Topology Drives Calcium Wave Propagation in 3D Astrocyte Networks

Abstract

Glial cells are non-neuronal cells that constitute the majority of cells in the human brain and significantly modulate information processing via permanent cross-talk with the neurons. Astrocytes are also themselves inter-connected as networks and communicate via chemical wave propagation. How astrocyte wave propagation depends on the local properties of the astrocyte networks is however unknown. In the present work, we investigate the influence of the characteristics of the network topology on wave propagation. Using a model of realistic astrocyte networks (>1000 cells embedded in a 3D space), we show that the major classes of propagations reported experimentally can be emulated by a mere variation of the topology. Our study indicates that calcium wave propagation is favored when astrocyte connections are limited by the distance between the cells, which means that propagation is better when the mean-shortest path of the network is larger. This unusual property sheds new light on consistent reports that astrocytes in vivo tend to restrict their connections to their nearest neighbors. IntroductionMore than half of the cells in the human brain are glial cells. These non-neuronal cells have recently been evidenced to play a direct active role in information transfer in the brain. Indeed astrocytes (the main subtype of glial cells) not only react to but can also modulate synaptic communication between neurons [8,16]. Astrocytes are also themselves inter-connected as networks on which chemical waves propagate [9]. Understanding astrocyte-astrocyte and astrocyte-neuron cross-talks is thus crucial to understanding the brain [8]. Chemical communication within astrocyte networks is characterized as elevations of intracellular calcium that propagate from cell to cell though protein channels called gap-junctions channels (GJC). However,

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“…Astrocytes in vivo exist within a 3D matrix compared to in vitro astrocytes, which grow on a flat surface that restricts diffusion of extracellular signals and gap-junction connections to cells within a 2D plane. Lallouette et al demonstrated in computational models of astrocytic Ca 2+ signalling that different types of intercellular Ca 2+ signalling, specifically regenerative long-range Ca 2+ waves and localised synchrony of Ca 2+ transients, could be replicated simply by changing the structure of the connections between cells [37].…”

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“…In the case of Figure 2E, for example, stimulated FM-encoding cells could trigger Ca 2+ signaling in neighboring cells in a regenerative fashion thus extending their tuned response in space. On the other hand, AFM cells, acting as propagation barriers, could shape the borders of this tuned response, eventually drawing the topographical features of the ensuing functional map (Lallouette and Berry, 2012). …”

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