Disentangling astroglial physiology with a realistic cell model in silico

Leonid P. Savtchenko (), Lucie Bard, Thomas P. Jensen, James P. Reynolds, Igor Kraev, Nikolay Medvedev, Michael G. Stewart, Christian Henneberger and Dmitri A. Rusakov ()
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Leonid P. Savtchenko: UCL Institute of Neurology, University College London
Lucie Bard: UCL Institute of Neurology, University College London
Thomas P. Jensen: UCL Institute of Neurology, University College London
James P. Reynolds: UCL Institute of Neurology, University College London
Igor Kraev: The Open University
Nikolay Medvedev: The Open University
Michael G. Stewart: The Open University
Christian Henneberger: UCL Institute of Neurology, University College London
Dmitri A. Rusakov: UCL Institute of Neurology, University College London

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-05896-w

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