Astrocyte-specific Ca²⁺ activity: Mechanisms of action, experimental tools, and roles in ethanol-induced dysfunction

Astrocytes are a subtype of non-neuronal glial cells that reside in the central nervous system. Astrocytes have extensive peripheral astrocytic processes that ensheathe synapses to form the tripartite synapse. Through a multitude of pathways, astrocytes can influence synaptic development and structural maturation, respond to neuronal signals, and modulate synaptic transmission. Over the last decade, strong evidence has emerged demonstrating that astrocytes can influence behavioral outcomes in various animal models of cognition. However, the full extent of how astrocytes influence brain function is still being revealed. Astrocyte calcium (Ca²⁺) signaling has emerged as an important driver of astrocyte-neuronal communication allowing intricate crosstalk through mechanisms that are still not fully understood. Here, we will review the field's current understanding of astrocyte Ca²⁺ signaling and discuss the sophisticated state-of-the-art tools and approaches used to continue unraveling astrocytes' interesting role in brain function. Using the field of pre-clinical ethanol (EtOH) studies in the context of alcohol use disorder, we focus on how these novel approaches have helped to reveal an important role for astrocyte Ca²⁺ function in regulating EtOH consumption and how astrocyte Ca²⁺ dysfunction contributes to the cognitive deficits that emerge after EtOH exposure in a rodent model.