GABA(B) 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(2+) signaling upon stimulation by γ-aminobutyric acid (GABA), resulting in the release of gliotransmitters. GABA-mediated Ca(2+) 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(2+) signaling, especially in young adult astrocytes of the PFC by confocal microscopy. The results show that GABA induces Ca(2+) signaling via the stimulation of the metabotropic GABA(B) receptor in astrocytes. GABA(B) receptor-mediated Ca(2+) signals greatly depend on intracellular Ca(2+) stores rather than on extracellular Ca(2+). Additionally, antagonists of the PLC/IP(3)-signaling cascade significantly reduced GABA(B) receptor-mediated Ca(2+) signaling in astrocytes. Moreover, inhibition of the G(i/o) signaling cascade did not have an effect on GABA(B)receptor-mediated Ca(2+) transients, suggesting that astrocytic GABA(B) receptors in the PFC of adolescent mice are coupled to the G(q)-GPCR signaling pathway exclusively.