Neuroscience and Neurobiology Commons^™

Endocytic Vesicle Rupture In The Pathogenesis And Propagation Of Neurodegenerative Proteinopathies, William P. Flavin

Dissertations

Numerous pathological amyloid proteins spread from cell-to-cell during neurodegenerative disease, facilitating the propagation of cellular pathology and disease progression. Understanding the mechanism by which disease-associated amyloid protein assemblies enter target cells and induce cellular dysfunction is therefore key to understanding the progressive nature of such neurodegenerative proteinopathies. In this study, we utilized an imaging-based assay to monitor the ability of disease-associated amyloid assemblies to induce the rupture of intracellular vesicles following endocytosis, as well as to elucidate the cellular consequences of this damaging mechanism of invasion. We observed that the ability to induce vesicle rupture is a conserved feature of …

The Effects Of Alcohol And Traumatic Brain Injury On Neural Stem Cell Responses, Son Trung Ton

Dissertations

Traumatic brain injury (TBI) is a major source of disability in modern societies. However, there are no good pharmacological strategies for treating long-term TBI complications because we do not fully understand the injury processes that occur afterward. Moreover, a significant percent of patients entering the emergency room with TBI have a blood alcohol level above the legal limit. Alcohol use and intoxication is a widespread issue in our society. Binge drinking is the most common way in which alcohol is consumed, and alarmingly, Americans of all age groups binge drink on a frequent basis. Despite the prevalence of alcohol intoxication …

Reef Society And The Tyranny Of Data, Robert Wintner

Animal Sentience

Modern science now approaches divergent processes in many areas, including health assessments of marine eco-systems and social aspects of marine species. Scientific data have long enjoyed a reputation for objectivity but incidents of science-for-hire, data spinning/skewing and political jading are more frequent than ever. In the field of reef creature sensitivity, technical treatises can “logically” explain away what a person of average education can clearly observe on any given reef. Western medicine discounted anecdotal evidence of any cure outside the 4% margin of error until those cures demanded attention and in some cases application. Modern science must now enter an …

Still Wondering How Flesh Can Feel, Gwen J. Broude

Animal Sentience

Reber believes he has simplified Chalmers’s “hard problem” of consciousness by arguing that subjectivity is an inherent feature of biological forms. His argument rests on the related notions of continuity of mind and gradual accretion of capacities across evolutionary time. These notions need to be defended, not just asserted. Because Reber minimizes the differences in mental faculties among species across evolutionary time, it becomes easier to assert, and perhaps believe, that sentience is already present in early biological forms. The more explicit we are about the differences among these mental faculties and the differences across species, the less persuasive is …

Protein Kinase M Zeta-Mediated Ltp Maintenance In The Non-Human Primate Hippocampus: A Role For Stress And Serotonergic Signaling In Affective Processing, Sasha L. Fulton

Theses and Dissertations

Early-Life Stress (ELS) is associated with vulnerability to mood disorder, but it’s not well understood how ELS contributes to deficits in cognitive function. Atypical PKMzeta is critical for LTP maintenance and memory. The current study aims to characterize the ELS phenotype with respect to this key marker of hippocampal LTP.

Robustness, Flexibility, And Sensitivity In A Multifunctional Motor Control Model, David N. Lyttle, Jeffrey P. Gill, Peter J. Thomas, Hillel J. Chiel

Faculty Scholarship

Motor systems must adapt to perturbations and changing conditions both within and outside the body. We refer to the ability of a system to maintain performance despite perturbations as “robustness,” and the ability of a system to deploy alternative strategies that improve fitness as “flexibility.” Different classes of pattern-generating circuits yield dynamics with differential sensitivities to perturbations and parameter variation. Depending on the task and the type of perturbation, high sensitivity can either facilitate or hinder robustness and flexibility. Here we explore the role of multiple coexisting oscillatory modes and sensory feedback in allowing multiphasic motor pattern generation to be …

Riding The Mind Lightning, William A. Fortuna

Capstones

Neuromodulation is the practice of applying external stimulation, either electric or magnetic, to the human in order to affect positive change. TDCS or transcranial direct current stimulation is a neuromodulatory technique using a 9-volt battery. Because of the simplicity of the device, and it's relatively low potential for harm, the technique is popular with both researchers and at-home enthusiasts. To find out whether this technique works the way some people say it does, I built my own.

Motor Control In Individuals With Multiple Sclerosis, David Arpin

Theses & Dissertations

This dissertation explored motor control in individuals with multiple sclerosis (MS) by quantifying the behavioral and neurophysiological deficits present in these individuals. We behaviorally quantified the precision of the ankle plantarflexor musculature of individuals with MS. Our results indicated that the individuals with MS had a greater amount of variability in the precision of the isometric ankle torques, and that this greater variability was related to decreased walking performance. To further explore whether these motor control deficits were due to aberrant cortical activity associated with planning motor actions, we used magnetoencephalography to assess the motor planning and execution stages of …

Global Gene Expression Profiling Of Healthy Human Brain And Its Application In Studying Neurological Disorders, Simarjeet K. Negi

Theses & Dissertations

The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed …

Mitogen And Morphogen Signaling Dysregulation: Pathophysiological Influence In Pancreatic Cancer And Alzheimer’S Disease, Eric Cruz

Theses & Dissertations

Although the etiology of a particular disease will vary, there are genetic and epigenetic bottlenecks that frequently converge resulting in dysregulation of mitogenic and morphogenetic signaling. This propensity is acutely experienced in malignancy and neurodegenerative disease.

Here, we have first investigated the role of dysregulated signaling in the context of pancreatic cancer (PC). Morphogenetic signaling has been regarded as a pleiotropic pathway with the potential to promote and inhibit metastatic features. Our investigation of bone morphogenetic protein 2 (BMP-2), an archetypical member of the BMP superfamily, has revealed the presence of extracellular, intracellular, and long non-coding RNA products. Our findings …

Target Validation And Pharmacological Characterization Of Novel Nmdar Modulators, Kiran Sapkota

Theses & Dissertations

The N-methyl-D aspartate receptors (NMDARs) are ligand-gated ion channels, which play important roles in learning and memory. Excessive activity of NMDARs is implicated in damage due to stroke and neurodegenerative diseases, whereas hypoactivity of NMDARs contributes to schizophrenia. The initial goal of my dissertation is to evaluate the potential role of the GluN2D-containing NMDARs in neuropathological, behavioral and cognitive alterations associated with schizophrenia and characterize the pharmacology and mechanisms of action of NMDAR modulators which could potentially be used to modulate these receptors in schizophrenia.

A subanesthetic dose of the NMDAR antagonist ketamine elicits symptoms of schizophrenia. This property led …

Selective Suppression Of The Α Isoform Of P38 Mapk Rescues Late-Stage Tau Pathology, Nicole Maphis, Shanya Jiang, Guixiang Xu, Olga N. Kokiko-Cochran, Saktimayee M. Roy, Linda J. Van Eldik, D. Martin Watterson, Bruce T. Lamb, Kiran Bhaskar

Sanders-Brown Center on Aging Faculty Publications

Background: Hyperphosphorylation and aggregation of tau protein are the pathological hallmarks of Alzheimer’s disease and related tauopathies. We previously demonstrated that the microglial activation induces tau hyperphosphorylation and cognitive impairment via activation of p38 mitogen-activated protein kinase (p38 MAPK) in the hTau mouse model of tauopathy that was deficient for microglial fractalkine receptor CX3CR1.

Method: We report an isoform-selective, brain-permeable, and orally bioavailable small molecule inhibitor of p38α MAPK (MW181) and its effects on tau phosphorylation in vitro and in hTau mice.

Results: First, pretreatment of mouse primary cortical neurons with MW181 completely blocked inflammation-induced p38α MAPK activation and AT8 …

Cochlear Implants And Related Neurotechnologies: Japanese Perspectives In Deaf Neuroethics, Zachary Clayton Abbott

Undergraduate University Honors Capstones

Asian neuroscience and neurotechnology (neuroS/T) research and development will surpass that of the United States and Europe, achieving a 60% increase in overall market growth, within the next decade. One area of ethical interest in neuroS/T involves auditory technologies: cochlear implants, middle ear prosthetics, bone-anchor hearing aids. A survey collected data on Japanese and U.S. attitudes of deafness as a disability, awareness of auditory technologies, and beliefs regarding psychosocial implications of such interventions. This survey is particularly timely because of shifts in attitudes toward these technologies and deaf identity between younger and older Japanese people in the direction of U.S. …

Animals Aren’T Persons, But Is It Time For A Neologism?, Helen Steward

Animal Sentience

Mark Rowlands argues that at least some animals are persons, based on the idea that (i) many animals have a property he calls “pre-reflective awareness,” (ii) the capacity for pre-reflective awareness is sufficient to satisfy the traditional Lockean definition of personhood, and (iii) satisfaction of the traditional Lockean definition of personhood is sufficient for being a person. I agree with (i) and can see that there is a persuasive case for (ii), but I think the case against (iii) blocks the conclusion that animals are persons. I suggest that we may need instead to coin a neologism in order to …

Reber’S Caterpillar Offers No Help, Carl Safina

Animal Sentience

Reber’s target article “Caterpillars, consciousness and the origins of mind” seems only to shift but not to address the question of where the mind is and how minds occur.

Striatal Dopaminergic Innervation Regulates Subthalamic Beta-Oscillations And Cortical-Subcortical Coupling During Movements: Preliminary Evidence In Subjects With Parkinson’S Disease, Andrea Canessa, Nicolo G. Pozzi, Gabriele Arnulfo, Joachim Brumberg, Martin M. Reich, Gianni Pezzoli, Maria F. Ghilardi, Cordula Matthies, Frank Steigerwald, Jens Volkman, Ioannis U. Isais

Publications and Research

Activation of the basal ganglia has been shown during the preparation and execution of movement. However, the functional interaction of cortical and subcortical brain areas during movement and the relative contribution of dopaminergic striatal innervation remains unclear. We recorded local field potential (LFP) activity from the subthalamic nucleus (STN) and high-density electroencephalography (EEG) signals in four patients with Parkinson’s disease (PD) off dopaminergic medication during a multi-joint motor task performed with their dominant and non-dominant hand. Recordings were performed by means of a fully-implantable deep brain stimulation (DBS) device at 4 months after surgery. Three patients also performed a single-photon …

Very Rapid Onset Cannabis Dependence Risk In Relation To Co-Occurring Use Of Other Psychoactive Drugs, Olga A. Vsevolozhskaya, Fernando A. Wagner, James C. Anthony

Biostatistics Presentations

Background: Epidemiological estimates for lifetime cumulative incidence indicate that for every 9-11 who start using cannabis, one becomes a case of the cannabis dependence syndrome (CDS) – i.e., roughly 9%-11%. More recent estimates clarify that CDS risk might be much lower among ’cannabis only’ users, due in part to the fact that many ’cannabis only’ users try the drug a few times and never again. We turned to Hill functional analysis in order to study CDS probability soon after 1st cannabis use, estimated across strata defined by the number of recent days of cannabis use, with an acknowledgment that a …

Ros Regulation Of Axonal Mitochondrial Transport, Pin-Chao Liao

Open Access Dissertations

Mitochondria perform critical functions including aerobic ATP production and calcium (Ca2+) homeostasis, but are also a major source of reactive oxygen species (ROS) production. To maintain cellular function and survival in neurons, mitochondria are transported along axons, and accumulate in regions with high demand for their functions. Oxidative stress and abnormal mitochondrial axonal transport are associated with neurodegenerative disorders. However, we know little about the connection between these two. Using primaryDrosophila neuronal cell culture and the third instar larval nervous system as in vitro and in vivo models, respectively, we studied mitochondrial transport under oxidative stress conditions. In vitro …

Transient Receptor Potential Cation Channel, Subfamilies V, Member 1 (Trpv1) And M, Member 1 (Trpm1) Contribute To Neural Signaling In Mouse Retina., Jennifer Noel

Electronic Theses and Dissertations

The retina processes light information through parallel pathways in order to extract and encode the visual scene. Light information is transmitted to the brain through approximately 30 ganglion cells (GCs), the retinal output neurons. Trp channels modulate the responses of retinal neurons within specific pathways. The study of the expression and function of the majority of Trp channels in the retina is largely in its infancy. My dissertation first investigated the expression and function of the transient receptor potential vanilloid-1 (TRPV1) receptor/channel in the retina. TRPV1, the first cloned and most highly studied Trp channel in the peripheral nervous system, …

Dopamine D1 Receptor Activity In The Basolateral Amygdala Is Important For Mediating Fear, Reward And Safety Discrimination Learning, Ka Ho Ng

Open Access Theses

Post traumatic stress disorder (PTSD) patients frequently show impairment in safety learning (Jovanovic, Kazama, Bachevalier, & Davis, 2012). Since the amygdala is known to be critical for emotional processing(Wassum & Izquierdo, 2015) and dopamine signaling in the amygdala is important for mediating both fear and reward learning, current experiments examined the role of dopamine signaling in the BLA in mediating both safety learning and reward seeking. We manipulated dopamine D1 receptor activity with a D1 receptor agonist (SKF 38393) or D1 receptor antagonist (SCH23390) either systemically or infused directly into the BLA 20 minutes prior to training rats in a …