Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K + and generate Ca 2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the nanoscopic, sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we have systematically evaluated the multi-scale morphology of protoplasmic astroglia to construct a realistic multi-compartmental cell model that can be biophysically interrogated in NEURON computational environment. This approach has been implemented as an astrocyte-model builder ASTRO. As a proof of concept, we explored a hippocampal astrocyte reconstructed in silico against a battery of physiological and imaging experiments. This exploration has unveiled some basic features of astroglial physiology inaccessible empirically, such as the characteristic length of membrane voltage propagation, membrane effects of local glutamate transport, spatiotemporal dynamics of intracellular K + redistribution, key Ca 2+ buffering properties, and some basic relationships between free Ca 2+ dynamics and experimental readout of fluorescent Ca 2+ indicators.
Biophysical underpinning of astroglial physiology probed with realistic cell models
L. Savtchenko,Lucie Bard,Thomas P Jansen,James P. Reynolds,I. Kraev,M. Medvidov,M. Stewart,C. Henneberger,D. Rusakov
Published 2018 in bioRxiv
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- Publication year
2018
- Venue
bioRxiv
- Publication date
2018-06-02
- Fields of study
Biology, Physics, Chemistry
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