Developmental Neuroscience Commons^™

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

Honors Capstone 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 …

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 …

The Role Of Histone Demethylases In Learning And Memory In The Mushroom Body Of Drosophila Melanogaster, Crystal Keung

Electronic Thesis and Dissertation Repository

Intellectual disability (ID) is a neurodevelopmental disorder associated with many epigenetic regulators and chromatin modifying enzymes like histone lysine methyltransferases (KMTs) and demethylases (KDMs). Here, I systematically investigate the role of 7 KDMs: Su(var)3-3, KDM2, Lid, CG2982, UTX, KDM4B, JHDM2, and 1 KMT: trr in the context of learning and memory using Drosophila melanogaster. Genetic knockdown of each gene in the mushroom body (MB) of flies are tested for short- and long-term memory impairment using courtship conditioning. Knockdown of 6 KDMs and trr resulted in memory loss. MB morphology was analyzed to determine potential cause of memory loss. …

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 …

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 and 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 …

Thyroxine-Dependent And -Independent Effects On Premature Aging And Myelination In Atrx Mutant Mice, Megan E. Rowland

Electronic Thesis and Dissertation Repository

ATRX is an ATP-dependent chromatin remodeler required to safeguard genomic integrity. Conditional deletion of Atrx in the mouse embryonic forebrain and anterior pituitary in Atrx^Foxg1Cre mice phenocopies mouse models of progeria which display increased DNA damage, coupled with reduced lifespan, growth and subcutaneous fat. These mice also have severely low circulating levels of insulin like growth factor 1 (IGF-1) and (T4) which have been reported in models of premature aging. Based on evidence that Igf1 is activated by the ligand-bound thyroid hormone receptor, I tested whether T4 supplementation could restore IGF-1 levels and ameliorate premature aging phenotypes in Atrx …

Using An Internal Auditory Stimulus To Activate The Developing Primary Auditory Cortex: A Fetal Fmri Study, Estee Goldberg

Electronic Thesis and Dissertation Repository

Insight into the rapidly developing brain in utero is scarce. Fetal functional magnetic resonance imaging (fMRI) is a technique used to gain awareness into the developmental process. Previous auditory task-based fMRI studies employed an external sound stimulus directly on the maternal abdomen. However, there has since been recommendation to cease doing so. We sought to investigate a reliable paradigm to study the development of fetal brain networks and postulate that by using an internal stimulus, such as the mother singing, it would result in activation of the fetal primary auditory cortex. Volunteers carrying singleton fetuses with a gestational age of …

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 …