Extracellular Calcium Influx Pathways in Astrocyte Calcium Microdomain Physiology

Astrocytes are complex glial cells that play many essential roles in the brain, including the fine-tuning of synaptic activity and blood flow. These roles are linked to fluctuations in intracellular Ca²⁺ within astrocytes. Recent advances in imaging techniques have identified localized Ca²⁺ transients within the fine processes of the astrocytic structure, which we term microdomain Ca²⁺ events. These Ca²⁺ transients are very diverse and occur under different conditions, including in the presence or absence of surrounding circuit activity. This complexity suggests that different signalling mechanisms mediate microdomain events which may then encode specific astrocyte functions from the modulation of synapses up to brain circuits and behaviour. Several recent studies have shown that a subset of astrocyte microdomain Ca²⁺ events occur rapidly following local neuronal circuit activity. In this review, we consider the physiological relevance of microdomain astrocyte Ca²⁺ signalling within brain circuits and outline possible pathways of extracellular Ca²⁺ influx through ionotropic receptors and other Ca²⁺ ion channels, which may contribute to astrocyte microdomain events with potentially fast dynamics.