Photolysis of Caged Ca²⁺ But Not Receptor-Mediated Ca²⁺ Signaling Triggers Astrocytic Glutamate Release

Abstract

Astrocytes in hippocampal slices can dynamically regulate synaptic transmission in a process mediated by increases in intracellular Ca²⁺. However, it is debated whether astrocytic Ca²⁺ signals result in release of glutamate. We here compared astrocytic Ca²⁺ signaling triggered by agonist exposure versus photolysis side by side. Using transgenic mice in which astrocytes selectively express the MrgA1 receptor, we found that receptor-mediated astrocytic Ca²⁺ signaling consistently triggered neuronal hyperpolarization and decreased the frequency of miniature excitatory postsynaptic currents (EPSCs). In contrast, photolysis of caged Ca²⁺ (o-nitrophenyl–EGTA) in astrocytes led to neuronal depolarization and increased the frequency of mEPSCs through a metabotropic glutamate receptor-mediated pathway. Analysis of transgenic mice in which astrocytic vesicular release is suppressed (dominant-negative SNARE mice) and pharmacological manipulations suggested that glutamate is primarily released by opening of anion channels rather than exocytosis. Combined, these studies show that photolysis but not by agonists induced astrocytic Ca²⁺ signaling triggers glutamate release.