Neuroscience and Neurobiology Commons^™

Examination Of The Effects Of Various Pharmacotherapies For Diabetes On Nicotine Intake And Pain Sensitivity, Sebastian Ortegon

Open Access Theses & Dissertations

Tobacco use and diabetes are major public health concerns. Prior work has suggested that persons with diabetes may exhibit greater susceptibility to nicotine dependence, and treatments for nicotine cessation are less effective. From existing literature, it is also unclear if neuropathic pain contributes to nicotine use in persons with diabetes. To address these issues, this Masterâ??s thesis first assessed the efficacy of diabetes pharmacotherapies on nicotine intake, food consumption, and water intake in rodent models of insulin resistance (Aim 1). Subsequent studies assessed the impact of analgesic medications on nicotine intake and neuropathic pain in rodent models that produce neuropathic …

Structural Molecular And Developmental Evidence For Cell-Type Diversity In Cnidarian Mechanosensory Neurons, Julia Baranyk, Kristen Malir, Miguel A.P. Silva, Sakura Rieck, Gracie Scheve, Nagayasu Nakanishi

Biological Sciences Faculty Publications and Presentations

Deploying a conserved mechanosensory neuron known as the concentric hair cell, cnidarians have evolved diverse mechanoreceptors from hydroid filiform tentacles to jellyfish statocysts. However, it is unknown whether cnidarian mechanoreceptor evolution has relied solely on repurposing a single ancestral mechanosensory neuron type. Here we report evidence for cell-type diversity of mechanosensory neurons in sea-anemone cnidarian Nematostella vectensis. Uncovered in the ectoderm of feeding tentacles are conventional type I hair cells and previously unrecognized type II hair cells differing in the structure of apical sensory apparatus and synapses. Moreover, we identify TRP channel-encoding gene polycystin-1 as a type-II-hair-cell-specific essential mediator of …

Structural Projections To The Nucleus Accumbens Link To Impulsive Components Of Human Risk Preference, Loreen Tisdall, Kelly H. Macniven, Josiah Leong, Renato Frey, Jörg Rieskamp, Ralph Hertwig, Brian Knutson, Rui Mata

Psychological Science Faculty Publications and Presentations

Functional responses in the Nucleus Accumbens (NAcc) to risk- and reward-related cues can predict real-life risk-taking behavior. Since NAcc activity depends on neurotransmission from connected brain regions, projections to the NAcc may also predict risk preference. To quantify risk preference, we employed latent variables previously derived in a comprehensive, independent study examining the psychometric structure of risk preference, which yielded a general risk preference factor as well as several specific factors, including a factor capturing impulsivity. Informed by previous work, we preregistered a set of hypotheses concerning the association between different risk preference factors and fractional anisotropy (or FA, which …

Effects Of Retinal Gonadotropin-Releasing Hormone On Reproductive Behavior And Retinal Activity In The Cichlid Fish, Astatotilapia Burtoni, Chase Anselmo

LSU Master's Theses

Many animals use visual signals to evade predators, forage for food, and communicate with conspecifics. Some animals that shift into and out of breeding stages, such as fish, can modulate their visual sensitivity to better adapt to changing internal and external conditions. Previous work in our lab demonstrated that females of the cichlid fish Astatotilapia burtoni have improved visual sensitivity when they enter reproductive readiness. However, little is known about how fish and vertebrates more broadly modulate visual sensitivity across their reproductive cycle. We hypothesized that the hormone and neuromodulator gonadotropin-releasing hormone (GnRH) could modulate visual sensitivity because GnRH is …

Core Concepts: Views From Physiology And Neuroscience, Jennifer E. Schaefer, Joel Michael

Biology Faculty Publications

Core concepts are “big ideas” that are central to a discipline, provide frameworks of understanding for disciplinary content, and aid student transfer of learning. Core concept lists have been developed for increasing numbers of higher education STEM disciplines. This mini-review uses physiology and neuroscience core concepts as examples to inform core concept pedagogies in these and other disciplines. The article reviews the development of physiology and neuroscience core concepts and compares the resulting concept lists. It then provides suggestions or “lessons learned” for educators and researchers who wish to utilize core concept pedagogies or who wish to develop core concepts …

Neural Correlates Of Socially Rewarding Memories In Posttraumatic Stress Disorder, Kyle P. Blidy

MUSC Theses and Dissertations

Significance. Memory disturbances for emotional content are central to PTSD, yet most research focuses on trauma memories. Recent evidence suggests that enhancing access to positive memories could improve mood, affect regulation, self-esteem, and integration of trauma memories. However, the neurocognitive mechanisms underlying positive memory encoding in PTSD are poorly understood. No study has examined memory for positive social items in PTSD, which is important because PTSD entails social withdrawal and reduced accessibility to positive memory. Additionally, positive memories embedded in a social context have enhanced subjective value and strengthening their accessibility may confer greater benefits to wellbeing compared to non-social …

Electric Potential Energy Optimized 3d Radial Sampling Trajectories For Mri, Christopher Huynh, Datta Singh Goolaub, Christopher K Macgowan

Faculty, Staff and Students Publications

A novel method for creating “golden” 3D center-out radial MRI sampling trajectories was developed and analyzed. This method, called ELECTRO (ELECTRic potential energy Optimized), uses repulsive forces to minimize electric potential energy. An objective function , the electric potential energies of all subsets of consecutive readouts in a 3D radial trajectory, and its reduced form were minimized using a multi-stage optimization strategy. A metric called normalized mean nearest neighbor angular distance (NMNA) was proposed for describing distributions of points on a sphere. ELECTRO and other relevant golden trajectories were compared in silico using NMNA and point spread function analysis. Consecutive …

Memory Modulation: Dominance Of Negative Visual Context Over Neutral Verbal Memory, Stas Kozak, Noa Herz, Maya Tocker, Yair Bar-Haim, Nitzan Censor

Department of Neurology Faculty Papers

Neutral memories can be modulated via intentional memory control paradigms such as directed forgetting. In addition, previous studies have shown that neutral visual memories can be modulated indirectly, via remember and forget instructions towards competing verbal memories. Here we show that direct modulation of neutral verbal memory strength is impaired by negative visual context, and that negative visual context is resistant to indirect memory modulation. Participants were directly instructed to intentionally remember or forget newly encoded neutral verbal information. Importantly, this verbal information was interleaved with embedded negative visual context. Results showed that negative visual context eliminated the well-documented effect …

Arid1a-Baf Coordinates Zic2 Genomic Occupancy For Epithelial-To-Mesenchymal Transition In Cranial Neural Crest Specification, Samantha M. Barnada, Aida Giner De Gracia, Cruz Morenilla-Palao, Maria Teresa López-Cascales, Chiara Scopa, Francis J. Waltrich, Harald M.M. Mikkers, Maria Elena Cicardi, Jonathan Karlin, Davide Trotti, Kevin A. Peterson, Samantha A. Brugmann, Gijs W.E. Santen, Steven B. Mcmahon, Eloísa Herrera, Marco Trizzino

Department of Biochemistry and Molecular Biology Faculty Papers

The BAF chromatin remodeler regulates lineage commitment including cranial neural crest cell (CNCC) specification. Variants in BAF subunits cause Coffin-Siris syndrome (CSS), a congenital disorder characterized by coarse craniofacial features and intellectual disability. Approximately 50% of individuals with CSS harbor variants in one of the mutually exclusive BAF subunits, ARID1A/ARID1B. While Arid1a deletion in mouse neural crest causes severe craniofacial phenotypes, little is known about the role of ARID1A in CNCC specification. Using CSS-patient-derived ARID1A induced pluripotent stem cells to model CNCC specification, we discovered that ARID1A-haploinsufficiency impairs epithelial-to-mesenchymal transition (EMT), a process necessary for CNCC delamination and migration from …

Parallel Electrophysiological Abnormalities Due To Covid-19 Infection And To Alzheimer’S Disease And Related Dementia, Yang Jiang, Jennifer Neal, Pradoldej Sompol, Görsev Yener, Xianghong Arakaki, Christopher M. Norris, Francesca R. Farina, Agustin Ibanez, Susanna Lopez, Abdulhakim Al-Ezzi, Voyko Kavcic, Bahar Güntekin, Claudio Babiloni, Mihály Hajós

Neurology Faculty Publications

Many coronavirus disease 2019 (COVID-19) positive individuals exhibit abnormal electroencephalographic (EEG) activity reflecting “brain fog” and mild cognitive impairments even months after the acute phase of infection. Resting-state EEG abnormalities include EEG slowing (reduced alpha rhythm; increased slow waves) and epileptiform activity. An expert panel conducted a systematic review to present compelling evidence that cognitive deficits due to COVID-19 and to Alzheimer’s disease and related dementia (ADRD) are driven by overlapping pathologies and neurophysiological abnormalities. EEG abnormalities seen in COVID-19 patients resemble those observed in early stages of neurodegenerative diseases, particularly ADRD. It is proposed that similar EEG abnormalities in …

The Left Ventricle Under Stress: Exploring The Impact Of Gestational Stress On Postpartum Cardiovascular Health, Archana Ramesh

Senior Theses

A woman’s cardiovascular system undergoes several changes to equip it for the physiological demands of pregnancy. The left ventricle (LV) is most susceptible to changes such as increased cardiac output and workload because it is the primary chamber in the heart that pumps oxygenated blood to the entire body. Some mothers may be unable to cope with the physiological demands, and ventricular hypertrophy, along with other cardiac remodeling that takes place during pregnancy, may bring light to underlying cardiovascular disease (CVD). The peripartum period often comes with heightened stress, disproportionately for certain populations, and this stress has been linked with …

Behavioral And Neural Evidence For Perceptual Inference Of Position, Sharif Saleki

Dartmouth College Ph.D Dissertations

Extensive neuroscientific research has advanced our knowledge of the mechanisms involved in the detection and recognition of visual stimuli. However, to guide flexible behavior in a changing world, the brain must also construct stable and coherent perceptual representations from retinal images that are often ambiguous. To resolve ambiguities and uncertainties, the visual system combines its input with other sources of information such as context and prior knowledge to infer the most likely interpretation of a scene. Thus, perception is inherently an inferential process that goes beyond simple detection or recognition of stimuli. Although inference has been studied in many areas …

Simultaneous Modulation Of Pulse Charge And Burst Period Elicits Two Differentiable Referred Sensations, T. R. Benigni, A. E. Pena, S. S. Kuntaegowdanahalli, J. J. Abbas, R. Jung

Biomedical Engineering Faculty Publications and Presentations

Objective. To investigate the feasibility of delivering multidimensional feedback using a single channel of peripheral nerve stimulation by complementing intensity percepts with flutter frequency percepts controlled by burst period modulation. Approach. Two dimensions of a distally referred sensation were provided simultaneously: intensity was conveyed by the modulation of the pulse charge rate inside short discrete periods of stimulation referred to as bursts and frequency was conveyed by the modulation of the period between bursts. For this approach to be feasible, intensity percepts must be perceived independently of frequency percepts. Two experiments investigated these interactions. A series of two alternative forced …

Characterization Of Stealth Liposome-Based Nanoparticles Encapsulating Acat1/Soat1 Inhibitor F26: Potential Therapeutics For Niemann-Pick Type C And Other Neurodegenerative Diseases., Junghoon Lee

Dartmouth College Ph.D Dissertations

Cholesterol dysregulation is implicated in neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Niemann-Pick type C disease (NPCD). This study focused on evaluating the potent ACAT1 inhibitor, F26, as a therapeutic strategy for NPCD. F26 demonstrated superior ACAT1 inhibition and efficacy compared to the previously studied inhibitor, F12511, both in vitro and in vivo. Notably, F26 exhibited enhanced pharmacokinetic properties, including prolonged duration of action and better brain retention, making it a more promising candidate for treating neurodegenerative diseases.

F26 was encapsulated in a liposome-based nanoparticle system, DSPE-PEG2000 with phosphatidylcholine (PC), for enhancing its …

Robust And Generalizable Representations In The Hippocampus, Hung-Tu Chen

Dartmouth College Ph.D Dissertations

An intelligent system must balance generalizing across similar experiences with maintaining the distinctiveness of each experience. This thesis explores how the hippocampus manages this balance through its neural representations to support adaptive behavior. In Chapter 1, I provide an overview of key hippocampal phenomena that contribute to this process, including remapping, splitter signal, and replay. In Chapter 2, I challenge the concept of random remapping by showing that it is possible to predict, better than chance, how a given experience will be encoded in the hippocampus across different subjects. This suggests that encoding of related experiences, which was previously thought …

The Effects Of Intermittent Fasting On Working Memory With A Covariate Of Exercise Among The Perimenopausal Population: A Randomized Controlled Trial, Karen Marie Veltri

Doctoral Dissertations and Projects

Intermittent fasting and exercise are tools to improve health. Current literature focuses on their impact on metabolic health and weight loss, leaving a gap in the research examining their effects on working memory during the menopause transition. The purpose of this study was to address this gap by recruiting perimenopausal participants and randomly assigning them to an experimental or a control group. The experimental group followed an 8/16 intermittent fasting regimen for two consecutive weeks. Both groups ate ad libitum without dietary restrictions. Participants completed a pre- and post-study Working Memory Questionnaire and self-reported average hours of exercise per week. …

Investigation Of The Endogenous Opioid Neural Circuitry In Pain, Erin Nicole Bobeck

Funded Research Records

No abstract provided.

Synaptotagmin-9 In Mouse Retina, Chris S. Mesnard, Cassandra L. Hays, Lou E. Townsend, Cody L. Barta, Channabasavaiah B. Gurumurthy, Wallace B. Whoreson

Neuroscience Faculty Publications

Synaptotagmin-9 (Syt9) is a Ca2+ sensor mediating fast synaptic release expressed in various parts of the brain. The presence and role of Syt9 in retina is unknown. We found evidence for Syt9 expression throughout the retina and created mice to conditionally eliminate Syt9 in a cre-dependent manner. We crossed Syt9fl/fl mice with Rho-iCre, HRGP-Cre, and CMV-Cre mice to generate mice in which Syt9 was eliminated from rods (rodSyt9CKO), cones (coneSyt9CKO), or whole animals (CMVSyt9). CMVSyt9 mice showed an increase in scotopic electroretinogram (ERG) b-waves evoked by bright flashes with no change in a-waves. Cone-driven photopic ERG b-waves were not significantly …

Cortisol And Alpha-Synuclein Stability In Saliva Under Varying Storage And Handling Conditions, Mo Zheng, Sujata Srikanth, Jeremiah Carpenter, Delphine Dean

Journal of the South Carolina Academy of Science

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairments and non-motor symptoms, significantly impacting patients' quality of life. Currently, cerebrospinal fluid (CSF) is the primary biofluid used for PD biomarker studies, notably α-synuclein, despite the invasive nature of lumbar puncture procedures. Recent work has shown that some of these PD biomarkers have been measured in saliva. As an alternative to CSF, saliva can be non-invasively self-collected by patients repeatedly over time to monitor biomarker levels. However, the stability of these biomarkers in saliva needs to be evaluated before saliva can be considered for patient self-collection studies. Therefore, …

Sex-Dependent Gene Expression Alterations In Social Defeat Stress Model Of Major Depression Disorder, Juan Diego Torres, Javier Vargas Medrano, Anapaula Themann, Elias Arellano Villanueva, Nina Mourao, Megan W. Szobody, Tori Sayers, Sriya Gullapalli, Tyler Torres, Sridhar Srinivasan, Anesu Karen Murambadoro, Kory Deshawn Punch, Kevin Valdez Garcia, Nikhilesh Anand, Kelsey Baker, Sergio Iniguez, Bharathi Shrikanth Gadad

Research Colloquium

Introduction: Major Depression Disorder (MDD) is a prevalent, recurrent, and chronic disorder that represents a leading cause of disability worldwide. Millions are affected with symptoms that go from constant sadness to even suicidal thoughts. In the U.S., major depression and fatal suicide have increased by 57.4% among adolescents and young adults. Myelin and inflammation-related genes have been found to play a role in individuals with MDD.

Methods: Adolescent males and females C57BL/6 mice underwent a vicarious defeat stress (VDS) procedure in which a mouse witnessed a conspecific being defeated. VDS and control (CON) mice underwent the Social Interaction (SI) test. …

Molecular Studies In Understanding Novel Curcumin-Glucoside Role In The Prevention Of Alpha-Synuclein Aggregation In Relevance To Parkinson's Disease, Natasha N. Quailes, Nina Mourao, Megan W. Szobody, Sridhar Srinivasan, Sriya Gullapalli, Elias Arellano Villanueva, Tyler Torres, Kory Deshawn Punch, Anesu Karen Murambadoro, Blake Martin, Kelsey Baker, Nikhilesh Anand, Hansapani Rodrigo, Bharathi Shrikanth Gadad

Research Colloquium

Background: The synuclein deposition in the brain of Parkinson’s Disease (PD) is the hallmark pathology of the neurodegenerative pathway. The transformation of alpha-synuclein into synuclein monomer, toxic oligomer, and insoluble fibrils are key steps in cell dysfunction. We synthesized a novel molecule, Curcumin-glucoside (Curc-gluc), which has good water solubility and a favorable partition coefficient.

Methods: The present study focuses on α-syn aggregation kinetics in the presence and absence of Curc-gluc and Curcumin; we also tested the effect of Copper (Cu) and Iron (Fe) Fe binding through a mathematical approach, biophysical techniques, and docking models. In the mathematical approach, we applied …

Cognition And Inflammation In Youth With Perinatal Hiv, Megan Niehaus, Julie Mannarino, Jacob Bolzenius, Tori Frerichs, Robert Paul

Undergraduate Research Symposium

Background: Perinatally acquired HIV (PHIV) remains a major global health challenge. Approximately 90% of the global population of PHIV reside in low- or middle-income countries (LMICs) where access to antiretroviral therapy (ART) remains incomplete, particularly for PHIV. With PHIV, the brain is exposed to the virus during critical periods of brain development without the immunological benefits from ART. Unlike adults with horizontally acquired HIV whose nadir CD4+ Tcell count is a strong correlate of cognitive difficulties that persist after sustained use of ART, cognitive symptoms among PHIV youth are independent of traditional HIV disease metrics. Prior studies indicate that PHIV …

Characterizing Border Associated Macrophages During Spinal Cord Regeneration, Addison Vogt, Dana Shaw, Mayssa Mokalled

Undergraduate Research Symposium

The human central nervous system has limited regenerative ability, with injuries to the spinal cord (SC) often resulting in paralysis. Alternatively, zebrafish have enhanced innate regenerative capacity and regain full motor function following spinal cord injury (SCI). Immune activation following SCI is necessary to provide a permissive environment for tissue repair, but the immune pathways necessary for SC regeneration are not well characterized. In previous data, we have found that while immune activation is persistent into the chronic phases of SCI response in mammals, zebrafish achieve full immune clearance within 48 days post SCI. We hypothesize that one key distinction …

Neurovascular Shifts, Sensory Sensitivity, And Pmdd In Autistic Women: Exploring Blood Flow Redirection, Mood Dysregulation, And Pain Tolerance During Menstruation, Piper Hutson, James Hutson

Faculty Scholarship

This article examines the relationship between Premenstrual Dysphoric Disorder (PMDD), neurovascular dynamics, and sensory sensitivities in autistic women during menstruation. The redirection of blood flow to the uterus during the menstrual cycle has been found to exacerbate cerebral perfusion deficits in neurodivergent individuals, particularly in the Prefrontal Cortex (PFC), which contributes to the mood dysregulation and emotional instability characteristic of PMDD. Autistic women, who often exhibit heightened sensory sensitivities, experience intensified discomfort during menstruation, as sensory overload and altered pain perception compound the emotional challenges of PMDD. These findings emphasize the need for neurodivergent-friendly menstrual products that mitigate both physical …

Environmental Contributions To Cognitive Development: The Role Of Cognitive Stimulation, Divyangana Rakesh, Katie A. Mclaughlin, Margaret Sheridan, Kathryn L. Humphreys, Maya L. Rosen

Neuroscience: Faculty Publications

Early environmental experiences influence children's cognitive and neural development. In particular, cognitive stimulation, defined as environmental inputs that engage the senses and provide learning opportunities for children, fosters acquisition of knowledge across various cognitive domains. Low levels of cognitive stimulation in early life may restrict learning opportunities, contributing to lasting consequences for neural development and later academic and occupational achievement. This review delves into the role of cognitive stimulation in neural development and related cognitive performance, available tools for measuring cognitive stimulation in various settings, and offers insights into future research directions. In addition, variability in cognitive stimulation, often linked …

The Seattle Amyotrophic Lateral Sclerosis (Als) Patient Project Database: Observational, Longitudinal, Dyadic Characterization Of People With Als And Their Partners, Suzanne C. Segerstrom, Edward J. Kasarskis

Neurology Faculty Publications

Introduction: The median survival time in ALS is approximately 3 years, but survival times range from less than a year to more than 10 years and much variance in disease course remains to be explained. As is true for physical outcomes, there is considerable variance in QOL, which is influenced by psychological health, coping, and social support, among other psychosocial factors. The Seattle ALS Patient Project Database (SALSPPD) provides a unique opportunity for researchers to address established and novel hypotheses about disease progression and QOL in ALS.

Methods: The SALSPPD is a longitudinal dataset of people with ALS (n = …

Resting-State Eeg Microstate Features For Major Depressive Disorder Classification, George M. V. Quinn

Dissertations, Theses, and Capstone Projects

Neuroimaging studies have revealed consistent abnormalities in functional connectivity within specific neural networks that may serve as biomarkers for major depressive disorder (MDD). It is important to find inexpensive, non-invasive techniques that target these biomarkers to make diagnosis easier and more objective. EEG microstates are quasi-stable potential topographies that are thought to reflect the quasi-stable network activity of the underlying neural generators. MDD has been shown to alter features of the four canonical EEG microstates (A, B, C, D) with some conflicting results. The most consistent network abnormalities in MDD are found in the anterior default mode network, and this …

Voltage Set Points For Sodium Channel Inactivation: Intrinsic And Modulatory Mechanisms, Akshay Sharma

Dissertations, Theses, and Capstone Projects

During an action potential, voltage-gated sodium channels (VGSC) control sodium ion flow into the cytoplasm of cells by using membrane voltage to alter channel conformation. These membrane proteins exhibit three main functional conformations: closed, open, and fast-inactivated, with transitions between these states dependent on membrane voltage and kinetics. The channels open within 1 millisecond and swiftly transition from open to fast-inactivated within 1-2 milliseconds following membrane depolarization. Subsequent membrane repolarization resets the channels to the closed state. Notably, even at mildly depolarized potentials that preclude channel opening, VGSCs can undergo transitions between the closed and inactivated states, known as closed-state …

Repurposing Bt-11 To Treat Alzheimer’S Disease: Exploring The Glutathione-S-Transferase Lancl2 As A Target, Emily Birnbaum

Dissertations, Theses, and Capstone Projects

Approximately 99.6% of potential Alzheimer’s drugs fail, thus developing successful drugs is a high priority. The failure at developing successful drugs relates to the complex nature of the disease itself. Many components act together to trigger a cascade that ultimately results in neurodegeneration and cognitive dysfunction associated with the disease. In building a multiplex model of Alzheimer’s it is important to understand its specific biological mechanisms. One of these key pathological mechanisms is neuroinflammation. Understanding the pathways involved in neuroinflammation in Alzheimer’s is an urgent need, as it poses a promising avenue for future effective therapeutics. Specifically, as many investigational …

Meconium: A Potential Means To Predicting Later-Life Cognition, Leah Duran

Dissertations, Theses, and Capstone Projects

Maternal perinatal stress is a commonly experienced, yet chronically undiagnosed condition (CDC, 2010). Literature has suggested that perinatal stress exposure has long lasting implications of the developing child both physically and mentally (Behrman et al., 2007; Hobel et al., 2008; Bowman et al., 2004; Polanska et al., 2017; Van de Bergh et. al, 2020). The use of meconium in the clinical setting has become one that serves a purpose of detection in medical conditions like in utero drug exposure. Using meconium as a predictor for brain behavior, however, is still an emerging concept in the literature. It is quickly gaining …