scholarly journals Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

2021 ◽  
Vol 15 ◽  
Author(s):  
Andrey Yu. Verisokin ◽  
Darya V. Verveyko ◽  
Dmitry E. Postnov ◽  
Alexey R. Brazhe
Keyword(s):  
Spatial Dimension ◽  
Neuronal Firing ◽  
Synaptic Activity ◽  
Distributed Model ◽  
Cell Level ◽  
Regular Sequences ◽  
Overlapping Domains ◽  
Local Cell ◽  
Model Equations ◽  
Realistic Data

Neuronal firing and neuron-to-neuron synaptic wiring are currently widely described as orchestrated by astrocytes—elaborately ramified glial cells tiling the cortical and hippocampal space into non-overlapping domains, each covering hundreds of individual dendrites and hundreds thousands synapses. A key component to astrocytic signaling is the dynamics of cytosolic Ca2+ which displays multiscale spatiotemporal patterns from short confined elemental Ca2+ events (puffs) to Ca2+ waves expanding through many cells. Here, we synthesize the current understanding of astrocyte morphology, coupling local synaptic activity to astrocytic Ca2+ in perisynaptic astrocytic processes and morphology-defined mechanisms of Ca2+ regulation in a distributed model. To this end, we build simplified realistic data-driven spatial network templates and compile model equations as defined by local cell morphology. The input to the model is spatially uncorrelated stochastic synaptic activity. The proposed modeling approach is validated by statistics of simulated Ca2+ transients at a single cell level. In multicellular templates we observe regular sequences of cell entrainment in Ca2+ waves, as a result of interplay between stochastic input and morphology variability between individual astrocytes. Our approach adds spatial dimension to the existing astrocyte models by employment of realistic morphology while retaining enough flexibility and scalability to be embedded in multiscale heterocellular models of neural tissue. We conclude that the proposed approach provides a useful description of neuron-driven Ca2+-activity in the astrocyte syncytium.

scholarly journals Modeling of astrocyte networks: towards realistic topology and dynamics

2020 ◽  
Author(s):  
Darya V. Verveyko ◽  
Andrey Yu. Verisokin ◽  
Dmitry E. Postnov ◽  
Alexey R. Brazhe
Keyword(s):  
Spatial Dimension ◽  
Neuronal Firing ◽  
Synaptic Activity ◽  
Distributed Model ◽  
Cell Level ◽  
Regular Sequences ◽  
Overlapping Domains ◽  
Local Cell ◽  
Model Equations ◽  
Realistic Data

Neuronal firing and neuron-to-neuron synaptic wiring are currently widely described as orchestrated by astrocytes — elaborately ramified glial cells tiling the cortical an hippocampal space into non-overlapping domains, each covering hundreds of individual dendrites and hundreds thousands synapses. A key component to astrocytic signaling is the dynamics of cytosolic Ca2+which displays multiscale spatiotemporal patterns from short confined elemental Ca2+events (puffs) to Ca2+waves expanding through many cells. Here we synthesize the current understanding of astrocyte morphology, coupling local synaptic activity to astrocytic Ca2+in perisynaptic astrocytic processes and morphology-defined mechanisms of Ca2+regulation in a distributed model. To this end, we build simplified realistic data-driven spatial network templates and compile model equations as defined by local cell morphology. The input to the model is spatially uncorrelated stochastic synaptic activity. The proposed modeling approach is validated by statistics of simulated Ca2+transients at a single cell level. In multicellular templates we observe regular sequences of cell entrainment in Ca2+waves, as a result of interplay between stochastic input and morphology variability between individual astrocytes. Our approach adds spatial dimension to the existing astrocyte models by employment of realistic morphology while retaining enough flexibility and scalability to be embedded in multiscale heterocellular models of neural tissue. We conclude that the proposed approach provides a useful description of neuron-driven Ca2+-activity in the astrocyte syncytium.

scholarly journals Nonlinear Poisson effects in soft honeycombs

2014 ◽  
Vol 470 (2169) ◽  
pp. 20140363 ◽  
Author(s):  
L. Angela Mihai ◽  
Alain Goriely
Keyword(s):  
Poisson Ratio ◽  
Finite Elasticity ◽  
Tensile Load ◽  
Honeycomb Structure ◽  
Wall Material ◽  
Uniaxial Tensile ◽  
Cell Level ◽  
Standard Geometry ◽  
Local Cell ◽  
Nonlinear Elastic

We examine solid cellular structures within the theoretical framework of finite elasticity, whereby we assume that the cell wall material is nonlinear elastic. This enables us to identify new mechanical effects that appear in cellular materials when elastically deformed, and to explore the physical properties that influence them. We find that, when a honeycomb structure of hyperelastic material and standard geometry, such as rectangular-, hexagonal- or diamond-shaped cells, contains walls which are inclined relative to an applied uniaxial tensile load, these walls tend to expand both in the direction of the load and in the perpendicular direction, producing an apparent negative Poisson's ratio at local cell level. Moreover, we show that this (negative) Poisson ratio decreases as the magnitude of the tensile load increases. For these structures, Poisson's ratios greater than 0.5 are obtained in uniaxial compression. Similar effects in structures with linearly elastic cell walls do not occur.

scholarly journals AMPA Receptor Trafficking in Homeostatic Synaptic Plasticity: Functional Molecules and Signaling Cascades

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Guan Wang ◽  
James Gilbert ◽  
Heng-Ye Man
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Firing ◽  
Synaptic Activity ◽  
Homeostatic Plasticity ◽  
Signaling Cascades ◽  
Excitatory Synapses ◽  
Homeostatic Synaptic Plasticity ◽  
Ampar Trafficking ◽  
Entire Network ◽  
Homeostatic Response

Homeostatic synaptic plasticity is a negative-feedback response employed to compensate for functional disturbances in the nervous system. Typically, synaptic activity is strengthened when neuronal firing is chronically suppressed or weakened when neuronal activity is chronically elevated. At both the whole cell and entire network levels, activity manipulation leads to a global up- or downscaling of the transmission efficacy of all synapses. However, the homeostatic response can also be induced locally at subcellular regions or individual synapses. Homeostatic synaptic scaling is expressed mainly via the regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking and synaptic expression. Here we review the recently identified functional molecules and signaling pathways that are involved in homeostatic plasticity, especially the homeostatic regulation of AMPAR localization at excitatory synapses.

scholarly journals Analytical and numerical results for flow and shock formation in two-layer gravity currents

1998 ◽  
Vol 40 (1) ◽  
pp. 35-58 ◽  
Author(s):  
P. J. Montgomery ◽  
T. B. Moodie
Keyword(s):  
Numerical Solutions ◽  
Spatial Dimension ◽  
Gravity Currents ◽  
Numerical Results ◽  
Shock Formation ◽  
Inviscid Fluid ◽  
Weakly Nonlinear ◽  
Relaxation Scheme ◽  
Model Equations ◽  
The Stability

AbstractMany gravity driven flows can be modelled as homogeneous layers of inviscid fluid with a hydrostatic pressure distribution. There are examples throughout oceanography, meteorology, and many engineering applications, yet there are areas which require further investigation. Analytical and numerical results for two-layer shallow-water formulations of time dependent gravity currents travelling in one spatial dimension are presented. Model equations for three physical limits are developed from the hydraulic equations, and numerical solutions are produced using a relaxation scheme for conservation laws developed recently by S. Jin and X. Zin [6]. Hyperbolicity of the model equations is examined in conjunction with the stability Froude number, and shock formation at the interface of the two layers is investigated using the theory of weakly nonlinear hyperbolic waves.

scholarly journals SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia

2020 ◽  
Author(s):  
Aubin Moutal ◽  
Laurent F. Martin ◽  
Lisa Boinon ◽  
Kimberly Gomez ◽  
Dongzhi Ran ◽  
...  
Keyword(s):  
Viral Entry ◽  
Disease Transmission ◽  
Neuronal Firing ◽  
Synaptic Activity ◽  
Spike Protein ◽  
Angiogenic Factor ◽  
Neuropilin 1 ◽  
Neuropathic Pain Model ◽  
Asymptomatic Individuals ◽  
Endothelial Growth Factor

AbstractGlobal spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues unabated. Binding of SARS-CoV-2’s Spike protein to host angiotensin converting enzyme 2 triggers viral entry, but other proteins may participate, including neuropilin-1 receptor (NRP-1). As both Spike protein and vascular endothelial growth factor-A (VEGF-A) – a pro-nociceptive and angiogenic factor, bind NRP-1, we tested if Spike could block VEGF-A/NRP-1 signaling. VEGF-A–triggered sensory neuronal firing was blocked by Spike protein and NRP-1 inhibitor EG00229. Pro-nociceptive behaviors of VEGF-A were similarly blocked via suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A ‘silencing’ of pain via subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.

scholarly journals Glycolytic inhibition by 2-deoxy-d-glucose abolishes both neuronal and network bursts in an in vitro seizure model

2017 ◽  
Vol 118 (1) ◽  
pp. 103-113 ◽  
Author(s):  
Li-Rong Shao ◽  
Carl E. Stafstrom
Keyword(s):  
Neuronal Activity ◽  
Hippocampal Slices ◽  
Cellular Metabolism ◽  
Basal Membrane ◽  
Neuronal Firing ◽  
Synaptic Activity ◽  
Membrane Properties ◽  
Bath Application ◽  
Altered Glucose ◽  
Network Bursts

Neuronal activity is energy demanding and coupled to cellular metabolism. In this study, we investigated the effects of glycolytic inhibition with 2-deoxy-d-glucose (2-DG) on basal membrane properties, spontaneous neuronal firing, and epileptiform network bursts in hippocampal slices. The effect of glycolytic inhibition on basal membrane properties was examined in hippocampal CA1 neurons, which are not ordinarily active spontaneously. Intracellular application of 2-DG did not significantly alter the membrane input resistance, action-potential threshold, firing pattern, or input-output relationship of these neurons compared with simultaneously recorded neighboring neurons without intracellular 2-DG. The effect of glycolytic inhibition on neuronal firing was tested in spontaneously active hippocampal neurons (CA3) when synaptic transmission was left intact or blocked with AMPA, NMDA, and GABAA receptor antagonists (DNQX, APV, and bicuculline, respectively). Under both conditions (synaptic activity intact or blocked), bath application of 2-DG (2 mM) blocked spontaneous firing in ~2/3 (67 and 71%, respectively) of CA3 pyramidal neurons. In contrast, neuronal firing of CA3 neurons persisted when 2-DG was applied intracellularly, suggesting that glycolytic inhibition of individual neurons is not sufficient to stop neuronal firing. The effects of 2-DG on epileptiform network bursts in area CA3 were tested in Mg2+-free medium containing 50 µM 4-aminopyridine. Bath application of 2-DG abolished these epileptiform bursts in a dose-dependent and all-or-none manner. Taken together, these data suggest that altered glucose metabolism profoundly affects cellular and network hyperexcitability and that glycolytic inhibition by 2-DG can effectively abrogate epileptiform activity. NEW & NOTEWORTHY Neuronal activity is highly energy demanding and coupled to cellular metabolism. In this study, we demonstrate that glycolytic inhibition with 2-deoxy-d-glucose (2-DG) effectively suppresses spontaneous neuronal firing and epileptiform bursts in hippocampal slices. These data suggest that an altered metabolic state can profoundly affect cellular and network excitability, and that the glycolytic inhibitor 2-DG may hold promise as a novel treatment of drug-resistant epilepsy.

Measurement of spontaneous neuronal membrane activity by time lapse confocal microscopy

1995 ◽  
Vol 53 ◽  
pp. 972-973
Author(s):  
R H. Selinfreund ◽  
A. H. Cornell-Bell
Keyword(s):  
Membrane Potential ◽  
Confocal Microscopy ◽  
Patch Clamp ◽  
Electrical Activity ◽  
Time Lapse ◽  
Neuronal Firing ◽  
Neuronal Membrane ◽  
Pituitary Cells ◽  
Patch Clamp Recording ◽  
Spontaneous Electrical Activity

Cellular electrophysiological properties are normally monitored by standard patch clamp techniques . The combination of membrane potential dyes with time-lapse laser confocal microscopy provides a more direct, least destructive rapid method for monitoring changes in neuronal electrical activity. Using membrane potential dyes we found that spontaneous action potential firing can be detected using time-lapse confocal microscopy. Initially, patch clamp recording techniques were used to verify spontaneous electrical activity in GH4\C1 pituitary cells. It was found that serum depleted cells had reduced spontaneous electrical activity. Brief exposure to the serum derived growth factor, IGF-1, reconstituted electrical activity. We have examined the possibility of developing a rapid fluorescent assay to measure neuronal activity using membrane potential dyes. This neuronal regeneration assay has been adapted to run on a confocal microscope. Quantitative fluorescence is then used to measure a compounds ability to regenerate neuronal firing.The membrane potential dye di-8-ANEPPS was selected for these experiments. Di-8- ANEPPS is internalized slowly, has a high signal to noise ratio (40:1), has a linear fluorescent response to change in voltage.

Systematic zone-Axis orientation of NM-scale particles for microdiffraction

1990 ◽  
Vol 48 (4) ◽  
pp. 262-263
Author(s):  
E D Boyes ◽  
L Hanna
Keyword(s):  
Real Space ◽  
Dark Field ◽  
Zone Axis ◽  
High Symmetry ◽  
Lattice Imaging ◽  
Cell Level ◽  
Bright Field ◽  
Axis Orientation ◽  
Annular Dark Field ◽  
Target Designation

A VG HB501 FEG STEM has been modified to provide track whilst tilt [TWIT] facilities for controllably tilting selected and initially randomly aligned nanometer-sized particles into the high symmetry zone-axis orientations required for microdiffraction, lattice imaging and chemical microanalysis at the unit cell level. New electronics display in alternate TV fields and effectively in parallel on split [+VTR] or adjacent externally synchronized screens, the micro-diffraction pattern from a selected area down to <1nm2 in size, together with the bright field and high angle annular dark field [HADF] STEM images of a much wider [˜1μm] area centered on the same spot. The new system makes it possible to tilt each selected and initially randomly aligned small particle into a zone axis orientation for microdiffraction, or away from it to minimize orientation effects in chemical microanalysis. Tracking of the inevitable specimen movement with tilt is controlled by the operator, with realtime [60Hz] update of the target designation in real space and the diffraction data in reciprocal space. The spot mode micro-DP and images of the surrounding area are displayed continuously. The regular motorized goniometer stage for the HB501STEM is a top entry design but the new control facilities are almost equivalent to having a stage which is eucentric with nanometric precision about both tilt axes.

Video-microscopic measurement of cell-substratum traction forces generated by locomoting keratocytes

1993 ◽  
Vol 51 ◽  
pp. 188-189
Author(s):  
Tim Oliver ◽  
Michelle Leonard ◽  
Juliet Lee ◽  
Akira Ishihara ◽  
Ken Jacobson
Keyword(s):  
Silicone Rubber ◽  
Molecular Motors ◽  
Video Frame ◽  
Traction Forces ◽  
Cell Traction Forces ◽  
Latex Beads ◽  
Cell Traction ◽  
Local Cell ◽  
Microscopic Measurement ◽  
Kinetics Of

We are using video-enhanced light microscopy to investigate the pattern and magnitude of forces that fish keratocytes exert on flexible silicone rubber substrata. Our goal is a clearer understanding of the way molecular motors acting through the cytoskeleton co-ordinate their efforts into locomotion at cell velocities up to 1 μm/sec. Cell traction forces were previously observed as wrinkles(Fig.l) in strong silicone rubber films by Harris.(l) These forces are now measureable by two independant means.In the first of these assays, weakly crosslinked films are made, into which latex beads have been embedded.(Fig.2) These films report local cell-mediated traction forces as bead displacements in the plane of the film(Fig.3), which recover when the applied force is released. Calibrated flexible glass microneedles are then used to reproduce the translation of individual beads. We estimate the force required to distort these films to be 0.5 mdyne/μm of bead movement. Video-frame analysis of bead trajectories is providing data on the relative localisation, dissipation and kinetics of traction forces.

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