Molecular and Cellular Neuroscience Commons^™

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 …

Synaptic Transmission At The Photoreceptor Ribbon Synapse, Chris Mesnard

Theses & Dissertations

Synaptic transmission relies on the Ca²⁺-dependent release of neurotransmitters packaged into synaptic vesicles. Ribbon synapses have the capability to release multiple vesicles at a time in a highly coordinated and synchronized manner. Glutamate release from rod and cone photoreceptor cells involves presynaptic ribbons composed largely of the protein RIBEYE. To examine roles of ribbons in rods and cones, we studied mice in which GCamP3 replaced the B-domain of RIBEYE. We discovered that ribbons were absent from rods and cones of both knock-in mice possessing GCamP3 and conditional RIBEYE knockout mice. Mice lacking ribbons showed reduced temporal resolution and …

Evaluating Sex Differences In The Neuroimmune Response Following Neuroinflammation And Relief Due To Nanotheranostic Treatment, Brooke Deal

Electronic Theses and Dissertations

Until recently, the majority of preclinical neuroinflammatory studies were performed on males. Because of this, less is known about the female neuroinflammatory response to injury, formation of pain, or response to pain-relieving therapies. The neuroinflammatory response is multifaceted with neuronal, glial, and immune cells all contributing to the induction and resolution of neuroinflammation. During this response, macrophages typically undergo an upregulation of cyclooxygenase-2 (COX-2) leading to the production of prostaglandin E2 (PGE2), which is linked to neuronal sensitization and pain. Non-steroidal anti-inflammatory drugs (NSAIDs) attenuate PGE2 by the inhibition of COX-2. A limitation with NSAIDs is that due to the …

Swallowing Disrupts Tongue-Jaw Coordination During Chewing In A Rat Model Of Parkinson's Disease, Meejan Palhang, N. Charles, Francois Gould

Rowan-Virtua Research Day

The primary motor symptoms of Parkinson’s disease, including bradykinesia, rigidity, and tremor, are associated with difficulties regulating transitions between motor behaviors due to basal ganglia dysfunction. Chewing and swallowing, which are disordered in most patients with Parkinson’s disease, are two complex motor behaviors which overlap in time and share some neuromuscular components. The objective of this study is to identify how Parkinson’s disease affects the coordination of chewing and swallowing. We hypothesize that as a result of impaired regulation of shift between motor patterns, chewing cycles that occur with a swallow will be more affected that chewing cycles occurring in …

Transcriptional Regulation Of Stem Cell Function In The Drosophila Central Nervous System, Amalia S. Parra

Biology ETDs

Development of multicellular organisms depends on coordination of various molecular mechanisms to ensure proper tissue size and structure. This is accomplished through intrinsic and extrinsic cues that regulate cell growth and proliferation both spatially and temporally. These well-coordinated signals are present from early developmental stages and remain active throughout development to ensure tissue structure is appropriate for function. This is particularly important in early cell types that form specialized lineages such as stem cells or those found throughout the body such as epithelia. While much progress has been made in understanding growth regulatory mechanisms, several fundamental aspects remain unknown. This …

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …

Synaptic Properties Of Parabigeminal Circuits., Kyle Whyland

Electronic Theses and Dissertations

Subcortical structures of the visual system have been the subject of intense study in recent years, but there remain some important unanswered questions regarding the synaptic relationships linking the nuclei that comprise this important sensory network within the brain. In these studies, we use several modern and traditional approaches, including viral tract tracing, in vitro slice physiology, immunohistochemistry, optogenetics, and electron microscopy to characterize the circuits linking the superior colliculus (SC), parabigeminal nucleus (PBG), and lateral geniculate nucleus (LGN), with particular focus on GABAergic and cholinergic cell types. We found that the SC, an important visuomotor structure with connections to …

An Investigation Into Structural Plasticity In Peripheral Taste Neurons Associated With Taste Cell Turnover., Zachary Whiddon

Electronic Theses and Dissertations

The continual replacement of taste cells creates interesting questions regarding how the innervating neurons are impacted during this process. Here we ask how innervation within taste buds is affected when taste cell entry is inhibited and reestablished. Inhibition of sonic hedgehog signaling (Shh) is thought to inhibit taste cell turnover. Consistently, fewer new cells were added to individual taste buds after treatment with a Shh-inhibitor compared to vehicle treatment, and taste bud volume decreased after 16 days of treatment. We next examined how taste nerve fiber extension into the gustatory epithelium is affected by preventing taste cell turnover. Ten days …

Perineuronal Nets Are Not Required To Close The Critical Period For Ocular Dominance Plasticity., Emily Crouse

Electronic Theses and Dissertations

In the developing visual system, a transient critical period demarcates when neural circuits are most sensitive to visual experience. In the mouse, the critical period occurs between approximately postnatal day(P) 19 to 32. Closing one eye (monocular deprivation, MD) within the critical period shifts ocular dominance (OD) to be more responsive to the open eye. Nogo-66 Receptor 1 (NGR1) limits OD plasticity to the critical period yet it remains unknown how OD plasticity propagates through primary visual cortex or by which mechanisms NGR1 utilizes to confine said plasticity. In primary studies, NGR1 was selectively deleted in different cortical layers to …

Effects Of Acute And Repeated Alcohol Exposure On Expression Of Synaptic-Associated Genes In The Male And Female Mouse Mpfc, Dhruba Podder

Undergraduate Honors Theses

Alcohol use disorder (AUD) is a serious chronic brain disease; in 2021 there were ~29.5 million people in the U.S. diagnosed with AUD. Individuals with AUD often show cognitive impairment such as risky decision-making, difficulties with impulse control, and working memory deficits. This impairment is associated with structural and functional changes in the prefrontal cortex (PFC), an extensively interconnected region of the frontal lobe involved in executive control of goal-directed behaviors. Chronic alcohol exposure in rodents has been seen to cause deficits in performance in behavioral tasks which assess mPFC function such as working memory and behavioral flexibility. It is …

Morphological Characterization Of Two Transgenic Strategies For Genetic Access To Semilunar Granule Neurons In The Mouse Dentate Gyrus, David T. Rexford

Masters Theses

Granule cells (GCs) of the dentate gyrus (DG) have been understood as a homogeneous class of neurons exhibiting a characteristic limited firing pattern. A subtype of GC called a semilunar granule cell (SGC) has been identified exhibiting variant morphology, electrophysiology, and positioning from normal GCs. SGCs represent an emerging novel subpopulation of GCs, however, there is presently no genetic tool to access SGCs separately from normal GCs. To provide access for future in vivo studies of this population, we examined two genetic strategies for putative SGC specificity in mouse brain slices. Morphological analysis was performed for quantitative identification of putative …

Functional Domains Of The Hsv-1 Ul37 Protein In Virus Infectivity And Retrograde Transport In Neurons, Carolyn Clark

LSU Doctoral Dissertations

Herpes simplex virus type 1 is large alphaherpesvirus with 20 envelope proteins and 23 tegument proteins. Virus entry is via fusion of the viral envelope with cellular membranes mediated by a complex of viral glycoproteins. Glycoprotein B (gB) is the only fusogenic glycoprotein, while other viral glycoproteins and membrane proteins including gD, gH, gL, gK and UL20 membrane protein modulate gB’s fusogenicity. Previously, Our laboratory developed the HSV-1 (VC2) vaccines strain with partial deletions in the amino termini of gK (ΔgK(31–68)) and the UL20 membrane protein (ΔUL20(4–22)). VC2 enters epithelial cells only via endocytosis followed by release of the capsid …

Phenotypic And Target-Based Drug Discovery, Angelica Veronica Carmona

Theses & Dissertations

Batten Disease or Neuronal Ceroid Lipofuscinosis (NCL) is a group of rare, fatal, inherited pediatric neurodegenerative lysosomal storage disorders. NCLs are characterized by intracellular accumulation of an auto-fluorescent lipopigment called ceroid lipofuscin and neurodegeneration. Several forms of NCLs exist, some of which share some of the same features and symptoms but vary in severity and onset of symptoms with respect to age. Some common symptoms include progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and in the rare adult-onset, dementia. Subtypes of NCLs occur when one of 13 different genes are mutated, and only two subtypes …

Role Of Nucleus Accumbens Dopamine Receptor Signaling In The Suppression Of Punished Reward Seeking, Grace M. Joyner, Anna Caroline Toburen

Senior Theses

Previous studies have shown that within the nucleus accumbens (NAc), a brain region associated with motivation and reinforcement learning, activity of neurons expressing the dopamine D2 receptor (D2R neurons) act as a “break” on risky behavior associated with negative outcomes. Moreover, when these neurons are stimulated, rats were found to become more risk averse. However, the impact of dopamine signaling through NAc D2R neurons in risk avoidance is still unclear. To further explore the role of NAc dopamine signaling in punished reward-seeking, we tested rats in a novel punished food-seeking paradigm in which subjects are trained to choose between a …

Glycemic Challenge Is Associated With The Rapid Cellular Activation Of The Locus Ceruleus And Nucleus Of Solitary Tract: Circumscribed Spatial Analysis Of Phosphorylated Map Kinase Immunoreactivity, Arshad Khan

Selected Works Temporary Series

Rodent studies indicate that impaired glucose utilization or hypoglycemia is associated with the cellular activation of neurons in the medulla (Winslow, 1733) (MY), believed to control feeding behavior and glucose counterregulation. However, such activation has been tracked primarily within hours of the challenge, rather than sooner, and has been poorly mapped within standardized brain atlases. Here, we report that, within 15 min of receiving 2-deoxy-D-glucose (2-DG; 250 mg/kg, i.v.), which can trigger glucoprivic feeding behavior, marked elevations were observed in the numbers of rhombic brain (His, 1893) (RB) neuronal cell profiles immunoreactive for the cellular activation marker(s), phosphorylated p44/42 MAP …

Glycemic Challenge Is Associated With The Rapid Cellular Activation Of The Locus Ceruleus And Nucleus Of Solitary Tract: Circumscribed Spatial Analysis Of Phosphorylated Map Kinase Immunoreactivity, Khan

Departmental Papers (Biology)

Rodent studies indicate that impaired glucose utilization or hypoglycemia is associated with the cellular activation of neurons in the medulla (Winslow, 1733) (MY), believed to control feeding behavior and glucose counterregulation. However, such activation has been tracked primarily within hours of the challenge, rather than sooner, and has been poorly mapped within standardized brain atlases. Here, we report that, within 15 min of receiving 2-deoxy-D-glucose (2-DG; 250 mg/kg, i.v.), which can trigger glucoprivic feeding behavior, marked elevations were observed in the numbers of rhombic brain (His, 1893) (RB) neuronal cell profiles immunoreactive for the cellular activation marker(s), phosphorylated p44/42 MAP …

Cervical Spinal Cord Injury Leads To Injury And Altered Metabolism In The Lungs, Emily E. Huffman, Brittany E. Dong, Harrison A. Clarke, Lyndsay E. A. Young, Matthew S. Gentry, Derek B. Allison, Ramon C. Sun, Christopher M. Waters, Warren J. Alilain

Saha Cardiovascular Research Center Faculty Publications

High-cervical spinal cord injury often disrupts respiratory motor pathways and disables breathing in the affected population. Moreover, cervically injured individuals are at risk for developing acute lung injury, which predicts substantial mortality rates. While the correlation between acute lung injury and spinal cord injury has been found in the clinical setting, the field lacks an animal model to interrogate the fundamental biology of this relationship. To begin to address this gap in knowledge, we performed an experimental cervical spinal cord injury (N = 18) alongside sham injury (N = 3) and naïve animals (N = 15) to assess lung injury …

The Role Of The Kcc2 In Substance Use And Abuse: A Systematic Review [Protocol], Alfred Amendolara, Steven Salazar, Chad Thompson, Hyrum Wright, Andrew Payne

Annual Research Symposium

This poster presents the protocol for an ongoing systematic review investigating the role of potassium chloride co-transporter 2 (KCC2) in substance use, abuse, and addiction.

A Systematic Review: Toxoplasma Gondii Infection And Drugs Of Abuse, Amani Sastry

Annual Research Symposium

No abstract provided.

Appearance Of Two Distinct Clusters Of Glucose Dysregulation In Chronic Intractable Migraine, Roshni Jogin, Kaitlyn Mcfarland, Aparna Naik, Tanner Williford, Matthew Conway, Amar Paul, John A. Kriak, David W. Sant, Kyle B. Bills

Annual Research Symposium

No abstract provided.

Probing Amyloid-Beta Protein Structure And Dynamics With A Selective Antibody, Shikha Grover

Dissertations

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. The AD brain is characterized by significant neuronal loss and accumulation of insoluble fibrillar amyloid-β protein (Aβ) plaques and tau protein neurofibrillary tangles in the brain. However, over the last decade, many studies have shown that the neurodegenerative effect of Aβ may in fact be caused by various soluble oligomeric forms as opposed to the insoluble fibrils. Furthermore, the data suggest that a pre-fibrillar aggregated form, termed protofibrils, mediates direct neurotoxicity, and triggers a robust neuroinflammatory response.

Antibodies targeting the various conformation of Aβ are important therapeutic agents to prevent the progression …

Examining The Effect Of A Substituted Carbamate Positive Allosteric Modulator On (Alpha4)3(Beta2)2 And (Alpha4)2(Beta2)3 Nicotinic Acetylcholine Receptors, Josue Gaona, Musharaf Mohiuddin, Ayman K. Hamouda

School of Medicine Student Publications and Presentations

The α4β2 nicotinic acetylcholine receptors (nAChR) are the most abundant nAChR subtypes in the brain and exist in two distinct isoforms: (α4)2(β2)3 nAChR, the high sensitivity (HS) isoform, and (α4)3(β2)2 nAChR, the low sensitivity (LS) isoform. Given the pathophysiological and pharmacological importance of these brain receptors, there are ongoing efforts to develop pharmacophores that selectively potentiate α4β2 nAChRs (positive allosteric modulators, PAMs). PAMs selective to the α4β2 nAChRs would be beneficial for neuropsychiatric conditions such as nicotine addiction and Alzheimer’s disease. A chemical synthesis and high throughput screens at Amgen laboratories have identified a series of compounds that preferentially potentiate …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

High Volume Multiplex Staining Of Mouse Model In Alzheimer’S Associated Disease Pathology, Chloe Embry

Lewis Honors College Thesis Collection

Although neurodegenerative diseases are often clinically distinct, they typically share common pathological markers. One of the most common causes of clinical dementia is Alzheimer’s disease (AD). Pathologically, AD is defined by the presence of intercellular tangles composed of hyperphosphorylated tau proteins and extracellular plaques made of abnormally cleaved amyloid-beta proteins. However recent genome-wide association studies have also found that many of the predispositions for AD are located on or near genes highly expressed in microglia. In the healthy CNS, microglia act as the brain’s immune system and are chiefly involved in neuronal support and maintaining homeostasis throughout the CNS. Typically, …

The Role Of Schwann Cells In Nerve Injury: Forskolin-Mediated Camp Activation Upregulates Tnfα Expression Despite Nf-Κb Downregulation In Lps-Treated Schwann Cells, Caitlyn E. Henry, Angela L. Asirvatham Ph.D.

Student Research Poster Presentations 2023

Although Schwann cells are known to play a role in axonal regeneration following nerve injury and inflammation, the exact mechanism is unknown. This study explores two potential mechanisms: the NF-κB and cAMP pathways. The NF-κB pathway produces cytokines, such as TNFα, to regulate inflammation, whereas the cAMP pathway is anti-inflammatory and regulates Schwann cell proliferation via AKAP95 and cyclin D3. Although it is well-known that NF-κB and cAMP are involved in inflammation, not much is known regarding the effects of forskolin-mediated cAMP activation on LPS-mediated NF-κB activation in Schwann cells. In this study, RT4-D6P2T immortalized rat Schwann cells were treated …

Il-1r1 Within The Meningeal Lymphatic System, Nolan Abdelsayed

Lewis Honors College Thesis Collection

The meninges are made up of three membranes; the pia mater, arachnoid mater, and dura mater, that surround the brain and spinal cord. These specialized layers work in concert with cerebrospinal fluid (CSF), to protect the central nervous system by adding a layer of cushion and removing waste products from the CNS. Additionally, the meninges act as a physical barrier between the central nervous system and the periphery. The meningeal lymphatic system is a specialized group of vessels that lie within the meninges that assist in the flow of fluid and waste products from the brain. If the meningeal lymphatic …

Effects Of Hiv-1 Tat And Opiates On Gene Regulation Of Oligodendrocyte Lineage Cells: Identification Of Myrf As A Novel Target, Kelly M. Flounlacker

Theses and Dissertations

HIV-associated neurocognitive disorders remain pervasive even with increased efficacy/use of antiretroviral therapies. Opioid use/abuse among HIV+ individuals is documented to exacerbate deficits. White matter (WM) alterations (myelin pallor, volume/structural) detected by diffusion tensor imaging, are common observations in HIV+ individuals. Using transgenic mice expressing HIV-1 Tat, we examined effects of 2-6 weeks of Tat/morphine exposure on WM using genomic/biochemical methods. RNA sequencing of striatal tissue after 2-weeks revealed robust changes in mRNAs associated with oligodendrocyte populations/myelin integrity, including Transferrin, Ndrg1, and myelin regulatory factor (Myrf/Mrf), an oligodendrocyte-specific transcription factor involved in differentiation/maturation. Immunoblots conducted after 6-weeks exposure in …

Expression Of Htyr In Drosophila As A Novel Model Of Parkinson’S Disease, Madeleine Callan

Scripps Senior Theses

Parkinson’s disease is a debilitating and often deadly neurodegenerative disease affecting a growing and large population. Its etiology has long remained elusive, and because no other organisms have Parkinsonian-like diseases, it is difficult to study PD using model organisms. Neuromelanin (NM), an insoluble melanin synthesized in the dopaminergic synthesis pathway in DA neurons, has recently been implicated in PD as a major causal factor. At high levels in DA lysosomes, it functions as a proteostatic pathway inhibitor–blocking dopaminergic neurons from breaking down harmful molecules until the lysosomes eventually degenerate as well as triggering autophagy, inflammation, and total neurodegeneration. Recently, neuromelanin …

Interactions Between Hiv And Opioids On Antiretroviral Accumulation, The Blood Brain Barrier, And The Inflammatory Response In The Brain., Kara Rademeyer

Theses and Dissertations

The complex mechanisms related to HIV infection, neurodegeneration, and chronic neuroinflammation collectively describe neuroHIV (Hauser et al. 2007; Chang et al. 2014; Smith et al. 2014). Specifically, opioid abuse, poor penetration of antiretroviral (ARV) drugs, chronic inflammation and neuronal injury/degeneration are all implicated in neuroHIV (Fantuzzi et al. 2003; Letendre et al. 2004; Verani et al. 2005; Duncan and Sattentau 2011; Hong and Banks 2015; Simoes and Justino 2015; Olivier et al. 2018; Murphy et al. 2019; Osborne et al. 2020). For the first time, we demonstrate that morphine, fentanyl, and methadone in vivo alter the brain accumulation of ARVs, …

Age- And Sex-Dependent Alterations In Primary Somatosensory Neuronal Calcium Network Dynamics During Locomotion, Sami L. Case

Theses and Dissertations--Pharmacology and Nutritional Sciences

Over the past 30 years, the calcium (Ca2+) hypothesis of brain aging has provided clear evidence that hippocampal neuronal Ca2+ dysregulation is a key biomarker of aging. Indeed, age-dependent Ca2+-mediated changes in intrinsic excitability, synaptic plasticity, and activity have helped identify some of the mechanisms engaged in memory and cognitive decline. However, much of this work has been done at the single-cell level, mostly in slice preparations, and in restricted structures of the brain. Recently, our lab identified age- and Ca2+-related neuronal network dysregulation in the cortex of the anesthetized animal. Still, investigations in the awake animal are needed to …