Neuroscience and Neurobiology Commons^™

Arid1b And Macf1 In Murine Brain Development And Behavior, Jeffrey Jay Moffat

Theses & Dissertations

Intellectual disability (ID) and autism spectrum disorder (ASD) affect between one and three percent of the global population. These disorders represent a significant emotional and financial burden for affected individuals and their families. Treatment for these conditions remains limited because many of the key molecular factors and associated pathogenic mechanisms are still poorly understood.

In this report we examine two genes related to ASD and ID, AT-rich interactive domain-containing protein 1B (ARID1B) and Microtubule-actin crosslinking factor 1 (MACF1). ARID1B is a subunit of the mammalian BRG1/BRM associated factor (BAF) chromatin-remodeling complex, which broadly regulates gene expression. ARID1B also …

Neural Correlates Of Polysubstance Use: Differential And Interactive Effects Of Alcohol And Cannabis On The Adolescent Brain, Joseph Aloi

Theses & Dissertations

Two of the most commonly used and abused substances by adolescents in the United States are alcohol and cannabis, which are associated with adverse medical and psychiatric outcomes. Alcohol use and cannabis use during adolescence is also associated with an increased risk of alcohol use disorder (AUD) and/or cannabis use disorder (CUD) in adulthood as well as increased likelihood of relapse after successful treatment. Despite this, much of the previous work on the neurobiology of substance use disorders has focused on adult substance use. This work has shown that individuals with AUD and/or CUD show dysfunction within reward processing, emotion …

Tributyltin Inhibits Neural Induction Of Human Induced Pluripotent Stem Cells, Shigeru Yamada, Yusuke Kubo, Daiju Yamazaki, Yuko Sekino, Yoko Nomura, Sachiko Yoshida, Yusunari Kanda

Publications and Research

Tributyltin (TBT), one of the organotin compounds, is a well-known environmental pollutant. In our recent study, we reported that TBT induces mitochondrial dysfunction, in human-induced pluripotent stem cells (iPSCs) through the degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor. However, the effect of TBT toxicity on the developmental process of iPSCs was not clear. The present study examined the effect of TBT on the differentiation of iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the induction of iPSCs into the ectoderm, which is the …

An Expanded Toolkit For Gene Tagging Based On Mimic And Scarless Crispr Tagging In, David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael T Lee, Manish Jaiswal, Jose Luis Salazar, Yuchun He, Zhongyuan Zuo, Hugo J Bellen

Faculty, Staff and Students Publications

We generated two new genetic tools to efficiently tag genes in Drosophila. The first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in vivo based on Cre recombinase to avoid embryo injections. DH significantly increases integration efficiency compared to previous strategies and faithfully reports the expression pattern of genes and proteins. The second technique targets genes lacking coding introns using a two-step cassette exchange. First, we replace the endogenous gene with an excisable compact dominant marker using CRISPR making a null allele. Second, the insertion is replaced …

An Investigation Of Vocal Learning Propensity In Zebra Finch (Taeniopygia Guttata), Tatsuya Hayashi

Theses and Dissertations

The investigator attempted to predict the vocal learning propensity from either family pedigree or early vocal babbling (subsong). Pedigree trees suggest the possibility that vocal learning ability may depend on family. We failed to predict vocal learning propensity from subsong, but suggested that subsong may influence vocal learning outcome.

Targeting Pro-Inflammatory Function Of Microglia Using Small Molecules To Combat Neurodegeneration, Gabrielle C. Williams, Priya Prakash, Gaurav Chopra

The Summer Undergraduate Research Fellowship (SURF) Symposium

Microglia are the brain’s resident immune cells that are responsible for maintaining homeostasis in healthy conditions. During injury or infection, resting microglia get activated and produce pro-inflammatory cytokines such as IL-1b, IL-1a, IL-6, etc. along with reactive oxygen species like nitric oxide (NO) to combat neuroinflammatory diseases such as Alzheimer’s disease (AD). Inflammation is characterized by the activation of resident-immune cells in the brain called microglia that respond to the eat-me signals released by the toxic amyloid beta peptides as well as the dying neurons in the microenvironment. Recent studies have shown that activated microglia induce neuronal death by secreting …

Neural Coding Of An Auditory Pitch Illusion, Maria Alejandra Barrera, Mark Sayles, Ravinderjit Singh

The Summer Undergraduate Research Fellowship (SURF) Symposium

Pitch is an important perceptual dimension in audition, supporting auditory object segregation, melody recognition and lexical distinction. Huggins’ pitch, for example, is a phenomenon evoked by two sources of broadband noise presented binaurally with an inter-aural phase shift over a narrow frequency band. Huggins’ pitch and other dichotic pitches have been studied extensively using perceptual experiments. Several models have been proposed to explain and predict the perception of pitch; however, no studies have tried to record in vivo neuron responses to Huggins’ pitch (HP) nor have tried to explain how the HP is coded by neurons. The existence of pitches …

The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert

Graduate School of Biomedical Sciences Theses and Dissertations

Developmental timing is a key aspect of tissue and organ formation in which distinct cell types are generated through a series of steps from common progenitors. These progenitors undergo specific changes in gene expression that signifies both a distinct progenitor type and developmental time point that thereby specifies a particular cell fate at that stage of development. The nervous system is an important setting for understanding developmental timing because different cell types are produced in a certain order and the switch from stem cells to progenitors requires precise timing and regulation. Notable examples of such regulatory molecules include the RNA-binding …

Cortical And Subcortical Contributions To Long-Term Memory-Guided Visuospatial Attention, Maya L. Rosen, Chantal E. Stern, Kathryn J. Devaney, David C. Somers

Neuroscience: Faculty Publications

Long-term memory (LTM) helps to efficiently direct and deploy the scarce resources of the attentional system; however, the neural substrates that support LTM-guidance of visual attention are not well understood. Here, we present results from Fmri experiments that demonstrate that cortical and subcortical regions of a network defined by resting-state functional connectivity are selectively recruited for LTM-guided attention, relative to a similarly demanding stimulus-guided attention paradigm that lacks memory retrieval and relative to a memory retrieval paradigm that lacks covert deployment of attention. Memory-guided visuospatial attention recruited posterior callosal sulcus, posterior precuneus, and lateral intraparietal sulcus bilaterally. Additionally, 3 subcortical …

Rna Binding Proteins Co-Localize With Small Tau Inclusions In Tauopathy, Brandon F. Maziuk, Daniel J. Apicco, Anna Lourdes Cruz, Lulu Jiang, Peter E. A. Ash, Edroaldo Lummertz De Rocha, Cheng Zhang, Wai Haung Yu, John Leszyk, Jose F. Abisambra, Hu Li, Benjamin Wolozin

Sanders-Brown Center on Aging Faculty Publications

The development of insoluble, intracellular neurofibrillary tangles composed of the microtubule-associated protein tau is a defining feature of tauopathies, including Alzheimer’s disease (AD). Accumulating evidence suggests that tau pathology co-localizes with RNA binding proteins (RBPs) that are known markers for stress granules (SGs). Here we used proteomics to determine how the network of tau binding proteins changes with disease in the rTg4510 mouse, and then followed up with immunohistochemistry to identify RNA binding proteins that co-localize with tau pathology. The tau interactome networks revealed striking disease-related changes in interactions between tau and a multiple RBPs, and biochemical fractionation studies demonstrated …

Cholinergic Control Of Cortical Circuit Activity, Rajan Dasgupta

Dissertations and Theses (Open Access)

Cholinergic neurons of the basal forebrain send extensive projections to all regions of the neocortex and are critically involved in a diverse array of cognitive functions, including sensation, attention and learning. Cholinergic signaling also plays a crucial role in the moment-to-moment control of ongoing cortical state transitions that occur during periods of wakefulness. Yet, the underlying circuit mechanisms of synaptic cholinergic function in the neocortex remain unclear. Moreover, acetylcholine continues to be widely viewed as a slow and diffuse neuromodulator, despite the preponderance of in vivo evidence demonstrating rapid cholinergic function. In this study, we used a combination of optogenetics …

Ischemic Stroke Damage Is Reduced By Inhibition Of Il-6 Signaling With To Cilizumab, Jacob Hudobenko

Dissertations and Theses (Open Access)

Introduction:

Stroke is the leading cause of serious long-term disability and is the 5^th leading cause of death causing approximately 130,000 deaths in the United States every year {1}. Stroke is also the 2^nd leading cause of death in American women {2}. Women are 33% more likely to require nursing home care then men, have a higher lifetime risk of stroke and are 13% less likely to receive thrombolytic (clot busting) treatment than men {2}. Interleukin 6 (IL-6) is a pro-inflammatory cytokine involved in the regulation of the immune system in multiple disease states such as rheumatoid …

Organization And Development Of Cholinergic Input To The Mouse Visual Thalamus., Guela Sokhadze

Electronic Theses and Dissertations

Cholinergic signaling plays a vital role in modulating the flow of sensory information through thalamic circuits in a state-dependent manner. In the dorsal lateral geniculate nucleus (dLGN), the thalamic visual relay, release of acetylcholine (ACh) contributes to enhanced thalamocortical transfer of retinal signal during behavioral states of arousal, wakefulness, and sleep/wake transitions. Moreover, ACh modulates activity of the thalamic reticular nucleus (TRN), a structure which provides inhibitory input to dLGN. While several cholinergic nuclei have been shown to innervate dLGN and TRN, it is unclear how projections from each area are organized. Furthermore, little is known of how or when …

Characterization Of Theranostic Peptides For Glioblastoma Multiforme, Aaron Mellesmoen

All NMU Master's Theses

Glioblastoma multiforme (GBM) is a type of primary CNS tumor in which viable treatment options do not exist. Standard of care including tumor resection, chemotherapy, and radiation does little to extend the 5-year survival expectancy past 5.1%. Herein, two small-peptide molecules with inherent antitumor activity, blood-brain barrier permeability, and capability for tumor-specific drug deliverance and intraoperative visualization (termed theranostic) were of focus. Confocal microscopy was employed to characterize in vitro specificity of chlorotoxin, a 4 kDa scorpion venom peptide, and rBSG, the recombinant 25 kDa non-glycosylated extracellular domain of extracellular matrix metalloproteinase inducer (EMMPRIN; Basigin) isoform …

Ube4b Levels Determine The Efficacy Of Egfr And Stat5 Inhibitors In Treatment Resistant Neuroblastoma, David James Savage

Dissertations and Theses (Open Access)

Neuroblastoma is the most common malignancy in infants. Overexpression of the epidermal growth factor receptor (EGFR) in neuroblastoma tumors can result in enhanced EGFR signaling, uncontrolled proliferation, and may provide a mechanism for chemotherapy resistance. UBE4B, an E3/E4 ubiquitin ligase, ubiquitinates the EGFR and promotes its lysosomal degradation ultimately attenuating EGFR signaling. Interestingly, the UBE4B gene lies in a chromosomal region (1p36) whose loss is correlated with poor patient outcomes due to inefficient EGFR degradation and enhanced cell proliferation. We examined whether depletion of UBE4B in a chemoresistant neuroblastoma cell line would affect tumor responses to drugs that specifically target …

The Role Of Perivascular Fibrosis In Post-Stroke Glymphatic Impairment And Cerebral Amyloid Angiopathy, Matthew D. Howe

Dissertations and Theses (Open Access)

In healthy brain tissue, toxic amyloid-β (Aβ) proteins are transported by the pulsatile flow of cerebrospinal fluid (CSF) along perivascular drainage pathways. Ischemic stroke may disrupt this process, leading to a perivascular build-up of Aβ, termed cerebral amyloid angiopathy (CAA). I hypothesize that an abnormal pattern of extracellular matrix deposition within the vascular basement membrane, termed fibrosis, impairs Aβ drainage from the aged brain after stroke. I further hypothesize that inhibition of astrocytic transforming growth factor-β (TGF-β) signaling can reverse these phenotypes. Finally, I also hypothesize that serum biomarkers of perivascular fibrosis can be used to diagnose CAA following intracerebral …

Population Codes And Their Correlates In Decision Making, Neda Shahidi

Dissertations and Theses (Open Access)

This dissertation was organized in two parts: in part 1, we discussed Neural Correlates of Perceptual Accuracy” and in part 2 we discussed “Strategy encoding in Prefrontal Cortex”.

Abstract of part 1_The accurate transmission of electrical signals within neocortex is central to sensory perception and cognition. Theoretical studies have long proposed that the temporal coordination of cortical spiking activity controls signal transmission and cognitive function. In reality, whether and how the precise temporal coordination in neuronal populations during wakefulness influences perception remains a mystery. Here, we simultaneously recorded populations of neurons in early and mid-level visual cortex (areas V1 …

Examining The Associative Learning And Accumbal Dopaminergic Mechanisms Of Caffeine Reinforcement, Curtis Bradley

Electronic Theses and Dissertations

Caffeine is the most consumed psychoactive substance in the world, and most caffeine consumption in coffee and energy drinks is intended to produce a psychoactive effect. However, caffeine is not a primary reinforcer in preclinical paradigms – non-human species do not reliably take the drug to produce a psychoactive effect. However, caffeine is a ‘reinforcement enhancer’ in preclinical models; the effects of caffeine increase the motivation to obtain other non-drug reinforcers. The overall goal of this project was to determine if these reinforcement enhancing effects of caffeine could promote caffeine self-administration and to subsequently investigate the behavioral and neurochemical underpinnings …

'Neurophobia,' A Reply To Patterson, Peter A. Alces

Faculty Publications

No abstract provided.

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, Bradley Serpa

Master of Science in Integrative Biology Theses

Driven by the communication of dopamine, the vertebrate reward system has been evolutionarily conserved to maintain survival and optimize fitness. The neural circuits governing this system integrate sensory stimuli to produce appropriate, self-preserving responses that underlie experience-based learning. In the most primitive vertebrates, dopamine release in neuronal circuits drives homeostatic behaviors, such as seeking nutrients, finding a mate, or avoiding danger. From agnathans to mammals, dopaminergic synthesis and signaling genes and molecules, along with neuronal pathways and reward system-based behaviors, remain highly conserved. Dopamine signaling proteins include two classes of metabotropic G-Protein Receptor Coupled Dopamine Receptors, D1-like (DRD1) and D2-like …

Idiosyncratic, Retinotopic Bias In Face Identification Modulated By Familiarity, Matteo Visconti Di Oleggio Castello, Morgan Taylor, Patrick Cavanagh, Maria Ida Gobbini

Dartmouth Scholarship

The perception of gender and age of unfamiliar faces is reported to vary idiosyncratically across retinal locations such that, for example, the same androgynous face may appear to be male at one location but female at another. Here we test spatial heterogeneity for the recognition of the identity of personally familiar faces in human participants. We found idiosyncratic biases that were stable within participants and that varied more across locations for low as compared to high familiar faces. These data suggest that like face gender and age, face identity is processed, in part, by independent populations of neurons monitoring restricted …

An Interview With Cesare Montecucco, Mandë Holford, Andreas Rummel

Publications and Research

Cesare Montecucco is a member of the board of various leading scientific journals. His research focus is on the regeneration of the peripheral nervous system and on the mechanisms of action of toxins and related diseases, including tetanus, botulism, anthrax and Helicobacter pylori-associated diseases. In this interview, we talked to Cesare Montecucco about his career, learning and culture.

Complexities And Challenges Of Nonduality, Elizabeth Stephens

CONSCIOUSNESS: Ideas and Research for the Twenty-First Century

States of consciousness referred to as nonduality, awakening, enlightenment, moksha, peak experience, unitive states, or void states, among other terms, have garnered increasing secular attention and have become a topic of psychological and neuroscientific research. A review of the literature revealed many challenges to studying this set of states, such as inconsistent conceptualizations, a variety of models and theories, and conflicting descriptions indicating that the actual experience may not live up to the superlative descriptions found in historical texts or the expectations put forth by nondual teachers. A great deal more empirical research on this topic is needed, and researchers …

Prmt5-Mediated Regulation Of Developmental Myelination, Antonella Scaglione, Julia Patzig, Jialiang Liang, Rebecca Frawley, Jabez Bok, Angeliki Mela, Camila Yattah, Jingxian Zhang, Shun Xie Teo, Ting Zhou, Shuibing Chen, Emily Bernstein, Peter Canoll, Ernesto Guccione, Patricia Casaccia

Publications and Research

Oligodendrocytes (OLs) are the myelin-forming cells of the central nervous system. They are derived from differentiation of oligodendrocyte progenitors through a process requiring cell cycle exit and histone modifications. Here we identify the histone arginine methyl-transferase PRMT5, a molecule catalyzing symmetric methylation of histone H4R3, as critical for developmental myelination. PRMT5 pharmacological inhibition, CRISPR/cas9 targeting, or genetic ablation decrease p53-dependent survival and impair differentiation without affecting proliferation. Conditional ablation of Prmt5 in progenitors results in hypomyelination, reduced survival and differentiation. Decreased histone H4R3 symmetric methylation is followed by increased nuclear acetylation of H4K5, and is rescued by pharmacological inhibition of …

Immature Auditory Evoked Potentials In Children With Moderate-Severe Developmental Language Disorder., Elaine Yuen Ling Kwok, Marc F Joanisse, Lisa Archibald, Janis Oram Cardy

Health and Rehabilitation Sciences Publications

Purpose: Immature auditory processing has been proposed to underlie language impairments in children with developmental language disorder (DLD; also known as specific language impairment). Using newly available normative auditory evoked potential (AEP) waveforms, we estimated AEP maturity in individual children with DLD and explored whether this maturational index was related to their language abilities.

Method: AEPs were elicited by 225 trials of a 490-Hz pure tone. Using intraclass correlation and our previously established normative AEP waveforms of 7- to 10-year-old children with typical development, we estimated the age equivalent of the AEPs (AEP-age) from 21 children with DLD. The relation …

Doxorubicin-Induced Elevated Oxidative Stress And Neurochemical Alterations In Brain And Cognitive Decline: Protection By Mesna And Insights Into Mechanisms Of Chemotherapy-Induced Cognitive Impairment ("Chemobrain"), Jeriel T. R. Keeney, Xiaojia Ren, Govind Warrier, Teresa Noel, David K. Powell, Jennifer M. Brelsfoard, Rukhsana Sultana, Kathryn E. Saatman, Daret K. St. Clair, D. Allan Butterfield

Chemistry Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice …

Modeling Semantic Encoding In A Common Neural Representational Space, Cara E. Van Uden, Samuel A. Nastase, Andrew C. Connolly, Ma Feilong, Isabella Hansen, M Ida Gobbini, James V. Haxby

Dartmouth Scholarship

Encoding models for mapping voxelwise semantic tuning are typically estimated separately for each individual, limiting their generalizability. In the current report, we develop a method for estimating semantic encoding models that generalize across individuals. Functional MRI was used to measure brain responses while participants freely viewed a naturalistic audiovisual movie. Word embeddings capturing agent-, action-, object-, and scene-related semantic content were assigned to each imaging volume based on an annotation of the film. We constructed both conventional within-subject semantic encoding models and between-subject models where the model was trained on a subset of participants and validated on a left-out participant. …

Ca2+, Astrocyte Activation And Calcineurin/Nfat Signaling In Age-Related Neurodegenerative Diseases, Pradoldej Sompol, Christopher M. Norris

Sanders-Brown Center on Aging Faculty Publications

Mounting evidence supports a fundamental role for Ca²⁺ dysregulation in astrocyte activation. Though the activated astrocyte phenotype is complex, cell-type targeting approaches have revealed a number of detrimental roles of activated astrocytes involving neuroinflammation, release of synaptotoxic factors and loss of glutamate regulation. Work from our lab and others has suggested that the Ca²⁺/calmodulin dependent protein phosphatase, calcineurin (CN), provides a critical link between Ca²⁺ dysregulation and the activated astrocyte phenotype. A proteolyzed, hyperactivated form of CN appears at high levels in activated astrocytes in both human tissue and rodent tissue around regions of amyloid and …

Regulation Of Epithelial Sodium Channels In Vasopressin Neurons In The Hypothalamus, Natalie Jean Mills

LSU Doctoral Dissertations

Salt-sensitive individuals have blood pressure that is unusually sensitive to salt intake. Because salt-sensitivity is a common disorder and may cause high blood pressure, it is a significant public health concern. All three epithelial Na⁺ channel (ENaC) subunits (a, b, and g) and the mineralocorticoid receptor (MR), a known regulator of ENaC, are expressed by vasopressin (VP) synthesizing magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei. A growing body of evidence indicates that epithelial Na⁺ channels (ENaCs) in the hypothalamus play a significant role in the development of salt-sensitivity. My dissertation research tests the hypothesis …