Revisiting astrocytic calcium signaling in the brain

Abstract

Astrocytes, characterized by complex spongiform morphology, participate in various physiological processes, and abnormal changes in their calcium (Ca²⁺) signaling are implicated in central nervous system disorders. However, medications targeting the control of Ca²⁺ have fallen short of the anticipated therapeutic outcomes in clinical applications. This underscores the fact that our comprehension of this intricate regulation of calcium ions remains considerably incomplete. In recent years, with the advancement of Ca²⁺ labeling, imaging, and analysis techniques, Ca²⁺ signals have been found to exhibit high specificity at different spatial locations within the intricate structure of astrocytes. This has ushered the study of Ca²⁺ signaling in astrocytes into a new phase, leading to several groundbreaking research achievements. Despite this, the comprehensive understanding of astrocytic Ca²⁺ signaling and their implications remains challenging area for future research.

Keywords: Astrocyte; Ca2+ signaling; Central nervous system; Ion channel; Synapse.

Fig. 1

Astrocytes present a complex morphological appearance. Schematic representation of the astrocyte structure.

Fig. 2

Different Ca²⁺ channels exist in the cell and organelle membranes. Ca²⁺ channels are expressed on both the plasma membrane and the membrane of organelles, as discussed in this review. GPCRs: G-protein coupled metabotropic receptors, PLC: phospholipase C, IP₃R: inositol triphosphate receptor, MAM: mitochondria-associated ER membranes, MCU: mitochondrial Ca²⁺ uniporter, mPTP: mitochondrial permeability transition pore, VGCC: voltage-gated Ca²⁺ channel, TRP: transient receptor potential channels, P2XR: P2X receptors.

Fig. 3

Three modes of interaction between neurons and astrocytes. (a) Ca²⁺ events in perisynaptic astrocytic leaflets induce the release of signaling molecules that affect neuronal excitability, synaptic plasticity, and transmission. (b) Astrocytic Ca²⁺ signaling involves the territories of multiple synapses, which affect their plasticity/ activity. (c) Ca²⁺ events propagate through the astrocytic network and control information processing throughout the network of neurons.