The inhibitory neurotransmitter GABA evokes long-lasting Ca(2+) oscillations in cortical astrocytes.
Studies over the last decade provided evidence that in a dynamic interaction with neurons glial cell astrocytes contribut to fundamental phenomena in the brain. Most of the knowledge on this derives, however, from studies monitoring the astrocyte Ca(2+) 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 the astrocyte response to GABA in the mouse somatosensory and temporal cortex was studied. In slices from developing (P15-20) and adult (P30-60) mice, it was found that in a subpopulation of astrocytes GABA evoked somatic Ca(2+) oscillations. This response was mediated by GABAB receptors and involved both Gi/o protein and inositol 1,4,5-trisphosphate (IP3 ) signalling pathways. In vivo experiments from young adult mice, revealed that also cortical astrocytes in the living brain exibit GABAB receptor-mediated Ca(2+) elevations. At all astrocytic processes tested, local GABA or Baclofen brief applications induced long-lasting Ca(2+) oscillations, suggesting that all astrocytes have the potential to respond to GABA. Finally, in patch-clamp recordings it was found that Ca(2+) oscillations induced by Baclofen evoked astrocytic glutamate release and slow inward currents (SICs) in pyramidal cells from wild type but not IP3 R2(-/-) mice, in which astrocytic GABAB receptor-mediated Ca(2+) elevations are impaired. These data suggest that cortical astrocytes in the mouse brain can sense the activity of GABAergic interneurons and through their specific recruitment contribut to the distinct role played on the cortical network by the different subsets of GABAergic interneurons.
Neuroscience Institute, National Research Council (CNR) and Department of Biomedical Sciences, University of Padova, via U.Bassi 58/B, Padova, 35121, Italy.
Letizia
L
Mariotti
Neuroscience Institute, National Research Council (CNR) and Department of Biomedical Sciences, University of Padova, via U.Bassi 58/B, Padova, 35121, Italy.
Gabriele
G
Losi
Neuroscience Institute, National Research Council (CNR) and Department of Biomedical Sciences, University of Padova, via U.Bassi 58/B, Padova, 35121, Italy.
Michele
M
Sessolo
Neuroscience Institute, National Research Council (CNR) and Department of Biomedical Sciences, University of Padova, via U.Bassi 58/B, Padova, 35121, Italy.
Iacopo
I
Marcon
Neuroscience Institute, National Research Council (CNR) and Department of Biomedical Sciences, University of Padova, via U.Bassi 58/B, Padova, 35121, Italy.
Giorgio
G
Carmignoto
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D027341:Excitatory Amino Acid Transporter 1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D018682:GABA Agents / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000187:drug effects* / Q000235:genetics; D059906:Neuroimaging; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D012235:Rhodamines / Q000493:pharmacokinetics; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018683:Excitatory Amino Acid Agents; D027341:Excitatory Amino Acid Transporter 1; D018682:GABA Agents; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012235:Rhodamines; C493393:Slc1a3 protein, mouse; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; C050829:sulforhodamine 101; D002118:Calcium
GABAB receptor; calcium; somatosensory cortex; temporal cortex