski

Arts & Sciences Electronic Theses and Dissertations

Aberrant reward-related behavior, including impulsive and risk-taking behaviors, is a common feature of externalizing psychopathology (e.g., attention deficit hyperactivity disorder, antisocial personality disorder, and substance-use disorders). Through imaging studies, these behaviors have been linked to dysregulated reactivity within a diffuse reward-related corticostriatal neural network, including the striatum, frontal regions (namely orbital, ventromedial, and dorsolateral cortices), the insula, and the hippocampus. Because variability in risk-taking behavior and related psychopathology is moderately-to-largely heritable (i.e., with estimates ranging from 40 – 80%), a genetically-informed approach is well-positioned to provide valuable insight into the etiology of reward-related neural and behavioral phenotypes that characterize externalizing …

Assessing The Morphology Of Vesicles In Inhibitory Symmetric Synapses In Safety And Fear Conditions In The Rat Lateral Amygdala, Valerie Kress

Honors Scholar Theses

There is a significant lack of research on vesicle morphology in inhibitory synapses in the rat lateral amygdala. Published research focuses heavily on excitatory synapses in different parts of the rat brain and even this research rarely focuses on the different vesicle types in axons. It is reported that in these axons, synaptic vesicles traditionally contain neurotransmitters while small dense core vesicles contain active zone proteins and large dense core vesicles contain neuropeptides. This study aims to find correlations between vesicle morphology, location, contents, and potential function of each of the different types of vesicle in inhibitory axons.

After reviewing …

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

Visual Modulation Of Resting State Α Oscillations, Kelly Webster, Tony Ro

Publications and Research

Once thought to simply reflect passive cortical idling, recent studies have demonstrated that α oscillations play a causal role in cognition and perception. However, whether and how cognitive or sensory processes modulate various components of the α rhythm is poorly understood. Sensory input and resting states were manipulated in human subjects while electroencephalography (EEG) activity was recorded in three conditions: eyes-open fixating on a visual stimulus, eyes-open without visual input (darkness), and eyes-closed without visual input (darkness). We show that α power and peak frequency increase when visual input is reduced compared to the eyes open, fixating condition. These results …

The Role Of Adult Hippocampal Neurogenesis In Depression-Relevant Reward-Related Behaviours, Katrina Zmavc

Electronic Thesis and Dissertation Repository

The variability in the symptomatology of depressive disorders and antidepressant treatment response has led to an increased interest in the molecular, cellular, and circuit mechanisms of many aspects of affect. Evidence suggests a reduction in adult hippocampal neurogenesis (AHN) is associated with an increase in depression-like behaviour, though much of this evidence has been from studies using aversive tests (e.g., forced swim test). Here, I used touchscreen operant chambers, which allow for non-aversive and translational testing, to test the hypothesis that AHN plays a contributing role in emotion regulation. A panel of three touchscreen tests were chosen to assess different …

Bridge To Neuroscience Workshop: An Effective Educational Tool To Introduce Principles Of Neuroscience To Hispanics Students, Alexandra Colon-Rodriguez, Chelsea T. Tiernan, Eileen S. Rodriguez-Tapia, William D. Atchison

Peer Reviewed Articles

Neuroscience as a discipline is rarely covered in educational institutions in Puerto Rico. In an effort to overcome this deficit we developed the Bridge to Neuroscience Workshop (BNW), a full-day hands-on workshop in neuroscience education. BNW was conceived as an auxiliary component of a parent recruitment program called Bridge to the PhD in Neuroscience Program (BPNP). The objectives of BNW are to identify promising students for BPNP, and to increase awareness of neuroscience as a discipline and a career option. BNW introduces basic concepts in neuroscience using a variety of educational techniques, including mini-lectures, interactive discussions, case studies, experimentation, and …

Identification Of Visual Attentional Regions Of The Temporoparietal Junction In Individual Subjects Using A Vivid, Novel Oddball Paradigm, Kathryn J. Devaney, Maya L. Rosen, Emily J. Levin, David C. Somers

Neuroscience: Faculty Publications

The Temporoparietal Junction (TPJ) of the cerebral cortex is a functionally heterogeneous region that also exhibits substantial anatomical variability across individuals. As a result, the precise functional organization of TPJ remains controversial. One or more regions within TPJ support visual attention processes, but the “attention TPJ” is difficult to functionally observe in individual subjects, and thus is typically identified by averaging across a large group of subjects. However, group-averaging also blurs localization and can obscure functional organization. Here, we develop and test an individual-subject approach to identifying attentional TPJ. This paradigm employs novel oddball images with a strong visual drive …

Alzheimer's And Amyloid Beta: Amyloidogenicity And Tauopathy Via Dyshomeostatic Interactions Of Amyloid Beta, Jordan Tillinghast

Senior Honors Theses

This paper reviews functions of Amyloid-β (Aβ) in healthy individuals compared to the consequences of aberrant Aβ in Alzheimer’s disease (AD). As extraneuronal Aβ accumulation and plaque formation are characteristics of AD, it is reasonable to infer a pivotal role for Aβ in AD pathogenesis. Establishing progress of the disease as well as the mechanism of neurodegeneration from AD have proven difficult (Selkoe, 1994). This thesis provides evidence suggesting the pathogenesis of AD is due to dysfunctional neuronal processes involving Aβ’s synaptic malfunction, abnormal interaction with tau, and disruption of neuronal homeostasis. Significant evidence demonstrates that AD symptoms are partially …

The Dolphin Brain - A Digital Presentation, Laura Taylor, Cally Gurley, Samia Pratt, David Mokler

Biomedical Sciences Faculty Projects

This digital presentation has been reproduced from the 2019 University of New England Ketchum Gallery exhibition of original artwork, scientific data, and materials from the Peter J. Morgane Research Collection on the Cetacean Brain, 1962-2004.

Validation Of Metabolic And Immunologic Biomarkers Tnf-A, Igf, Il-6, Crp And Hair Cortisol In The Common Marmoset, Sushmita Adhikari, Mariah Wulf, Aaryn Mustoe Phd, Jeffrey French Phd

Theses/Capstones/Creative Projects

The common marmoset is a good model for research because they are easy to house and have complex social relationships (French et al., 2019). Marmosets are sensitive to social isolation, and when introduced to a stressor, the HPA axis is activated (Saltzman & Abbott, 2011). The purpose of this experiment is to validate marmosets as a translational model for stress due to social relationships in humans. This is done by validating biomarker concentration levels at baseline, then comparing the concentration when introduced to a stressor. The biomarkers IL-6, CRP, IGF-1 and TNF-a were tested using a serum assay, then running …

The Role Of Gamma Oscillations And Cortical Inhibition In The Development Of Working Memory In Adolescence, Christopher P. Walker

Dissertations & Theses (Open Access)

Adolescence is a dynamic period of social, cognitive, and biological changes. In particular, working memory, the ability to actively encode and maintain information over a short period of time, develops early in childhood and gradually increases in capacity and stability during adolescence. The precise neurophysiological mechanism by which working memory capacity increases during adolescence is unclear. The objective of this investigation was to evaluate the role of cortical gamma-band (> 30 Hz) oscillations—which are associated with working memory in adults—for the development of working memory capacity in adolescents, and to identify the extent to which the temporal profile of gamma-aminobutyric …

Computational Neuroscience, Michelle Greene, Ns/Py 357 Students

Open Educational Resources

In Fall 2019, the Computational Neuroscience class at Bates College collaborated to begin an open textbook. Eight students across three majors collaborated to present the content they were learning to students who were similar to themselves. This project serves both pedagogical and social goals. By writing for fellow students, we leveraged the power of teaching for learning. By bringing together students of diverse academic backgrounds, we leveraged the power of peer instruction. Finally, by writing in the open, students not only brought their best work forward, but are working to contribute to an open knowledge environment that democratizes information. This …

Effects Of Mercury On The Dopamine Transporter Cell Surface Expression In Pc12 Cells, Christina Hui

Student Theses

Environmental factors, such as heavy metal exposures, have been suggested to have an impact not only on neurodegenerative disease, such as Parkinson’s disease, but also on psychostimulants abuse and their toxicity. In this study, two questions were addressed: 1) effects of mercuric chloride on parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP⁺) induced cytotoxicity and 2) effects of mercuric chloride on cell surface dopamine transporter. Pheochromocytorma cells (PC12) were treated with various concentrations of mercuric chloride (0.02~2.0 ppm) for 4 hours with and without 0.1 mM MPP⁺. Significant potentiation of toxicity was observed when there was co-treatment with 0.5 ppm …

Distinct Aspects Of The Early Environment Contribute To Associative Memory, Cued Attention, And Memory-Guided Attention: Implications For Academic Achievement, Maya L. Rosen, Andrew N. Meltzoff, Margaret A. Sheridan, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Childhood socioeconomic status (SES) is associated with numerous aspects of cognitive development and disparities in academic achievement. The specific environmental factors that contribute to these disparities remain poorly understood. We used observational methods to characterize three aspects of the early environment that may contribute to SES-related differences in cognitive development: violence exposure, cognitive stimulation, and quality of the physical environment. We evaluated the associations of these environmental characteristics with associative memory, cued attention, and memory-guided attention in a sample of 101 children aged 60–75 months. We further investigated whether these specific cognitive abilities mediated the association between SES and academic …

Cholesterol: A Possible Mediator Of Apoe Risk For Alzheimer's Disease, Michelle Marie Dunk

Theses and Dissertations

Despite the well-established link between the ε4 allele of the apolipoprotein E (APOE) gene and AD, the underlying mechanisms that mediate the risk of developing AD remain elusive. Literature on the role of APOE in cholesterol metabolism suggests that blood cholesterol may be a key factor in the development of AD pathology. Current study aims to investigate whether total cholesterol differs by APOE status and whether this relationship is predictive of AD diagnosis and its biomarkers. Baseline total cholesterol, APOE status, AD diagnosis, global cognitive function, brain Aβ, plasma Aβ40 and Aβ42, and cerebrospinal fluid (CSF) Aβ, tau, and phosphorylated …

Reexamining Object-Based Visual Attention: Understanding The Nature Of Direction-Dependent Attention Shifts, Adam Joseph Barnas

Theses and Dissertations

Attentional selection is a process by which relevant sensory stimuli are afforded enhanced priority for processing over and above irrelevant sensory stimuli. Object-based attention is a form of selection that leads to preferential processing of visual information contained in/on an attended object versus an unattended object. Observers typically exhibit enhanced performance to a target at an invalidly cued same object location compared to a different-object location, which results in a same object advantage as measured by the response time (RT) difference between these two target locations. A growing body of research has shown that object-based effects are small, inconsistent, and …

Functional Analysis In The Home Setting Of An Older Adult With Neurocognitive Disorder, Emily Norton

Masters Theses

Currently within the behavioral gerontology literature there are no published studies that include a functional assessment in the home setting. The primary goal of the present study was to address this gap by conducting a functional analysis on a challenging behavior of an older adult with neurocognitive disorder in the home. This study occurred in two phases. During phase one, researchers conducted an antecedent functional analysis on the bizarre speech of an 81-year-old female with suspected dementia across four conditions (television on, no interactions initiated; television on, interactions initiated; television off, no interactions initiated; television off, interactions initiated). Results from …