Neuroscience and Neurobiology Commons^™

A Novel Switch-Like Function Of Delta-Catenin In Dendrite Development, Ryan Baumert

Dissertations and Theses (Open Access)

The formation of neuronal networks in the brain is tightly regulated, and dependent on the morphology of dendrites, the branch-like signal-receiving structures extending from neurons. Disruptions in dendrite development, or dendritogenesis, can lead to the atypical neuronal connectivity associated with multiple neurodevelopmental diseases. My research addresses molecular processes that underlie dendritogenesis via analysis of a pair of novel interactions involving the protein delta-catenin.

In neurons, delta-catenin localizes to dendrites and synapses, where it functions in their development and maintenance. Structurally, delta-catenin possesses a central Armadillo domain and a C-terminal PDZ-binding motif. This motif associates with PDZ domain-containing proteins, and is …

The Effect Of Traumatic Brain Injury On Tau Pathology By A Potential Seeding Mechanism, George Edwards Iii

Dissertations and Theses (Open Access)

The misfolding, aggregation and accumulation of specific proteins is the overarching concept in protein misfolding disorders (PMDs). The microtubule associated protein tau is known to form insoluble filaments known as neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau (pTau) found in a subset of PMDs called tauopathies, such as Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE), among others. Misfolded tau engenders a structurally alternative intermediate conformation that is prone to aggregate having amyloidogenic properties. Formation of amyloids, such as tau aggregates, is proposed to follow a nucleation-polymerization model where misfolded, soluble oligomeric seeds can trigger native proteins to misfold and …

Modeled Microgravity Induces Neutrophil Extracellular Trap (Net)Osis Formation And Reduced Phagocytosis Of Polymorphonuclear Neutrophils, Amber M. Paul

Publications

Spaceflight can dysregulate immunity, by way of increasing granulocytes numbers with impaired function. Polymorphonuclear neutrophils (PMN) are granulocytes that are first responders to infection or injury, and consist of the largest pool of immune cells in humans. PMNs function during innate immunity, through phagocytosis and promotion of inflammation, via the release of reactive oxygen species (ROS) mediators and granule-containing enzymes, such as myeloperoxidase (MPO) and NADPH oxidase-2 (NOX-2). In addition, neutrophil extracellular trap (NET) formation is another mechanism of PMN surveillance that works independently of engulfment phagocytosis, and is a last resort function that can induce NETosis or PMN-specific cell …

Characterization Of Sensory And Shelter Enrichment In The Rodent Research Habitat, Amber M. Paul, Yasaman Shirazi-Fard, America Reyes, Moniece Lowe, Margareth Cheng-Campbell, Sungshin Choi, Eduardo Almeida, April Ronca, Ruth K. Globus

Publications

The ISS provides a platform for conducting Rodent Research (RR) in microgravity and 9 missions have been successfully conducted. The results from these experiments have begun to provide new insights into the effects of spaceflight on mammalian physiological systems. After RR-1-4, the Flight IACUC required inclusion of additional cage enrichment into the Rodent Habitats (RH) to “enhance animal well-being by providing animals with sensory and motor stimulation, through structures and resources that facilitate the expression of species typical behaviors”. A Hut, in the form of a rigid, mesh igloo-like shelter was implemented beginning with RR-5. The potential influence of the …

Biological And Practical Implications Of Genome-Wide Association Study Of Schizophrenia Using Bayesian Variable Selection, Benazir Rowe, Xiangning Chen, Zuoheng Wang, Jingchun Chen, Amei Amei

School of Medicine Faculty Research

Genome-wide association studies (GWAS) have identified over 100 loci associated with schizophrenia. Most of these studies test genetic variants for association one at a time. In this study, we performed GWAS of the molecular genetics of schizophrenia (MGS) dataset with 5334 subjects using multivariate Bayesian variable selection (BVS) method Posterior Inference via Model Averaging and Subset Selection (piMASS) and compared our results with the previous univariate analysis of the MGS dataset. We showed that piMASS can improve the power of detecting schizophrenia-associated SNPs, potentially leading to new discoveries from existing data without increasing the sample size. We tested SNPs in …

Neuron Specific Gene 2 (Nsg2): A Novel Regulator Of Excitatory Neurotransmission Via Ampa Receptor Trafficking At A Subset Of Glutamatergic Synapses, Praveen Chander

Biomedical Sciences ETDs

Members of the Neuron-Specific Gene family (NSG1-3) play critical roles in excitatory synaptic transmission via regulation of AMPA receptor surface expression within the post-synaptic density (PSD). While NSG1 and NSG3 regulate AMPAR recycling and endocytosis, respectively, the function of NSG2 has remained elusive. Here we undertook a series of studies to assess the role of NSG2 in excitatory synaptic transmission. We found that a portion of NSG2 punctae localized with HOMER1 and surface AMPARs at excitatory synapses and that NSG2 AMPAR subunits in mouse brain. Knockout of NSG2 selectively impaired the frequency of AMPA mEPSCs, while overexpression caused a significant …

Altered Proteasome Expression And Nuclear Factor (Erythroid-Derived 2)-Like Signaling In Experimental Autoimmune Encephalomyelitis, Kara Leasure Shanley

Biomedical Sciences ETDs

Multiple sclerosis (MS) is a complex neurological disorder characterized by the interactions between heightened inflammation, oxidative stress and neurodegeneration. We and others have previously demonstrated that proteasome dysfunction and its consequences are also important factors in the pathology of both MS and its rodent model, experimental autoimmune encephalomyelitis (EAE). While proteasome subunit alterations in EAE have been observed, the underlying mechanisms are poorly understood. The first goal of this dissertation was to characterize the mechanisms that regulate proteasome expression and composition in neural cells in EAE and in vitro.

Immunohistochemical analysis of the EAE spinal cord shows changes in …

Simulated Biological Fluid Exposure Changes Nanoceria’S Surface Properties But Not Its Biological Response, Robert A. Yokel, Matthew L. Hancock, Benjamin Cherian, Alexandra J. Brooks, Marsha L. Ensor, Hemendra J. Vekaria, Patrick G. Sullivan, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce³⁺ and Ce⁴⁺, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria’s surface properties …

Clinical Drug Development For Dementia With Lewy Bodies: Past And Present, Garam Lee, Jeffrey Cummings, Boris Decourt, James B. Leverenz, Marwan N. Sabbagh

School of Medicine Faculty Research

Introduction: Dementia with Lewy bodies (DLB) is an under-researched area despite being the second most common type of degenerative dementia after Alzheimer’s disease. It is an area of unmet need with no approved symptomatic or disease-modifying therapies. The pharmacological management of DLB is complex and challenging because early trials of drugs for DLB have resulted in no demonstrable efficacy. Randomized controlled trials (RCTs) in the DLB population have only recently been initiated. Understanding results from previous and current clinical trials in DLB can provide insights for future research and development. Areas covered: We provide an overview of the DLB drug …

From The Human To The Planetary: Speculative Futures Of Care, Miriam Ticktin

Publications and Research

This is largely a theoretical, speculative essay that takes on the question of what ‘care’ looks like at a moment when climate change is increasingly taking center stage in public and political discussions. Starting with two new practices, namely, humanitarian care for nonhumans and One Health collaborations, I seek to determine what forms of political care can incorporate the well-being of future generations and future iterations of the earth. After an exploration of One Health as an approach to planetary care, I ask what its parts enable us to think, despite its limitations; I focus on the new human-nonhuman assemblages …

Overexpression Of Corticotropin-Releasing Factor In The Nucleus Accumbens Enhances The Reinforcing Effects Of Nicotine In Female Versus Male Rats., Uribe, Victor Correa, Briana Pinales, Rodolfo Flores, Bryan Cruz, Zhiyin Shan, Adriaan Bruijnzeel, Arshad Khan, Laura O'Dell

Departmental Papers (Biology)

This study assessed the role of stress systems in the nucleus accumbens (NAc) in promoting sex differences in the reinforcing effects of nicotine. Intravenous self-administration (IVSA) of various doses of nicotine was compared following overexpression of corticotropin-releasing factor (CRF) in the NAc of female and male rats. Ovariectomized (OVX) females were also included to assess the role of ovarian hormones in promoting nicotine reinforcement. Rats received intra-NAc administration of an adeno-associated vector that overexpressed CRF (AAV2/5-CRF) or green fluorescent protein (AAV2/5-GFP). All rats were then given extended access (23 h/day) to an inactive and an active lever that delivered nicotine. …

A Computational Study Of Sleep And The Hemispheres Of The Brain, Tera Ashley Glaze

Dissertations

Sleep and sleep cycles have been studied for over a century, and scientists have worked on modeling sleep for nearly as long as computers have existed. Despite this extensive study, sleep still holds many mysteries. Larger and more extensive sleep-wake models have been developed, and the circadian drive has been depicted in numerous fashions, as well as incorporated into scores of studies. With the ever-growing knowledge of sleep comes the need to find more ways to examine, quantify, and define it in the context of the most complex part of the human anatomy – the brain. Presented here is the …

Altering Social Cue Perception Impacts Honey Bee Aggression With Minimal Impacts On Aggression-Related Brain Gene Expression, James W. Harrison, Joseph H. Palmer, Clare C. Rittschof

Entomology Faculty Publications

Gene expression changes resulting from social interactions may give rise to long term behavioral change, or simply reflect the activity of neural circuitry associated with behavioral expression. In honey bees, social cues broadly modulate aggressive behavior and brain gene expression. Previous studies suggest that expression changes are limited to contexts in which social cues give rise to stable, relatively long-term changes in behavior. Here we use a traditional beekeeping approach that inhibits aggression, smoke exposure, to deprive individuals of aggression-inducing olfactory cues and evaluate whether behavioral changes occur in absence of expression variation in a set of four biomarker genes …

Network Structure And Dynamics Of Biological Systems, Deena R. Schmidt

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Analog Implementation Of The Hodgkin-Huxley Model Neuron, Zachary D. Mobille, George H. Rutherford, Jordan Brandt-Trainer, Rosangela Follmann, Epaminondas Rosa

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Impact Of Remembering Vs. Knowing On Strength Of Belief In Neuromyths, Kailee Jackola

Mahurin Honors College Capstone Experience/Thesis Projects

As technology advances, misinformation can be spread easier than ever before. Many things the general public believe to be true are either completely false or contradict research findings. However, many people are not willing to give up their belief in false information, even if there is evidence to refute it. Neuromyths are a particular type of widespread misinformation involving incorrect beliefs about brain function (e.g., people can be either left-or right brained). Understanding the origins of neuromyths is important, because it may relate to the strength of individuals’ belief in these myths. Therefore, it is important to determine whether remembering …

The Role Of The Visual Association Cortex In Scaffolding Prefrontal Cortex Development: A Novel Mechanism Linking Socioeconomic Status And Executive Function, Maya L. Rosen, Dima Amso, Katie A. Mclaughlin

Neuroscience: Faculty Publications

Socioeconomic status (SES) is associated with executive function (EF) and prefrontal cortex (PFC) development. However, understanding of the specific aspects of SES that influence development of EF and the PFC remains limited. We briefly review existing literature on proposed mechanisms linking SES with EF. Then, we present a novel conceptual model arguing that early cognitive stimulation shapes EF and PFC development. We propose that cognitive stimulation drives lower-level sensory and perceptual processes that may impact EF and PFC development through reciprocal connections between the ventral visual stream and PFC. We argue that caregivers guide attention and associative learning, which provides …

Voltage-Gated Potassium Channels Are Critical For Infrared Inhibition Of Action Potentials: An Experimental Study, Junqi Zhuo, Matthew T. Mcpheeters, Michael W. Jenkins, Hillel J. Chiel

Faculty Scholarship

Thermal block of unmyelinated axons may serve as a modality for control, suggesting a means for providing therapies for pain. Computational modeling predicted that potassium channels are necessary for mediating thermal block of propagating compound action potentials (CAPs) with infrared (IR) light. Our study tests that hypothesis. Results suggest that potassium channel blockers disrupt the ability of IR to block propagating CAPs in Aplysia californica nerves, whereas sodium channel blockers appear to have no significant effect. These observations validate the modeling results and suggest potential applications of thermal block to many other unmyelinated axons.

Analysis Of Connectivity In Emg Signals To Examine Neural Correlations In Muscular Activation Of Lower Leg Muscles For Postural Stability, Diana Mccrumb

Masters Theses

In quiet standing the central nervous systems implements a pre-programmed ankle strategy of postural control to maintain upright balance and stability. This strategy is comprised of a synchronized common neural drive being delivered to synergistically grouped muscles. In this study connectivity between EMG signals of unilateral and bilateral homologous muscle pairs, of the lower legs, during various standing balance conditions was evaluated using magnitude squared coherence (MSC) and mutual information (MI). The leg muscles of interest were the tibialis anterior (TA), medial gastrocnemius (MG), and the soleus (S) of both legs. MSC is a linear measure of the phase relation …

Auditory And Vestibular Control Of Inverted Pendulum Dynamics In Spatial Orientation, Lila Naheed Fakharzadeh

Link Foundation Modeling, Simulation and Training Fellowship Reports

Human standing balance requires continuously nulling the tendency to fall like an inverted pendulum, and this process relies on the convergence of information from multiple sensory modalities including vestibular, vision, audition, proprioception and somatosensation. Dynamic control of unstable balance is also a critical and difficult task in aviation and spaceflight. Pilots may lose orientation and vehicle control during unstable maneuvers like helicopter hovering in a degraded visual environment or during ambiguous vestibular signaling. It is therefore imperative to determine whether training with combinations of sensory modalities can aid the ability to balance in operational environments where some sensory signals can …

Neural Correlates Of Perceptual Switching While Listening To Bistable Auditory Streaming Stimuli, Nathan C. Higgins, David Frank Little, Breanne D. Yerkes, Karli M. Nave, Abin Kuruvilla-Mathew, M. Elhilai, Joel S. Snyder

Psychology Faculty Research

Understanding the neural underpinning of conscious perception remains one of the primary challenges of cognitive neuroscience. Theories based mostly on studies of the visual system differ according to whether the neural activity giving rise to conscious perception occurs in modality-specific sensory cortex or in associative areas, such as the frontal and parietal cortices. Here, we search for modality-specific conscious processing in the auditory cortex using a bistable stream segregation paradigm that presents a constant stimulus without the confounding influence of physical changes to sound properties. ABA_ triplets (i.e., alternating low, A, and high, B, tones, and _ gap) with a …

Influence Of Social Isolation During Prolonged Simulated Weightlessness By Hindlimb Unloading, Candice G.T. Tahimic, Amber M. Paul, Ann-Sofie Schreurs, Samantha M. Torres, Linda Rubinstein, Sonette Steczina

Publications

The hindlimb unloading (HU) model has been used extensively to simulate the cephalad fluid shift and musculoskeletal disuse observed in spaceflight with its application expanding to study immune, cardiovascular and central nervous system responses, among others. Most HU studies are performed with singly housed animals, although social isolation also can substantially impact behavior and physiology, and therefore may confound HU experimental results. Other HU variants that allow for paired housing have been developed although no systematic assessment has been made to understand the effects of social isolation on HU outcomes. Hence, we aimed to determine the contribution of social isolation …

Altered Gating Of KV1.4 In The Nucleus Accumbens Suppresses Motivation For Reward, Bernadette O'Donovan, Adewale Adeluyi, Erin L Anderson, Robert D. Cole, Jill R. Turner, Pavel I. Ortinski

Neuroscience Faculty Publications

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine …

Neural Correlates Of Decision Making Related To Information Security: Self-Control And Moral Potency, Robert West, Emily Budde, Qing Hu

Publications and Research

Security breaches of digital information represent a significant threat to the wellbeing of individuals, corporations, and governments in the digital era. Roughly 50% of breaches of information security result from the actions of individuals inside organizations (i.e., insider threat), and some evidence indicates that common deterrence programs may not lessen the insiders’ intention to violate information security. This had led researchers to investigate contextual and individual difference variables that influence the intention to violate information security policies. The current research builds upon previous studies and explores the relationship between individual differences in self-control and moral potency and the neural correlates …

Development And Sensory Experience Dependent Regulation Of Microglia In Barrel Cortex, Joshua C. Brumberg, John Kalambogias, Chia-Chien Chen, Safraz Khan, Titus Son, Carolyn Headlam, Cindy Lin

Publications and Research

The barrel cortex is within the primary somatosensory cortex of the rodent, and processes signals from the vibrissae. Much focus has been devoted to the function of neurons, more recently, the role of glial cells in the processing of sensory input has gained increasing interest. Microglia are the principal immune cells of the nervous system that survey and regulate the cellular constituents of the dynamic nervous system. We investigated the normal and disrupted development of microglia in barrel cortex by chronically depriving sensory signals via whisker trimming for the animals’ first postnatal month. Using immunohistochemistry to label microglia, we performed …

Visual Entrainment Of Perception-Related Neural Oscillations As A Mechanism For Maintaining Rhythmic Temporal Expectations Across A Wide Range Of Frequencies, Michael James Gray

Dissertations, Theses, and Capstone Projects

Visual sensitivity fluctuates rhythmically, in-synch with ongoing, EEG-recorded neural oscillations across a wide range of frequencies (~1-25hz). Some recent work has suggested that these perception-related neural oscillations can be entrained by rhythmic visual stimulation. Evidence is also emerging that the entrainment of ongoing oscillations in visual and auditory cortices is involved in rhythmic temporal expectations. In the introduction chapter, I attempt to bridge these bodies of literature and hypothesize that rhythmic visual stimuli automatically entrain ongoing, perception-related neural oscillations and that this mechanism supports the maintenance of rhythmic temporal expectations. Chapters 2 and 3 address this hypothesis from different angles. …

Neurogenesis Is Altered Between And Across Brain Regions After Neurodegeneration And Injury, Alice Perez

Dissertations, Theses, and Capstone Projects

Adult neurogenesis is the addition of new neurons in the adult brain. In mammals, neurogenesis is largely restricted to the hippocampus and olfactory bulb, which underlie learning, memory, and olfaction. In songbirds, new neurons are incorporated into telencephalic regions that subserve the production, perception, and maintenance of song. Studies of the regulation of neurogenesis have exclusively focused on a single brain region and within a single hemisphere. Interestingly, it has yet to be investigated whether there are correlations between numbers of new neurons across regions and hemispheres within the same animal. Here we examined these differences in a rat model …

Neural Correlates Of Automatic Emotional Processing And Emotion Regulation In Empathy And Psychopathy-Related Coldheartedness, Danielle Difilipo

Dissertations, Theses, and Capstone Projects

Psychopathy is a personality disorder that is defined, in part, by a lack of empathy. Psychopathy-related empathic deficits have been associated with atypical behavioral and neural responses to emotional facial expressions. Although the mirror neuron system (MNS) has been implicated in empathy, very few studies have examined the role of MNS functioning as it pertains to empathy impairments in psychopathy. Moreover, there is very little empirical research regarding emotion regulation in psychopathy, and specifically whether emotional responses can be intentionally upregulated. The present study sought to clarify whether the MNS is functionally intact in adults with subclinical psychopathic traits, particularly …

Murine Genetic Variance In Sugar And Fat-Conditioned Flavor Preferences: Roles Of Dopamine, Opioid And Nmda Receptors And Nutritive Sensing, Tamar T. Kraft

Dissertations, Theses, and Capstone Projects

As obesity and diabetes have emerged as a severe public health crisis, understanding the mechanisms underlying the consumption of sugars and fats has become a topic of vigorous study. From a biological standpoint, genetic dispositions, neurochemical and hormonal influences, and predetermined orosensory and postingestive signals that modulate the hunger and satiety process may govern physiological aspects of the obesity puzzle. In addition to an innate appetite and attraction for simple carbohydrates and fats, learning plays an important role in modulating preferences for sugar- and fat-rich foods in rodents, including inbred mouse strains. Marked genetic variance has been observed among murine …

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of the …