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Disentangling astroglial physiology with a realistic cell model in silico
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Disentangling astroglial physiology with a realistic cell model in silico
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Journal Article
Disentangling astroglial physiology with a realistic cell model in silico
2018
Overview
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 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 Ca
2+
buffers affect Ca
2+
waves and why the classical Ca
2+
sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca
2+
imaging.
Astrocytes have gained increasing attention for their roles in regulating neural circuits via neurotransmitter uptake, K + buffering, and ability to signal via Ca
2 +
transients. Here, the authors develop a computational modelling environment for astrocytes, akin to the NEURON environment, called ASTRO.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
