Neuroscience and Neurobiology Commons^™

A Novel Therapeutic Strategy For Alzheimer’S Disease: Sex-Dependent Mechanisms Altered By The Hdac Inhibitor Rg2833 In A Transgenic Rat Model, Kelechi Ndukwe

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is the most common cause of dementia. In the United States, AD affects about 6.2 million Americans and is projected to reach 13.8 million by 2050. Currently, there are no effective therapies for AD and therapies targeting epigenetic mechanisms have shown to be effective in improving cognitive performance in animal models of AD. However, until now no study has reported sex-dependent mechanisms leading to differential expression of genes that contribute to changes in AD pathology. From our in silico studies, we identified an FDA-approved drug, RG2833 (N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide) that penetrates the blood brain barrier and can potentially ameliorate …

Beyond The Symptom: The Biology Of Fatigue, David M. Raizen, Janet Mullington, Christelle Anaclet, Gerard Clarke, Hugo Critchley, Robert Dantzer, Ronald Davis, Kelly L. Drew, Josh Fessel, Patrick M. Fuller, Erin M. Gibson, Mary Harrington, W. Ian Lipkin, Elizabeth B. Klerman, Nancy Klimas, Anthony L. Komaroff, Walter Koroshetz, Lauren Krupp, Anna Kuppuswamy, Julie Lasselin, Laura D. Lewis, Pierre J. Magistretti, Heidi Y. Matos, Christine Miaskowski, Andrew H. Miller, Avindra Nath, Maiken Nedergaard, Mark R. Opp, Marylyn D. Ritchie, Dragana Rogulja, Asya Rolls, John D. Salamone

Psychology: Faculty Publications

A workshop titled “Beyond the Symptom: The Biology of Fatigue” was held virtually September 27–28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue. This workshop summary distills key issues discussed in this workshop and provides a …

Protocol For Optimizing Production And Quality Control Of Infective Ecohiv Virions, Hammodah Rawhi Hammodah Alfar, Daphne N. Pariser, Harry Chanzu, Smita Joshi, Daniёlle M. Coenen, Joshua Lykins, Kanakanagavalli Shravani Prakhya, Mary Jane Potash, Wei Chao, Jennifer Kelschenbach, David J. Volsky, Kelly Metcalf-Pate

Saha Cardiovascular Research Center Faculty Publications

EcoHIV is a model of HIV infection that recapitulates aspects of HIV-1 pathology in mice. However, there are limited published protocols to guide EcoHIV virion production. Here, we present a protocol for producing infective EcoHIV virions and essential quality controls. We describe steps for viral purification, titering, and multiple techniques to analyze infection efficacy. This protocol produces high infectivity in C57BL/6 mice which will aid investigators in generating preclinical data.

Hla-Ii-Dependent Neuroimmune Changes In Group A Streptococcal Necrotizing Fasciitis, Ganesh Ambigapathy, Santhosh Mukundan, Kumi Nagamoto-Combs, Colin Combs, Suba Nookala

Biomedical Sciences Faculty Publications

Streptococcus pyogenes (Group A Streptococcus, GAS) bacteria cause a spectrum of human diseases ranging from self-limiting pharyngitis and mild, uncomplicated skin infections (impetigo, erysipelas, and cellulitis) to highly morbid and rapidly invasive, life-threatening infections such as streptococcal toxic shock syndrome and necrotizing fasciitis (NF). HLA class II allelic polymorphisms are linked with differential outcomes and severity of GAS infections. The dysregulated immune response and peripheral cytokine storm elicited due to invasive GAS infections increase the risk for toxic shock and multiple organ failure in genetically susceptible individuals. We hypothesized that, while the host immune mediators regulate the immune responses against …

Attenuated Typicality Effect In Category-Based Inferences: Implications For Autism Spectrum Disorder, Janani Rajagopalan

Dissertations, Theses, and Capstone Projects

Individuals diagnosed with Autism Spectrum Disorder (ASD) often encounter challenges in assimilating atypical exemplars into their categorical prototypes, a cognitive hurdle that can impact their interpretative and integrative capacities. Addressing this problem, the present research sought to develop a robust methodological approach to reduce the effect of this disparity. We examined the elements embedded within the category's internal structure, with the intention of experimentally attenuating the pronounced typicality effect, which is often exaggerated in ASD.

Across four experiments, the thesis investigated the cognitive and neural underpinnings that shape the access to the typicality gradient intrinsic to a category's structure. The …

Brainwaves, Memory, And Reward, Rebecca Mccune

Dissertations, Theses, and Capstone Projects

The development of effective educational curricula for enhancing learning involves the crucial consideration of effort and rewards. In the realm of education, teachers commonly employ rewards as motivational tools. Traditionally, these rewards are given to students as a recognition of their successful performance. However, a thought-provoking idea emerges: What if we were to extend rewards to students not solely based on accurate answers, but also on the effort they invest, even in cases where their actual response might be incorrect? Our study explores the potential impact of this approach on the way information is absorbed and subsequently retained, specifically focusing …

Characterization Of Pathological Tau Mutants, Charles J. Mcdonald

Dissertations, Theses, and Capstone Projects

Tau is a protein expressed exclusively in glia and neurons in the central nervous system and implicated in several neurogenerative diseases called “tauopathies”. Among all the tauopathies, one third is characterized by the presence of genetic mutations leading to the synthesis of tau proteins with single amino acid substitutions at specific locations and affecting protein function. While most of the initial studies have emphasize the functional role of tau as modulator of the axonal cytoskeleton, it has recently been well accepted that tau is also an intrinsically disordered protein that tends to form membraneless organelles called coacervates, due to a …

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …

Electrophysiological Signatures Of Stress Adaptability In The Bnst-Vta Pathway, Yuka Miura

Dissertations, Theses, and Capstone Projects

Chronic stress has detrimental effects on psychological and physiological health. Incapability to adapt to chronic stress can lead to depression, anxiety disorders, and addiction. The brain regions critical for reward processing share diverse physiological and molecular changes linked to depressive-like behaviors as a result of chronic stress. Cumulative evidence shows that counteraction or prevention of these alterations in neurons, occasionally in a projection-specific manner, can enhance stress adaptation or resilience.

Chronic stress induces various changes in the brain, including in the bed nucleus of the stria terminalis (BNST) and the ventral tegmental area (VTA). The neural projections from the BNST …

Automatic Analysis Of The Frequency, Vigor, And Complexity Of Spontaneous Locomotion Bouts Of Mice With Loss And Gain Of Function Of The G Protein-Coupled Receptor Smoothened In Cholinergic Neurons, Aleksandra Feshchenko

Dissertations, Theses, and Capstone Projects

Locomotion, a fundamental behavior, is classically assessed using simple metrics of velocity and total distance moved in an open field. This behavior however offers rich data about the organization and breadth of actions an animal can take while only facing limitations due to the bio-mechanical constraints of the organism. Importantly, these actions are not biased towards a particular task-solution space imposed by many behavioral paradigms. Here, to analyze motor complexity in freely ambulating mice, we developed a method for the automatic and unbiased identification of locomotor bouts which we call Bout Finder (BF). This analysis utilizes Open Feld data to …

You Hurt My Feelings: Autonomic And Behavioral Responses To Social Exclusion And The Moderating Effect Of Psychopathic Traits, Liat Kofler

Dissertations, Theses, and Capstone Projects

Humans have a fundamental need to form and maintain social connections, and thus experiencing social exclusion is extremely distressing as it threatens this basic human need. Individuals who are socially excluded often respond aggressively, not only towards their ostracizers but also towards innocent bystanders, with ostracism being implicated in extreme acts of violence such as school shootings. However, individual differences in behavior exist within the context of social exclusion as not everyone responds aggressively after being ostracized. Identifying risk factors for retaliatory aggressive behavior following experiences of social exclusion may facilitate the development of targeted interventions aimed at mitigating such …

Examining Metacognitive Access To Low-Level Ensemble Representations, Vladimir Mudragel

Dissertations, Theses, and Capstone Projects

Ensemble perception is a process that allows our sensory systems to rapidly extract summary information about the stimuli in the environment. For example, we are able to get a sense of the average number of items in a group of similar items (Burr & Ross, 2008; Halberda, Sires, & Feigenson, 2006) or the average size of a group of similar shapes of different sizes (Ariely, 2001). It is theorized that the qualitative result of ensemble perception is that it provides a gist impression of the current environment, which then enables attentional processes in the brain to determine which parts of …

Metabolic Control Of Proliferation And Differentiation In Oligodendrocytes, Sami Sauma

Dissertations, Theses, and Capstone Projects

Oligodendrocytes (OLs) are specialized cells whose membrane extension, called myelin, wraps the axons providing insulation, trophic and metabolic support, and is essential for proper functioning of the central nervous system. Inappropriate myelin formation, damage or dysfunction of oligodendrocytes has been identified in several neurological disorders and often precedes the loss of neuronal cells. OLs derive from proliferating oligodendrocyte progenitor cells (OPCs), which exit from the cell cycle and undergo a series of transcriptional and epigenetic events, including histone post-translational modifications, resulting in morphological and functional changes. Our lab previously identified elevated levels of histone acetylation in proliferating OPCs during the …

Reviewing Research On Down Syndrome To Then Inform And Create A Children’S Book With A Child Protagonist Who Has Down Syndrome, Trey Williams

Honors Projects

Children's literature continually evolves, requiring a steadfast commitment to align with new insights into various disabilities for genuine and accurate portrayal. This project delves into leveraging research to craft a children's book featuring Bonnie Lynn, a protagonist with Down Syndrome, recognizing the growing presence of individuals with Down Syndrome in today's society and the imperative for empathetic understanding within this community.

Proceedings From The Third Annual Society For Neurosports Conference, Neurosports Editorial Staff

Journal for Sports Neuroscience

Proceedings from the Third Annual Society for NeuroSports Conference

Music Advocacy: The Cognitive Development, Behavioral And Emotional Management, And Academic Success That Music Education Provides Students In Louisiana’S Low Socioeconomic Elementary Schools, Cory D. Dugar

Doctoral Dissertations and Projects

There are many technological curricular activities in math and science classrooms, yet few are found in music classrooms. Although many elementary schools may be benefiting from advocacy for music and technology, many elementary schools in the state of Louisiana have lost funding for music programs. For the Louisiana Department of Education to act as an advocate for music education, there must be a thorough understanding of the benefits of music education. Extensive research is one way to suggest that elementary music classes can raise the cognitive capacity of elementary students and could be the catalyst for ensuring the upcoming generation’s …

Assessing Blood Oxygen Level–Dependent Signal Variability As A Biomarker Of Brain Injury In Sport-Related Concussion, Evan D. Anderson, Tanveer Talukdar, Grace Goodwin, Valentina Di Pietro, Kamal M. Yakoub, Christopher E. Zwilling, David Davies, Antonio Belli, Aron K. Barbey

Center for Brain, Biology, and Behavior: Faculty Publications

Mild traumatic brain injury is a complex neurological disorder of significant concern among athletes who play contact sports. Athletes who sustain sport-related concussion typically undergo physical examination and neurocognitive evaluation to determine injury severity and return-to-play status. However, traumatic disruption to neurometabolic processes can occur with minimal detectable anatomic pathology or neurocognitive alteration, increasing the risk that athletes may be cleared for return-to-play during a vulnerable period and receive a repetitive injury. This underscores the need for sensitive functional neuroimaging methods to detect altered cerebral physiology in concussed athletes. The present study compared the efficacy of Immediate Post-concussion Assessment and …

Self-Supervised Pretraining And Transfer Learning On Fmri Data With Transformers, Sean Paulsen

Dartmouth College Ph.D Dissertations

Transfer learning is a machine learning technique founded on the idea that knowledge acquired by a model during “pretraining” on a source task can be transferred to the learning of a target task. Successful transfer learning can result in improved performance, faster convergence, and reduced demand for data. This technique is particularly desirable for the task of brain decoding in the domain of functional magnetic resonance imaging (fMRI), wherein even the most modern machine learning methods can struggle to decode labelled features of brain images. This challenge is due to the highly complex underlying signal, physical and neurological differences between …

The Directional Effect Of Target Position On Spatial Selective Auditory Attention, Heesung Park

Dissertations, 2020-current

Spatial selective auditory attention plays a crucial role in listening in a mixture of competing speech sounds. Previous neuroimaging studies have reported alpha band neural activity modulated by auditory attention, along with the alpha lateralization corresponding to attentional focus. A greater cortical representation of the attended speech envelope compared to the ignored speech envelope was also found, a phenomenon known as 'neural speech tracking’. However, little is known about the neural activities when attentional focus is directed on speech sounds from behind the listener, even though understanding speech from behind is a common and essential aspect of daily life. The …

Nmda Receptor Inhibition On Rodent Optimal Decision-Making In The Diminishing Returns Task, Seth Foust

Research Psychology Theses

There has been growing interest in using N-methyl-D-aspartate (NMDA) receptor antagonists as treatments for mood disorders, but there is still much to learn about their cognitive effects. Research shows NMDA receptors can affect decision-making, and the antagonist MK-801 has had varying effects in rodents. Specifically, some have reported impairments in working memory while foraging behaviors remained intact, while others have demonstrated changes in choice behavior related to delay or risk in behavior tasks. We investigated the role of NMDA receptors in the specific paradigm of optimal decision-making to further confirm MK-801’s effects and to explore whether inhibiting NMDA receptors alters …