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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.

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DOI (Digital Object Identifier) Link: https://doi.org/10.1038/s41467-018-05896-w
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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.

Item Type: Journal Item
Copyright Holders: 2018 The Authors
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/School: Faculty of Science, Technology, Engineering and Mathematics (STEM)
Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Item ID: 56588
Depositing User: Igor Kraev
Date Deposited: 14 Sep 2018 10:31
Last Modified: 21 May 2019 11:30
URI: http://oro.open.ac.uk/id/eprint/56588
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