On the determinants of calcium wave propagation distance in astrocyte networks: nonlinear gap junctions and oscillatory modes

Abstract

A new paradigm has recently emerged in brain science whereby glial cells should be considered on a par with neurons to understand higher brain functions. In particular, astrocytes, the main type of glial cells in the cortex, are thought to form a gap-junction-coupled syncytium supporting cell-cell communication via propagating calcium (Ca2+) waves. The propagation properties of these waves and their relations to intracellular signalling dynamics are however poorly understood. Here, we propose a novel model of the gap-junctional route for intercellular Ca2+ wave propagation in astrocytes that yields two major predictions. First, we show that long-distance regenerative signalling requires gap junctions with nonlinear transport properties. Second, we show that even with nonlinear gap junctions, long-distance regenerative signalling is favoured when internal Ca2+ dynamics implements frequency modulation-encoding oscillations with pulsating dynamics, while amplitude modulation-encoding dynamics tends to restrict the propagation range. As a result, spatially heterogeneous molecular properties and/or weak couplings give rise to rich spatiotemporal dynamics and support complex propagation behaviours. These results suggest that the large variability of the wave propagation range that is consistently reported by experimental studies, is a result of the association of nonlinear gap junctions with heterogeneous astrocyte populations and/or low coupling

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