Calcium-Dependent Signaling in Astrocytes: Downstream Mechanisms and Implications for Cognition

Astrocytes are glial cells recognized for their diverse roles in regulating brain circuit structure and function. They can sense and adapt to changes in the microenvironment due to their unique structural and biochemical properties. A key aspect of astrocytic function involves calcium (Ca²⁺)-dependent signaling, which serves as a fundamental mechanism for their interactions with neurons and other cells in the brain. However, while significant progress has been made in understanding the spatio-temporal properties of astrocytic Ca²⁺ signals, the downstream molecular pathways and exact mechanisms through which astrocytes decode these signals to regulate homeostatic and physiological processes remain poorly understood. To address this topic, we review here the available literature on the sources of intracellular Ca²⁺, as well as its downstream mechanisms and signaling pathways. We review the well-studied Ca²⁺-dependent exocytosis but draw attention to additional intracellular Ca²⁺-dependent mechanisms that are less understood and are, most likely, highly influential for many other cellular functions. Finally, we review how intracellular Ca²⁺ is thought to underlie neuron-astrocyte signaling in brain regions involved in cognitive processing.