Neuroscience and Neurobiology Commons^™

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 …

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 …

Competitive And Noncompetitive Credit Assignment To Reward Cues In The Lateral Orbitofrontal Cortex, Mihwa Kang

Dissertations, Theses, and Capstone Projects

This dissertation investigates the mechanisms underlying variations in credit assignment to reward cues, with a focus on the lateral orbitofrontal cortex (lOFC). The lOFC has long been implicated in signaling reward expectancies, with controversy as to whether it signals the economic value of future outcomes, their sensory features to guide behavior or both. However, whether the lOFC signals the relative (competition-dependent) or absolute (contiguity-dependent) credit of cues is unknown. To address this, I employed a combination of novel behavioral assays, in-vivo electrophysiological recordings and optogenetic stimulation in rats. In Chapter 2, I tested the suitability of a self-initiating variant of …

Novel Psychoplastogen Dm506 Reduces Cue-Induced Heroin-Seeking And Inhibits Tonic Gaba Currents In The Prelimbic Cortex, Kassandra Looschen, Shailesh N. Khatri, Malabika Maulik, Colin Salisbury, Alaina F. Carman, Katilyn Corriveau, Colton Smith, Dina Manetti, Maria Novella Romanelli, Hugo R. Arias, Cassandra D. Gipson, Swarup Mitra

Markey Cancer Center Faculty Publications

Opioid use disorder is a major public health crisis that is manifested by persistent drug-seeking behavior and high relapse frequency. Most of the available treatments rely on targeting opioid receptors using small molecules that do not provide sustained symptom alleviation. Psychoplastogens are a novel class of non-opioid drugs that produce rapid and sustained effects on neuronal plasticity, intended to produce therapeutic benefits. Ibogalogs are synthetic derivatives of iboga alkaloids that lack hallucinogenic or adverse side effects. In the current study, we examine the therapeutic potential of DM506, a novel ibogalog lacking any cardiotoxic or hallucinogenic effects, in cue-induced seeking behavior …

Large Deviation Theory In Stochastic Processes: Applications To Biological Modeling, Moshe C. Silverstein

Dissertations

This dissertation delves into developing and applying stochastic models to analyze complex biological systems. It leverages Large Deviation Theory (LDT) to gain insights into these systems, focusing on two key examples: neural networks and calcium signaling dynamics. Traditional deterministic methods frequently fail to capture biological processes' randomness and inherent variability. Meanwhile, many stochastic approaches struggle to be mathematically tractable or provide accessible insights. The approach introduced in this study provides rigorous mathematical frameworks to enhance understanding of these stochastic behaviors while remaining tractable and insightful.

A stochastic model for a random biological neural network is constructed that addresses the dependencies …

The Neuroscience Of Mindfulness Based Art Therapy: A Literature Review, Elizabeth Strasser

Expressive Therapies Capstone Theses

Art therapy and neuroscience are two fields which are currently growing and expanding with the development of new technology which allows for therapists and scientists to advance their understanding of how the brain and the body respond to the world around us. The interaction between the brain, body, and environment is complex, and for the sake of clarity for this thesis this interaction will be conceptualized through the lens of the body-mind model, polyvagal theory, neuroaesthetics, the flow state, mindfulness, sensory engagement, and art as therapy. Neuroscience in relation to psychology can be used to develop a deeper understanding of …

Unraveling The Role Of Hid-1: Insights Into Sgii Regulation, Breanna L. Sellers

Electronic Theses and Dissertations

The regulated secretory pathway is important for the secretion of hormones and neuropeptides from large dense core vesicles (LDCVs). Dysregulation of the biogenesis of LDCVs can result in metabolic and neurological diseases. Recent studies have suggested that the peripheral membrane protein HID-1 plays a role in the sorting and storage of granins which contribute to LDCV biogenesis. To further understand how HID-1 influences the regulation of granins, we investigated potential HID-1 interactors. We determined that while HID-1 is likely functioning in the same pathway as USP25, a deubiquitinating enzyme (DUB), the cause of reduced cellular SgII levels is likely not …

Slow Ramping Emerges From Spontaneous Fluctuations In Spiking Neural Networks, Jake Gavenas, Ueli Rutishauer, Aaron Schurger, Uri Maoz

Psychology Faculty Articles and Research

The capacity to initiate actions endogenously is critical for goal-directed behavior. Spontaneous voluntary actions are typically preceded by slow-ramping activity in medial frontal cortex that begins around two seconds before movement, which may reflect spontaneous fluctuations that influence action timing. However, the mechanisms by which these slow ramping signals emerge from single-neuron and network dynamics remain poorly understood. Here, we developed a spiking neural-network model that produces spontaneous slow ramping activity in single neurons and population activity with onsets ~2 s before threshold crossings. A key prediction of our model is that neurons that ramp together have correlated firing patterns …

Multiple Guidance Mechanisms Control Axon Growth To Generate Precise T-Shaped Bifurcation During Dorsal Funiculus Development In The Spinal Cord, Bridget M. Curran, Kelsey R. Nickerson, Andrea R. Yung, Lisa V. Goodrich, Alexander Jaworski, Marc Tessier-Lavigne, Le Ma

Farber Institute for Neuroscience Faculty Papers

The dorsal funiculus in the spinal cord relays somatosensory information to the brain. It is made of T-shaped bifurcation of dorsal root ganglion (DRG) sensory axons. Our previous study has shown that Slit signaling is required for proper guidance during bifurcation, but loss of Slit does not affect all DRG axons. Here, we examined the role of the extracellular molecule Netrin-1 (Ntn1). Using wholemount staining with tissue clearing, we showed that mice lacking Ntn1 had axons escaping from the dorsal funiculus at the time of bifurcation. Genetic labeling confirmed that these misprojecting axons come from DRG neurons. Single axon analysis …

Long-Term Neurodevelopmental Outcomes Post-Chronic Midazolam Exposure During Early Life, Nghi M. Nguyen

Theses & Dissertations

In recent decades, the rising number of neonates born in the Neonatal Intensive Care Unit (NICU) due to prematurity has raised concerns about their overall well-being and development. Premature neonates are at higher risk of health complications and often require invasive procedures. These invasive procedures often induce stress and agitation, prompting physicians and healthcare providers to provide sedation or general anesthesia to manage discomfort. Epidemiological studies of human patients have revealed a correlation between childhood exposure to general anesthetic and sedative agents and subsequent cognitive deficits. This association is also supported in animal models, which shows that exposure to anesthetics …

The Effect Of Acute Social Isolation On Neural Molecular Responses In Components Of The Social Decision-Making Network, Patricia C. Lopes, Madeleine Chang, Faith Holloway, Biola Fatusin, Sachin Patel, Chandler Siemonsma, Morgan Kindel

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Prolonged or chronic social isolation has pronounced effects on animals, ranging from altered stress responses, increased anxiety and aggressive behaviour, and even increased mortality. The effects of shorter periods of isolation are much less well researched; however, short periods of isolation are used routinely for testing animal behaviour and physiology. Here, we studied how a 3 h period of isolation from a cagemate affected neural gene expression in three brain regions that contain important components of the social decision-making network, the hypothalamus, the nucleus taeniae of the amygdala, and the bed nucleus of the stria terminalis, using a gregarious bird …

Prelimbic Neuronal Ensembles In Natural Reward Seeking, Roger Ian Grant

MUSC Theses and Dissertations

External cues can become powerful motivators of behavior when paired with rewarding stimuli, such as natural rewards or drugs of abuse, as is the case in individuals with substance use disorder (SUD). The dorsomedial prefrontal cortex (dmPFC) has been implicated as a neural substrate which encodes cue-reward associations and has been shown to exert top-down control over both natural and drug reward seeking. We and others have shown that activity within the dmPFC is heterogeneous during reward seeking, with some neurons displaying excitatory responses to reward-predictive cues, and others showing inhibitory responses to the same cues. Furthermore, this response heterogeneity …

Investigating The Role Of Insulin-Like Signaling In Paclitaxel-Induced Nociceptive Hypersensitivity Using Drosophila Melanogaster, Sreepradha Sridharan

Dissertations and Theses (Open Access)

Paclitaxel (PTX), a chemotherapeutic that alters microtubule dynamics, is known to induce nociceptive hypersensitivity and sensory neuron damage in human patients and in Drosophila larvae. We used a modified feeding protocol to establish a genetically tractable Drosophila model of PTX-induced hypersensitivity. Larvae fed PTX exhibited hypersensitivity to thermal and mechanical stimuli. Thermal hypersensitivity was observed at low concentrations of PTX (even below 1 μM per ml of food), begins within 8 hours of PTX feeding, and did not completely resolve at the larval stage. Live imaging of peripheral thermal nociceptors showed that this hypersensitivity precedes observable neuronal damage. At low …

The Role Of The Circadian Clock In The Paraventricular Nucleus Of The Hypothalamus In Diurnal Energy Balance, Rachel Van Drunen

Dissertations and Theses (Open Access)

Circadian rhythms are internal biological rhythms that drive oscillations in physiology and metabolism. Maintained at the level of individual cells throughout the body, the circadian clock is necessary for driving tissue-specific temporal programs of energy balance. Though loss of the circadian transcription factor, BMAL1, in the paraventricular nucleus (PVN) of the hypothalamus has revealed its importance in driving rhythms in energy intake and metabolism, its transcriptional functions across time and in individual cell types in the PVN are not well understood. In this study, we show that loss of BMAL1 in the PVN not only results in arrhythmicity in processes …

Decision-Making In Rats: Effects Of Drug Abuse, Safa Binte Hossain

Open Access Theses & Dissertations

Decision-making is a critical cognitive function, often impaired by substance abuse. Understanding the underlying mechanisms in both human and animal models is essential for developing effective treatments. This thesis aims to study approach-avoid decision-making in rats and focuses on the impacts of oxycodone self-administration and alcohol abuse on approach-avoid decision-making.We hypothesize that oxycodone self-administration will alter decision-making in female rats, revealing sex differences and distinct psychometric functions, alcohol habituation will similarly affect decision-making in male rats. The study involved 23 Long Evans rats (11 males and 12 females) for decision-making behavioral study connecting multiple levels of rewards and costs combinations. …