Molecular and Cellular Neuroscience Commons^™

Serotonergic System And Gait: Dorsal Raphe Nucleus As A Control System For Gait, Nahal Farhani

Electronic Thesis and Dissertation Repository

In advanced stages of Parkinson Disease (PD), gait and postural abnormalities emerge. These symptoms are not prominent at early stages of PD despite significant dopaminergic neuronal loss. Gait abnormalities are largely not responsive to levodopa. Therefore, other types of neurons might be responsible for gait abnormalities of the PD.

Since the reticulospinal tract (RET) is mainly implicated in the control of axial muscles, the degeneration of this pathway or populations of neurons controlling this pathway might be responsible for axial symptoms. However, there is limited data about the neurons controlling the RET. Our aim in this study is to delineate …

Genetic And Acute Cpeb1 Depletion Ameliorate Fragile X Pathophysiology, Tsuyoshi Udagawa, Natalie Farny, Mira Jakovcevski, Hanoch Kaphzan, Juan Alarcon, Shobha Anilkumar, Maria Ivshina, Jessica Hurt, Kentaro Nagaoka, Vijayalaxmi Nalavadi, Lori Lorenz, Gary Bassell, Schahram Akbarian, Sumantra Chattarji, Eric Klann, Joel Richter

Natalie G. Farny

Fragile X syndrome (FXS), the most common cause of inherited mental retardation and autism, is caused by transcriptional silencing of FMR1, which encodes the translational repressor fragile X mental retardation protein (FMRP). FMRP and cytoplasmic polyadenylation element-binding protein (CPEB), an activator of translation, are present in neuronal dendrites, are predicted to bind many of the same mRNAs and may mediate a translational homeostasis that, when imbalanced, results in FXS. Consistent with this possibility, Fmr1(-/y); Cpeb1(-/-) double-knockout mice displayed amelioration of biochemical, morphological, electrophysiological and behavioral phenotypes associated with FXS. Acute depletion of CPEB1 in the hippocampus of adult Fmr1(-/y) mice …

Behavioral, Neurobiological, And Genetic Analysis Of The Circadian Mutant Duper, Emily Nicole Corbett Manoogian

Doctoral Dissertations

The recently discovered circadian mutant hamster duper has a short period of ~23 hours and exhibits exaggerated phase shifts in response to a 15-min light pulse. To increase the understanding of the duper mutation, I performed behavioral, neurobiological, and genetic experiments. Behavioral studies using photic and non-photic stimuli found that large phase shifts exhibited by duper hamsters are specific to photic cues, but not to phase. Additionally, 2/3 of duper hamsters, but no WTs, displayed transient ultradian wheel-running patterns when transferred from light to dark at CT 18. This suggests that the mutation may weaken coupling among components of the …

Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells, Amanda M. Hussey

Doctoral Dissertations

Proper detection is the key to studying any processes on the cellular scale. Nowhere is this more evident than in the tight space which confines the synaptic cleft. Being able to ascertain the location of receptors on live neurons is fundamental to our understanding of not only how these receptors interact and move inside the cell but also how neurons function. Most detection methods rely on significantly altering the receptor; both tagging with a fluorescent protein or targeting the receptor by a fluorescent reporter in the form of a small molecule causes significant difficulties. These localization techniques often result in …

Non-Canonical Activation Of Nrf2 By Dimercaptopropanol As A Treatment For Huntington's Disease, Margaret Lauren Tindale

Electronic Thesis and Dissertation Repository

Mitochondrial dysfunction and elevated reactive oxygen species (ROS) levels are strongly implicated in various neurodegenerative disorders, including Huntington’s disease (HD). Expression of the mutant Huntingtin protein (mHTT) containing an expanded polyglutamine repeat is associated with oxidative stress and toxicity in striatal neurons. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor responsible for regulating expression of a diverse array of antioxidant and cytoprotective genes. Most known Nrf2-activating compounds act through the canonical pathway by mimicking a transient oxidative insult, and treatment effects are short-lived. This study reveals an increase in striatal cell viability, and a reduction in …

Mechanisms Of Neuroprotection Against Ischemic Insult By Stress-Inducible Phosphoprotein-1, Jason Xu

Electronic Thesis and Dissertation Repository

Stress-inducible phosphoprotein-1 (STI1) levels are increased in the brain following ischemia. STI1 is a co-chaperone for Hsp70/Hsp90 modulating protein folding. STI1 can also be secreted by a number of cells and function to activate extracellular signalling by the prion protein (PrP^C) and type-I bone morphogenetic protein receptor ALK2. However, the mechanisms by which STI1 can protect neurons against ischemia are currently unknown. A caspase-3 reporter mouse line was used to evaluate the consequences of increased extracellular STI1 levels. Neurons were treated with recombinant STI1 and specific agonists/antagonists for PrP^C, α7nAChR, and ALK2 prior to oxygen-glucose deprivation …

Reactive Oxygen Species-Mediated Neurodegeneration Is Independent Of The Ryanodine Receptor In Caenorhabditis Elegans, Lyndsay E.A. Young, Daniel C. Williams

Journal of the South Carolina Academy of Science

Despite the significant impacts on human health caused by neurodegeneration, our understanding of the degeneration process is incomplete. The nematode Caenorhabditis elegans is emerging as a genetic model organism well suited for identification of conserved cellular mechanisms and molecular pathways of neurodegeneration. Studies in the worm have identified factors that contribute to neurodegeneration, including excitotoxicity and stress due to reactive oxygen species (ROS). Disruption of the gene unc-68, which encodes the ryanodine receptor, abolishes excitotoxic cell death, indicating a role for calcium (Ca²⁺) signaling in neurodegeneration. We tested the requirement for unc-68 in ROS-mediated neurodegeneration using the …

Characterizing The Rogfp2-Orp1 Fluorescent Biosensor For Detecting Oxidative Stress In Mammalian Cells, Sara A. Doan, Stevie Norcross, Mathew Tantama

The Summer Undergraduate Research Fellowship (SURF) Symposium

Parkinson’s disease is a neurodegenerative disease involving the death of neurons in the substantia nigra and loss of the neurotransmitter, dopamine. The disease leads to progressive loss of motor control. Exact causes and mechanisms by which Parkinson’s disease proceeds are unknown, however, previous experiments determine oxidative stress in mitochondria as a factor that results in cell death. Strategies have been implemented to generate fluorescent biosensors to monitor reactive oxygen species (ROS) concentrations while simultaneously measuring the spatiotemporal distribution and correlation between the ROS, cellular function and organelle. Orp1, an enzyme found in yeast, is a sensitive oxidizing species and when …

Developing A Contrast Agent For The In Vivo Detection Of Apoptosis, Mary R. Cobb

Electronic Thesis and Dissertation Repository

Currently, there is no way to assess apoptotic cell death in living organisms. We have developed a novel contrast agent targeted toward the detection of caspase-3 activity, the key enzymatic mediator of apoptosis. Our contrast agent consists of a dual magnetic resonance imaging/fluorescent probe coupled to a cell penetrating peptide (CPP) sequence by a peptide backbone containing a caspase-3 cleavage site. The CPP allows the agent to cross cell membranes and the blood brain barrier. In cells undergoing apoptosis, activated caspase-3 will cleave the agent removing the CPP and trapping the imaging probes inside the cell.

The purpose of this …

Muscarinic Attenuation Of Mnemonic Rule Representation In Macaque Dorsolateral Prefrontal Cortex During A Pro- And Anti-Saccade Task, Alex J. Major

Electronic Thesis and Dissertation Repository

Maintenance of context is necessary for execution of appropriate responses to diverse environmental stimuli. The dorsolateral prefrontal cortex (DLPFC) plays a pivotal role in executive function, including working memory and representation of abstract rules, and is modulated by the ascending cholinergic system through nicotinic and muscarinic receptors. Muscarinic receptors’ effect on local primate DLPFC neural activity in vivo during cognitive tasks remains poorly understood. Here we examined the effects of muscarinic receptor blockade on rule-related activity in the macaque prefrontal cortex by combining iontophoretic application of the general muscarinic receptor antagonist scopolamine with single-unit recordings while monkeys performed a rule-guided …

Characteristics Of Exocytosis And Endocytosis In Photoreceptors, Karlene M. Cork

Theses & Dissertations

Photoreceptors signal changes in light intensity to downstream retinal neurons through the exocytosis of glutamate-containing synaptic vesicles. The maintenance of the vesicle exocytosis and endocytosis process is essential for ongoing synaptic signaling. This study investigated the properties of exocytosis and endocytosis in photoreceptors and their role in ongoing neurotransmission.

I used electrophysiology and imaging techniques to study the properties of vesicle exocytosis and endocytosis in photoreceptors. First, we examined baseline release in photoreceptors that occurs in the absence of depolarizing stimulation. We measured mEPSCs in whole cell patch clamp recordings from horizontal cells. After inhibiting Ca²⁺ influx and efflux …

Analysis Of Mitochondrial Turnover In Neuromuscular Junctions Of Parkin Mutants, Kenny Nguyen, Hyun Sung, Peter J. Hollenbeck

The Summer Undergraduate Research Fellowship (SURF) Symposium

The accumulation of dysfunctional or damaged mitochondria in neurons has been linked to the pathogenesis of many neurodegenerative diseases, such as Parkinson’s disease. It has been proposed that proteins PINK1 and Parkin regulate mitochondrial quality control by selectively targeting depolarized mitochondria for autophagic degradation, a process known as mitophagy. Though previously analyzed in the cell bodies and axons of neurons, the role of the PINK1/Parkin pathway in the synapse is unclear, and it is not known whether mitochondrial turnover occurs in the neuromuscular junctions (NMJs). To study this, intact Drosophila nervous systems were analyzed in vivo by performing gentle dissections …

A Screen To Identify Saga-Activated Genes That Are Required For Proper Photoreceptor Axon Targeting In Drosophila Melanogaster, Kaelan J. Brennan, Vikki M. Weake, Jingqun Q. Ma

The Summer Undergraduate Research Fellowship (SURF) Symposium

The inherited human genetic disease spinocerebellar ataxia type 7 (SCA7) is characterized by progressive neurodegeneration and visual impairment that ultimately leads to blindness. SCA7 results from a mutation in the human ATXN7 gene that causes an expansion of polyglutamine tracts in this gene’s corresponding protein. Human ATXN7 protein serves as a component of the deubiquitylase (DUB) module of the large, multi-subunit complex Spt-Ada-Gcn acetyltransferase, or SAGA. SAGA is a transcriptional coactivator and histone modifier that functions to deubiquitylate histone H2B and allow for transcription of SAGA-mediated genes to occur. In Drosophila, mutations in SAGA DUB’s Nonstop and sgf11 components …

Microengineering The Neural Tube, Christopher Demers

Electronic Theses and Dissertations

Early embryonic development is a complex and highly regulated orchestra of instructive cues that collectively guide naïve stem cells towards progressively more specialized fates. In the neural tube, the precursor structure to the brain and spinal cord, these signals emanate from ‘organizing centers’ surrounding the neural tube. These organizing centers send out soluble cues or morphogens that diffuse tens to hundreds of microns to recipient cells residing in the neural tube. Re-creating this dynamic landscape of cues in vitro is impossible using standard cell culture tools and techniques. However, microfluidics is perfectly suited to fill this gap, allowing precise control …

Canonical Bmp Signaling Is Required For Allodynia In Drosophila Melanogaster, Taylor L. Follansbee

All Theses And Dissertations

In the United States alone over 100 million people suffer from chronic pain and unfortunately, even still, there is a lack in scientific understanding for the mechanisms of abnormal pain sensitivity. The present study utilized a candidate gene approach to identify novel components required for modulation of the tissue damage induced pain sensitization pathway in Drosophila melanogaster. We have shown that RNAi silencing of decapentaplegic (dpp), a member of the Bone Morphogenetic Protein (BMP) signaling pathway, specifically in the class IV multidendritic nociceptor neurons significantly attenuated UV-induced nociceptive sensitization. Furthermore, overexpression of dpp in nociceptor neurons was sufficient to …

Hippocalcin Response To Calcium: Do Conserved Tryptophans – W30 Or W103 – Matter?, Sunkesula K. Sagar

Graduate School of Biomedical Sciences Theses and Dissertations

Changes in intracellular calcium levels play a very important role in cell signaling, in turn, affecting neuronal functions such as memory, learning and cell death. A class of proteins called Neuronal Calcium Sensor (NCS) proteins serves to modulate the functioning of the neuronal cells in response to changes in calcium levels, and prevent neuronal apoptosis. Structurally, all NCS proteins have 4 calcium-binding EF hand motifs, although EF1 does not bind to calcium in many members. All NCS proteins have an acyl modification at the N- terminus – where a myristoyl group is added post-translationally. Hippocalcin (HPCA) is an NCS protein, …

Structure And Composition Of Postsynaptic Densities, Madeline Farley

Dissertations & Theses (Open Access)

Communication between neurons within the brain occurs at chemical synapses and is fundamental for all brain functions. Modulation of the strength of communication is controlled by both presynaptic and postsynaptic mechanisms and is termed synaptic plasticity. One postsynaptic structure postulated to regulate synaptic strength is the postsynaptic density (PSD), a large electron dense protein complex located just below the synaptic membrane. The PSD, which is composed of signaling, scaffold and cytoskeletal proteins, supports and organizes neurotransmitter receptors within the synaptic membrane in addition to bridging signaling with the actin cytoskeletal network. The protein composition and structure of PSDs is known …

Modulation Of Synaptic Plasticity By Hippocampal Theta Rhythm, Clayton Law

Electronic Thesis and Dissertation Repository

The hippocampal theta rhythm facilitates memory formation. This study investigated the temporal relation of long-term potentiation (LTP) with the hippocampal theta rhythm. Theta rhythm consists of a wave of somatodendritic depolarization, but the depolarization of apical and basal dendrites of hippocampal CA1 pyramidal cells peak at a similar theta phase. Thus, we hypothesize that the population spike excitability evoked by excitation of the apical and basal dendrites peak at a similar phase of the theta rhythm. We also expect that LTP at the basal and apical dendritic synapses to be maximal at a similar theta phase.

Rats (~300 g) were …

Investigating Subcellular Localization Of Tpa And Pai-1 In The Mammalian Circadian Clock, Grayson T Hunley

Chancellor’s Honors Program Projects

No abstract provided.

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

Exercise-Induced Adult Neruogenesis And The Seizure Threshold: The Role Of Cox-2, Gina Kim

Honors Capstone Projects - All

Neurogenesis, the generation of new neurons, is most prevalent when the brain is being formed during pre-natal development. However, this process continues in select areas in the brain during adult life as well. One such area in the brain is the dentate gyrus (DG) of the hippocampus, an area known to be associated with learning and memory. In this region, neurogenesis is believed to contribute to neuroplasticity as well as improving its functions in learning and memory. Interestingly, this synthesis of neurons is increased by physical activity—predominantly running—and by seizures originating in the limbic system. The increased excitatory neuronal activity …

Inverse Changes In Ghrelin And A2a Receptor Gene Expression Levels In The Hippocampus Of Heart Failure Canines Following Spinal Cord Stimulation, Benjamin E. Jewett

Undergraduate Honors Theses

Myocardial infarction (MI), often referred to as a heart attack, is a serious health issue in the United States. There is a well-documented link between MI and major depressive disorder (MDD), with a high incidence of MDD occurring after an MI. Overlapping pathologies have been observed within the hippocampus of the brain in animal models of MI and depression. These observations suggest that pathobiological cross-talk between the heart and brain could have a role in the etiology of MDD that occurs after an MI. Spinal cord stimulation (SCS) has previously been shown to have both cardioprotective and neuroprotective effects post-MI, …

Death Associated Protein Kinase (Dapk) -Mediated Neurodegenerative Mechanisms In Nematode Excitotoxicity, John S. Del Rosario, Katherine Genevieve Feldmann, Towfiq Ahmed, Uzair Amjad, Bakkeung Ko, Junhyung An, Tauhid Mahmud, Maha Salama, Shirley Mei, Daniel Asemota, Itzhak Mano

Publications and Research

Background: Excitotoxicity (the toxic overstimulation of neurons by the excitatory transmitter Glutamate) is a central process in widespread neurodegenerative conditions such as brain ischemia and chronic neurological diseases. Many mechanisms have been suggested to mediate excitotoxicity, but their significance across diverse excitotoxic scenarios remains unclear. Death Associated Protein Kinase (DAPK), a critical molecular switch that controls a range of key signaling and cell death pathways, has been suggested to have an important role in excitotoxicity. However, the molecular mechanism by which DAPK exerts its effect is controversial. A few distinct mechanisms have been suggested by single (sometimes contradicting) studies, and …

Coding Of Social Signals By Glutamatergic And Gabaergic Neurons In The Social Neural Network, Megan Moore

Georgia State Undergraduate Research Conference

No abstract provided.

Characterizing Orphan Gpcrs In Molluscan Neurons Through Bioinformatics, Preetham Ganupuru

Georgia State Undergraduate Research Conference

No abstract provided.

Does The Crayfish Tail Fan Sense Chemicals, Semira Adella, Imon Allen, Tyler Flot

Georgia State Undergraduate Research Conference

No abstract provided.

Establishing A Synaptoneurosome Preparation To Investigate Memory Formation Of A Meal, Alexa Faulkner, Amy P. Ross

Georgia State Undergraduate Research Conference

No abstract provided.

Circadian Rhythmic Localization Of Tpa And Pai-1 In The Scn 2.2 Cell Culture May Provide Evidence For Determining The Mechanism Of Gating Photic Phase Shifts, Grayson T Hunley

EURēCA: Exhibition of Undergraduate Research and Creative Achievement

Mammalian circadian rhythms are controlled by a central pacemaker located in the suprachiasmatic nucleus (SCN) of the brain. The SCN exhibits endogenous rhythms in neuronal activity and entrains to external stimuli, particularly light. Interestingly, phase shifts in response to light only occur at night and the mechanisms gating phase shifting are not well characterized. Our lab demonstrated that the extracellular protease, tissue-type plasminogen activator (tPA) and its inhibitor, plasminogen activator inhibitor (PAI-1), help gate phase shifting. Total tPA and PAI-1 expression are rhythmic in mouse SCN. These proteins mediate different functions depending on their exact subcellular localization. Therefore, knowing where …

Abnormal Hippocampal Activation In Freely Behaving Mice Deficient For The Vesicular Acetylcholine Transporter, Shahin Moallem

Electronic Thesis and Dissertation Repository

Acetylcholine (Ach) has a fundamental role in cortical activation. The activation of the hippocampus, a cortex implicated in cognitive and sensorimotor functions, is characterized by an increase in power and frequency of oscillations in the theta (4-10 Hz) and gamma (30-100 Hz) frequency range. We studied hippocampal activation in two mutant mouse lines with deficiency in cholinergic functionality: VAChT KD^HET (HET), and VAChT^{Nkx2.1-Cre-flox/flox} (KO). We hypothesized that the mutant mice, relative to wild-type (WT) mice, will manifest abnormal theta and gamma oscillations during different behaviors, and in response to muscarinic cholinergic antagonist scopolamine hydrochloride and to the NMDA …

Comparison Between Coated Vs. Uncoated Suture Middle Cerebral Artery Occlusion In The Rat As Assessed By Perfusion/Diffusion Weighted Imaging, James Bouley, Marc Fisher, Nils Henninger

Nils Henninger

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated …