Biophysical underpinning of astroglial physiology probed with realistic cell models
Leonid P. Savtchenko, Lucie Bard, Thomas P. Jensen, James P. Reynolds, Igor Kraev, Mikola Medvedev, Michael G. Stewart, Christian Henneberger, Dmitri A. Rusakov
Received: 16th May 18
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 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 Ca2+ buffering properties, and some basic relationships between free Ca2+ dynamics and experimental readout of fluorescent Ca2+ indicators.
Read in full at bioRxiv.
This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.