The inhibitory neurotransmitter GABA evokes long-lasting Ca2+ oscillations in cortical astrocytes

Studies over the last decade provided evidence that in a dynamic interaction with neurons glial cell astrocytes contribute to fundamental phenomena in the brain. Most of our knowledge on this derives, however, from studies monitoring the astrocyte Ca2+ response to glutamate. Whether astrocytes can similarly respond to other neurotransmitters, including the inhibitory neurotransmitter GABA, is relatively unexplored. By using confocal and two photon laser-scanning microscopy we studied the astrocyte response to GABA in the mouse somatosensory and temporal cortex. In slices from developing (P15-20) and young adult (P30-60) mice, we found that in a subpopulation of astrocytes GABA evoked somatic Ca2+ oscillations. This response was mediated by GABAB receptors and involved both Gi/o protein and inositol 1,4,5-trisphosphate (IP3) signaling pathways. In vivo experiments from young adult mice, revealed that also cortical astrocytes in the living brain exibit GABAB receptor-mediated Ca2+ elevations. At all astrocytic processes tested, local GABA or baclofen brief applications induced long-lasting Ca2+ oscillations, suggesting that all astrocytes have the potential to respond to GABA. Finally, in patch-clamp recordings we found that Ca2+ oscillations induced by baclofen evoked astrocytic glutamate release and slow inward currents in pyramidal cells from wild type but not IP3R2 -/- mice, in which astrocytic GABAB receptor-mediated Ca2+ elevations are impaired. Our data suggest that cortical astrocytes in the mouse brain can sense the activity of GABAergic interneurons and through their specific recruitment contribute to the distinct role played on the cortical network by the different subsets of GABAergic interneurons.