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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• Item ORO ID
• 56588
• Item Type
• Journal Item
• ISSN
• 2041-1723
• Project Funding Details

• Funded Project Name	Project ID	Funding Body
  Principal Fellowship	101896	Wellcome Trust
  Principal Fellowship	212251/ Z/18/Z	Wellcome Trust
  Advanced Grant	323113-NETSIGNAL	European Research Council
  ITN Extrabrain	606950 EXTRABRAIN	European Union FP7
  DFG	Not Set	German Research Foundation
  SFB1089 B03	Not Set	German Research Foundation
  SPP1757	Not Set	German Research Foundation
  HE6949/1	Not Set	German Research Foundation
  HE6949/3	Not Set	German Research Foundation
  ITN EUGlia	Not Set	European Commission
  Human Frontiers Science Program	Not Set	Not Set
  NRW Rückkehrerprogramm	Not Set	Not 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