1. Stochastic Spatially-Extended Simulations Predict the Effect of ER Distribution on Astrocytic Microdomain Ca2+ Activity
- Author
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Hugues Berry, Audrey Denizot, Erik De Schutter, Corrado Calì, Okinawa Institute of Science and Technology Graduate University (OIST), Neuroscience Institute Cavalieri Ottolenghi [Turin] (NICO), Università degli studi di Torino = University of Turin (UNITO), Artificial Evolution and Computational Biology (BEAGLE), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Inria Grenoble - Rhône-Alpes, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Computational neuroscience ,Chemistry ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Endoplasmic reticulum ,Lipid microdomain ,Central nervous system ,astrocytes ,tripartite synapses ,reaction-diffusion simulations ,Synapse ,calcium microdomain ,Cytosol ,medicine.anatomical_structure ,computational neuroscience ,medicine ,Biophysics ,Premovement neuronal activity ,Astrocyte - Abstract
International audience; Astrocytes are cells of the central nervous system that can regulate neuronal activity. Most astrocyte-neuron communication occurs at so-called tripartite synapses, where calcium signals are triggered in astrocytes by neuronal activity, resulting in the release of neuroactive molecules by the astrocyte. Most astrocytic Ca 2+ signals occur in very thin astrocytic branchlets, containing low copy number of molecules, so that reactions are highly stochastic. As those sub-cellular compartments cannot be resolved by diffraction-limited microscopy techniques, stochastic reaction-diffusion computational approaches can give crucial insights on astrocyte activity. Here, we use our stochastic voxel-based model of IP 3 R-mediated Ca 2+ signals to investigate the effect of the distance between the synapse and the closest astrocytic endoplasmic reticulum (ER) on neuronal activityinduced Ca 2+ signals. Simulations are performed in three dimensional meshes characterized by various ER-synapse distances. Our results suggest that Ca 2+ peak amplitude, duration and frequency decrease rapidly as ER-synapse distance increases. We propose that this effect mostly results from the increased cytosolic volume of branchlets that are characterized by larger ER-synapse distances. In particular, varying ER-synapse distance with constant cytosolic volume does not affect local Ca 2+ activity. This study illustrates the insights that can be provided by three-dimensional stochastic reaction-diffusion simulations on the biophysical constraints that shape the spatio-temporal characteristics of astrocyte activity at the nanoscale.
- Published
- 2021