Loose excitation–secretion coupling in astrocytes

Abstract

Astrocytes play an important housekeeping role in the central nervous system. Additionally, as secretory cells, they actively participate in cell-to-cell communication, which can be mediated by membrane-bound vesicles. The gliosignaling molecules stored in these vesicles are discharged into the extracellular space after the vesicle membrane fuses with the plasma membrane. This process is termed exocytosis, regulated by SNARE proteins, and triggered by elevations in cytosolic calcium levels, which are necessary and sufficient for exocytosis in astrocytes. For astrocytic exocytosis, calcium is sourced from the intracellular endoplasmic reticulum (ER) store, although its entry from the extracellular space contributes to cytosolic calcium dynamics in astrocytes. Here, we discuss calcium management in astrocytic exocytosis and the properties of the membrane-bound vesicles that store gliosignaling molecules, including the vesicle fusion machinery and kinetics of vesicle content discharge. In astrocytes, the delay between the increase in cytosolic calcium activity and the discharge of secretions from the vesicular lumen is orders of magnitude longer than that in neurons. This relatively loose excitation-secretion coupling is likely tailored to the participation of astrocytes in modulating neural network processing.

Astrocytic signaling supports hippocampal–prefrontal theta synchronization and cognitive function

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Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness

“…Indeed, the time course of astrocytic activity is several orders of magnitude slower than neurons (Vardjan et al, 2015). This makes astrocytes good candidates to receive, integrate and relay information about the neuromodulatory state of the brain, such that their impact on neuronal and brain function has become increasingly relevant in the scope of behavioral states (Chen et al, 2012; Ding et al, 2013; Hirase et al, 2014; Panatier at al., 2006; Schmitt et al, 2012; Paukert et al, 2014).…”