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 journalArticle

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.

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

Fingerprint

Astrocytes
Neurons
Interneurons
Switches
GABA Agents
Metabotropic Glutamate Receptors
Pyramidal Cells
Glutamate Receptors
GABA-A Receptors
Knockout Mice
Synaptic Transmission
Neuroglia
Synapses
gamma-Aminobutyric Acid
Glutamic Acid
Neural networks

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Perea, G., Gómez, R., Mederos, S., Covelo, A., Ballesteros, J. J., Schlosser, L., ... Araque, A. (2016). Activity-dependent switch of gabaergic inhibition into glutamatergic excitation in astrocyte-neuron networks. eLife, 5(DECEMBER2016), [e20362]. DOI: 10.7554/eLife.20362

Activity-dependent switch of gabaergic inhibition into glutamatergic excitation in astrocyte-neuron networks. / Perea, Gertrudis; Gómez, Ricardo; Mederos, Sara; Covelo, Ana; Ballesteros, Jesús J.; Schlosser, Laura; Hernández-Vivanco, Alicia; Martín-Fernández, Mario; Quintana, Ruth; Rayan, Abdelrahman; Díez, Adolfo; Fuenzalida, Marco; Agarwal, Amit; Bergles, Dwight E.; Bettler, Bernhard; Manahan-Vaughan, Denise; Martín, Eduardo D.; Kirchhoff, Frank; Araque, Alfonso.

In: eLife, Vol. 5, No. DECEMBER2016, e20362, 24.12.2016.

Research output: Contribution to journalArticle

Perea, G, Gómez, R, Mederos, S, Covelo, A, Ballesteros, JJ, Schlosser, L, Hernández-Vivanco, A, Martín-Fernández, M, Quintana, R, Rayan, A, Díez, A, Fuenzalida, M, Agarwal, A, Bergles, DE, Bettler, B, Manahan-Vaughan, D, Martín, ED, Kirchhoff, F & Araque, A 2016, 'Activity-dependent switch of gabaergic inhibition into glutamatergic excitation in astrocyte-neuron networks' eLife, vol 5, no. DECEMBER2016, e20362. DOI: 10.7554/eLife.20362
Perea G, Gómez R, Mederos S, Covelo A, Ballesteros JJ, Schlosser L et al. Activity-dependent switch of gabaergic inhibition into glutamatergic excitation in astrocyte-neuron networks. eLife. 2016 Dec 24;5(DECEMBER2016). e20362. Available from, DOI: 10.7554/eLife.20362
Perea, Gertrudis ; Gómez, Ricardo ; Mederos, Sara ; Covelo, Ana ; Ballesteros, Jesús J. ; Schlosser, Laura ; Hernández-Vivanco, Alicia ; Martín-Fernández, Mario ; Quintana, Ruth ; Rayan, Abdelrahman ; Díez, Adolfo ; Fuenzalida, Marco ; Agarwal, Amit ; Bergles, Dwight E. ; Bettler, Bernhard ; Manahan-Vaughan, Denise ; Martín, Eduardo D. ; Kirchhoff, Frank ; Araque, Alfonso. / Activity-dependent switch of gabaergic inhibition into glutamatergic excitation in astrocyte-neuron networks. In: eLife. 2016 ; Vol. 5, No. DECEMBER2016.
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