Neuroscience and Neurobiology Commons^™

Cx43 Expression Increases In Response To Increased Temperature Incubation In The Developing Chicken Embryonic Brain, Erick A. Barrios

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We used the chicken embryo model to examine whether altered incubation temperature during chicken embryo development would alter the protein expression of heat shock protein 70 (hsp70), hsp90, and connexin 43 (cx43) in the brain. We incubated eggs in either optimal (37.6° C, Con), increased (39.6° C, +2), or decreased (35.6° C, -2) temperature conditions until they reached embryonic day 16 (E16). The -2 condition significantly increased incidence of embryonic mortality. As shown in the literature, the development of the eggs was accelerated or decelerated due to increased or decreased temperature respectively. To control for this, we incubated eggs at …

Cx43 Expression Increases In Response To Increased Temperature Incubation In The Developing Chicken Embryonic Brain, Erick A. Barrios

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We used the chicken embryo model to examine whether altered incubation temperature during chicken embryo development would alter the protein expression of heat shock protein 70 (hsp70), hsp90, and connexin 43 (cx43) in the brain. We incubated eggs in either optimal (37.6°C, Con), increased (39.6°C, +2), or decreased (35.6°C, -2) temperature conditions until they reached embryonic day 16 (E16). The -2 condition significantly increased incidence of embryonic mortality. As shown in the literature, the development of the eggs was accelerated or decelerated due to increased or decreased temperature respectively. To control for this, we incubated eggs at optimal temperature (37.6°C) …

Upstream Regulators Of Vrac Activation In Human 1321n1 Astrocytoma Cells, Courtney Elyse Moore

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Cells rely on a constant volume not only for structural stability but also for normal homeostatic processes to occur. In the brain and CNS, cells can regain their normal volume through a process termed regulatory volume decrease (RVD). A key component of a cells' response to cell swelling is the activation of channel(s) responsible for the efflux of chloride current, ICl,swell. Volume regulated anion channels (VRAC) which mediate ICl,swell have been implicated in controlling cell volume during RVD, but the mechanisms which activate this channel are not completely understood. In this study, I examined the role of G protein-coupled signaling …

The Hypercapnic Ventilatory Response And Behavior In Ca2+-Activated K+ (Bk) Channel Knock Out Mice And T-Cell Death-Associated Gene 8 (Tdag8) Receptor Knock Out Mice, Christine Annette Ratliff-Rang

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Some acid sensing areas in the brain control the expression of breathing and anxiety/fear including the locus coeruleus (LC) (Redmond & Huang, 1979) and the nucleus tractus solitarius (NTS). It has been found that knocking out T-cell death-associated gene 8 (TDAG8), a chemosensor, attenuates CO2 induced fear phenotypes in mice. However their hypercapnic ventilatory response (HCVR) has not yet been looked at. Also, BK channels are large-conductance, calcium-activated potassium channels that are activated by increases in concentration of intracellular calcium ions. It has been found that BK KO rats have an increase in their HCVR (Patrone et al., 2014) however …

Is Mitochondrial Development Impaired In Hyperoxic Rats And Does This Underpin The Blunting Of The Acute Hypoxic Ventilatory Response?, Tariq Hasan Fayyad

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Carotid body (CB) responses to hypoxia are low at birth and increase over time to mature responses. Using an in vitro rat CB-carotid sinus nerve (CSN) preparation, Kholwadwala and Donnelly (1992) demonstrated that the CSN activity in response to hypoxia increased from low levels to robust adult responses after two weeks. This time course of maturation was paralleled by an increase in TASK channel sensitivity to hypoxia in the O2-sensing Type I cells (Kim et al, 2011). Previous studies have indicated that a fall in Type I cell mitochondrial volume and an increase in the rate of oxidative phosphorylation may …

Measuring The Effects Of High-Fat Diet On Breathing And Oxygen-Sensitivity Of The Carotid Body Type I Cell, Ryan J. Rakoczy

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The carotid bodies (CB), the primary peripheral chemoreceptors, respond to changes in blood gases with neurotransmitter release, thereby increasing carotid sinus nerve firing frequency and ultimately correcting the pattern of breathing. It has previously been demonstrated that acute application of the adipokine leptin caused perturbations of intracellular calcium and membrane ion movement in isolated CB Type I cells (Pye et al, 2015) and augmented the response of the intact CB to hypoxia (Pye et al, 2016). This study's aim was to examine, in-vivo, if elevated leptin modulated CB function and breathing. Rats were fed high-fat chow or control chow for …

Investigating The Role Of An Sk Channel Activator On Survival And Motor Function In The Sod1-G93a, Als Mouse Model, Matthew Thomas Dancy

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Amyotrophic Lateral Sclerosis (ALS) is a fatal, adult-onset progressive degenerative motor neuron disease that is characterized by muscle atrophy and weakness due to the loss of upper and lower motor neurons. Average survival time for individuals diagnosed with the disease is three to five years; currently there is no cure and only one drug approved by the Food and Administration (FDA). Scientists have proposed various theories in order to solve the mystery which surrounds ALS. One of these theories hypothesizes how hyperexcitability and excitotoxicity leads to the death of motor neurons. In this study, we will address ways of combatting …

Cross Sensitization Of Depressive-Like Behavior Through Two Depression Related Paradigms: Maternal Separation And Its Effect On The Forced Swim Test In The Guinea Pig, Amanda Danielle Schreibeis

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Separation and Its Effect on the Forced Swim Test In the Guinea Pig Early-life stress such as parental neglect, absence, or abandonment, has been hypothesized to increase the susceptibility for developing depression later in life via sensitization of stress-responsive physiological systems (e.g., pro-inflammatory cytokines, hypothalamic-pituitary-adrenal axis). Guinea pigs offer a potential model, but study has been limited to behavioral observations obtained during maternal separation tests. This thesis examined the generalization of this response by asking whether it would cross-sensitize to behavior in another depressive-related paradigm, the forced swim test. In three experiments, pups underwent three forced swim trials, in shallower …

Sk Channel Clustering In Sod1-G93a Motoneurons, Saihari Shekar Dukkipati

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Amyotrophic lateral sclerosis (ALS) is a devastating neuromuscular disease that currently has no cure and extremely limited treatment options. The specific mechanisms that underlie motoneuron degeneration and death, which are classical features of this disease, are mostly unknown. This thesis tests the hypothesis that small-conductance calcium-activated potassium channels (SK) may be downregulated in ALS motoneurons, as suggested by computational modelling. SK channel expression was measured in spinal alpha-motoneuron cell bodies or somata of wildtype (WT) and mutant (mt) SOD1-G93A mice, a transgenic animal model of ALS. Quantitative immunohistochemical analysis of the developmental expression of SK channel isoforms SK2 and SK3 …

Social Buffering By Unfamiliar Adult Males In Preweaning Guinea Pigs (Cavia Pocellus): The Effects On Hpa Activity And Fos Induction In The Medial Prefrontal Cortex, Withayapon Watanasriyakul

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Social buffering, a phenomenon in which the presence of a social partner can reduce stress responses, is often most effective between strongly attached partners. Our laboratory previously found a surprising buffering effect of the hypothalamic-pituitary-adrenal (HPA) response in preweaning guinea pigs by unfamiliar adult males. It was hypothesized that this HPA-buffering effect was driven by social interactions between the two partners and may involve an activation of the prelimbic cortex. Therefore, the current study examined these potential associations. To limit social interactions, the adult male was anesthetized in one condition compared to another condition where the adult male remained conscious. …

The Use Of Doublecortin To Quantify The Effects Of Pharmacological Treatment On Neurogenesis And Functional Recovery After Stroke, Amber Lee Hensley

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Ischemic strokes account for 87% of all strokes and can have debilitating effects on language, sensory, and motor skills. Currently, tPA is the only medication approved by the FDA for the treatment of ischemic stroke, but the window of time to administer the drug is very small. In this thesis, we investigate the use of a simvastatin and fluoxetine drug combination (FS) as a possible treatment for ischemic stroke victims. To analyze the effects of FS on neurogenesis and functional recovery, we utilize the Montoya Staircase and quantify the amount of neurogenesis using doublecortin. Although the results of this study …

Examination Of A Post-Stroke Drug Treatment For Its Effect On Blood Brain Barrier Permeability, And Gene Expression Changes In The Peri-Infarct Region, Ankita Anil Patel

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In this current study, we have investigated this a combination of fluoxetine, simvastatin and ascorbic acid administered daily beginning at 20-26 hours after stroke induction. We hope to understand therapeutic abilities by studying its effectiveness on the blood brain barrier permeability and gene expression changes of the microglial subtypes involved in neuro-inflammation and neurogenesis factors in the peri-infarct region. Our results indicate that S-enantiomer of fluoxetine may be more beneficial compared to the R-enantiomer. The S-enantiomer was effective in tightening the blood brain barrier in contrast to the R-enantiomer, in which the latter showed a greater Evans Blue dye permeability …

Correlations Between Sensory Encoding And Central Morphology Of Muscle Proprioceptors In The Rat, Hanna Marie Gabriel

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Until now, observations regarding the central morphology and organization of Ia, group II and Ib Golgi tendon organ afferents have been confined to the cat model. As the use of rodents in the study of the development and organization of segmental spinal cord circuitry increases, a complete account of the peripheral encoding and central connectivity of rodent muscle proprioceptors is necessary. The data presented in this study establish the central morphology and spatial distribution of 12 (4 of each class) functionally phenotyped muscle proprioceptor afferents in the rat by intracellular labeling with Neurobiotin. Each afferent type showed a characteristic central …

Effect Of Somatostatin On Voltage-Gated Calcium Influx In Isolated Neonatal Rat Carotid Body Type I Cells, Eric J. Dunn

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Somatostatin (SST) is a neuropeptide hormone that regulates the release of secondary hormones. Evidence suggests SST plays a neuromodulatory role due to its distribution throughout the central nervous system. Interestingly, SST has been suggested to affect the carotid body, the small peripheral chemoreceptors that regulate breathing. It has been shown that the peripheral chemoreflex sensitivity to CO2 and hypoxia is reduced by SST in humans (Pedersen et al., 1999; Pandit et al., 2014). SST has also been found to inhibit whole cell Ca2+ currents recorded from adult rat carotid body type I cells (e Silva & Lewis, 1995), but the …

Characterization Of Calbindin Positive Interneurons Within The Ventral Horn Of The Mouse Spinal Cord, Taylor L. Floyd, David R. Ladle

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Sensory-motor circuits in the spinal cord integrate sensory feedback from muscles and modulate locomotor behavior. Although we know how the sensory-motor system generally works, the main issue lies in identifying all neurons involved and understanding their interrelationships. Many interneurons contribute to sensory-motor circuits and have been well studied. For example, Renshaw cells (RC) are inhibitory interneurons that prevent motor neurons from over-activity. A distinguishing feature of RCs is that they are the only interneurons within the ventral-most region of the spinal cord expressing the calcium binding protein calbindin (CB). Recent studies have found other subpopulations of ventral horn interneurons outside …

Sensorimotor Analysis Of Oxaliplatin Treated Rats, Krystyna Blanka Wieczerzak

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There is currently no direct evidence that chemotherapy induced peripheral neuropathy (CIPN) necessarily explains the sensorimotor deficits seen in 90% patients treated with oxaliplatin (OX). Some patients develop sensory symptoms without CIPN. Our laboratory reported abnormal signaling from IA afferents in OX treated rats with no evidence of neuropathy. We hypothesized that in the absence of CIPN, the behavioral disability is associated with impaired sensory encoding in OX treated rats. The purpose of this study was to investigate the sensorimotor abilities of OX treated rats. The battery of behavioral tests was designed to address proprioception and sensorimotor integration. In the …

Metabolic Characterization Of Mpnst Cell Lines, Christopher A. Waker

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Malignant transformation is the process by which cells develop cancer properties. While many causes for malignant transformation are known (i.e. common genetic mutations and/or exposure to toxins or viruses), the basic requirements that allow a cell to stay alive with altered nutrient and energy requirements are just now being studied. In some tumor types malignant cells undergo changes that result in metabolic differences compared to normal cells. These can include defects in mitophagy resulting in an accumulation of dysfunctional mitochondria and/or a metabolic switch resulting in increased glycolysis, termed the Warburg effect. Increased tumor growth and metastasis have also been …

Functional Mri Mapping Of Visual Function And Selective Attention For Performance Assessment And Presurgical Planning Using Conjunctive Visual Search, Jason G. Parker, Eric J. Zalusky, Cemil Kirbas

Wright State Research Institute Publications

Background

Accurate mapping of visual function and selective attention using fMRI is important in the study of human performance as well as in presurgical treatment planning of lesions in or near visual centers of the brain. Conjunctive visual search (CVS) is a useful tool for mapping visual function during fMRI because of its greater activation extent compared with high-capacity parallel search processes.

Aims

The purpose of this work was to develop and evaluate a CVS that was capable of generating consistent activation in the basic and higher level visual areas of the brain by using a high number of distractors …

The Camkkβ Inhibitor Sto-609 Causes Artefacts In Ca2+ Imaging And Selectively Inhibits Bkca In Mouse Carotid Body Type I Cells, Jennifer G. Jurcsisn

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It has previously been reported that AMP-activated protein kinase (AMPK) may be critical for hypoxic chemotransduction in carotid body type I cells (Wyatt et al, 2007). This study sought to determine the importance of the regulatory upstream kinase of AMPK, CamKKβ, in the acute response to hypoxia in isolated mouse type I cells.

Initial studies indicated several previously unreported artefacts associated with using the CamKKβ inhibitor STO-609 and calcium imaging techniques. Strong STO-609 autofluorescence meant that Fura-2 could not be used and X-Rhod-1 imaging revealed that STO-609 quenched fluorescence even in the absence of intracellular Ca2+. The whole-cell configuration of …

Investigating Anatomical And Molecular Aspects Of Proprioceptive Sensory Neuron Diversity Using A Transgenic Mouse Model, Martha Jean Sonner

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Muscle spindles (MS) and Golgi tendon organs (GTOs) are encapsulated, stretch-activated sensory receptors housed within skeletal muscles, yet their functional contributions to proprioceptive monitoring of limb movements are quite different. For example, MS are responsible for detecting stretch of muscle fibers, and GTOs provide feedback regarding muscle tension during contraction. Peripheral axons extending from proprioceptive sensory neurons (PSNs) in the dorsal root ganglia supply MS and GTOs. MS are innervated by Group Ia and II sensory fiber endings, while GTOs are innervated by a single Group Ib sensory fiber. The developmental processes guiding axons from PSNs to their targets and …

Effects Of Transcranial Direct Current Stimulation On Expression Of Immediate Early Genes (Ieg's), Jessica Wagner

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Transcranial direct current stimulation (tDCS) has been utilized in human studies to modulate a multitude of psychological, cognitive, and psychiatric disorders. There have been positive behavioral results in human subjects but our knowledge of biological processes occurring during stimulation to elicit behavioral outcomes is limited. Our study utilizes a rodent tDCS (R-tDCS) model in which Sprague Dawley rats receive tDCS in order to examine whether tDCS affects neuronal activation. We examined two immediate early genes (IEG's), cFos and zif268, in order to discern if tDCS affects neuronal activation. Our findings indicate that tDCS does affect neuronal activation by means of …

Acceleration Of Image Analyst Training With Transcranial Direct Current Stimulation, R. Andy Mckinley, Lindsey Mcintire, Nathaniel Bridges, Charles Goodyear, Michael Patrick Weisend

Wright State Research Institute Publications

Humans today are routinely and increasingly presented with vast quantities of data that challenge their capacity for efficient processing. To restore the balance between man and machine, it is worthwhile to explore new methods for enhancing or accelerating this capacity. This study was designed to investigate the efficacy of transcranial DC stimulation (tDCS) to reduce training time and increase proficiency in spatial recognition using a simulated synthetic aperture radar (SAR) task. Twenty-seven Air Force active duty members volunteered to participate in the study. Each participant was assigned to 1 of 3 stimulation groups and received two, 90-min training sessions on …

Impact Of Tdcs On Performance And Learning Of Target Detection: Interaction With Stimulus Characteristics And Experimental Design, Brian A. Coffman, M. C. Trumbo, R. A. Flores, Christopher M. Garcia, A. J. Van Der Merwe, Eric M. Wassermann, Michael Patrick Weisend, Vincent P. Clark

Wright State Research Institute Publications

We have previously found that transcranial direct current stimulation (tDCS) over right inferior frontal cortex (RIFC) enhances performance during learning of a difficult visual target detection task (Clark et al., 2012). In order to examine the cognitive mechanisms of tDCS that lead to enhanced performance, here we analyzed its differential effects on responses to stimuli that varied by repetition and target presence, differences related to expectancy by comparing performance in single- and double-blind task designs, and individual differences in skin stimulation and mood. Participants were trained for 1 h to detect target objects hidden in a complex virtual environment, while …

Hcn1 Immunoreactivity Of Α-Motoneurons Following Peripheral Nerve Injury, Saif Ahmed

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Peripheral axotomy causes significant alterations in intrinsic motoneuron activity and excitability. Despite successful reinnervation of peripheral targets after injury, the recovery of motor function is incomplete. Following axotomy in the adult cat, there is an increase in the afterhyperpolarization (AHP) of the action potential in specific motoneuron types. AHP duration can be inversely correlated with the amount of Ih or sag current and further shaped through SK (Small conductance calcium-activated potassium) channel currents (Gustafsson and Pinter, 1985; Kuno, Miyata, and Muñoz-Martinez, 1974a). Hyperpolarizing-cyclic nucleotide gated (HCN) channels underlie sag currents and are critical to neuronal function by their unique property …

Comparing Two Different Statins In A Delayed Pharmacological Treatment For Ischemic Stroke, Kailyn M. Hagerty

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Stroke is one of the leading causes of death and the top cause of long term disability. Currently there exists no standardized treatment of care for ischemic stroke patients during the days following stroke other than giving aspirin. A drug combination containing fluoxetine, one of two statins, and ascorbic acid was used to try and improve motor function following strokes in rats. Endothelin induced stroke survival surgery was performed on the right cortex of Long Evans and Sprague Dawley rats. Functional tests were completed pre- and post-surgery and immunohistochemistry was carried out to analyze infarct volume, angiogenesis, and the glial …

Quantitative Analysis Of Glycinergic Neurons Including Ia Inhibitory Interneurons In The Ventral Spinal Cord Using A Bac-Glyt2-Egfp Transgenic Mouse Model, Palak Rajeshkumar Painter

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We are interested in understanding the development of reciprocal inhibition, an important sensory-motor circuit that prevents co-contraction of antagonist muscles during locomotion. This effect is mediated by a subset of glycinergic neurons termed Ia inhibitory interneurons (IaINs). Transgenic mouse models are useful in helping to identify subsets of neurons in developing animals. In this thesis we first wanted to test the BAC-GlyT2-eGFP mice model by measuring GFP expression overlap in neurons with glycine in late-stage embryos (E17.5) and early postnatal animals (P0/P1). Our results suggest more than 98% of glycinergic neurons at these stages also express GFP in GlyT2-EGFP transgenic …

The Use Of Forelimb Asymmetry Functional Tests To Determine Motor Recovery With Various Drug Treatments Following Endothelin-Induced Stroke, Kelly Rebecca Leach

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Our laboratory has found increased functional recovery post-stroke with Long Evans rats that received a combination of fluoxetine, simvastatin, and vitamin C. The objectives of this study were to test that treatment and other drug combinations on Sprague Dawley rats, to determine whether Forelimb Asymmetry is a reliable behavioral measure for stroke studies, and to determine the most optimal surgical procedure on Sprague Dawley rats. There were more significant increases in functional recovery observed on the Forelimb Asymmetry than on Montoya Staircase behavioral tests, but there were no significant differences between treatment groups and control. The largest number of rats …

Expressing Human Orai3 In Insect Cells For Pharmacological Studies, Orville R. Bennett

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The Orai3 protein forms a Ca2+ channel with a pharmacological profile distinct from its close relative, the store-operated Ca2+ channel Orai1. Though closely related to Orai1, the function of Orai3 in humans is still unclear. This study attempts to contribute to the body of knowledge by undertaking a pharmacological analysis of Orai3 in insect cells. We describe here the creation of a vector capable of expressing the mammalian Orai3 gene on an insect background. We demonstrate the ability to induce gene expression of Orai3 in these insect cells, and then assess the effectiveness of this system by characterizing the pharmacological …

Transcranial Direct Current Stimulation’S Effect On Novice Versus Experienced Learning, L. M. Bullard, E. S. Browning, Vincent P. Clark, Brian A. Coffman, Christopher M. Garcia, R. E. Jung, A. J. Van Der Merwe, K. M. Paulson, A. A. Vakhtin, C. L. Wootton, Michael Patrick Weisend

Wright State Research Institute Publications

Transcranial direct current stimulation (TDCS) is a non-invasive form of brain stimulation applied via a weak electrical current passed between electrodes on the scalp. In recent studies, TDCS has been shown to improve learning when applied to the prefrontal cortex (e.g., Kincses et al. in Neuropsychologia 42:113–117, 2003; Clark et al. Neuroimage in 2010). The present study examined the effects of TDCS delivered at the beginning of training (novice) or after an hour of training (experienced) on participants’ ability to detect cues indicative of covert threats. Participants completed two 1-h training sessions. During the first 30 min of each training …

Environmental Enrichment-Mediated Neuroprotection Against Traumatic Brain Injury:Role Of Brain-Derived Neurotrophic Factor, Kyle Leann Traver

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Each year there are over 1.7 million traumatic brain injuries (TBI) in the United States causing long-term health deficits and significant medical costs. This growing epidemic has led researchers to find methods for treating and preventing these injuries. Environmental Enrichment (EE) is an innovative technique shown to improve cognitive and functional outcomes following a TBI; however, the beneficial effects before injury have not been established. Brain-Derived Neurotrophic Factor (BDNF) has been determined as a neuroprotective biomolecule in TBI. This research examined these two protective components and their roles in TBI. It was hypothesized that BDNF mRNA and protein levels would …