Neuroscience and Neurobiology Commons^™

Restructuring Of The Axon Initial Segment In Mouse Models Of Neurodevelopmental Disorders, Rachel Ali Rodriguez

UNLV Theses, Dissertations, Professional Papers, and Capstones

Neurodevelopmental disorders (NDDs) affect more than 36% of children in countries with low- and middle- incomes (Boivin, 2015; McCoy, 2016). Interestingly, these heterogeneous disorders share a high incidence of epileptic seizures, suggesting a shared pathology. Seizures result when neuronal firing activity becomes disturbed and neurons fire excessively or in unregulated patterns. A key site in the control of neuronal firing patterns is the axon initial segment (AIS), where the local density of proteins and the morphology of the AIS in part determine the firing of neurons. We hypothesized that a disruption in the morphology and/or composition of the AIS can …

An Autism-Causing Variant Misregulates Selective Autophagy To Alter Axon Targeting And Behavior, Tyler Buddell

Theses and Dissertations

Neurodevelopmental disorders cause debilitating disruptions to the cellular mechanisms that underlie development of the brain. Unfortunately, the complexities of neurodevelopmental disorders make them difficult to study, and the molecular mechanisms perturbed by these disorders remain elusive. Better understanding of neurodevelopmental mechanisms, and the related genes involved, will likely yield new insight into neurodevelopmental disorders. A gene that has been associated with a number of neurodevelopmental disorders is the calcium voltage-gated channel subunit alpha1 C (CACNA1C) gene. Common and rare variants of the CACNA1C gene have been associated with autism and other neurodevelopmental disorders including schizophrenia, bipolar disorder and ADHD. However, …

Understanding Object Motion Encoding In The Mammalian Retina., Victor Julian Depiero

Electronic Theses and Dissertations

Phototransduction, transmission of visual information down the optic nerve incurs delays on the order of 50 – 100ms. This implies that the neuronal representation of a moving object should lag behind the object’s actual position. However, studies have demonstrated that the visual system compensates for neuronal delays using a predictive mechanism called phase advancing, which shifts the population response toward the leading edge of a moving object’s retinal image. To understand how this compensation is achieved in the retina, I investigated cellular and synaptic mechanisms that drive phase advancing. I used three approaches, each testing phase advancing at a …

The Genetics Of Olfactory And Visually Guided Attractive Behaviors In Aedes Aegypti Mosquito, Joshua Ibukun Raji

FIU Electronic Theses and Dissertations

Mosquitoes detect their hosts and seek suitable resources crucial for survival by integrating chemosensory, thermal, and visual cues. The diversity of the cues involved in mosquito attractive behaviors has made the design of behavioral control strategies a challenge. The genetic basis of mosquito attractive behaviors can now be determined using genome editing. The contribution of the IR8a chemosensory pathway was uncovered by disrupting the IR8a co- receptor in Aedes aegypti using CRISPR/Cas9. Ir8a mutant female mosquitoes are not attracted to lactic acid, a behaviorally active component of human sweat, and lack odor-evoked responses to acidic volatiles. The loss of Ir8a …

The Functional Conservation Of Frazzled In Insects, Benjamin Wadsworth

Graduate Theses and Dissertations

Axons in the developing embryo receive and react to signals that direct their growth to reach target tissues at specified locations. The signal pathways that direct midline crossing of axons during embryonic development have been comprehensively examined in the past years using the Drosophila ventral nerve cord or the spinal cord as a model system. A number of these signaling mechanisms are conserved, however disparities have been found between species in general strategy or the molecular signals controlling the response of axons to guidance cues.

The Netrin-Frazzled pathway has been shown to aid in midline crossing of axons in the …

Trpm4 Ion Channels In Pre-Bo¨Tzinger Complex Interneurons Are Essential For Breathing Motor Pattern But Not Rhythm, Marina Cristina D. Picardo, Yae K. Sugimura, Kaitlyn E. Dorst, Prajkta S. Kallurkar, Victoria T. Akins, Xingru Ma, Ryoichi Teruyama, Romaine Guinamard, Kaiwen Kam, Margaret Saha, Christopher A. Del Negro

Christopher Del Negro

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and …

Gene Co-Expression Analysis Of The Human Substantia Nigra Identifies Bmp2 As A Neurotrophic Factor That Can Promote Neurite Growth In Cells Overexpressing Wild-Type Or A53t Α-Synuclein, Susan R. Goulding, Aideen M. Sullivan, Gerard W. O'Keeffe, Louise M. Collins

Department of Biological Sciences Publications

Introduction: α-synuclein-induced degeneration of dopaminergic neurons has been proposed to be central to the early progression of Parkinson's disease. This highlights the need to identify factors that are neuroprotective or neuroregenerative against α-synuclein-induced degeneration. Due to their potent neurotrophic effects on nigrostriatal dopaminergic neurons, we hypothesized that members of the bone morphogenetic protein (BMP) family have potential to protect these cells against α-synuclein. Methods: To identify the most relevant BMP ligands, we used unbiased gene co-expression analysis to identify all BMP family members having a significant positive correlation with five markers of dopaminergic neurons in the human substantia nigra (SN). …

Comparison Of Nickel And Cobalt Induced Hypoxic Cell Models Using Cell Proliferation Assay, Melissa Delcasale

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is an imbalance in oxygen delivery and oxygen consumption, ultimately affecting cell survival. Low levels of oxygen diminish adenosine triphosphate synthesis resulting from a decline in oxidative phosphorylation in the mitochondria, therefore inducing apoptosis and cell death. To create a hypoxia mimicked environment, we used hypoxia mimetic compounds cobalt and nickel to treat human neuroblastoma (NMB) cells. Using hypoxic mimic human neuronal cell models, we examined and compared the effects of compound-induced hypoxia on NMB cell proliferation. The cells were treated with 100mM and 300mM concentrations of each compound at 24- and 48-hour intervals. To investigate cell proliferation, the …

Evolutionary Expansions And Neofunctionalization Of Ionotropic Glutamate Receptors In Cnidaria, Ellen G. Dow

FIU Electronic Theses and Dissertations

Reef ecosystems are composed of a variety of organisms, transient species of fish and invertebrates, microscopic bacteria and viruses, and structural organisms that build the living foundation, coral. Sessile cnidarians, corals and anemones, interpret dynamic environments of organisms and abiotic factors through a molecular interface. Recognition of foreign molecules occurs through innate immunity via receptors identifying conserved molecular patterns. Similarly, chemosensory receptors monitor the environment through specific ligands. Chemosensory receptors include ionotropic glutamate receptors (iGluRs), transmembrane ion channels involved in chemical sensing and neural signal transduction. Recently, an iGluR homolog was implicated in cnidarian immunological resistance to recurrent infections of …

Jet Lag: What’S Light Got To Do With It?, Melissa Richardson

Adventist Human-Subject Researchers Association

Jet lag results in memory loss and sleepiness. Current treatments for jet lag focus on symptoms and not the cause of jet lag; disrupted light environment. This study in mice, uncovered mechanisms of how light regulates jet lag recovery and memory. This work informs our future studies in humans.

Detecting The Cold: Do Innexins Function In Cold Nociception?, Rachel Barborek

Senior Honors Projects, 2010-2019

Nociception is the perception of and response to harmful stimuli. Nociception is essential for minimizing tissue damage, but aberrant nociceptive pathways can result in chronic pain. Chronic pain in the U.S. is commonly managed with wide-acting opioids, and precisely defining the components of nociceptive pathways could uncover novel targets for pain therapies. I hypothesize that the vitally quick process of nociception would utilize electrical synapses because they transmit signals between neurons more quickly than chemical synapses do. This study, therefore, aims to uncover the potential role of the eight Drosophila melanogaster gap junction proteins, the Innexins, in cold nociception. Wild …

Human Anatomy And Physiology I: Course Map With Expected Learning Outcomes, Carlos Liachovitzky

Open Educational Resources

This document contains a list with all the Anatomy and Physiology I expected learning outcomes organized by topics, and grouped into ten units: 1. Introduction to A&P: body plan & organization; 2. Introduction to A&P: homeostasis; 3. The chemical level of organization; 4. Levels of organization: the cellular level of organization; 5. Levels of organization: the tissue level of organization; 6. Support and movement: integumentary system; 7. Support and movement: skeletal system & articulations; 8. Support and movement: muscular system; 9. Regulation, integration, and control: nervous system; 10. Regulation, integration, and control: special senses

Each learning outcome is referred to …

Defects In Fetal Mouth Movement And Pharyngeal Patterning Underlie Cleft Palate Caused By Retinoid Deficiency., Regina Friedl

Electronic Theses and Dissertations

Cleft palate is a common birth defect. Etiologic mechanisms of palate cleft include defects in palate morphogenesis, mandibular growth, or spontaneous fetal mouth movement. Cleft palate linked to deficient fetal mouth movement has been demonstrated directly only in a single experimental model of loss of neurotransmission. Here, using retinoid deficient mouse embryos, we demonstrate directly for the first time that deficient fetal mouth movement and cleft palate occurs as a result of mis-patterned development of pharyngeal peripheral nerves and cartilages. Retinoid deficient embryos were generated by inactivation of retinol dehydrogenase 10 (Rdh10), which is critical for production of …

The 5-Ht1a-R Knockout Mouse As A Model Of Later Life Anxiety Disorders: Implications For Sex Differences, Tatyana Budylin

Dissertations, Theses, and Capstone Projects

Anxiety affects nearly twice as many women as it affects men across all cultures and economic groups. Importantly, girls have a higher chance of inheriting anxiety disorders than boys, and many anxiety disorders appear at a very young age. However, little is known about sex differences in brain and behavioral development and how they relate to anxiety in adulthood. Serotonin 1A receptor (5-HT_1A-R) mediated signaling has been implicated in depression and anxiety, however most studies that focus on the involvement of the 5-HT_1A-R have been conducted in adults. Little is known about how the 5-HT_{1A …}

Law And Biology: Toward An Integrated Model Of Human Behavior, Owen D. Jones

Owen Jones

As first year law students unhappily discover, the meaning of "law" is frustratingly protean, shifting by usage and user. Depending on whom you ask, law is a system of rules, a body of precedents, a legislative enactment, a collection of norms, a process by which social goals are pursued, or some dynamic mixture of these. Law's principal purpose is to define and protect individual rights, to ensure public order, to resolve disputes, to redistribute wealth, to dispense justice, to prevent or compensate for injury, to optimize economic efficiency, or perhaps to do something else. And yet one thing is irreducibly …

Testing The Impact Of Prebiotics On Anxiety-Like Behaviors In Aged Male Rats, Nicholai Shaw, Marny Ehmann, Kenia Urena-Gonzalez, Anna Langholz, Peter Stewart, Jared Stygstra, Emily Zolman, Erin English, Alli Lindquist, Elizabeth Woodford

18th Annual Celebration of Undergraduate Research and Creative Activity (2019)

The composition of gut microbiota has direct impacts on neural structure, neurochemistry, and behavior. Specifically, the gut microbiota has been shown to modulate anxiety-like behaviors. In addition, administering prebiotics, compounds that promote the growth of commensal bacteria, has been demonstrated to reduce anxiety and anxiety-related behaviors. However, this effect has yet to be tested in older animals despite anxiety being implicated as a most common disorder in adult populations. Therefore, this study seeks to fill this knowledge gap by investigating the link between prebiotic interventions and anxiety-like behaviors in aged populations. It was hypothesized that older rats treated with the …

The Effects Of Bacterial Endotoxin Lps On Synaptic Transmission At The Neuromuscular Junction, Robin L. Cooper, Micaiah Mcnabb, Jeremy Nadolski

Biology Faculty Publications

The direct action of bacterial lipopolysaccharides (LPS) endotoxin was shown to enhance synaptic transmission and hyperpolarize the membrane potential at low doses, but block glutamatergic receptors and decrease observable spontaneous events at a high dosage. The dosage effects are LPS type specific. The hyperpolarization is not due to voltage-gated potassium channels or to activation of nitric oxide synthase (NOS). The effects are induced directly by LPS, independent of an immune response.

Role Of Withaferin A As A Neuroprotectant Against Beta Amyloid Induced Toxicity And Associated Mechanism, Sneham Tiwari

FIU Electronic Theses and Dissertations

Neurological disorders are the biggest concern globally and ageing contributes in worsening the disease scenarios. In AD or AD like diseases, there is abnormal accumulation of extracellular amyloid beta produced due to abnormal processing of the transmembrane amyloid precursor protein, by β and γ-secretases. It spreads in the cortical and limbic regions of the brain leading to neuronal toxicity, impairment in memory and neurological functions. Aβ deposition in the CNS is common in aging HIV patients. Neurotoxic protein Tat, results in increased Aβ in combination with drugs of abuse cocaine. We examined the role of Withaferin A, against Aβ induced …

Cognition And The Brain Of Brood Parasitic Cowbirds., David F Sherry, Mélanie F Guigueno

Psychology Publications

Cowbirds are brood parasites. Females lay their eggs in the nests of other species, which then incubate the cowbird eggs and raise the young cowbirds. Finding and returning to heterospecific nests presents cowbirds with several cognitive challenges. In some species, such as brown-headed cowbirds (Molothrus ater), females but not males search for and remember the locations of potential host nests. We describe recent research on sex differences in cognition and the hippocampus associated with this sex difference in search for host nests. Female brown-headed cowbirds perform better than males on some, but not all, tests of spatial memory and females …

Trpm4 Ion Channels In Pre-Bo¨Tzinger Complex Interneurons Are Essential For Breathing Motor Pattern But Not Rhythm, Marina Cristina D. Picardo, Yae K. Sugimura, Kaitlyn E. Dorst, Prajkta S. Kallurkar, Victoria T. Akins, Xingru Ma, Ryoichi Teruyama, Romaine Guinamard, Kaiwen Kam, Margaret Saha, Christopher A. Del Negro

Arts & Sciences Articles

Inspiratory breathing movements depend on pre-Bötzinger complex (preBötC) interneurons that express calcium (Ca2+)-activated nonselective cationic current (ICAN) to generate robust neural bursts. Hypothesized to be rhythmogenic, reducing ICAN is predicted to slow down or stop breathing; its contributions to motor pattern would be reflected in the magnitude of movements (output). We tested the role(s) of ICAN using reverse genetic techniques to diminish its putative ion channels Trpm4 or Trpc3 in preBötC neurons in vivo. Adult mice transduced with Trpm4-targeted short hairpin RNA (shRNA) progressively decreased the tidal volume of breaths yet surprisingly increased breathing frequency, often followed by gasping and …

A Cross-Species Analysis Reveals A General Role For Piezo2 In Mechanosensory Specialization Of Trigeminal Ganglia From Tactile Specialist Birds, Eve R. Schneider, Evan O. Anderson, Viktor V. Feketa, Marco Mastrotto, Yury A. Nikolaev, Elena O. Gracheva, Sviatoslav N. Bagriantsev

Biology Faculty Publications

A major challenge in biology is to link cellular and molecular variations with behavioral phenotypes. Here, we studied somatosensory neurons from a panel of bird species from the family Anatidae, known for their tactile-based foraging behavior. We found that tactile specialists exhibit a proportional expansion of neuronal mechanoreceptors in trigeminal ganglia. The expansion of mechanoreceptors occurs via neurons with intermediately and slowly inactivating mechanocurrent. Such neurons contain the mechanically gated Piezo2 ion channel whose expression positively correlates with the expression of factors responsible for the development and function of mechanoreceptors. Conversely, Piezo2 expression negatively correlates with expression of molecules mediating …

The Effects Of Ocular Dominance On Visual Processing In College Students, William Alexander Holland

James Madison Undergraduate Research Journal (JMURJ)

The role of ocular dominance in processing visual memory and analytic tasks is unknown. Research has variably showed both significant effects and no effect of ocular dominance on visual perception, motor control, and sports performance. The goal of this study was to determine if there is a relationship between ocular dominance and visual processing under a variety of computer gaming tasks. This was accomplished by first determining subjects’ ocular dominance through the Miles test, and then examining the subjects’ visual performance on four different Lumosity games under three conditions: left eye, right eye, and both eyes. Results suggest a relationship …

Molecular Analysis Of Cone Photoreceptor Genesis From A Specific Retinal Progenitor Population, Diego F. Buenaventura

Dissertations, Theses, and Capstone Projects

There are two types of photosensitive cells of the retina that contribute to image formation: Cone photoreceptors that mediate color discrimination and rods that provide photosensitivity in low-light conditions. Given the importance of cones in high acuity and color vision, deficiencies in this cell type that result from ailments such as retinitis pigmentosa and macular degeneration can lead to a debilitating loss of vision. Currently, one of the most pressing goals in the field of retinal development is the elucidation of the gene regulatory networks (GRN) involved in inducing an undifferentiated cell into becoming a functional cone photoreceptor.

Recently, an …

The Role Of H3k4 Methyltransferases In Drosophila Memory, Nicholas Raun

Electronic Thesis and Dissertation Repository

Gene transcription required for long-term memory requires the modification of histones. However, there are still many uncertainties about the identity and spatial expression of genes regulated by histone modifications during memory related processes. In this project I examined the role of Drosophila melanogaster methyltransferases Set1 and trx in courtship memory. Genetic knockdown of Set1 and trx in the mushroom body (MB) revealed that Set1 was necessary for short- and long-term memory, while trx was only required for long-term memory. Transcriptional profiling of MBs following trx-knockdown revealed expression changes in MB-enriched genes and genes involved in RNA processing. Among the …

Analysis Of The Genetic And Neurological Components Of Opioid Addiction, With Public Health Perspectives Of The Opioid Epidemic In The United States Of America, Janhavi A. Dubhashi

DISCOVERY: Georgia State Honors College Undergraduate Research Journal

Opioid addiction has reached epidemic levels around the world, with over-prescription of opioid pain relievers being an often-cited reason for the epidemic in the USA. This project looks at opioid addiction from three perspectives: a review of literature dealing with the neural pathways involved in opioid use and addiction; the underlying genetic differences that can increase the risk of opioid use disorder; and an overview of the public health aspects of the epidemic. The paper will conclude with a review of current and new treatments based upon a growing neurobiological and molecular understanding of opioid use disorder.

Molecular Mechanism Of Neurodegeneration Induced By 4-Nonylphenol, Michelle Alejandra Aranda

Open Access Theses & Dissertations

Neurodegeneration, a progressive loss of nerve cells, occurs in many neurological disorders, including Alzheimer's disease (AD) and Parkinson's diseases (PD), as well as in dementia. The pathogenesis of these diseases is unknown, and recent evidence suggests that environmental factors, which act as endocrine-disrupting compounds (EDCs) could play a significant role in developing the disease process. 4-Nonylphenol (4-NP), an EDC, and a ubiquitous environmental toxin has been shown to affect brain development and may cause neurodegeneration. 4-NP is produced in large quantities in the U.S. and used as raw materials for making detergents, pesticides, plastics, paints, cosmetics, rubber, and other industrial/household …

Shining Light On An Amygdala -- Brainstem Connection Important For Attention Processing, Jose Carlos Cano

Open Access Theses & Dissertations

We are continuously being exposed to an exorbitant amount of sensory information, which should result overwhelming. However, the nervous system operates several intrinsic sensory filtering mechanisms that allow us to cope with such sensory cluttering and shape appropriate behavior. Sensorimotor gating is a pre-attentive neuronal filtering mechanism that gates superfluous sensory information, and orients attentional resources towards salient information processing. Its relevance becomes in individuals suffering from schizophrenia and several otherwise unrelated neuropsychiatric disorders where sensorimotor gating is impaired. To understand the neural impaired mechanisms, extensive research studies have focused on first identifying the neural substrates underlying sensorimotor gating. This …

Data Collection Curated With An Application Ontology Describes The Methods And Results Upon Performing An Ex-Vivo Voltage-Clamp Assay On Outer Hair Cells Of The Mammalian Cochlea, Brenda Farrell, Jason Bengtson

Research Data

This data collection describes the electrical properties of outer hair cells isolated from the mammalian cochlea of the domestic guinea pig. This data was obtained by performing whole-cell patch clamp voltage clamp assay on cells and monitoring the electrical admittance during a DC voltage ramp. The membrane capacitance was then calculated at each membrane potential from this admittance, and the voltage-independent and voltage-dependent membrane capacitance was determined upon further analysis. In some case the DC conductance was also measured by interrogation of the cell with voltage-step function which was calculated from the change in the mean steady-state current with respect …

Investigating The Role Of Neuronal Aging In Fragile X-Associated Tremor/Ataxia Syndrome, Katlin Marie Hencak

Honors Undergraduate Theses

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an X-linked late-onset neurodegenerative disorder caused by a noncoding trinucleotide repeat expansion in the FMR1 gene. This gene produces fragile x mental retardation protein (FMRP), an RNA binding protein whose targets are involved in brain development and synaptic plasticity. One of the proposed mechanisms of FXTAS pathogenesis is an RNA gain-of-function in which the repeat expansion causes toxic mRNA that sequesters important proteins in the cell, interfering with their functions. Another suggested method of pathogenesis is through a mutant protein called FMRpolyG. This protein results from repeat-associated non-AUG (RAN) translation, in which the expanded …

A Composite Review Of The Proposed Molecular Mechanisms And Genetic Components Underlying Parkinson’S Disease, Paige Brodrick

Scripps Senior Theses

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the progressive death of dopaminergic neurons present in the substantia nigra. The clinical presentation of PD includes tremors, slowed movement (bradykinesia), muscle and limb rigidity, and difficulty with walking and balancing. While many environmental factors can affect the onset and progression of the disease, genetic mutations have a large influence. Of the identified PD-linked genetic mutations, mutations in the leucine-rich repeat kinase 2 (LRRK2) are one of the most common genetic causes of PD. Located in endosomes, LRRK2 has been shown to play a role in the sorting and endocytosis …