GABAB receptors mediate intracellular calcium release in astrocytes of the prefrontal cortex

The prefrontal cortex (PFC) is a cortical brain region whose multifaceted functions are based on a complex interplay between excitatory pyramidal neurons, inhibitory GABAergic interneurons and astrocytes maintaining a fine-tuned excitation/inhibition balance (E/I balance). The regulation of the E/I balance in cortical network is crucial as the disruption leads to impairments in PFC-associated behavior and pathologies. Astrocytes express specific GABA receptors that mediate intracellular Ca2+ signaling upon stimulation by {gamma}-aminobutyric acid (GABA), resulting in the release of gliotransmitters directly impacting information processing. However, the signaling pathway leading to GABA-induced Ca2+ signaling in astrocytes of the PFC is not well understood. Here we took advantage of GLAST-promoter driven GCaMP6s expression in astrocytes to study GABAergic Ca2+ signaling in PFC astrocytes by confocal microscopy. The results show that GABA induces Ca2+ signaling via the stimulation of the metabotropic GABAB receptor in astrocytes. GABAB receptor-mediated Ca2+ signals greatly depend on intracellular Ca2+ stores rather than on extracellular Ca2+. Additionally, antagonists of the PLC/IP3-signaling cascade significantly reduced GABAB receptor-mediated Ca2+ signaling in astrocytes, suggesting that astrocytic GABAB receptors in the PFC are coupled to the Gq-GPCR signaling pathway.