Disentangling astroglial physiology with a realistic cell model in silico

Savtchenko, Leonid P.; Bard, Lucie; Jensen, Thomas P.; Reynolds, James P.; Kraev, Igor; Medvedev, Nikolay; Stewart, Michael G.; Henneberger, Christian and Rusakov, Dmitri A. (2018). Disentangling astroglial physiology with a realistic cell model in silico. Nature Communications, 9(1), article no. 3554.

DOI: https://doi.org/10.1038/s41467-018-05896-w

Abstract

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging.

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About

  • Item ORO ID
  • 56588
  • Item Type
  • Journal Item
  • ISSN
  • 2041-1723
  • Project Funding Details
  • Funded Project NameProject IDFunding Body
    Principal Fellowship101896Wellcome Trust
    Principal Fellowship212251/ Z/18/ZWellcome Trust
    Advanced Grant323113-NETSIGNALEuropean Research Council
    ITN Extrabrain606950 EXTRABRAINEuropean Union FP7
    DFGNot SetGerman Research Foundation
    SFB1089 B03Not SetGerman Research Foundation
    SPP1757Not SetGerman Research Foundation
    HE6949/1Not SetGerman Research Foundation
    HE6949/3Not SetGerman Research Foundation
    ITN EUGliaNot SetEuropean Commission
    Human Frontiers Science ProgramNot SetNot Set
    NRW RückkehrerprogrammNot SetNot Set
  • Academic Unit or School
  • Faculty of Science, Technology, Engineering and Mathematics (STEM)
    Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
  • Copyright Holders
  • © 2018 The Authors
  • Depositing User
  • Igor Kraev

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