Cholinergic Control Of Cortical Circuit Activity, 2018 The University of Texas M D Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences
Cholinergic Control Of Cortical Circuit Activity, Rajan Dasgupta
UT GSBS 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 ...
Organization And Development Of Cholinergic Input To The Mouse Visual Thalamus., 2018 University of Louisville
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 ...
Modeling And Mapping Addiction In The Zebrafish, Danio Rerio, 2018 Kennesaw State University
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 ...
Neurexin Directs Partner-Specific Synaptic Connectivity In C. Elegans, 2018 University of Massachusetts Medical School
Neurexin Directs Partner-Specific Synaptic Connectivity In C. Elegans, Alison Philbrook, Shankar Ramachandran, Christopher M. Lambert, Devyn Oliver, Jeremy Florman, Mark J. Alkema, Michele Lemons, Michael M. Francis
Open Access Articles
In neural circuits, individual neurons often make projections onto multiple postsynaptic partners. Here, we investigate molecular mechanisms by which these divergent connections are generated, using dyadic synapses in C. elegans as a model. We report that C. elegans nrx-1/neurexin directs divergent connectivity through differential actions at synapses with partnering neurons and muscles. We show that cholinergic outputs onto neurons are, unexpectedly, located at previously undefined spine-like protrusions from GABAergic dendrites. Both these spine-like features and cholinergic receptor clustering are strikingly disrupted in the absence of nrx-1. Excitatory transmission onto GABAergic neurons, but not neuromuscular transmission, is also disrupted. Our ...
Loss Of Sarm1 Does Not Suppress Motor Neuron Degeneration In The Sod1g93a Mouse Model Of Amyotrophic Lateral Sclerosis, 2018 University of Massachusetts Medical School
Loss Of Sarm1 Does Not Suppress Motor Neuron Degeneration In The Sod1g93a Mouse Model Of Amyotrophic Lateral Sclerosis, Owen M. Peters, Elizabeth A. Lewis, Jeannette M. Osterloh, Alexandra Weiss, Johnny Salameh, Jake P. Metterville, Robert H. Brown Jr., Marc R. Freeman
Neurobiology Publications and Presentations
Axon degeneration occurs in all neurodegenerative diseases, but the molecular pathways regulating axon destruction during neurodegeneration are poorly understood. Sterile Alpha and TIR Motif Containing 1 (Sarm1) is an essential component of the prodegenerative pathway driving axon degeneration after axotomy and represents an appealing target for therapeutic intervention in neurological conditions involving axon loss. Amyotrophic lateral sclerosis (ALS) is characterized by rapid, progressive motor neuron degeneration and muscle atrophy, causing paralysis and death. Patient tissue and animal models of ALS show destruction of upper and lower motor neuron cell bodies and loss of their associated axons. Here, we investigate whether ...
Could Extracellular Micrornas Act As A Novel Biomarkers Of Temporal Lobe Epilepsy?, 2018 Royal College of Surgeons in Ireland
Could Extracellular Micrornas Act As A Novel Biomarkers Of Temporal Lobe Epilepsy?, Rana Raoof
Epilepsy diagnosis is always a challenging process. A detailed clinical history is the main tool used for diagnosis and classification; however, it is often incomplete and misleading. Electroencephalography and neuroimaging have their role in assisting the diagnosis but, still, they cannot confirm or rule out epilepsy. This is reflected clinically as a high figure of epilepsy misdiagnosis, where about one third of patients are being misdiagnosed. The identification of a reliable molecular biomarker for epilepsy will not only allow for a definitive diagnosis of seizures and epilepsy but as well help in the disease classification, individualize the treatment options and ...
Endocytosis And The Nitric Oxide-Dependent Release Of Chloride, 2018 Louisiana State University and Agricultural and Mechanical College
Endocytosis And The Nitric Oxide-Dependent Release Of Chloride, Vernon K. Dunn Jr
LSU Doctoral Dissertations
Understanding the regulation of retinal synapses is a key step in elucidating the processing of information in the retina. Our lab has previously shown that nitric oxide (NO) can alter the synaptic response properties of amacrine cells by releasing Cl- from internal acidic compartments. This alteration in the Cl- gradient brings about a positive shift in the reversal potential of the GABA-gated current, which can convert inhibitory synapses into excitatory synapses. Recently, we have shown that the cystic fibrosis transmembrane regulator (CFTR) Cl- channel is involved in the Cl- release. Here, we test the hypothesis that (acidic) synaptic vesicles are ...
Mapping Molecular Datasets Back To The Brain Regions They Are Extracted From: Remembering The Native Countries Of Hypothalamic Expatriates And Refugees, Arshad M. Khan, Alice H. Grant, Anais Martinez, Gully Apc Burns, Brendan S. Thatcher, Vishwanath T. Anekonda, Benjamin W. Thompson, Zachary S. Roberts, Daniel H. Moralejo, James E. Blevins
Arshad M. Khan, Ph.D.
Carbonic Anhydrase Inhibition Selectively Prevents Amyloid B Neurovascular Mitochondrial Toxicity, 2018 New York University
Carbonic Anhydrase Inhibition Selectively Prevents Amyloid B Neurovascular Mitochondrial Toxicity, María E. Solesio, Pablo M. Peixoto, Ludovic Debure, Stephen M. Madamba, Mony J. De Leon, Thomas Wisniewski, Evgeny V. Pavlov, Silvia Fossati
Publications and Research
Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer’s disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid b (Ab)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Ab, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Ab, without affecting metabolic function. ATZ was effective at concentrations 10 times ...
Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, 2018 Central South University
Ephrinb3 Modulates Hippocampal Neurogenesis And The Reelin Signaling Pathway In A Pilocarpineinduced Model Of Epilepsy, Tian-Tian Liu, Yi Li, Yi Shu, Bo Xiao, Li Feng
Open Access Articles
EphrinB3 is important in the regulation of cell proliferation, differentiation and migration via cellcell contact, and can activate the reelin pathway during brain development. However, the effect of ephrinB3 on hippocampal neurogenesis and the reelin pathway in epilepsy remains to be fully elucidated. In the present study, the expression of ephrinB3 in pilocarpineinduced status epilepticus (SE) rats was investigated. SYBR Greenbased reverse transcriptionquantitative polymerase chain reaction analysis, immunohistochemical labeling and western blot analysis were used to detect the gene and protein expression levels of ephrinB3 and reelin pathway proteins. Immunofluorescence staining of doublecortin (DCX) was utilized to analyze hippocampal neurogenesis ...
Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, 2018 Washington University in St. Louis
Exploiting Click-Chemistry And Microfluidics To Map The Neuronal Itinerary Of App Processing And Amyloid-Beta Generation, Namratha Srinivas
Engineering and Applied Science Theses & Dissertations
Alzheimer’s disease (AD) is a chronic neurodegenerative disease and is the sixth leading cause of death in the United States with approximately 5.5 million Americans diagnosed with it. The neuropathological hallmark includes extracellular senile plaques and intraneuronal neurofibrillary tangles. Recent GWAS studies have identified genes associated with AD, and have revealed several classes of genes implicated in disease pathogenesis. In particular, three general pathways associated with an increased risk of AD included: 1) cholesterol metabolism, innate immune system, and the membrane trafficking. Our lab has focused on intracellular trafficking as it relates to the processing of amyloid precursor ...
Expression Of An Arc-Immunoreactive Protein In The Adult Zebrafish Brain Increases In Response To A Novel Environment, 2018 Georgia Southern University - Armstrong
Expression Of An Arc-Immunoreactive Protein In The Adult Zebrafish Brain Increases In Response To A Novel Environment, Robert A. Mans, Kyle D. Hinton, Amanda E. Rumer, Kourtnei A. Zellner, Emily A. Blankenship, Lia M. Kerkes, Michael J. Hamilton, Theresa R. Reilly, Cicely H. Payne
Georgia Journal of Science
Zebrafish are a powerful research tool in the field of neuroscience, offering several logistical and physiological advantages over rodents as a research model. However, the molecular dynamics of this model organism, especially with regards to learning and memory, are scarcely known. The current study explored the zebrafish brain for the presence of a protein bearing a similar function to the activity-regulated, cytoskeleton-associated protein (Arc), a critical player in synaptic plasticity. The adult zebrafish brain was found to express a protein with immunoreactivity against the anti-Arc antibody H-300. Immunoreactivity was detected ubiquitously, especially in areas known as adult progenitor cell zones ...
Precision Gene Therapy For Charcot-Marie-Tooth Disease: From Identifying Genetic Modifiers To Developing Allele-Specific Therapies, Kathryn H. Morelli Ph.D.
Electronic Theses and Dissertations
Charcot-Marie-Tooth Disease (CMT) is a clinically and genetically heterogeneous collection of inherited peripheral neuropathies generally characterized by progressive muscle atrophy, weakness, and loss of sensation in the distal extremities. This inherited disorder, for which there is currently no curative treatment, is the most common inherited disease of the peripheral nervous system, affecting 1:2,500 individuals worldwide.
Clinically, CMT is broadly divided into demyelinating (type 1) and axonal (type 2) forms. Although the clinical presentation can vary greatly in severity and progression within individual patients. Genetically, over 1,000 mutations in over 80 loci in the human genome have been ...
Ethical Analysis Of Brain Augmentation Through Nanotechnology, 2018 University of Puget Sound
Ethical Analysis Of Brain Augmentation Through Nanotechnology, Austin Caras, James Dejesus
Sound Decisions: An Undergraduate Bioethics Journal
The use of nanoparticles for drug delivery and neural cell manipulation may soon allow for organic and electronic brain augmentations. Medical technology being used for cognitive enhancement brings a host of ethical questions related to safety, justice, privacy, and individuality. Issues concerning medical consent and intellectual property will be skewed as neuroscience expands our understanding of the brain, growing our capacity to read and modify it. Socioeconomic strata may realign based on augmentations and employment opportunities may become dependent on specific cognitive enhancements. Long-term effects of unregulated nanoparticle usage could elicit an environmental or human health disaster. The potential ...
Characterizing Tau In The Nucleus, 2018 James Madison University
Characterizing Tau In The Nucleus, Shaw Grindle Camphire, Madeline Louise Henwood
Senior Honors Projects, 2010-current
A hallmark of Alzheimer’s Disease (AD) is the aggregation of hyperphosphorylated tau protein into neurofibrillary tangles. Tau localizes to both the cytoplasm and the nucleus of neuronal cells; however, its nuclear role has not been fully defined. Tau has recently been shown to bind to purine-pyrimidine (R/Y) repeats in DNA and stabilize them into Z-DNA. Evidence from our lab suggests that the binding of tau to R/Y repeats causes transcriptional changes of the NOS1 gene. Six major isoforms of tau exist in neurons. These isoforms fall into two groups, denoted as 3R tau and 4R tau, and ...
T Cell Mediated Cytotoxicity In The Mptp Mouse Model Of Parkinson's Disease, 2018 University of Nebraska Medical Center
T Cell Mediated Cytotoxicity In The Mptp Mouse Model Of Parkinson's Disease, Rebecca A. Wilshusen
Theses & Dissertations
Increasing evidence suggests that neurotoxic inflammatory activities affect the pathogenesis and progression of PD. Neuroinflammatory processes also produce oxidized and modified self-central nervous system (CNS) proteins which lead to dysfunction, mis-folding, aggregation, and retention of those oxidized products. In PD, nitrated α-synuclein (N-α-syn) is found aggregated within the cytoplasm and Lewy bodies of dopaminergic neurons within the substantia nigra and is released to the extraneuronal environment by dying and damaged neurons. Previous studies have shown that after 1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) intoxication, adoptive transfer of effector T cells (Teff) exacerbates microglial-mediated neuroinflammation and amplifies dopaminergic neurodegeneration with ...
Is Concussion-Related Sleep Disturbance Present After Return To Play In College Athletes?, 2018 University of Connecticut
Is Concussion-Related Sleep Disturbance Present After Return To Play In College Athletes?, Alexander Gallaer
Honors Scholar Theses
As one of the most commonly experienced symptoms, the ramifications of sleep disruption as a result of concussion are potentially great, yet widely unexplored. Particularly troublesome is murky data regarding the length of sleep disruption following a concussion. By analyzing self-reported sleep data via the Pittsburgh Sleep Quality Index, this study seeks to investigate potential differences in sleep quality between injured college athletes 40 days after they have been cleared to play and matched controls. Data was analyzed using ANOVA analysis as well as Pearson correlation. No significant differences were found in sleep quality between groups, nor was there a ...
Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin
Senior Honors Theses
The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research ...
A Role Of Vitamin B2 In Reducing Amyloid-Beta Toxicity In A Caenorhabditis Elegans Alzheimer’S Disease Model, 2018 East Tennessee State University
A Role Of Vitamin B2 In Reducing Amyloid-Beta Toxicity In A Caenorhabditis Elegans Alzheimer’S Disease Model, Muhammad Tukur Ameen
Electronic Theses and Dissertations
Alzheimer’s disease (AD) is associated with amyloid-beta peptide deposition and loss of mitochondrial function. Using a transgenic C. elegans AD worm model expressing amyloid-beta in body wall muscle, we determined that supplementation with either of the forms of vitamin B2, flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) protected against amyloid-beta mediated paralysis. FMN and FAD were then assayed to determine effects on ATP, oxygen consumption, and reactive oxygen species (ROS) with these compounds not significantly improving any of these mitochondrial bioenergetic functions. Knockdown of the daf-16/FOXO transcriptional regulator or the FAD synthase enzyme completely abrogated the ...
Examining The Appropriate Recovery Interval Following Maximal Exertion For Baseline Computerized Neurocognitive Testing (Cnt), 2018 University of Arkansas, Fayetteville
Examining The Appropriate Recovery Interval Following Maximal Exertion For Baseline Computerized Neurocognitive Testing (Cnt), Samantha Mohler
Theses and Dissertations
Background: Computerized neurocognitive testing is part of the recommended multi-faceted approach to SRC assessment. Prior research has suggested that maximal exertion negatively effects CNT test scores. Purpose: To identify the appropriate timing of the administration of CNT following maximal exertion in healthy college-aged students. Study Design: Random cross-over, repeated measures design. Methods: Participants will be administered CNT on four different visits, with at least one week between administrations. A VO2 max treadmill test will be performed before CNT administration during three of the four trials. Following the VO2 max test, participants will rest for <2 minutes (immediate), 10-minutes, or 20-minutes before taking CNT. The fourth trial, without maximal exertion preceding CNT administration, will serve as the control. All trials will be randomly-counterbalanced to negate practice effects. RESULTS: There was a significant within-subjects effect for prescribed post-exertion recovery intervals on total symptom scores (Wilks λ = .62, F [3, 23] = 4.64, p = .01, η2= .38). Total symptom scores were significantly higher at the immediate (p < .002), 10-minutes (p = .018), and 20-minutes (p = .011) post-exertion recovery intervals compared to baseline. Additionally, a significantly positive within-subjects effect for prescribed post exertion recovery was observed for processing speed (p=.009, Wilks λ = .60, F [3, 27] = 5.9, η2 = .396). No significant effect was observed for visual memory (p = .07), verbal memory (p = .06), or reaction time (p = .40). CONCLUSION: Baseline symptom scores were negatively influenced processing speed was enhanced by maximal exertion. These changes continue to be elevated 20 minutes post-exertion. Moreover, cognitive performance was not significantly impaired following maximal exercise. To obtain more accurate baseline symptom scores, and allow processing speed composites to return to normal, sports medicine professionals should wait at least 20 minutes following maximal exertion before administering CNT.