Neurosciences Commons^™

Developmental Steps For A Functional Three-Dimensional Cell Culture System For The Study Of Asymmetrical Division Of Neural Stem Cells, Martina Zamponi

Biomedical Engineering Theses & Dissertations

Stem cells are a cell type present during and following development, which possess self- renewal properties, as well as the ability to differentiate into specific cells. Asymmetrical division is the cellular process that allows stem cells to produce one differentiated and one un-differentiated daughter cell during the same mitotic event. Insights in the molecular mechanisms of such process are minimal, due to the absence of effective methods for its targeted study. Currently, traditional methods of investigation include monolayer cell culture and animal models. The first poses structural limitations to the accurate representation of human tissue and cell structures, while animal …

Therapeutic Modulation Of Alzheimer’S Disease With Biological (Hucbs) And Pharmacological (Lispro) Approaches, Md Ahsan Habib

USF Tampa Graduate Theses and Dissertations

Dementia is the top global public health threat of the twenty first century. Within the dementia spectrum, Alzheimer’s disease (AD) is the most common type of dementia that occurs with aging and accounts for about 60% - 80% of diagnosed cases. But currently available discoveries failed to develop disease-modifying therapies for all patients living with AD. Recent discoveries can only partially slow down cognitive decline in a small subset of patients with limited effectiveness. The heterogeneity and complexity of the pathophysiology of AD indicate that a single drug approach may not be sufficient to prevent disease onset and progression. Human …

Blocking Nmdar Disrupts Spike Timing And Decouples Monkey Prefrontal Circuits: Implications For Activity-Dependent Disconnection In Schizophrenia, Jennifer L. Zick, Rachael K. Blackman, David A. Crowe, Bagrat Amirikian, Adele L. Denicola, Theoden I. Netoff, Matthew V. Chafee

Faculty Authored Articles

We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist. These results suggest that a disruption of spike timing and effective connectivity …

Local Bdnf Delivery To The Injured Cervical Spinal Cord Using An Engineered Hydrogel Enhances Diaphragmatic Respiratory Function., Biswarup Ghosh, Zhicheng Wang, Jia Nong, Mark W. Urban, Zhiling Zhang, Victoria A. Trovillion, Megan C. Wright, Yinghui Zhong, Angelo C. Lepore

Farber Institute for Neuroscience Faculty Papers

We developed an innovative biomaterial-based approach to repair the critical neural circuitry that controls diaphragm activation by locally delivering brain-derived neurotrophic factor (BDNF) to injured cervical spinal cord. BDNF can be used to restore respiratory function via a number of potential repair mechanisms; however, widespread BDNF biodistribution resulting from delivery methods such as systemic injection or lumbar puncture can lead to inefficient drug delivery and adverse side effects. As a viable alternative, we developed a novel hydrogel-based system loaded with polysaccharide-BDNF particles self-assembled by electrostatic interactions that can be safely implanted in the intrathecal space for achieving local BDNF delivery …

Spinal Control Of Locomotion: Individual Neurons, Their Circuits And Functions, Marie-Pascale Côté, Lynda M. Murray, Maria Knikou

Publications and Research

Systematic research on the physiological and anatomical characteristics of spinal cord interneurons along with their functional output has evolved for more than one century. Despite significant progress in our understanding of these networks and their role in generating and modulating movement, it has remained a challenge to elucidate the properties of the locomotor rhythm across species. Neurophysiological experimental evidence indicates similarities in the function of interneurons mediating afferent information regarding muscle stretch and loading, being affected by motor axon collaterals and those mediating presynaptic inhibition in animals and humans when their function is assessed at rest. However, significantly different muscle …

Apoe And Alzheimer’S Disease: Neuroimaging Of Metabolic And Cerebrovascular Dysfunction, Jason A. Brandon, Brandon C. Farmer, Holden C. Williams, Lance A. Johnson

Physiology Faculty Publications

Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for late onset Alzheimer’s Disease (AD), and is associated with impairments in cerebral metabolism and cerebrovascular function. A substantial body of literature now points to E4 as a driver of multiple impairments seen in AD, including blunted brain insulin signaling, mismanagement of brain cholesterol and fatty acids, reductions in blood brain barrier (BBB) integrity, and decreased cerebral glucose uptake. Various neuroimaging techniques, in particular positron emission topography (PET) and magnetic resonance imaging (MRI), have been instrumental in characterizing these metabolic and vascular deficits associated with this important AD risk factor. In …

Mir126-5p Downregulation Facilitates Axon Degeneration And Nmj Disruption Via A Non-Cell-Autonomous Mechanism In Als., Roy Maimon, Ariel Ionescu, Avichai Bonnie, Sahar Sweetat, Shane Wald-Altman, Shani Inbar, Tal Gradus, Davide Trotti, Miguel Weil, Oded Behar, Eran Perlson

Farber Institute for Neuroscience Faculty Papers

Axon degeneration and disruption of neuromuscular junctions (NMJs) are key events in amyotrophic lateral sclerosis (ALS) pathology. Although the disease's etiology is not fully understood, it is thought to involve a non-cell-autonomous mechanism and alterations in RNA metabolism. Here, we identified reduced levels of miR126-5p in presymptomatic ALS male mice models, and an increase in its targets: axon destabilizing Type 3 Semaphorins and their coreceptor Neuropilins. Using compartmentalized

Improving Resident Confidence And Efficiency During Stroke Alerts Through Simulation Training, Megan Margiotta, Md, Danielle Wilhour, Md, Elan Miller, Md, Robin D'Ambrosio, Bsn, Scrn, Maria Carissa Pineda, Md, Fred Rincon, Md, Rodney Bell, Md, Diana Tzeng, Md

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

Objectives

• Teach incoming neurology residents how to respond efficiently and appropriately to stroke alerts
• Improve the confidence level of residents during stroke alerts

The Effects Of Habits On Motor Skill Learning, Nicola J. Popp, Atsushi Yokoi, Paul L. Gribble, Jörn Diedrichsen

BrainsCAN Publications

Skill learning involves the formation of stable motor patterns. In musical and athletic 3 training, however, these stable patterns can also impede the attainment of higher levels 4 of performance, and hence constitute a motor habit. We developed an experimental 5 paradigm to induce a specific motor pattern in a sequence production task and 6 investigated how it affected subsequent optimization over a 3-week training period. 7 Participants initially practiced small segments of 2 to 3 finger movements, which were 8 then combined to form longer sequences. This initial training induced a persistent 9 chunking behavior, with shorter inter-press-intervals within …

Disorganized Gyrification Network Properties During The Transition To Psychosis, Tushar Das, Stefan Borgwardt, Daniel J. Hauke, Fabienne Harrisberger, Undine E. Lang, Anita Riecher-Rössler, Lena Palaniyappan, André Schmidt

Brain and Mind Institute Researchers' Publications

IMPORTANCE There is urgent need to improve the limited prognostic accuracy of clinical instruments to predict psychosis onset in individuals at clinical high risk (CHR) for psychosis. As yet, no reliable biological marker has been established to delineate CHR individuals who will develop psychosis from those who will not. OBJECTIVES To investigate abnormalities in a graph-based gyrification connectome in the early stages of psychosis and to test the accuracy of this systems-based approach to predict a transition to psychosis among CHR individuals. DESIGN, SETTING, AND PARTICIPANTS This investigation was a cross-sectional magnetic resonance imaging (MRI) study with follow-up assessment to …

Pip2 Modulation Of Afterhyperpolarizations In Magnocellular Supraoptic Neurons, Matthew Karl Kirchner

Theses and Dissertations (ETD)

Magnocellular neurosecretory cells (MNCs) are large oxytocin (OT)- and vasopressin (VP)-releasing neurons that secrete these hormones into the circulatory system in response to physiological stimuli. These cells exhibit unique phasic and burst firing patterns to release these peptides into the circulatory system where they primarily control milk ejection and parturition (OT) as well as salt-water balance and vasoconstriction (VP). This firing is underlain by intrinsic ionic mechanisms that shape the duration and frequency of these bursts. One of these mechanisms is the Ca2+-dependent afterhyperpolarization (AHP), which activates during bursts and causes spike frequency adaptation. This afterhyperpolarization has three distinct conductances: …

Defining The Radioresponse Of Mossy Cells, Devon Ivy

Electronic Theses, Projects, and Dissertations

Clinical radiotherapy is used to treat a variety of brain tumors within the central nervous system. While effective, it can result in progressive and debilitating cognitive impairment that can diminish quality of life. These impairments have been linked to hippocampal dysfunction and corresponding deficits in spatial learning and memory. Mossy cells are a major population of excitatory neurons located within the dentate hilus and highly involved in hippocampal circuitry. They play critical roles in spatial navigation, neurogenesis, memory, and are particularly vulnerable to a variety of neurotoxic insults. However, their sensitivity to ionizing radiation has yet to be investigated in …

Submandibular Mechanical Stimulation Of Upper Airway Muscles To Treat Obstructive Sleep Apnea, Ferhat Erdogan

Dissertations

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to keep a patent airway during respiration in wakefulness and sleep. The activity of genioglossus, the primary tongue-protruding muscle playing an important role in this coordination, is known to be modulated by several reflex pathways mediated through the mechanoreceptors of the upper airways. The main objective is to investigate the effectiveness of activating these reflex pathways with mechanical stimulations, for the long-term goal of improving the upper airway patency during disordered breathing in sleep. The genioglossus response is examined during mandibular and sub-mandibular mechanical stimulations in healthy subjects during …

Cortical Statistical Correlation Tomography Of Eeg Resting State Networks, Chuang Li, Han Yuan, Guofa Shou, Yoon-Hee Cha, Sridhar Sunderam, Walter Besio, Lei Ding

Biomedical Engineering Faculty Publications

Resting state networks (RSNs) have been found in human brains during awake resting states. RSNs are composed of spatially distributed regions in which spontaneous activity fluctuations are temporally and dynamically correlated. A new computational framework for reconstructing RSNs with human EEG data has been developed in the present study. The proposed framework utilizes independent component analysis (ICA) on short-time Fourier transformed inverse source maps imaged from EEG data and statistical correlation analysis to generate cortical tomography of electrophysiological RSNs. The proposed framework was evaluated on three sets of resting-state EEG data obtained in the comparison of two conditions: (1) healthy …

Novel Tnf Receptor-1 Inhibitors Identified As Potential Therapeutic Candidates For Traumatic Brain Injury, Rachel K. Rowe, Jordan L. Harrison, Hongtao Zhang, Adam D. Bachstetter, David P. Hesson, Bruce F. O'Hara, Mark I. Greene, Jonathan Lifshitz

Sanders-Brown Center on Aging Faculty Publications

Background: Traumatic brain injury (TBI) begins with the application of mechanical force to the head or brain, which initiates systemic and cellular processes that are hallmarks of the disease. The pathological cascade of secondary injury processes, including inflammation, can exacerbate brain injury-induced morbidities and thus represents a plausible target for pharmaceutical therapies. We have pioneered research on post-traumatic sleep, identifying that injury-induced sleep lasting for 6 h in brain-injured mice coincides with increased cortical levels of inflammatory cytokines, including tumor necrosis factor (TNF). Here, we apply post-traumatic sleep as a physiological bio-indicator of inflammation. We hypothesized the efficacy of novel …

Neural Responses To Naturalistic Clips Of Behaving Animals Under Two Different Task Contexts, Samuel A. Nastase, Yaroslav O. Halchenko, Andrew C. Connolly, M. Ida Gobbini, James V. Haxby

Dartmouth Scholarship

The human brain rapidly deploys semantic information during perception to facilitate our interaction with the world. These semantic representations are encoded in the activity of distributed populations of neurons (Haxby et al., 2001; McClelland and Rogers, 2003; Kriegeskorte et al., 2008b) and command widespread cortical real estate (Binder et al., 2009; Huth et al., 2012). The neural representation of a stimulus can be described as a location (i.e., response vector) in a high-dimensional neural representational space (Kriegeskorte and Kievit, 2013; Haxby et al., 2014). This resonates with behavioral and theoretical work describing mental representations of objects and actions as being …

Regional Microglia Are Transcriptionally Distinct But Similarly Exacerbate Neurodegeneration In A Culture Model Of Parkinson's Disease., Eric Wildon Kostuk, Jingli Cai, Lorraine Iacovitti

Department of Neuroscience Faculty Papers

BACKGROUND: Parkinson's disease (PD) is characterized by selective degeneration of dopaminergic (DA) neurons of the substantia nigra pars compacta (SN) while neighboring ventral tegmental area (VTA) DA neurons are relatively spared. Mechanisms underlying the selective protection of the VTA and susceptibility of the SN are still mostly unknown. Here, we demonstrate the importance of balance between astrocytes and microglia in the susceptibility of SN DA neurons to the PD mimetic toxin 1-methyl-4-phenylpyridinium (MPP

METHODS: Previously established methods were used to isolate astrocytes and microglia from the cortex (CTX), SN, and VTA, as well as embryonic midbrain DA neurons from the …

Organic Cation Transporter 3: A Cellular Mechanism Underlying Rapid, Non-Genomic Glucocorticoid Regulation Of Monoaminergic Neurotransmission, Physiology, And Behavior, Paul J. Gasser, Christopher A. Lowry

Biomedical Sciences Faculty Research and Publications

Corticosteroid hormones act at intracellular glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) to alter gene expression, leading to diverse physiological and behavioral responses. In addition to these classical genomic effects, corticosteroid hormones also exert rapid actions on physiology and behavior through a variety of non-genomic mechanisms, some of which involve GR or MR, and others of which are independent of these receptors. One such GR-independent mechanism involves corticosteroid-induced inhibition of monoamine transport mediated by “uptake₂” transporters, including organic cation transporter 3 (OCT3), a low-affinity, high-capacity transporter for norepinephrine, epinephrine, dopamine, serotonin and histamine. Corticosterone directly and acutely inhibits …

Cdk5 Inhibition Resolves Pka/Camp-Independent Activation Of Creb1 Signaling In Glioma Stem Cells, Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Hithardhi Duggireddy, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel J. Brat

Neurology Faculty Publications

Cancer stem cells promote neoplastic growth, in part by deregulating asymmetric cell division and enhancing self-renewal. To uncover mechanisms and potential therapeutic targets in glioma stem cell (GSC) self-renewal, we performed a genetic suppressor screen for kinases to reverse the tumor phenotype of our Drosophila brain tumor model and identified dCdk5 as a critical regulator. CDK5, the human ortholog of dCdk5 (79% identity), is aberrantly activated in GBMs and tightly aligned with both chromosome 7 gains and stem cell markers affecting tumor-propagation. Our investigation revealed that pharmaceutical inhibition of CDK5 prevents GSC self-renewal in vitro and in xenografted tumors, at …

Electrophysiological Biomarkers Of Chemotherapy-Related Cognitive Impairment In Hematological Malignancy Patients, David E. Anderson

Theses & Dissertations

Multiple cancer populations frequently report cognitive impairment following treatment with chemotherapy agents (“chemo-brain”). Impaired neuropsychological performance is commonly reported in cognitive domains of attention and executive function. Understanding neural mechanisms underlying cognitive impairments is essential to developing prevention and rehabilitation strategies. Brain imaging studies frequently show chemotherapy-related impairments within the attentional control network, which is comprised of a constellation of cortical regions that govern reportedly impaired cognitive functions. In the current dissertation research, I developed a novel electrophysiology battery aimed at recording near-instantaneous neural activity within the attentional control network during cognitive task performance. Cancer patients diagnosed with hematological malignancy …