Activity-dependent switch of gabaergic inhibition into glutamatergic excitation in astrocyte-neuron networks

Gertrudis Perea, Ricardo Gómez, Sara Mederos, Ana Covelo, Jesús J. Ballesteros, Laura Schlosser, Alicia Hernández-Vivanco, Mario Martín-Fernández, Ruth Quintana, Abdelrahman Rayan, Adolfo Díez, Marco Fuenzalida, Amit Agarwal, Dwight E. Bergles, Bernhard Bettler, Denise Manahan-Vaughan, Eduardo D. Martín, Frank Kirchhoff, Alfonso Araque

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

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 (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (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.

Original languageEnglish (US)
Article numbere20362
JournaleLife
Volume5
Issue numberDECEMBER2016
DOIs
StatePublished - Dec 24 2016

Bibliographical note

Funding Information:
Ministerio de Econom?a y Competitividad Consolider, CSD2010-00045 Gertrudis Perea Ministerio de Econom?a y Competitividad Ramon y Cajal Program, RYC-2012-12014 Gertrudis Perea Ministerio de Econom?a y Competitividad BFU2013-47265R Gertrudis Perea Ministerio de Econom?a y Competitividad BFU2016-75107=P Gertrudis Perea Ministerio de Econom?a y Competitividad Juan de la Cierva Program, JCI-2011-09144 Ricardo G?mez Ministerio de Econom?a y Competitividad IJCI-2014-19136 Ricardo Gomez International Graduate School of Neuroscience IGSN. FNO 01/114 Abdelrahman Rayan Fondo Nacional de Desarrollo Cient?fico y Tecnol?gico 1130614 Marco Fuenzalida Millennium Nucleus NUMIND NC-130011 Marco Fuenzalida Schweizerischer Nationalfonds zur F?rderung der Wissenschaftlichen Forschung 3100 A0-117816 Bernhard Bettler Deutsche Forschungsgemeinschaft SFB 874/B1 Denise Manahan-Vaughan Ministerio de Econom?a y Competitividad BFU2011-26339 Eduardo D Mart?n European Social Fund INCRECyT project Eduardo D Mart?n European Commission FP7-People ITN-237956, EdU-Glia Frank Kirchhoff Deutsche Forschungsgemeinschaft SPP 1757 Frank Kirchhoff Deutsche Forschungsge meinschaft SFB 894 Frank Kirchhoff Human Frontier Science Program RGP0036/2014 Alfonso Araque National Institute of Neurological Disorders and Stroke NIH-NINDS (R01NS097312-01) Alfonso Araque The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© Perea et al.

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