title: Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.
abstract: Interneurons are critical for proper neural network function and can activate Ca2+signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibitionvspotentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAAreceptors, potentiation involved astrocyte GABABreceptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABABreceptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.
authors.affiliation: Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain.
authors.forename: Gertrudis
authors.identifier: 0000-0001-5924-9175
authors.initials: G
authors.lastname: Perea
authors.affiliation: Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain.|Cellular and Systems Neurobiology, Systems Biology Program, Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gómez
authors.affiliation: Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Mederos
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, United States.
authors.forename: Ana
authors.initials: A
authors.lastname: Covelo
authors.affiliation: Albacete Science and Technology Park, Institute for Research in Neurological Disabilities, University of Castilla-La Mancha, Albacete, Spain.|Department of Neurophysiology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
authors.forename: Jesús J
authors.initials: JJ
authors.lastname: Ballesteros
authors.affiliation: Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Schlosser
authors.affiliation: Consejo Superior de Investigaciones Científicas, Instituto Cajal, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Vivanco
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, United States.
authors.forename: Mario
authors.initials: M
authors.lastname: Martín-Fernández
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, United States.
authors.forename: Ruth
authors.initials: R
authors.lastname: Quintana
authors.affiliation: Department of Neurophysiology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
authors.forename: Abdelrahman
authors.initials: A
authors.lastname: Rayan
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, United States.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Díez
authors.affiliation: Center of Neurobiology and Brain Plasticity, Institute of Physiology, Faculty of Science, Universidad de Valparaíso, Valparaiso, Chile.
authors.forename: Marco
authors.initials: M
authors.lastname: Fuenzalida
authors.affiliation: Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, United States.
authors.forename: Amit
authors.identifier: 0000-0001-7948-4498
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, United States.
authors.forename: Dwight E
authors.initials: DE
authors.lastname: Bergles
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Bettler
authors.affiliation: Department of Neurophysiology, Faculty of Medicine, Ruhr University Bochum, Bochum, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Manahan-Vaughan
authors.affiliation: Albacete Science and Technology Park, Institute for Research in Neurological Disabilities, University of Castilla-La Mancha, Albacete, Spain.
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Martín
authors.affiliation: Molecular Physiology, Center for Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
authors.affiliation: Department of Neuroscience, University of Minnesota, Minneapolis, United States.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Araque
mesh_terms: D000200:Action Potentials; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D018683:Excitatory Amino Acid Agents / Q000378:metabolism*; D018682:GABA Agents / Q000378:metabolism*; D006624:Hippocampus / Q000502:physiology*; D007395:Interneurons / Q000502:physiology*; D018345:Mice, Knockout; D009415:Nerve Net; D016571:Neural Networks, Computer; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism
chemical_list: D018683:Excitatory Amino Acid Agents; D018682:GABA Agents; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate
keywords: astrocytes; interneuron; mouse; neuron-glia interactions; neuroscience; rat; synaptic plasticity