Open Access. Powered by Scholars. Published by Universities.®
Articles 1 - 14 of 14
Full-Text Articles in Entire DC Network
Isoform-Specific Roles Of Extracellular Signal-Regulated Kinases In Pain, Benedict Alter
Isoform-Specific Roles Of Extracellular Signal-Regulated Kinases In Pain, Benedict Alter
All Theses and Dissertations (ETDs)
ABSTRACT OF THE DISSERTATION Isoform-specific roles of Extracellular Signal-Regulated Kinases in pain by Benedict Joseph Alter Doctor of Philosophy in Biology and Biomedical Sciences Neurosciences Washington University in St. Louis, 2012 Professor Robert Gereau, Chairperson The extracellular signal-regulated kinase: ERK) isoforms, ERK1 and ERK2, are believed to be key signaling molecules in nociception and nociceptive sensitization. Studies utilizing inhibitors targeting the shared ERK1/2 upstream activator, mitogen-activated protein kinase kinase: MEK), and transgenic mice expressing a dominant negative form of MEK have established the importance of ERK1/2 signaling. However, these techniques do not discriminate between ERK1 and ERK2. To dissect the …
Characterization Of Normal Development And Injury In The Premature Baboon Brain, Jennifer Griffith
Characterization Of Normal Development And Injury In The Premature Baboon Brain, Jennifer Griffith
All Theses and Dissertations (ETDs)
Nearly 13% of infants born in the United States each year are preterm - that is, born before 37 weeks gestation. Although improvements in clinical care have contributed to survival rates that now exceed 85%, premature infants are at high risk for motor, sensory, cognitive and behavioral disabilities. In order to develop therapeutic interventions to prevent these adverse neurodevelopmental outcomes, we must first understand the nature of cerebral injury associated with premature birth and the mechanisms by which it leads to altered brain development. A baboon: Papio papio) model of preterm birth was used to evaluate cerebral development from 90 …
Information Processing In A Midbrain Visual Pathway, Dihui Lai
Information Processing In A Midbrain Visual Pathway, Dihui Lai
All Theses and Dissertations (ETDs)
Visual information is processed in brain via the intricate interactions between neurons. We investigated a midbrain visual pathway: optic tectum and its isthmic nucleus) that is motion sensitive and is thought as part of attentional system. We determined the physiological properties of individual neurons as well as their synaptic connections with intracellular recordings. We reproduced the center-surround receptive field structure of tectal neurons in a dynamical recurrent feedback loop. We reveal in a computational model that the anti-topographic inhibitory feedback could mediate competitive stimulus selection in a complex visual scene. We also investigated the dynamics of the competitive selection in …
Serum Response Factor Regulates Multiple Aspects Of Central Nervous System Development, Puo Yuan Lu
Serum Response Factor Regulates Multiple Aspects Of Central Nervous System Development, Puo Yuan Lu
All Theses and Dissertations (ETDs)
SRF is a highly evolutionary conserved activity-dependent transcription factor. Previous studies have shown that neuron-specific deletion of SRF results in deficits in tangential cell migration, guidance-dependent circuit assembly, activity-dependent gene expression, and synaptic plasticity in the hippocampus. However, very little is known in terms of whether SRF participates in earlier aspects of central nervous system development such as neuronal projection establishment, cell-fate specifications, and neural stem cell homeostasis and survival. We report that SRF is critical for development of major axonal tracts in the forebrain. Conditional mutant mice lacking SRF in neural progenitor cells: Srf-Nestin-cKO) exhibit striking deficits in cortical …
Neural Adaptation And The Effect Of Interelectrode Spacing On Epidural Electrocorticography For Brain-Computer Interfaces, Adam Rouse
All Theses and Dissertations (ETDs)
Electrocorticography: ECoG) is increasingly being identified as a safe and reliable recording technique for both Brain-Computer Interface: BCI) applications as well as neurophysiology studies. This thesis describes some of the first real-time closed-loop BCI studies of chronic ECoG in non-human primates. Epidural microECoG electrodes developed in our lab were implanted in three monkeys with the electrode array centered over primary motor cortex: M1). Monkeys were then trained to perform a one-dimensional BCI task. The BCI control scheme was independent of any prior screening for task-related activity. All three monkeys successfully learned to perform the task with multiple control configurations and …
Occulomotor Function And Locomotion In Parkinson's Disease, Corey Lohnes
Occulomotor Function And Locomotion In Parkinson's Disease, Corey Lohnes
All Theses and Dissertations (ETDs)
Many persons with Parkinson's disease: PD) experience difficulty turning that can lead to freezing of gait, falls, and an increased risk of fall-related injuries. We hypothesized, based on previous literature, that turning difficulty and freezing during turning may be related to deficits in the ability to switch from one motor pattern to another: Chapter 2). We further hypothesized that deficits in oculomotor control, particularly in the case of voluntary saccades, also contribute to the pathogenesis of turning difficulty since turning is normally initiated with an eye movement: Chapter 3). Finally, we hypothesized that current treatment approaches including pharmacological and surgical …
Identification Of Novel Fluid Biomarkers For Alzheimer's Disease, Rebecca Craig-Schapiro
Identification Of Novel Fluid Biomarkers For Alzheimer's Disease, Rebecca Craig-Schapiro
All Theses and Dissertations (ETDs)
Clinicopathological studies suggest that Alzheimer's disease: AD) pathology begins to appear ~10-20 years before the resulting cognitive impairment draws medical attention. Biomarkers that can detect AD pathology in its early stages and predict dementia onset and progression would, therefore, be invaluable for patient care and efficient clinical trial design. To discover such biomarkers, we measured AD-associated changes in the cerebrospinal fluid: CSF) using an unbiased proteomics approach: two-dimensional difference gel electrophoresis with liquid chromatography tandem mass spectrometry). From this, we identified 47 proteins that differed in abundance between cognitively normal: Clinical Dementia Rating [CDR] 0) and mildly demented: CDR 1) …
Fast Neuronal Imaging Using Objective Coupled Planar Illumination Microscopy, Diwakar Turaga
Fast Neuronal Imaging Using Objective Coupled Planar Illumination Microscopy, Diwakar Turaga
All Theses and Dissertations (ETDs)
Complex computations performed by the brain are produced by activities of neuronal populations. There is a large diversity in the functions of each individual neuron, and neuronal activities occur in the time scale of milliseconds. In order to gain a fundamental understanding of the neuronal populations, one has to measure activity of each neuron at high temporal resolution, while investigating enough neurons to encapsulate the neuronal diversity. Traditional neurotechniques such as electrophysiology and optical imaging are constrained by the number of neurons whose activities can be simultaneously measured or the speed of measuring such activities. We have developed a novel …
Developing High-Density Diffuse Optical Tomography For Neuroimaging, Brian White
Developing High-Density Diffuse Optical Tomography For Neuroimaging, Brian White
All Theses and Dissertations (ETDs)
Clinicians who care for brain-injured patients and premature infants desire a bedside monitor of brain function. A decade ago, there was hope that optical imaging would be able to fill this role, as it combined fMRI's ability to construct cortical maps with EEG's portable, cap-based systems. However, early optical systems had poor imaging performance, and the momentum for the technique slowed. In our lab, we develop diffuse optical tomography: DOT), which is a more advanced method of performing optical imaging. My research has been to pioneer the in vivo use of DOT for advanced neuroimaging by: 1) quantifying the advantages …
Molecular Dissection Of Ia Channels In Cortical Pyramidal Neurons, Aaron Norris
Molecular Dissection Of Ia Channels In Cortical Pyramidal Neurons, Aaron Norris
All Theses and Dissertations (ETDs)
The rapidly activating and inactivating voltage-gated K+: Kv) current, I A, is broadly expressed in neurons and is a key regulator of action potential repolarization, repetitive firing, back propagation: into dendrites) of action potentials, and responses to synaptic inputs. Interestingly, results from previous studies on a number of neuronal cell types, including hippocampal, cortical and spinal neurons, suggest that macroscopic I A is composed of multiple components and that each component is likely encoded by distinct Kv channel α-subunits. The goals of the experiments presented here were to test this hypothesis and to determine the molecular identities of the …
Movement Function Follows Spatial Form: Coordinate System Implications For Online Visual Feedback Control Of The Hand, Justin Brooks
Movement Function Follows Spatial Form: Coordinate System Implications For Online Visual Feedback Control Of The Hand, Justin Brooks
All Theses and Dissertations (ETDs)
Closed loop visual feedback control of the hand is essential for accurate reaching movements. Without visual signals of either the hand or target position, reaches are inaccurate and imprecise; therefore the brain uses a relative positional signal to control movements online. Previous studies suggest that movements are planned and represented in a polar coordinate system and that the dimensions, direction and extent are independently specified and processed. We were interested to find out whether there was behavioral evidence for the independent control of hand direction and extent as a movement unfolded. We asked subjects to make a reaching movement in …
Mitofusin 2 Regulated Transport Of Mitochondria Is Necessary For Axonal Integrity, Albert Misko
Mitofusin 2 Regulated Transport Of Mitochondria Is Necessary For Axonal Integrity, Albert Misko
All Theses and Dissertations (ETDs)
The ubiquitous finding of axonal degeneration in a number of the most prevalent neuropathologies marks the importance of understanding axonal biology and the axonal self-destruct mechanism. Though our understanding of axonal degeneration remains largely incomplete, several down-steam steps of the molecular cascade have been elucidated. While this insight has emerged from models of axon degeneration following physical injury or toxic insult, a more comprehensive understanding of the upstream events may be gained from studying primary axonopathies with defined genetic causes. This dissertation aims to elucidate a molecular mechanism underlying the loss of axons in Charcot-Marie-Tooth Disease type 2A, which is …
Allosteric Modulation Of Metabotropic Glutamate Receptor 5 As A Treatment For Pain, Michael Montana
Allosteric Modulation Of Metabotropic Glutamate Receptor 5 As A Treatment For Pain, Michael Montana
All Theses and Dissertations (ETDs)
Metabotropic glutamate receptor 5: mGlu5) has been suggested to play a role in the development and maintenance of chronic pain. mGlu5 is expressed at synapses throughout the pain neuraxis where it is believed to modulate the function of ion channels that underlie nociceptive transduction and transmission. Injections of mGlu5 agonists cause hypersensitivity or nocifensive behavior when administered peripherally, intrathecally, and centrally. In addition, pharmacological antagonism of mGlu5 has been suggested to be analgesic in a variety of animal pain models. Unfortunately, the selectivity of antagonists used in these studies has been called into question, suggesting that at least some of …
Calcium-Stimulated Adenylyl Cyclases Are Critical Modulators Of Fear Learning And Experience-Dependent Plasticity, Lindsay Wieczorek
Calcium-Stimulated Adenylyl Cyclases Are Critical Modulators Of Fear Learning And Experience-Dependent Plasticity, Lindsay Wieczorek
All Theses and Dissertations (ETDs)
Stress can exacerbate psychiatric disease, often resulting in cognitive deficits. Consequently, a better understanding of what modulates stress-facilitated memory processing will help identify new targets for possible therapeutic intervention. Recent evidence suggests a role of the Ca2+-stimulated adenylyl cyclases: AC), AC1 and AC8, in modulating fear memory. Ca2+-stimulated AC activity couples neuronal activity and intracellular Ca2+ increases to the production of cAMP, and therefore, can very tightly regulate signal transduction after learning; yet, the details by which this occurs are not well understood. In this dissertation, I first investigated the temporal and regional importance of Ca2+-stimulated AC activity during different …