GABA 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 networks is crucial as the disruption leads to impairments in PFC-associated behavior and pathologies. Astrocytes express specific GABA receptors that mediate intracellular Ca signaling upon stimulation by γ-aminobutyric acid (GABA), resulting in the release of gliotransmitters. GABA-mediated Ca signaling in astrocytes has been of great interest in the past; however, especially, the signaling pathway greatly varies across brain regions and from development to adulthood. Here we took advantage of GLAST-promoter driven GCaMP6s expression in astrocytes to study GABAergic Ca signaling, especially in young adult astrocytes of the PFC by confocal microscopy. The results show that GABA induces Ca signaling via the stimulation of the metabotropic GABA receptor in astrocytes. GABA receptor-mediated Ca signals greatly depend on intracellular Ca stores rather than on extracellular Ca. Additionally, antagonists of the PLC/IP-signaling cascade significantly reduced GABA receptor-mediated Ca signaling in astrocytes. Moreover, inhibition of the G signaling cascade did not have an effect on GABAreceptor-mediated Ca transients, suggesting that astrocytic GABA receptors in the PFC of adolescent mice are coupled to the G-GPCR signaling pathway exclusively.