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Noise-Driven Synchronization of Coupled Neural Networks
Wednesday, March 2, 2016 (SDPC)/cholesterol membrane, and 5HT to determine if binding of the ligand causes protein reassembly and channel opening. 3112-Pos Board B489 Key Differences in Molecular Transport Mechanisms of Uncoupling Proteins Gabriel Macher1, Melanie Ko¨hler2, Anne Rupprecht1, Peter Hinterdorfer2, Elena Pohl1. 1 Institute of Physiology, Pathophysiology and Biophysics, University of Veterinary Medicine, Vienna, Austria, 2Institute of Biophysics, Johannes Kepler University, Linz, Austria. Mitochondrial membrane uncoupling protein 1 (UCP1) facilitates proton leak to support non-shivering thermogenesis in brown adipose tissue. The transport function of other UCPs is controversially discussed. It was proposed that in addition to protons, other substrates can be transported. Moreover, the molecular mechanism of UCP regulation is insufficiently understood, although it is generally accepted that its transport is regulated by free fatty acids (FFA) and purine nucleotides (PN). Here we tested the hypothesis that regulation differs between members of UCP family leading to differences in their functions [1]. We evaluated binding forces and the degree of inhibition by PNs, comparing the data obtained using recognition force microscopy and electrophysiological measurements of recombinant proteins reconstituted in planar bilayer membranes [2]. We reveal that, in contrast to UCP1, other UCPs can be fully inhibited by all PNs, as KD increases with a decrease in phosphorylation. Furthermore, three arginines (R84, R183, R277) in the PN-binding pocket are involved in UCP1 inhibition to different extents. This result disagrees with previously proposed mechanisms, suggesting that only R277 is responsible for 100% inhibition. Moreover, FFAs can compete with all PNs bound to UCP1, but only with triphosphate-PNs bound to UCP3. Our results demonstrate the different regulation across a family of highly homologous uncoupling proteins, which, in the case of UCP1 and UCP3, are even expressed in the same tissue. We anticipate that the differences in the molecular mechanism of UCPs can be useful in understanding their physiological functions. [1] Rupprecht A, Sokolenko EA, Beck V, Ninnemann O, Jaburek M, et al. (2010) Biophys J; 98: 1503-1511. [2] Zhu R, Rupprecht A, Ebner A, Haselgrubler T, Gruber HJ, Hinterdorfer P, Pohl EE. (2013) J Am Chem Soc; 135:3640-3646. 3113-Pos Board B490 Water Pathway Analysis of Multi-Drug Efflux Transporter AcrB Tsutomu Yamane1, Ryotaro Koike2, Motonori Ota2, Satoshi Murakami3, Akinori Kidera1, Mitsunori Ikeguchi1. 1 Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan, 2Graduate School of Information Science, Nagoya University, Nagoya, Japan, 3Graduate School of Bioscience & Bioengineering, Tokyo Institute of Technology, Yokohama, Japan. The multi-drug efflux transporter AcrB exists in the inner membrane region of E. coli., and exports wide variety of noxious compounds using proton motive force as an energy source in Gram-negative bacteria. From the results of x-ray crystallography, the followings were found: (1) AcrB adopts asymmetric structure comprising three protomers with different structures, which correspond to access (A), binding (B) and extrusion (E) state of drugs, (2) three titratable residues (Asp407, Asp408 and Lys940), which locate in the middle of the transmembrane domain, form the protonation site (PS), and the Lys940 in E state adopts the different conformation from those of other states. These results suggest that AcrB exports drugs through the cyclic structural change among three states by using proton motive force generated by the change of protonation state in PS, which are called ‘‘functional rotation’’. We have studied the functional rotation mechanism of AcrB by using the Motion-tree method, which is a new procedure to describe the structural change as rigid body motions with a hierarchal manner. Our results have elucidated how convert the proton motive force generated from PS to the large structural change of AcrB. In the present study, to clarify the proton transfer process in the transmembrane domain, we searched the water pathways from the PS by using CAVER and 3D-RISM methods. As the results from CAVER method, A and B state protomers observed pathways from the PS to the periplasm side, and E state protomer observed a pathway from PS to the cytoplasm side. In addition, the results of 3DRISM method suggest that B and E state pathways have an ability to permeate water molecules. These results were consistent with the protonation states of each protomers estimated from structural change process from Motion-tree method.
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Computational Neuroscience 3114-Pos Board B491 Modeling the Oscillating Dipole Properties of Electric Organ Discharge in the Weakly Electric Fish, Eigenmannia Bela Joos1, Michael R. Markham2, Yanna Steimle1, John E. Lewis3, Morris E. Catherine4. 1 Physics, University of Ottawa, Ottawa, ON, Canada, 2Biology, University of Oklahoma, Norman, OK, USA, 3Biology, University of Ottawa, Ottawa, ON, Canada, 4Neuroscience, Ottawa Hospital Research Institute, Ottawa, ON, Canada. One of the most studied weakly electric fish, Eigenmannia produces a continuous high frequency electric organ discharge (EOD) used to sense nearby objects and communicate with conspecifics. The EOD of an individual fish has a characteristic frequency (within the species range, 250-600 Hz) which it shifts when necessary to avoid jamming. The nearly dipolar oscillating electric field yields zero net current and is generated by parallel columns of identical, synchronously discharging electrocyte cells. Recent findings from whole fish respirometry (during high-frequency signaling over a range of frequencies) have renewed interest in the frequency-dependent energetics of the EODs (Lewis et al 2014 J Neurosci 34:197) but the modeling based on past analyses is missing some key features of the in-vivo electrolyte operation. We have constructed a model for the neurally-driven electrocyte action potentials (APs) that underlie the EOD. APs are initiated by brief postsynaptic cation influxes through AChR channels at each electrocyte’s innervated posterior end. This yields a head positive current while the anterior end serves mainly as a capacitor whose discharge yields the head negative current of the oscillating dipole cycle. To maintain the appropriate [Na]in and [K]out levels, Na/K-ATPase pumps run continuously. Modeling the activity of this ATP consuming protein gives us access to electrocyte energetics and frequency-dependent EOD efficiency. Modeling the posterior-anterior current flows gives us access to the electric field patterns produced by the electrocytes. 3115-Pos Board B492 Resonances and Spectral Characteristics of a Neural Network for the Song Motor Pathway in Birds Cristiano Giordani1, Hector Fabio Rivera-Gutierrez1, Ruggero Micheletto2. 1 Universidad de Antioquia, Medellin, Colombia, 2Yokohama City University, Yokohama, Japan. Birdsong is a complex learned behavior regulated in an intricate way. Neuromuscular coordination of different muscular sets is necessary for producing high quality and consistent songs. We developed a realistic neural network that emulates neurons from the High Vocal centre (HVc) and the robust nucleus of the archistriatum (RA) neurons that drive the muscles to generate birdsong sounds. We used modern computational tools and neural architecture to simulate the entire motor pathway up to the physical oscillator muscle system and its spectral characteristics. Several network parameter dependences were analysed and elucidated. An optimal network size within 10 to 25 neurons within which minimal and smooth frequency variations occur, was found. Beyond that range we observe, instead, strong frequency dependence. Moreover, response frequency is influenced by the pathway input current; also in this case frequency response keeps smooth within a certain range of current, but shows interesting resonant values where negative peaks are observed. Resonant values are found in respect to the non-linear dissipation constant of the equation of motion for the bird’s labial oscillation and also in respect of the network background noise level (stochastic resonance). This work demonstrate that is possible to achieve a realistic computational model for the motor pathway leading to generation of sounds in birds, which contributes to the understanding of its spectral and dynamical fundamental properties and characteristics. 3116-Pos Board B493 Noise-Driven Synchronization of Coupled Neural Networks Anis Yuniati, Te-Lun Mai, Chi-Ming Chen. Department of Physics, National Taiwan Normal University, Taipei, Taiwan. The brain is complex network of dynamical system. For this reason, the interaction between different brain areas can be modeled as a large-scale network which is important in functional brain dynamics, and it closely related to the brain disorder. In recent years, the significant progress about the understanding of the relation between the structure and dynamical properties of the networks has developed. It describes that the complex dynamic behavior such as synchronization of coupled dynamical system plays a crucial role in a brain function and dysfunction. In our simulations, we construct a coupled neural
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network that are in different activity states, the synchronous firing state (SFS) network represents the healthy nerve cells and background activity state (BAS) network represents the damaged nerve cells. We identify their interaction by varying the synaptic coupling strength of inter-network interactions. The Hodgkin-Huxley (HH) neuronal model is biologically plausible and spike timing dependent plasticity (STDP) or inverse STDP mechanisms are considered restructuring the coupling strength of the synapses. In this study, we find that SFS network can induce the synchronous firing in the BAS network by enhancing the coupling strength between the coupled networks. Here, we identify the threshold of coupling strength, in which the BAS network keep their synchronous state after disconnecting the inter-connections from SFS network. Thus, this method can be considered as a new treatment to repair a damage brain after injury or because of some disease. Then, we analyze the network properties such as the degree distribution, the characteristic path length and the cluster coefficient of the network to propose the design of intra-network neurons distribution and the design of the inter-connection probability which can give a better result than random neurons distribution or random internetwork connections. 3117-Pos Board B494 A Unified Framework for Neuronal Spikes, Seizures, Spreading Depression, and Ischemia-Induced Anoxic Depolarization Ghanim Ullah1, Yina Wei2, Steven J. Schiff3. 1 Physics, University of South Florida, Tampa, FL, USA, 2Cell Biology and Neuroscience, University of California, Riverside, CA, USA, 3Neural Engineering, Engineering Science and Mechanics, Neurosurgery, and Physics, The Pennsylvania State University, University Park, PA, USA. The pathological phenomena of seizures and spreading depression have long been considered separate physiological events in the brain. By incorporating conservation of particles and charge, and accounting for the energy required to restore ionic gradients and cell swelling we extend the classic HodgkinHuxley formalism to uncover a unification of neuronal membrane dynamics. By examining the dynamics as a function of potassium and oxygen, we now account for a wide range of neuronal activities, from spikes to seizures, spreading depression, mixed seizure and spreading depression states, and the terminal anoxic ‘‘wave of death.’’ Such a unified framework demonstrates that all of these dynamics lie along a continuum of the repertoire of the neuron membrane [1, 2]. We demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. The use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial Kþ buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia [3]. Our results demonstrate that unified frameworks for neuronal dynamics are feasible, can be achieved using existing biological structures and universal physical conservation principles, and may be of substantial importance in enabling our understanding of brain activity and in the control of pathological states. [1] Wei, Ullah, and Schiff (2014) J.Neurosci. 34: 11733. [2] Wei, Ullah, Ingram, Schiff (2014) J. Neurophysiol. 112: 213. [3] Ullah et al (2015) PLoS Comp. Biol. 11: e1004413. 3118-Pos Board B495 Cell Volume in Brain Pathologies: Anions-Controlled Neural and Glial Swelling in Spreading Depolarization and Increased Neuronal Susceptibility to Ischemic Injury due to Large Extracellular Space Niklas Hubel. University of South Florida, Tampa, FL, USA. Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little about the dynamics of cell and tissue swelling, and the differential changes in the volumes of neurons and glia during pathological states such as spreading depolarizations (SD) and epileptic seizures. By combining the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations, and simultaneous neuronal and astroglial volume changes into a comprehensive model, we elucidate why glial cells swell more than neurons in SD and the special case of ischemia-induced anoxic depolarization (AD). We explore the relative contributions of the two cell types to tissue swelling and our results demonstrate that anion channels, particularly Cl-, are intrinsically connected to cell swelling. Blocking these currents prevents changes in cell volume. Our model is simple, physiologically realistic, and
derived from the first physical principles of electroneutrality, osmosis and conservation of particles. We provide new insights into numerous studies related to neuronal and glial volume changes in SD that otherwise seem contradictory. The theory is broadly applicable to swelling in other cell types and conditions. In a complimentary research we found that the brain region-specific extracellular volume fraction has a strong effect on the recoverability of neurons from AD. Glial-vascular Kþ clearance and Naþ /Kþ -exchange pumps are key to the cell’s recovery, and the large extracellular space in the upper brain regions leads to impaired Naþ/Kþ-exchange pumps so that they function at reduced capacity. Hence they are unable to bring the cell out of AD after oxygen and glucose is restored, leading to permanent cell damage. 3119-Pos Board B496 Multi-Scale Spatial Simulations Reveal the Effect of Dopamine Transporter Localization on Dopamine Neurotransmission Cihan Kaya1, Ethan R. Block2, Alexander Sorkin2, James R. Faeder1, Ivet Bahar1. 1 Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA, 2Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA. The neurotransmitter dopamine (DA) is involved in various signaling processes in the central nervous system (CNS) such as motivation, motor, reward valuation and endocrinal regulation. The expression levels of dopamine transporters (DAT), which function to clear extracellular (EC) DA, are high in dopaminergic neurons. Dopaminergic signaling relies on the localization and distribution of transporters and receptors not only at the synapses, but also at the extrasynaptic regions. Furthermore, the localization of DATs in synaptic areas, their conformational dynamics and intermolecular interactions during reuptake and release of DA, and DAT endocytosis are key processes that regulate dopaminergic signaling. Information on the spatiotemporal properties on DA release and reuptake mechanisms is limited due to limitations in current imaging techniques and difficulty of dealing with multi-scales in these models. However, fluorescence and electron microscopy provides significant information about the localization of the DATs and axonal varicosities where the DA release event occurs. This information could be transferred into a 3D reconstruction of the dopaminergic neurons and generating a multi-scale spatial model of DA-DAT transport mechanism and trafficking provides an understanding of the dynamics of system. The spatial multi-model is simulated with a hybrid solver able to solve particle based stochastic simulations and ordinary or partial differential equations. Overall, model will provide information to connect DAT trafficking and resulting localization and concentration to DA neurotransmission. 3120-Pos Board B497 Synthetic Persons Otto E. Rossler. Mathematics and Science, University of Tubingen, Tubingen, Germany. Person theory has two architects, Immanuel Kant and Robert Spaemann. In biology, you first need a brain theory. Here the brain equation can be used. On its basis, a specific symmetric coupling between two has been proposed to imply personogenesis. The model implies a causal therapy of autism which is extendable to mirror-competent bonding animals and AIs. So far, the therapy has never been tried out. (Compare the book ‘‘Chaotic Harmony’’ by A. Sanayei and O.E. Rossler, Springer Verlag Heidelberg 2014.)
Single-Molecule Spectroscopy 3121-Pos Board B498 Advancing 3D Single Molecule Tracking by Time-Gating and Fast Simultaneous Spinning Disk Imaging for Contextual Information Dominik G. Stich1, Matthew S. DeVore1, Ce´dric Cleyrat2, Mary L. Phipps1, Bridget S. Wilson2, Peter M. Goodwin1, James H. Werner1. 1 Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Los Alamos, NM, USA, 2Department of Pathology and Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM, USA. Three dimensional single molecule tracking is an essential technique for investigating biomolecular trafficking and signaling. Here we report the latest improvements to our confocal based tracking system. First, we added a Nipkow spinning disk imaging system. This system takes images of the plane of
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Computational Neuroscience 3114-Pos Board B491 Modeling the Oscillating Dipole Properties of Electric Organ Discharge in the Weakly Electric Fish, Eigenmannia Bela Joos1, Michael R. Markham2, Yanna Steimle1, John E. Lewis3, Morris E. Catherine4. 1 Physics, University of Ottawa, Ottawa, ON, Canada, 2Biology, University of Oklahoma, Norman, OK, USA, 3Biology, University of Ottawa, Ottawa, ON, Canada, 4Neuroscience, Ottawa Hospital Research Institute, Ottawa, ON, Canada. One of the most studied weakly electric fish, Eigenmannia produces a continuous high frequency electric organ discharge (EOD) used to sense nearby objects and communicate with conspecifics. The EOD of an individual fish has a characteristic frequency (within the species range, 250-600 Hz) which it shifts when necessary to avoid jamming. The nearly dipolar oscillating electric field yields zero net current and is generated by parallel columns of identical, synchronously discharging electrocyte cells. Recent findings from whole fish respirometry (during high-frequency signaling over a range of frequencies) have renewed interest in the frequency-dependent energetics of the EODs (Lewis et al 2014 J Neurosci 34:197) but the modeling based on past analyses is missing some key features of the in-vivo electrolyte operation. We have constructed a model for the neurally-driven electrocyte action potentials (APs) that underlie the EOD. APs are initiated by brief postsynaptic cation influxes through AChR channels at each electrocyte’s innervated posterior end. This yields a head positive current while the anterior end serves mainly as a capacitor whose discharge yields the head negative current of the oscillating dipole cycle. To maintain the appropriate [Na]in and [K]out levels, Na/K-ATPase pumps run continuously. Modeling the activity of this ATP consuming protein gives us access to electrocyte energetics and frequency-dependent EOD efficiency. Modeling the posterior-anterior current flows gives us access to the electric field patterns produced by the electrocytes. 3115-Pos Board B492 Resonances and Spectral Characteristics of a Neural Network for the Song Motor Pathway in Birds Cristiano Giordani1, Hector Fabio Rivera-Gutierrez1, Ruggero Micheletto2. 1 Universidad de Antioquia, Medellin, Colombia, 2Yokohama City University, Yokohama, Japan. Birdsong is a complex learned behavior regulated in an intricate way. Neuromuscular coordination of different muscular sets is necessary for producing high quality and consistent songs. We developed a realistic neural network that emulates neurons from the High Vocal centre (HVc) and the robust nucleus of the archistriatum (RA) neurons that drive the muscles to generate birdsong sounds. We used modern computational tools and neural architecture to simulate the entire motor pathway up to the physical oscillator muscle system and its spectral characteristics. Several network parameter dependences were analysed and elucidated. An optimal network size within 10 to 25 neurons within which minimal and smooth frequency variations occur, was found. Beyond that range we observe, instead, strong frequency dependence. Moreover, response frequency is influenced by the pathway input current; also in this case frequency response keeps smooth within a certain range of current, but shows interesting resonant values where negative peaks are observed. Resonant values are found in respect to the non-linear dissipation constant of the equation of motion for the bird’s labial oscillation and also in respect of the network background noise level (stochastic resonance). This work demonstrate that is possible to achieve a realistic computational model for the motor pathway leading to generation of sounds in birds, which contributes to the understanding of its spectral and dynamical fundamental properties and characteristics. 3116-Pos Board B493 Noise-Driven Synchronization of Coupled Neural Networks Anis Yuniati, Te-Lun Mai, Chi-Ming Chen. Department of Physics, National Taiwan Normal University, Taipei, Taiwan. The brain is complex network of dynamical system. For this reason, the interaction between different brain areas can be modeled as a large-scale network which is important in functional brain dynamics, and it closely related to the brain disorder. In recent years, the significant progress about the understanding of the relation between the structure and dynamical properties of the networks has developed. It describes that the complex dynamic behavior such as synchronization of coupled dynamical system plays a crucial role in a brain function and dysfunction. In our simulations, we construct a coupled neural
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Wednesday, March 2, 2016
network that are in different activity states, the synchronous firing state (SFS) network represents the healthy nerve cells and background activity state (BAS) network represents the damaged nerve cells. We identify their interaction by varying the synaptic coupling strength of inter-network interactions. The Hodgkin-Huxley (HH) neuronal model is biologically plausible and spike timing dependent plasticity (STDP) or inverse STDP mechanisms are considered restructuring the coupling strength of the synapses. In this study, we find that SFS network can induce the synchronous firing in the BAS network by enhancing the coupling strength between the coupled networks. Here, we identify the threshold of coupling strength, in which the BAS network keep their synchronous state after disconnecting the inter-connections from SFS network. Thus, this method can be considered as a new treatment to repair a damage brain after injury or because of some disease. Then, we analyze the network properties such as the degree distribution, the characteristic path length and the cluster coefficient of the network to propose the design of intra-network neurons distribution and the design of the inter-connection probability which can give a better result than random neurons distribution or random internetwork connections. 3117-Pos Board B494 A Unified Framework for Neuronal Spikes, Seizures, Spreading Depression, and Ischemia-Induced Anoxic Depolarization Ghanim Ullah1, Yina Wei2, Steven J. Schiff3. 1 Physics, University of South Florida, Tampa, FL, USA, 2Cell Biology and Neuroscience, University of California, Riverside, CA, USA, 3Neural Engineering, Engineering Science and Mechanics, Neurosurgery, and Physics, The Pennsylvania State University, University Park, PA, USA. The pathological phenomena of seizures and spreading depression have long been considered separate physiological events in the brain. By incorporating conservation of particles and charge, and accounting for the energy required to restore ionic gradients and cell swelling we extend the classic HodgkinHuxley formalism to uncover a unification of neuronal membrane dynamics. By examining the dynamics as a function of potassium and oxygen, we now account for a wide range of neuronal activities, from spikes to seizures, spreading depression, mixed seizure and spreading depression states, and the terminal anoxic ‘‘wave of death.’’ Such a unified framework demonstrates that all of these dynamics lie along a continuum of the repertoire of the neuron membrane [1, 2]. We demonstrate the spontaneous transition between epileptic seizure and spreading depression states as the cell swells and contracts in response to changes in osmotic pressure. The use of volume as an order parameter further revealed a dynamical definition for the experimentally described physiological ceiling that separates seizure from spreading depression, as well as predicted a second ceiling that demarcates spreading depression from anoxic depolarization. Our model highlights the neuroprotective role of glial Kþ buffering against seizures and spreading depression, and provides novel insights into anoxic depolarization and the relevant cell swelling during ischemia [3]. Our results demonstrate that unified frameworks for neuronal dynamics are feasible, can be achieved using existing biological structures and universal physical conservation principles, and may be of substantial importance in enabling our understanding of brain activity and in the control of pathological states. [1] Wei, Ullah, and Schiff (2014) J.Neurosci. 34: 11733. [2] Wei, Ullah, Ingram, Schiff (2014) J. Neurophysiol. 112: 213. [3] Ullah et al (2015) PLoS Comp. Biol. 11: e1004413. 3118-Pos Board B495 Cell Volume in Brain Pathologies: Anions-Controlled Neural and Glial Swelling in Spreading Depolarization and Increased Neuronal Susceptibility to Ischemic Injury due to Large Extracellular Space Niklas Hubel. University of South Florida, Tampa, FL, USA. Cell volume changes are ubiquitous in normal and pathological activity of the brain. Nevertheless, we know little about the dynamics of cell and tissue swelling, and the differential changes in the volumes of neurons and glia during pathological states such as spreading depolarizations (SD) and epileptic seizures. By combining the Hodgkin-Huxley type spiking dynamics, dynamic ion concentrations, and simultaneous neuronal and astroglial volume changes into a comprehensive model, we elucidate why glial cells swell more than neurons in SD and the special case of ischemia-induced anoxic depolarization (AD). We explore the relative contributions of the two cell types to tissue swelling and our results demonstrate that anion channels, particularly Cl-, are intrinsically connected to cell swelling. Blocking these currents prevents changes in cell volume. Our model is simple, physiologically realistic, and
derived from the first physical principles of electroneutrality, osmosis and conservation of particles. We provide new insights into numerous studies related to neuronal and glial volume changes in SD that otherwise seem contradictory. The theory is broadly applicable to swelling in other cell types and conditions. In a complimentary research we found that the brain region-specific extracellular volume fraction has a strong effect on the recoverability of neurons from AD. Glial-vascular Kþ clearance and Naþ /Kþ -exchange pumps are key to the cell’s recovery, and the large extracellular space in the upper brain regions leads to impaired Naþ/Kþ-exchange pumps so that they function at reduced capacity. Hence they are unable to bring the cell out of AD after oxygen and glucose is restored, leading to permanent cell damage. 3119-Pos Board B496 Multi-Scale Spatial Simulations Reveal the Effect of Dopamine Transporter Localization on Dopamine Neurotransmission Cihan Kaya1, Ethan R. Block2, Alexander Sorkin2, James R. Faeder1, Ivet Bahar1. 1 Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA, 2Department of Cell Biology and Physiology, University of Pittsburgh, Pittsburgh, PA, USA. The neurotransmitter dopamine (DA) is involved in various signaling processes in the central nervous system (CNS) such as motivation, motor, reward valuation and endocrinal regulation. The expression levels of dopamine transporters (DAT), which function to clear extracellular (EC) DA, are high in dopaminergic neurons. Dopaminergic signaling relies on the localization and distribution of transporters and receptors not only at the synapses, but also at the extrasynaptic regions. Furthermore, the localization of DATs in synaptic areas, their conformational dynamics and intermolecular interactions during reuptake and release of DA, and DAT endocytosis are key processes that regulate dopaminergic signaling. Information on the spatiotemporal properties on DA release and reuptake mechanisms is limited due to limitations in current imaging techniques and difficulty of dealing with multi-scales in these models. However, fluorescence and electron microscopy provides significant information about the localization of the DATs and axonal varicosities where the DA release event occurs. This information could be transferred into a 3D reconstruction of the dopaminergic neurons and generating a multi-scale spatial model of DA-DAT transport mechanism and trafficking provides an understanding of the dynamics of system. The spatial multi-model is simulated with a hybrid solver able to solve particle based stochastic simulations and ordinary or partial differential equations. Overall, model will provide information to connect DAT trafficking and resulting localization and concentration to DA neurotransmission. 3120-Pos Board B497 Synthetic Persons Otto E. Rossler. Mathematics and Science, University of Tubingen, Tubingen, Germany. Person theory has two architects, Immanuel Kant and Robert Spaemann. In biology, you first need a brain theory. Here the brain equation can be used. On its basis, a specific symmetric coupling between two has been proposed to imply personogenesis. The model implies a causal therapy of autism which is extendable to mirror-competent bonding animals and AIs. So far, the therapy has never been tried out. (Compare the book ‘‘Chaotic Harmony’’ by A. Sanayei and O.E. Rossler, Springer Verlag Heidelberg 2014.)
Single-Molecule Spectroscopy 3121-Pos Board B498 Advancing 3D Single Molecule Tracking by Time-Gating and Fast Simultaneous Spinning Disk Imaging for Contextual Information Dominik G. Stich1, Matthew S. DeVore1, Ce´dric Cleyrat2, Mary L. Phipps1, Bridget S. Wilson2, Peter M. Goodwin1, James H. Werner1. 1 Center for Integrated Nanotechnologies, Los Alamos National Laboratory, Los Alamos, NM, USA, 2Department of Pathology and Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM, USA. Three dimensional single molecule tracking is an essential technique for investigating biomolecular trafficking and signaling. Here we report the latest improvements to our confocal based tracking system. First, we added a Nipkow spinning disk imaging system. This system takes images of the plane of