Neuroscience and Neurobiology Commons^™

Her9/Hes4 Is Required For Retinal Photoreceptor Development, Maintenance, And Survival, Cagney E. Coomer, Stephen G. Wilson, Kayla F. Titialii-Torres, Jessica D. Bills, Laura A. Krueger, Rebecca A. Petersen, Evelyn M. Turnbaugh, Eden L. Janesch, Ann C. Morris

Biology Faculty Publications

The intrinsic and extrinsic factors that regulate vertebrate photoreceptor specification and differentiation are complex, and our understanding of all the players is far from complete. Her9, the zebrafish ortholog of human HES4, is a basic helix-loop-helix-orange transcriptional repressor that regulates neurogenesis in several developmental contexts. We have previously shown that her9 is upregulated during chronic rod photoreceptor degeneration and regeneration in adult zebrafish, but little is known about the role of her9 during retinal development. To better understand the function of Her9 in the retina, we generated zebrafish her9 CRISPR mutants. Her9 homozygous mutants displayed striking retinal phenotypes, including decreased …

Gene Regulation And Cell Fate Choice In The Developing Vertebrate Retina, Sruti Patoori

Dissertations, Theses, and Capstone Projects

The diverse neuronal cell types in the vertebrate retina all originate from multipotent retinal progenitor cells (RPCs). These undergo a series of molecular changes driven by developmental gene regulatory networks (GRNs) as they divide to generate RPCs which are more restricted in their potential fates. It is crucial to understand these GRNs and changes to gene expression in order to understand how cell identity is established during retinal development. In particular, the GRN that promotes the development of cone photoreceptors and horizontal cells is not well-defined. This work focuses on two approaches to further elucidate the components of this regulatory …

Mental Associations And Music Therapy: Including The History Of Associationism And The Neurology Of Associations, Dianna Rose

Expressive Therapies Capstone Theses

Associations are formed in our minds based upon three elements: sensory experience, emotions, and memories. These associations, unique to each individual, dictate thoughts, beliefs, behaviors, and actions. Some are necessary and supportive, while others can be maladaptive. Established associations can be changed, and new associations can be formed, to align with a client’s goals. The literature presents a strong history of associationism, as well as a body of research that demonstrates the neurological processes of how mental associations are formed. There are also studies showing how music activates the brain. However, there is a lack of research which draws direct …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Biology - All Scholarship

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

Sexually Dimorphic Alterations In Brain Morphology Of Astrocyte Conditional System Xc- Knockout Mice, Gabrielle Emily Samulewicz

Renée Crown University Honors Thesis Projects - All

Astrocytes play a vital role in orchestrating the precise brain wiring that occurs during development and are essential for maintaining homeostasis into adulthood. The cystine/glutamate antiporter, system xc-, in the central nervous system is especially abundant in astrocytes and itself is known to contribute importantly to the basal extracellular glutamate concentration as well as the intracellular and extracellular glutathione levels, either of which, if perturbed, could alter brain development and/or contribute to degeneration. Thus, to determine whether loss of astrocyte system xc- might alter brain morphology, I studied a conditional astrocyte system xc- knockout mouse (AcKO). Tissue was harvested from …

Molecular And Behavioral Studies In Cdkl5 Deficiency Disorder, Ethan Schroeder

Theses & Dissertations

CDKL5 Deficiency Disorder (CDD) is an X-linked neurodevelopmental disorder associated with epilepsy, developmental retardation, autism, and related phenotypes. Currently, there is no cure available for the disorder. Thus, the identification of cellular and molecular aberrations in this disorder and the generation and validation of mouse models that recapitulate core aspects of the disorder are a pressing need in the field. Our studies are aimed at filling this gap.

Mutations in the CDKL5 gene, encoding CDKL5, have been identified in this disorder. CDKL5 is a protein with homology to the serine-threonine kinases and incompletely characterized function. Mutations in CDKL5 are predominately …

Neurocognitive Risk Factors And Current Intervention Strategies For Survivors Of Pediatric Acute Lymphoblastic Leukemia, Abigail Taber

Senior Honors Theses

The improved survival rate for pediatric cancer patients is one of the greatest triumphs of recent medicine, but the late effects faced by these survivors have been uncovered through this new population of survivors. Many survivors of pediatric acute lymphoblastic leukemia (ALL) experience cognitive deficits in areas such as attention, memory, processing speed, and academic achievement following cancer treatment. Recent research has pointed to chemotherapeutic agents, host risk factors, and genetic predispositions as perpetrators of these deficits, although other factors are also under investigation. Consequently, the search for appropriate interventions for the amelioration of these deficits has dominated the literature …

Reorganization Of The Human Ventricular-Subventricular Zone Neural Stem Cell Niche In Fetal-Onset Hydrocephalus, Saurabh Kumar

University Scholar Projects

Fetal-onset hydrocephalus is a relatively common birth defect occurring in 1-2 cases per thousand births and is characterized by abnormally expanded brain ventricles. Current diagnosis for this complex pathology often involves relatively simple metrics and heavy reliance on clinician experience over objective measures. Those affected often suffer chronic headaches and cognitive deficits and may present with a bulging skill. Shunting is considered the standard treatment for communicating hydrocephalus (i.e. cerebrospinal fluid flow is physically unobstructed in the ventricular system). Shunting remains a highly invasive procedure often performed during the critical period of infancy and has a high failure rate of …

Amygdala And Neocortical Structural Volume Analysis In The Shank3b Mutant Mouse Model Of Autism Spectrum Disorder, Preet Sawhney

Honors Scholar Theses

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is characterized by abnormal social behavior, deficits in communication, and motor stereotypy. The SHANK3 gene, responsible for the generation of a scaffolding protein that is integral for the development of synapses, has been identified as one of the primary candidate genes implicated in the disorder. Shank3B is the rodent homolog for this gene. Research has shown that when this gene is disrupted in rodent models (e.g., via knock-out (KO)), ASD-like behaviors result. These include deficits in social interaction, increased anxiety, and repetitive self-grooming. The current study aimed to identify a physiological …

Safe Sleep: Developmental Implications For Hospitalized Infants, Katherine Kohlsaat

Senior Honors Projects

The rate at which an infant develops both physically and cognitively is significant during sleep, as this is the time when the entire body can dedicate its efforts to this cause. Parents of healthy infants follow the guidelines set by the American Academy of Pediatrics (AAP) relating to safe sleep, and since their introduction in 1992, the rate of Sudden Infant Death Syndrome (SIDS) has decreased by 40% (Center for Disease Control and Prevention, 2016). However, if an infant has been hospitalized since birth due to necessary invasive procedures such as open-heart surgery, these protocols cannot be initially implemented. Common …

Formation, Organization, And Synaptic Properties Of Circuits Between Thalamic Reticular Nucleus And Dorsal Lateral Geniculate Nucleus., Peter W. Campbell

Electronic Theses and Dissertations

The thalamic reticular nucleus (TRN) is an interface between thalamus and cortex that regulates thalamocortical rhythms and modulates sensory processing. Thalamocortical axon collaterals provide feedforward excitatory input onto GABAergic TRN neurons, which in turn convey feedback inhibition to dorsal thalamus. Here we used the mouse visual system to study the organization, pattern of innervation and functional responses between TRN and the dorsal lateral geniculate nucleus (dLGN). We used genetically modified mice to target components of this feedback loop (feedforward: CRH-Cre; feedback: GAD65 or SST-Cre) and we created Math 5^-/- strains to examine the impact of visual deaffrentation in these …

Sedative And Neurotoxic Properties Of Brexanolone Compared To Midazolam In The Developing Rodent Brain, Jacob Huffman

Dissertations

The developing brain is susceptible to extensive neurotoxicity following exposure to sedative/anesthetic drugs (SADs). Every year hundreds of thousands of children around the world are exposed to SADs with no viable non-neurotoxic agents approved for clinical use. Allopregnanolone (AlloP) has well-established sedative effects in adults and neonates. AlloP and many SADs produce sedation/anesthesia through allosteric modulation of GABA_A receptors, which is one of two principal mechanisms behind SAD-induced neurotoxicity. Evidence suggests AlloP has the unique capacity to regulate key apoptotic factors in adults and is widely involved with critical stages of neurodevelopment, indicating this neurosteroid might serve as a …

Developing Tadpoles Exhibit Metabolic And Organ Size Plasticity In Competitive Rearing Environments, Emma Kimberly

Undergraduate Honors Thesis Projects

Abstract

Plasticity is the ability of an organism to respond to environmental variation by expressing different phenotypes. In Red-eyed treefrog tadpoles, Agalychnis callidryas, competitive environments induce long guts and short tails. Despite having a larger gut, tadpoles reared with competition do not increase intake when food becomes available. Pilot data suggest that this is because they have lower metabolic rates. The ability to maintain a larger gut with a depressed metabolic rate is confusing because guts are energetically expensive, and suggests that another energetic trade-off is taking place. The purpose of this study was to investigate the effect of …

Effect Of Reduced Neurogenesis On Microglial Activation, Amelia Smith

Honors Scholars Collaborative Projects

The geriatric population of America has grown exponentially in the past century. Health degradations and expensive medical care are characteristic of this population with many of these costs due to age-related cognitive decline. It is essential to completely understand the mechanisms of normal and abnormal aging in the search for treatments for cognitive decline. A reduction of neurogenesis is a common factor in aging, but this reduction is even more drastic in individuals experiencing cognitive decline. It is unclear what effect reduced neurogenesis has on the extracellular environment, including glial cells. In particular, changes in microglial activation could be related …

The Effect Of Physical Activity And S-Equol On Neurogenesis In The Hiv-1 Transgenic Rat, Jeremy M. Lapointe

Senior Theses

The aim of this thesis is to investigate the effect of physical activity and the administration of s-equol on rates of neurogenesis in HIV-1 transgenic rats. HIV-1 is a neurodegenerative disease that leads to the wide range of cognitive impairment described as HAND. Neurogenesis is a newly discovered process that involves the birth of new neurons during our adult life within the dentate gyrus of the hippocampus. Therefore, inducing neurogenesis may be a proper therapeutic that can mitigate some of the cognitive destruction seen as a result of HIV-1 infection. Physical activity has shown to increase the rate of neurogenesis …

Transcutaneous Auricular Vagus Nerve Stimulation-Paired Rehabilitation For Oromotor Feeding Problems In Newborns: An Open-Label Pilot Study, Bashar W. Badran, Dorothea D. Jenkins, Daniel Cook, Sean Thompson, Morgan Darcy, William H. Devries, Georgia Mappin, Philipp Summers, Marom Bikson, Mark S. George

Publications and Research

Neonates born premature or who suffer brain injury at birth often have oral feeding dysfunction and do not meet oral intake requirements needed for discharge. Low oral intake volumes result in extended stays in the hospital (>2 months) and can lead to surgical implant and explant of a gastrostomy tube (G-tube). Prior work suggests pairing vagus nerve stimulation (VNS) with motor activity accelerates functional improvements after stroke, and transcutaneous auricular VNS (taVNS) has emerged as promising noninvasive form of VNS. Pairing taVNS with bottle-feeding rehabilitation may improve oromotor coordination and lead to improved oral intake volumes, ultimately avoiding the …

Pornography: Adolescent Brain Development & Addiction, William K. Canady

National Youth Advocacy & Resilience Conference

This presentation will explain the historical development of pornography. It will highlight three segments: 1- Porn’s impact on brain development of reward pathways, ultimately increasing the appetite for more porn. 2- Porn can be a false substitute for real intimacy, resulting in decreased sexual satisfaction with a real person and increased verbal and physical aggression. 3- Porn promotes sex trafficking, promotes multiple sex partners and reduced STD prevention.

Effects Of Novel Tool Use: Cortical And Functional Measures In Children Using A Prosthetic Simulator, Chris Copeland

UNO Student Research and Creative Activity Fair

As of 2005, there were a total of 1.6 million people living with the loss of a limb, with this population projected to double to 3.6 million by 2050 [1]. While prostheses aim to enhance the function of these individuals, it is estimated that 45% of pediatric prosthetic users reject their prosthesis [2]. The literature which describes the neurological control mechanisms of prosthetic use is sparse and often low-powered due to an inadequate number of participants. However, prosthetic simulators may be a solution to chronically low-powered prosthetic-centric studies by serving as functional homologues, though this has yet to be tested. …

Antagonistic Regulation Of Circadian Output And Synaptic Development By Jetlag And The Dyschronic-Slowpoke Complex, Angelique Lamaze, James E.C. Jepson, Oghenerukevwe Akpoghiran, Kyunghee Koh

Department of Neuroscience Faculty Papers

Circadian output genes act downstream of the clock to promote rhythmic changes in behavior and physiology, yet their molecular and cellular functions are not well understood. Here we characterize an interaction between regulators of circadian entrainment, output, and synaptic development in Drosophila that influences clock-driven anticipatory increases in morning and evening activity. We previously showed the JETLAG (JET) E3 ubiquitin ligase resets the clock upon light exposure, whereas the PDZ protein DYSCHRONIC (DYSC) regulates circadian locomotor output and synaptic development. Surprisingly, we find that JET and DYSC antagonistically regulate synaptic development at the larval neuromuscular junction, and reduced JET activity …

Neurodevelopment Outcome Of Neonates Treated With Intraventricular Colistin For Ventriculitis Caused By Multiple Drug-Resistant Pathogens-A Case Series, Kashif Hussain, Muhammad Sohail Salat, Gul Ambreen, Javaid Iqbal

Department of Biological & Biomedical Sciences

Background: Multiple-drug-resistant Gram-negative bacteria (MDR-GNB)-associated neonatal ventriculitis is a life-threatening complication that needs timely diagnosis and effective treatment with broad-spectrum antimicrobials in critical-care settings. Inadequate penetration of antibiotics through the blood-brain barrier also demands an intraventricular (IVT) route of administration. This study reports mortality and neurodevelopmental sequelae of neonates till 18 months of age, who received IVT-colistin for treating MDR-GNB associated ventriculitis.
Methods: In a case series of seven neonates with ventriculitis due to MDR-GNB at NICU of Aga Khan University Hospital, Pakistan, between June 2015 and 2018, we reviewed IVT-colistin therapy in critically ill neonates. Treatment outcomes were assessed …

Cis-Regulatory Analysis Of Onecut1 Expression In Fate-Restricted Retinal Progenitor Cells, Sruti Patoori, Nathalie Jean-Charles, Ariana Gopal, Sacha Sulaiman, Sneha Gopal, Brian Wang, Benjamin Souferi, Mark Emerson

Publications and Research

Background: The vertebrate retina consists of six major classes of neuronal cells. During development, these cells are generated from a pool of multipotent retinal progenitor cells (RPCs) that express the gene Vsx2. Fate-restricted RPCs have recently been identified, with limited mitotic potential and cell fate possibilities compared to multipotent RPCs. One population of fate-restricted RPCs, marked by activity of the regulatory element ThrbCRM1, gives rise to both cone photoreceptors and horizontal cells. These cells do not express Vsx2, but co-express the transcription factors (TFs) Onecut1 and Otx2, which bind to ThrbCRM1. The components of the gene regulatory networks that control …

Assessing The Role Of Planar Cell Polarity Protein Ptk7 In Axon Pathfinding Of Spinal Commissural Neurons, Joseph Paul Miano

Theses and Dissertations

Axon pathfinding is a fundamental step that establishes the vast networks of the nervous system. Understanding this process is important because disruptions to these neural networks can impair quality of life. During axon pathfinding, an axon’s growth cone comes in contact with a variety of secreted chemotropic signaling cues that control growth cone behavior through activation of signal transduction pathways which cause changes to the cytoskeleton. One such pathway is the Planar Cell Polarity (PCP) signal transduction pathway that responds to gradients of non-canonical Wnt ligands. PCP has a well-known role in axon pathfinding, including axon pathfinding in the spinal …

Focal Augmentation Of Somatostatin Interneuron Function And Subsequent Circuit Effects In Developmentally Malformed, Epileptogenic Cortex, Nicole Ekanem

Theses and Dissertations

Drug-resistant epilepsy (DRE) is a common clinical sequela of developmental cortical malformations such as polymicrogyria. Unfortunately, much remains unknown about the aberrant GABA-mediated circuit alterations that underlie DRE's onset and persistence in this context. To address this knowledge gap, we utilized the transcranial freeze lesion model in optogenetic mice lines (Somatostatin (SST)-Cre or Parvalbumin (PV)-Cre x floxed channelrhodopsin-2) to dissect features of the SST, PV, and pyramidal neuron microcircuit that are potentially associated with DRE. Investigations took place within developmental microgyria’s known pathological substrate, the adjoined and epileptogenic paramicrogyral region (PMR). As well, microcircuit relationships within the previously unexplored range …

Tissue-Specific Regulation Of Pnmt By Intron Retention During Neural Development, Meeti Mehta

Digital Repository: Showcase of Undergraduate Research Excellence

No abstract provided.

Characterizing The Requirements For The Matricellular Protein, Dccn, In Nervous System Function, Elizabeth L. Catudio Garrett

Graduate Student Theses, Dissertations, & Professional Papers

The brain is organized as a complex network of specialized neurons that communicate via a combination of electrical and chemical signals. Our brains function to generate movement, control organ function, or direct complex behaviors; all of which requires the ability to regulate the flow of communication between circuits and networks. Work in this thesis addresses two areas of neuron communication: first, how does the release of more than one neurotransmitter from a single neuron impact behavior, and second, are matricellular proteins (MCPs) key contributors to synaptic transmission and neuron function? The conserved CCN family of MCPs have a …

C-Jun Nh2-Terminal Kinase Signaling Controls Cellular Mechanisms Of Guided Cortical Interneuron Migration, Skye Eleanor Smith

Graduate Theses, Dissertations, and Problem Reports (ETD)

The cerebral cortex is an intricately organized brain structure responsible for high-level functions including sensory perception, movement, memory, language, and cognition. During corticogenesis, cortical excitatory neurons and inhibitory interneurons migrate from their respective progenitor zones into the developing cerebral cortex, deposit in the correct cortical layer, and establish connections with their appropriate synaptic partners. The balance between excitation and inhibition is critical for cortical circuitry development and function. Aberrant migration of inhibitory interneurons can alter the formation of cortical circuitry and lead to several neurodevelopmental disorders including epilepsy, autism spectrum disorder, and schizophrenia. Therefore, elucidating the mechanisms responsible for inhibitory …

Impact Of A Multimodal Exercise Program On Tibial Bone Health In Adolescents With Development Coordination Disorder: An Examination Of Feasibility And Potential Efficacy, Jocelyn L. Tan, Aris Siafarikas, Timo Rantalainen, Nicolas H. Hart, Fleur Mcintyre, Beth Hands, Paola Chivers

Research outputs 2014 to 2021

© 2020, International Society of Musculoskeletal and Neuronal Interactions. All rights reserved. Objectives: Developmental coordination disorder (DCD) compromises bone health purportedly due to lower levels of physical activity. The potential of an exercise intervention to improve bone health parameters in adolescents with DCD has not previously been studied. This study thus aimed to determine the impact of a multimodal exercise intervention on bone health in this population at-risk of secondary osteoporosis. Methods: Twenty-eight adolescents (17 male, 11 female) aged between 12-17 years (Mage =14.1) with DCD participated in a twice weekly, 13-week generalised multimodal exercise intervention. Peripheral quantitative computed tomography …

Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm

Theses and Dissertations

Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects …

Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen

Theses & Dissertations

Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …

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 …