Modeling the Contributions of Ca2+ Flows to Spontaneous Ca2+ Oscillations and Cortical Spreading Depression-Triggered Ca2+ Waves in Astrocyte Networks

Astrocytes participate in brain functions through Ca²⁺ signals, including Ca²⁺ waves and Ca²⁺ oscillations. Currently the mechanisms of Ca²⁺ signals in astrocytes are not fully clear. Here, we present a computational model to specify the relative contributions of different Ca²⁺ flows between the extracellular space, the cytoplasm and the endoplasmic reticulum of astrocytes to the generation of spontaneous Ca²⁺ oscillations (CASs) and cortical spreading depression (CSD)-triggered Ca²⁺ waves (CSDCWs) in a one-dimensional astrocyte network. This model shows that CASs depend primarily on Ca²⁺ released from internal stores of astrocytes, and CSDCWs depend mainly on voltage-gated Ca²⁺ influx. It predicts that voltage-gated Ca²⁺ influx is able to generate Ca²⁺ waves during the process of CSD even after depleting internal Ca²⁺ stores. Furthermore, the model investigates the interactions between CASs and CSDCWs and shows that the pass of CSDCWs suppresses CASs, whereas CASs do not prevent the generation of CSDCWs. This work quantitatively analyzes the generation of astrocytic Ca²⁺ signals and indicates different mechanisms underlying CSDCWs and non-CSDCWs. Research on the different types of Ca²⁺ signals might help to understand the ways by which astrocytes participate in information processing in brain functions.