Astrocyte Networks and Intercellular Calcium Propagation

Abstract

Astrocytes organize in complex networks through connections by gap junction channels that are regulated by extra- and intracellular signals. Calcium signals generated in individual cells can propagate across these networks in the form of intercellular calcium waves, mediated by diffusion of second messengers molecules such as inositol 1,4,5-trisphosphate. The mechanisms underpinning the large variety of spatiotemporal patterns of propagation of astrocytic calcium waves, however, remains a matter of investigation. In the last decade, awareness has grown on the morphological diversity of astrocytes as well as their connections in networks, which seem dependent on the brain area, developmental stage, and the ultrastructure of the associated neuropile. It is speculated that this diversity underpins an equal functional variety, but the current experimental techniques are limited in supporting this hypothesis because they do not allow to resolve the exact connectivity of astrocyte networks in the brain. With this aim, we present a general framework to model intercellular calcium wave propagation in astrocyte networks and use it to specifically investigate how different network topologies could influence shape, frequency, and propagation of these waves.