Developmental Neuroscience Commons^™

Unraveling Hemispheric Specializations In The Mouse Auditory Cortex: From Diseased Model Comparisons To Development, Demetrios Neophytou

Dissertations, Theses, and Capstone Projects

Hemispheric specialization is a fundamental organizing principle of mature auditory cortical function, allowing the left and right Auditory Cortex (ACx) to perform complementary computations on complex sounds. This division of labor is conserved across species, and mice recapitulate key forms of auditory cortical lateralization, providing access to the synaptic and circuit mechanisms that generate it. Disrupted hemispheric organization is also associated with neurodevelopmental disorders characterized by severe communication impairments, including Rett Syndrome (RTT). Despite this, we know little about how lateralized auditory circuits are assembled during development or why they become differentially vulnerable to neurodevelopmental disruption. Here, using a mouse …

Exploring Anticholinergic Neurotoxicity: Diphenhydramine's Impact On Neuro-2a Cell Morphology, Expression, And Viability, Jordan B. Mcintyre

Honors Undergraduate Theses

Anticholinergic medications, such as diphenhydramine (commonly known as Benadryl), are increasingly recognized for their association with cognitive impairment and neurodegenerative disease. These medications, which inhibit the action of acetylcholine, a neurotransmitter essential for the formation and utilization of the central and peripheral nervous system, have been implicated in conditions such as dementia and may impact fundamental cellular processes like neurogenesis and cell proliferation. This study investigates the effects of diphenhydramine on neurogenesis when introduced to Neuro-2a cells during differentiation. For all studies cells were plated on coverslips or in 6-well plates with differentiation media containing 0 ng/mL, 50 ng/mL, …

The Role Of Androgen Receptor And B2/Alu Sine Rna Interaction In Hippocampal Dendritic Development, Troy A. Richter

Graduate Doctoral Dissertations

Once dismissed as “junk”, transposable elements have recently gained recognition for their regulatory roles, especially in the brain. During development, circulating androgens promote proper morphological development of hippocampal neurons. We and others have shown that murine B2 SINE RNA is a regulator in the rodent hippocampus. It is unknown, however, if B2 is necessary for the proper development of hippocampal neurons. This dissertation investigates the role of murine B2 in the development of primary hippocampal neurons in combination with androgen treatment. We first examined the role of ALU SINE and androgen receptor in a prostate cancer cell model and found …

Wired For Success: A Neurobiological Approach To Improving The Academic Outcomes Of Middle School Boys, Allison Emery

University Honors Theses

Male accomplishment in scholastic settings has been declining globally for the last decade, leading to long-term consequences for boys and men. Possible neurobiological underpinnings of the gender gap in education are discussed in this literature review. While male and female differences have, in the past, largely been considered socialized, recent science also confirms neurobiological variances between male and female development. These distinctions are assessed for their potential ties to the decline in male academic success, and are correlated to classroom practices, strategies and interventions meant to increase boys' engagement and performance.

Individual Differences In Age And Testosterone Are Uniquely Associated With Neural Oscillatory Activity Serving Verbal Working Memory In Children And Adolescents, Abraham D. Killanin

Theses & Dissertations

During the sensitive period of adolescence, the human brain undergoes dynamic changes in structure and function resulting in vast executive function gains. Verbal working memory (VWM) is one executive function that serves as a foundation to language acquisition, reading, and learning. Many have examined the development of VWM in youth, but few have probed age-related changes in the underlying neural oscillatory dynamics, and none have examined testosterone-related changes. We recorded magnetoencephalography during a modified Sternberg VWM task in 82 youth participants aged 6 – 14 years old and collected salivary testosterone samples. Significant oscillatory responses were identified and imaged using …

Changes In The Epigenetic Landscape Of Oligodendrocyte Progenitor Cells With Time, David K. Dansu

Dissertations, Theses, and Capstone Projects

Most neonatal oligodendrocyte progenitors (nOPCs) give rise to myelinating oligodendrocytes during development, while a proportion are retained as proliferative undifferentiated cells in the adult brain (aOPCs). Previous studies have reported distinct properties for those two populations but the molecular mechanisms underlying these intrinsic differences are not well understood. Using RNA-sequencing and unbiased histone proteomics analysis, we identify transcripts and histone marks that are higher in aOPCs than nOPCs. The genome-wide ChIP-sequencing analysis of chromatin from aOPCs compared to nOPCs detects greater occupancy of the H4K8ac mark at loci corresponding to the higher transcript levels of oligodendrocyte-specific transcription factors and lipid …

Microglia Refine Early Multisensory Circuits In The Lateral Cortex Of The Inferior Colliculus In A Complement-Dependent Manner, Shaida Hamidi

Masters Theses, 2020-current

Microglia cells (MGCs), the resident macrophage of the brain, play a pivotal role in synaptic pruning of newly established circuits during early critical periods. Classical complement cascade signaling enables MGCs to identify unnecessary or underutilized contacts and specifically target them for removal and subsequent degradation. Such recognition and engulfment behaviors require receptor-ligand interactions, whereby “eat me” tags (complement component 3, C3) bind their cognate receptor (complement receptor 3, CR3) expressed on MGCs. Compromised complement signaling in certain systems results in under-pruning or unrefined map configurations, and is thought perhaps to underlie certain autism-related behavioral phenotypes (e.g. sensory hypersensitivities, decreased social …

The Genomics Of Autism-Related Genes Il1rapl1 And Il1rapl2: Insights Into Their Cortical Distribution, Cell-Type Specificity, And Developmental Trajectories, Jacob Weaver

MUSC Theses and Dissertations

Neuropsychiatric disorders have a significant impact on modern society. These disorders affect a large percentage of the population: schizophrenia has a world-wide prevalence of 1% and autism spectrum disorders (ASD) affects 1 in 59 school-aged children in the US. There is substantial evidence that most neuropsychiatric disorders have a genetic component. Thus, with the advent of high throughput sequencing much effort has gone into identifying genetic variants associated with these disorders. The emerging picture from these studies is a complex one where hundreds of genes with small effects interact with a varied landscape of common variants to result in disease. …

Effects Of Development On Hpa Function Following Pubertal Stress, Brittany D. Elliott

Graduate Theses, Dissertations, and Problem Reports (ETD)

For women, two of the greatest risk factors for affective disorders are adversity experienced during puberty and later becoming pregnant. We have created a translationally relevant mouse model where we address these complex risk factors. Previously, we discovered that pregnant mice (dams) that experienced chronic variable stress (CVS) during puberty display a blunted hypothalamic-pituitary-adrenal (HPA) response when exposed to an acute stressor. Interestingly, this alteration only first becomes apparent during pregnancy, which is a sensitive period for these effects due to normative neuroendocrine changes. Further investigation of the mechanisms underlying this dysfunction revealed altered gene expression in the paraventricular nucleus …

Targeting Ampa Receptor Modulation During Early Life Adversity: A Mediator For Threat Associated Memories, Roseanna M. Zanca

Dissertations, Theses, and Capstone Projects

Early life adversity (ELA) is the exposure to a single or to multiple traumatic events before the age of 18 that go beyond the child’s coping. These adverse events are often exacerbated during adolescence particularly when cognitive performance is compromised. Adolescents who experienced ELA may show symptoms of post-traumatic stress disorder (PTSD), while not vividly recalling the early life trauma. These individuals show atypical connectivity between prefrontal-amygdala and hippocampus, all of which is associated with an increased risk of experiencing a traumatic event again later in life. While clinical research has increasingly stressed the importance in addressing the long-lasting consequences …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

University Scholar Projects

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

The Influence Of Autism Linked Gene Topoisomerase 3b (Top3b) On Neural Development In Zebrafish, Sydney Doolittle

Honors College Theses

Autism Spectrum Disorder is a class of developmental disabilities characterized by a spectrum of social, communication, and behavioral impairments in affected individuals. Studies have shown these defects stem from abnormal brain development during critical periods during early development. The underlying genetic cause of these impairments is not well understood but is believed to be a combination of a complex pairing of genetic and environmental factors. One of the genetic factors that has been recognized to influence the phenotypic symptoms of ASD is the enzyme topoisomerase 3β (top3β.) Topoisomerases are responsible for the prevention of supercoiling during DNA replication. Top3β is …

The Role Of Glt-1 Signaling In Oligodendrocytes During Development And Myelin Repair, Elizabeth Thomason

Theses and Dissertations

The differentiation of oligodendrocyte progenitor cells (OPCs) into myelinating oligodendrocytes (OLGs) requires an increase in the complexity of process morphology, alterations in membrane trafficking, and the production of myelin proteins. Branching and process extension have already been shown to follow glutamate signaling through OLG-expressed excitatory amino acid transporters (EAATs), mostly via GLT-1. It is of note that glutamate homeostasis often goes awry in multiple sclerosis (MS), the main demyelinating disease in humans. Thus, we have sought to gain an understanding of the role that GLT-1 plays under the myelination and remyelination conditions that arise during natural development of OLGs and …

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 …

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 …

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 …

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 …

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 …

Characterizing The Cellular Nature Of The Physical Interactions Necessary For Collective Neuron Migration, Rebecca Vareed

Theses and Dissertations

Neuronal migration is an essential process in the development of the nervous system. Neurons are born in one location and migrate sizable distances to their final location. In many other developmental processes, cells migrate as collectives, where the migration of one cell influences the migration of another cell; this process has yet to be shown in the developing central nervous system. Using the conserved tangential migration of facial branchiomotor neurons (FBMNs), I aim to determine the nature of the collective migration in the developing nervous system. Here, two models of FBMN collective migration are tested: the “Pioneer” model, where following …

Glial Cell Expansion And Intercellular Signaling In The Developing Medial Nucleus Of The Trapezoid Body (Mntb), Ashley N. Brandebura

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neural circuit formation is a complex process involving coordinated communication between neurons, glia and vascular-associated cells (VACs). Each cell type is responsible for a unique transcriptional and translational contribution to tissue maturation. Deciphering the intercellular signaling patterns which guide neural circuit formation during normal development is thus an essential step in understanding which components of neural circuit formation go awry in neurodevelopmental disorders. The medial nucleus of the trapezoid body (MNTB), located in the auditory brainstem, was used as a model system to study the dynamics of neural circuit formation because it contains a mostly homogeneous population of postsynaptic neurons …

Polarity And Competition In The Development Of The Calyx Of Held Terminal In The Medial Nucleus Of The Trapezoid Body In The Mouse, Paul Steven Holcomb

Graduate Theses, Dissertations, and Problem Reports (ETD)

In the auditory brainstem, the connection between globular bushy cells of the anteroventral cochlear nucleus and principal cells (PCs) of the medial nucleus of the trapezoid body (MNTB) is created by one of the largest nerve terminals in the central nervous system, the calyx of Held (CH). The characteristics of the CH:MNTB connection—a short developmental period (48-72 hours), accessibility for recording from pre- and postsynaptic components, and clear monoinnervated end point—make this system an ideal model system for studying nervous system development. Model systems undergo stereotyped stages of development, including exuberant overinnervation, competition between terminals, and a refinement of innervation …

Complementary Multimodal Compartments In The Developing Inferior Colliculus, Roxana Behrooz

Senior Honors Projects, 2010-2019

The auditory system is responsible for detecting, encoding, and deciphering hearing. The inferior colliculus (IC) is a major relay hub situated in the midbrain, that is subdivided into a central nucleus, and surrounding dorsal and lateral cortices. The central nucleus of the inferior colliculus (CNIC) is organized tonotopically based on a frequency gradient and strictly processes auditory information. In contrast, recent studies show that the lateral cortex of the inferior colliculus (LCIC) is actually multimodal, receiving inputs from not just auditory sources, but also somatosensory and visual structures. The precise organization of patterned inputs to the LCIC and their development …

The Role Of Daf-19 In Non-Ciliated Neurons: How Is Neural Development Regulated By Different Daf-19 Isoforms?, Zabdiel Ek Vazquez

Lawrence University Honors Projects

A degenerative disease-like phenotype, specifically reduction in synaptic protein levels in adult worms, is correlated with loss-of-function of the only RFX transcription factor gene, daf-19, in C. elegans. This gene encodes four known transcription factor isoforms, two of which are correlated with particular functions. The DAF-19C isoform activates genes responsible for cilia development, while DAF-19M is needed for cilia specification in males. A comparison of the transcriptome of daf-19 null and isogenic wild type adult worms suggests both positive and negative regulation of gene expression is correlated with the presence of DAF-19 proteins. We have assessed DAF-19 regulation …

Acth Prevents Deficits In Fear Extinction Associated With Early Life Seizures, Andrew T. Massey, David K. Lerner, Gregory L. Holmes, Rod C. Scott, Amanda Hernan

Dartmouth Scholarship

Objective: Early life seizures (ELS) are often associated with cognitive and psychiatric comorbidities that are detrimental to quality of life. In a rat model of ELS, we explored long-term cognitive outcomes in adult rats. Using ACTH, an endogeneous HPA-axis hormone given to children with severe epilepsy, we sought to prevent cognitive deficits. Through comparisons with dexamethasone, we sought to dissociate the corticosteroid effects of ACTH from other potential mechanisms of action.

Results: Although rats with a history of ELS were able to acquire a conditioned fear learning paradigm and controls, these rats had significant deficits in their ability to extinguish …

Dual Functions For Insulinoma-Associated 1 In Retinal Development, Marie A. Forbes-Osborne

Theses and Dissertations--Biology

Proper visual system function requires tightly controlled proliferation of a pool of relatively homogeneous retinal progenitor cells, followed by the stepwise specification and differentiation of multiple distinct cell types. These retinal cells, both neuronal and glial, must be generated in the correct numbers, and the correct laminar location to permit the formation of synaptic connections between individual cell types. After synapses are made, constant signaling is required as part of normal retinal function, and to maintain cellular identity and connectivity. These processes rely on both extrinsic and intrinsic signaling, with regulation of gene expression by cascades of transcription factors having …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

University Scholar Projects

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …

Astroglial Boundary Formation And Epha4 Signaling In Neuroblast Migration, Nicholas B. Gallo

Honors Scholar Theses

Adult neurogenesis, the process of generating new neurons from neural precursors, is a highly complex process that is limited to two specific areas of the brain, the dentate gyrus of the hippocampus and the subventricular zone (SVZ). Despite continued research investigating neurogenesis in these two regions, we still lack a fundamental understanding of the molecular mechanisms of neural cell division, migration, differentiation, and integration in the postnatal brain. In particular, the rostral migratory stream (RMS), which is a cellular migratory route for newly generated neuronal precursors that travel from the SVZ to the olfactory bulb, will provide a useful model …

The Mammalian Neocortex New Pyramidal Neuron: A New Conception, Miguel Marín-Padilla

Dartmouth Scholarship

The new cerebral cortex (neocortex) and the new type of pyramidal neuron are mammalian innovations that have evolved for operating their increasing motor capabilities while essentially using analogous anatomical and neural makeups. The human neocortex starts to develop in 6-week-old embryos with the establishment of a primordial cortical organization, which resembles the primitive cortices of amphibian and reptiles. From the 8th to the 15th week of age, new pyramidal neurons, of ependymal origin, are progressively incorporated within this primordial cortex forming a cellular plate that divides its components into those above it (neocortex first layer) and those below it (neocortex …