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Reduced representation of neural networks
Title
Reduced representation of neural networks.
Creator
Stefanescu, Roxana A., Charles E. Schmidt College of Science, Department of Physics
Abstract/Description
Experimental and computational investigations addressing how various neural functions are achieved in the brain converged in recent years to a unified idea that the neural activity underlying most of the cognitive functions is distributed over large scale networks comprising various cortical and subcortical areas. Modeling approaches represent these areas and their connections using diverse models of neurocomputational units engaged in graph-like or neural field-like structures. Regardless of...
Show moreExperimental and computational investigations addressing how various neural functions are achieved in the brain converged in recent years to a unified idea that the neural activity underlying most of the cognitive functions is distributed over large scale networks comprising various cortical and subcortical areas. Modeling approaches represent these areas and their connections using diverse models of neurocomputational units engaged in graph-like or neural field-like structures. Regardless of the manner of network implementation, simulations of large scale networks have encountered significant difficulties mainly due to the time delay introduced by the long range connections. To decrease the computational effort, it is common to assume severe approximations to simplify the descriptions of the neural dynamics associated with the system's units. In this dissertation we propose an alternative framework allowing the prevention of such strong assumptions while efficiently representing th e dynamics of a complex neural network. First, we consider the dynamics of small scale networks of globally coupled non-identical excitatory and inhibitory neurons, which could realistically instantiate a neurocomputational unit. We identify the most significant dynamical features the neural population exhibits in different parametric configuration, including multi-cluster dynamics, multi-scale synchronization and oscillator death. Then, using mode decomposition techniques, we construct analytically low dimensional representations of the network dynamics and show that these reduced systems capture the dynamical features of the entire neural population. The cases of linear and synaptic coupling are discussed in detail. In chapter 5, we extend this approach for spatially extended neural networks., We consider the dynamical behavior of a neural field-like network, which incorporates many biologically realistic characteristics such as heterogeneous local and global connectivity as well as dispersion in the neural membrane excitability. We show that in this case as well, we can construct a reduced representation, which may capture well the dynamical features of the full system. The method outlined in this dissertation provides a consistent way to represent complex dynamical features of various neural networks in a computationally efficient manner.
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Date Issued
2009
PURL
http://purl.flvc.org/FAU/369387
Subject Headings
Molecular neurobiology, Neural networks (Neurobiology), Brain, Mathematical models, Cognitive neuroscience, Recognition (Psychology)
Format
Document (PDF)
Functional roles of L1-Cam/Neuroglian in the nervous system of Drosophila Melanogaster
Title
Functional roles of L1-Cam/Neuroglian in the nervous system of Drosophila Melanogaster.
Creator
Kudumala, Sirisha, Godenschwege, Tanja A., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Neuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic...
Show moreNeuronal cell adhesion molecules of L1 family play a critical role in proper nervous system development. Various mutations on human L1-CAM that lead to severe neurodevelopmental disorders like retardation, spasticity etc. termed under L1 syndrome. The vertebrr their roles in axon pathfinding, neurite extension and cell migration, howeverate L1CAM and its homolog in Drosophila, neuroglian (nrg) have been well studied fo, much less is known about the mechanisms by which they fine tune synaptic connectivity to control the development and maintenance of synaptic connections within neuronal circuits. Here we characterized the essential role of nrg in regulating synaptic structure and function in vivo in a well characterized Drosophila central synapse model neuron, the Giant Fiber (GF) system. Previous studies from our lab revealed that the phosphorylation status of the tyrosine in the Ankyrin binding FIGQY motif in the intracellular domain of Nrg iscrucial for synapse formation of the GF to Tergo-Trochanteral Motor neuron (TTMn) synapse in the GF circuit. The present work provided us with novel insights into the role of Nrg-Ank interaction in regulating Nrg function during synapse formation and maintenance. By utilizing a sophisticated Pacman based genomic rescue strategy we have shown that dynamic regulation of the Neuroglian–Ankyrin interaction is required to coordinate transsynaptic development in the GF–TTMn synapse. In contrast, the strength of Ankyrin binding directly controls the balance between synapse formation and maintenance at the NMJ. Human L1 pathological mutations affect different biological processes distinctively and thus their proper characterization in vivo is essential to understand L1CAM function. By utilizing nrg14;P[nrg180ΔFIGQY] mutants that have exclusive synaptic defects and the previously characterized nrg849 allele that affected both GF guidance and synaptic function, we were able to analyze pathological L1CAM missense mutations with respect to their effects on guidance and synapse formation in vivo. We found that the human pathological H210Q, R184Q and Y1070C, but not the E309K and L120V L1CAM mutations affect outside-in signaling via the FIGQY Ankyrin binding domain which is required for synapse formation and not for axon guidance while L1CAM homophilic binding and signaling via the ERM motif is essential for axon guidance in Drosophila.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00004131, http://purl.flvc.org/fau/fd/FA00004131
Subject Headings
Cell adhesion molecules, Cellular signal transduction, Cognitive neuroscience, Cognitive neuroscience, Drosophila melanogaster, Molecular neurobiology
Format
Document (PDF)
Potential therapies and neuroprotective cascades in anoxia tolerant freshwater turtle Trachemys scripta ellegans
Title
Potential therapies and neuroprotective cascades in anoxia tolerant freshwater turtle Trachemys scripta ellegans.
Creator
Nayak, Gauri., Charles E. Schmidt College of Science, Department of Biomedical Science
Abstract/Description
Mammalian neurons exhibit extreme sensitivity to oxygen deprivation and undergo rapid and irreversible degeneration when oxygen supply is curtailed. Though several neuroprotective pathways are activated during oxygen deprivation, their analyses are masked by the complex series of pathological events which are triggered simultaneously. Such events can be analyzed in the anoxia tolerant fresh water turtle, which can inherently survive the conditions of oxygen deprivation and post-anoxic...
Show moreMammalian neurons exhibit extreme sensitivity to oxygen deprivation and undergo rapid and irreversible degeneration when oxygen supply is curtailed. Though several neuroprotective pathways are activated during oxygen deprivation, their analyses are masked by the complex series of pathological events which are triggered simultaneously. Such events can be analyzed in the anoxia tolerant fresh water turtle, which can inherently survive the conditions of oxygen deprivation and post-anoxic reoxygenation without brain damage. It is likely in such a model that modulation of a particular molecular pathway is adaptive rather than pathological. The major objective behind this study was to analyze the intracellular signaling pathways mediating the protective effects of adenosine, a potential neuromodulator, and its effect on cell survival by influencing the key prosurvival proteins that prevent apoptosis. In vivo and in vitro studies have shown that adenosine acts as a neuroprotective metabolite and its action can be duplicated or abrogated using specific agonist and antagonists. Stimulating the adenosine receptors using selective A1 receptor agonist N6-cyclopentyladenosine (CPA) activated the presumed prosurvival ERK and P13-K/AKT cascade promoting cell survival, and suppression of the receptor using the selective antagonist DPCPX (8- cyclopentyl-1,3-dipropylxanthine) activated the prodeath JNK and P38 pathways. The complex regulation of the MAPK's/AKT signaling cascades was also analyzed using their specific inhibitors. The inhibiton of the ERK and AKT pathway increased cell death, indicating a prosurvival role, whereas inhibiton of the JNK and p38 pathway increased cell survival in this model. In vitro studies have also shown a high Bcl-2/BAX ratio during anoxia and reoxygenation, indicating a strong resistance to cell death via apoptosis., Silencing of the anti-apoptotic Bcl-2 gene using specific siRNA upregulated levels of prodeath BAX, thus altering the Bcl-2/BAX ratio and elevating cleaved Caspase-3 levels leading to increased cell death. Another promising neuroprotective target which we analyzed was Neuroglobin, which was induced during oxygen crisis and silencing this gene indicated that its plays a major role in modulation of ROS. This study strongly emphasizes the advantages of an alternate animal model in elucidating neuroprotective mechanisms and revealing novel therapeutic targets which could eventually help clinicians to design new stroke therapies based on naturally tolerant organisms.
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Date Issued
2009
PURL
http://purl.flvc.org/FAU/186762
Subject Headings
Turtles, Physiology, Adenosine, Receptors, Cellular signal transduction, Molecular neurobiology, Apoptosis, Research, Cellular control mechanisms
Format
Document (PDF)
Molecular mechanisms of neuroprotection in the anoxia tolerant freshwater turtle
Title
Molecular mechanisms of neuroprotection in the anoxia tolerant freshwater turtle.
Creator
Kesaraju, Shailaja., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Cardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of...
Show moreCardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of this study is to understand the modulation of key molecular mechanisms involving stress proteins and VEGF that offer neuroprotection and enhance cell survival in the freshwater turtle through anoxia and reoxygenation. In vivo analyses have shown that anoxia induced stress proteins (Hsp72, Hsp60, Grp94, Hsp60, Hsp27, HO-1); modest changes in the Bcl2/Bax ratio and no change in cleaved caspase-3 expression suggesting resistance to neuronal damage. These results were corroborated with immunohistochemical evidence indicating no damage in turtle brain when subjected to the stress of anoxia and A/R. To understand the functional role of Hsp72, siRNA against Hsp72 was utilized to knockdown Hsp72 in vitro (neuronally enriched primary cell cultures established from the turtle). Knockdown cultures were characterized by increased cell death associated with elevated ROS levels. Silencing of Hsp72 knocks down the expression of Bcl2 and increases the expression of Bax, thereby decreasing the Bcl2/Bax ratio. However, there was no increase in cytosolic Cytochrome c or the expression levels of cleaved Caspase-3. Significant increase in AIF was observed in the knockdown cultures that increase through anoxia and reoxygenation, suggesting a caspase independent pathway of cell death., Expression of the master regulator of hypoxia, HIF1 alpha and its target gene, VEGF, were analyzed at the mRNA and protein levels. The results showed no significant increase in HIF-1 alpha levels but anoxia VE GF The levels of stress proteins and VEGF returned to control levels during reoxygenation suggesting robust ROS protection mechanisms through reoxygenation. The present study thereby emphasizes Trachemys scripta as an advantageous model to examine anoxia and reoxygenation survival without major damage to the brain due to it's modulation of molecular mechanisms.
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Date Issued
2008
PURL
http://purl.flvc.org/FAU/165943
Subject Headings
Turtles, Physiology, Anoxemia, Proteins, Chemical modification, Oxygen, Physiological effect, Molecular neurobiology
Format
Document (PDF)
Regulation of rapid signaling at the cone ribbon synapse via distinct pre- and postsynaptic mechanisms
Title
Regulation of rapid signaling at the cone ribbon synapse via distinct pre- and postsynaptic mechanisms.
Creator
Rowan, Matthew JM., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Background: Light-adaptation is a multifaceted process in the retina that helps adjust the visual system to changing illumination levels. Many studies are focused on the photochemical mechanism of light-adaptation. Neural network adaptation mechanisms at the photoreceptor synapse are largely unknown. We find that large, spontaneous Excitatory Amino Acid Transporter (EAATs) activity in cone terminals may contribute to cone synaptic adaptation, specifically with respect to how these signals...
Show moreBackground: Light-adaptation is a multifaceted process in the retina that helps adjust the visual system to changing illumination levels. Many studies are focused on the photochemical mechanism of light-adaptation. Neural network adaptation mechanisms at the photoreceptor synapse are largely unknown. We find that large, spontaneous Excitatory Amino Acid Transporter (EAATs) activity in cone terminals may contribute to cone synaptic adaptation, specifically with respect to how these signals change in differing conditions of light. EAATs in neurons quickly transport glutamate from the synaptic cleft, and also elicit large thermodynamically uncoupled Cl- currents when activated. We recorded synaptic EAAT currents from cones to study glutamate-uptake events elicited by glutamate release from the local cone, and from adjacent photoreceptors. We find that cones are synaptically connected via EAATs in dark ; this synaptic connection is diminished in light-adapted cones. Methods: Whole-cell patch-clamp was performed on dark- and transiently light-adapted tiger salamander cones. Endogenous EAAT currents were recorded in cones with a short depolarization to -10mV/2ms, while spontaneous transporter currents from network cones were observed while a local cone holding at -70mV constantly. DHKA, a specific transporter inhibitor, was used to identify EAAT2 currents in the cone terminals, while TBOA identified other EAAT subtypes. GABAergic and glycinergic network inputs were always blocked with picrotoxin and strychnine. Results: Spontaneous EAAT currents were observed in cones held constantly at -70mV in dark, indicating that the cones received glutamate inputs from adjacent photoreceptors. These spontaneous EAAT currents disappeared in presence of a strong light, possibly because the light suppressed glutamate releases from the adjacent photoreceptors. The spontaneous EAAT currents were blocked with TBOA, but not DHKA, an inhibitor for EAAT2 subtype, suggesting that a, non-EAAT 2 subtype may reside in a basal or perisynaptic area of cones, with a specialized ability to bind exocytosed glutamate from adjacent cones in dark. Furthermore, these results could be artificially replicated by dual-electrode recordings from two adjacent cones. When glutamate release was elicited from one cone, the TBOA-sensitive EAAT currents were observed from the other cone. Conclusions: Cones appear to act like a meshwork, synaptically connected via glutamate transporters. Light attenuates glutamate release and diminishes the cone-cone synaptic connections. This process may act as an important network mechanism for cone light adaptation.
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Date Issued
2011
PURL
http://purl.flvc.org/FAU/3337186
Subject Headings
Synapses, Neural transmission, VIsual perception, Presynaptic receptors, Molecular neurobiology, Glutamic acid, Neural receptors, Cellular signal transduction, Retina, Cytology
Format
Document (PDF)