Disentangling astroglial physiology with a realistic cell model in silico.

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.