Format

Send to

Choose Destination
Nat Commun. 2018 Sep 3;9(1):3554. doi: 10.1038/s41467-018-05896-w.

Disentangling astroglial physiology with a realistic cell model in silico.

Author information

1
UCL Institute of Neurology, University College London, London, WC1N 3BG, UK. skaalsa@ucl.ac.uk.
2
UCL Institute of Neurology, University College London, London, WC1N 3BG, UK.
3
The Open University, Milton Keynes, MK7 6AA, UK.
4
Institute of Cellular Neurosciences, University of Bonn, Bonn, 53105, Germany.
5
German Center of Neurodegenerative Diseases (DZNE), Bonn, 53127, Germany.
6
UCL Institute of Neurology, University College London, London, WC1N 3BG, UK. d.rusakov@ucl.ac.uk.

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.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center