Neuroscience and Neurobiology Commons^™

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 …

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 …

Lpa Receptors Modulate Gene Expression During Oligodendrocyte Differentiation, Samantha A. Spencer

Theses and Dissertations

LPA, produced by the lysoPLD activity of ATX, binds its cognate receptors and regulates the development of multiple brain cells, including oligodendrocytes (OLGs). OLGs progress through a lineage from precursor (OPC) to early OLG to immature OLG, until finally the cells mature and enwrap axons to enable saltatory conduction and provide trophic support. The studies in this dissertation characterized the receptors LPA4 and LPA6 as inhibitors of OPC differentiation. Western blot analysis of MS patient lesion tissue found a negative correlation between ATX levels and levels of LPA4 and LPA6. A previously created homology model for LPA4 was used to …

The Role Of Gamma Oscillations And Cortical Inhibition In The Development Of Working Memory In Adolescence, Christopher P. Walker

Dissertations and Theses (Open Access)

Adolescence is a dynamic period of social, cognitive, and biological changes. In particular, working memory, the ability to actively encode and maintain information over a short period of time, develops early in childhood and gradually increases in capacity and stability during adolescence. The precise neurophysiological mechanism by which working memory capacity increases during adolescence is unclear. The objective of this investigation was to evaluate the role of cortical gamma-band (> 30 Hz) oscillations—which are associated with working memory in adults—for the development of working memory capacity in adolescents, and to identify the extent to which the temporal profile of gamma-aminobutyric …

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

Dissertations and Theses (Open Access)

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

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

The Role Of Progesterone Receptor In The Developing Medial Preoptic Nucleus, Diana Lalitsasivimol

Legacy Theses & Dissertations (2009 - 2024)

Numerous neurodevelopmental and neuropsychiatric diseases have a distinct sex bias in

Developmental Changes In The Activation And Structure Of The Contextual Fear Neural Circuit From Infancy To Adulthood, Anthony John Santarelli

Legacy Theses & Dissertations (2009 - 2024)

The contextual fear circuit, centered on the basolateral nucleus of the amygdala (BLA), is comprised of projections from the hippocampal formation and prefrontal cortex, and mediates an animals ability to learn and predict associations between the environment and biologically relevant stimuli. While the function and structure of this circuit has been well characterized in adult species, relatively little is known about its development as an animal transitions from infancy to adulthood. Recent evidence has begun to suggest that infants, juveniles, and adolescents may show remarkable heterogeneity in the behavioral, activational, and structural properties of the circuit. In this thesis, I …

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 …

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 …

Contextual Fear Memory Modulates Psd95 Phosphorylation, Ampar Subunits, Pkmζ And Pi3k Differentially Between Adult And Juvenile Rats, Roseanna M. Zanca, Shirley Sanay, Jorge A. Avila, Edgar Rodriguez, Harry N. Shair, Peter A. Serrano

Publications and Research

It is well known that young organisms do not maintain memories as long as adults, but the mechanisms for this ontogenetic difference are undetermined. Previous work has revealed that the α-amino-3-hydroxy-5-methyl-4isoxazolepropionic acidreceptor (AMPAr)subunits aretraffickedinto the synaptic membranefollowing memory retrieval in adults. Additionally, phosphorylated PSD-95-pS295 promotes AMPAr stabilization at the synapse. We investigated these plasticity related proteins as potential mediators in the differential contextual stress memory retrieval capabilities observed between adult and juvenile rats. Rats were assigned to either pedestal stress (1h) or no stress control (home cage). Each animal was placed alone in an open field for 5minat the base …

The Inter-Subject Correlation Of Eeg In Response To Naturalistic Stimuli, Samantha S. Cohen

Dissertations, Theses, and Capstone Projects

Inter-subject correlation is a measure of the similarity of the brain activity of a group of people as they respond to the same naturalistic stimulus, typically a story or video, meant to simulate a real world experience. This thesis tests the hypothesis that the correlation of the brain responses of a group of people is indicative of stimulus engagement. The rationale is that the content of the stimulus drives brain activity in a consistent manner, while internal thoughts are divergent and result in uncorrelated activity. The inter-subject correlation (ISC) of neural responses have previously been assessed with fMRI, EEG, and …

Role Of Mcp-1 And Ccr2 In Ethanol-Induced Neuroinflammation And Neurodegeneration In The Developing Brain, Kai Zhang, Haiping Wang, Mei Xu, Jacqueline A. Frank, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Background: Neuroinflammation and microglial activation have been implicated in both alcohol use disorders (AUD) and fetal alcohol spectrum disorders (FASD). Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. FASD is the leading cause of mental retardation, and one of the most devastating outcomes of FASD is the loss of neurons in the central nervous system (CNS). The underlying molecular mechanisms, however, remain unclear. We hypothesize that MCP-1/CCR2 signaling mediates ethanol-induced neuroinflammation and microglial activation, which exacerbates neurodegeneration in the developing brain.

Methods: C57BL/6 mice and …

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …

The Variability Of Neural Responses To Naturalistic Videos Change With Age And Sex, Agustin Petroni, Samantha Cohen, Lei Ai, Nicolas Langer, Simon Henin, Tamara Vanderwal, Michael P. Milham, Lucas C. Parra

Publications and Research

Neural development is generally marked by an increase in the efficiency and diversity of neural processes. In a large sample (n=114) of human children and adults with ages ranging from 5 to 44 yr, we investigated the neural responses to naturalistic video stimuli. Videos from both real-life classroom settings and Hollywood feature films were used to probe different aspects of attention and engagement. For all stimuli, older ages were marked by more variable neural responses. Variability was assessed by the intersubject correlation of evoked electroencephalographic responses. Young males also had less-variable responses than young females. These results were replicated in …

Disc1 Knockout Rats Reveal Sexually Dimorphic Patterns Of Impairment Across Development, Stephanie S. Desrochers

Honors Theses

Schizophrenia is a chronic disorder characterized by three symptom categories: positive (hallucinations, delusions), negative (anhedonia, anxiety), and cognitive (sensory processing and memory deficits). We worked with a biallelic deletion of the Disrupted-in-schizophrenia-1 (DISC1) gene in Sprague-Dawley rats to facilitate our understanding of the biological bases of schizophrenia. Mutations of DISC1 are associated with a higher prevalence of schizophrenia. Adult DISC1 knockout, compared to wildtype, rats display features of schizophrenia-like outcomes in rodent models. The present study investigated the progression of the cognitive symptom deficits in prepulse inhibition (PPI), assessing animals at postnatal days 17 (pre-weaning), 26 (post-weaning), 39 (adolescent), and …

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 …

Chickens’ Brains, Like Ours, Are Lateralized, Lesley J. Rogers

Animal Sentience

This commentary draws attention to yet another attribute that has been instrumental in demonstrating the cognitive abilities of domestic chicks: lateralization of brain function. The discovery of lateralization in domestic chicks was part of the first evidence showing that humans are not unique in this respect. The effects on cognitive ability of sensory stimulation in critical stages of development have implications for the welfare of chicks, as well as other species.

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 …

Glyphosate Induces Neurotoxicity In Zebrafish, Nicole M. Roy, Bruno Carneiro, Jeremy Ochs

Biology Faculty Publications

Glyphosate based herbicides (GBH) like Roundup^® are used extensively in agriculture as well as in urban and rural settings as a broad spectrum herbicide. Its mechanism of action was thought to be specific only to plants and thus considered safe and non-toxic. However, mounting evidence suggests that GBHs may not be as safe as once thought as initial studies in frogs suggest that GBHs may be teratogenic. Here we utilize the zebrafish vertebrate model system to study early effects of glyphosate exposure using technical grade glyphosate and the Roundup^® Classic formulation. We find morphological abnormalities including cephalic and …

The Neurophysiology Of Intersensory Selective Attention And Task Switching, Jeremy W. Murphy

Dissertations, Theses, and Capstone Projects

Our ability to selectively attend to certain aspects of the world and ignore others is fundamental to our day-to-day lives. The need for selective attention stems from capacity limitations inherent in our perceptual and cognitive processing architecture. Because not every elemental piece of our environment can be fully processed in parallel, the nervous system must prioritize processing. This prioritization is generally referred to as selective attention. Meanwhile, we are faced with a world that is constantly in flux, such that we have to frequently shift our attention from one piece of the environment to another and from one task to …

Temporal Localization Of Insulin-Like Growth Factor 1 (Igf1) Positive Cells In Developing Hypothyroid Brain, Shelby Anne Kline

All Graduate Theses, Dissertations, and Other Capstone Projects

Hypothyroidism has been known to result in numerous neuroanatomical defects in the developing brain. To investigate further into the mechanism in which these defects are obtained, local brain insulin-like growth factor 1 (Igf1) was investigated in relation to the hypothyroid brain. There are many similarities between hypothyroidism and the Igf1 deficient brain. Additionally, TH (thyroid hormone) is known to interact with Igf1. Therefore, the purpose of this study was to investigate the effect of induced congenital hypothyroidism on the temporal expression of Igf1-positive cells in the brain. To investigate the relationship between TH and Igf1 in the brain, we inhibited …

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 …

Evaluation Of The Developmental Toxicity Of Lead In The Danio Rerio Body, Nicole M. Roy, Sarah Dewolf, Bruno Carneiro

Biology Faculty Publications

Lead has been utilized throughout history and is widely distributed and mobilized globally. Although lead in the environment has been somewhat mitigated, the nature of lead and its extensive uses in the past prohibit it from being completely absent from our environment and exposure to lead is still a public health concern. Most studies regarding lead toxicity have focused on the brain. However, little is found in the literature on the effects of lead in other tissues. Here, we utilize the zebrafish model system to investigate effects of lead exposure during early developmental time windows at 24, 48 and 72 …

Attention Shapes Our Expectations And Perceptions: The Neural Mechanisms Of Top-Down Attention During Adulthood And Development, Snigdha Banerjee

Dissertations, Theses, and Capstone Projects

Top-down attention is the focusing of attention at one's will through knowledge regarding a current task. There is evidence that top-down attention involves the modulation of sensory cortices by higher order regions. However, the mechanisms of top-down attention across sensory modalities, its influence on early sensory inputs, as well as interactions with motivational systems remain unclear. We performed the following set of electrophysiological experiments in typically developed adults and adolescents to examine these areas. 1) The supramodal attentional theory holds that parietally-based attentional mechanisms are shared across sensory modalities. We tested the supramodal theory by examining if lateralized parieto-occipital alpha-band …

Biological Motion Processing In Typical Development And In The Autism Spectrum, Aaron Krakowski

Dissertations, Theses, and Capstone Projects

Biological motion (BM) analysis and interpretation is a fundamental process of human neurocognition that has been only minimally explored neurophysiologically. In addition to its importance in understanding the underlying roots and development of social cognition, BM processing is a prime candidate domain for exploring the underlying etiology of social cognitive disorders such as the autism spectrum.

In an initial experiment, typical adults observed BM point-light displays of a human actor (UM) as well as their spatially scrambled counterparts (SM), in both an unattended distractor task as well as an explicit attention task. Results showed a neurophysiological response manifested as three …

Inter- And Intralimb Adaptations To A Sensory Perturbation During Activation Of The Serotonin System After A Low Spinal Cord Transection In Neonatal Rats, Misty M. Strain, Sierra D. Kauer, Tina Kao, Michele R. Brumley

Publications and Research

Activation of the serotonin system has been shown to induce locomotor activity following a spinal cord transection. This study examines how the isolated spinal cord adapts to a sensory perturbation during activation of the serotonergic system. Real-time and persistent effects of a perturbation were examined in intact and spinal transected newborn rats. Rats received a spinal surgery (sham or low thoracic transection) on postnatal day 1 and were tested 9 days later. At test, subjects were treated with the serotonergic receptor agonist quipazine (3.0 mg/kg) to induce stepping behavior. Half of the subjects experienced range of motion (ROM) restriction during …

The Development Of Sleep-Wake Rhythms And The Search For Elemental Circuits In The Infant Brain, Mark S. Blumberg, Andrew J. Gall, William D. Todd

Faculty Publications

Despite the predominance of sleep in early infancy, developmental science has yet to play a major role in shaping concepts and theories about sleep and its associated ultradian and circadian rhythms. Here we argue that developmental analyses help us to elucidate the relative contributions of the brainstem and forebrain to sleep-wake control and to dissect the neural components of sleep-wake rhythms. Developmental analysis also makes it clear that sleep-wake processes in infants are the foundation for those of adults. For example, the infant brainstem alone contains a fundamental sleep-wake circuit that is sufficient to produce transitions among wakefulness, quiet sleep, …

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 …