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

Abstract

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 γ-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 GABA_B receptor in astrocytes. GABA_B 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 GABA_B receptor-mediated Ca²⁺ signaling in astrocytes, suggesting that astrocytic GABA_B receptors in the PFC are coupled to the G_q-GPCR signaling pathway.