Neuroscience and Neurobiology Commons^™

Testing The Efficacy Of Lsn2463359, A Metabotropic Glutamate 5 Receptor Positive Allosteric Modulator, In Animal Models Of Schizophrenia, Dierdre M. Freamon

Seton Hall University Dissertations and Theses (ETDs)

For many years the dominant theory surrounding the cause of schizophrenia was focused on elevated dopamine levels found in critical areas of the brain. Recently a new theory has emerged pointing to elevated glutamate levels resulting from hypofunction of NMDA receptors and hypoactivity of GABAergic neurons which normally inhibit glutamatergic cells in a tonic manner. Therefore, while traditional antipsychotics directly block dopamine receptors, some of the newly generated compounds are designed to modulate glutamate to normal levels.

I propose testing the efficacy of the metabotropic glutamate 5 receptor modulator LSN2463359, previously shown to act as an indirect agonist of the …

Special Muscles, Annamaria C. Scaccia

Capstones

Special Muscles is a documentary that explores living with Duchenne muscular dystrophy, a fatal degenerative disease that weakens the muscles at an aggressive rate. The film will give an uncensored look at how one family copes with inevitability of the disease and their journey chasing a promising experimental cure.

Special Muscles follows 7-year-old Pietro Scarso and his family as they face the challenges, complications and promise of treating Pietro’s progressive muscle disorder. The film travels from New York to Los Angeles to Philadelphia to document the Scarso family’s race against time as Pietro undergoes a 96-week clinical trial for Eteplirsen, …

Reliability And Validity Of Neurobehavioral Function On The Psychology Experimental Building Language Test Battery In Young Adults, Brian J. Piper, Shane Mueller, Alexander R. Geerken, Kyle L. Dixon, Gregory Kroliczak, Reid H. Olsen, Jeremy K. Miller

Michigan Tech Publications, Part 1

Background. The Psychology Experiment Building Language (PEBL) software consists of over one-hundred computerized tests based on classic and novel cognitive neuropsychology and behavioral neurology measures. Although the PEBL tests are becoming more widely utilized, there is currently very limited information about the psychometric properties of these measures.

Methods. Study I examined inter-relationships among nine PEBL tests including indices of motor-function (Pursuit Rotor and Dexterity), attention (Test of Attentional Vigilance and Time-Wall), working memory (Digit Span Forward), and executive-function (PEBL Trail Making Test, Berg/Wisconsin Card Sorting Test, Iowa Gambling Test, and Mental Rotation) in a normative sample (N = 189, …

Rat Hind Limb Nociceptive Withdrawal Response Depends On Initial Paw Position But Not Stimulus Location, Kimberly Seamon

Senior Honors Projects, 2010-2019

There have been numerous studies in non-human animals on the effect of stimulus location on the NWR and at least a few studies that address the role of initial posture. However, all of these studies were conducted in anesthetized, decerebrated, or spinalized mammals. Since descending modulation and long loop reflexes may influence the NWR, the anesthetized spinalized/decerebrated animal may not be an adequate model of normal animals. Therefore, the primary aim of this study was to determine the effect of the stimulus location and initial paw position on the direction and magnitude of the nociceptive withdrawal response to heat stimulus …

Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and second most common neurodegenerative disorder. PD is characterized by the selective loss of dopaminergic neurons and dopamine neurotransmitter within the substantia nigra and termini in the striatum. Progressive loss of dopaminergic neurons occurs over many years in PD, and by the time movement disorder symptoms manifest, up to 50-70% of dopaminergic neurons have been lost. Several aspects of PD pathology have been described in detail, but a better understanding of PD progression is needed to develop more efficient treatments.

Motor symptoms associated with PD do not manifest until significant …

Development Of Manganese-Enhanced Magnetic Resonance Imaging (Memri) Methods To Study Pathophysiology Underlying Neurodegenerative Diseases In Murine Models, Aditya N. Bade

Theses & Dissertations

Manganese-enhanced magnetic resonance imaging (MEMRI) opens the great opportunity to study complex paradigms of central nervous system (CNS) in freely behaving animals and reveals new pathophysiological information that might be otherwise difficult to gain. Due to advantageous chemical and biological properties of manganese (Mn²⁺), MEMRI has been successfully applied in the studies of several neurological diseases using translational animal models to assess comprehensive information about neuronal activity, morphology, neuronal tracts, and rate of axonal transport. Although previous studies highlight the potential of MEMRI for brain imaging, the limitations concerning the use of Mn²⁺ in living animals and …

Analysis Of Neuronal Sequences Using Pairwise Biases, Zachary Roth

Department of Mathematics: Dissertations, Theses, and Student Research

Sequences of neuronal activation have long been implicated in a variety of brain functions. In particular, these sequences have been tied to memory formation and spatial navigation in the hippocampus, a region of mammalian brains. Traditionally, neuronal sequences have been interpreted as noisy manifestations of neuronal templates (i.e., orderings), ignoring much richer structure contained in the sequences. This paper introduces a new tool for understanding neuronal sequences: the bias matrix. The bias matrix captures the probabilistic tendency of each neuron to fire before or after each other neuron. Despite considering only pairs of neurons, the bias matrix captures the best …

Chronic Systemic Immune Dysfunction In African-Americans With Small Vessel-Type Ischemic Stroke, Candice M. Brown, Cheryl D. Bushnell, Gregory P. Samsa, Larry B. Goldstein, Carol A. Colton

Neurology Faculty Publications

The incidence of small vessel-type (lacunar) ischemic strokes is greater in African-Americans compared to whites. The chronic inflammatory changes that result from lacunar stroke are poorly understood. To elucidate these changes, we measured serum inflammatory and thrombotic biomarkers in African-Americans at least 6 weeks post-stroke compared to control individuals. Cases were African-Americans with lacunar stroke (n = 30), and controls were age-matched African-Americans with no history of stroke or other major neurologic disease (n = 37). Blood was obtained > 6 weeks post-stroke and was analyzed for inflammatory biomarkers. Freshly isolated peripheral blood mononuclear cells were stimulated with lipopolysaccharide …

Disentangling Embodied Cognition: An Examination Of The State, Problems, And Possibilities Of Embodied Cognition, Cody Cash

Graduate Theses and Dissertations

Embodied cognition has received a fair amount of attention in philosophical, neuroscientific, and robotic research during the past several decades, yet the precise nature of its goals, methods, and claims are unclear. This dissertation will ascertain and examine the primary themes in the field of embodied cognition as well as why, and if, they offer significant challenges to traditional cognitive science models. Though many theories believe they are providing accounts that should replace traditional models, to do so they will have to overcome the very difficult challenge of arguing that mental content and capabilities derived from sensorimotor activity can continue …

Dopaminergic Modulation Of Medial Prefrontal Cortex Deactivation In Parkinson Depression, Anders H. Andersen, Charles D. Smith, John T. Slevin, Richard J. Kryscio, Catherine A. Martin, Frederick A. Schmitt, Lee X. Blonder

Neuroscience Faculty Publications

Parkinson's disease (PD) is associated with emotional abnormalities. Dopaminergic medications ameliorate Parkinsonian motor symptoms, but less is known regarding the impact of dopaminergic agents on affective processing, particularly in depressed PD (dPD) patients. The aim of this study was to examine the effects of dopaminergic pharmacotherapy on brain activation to emotional stimuli in depressed versus nondepressed Parkinson disease (ndPD) patients. Participants included 18 ndPD patients (11 men, 7 women) and 10 dPD patients (7 men, 3 women). Patients viewed photographs of emotional faces during functional MRI. Scans were performed while the patient was taking anti-Parkinson medication and the day after …

Investigating The Influences Of Language Delay And/Or Familial Risk For Dyslexia On Brain Structure In 5-Year-Olds, Nora Maria Raschle, Bryce Larkin Chessell Becker, Sara Smith, Lynn Valérie Fehlbaum, Yingying Wang, Nadine Gaab

Center for Brain, Biology, and Behavior: Faculty Publications

Early language delay has often been associated with atypical language/literacy development. Neuroimaging studies further indicate functional disruptions during language and print processing in school-age children with a retrospective report of early language delay. Behavioral data of 114 5-year-olds with a retrospective report of early language delay in infancy (N = 34) and those without (N = 80) and with a familial risk for dyslexia and those without are presented. Behaviorally, children with a retrospective report of early language delay exhibited reduced performance in language/reading-related measures. A voxel-based morphometry analysis in a subset (N = 46) demonstrated an association between reduced …

The New York Head—A Precise Standardized Volume Conductor Model For Eeg Source Localization And Tes Targeting, Yu Huang, Lucas C. Parra, Stefan Haufe

Publications and Research

In source localization of electroencephalograpic (EEG) signals, as well as in targeted transcranial electric current stimulation (tES), a volume conductor model is required to describe the flow of electric currents in the head. Boundary element models (BEM) can be readily computed to representmajor tissue compartments, but cannot encode detailed anatomical information within compartments. Finite element models (FEM) can capture more tissue types and intricate anatomical structures, but with the higher precision also comes the need for semiautomated segmentation, and a higher computational cost. In either case, adjusting to the individual human anatomy requires costlymagnetic resonance imaging (MRI), and thus head …

Partial Covariance Based Functional Connectivity Computation Using Ledoit-Wolf Covariance Regularization, Matthew R. Brier, Anish Mitra, John E. Mccarthy, Beau M. Ances, Abraham Z. Snyder

Mathematics Faculty Research

Highlights •We use the well characterized matrix regularization technique described by Ledoit and Wolf to calculate high dimensional partial correlations in fMRI data. •Using this approach we demonstrate that partial correlations reveal RSN structure suggesting that RSNs are defined by widely and uniquely shared variance. •Partial correlation functional connectivity is sensitive to changes in brain state indicating that they contain functional information. Functional connectivity refers to shared signals among brain regions and is typically assessed in a task free state. Functional connectivity commonly is quantified between signal pairs using Pearson correlation. However, resting-state fMRI is a multivariate process exhibiting a …

A Global Perspective On The Influence Of Environmental Exposures On The Nervous System, Desire Tshala-Katumbay, Jean-Claude Mwanza, Diane S. Rohlman, Gladys E. Maestre, Reinaldo B. Oria

School of Medicine Publications

Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, …

Flexible Gating Of Contextual Influences In Natural Vision, Odelia Schwartz

Mathematics Colloquium Series

An appealing hypothesis suggests that neurons represent inputs in a coordinate system that is matched to the statistical structure of images in the natural environment. I discuss theoretical work on unsupervised learning of statistical regularities in natural images. In the model, Bayesian inference amounts to a generalized form of divisive normalization, a canonical computation that has been implicated in many neural areas. In our framework, divisive normalization is flexible: it is recruited only when the image is inferred to contain dependencies, and muted otherwise. I particularly focus on recent work in which we have applied this approach to understanding spatial …

Loss Of Glycosaminoglycan Receptor Binding After Mosquito Cell Passage Reduces Chikungunya Virus Infectivity, Amber M. Paul, Dhiraj Acharya, John F. Anderson, Faqing Huang, Fengwei Bai

Publications

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell derived CHIKV (CHIKVmos) has slower replication than mammalian cell derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic …

Suppression Of Locomotor Activity In Female C57bl/6j Mice Treated With Interleukin-1Β: Investigating A Method For The Study Of Fatigue In Laboratory Animals, David R. Bonsall, Hyunji Kim, Awa Ndiaye, Abbey Petronzio, Grace Mckay-Corkum, Penny C. Molyneux, Thomas E. Scammell, Mary E. Harrington

Psychology: Faculty Publications

Fatigue is a disabling symptom in patients with multiple sclerosis and Parkinson’s Disease, and is also common in patients with traumatic brain injury, cancer, and inflammatory disor- ders. Little is known about the neurobiology of fatigue, in part due to the lack of an approach to induce fatigue in laboratory animals. Fatigue is a common response to systemic challenge by pathogens, a response in part mediated through action of the pro-inflammatory cytokine interleukin-1 beta (IL-1β). We investigated the behavioral responses of mice to IL-1β. Female C57Bl/6J mice of 3 ages were administered IL-1β at various doses i.p. Interleukin-1β reduced locomotor …

White Matter Microstructure Contributes To Age-Related Declines In Task-Induced Deactivation Of The Default Mode Network, Christopher A. Brown, Jonathan G. Hakun, Zude Zhu, Nathan F. Johnson, Brian T. Gold

Neuroscience Faculty Publications

Task-induced deactivations within the brain’s default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) …

The Effects Of Modafinil And Atomoxetine On Dopamine Signaling In The Striatal Subregions Of The Rat, Martin Bobak

Theses and Dissertations

In an effort to combat diseases and disorders that impede our health, comfort and well-being, an abundance of prescription drugs have emerged in the past 60 years. Many prescription drugs have remarkable efficacy for treating the primary symptoms of these diseases and disorders; however, some drugs carry negative side effects that impose their own adverse symptoms, albeit, often to a lesser degree than the primary symptoms. Thus, one of the main objectives of the pharmaceutical industry is to innovate and develop novel therapeutics, which remediate the primary symptoms of disease and lack undesirable negative side effects. However, in order to …

The Hand Of Homo Naledi, Tracy L. Kivell, Andrew S. Deane, Matthew W. Tocheri, Caley M. Orr, Peter Schmid, John Hawks, Lee R. Berger, Steven E. Churchill

Neuroscience Faculty Publications

A nearly complete right hand of an adult hominin was recovered from the Rising Star cave system, South Africa. Based on associated hominin material, the bones of this hand are attributed to Homo naledi. This hand reveals a long, robust thumb and derived wrist morphology that is shared with Neandertals and modern humans, and considered adaptive for intensified manual manipulation. However, the finger bones are longer and more curved than in most australopiths, indicating frequent use of the hand during life for strong grasping during locomotor climbing and suspension. These markedly curved digits in combination with an otherwise human-like …

Distributed Encoding Of Spatial And Object Categories In Primate Hippocampal Microcircuits, Ioan Opris, Lucas M. Santos, Greg A. Gerhardt, Dong Song, Theodore W. Berger, Robert E. Hampson, Sam A. Deadwyler

Neuroscience Faculty Publications

The primate hippocampus plays critical roles in the encoding, representation, categorization and retrieval of cognitive information. Such cognitive abilities may use the transformational input-output properties of hippocampal laminar microcircuitry to generate spatial representations and to categorize features of objects, images, and their numeric characteristics. Four nonhuman primates were trained in a delayed-match-to-sample (DMS) task while multi-neuron activity was simultaneously recorded from the CA1 and CA3 hippocampal cell fields. The results show differential encoding of spatial location and categorization of images presented as relevant stimuli in the task. Individual hippocampal cells encoded visual stimuli only on specific types of trials in …

The Foot Of Homo Naledi, W. E. H. Harcourt-Smith, Z. Throckmorton, K. A. Congdon, B. Zipfel, Andrew S. Deane, M. S. M. Drapeau, S. E. Churchill, L. R. Berger, J. M. Desilva

Neuroscience Faculty Publications

Modern humans are characterized by a highly specialized foot that reflects our obligate bipedalism. Our understanding of hominin foot evolution is, although, hindered by a paucity of well-associated remains. Here we describe the foot of Homo naledi from Dinaledi Chamber, South Africa, using 107 pedal elements, including one nearly-complete adult foot. The H. naledi foot is predominantly modern human-like in morphology and inferred function, with an adducted hallux, an elongated tarsus, and derived ankle and calcaneocuboid joints. In combination, these features indicate a foot well adapted for striding bipedalism. However, the H. naledi foot differs from modern humans in having …

Predicting Phase Resetting Due To Multiple Stimuli, Kelsey M. Vollmer, Davy C. Vanderweyen, Derek R. Tuck, Sorinel A. Oprisan

Journal of the South Carolina Academy of Science

We generalized the phase resetting curve (PRC) to a more realistic case of neural oscillators receiving two or more inputs per cycle. The PRC tabulates the transient change in the firing period of a neuron due to an external perturbation, such as a presynaptic stimulus. We used a conductance-based model neuron to estimate experimentally the two-stimulus PRC and compared the results against our mathematical prediction based on the assumption of instantaneous recurrent stimulation. Within the limits of the recurrent stimulation assumptions, we found that the newly introduced prediction for the two-stimulus PRC matched experimental measurements. Our new results open the …

Reactive Oxygen Species-Mediated Neurodegeneration Is Independent Of The Ryanodine Receptor In Caenorhabditis Elegans, Lyndsay E.A. Young, Daniel C. Williams

Journal of the South Carolina Academy of Science

Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode Caenorhabditis elegans is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene unc-68, which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca²⁺) signaling in neurodegeneration. We tested the requirement for unc-68 in ROS-mediated neurodegeneration using the …

Apoe Stabilization By Exercise Prevents Aging Neurovascular Dysfunction And Complement Induction, Ileana Soto Reyes, Leah C. Graham, Hannah J. Richter, Stephen N. Simeone, Jake E. Radell, Weronika Grabowska, W. Keith Funkhouser, Megan C. Howell, Gareth R. Howell

College of Science & Mathematics Departmental Research

Aging is the major risk factor for neurodegenerative diseases such as Alzheimer's disease, but little is known about the processes that lead to age-related decline of brain structures and function. Here we use RNA-seq in combination with high resolution histological analyses to show that aging leads to a significant deterioration of neurovascular structures including basement membrane reduction, pericyte loss, and astrocyte dysfunction. Neurovascular decline was sufficient to cause vascular leakage and correlated strongly with an increase in neuroinflammation including up-regulation of complement component C1QA in microglia/monocytes. Importantly, long-term aerobic exercise from midlife to old age prevented this age-related neurovascular decline, …

Age-Related Sexual Dimorphism In Temporal Discrimination And In Adult-Onset Dystonia Suggests Gabaergic Mechanisms, John Butler, Ines M. Beiser, Laura Williams, Eavan Mcgovern, Fiona Molloy, Timothy Lynch, Dan G. Healy, Helena Moore, Richard Walsh, Richard B. Reilly, Sean O'Riordan, Cathal Walsh, Michael Hutchinson

Articles

Background: Adult-onset isolated focal dystonia (AOIFD) presenting in early adult life is more frequent in men, whereas in middle age it is female predominant. Temporal discrimination, an endophenotype of adult-onset idiopathic isolated focal dystonia, shows evidence of sexual dimorphism in healthy participants. Objectives: We assessed the distinctive features of age-related sexual dimorphism of (i) sex ratios in dystonia phenotypes and (ii) sexual dimorphism in temporal discrimination in unaffected relatives of cervical dystonia patients. Methods: We performed (i) a meta-regression analysis of the proportion of men in published cohorts of phenotypes of adult-onset dystonia in relation to their mean age of …

Involvement Of The Right Hemisphere In Reading Comprehension: A Dti Study, Tzipi Horowitz-Kraus, Yingying Wang, Elena Plante, Scott K. Holland

Center for Brain, Biology, and Behavior: Faculty Publications

The Simple View of reading emphasizes the critical role of two factors in normal reading skills: word recognition and reading comprehension. The current study aims to identify the anatomical support for aspects of reading performance that fall within these two components. Fractional anisotropy (FA) values were obtained from Diffusion Tensor images in twenty-one typical adolescents and young adults using the Tract Based Spatial Statistics (TBSS) method. We focused on the Arcuate Fasciculus (AF) and Inferior Longitudinal Fasciculus (ILF) as fiber tracts that connect regions already implicated in the distributed cortical network for reading. Our results demonstrate dissociation between word-level and …

The Neurochemistry And Social Flow Of Singing: Bonding And Oxytocin, Jason R. Keeler, Brittany L. Neuser, John M. Spitsbergen, Daniel J.M. Waters, John-Mary Vianney

BRAIN Lab Research

Music is used in healthcare to promote physical and psychological well-being. As clinical applications of music continue to expand, there is a growing need to understand the biological mechanisms by which music influences health. Here we explore the neurochemistry and social flow of group singing. Four participants from a vocal jazz ensemble were conveniently sampled to sing together in two separate performances: pre-composed and improvised. Concentrations of plasmaoxytocin and adrenocorticotropichormone (ACTH) were measured before and after each singing condition to assess levels of social affiliation, engagement and arousal. Avalidated assessment off low state was administered after each singing condition to …

Isoflurane Inhibits Synaptic Vesicle Exocytosis Through Reduced Ca2+ Influx, Not Ca2+-Exocytosis Coupling, Joel Baumgart, Zhen-Yu Zhou, Masato Hara, Daniel Cook, Michael Hoppa

Dartmouth Scholarship

Identifying presynaptic mechanisms of general anesthetics is critical to understanding their effects on synaptic transmission. We show that the volatile anesthetic isoflurane inhibits synaptic vesicle (SV) exocytosis at nerve terminals in dissociated rat hippocampal neurons through inhibition of presynaptic Ca2+ influx without significantly altering the Ca2+ sensitivity of SV exocytosis. A clinically relevant concentration of isoflurane (0.7 mM) inhibited changes in [Ca2+]i driven by single action potentials (APs) by 25 ± 3%, which in turn led to 62 ± 3% inhibition of single AP-triggered exocytosis at 4 mM extracellular Ca2+ ([Ca2+]e). Lowering external Ca2+ to match the isoflurane-induced reduction in …

Characterizing The Rogfp2-Orp1 Fluorescent Biosensor For Detecting Oxidative Stress In Mammalian Cells, Sara A. Doan, Stevie Norcross, Mathew Tantama

The Summer Undergraduate Research Fellowship (SURF) Symposium

Parkinson’s disease is a neurodegenerative disease involving the death of neurons in the substantia nigra and loss of the neurotransmitter, dopamine. The disease leads to progressive loss of motor control. Exact causes and mechanisms by which Parkinson’s disease proceeds are unknown, however, previous experiments determine oxidative stress in mitochondria as a factor that results in cell death. Strategies have been implemented to generate fluorescent biosensors to monitor reactive oxygen species (ROS) concentrations while simultaneously measuring the spatiotemporal distribution and correlation between the ROS, cellular function and organelle. Orp1, an enzyme found in yeast, is a sensitive oxidizing species and when …