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 (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.
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Funding
Ministerio de Economía y Competitividad
- Gertrudis Perea
- Ricardo Gómez
European Commission
- Frank Kirchhoff
- Alfonso Araque
Deutsche Forschungsgemeinschaft
- Denise Manahan-Vaughan
- Frank Kirchhoff
Human Frontier Science Program
- 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.
Ethics
Animal experimentation: All the procedures for handling and sacrificing animals followed the European Commission guidelines for the welfare of experimental animals (2010/63/EU), US National Institutes of Health and the Institutional Animal Care and Use Committee at the University of Minnesota (USA). The use of astrocyte-specific GABBR1 knockout mice was approved by the Saarland state´s "Landesamt fÃ1/4r Gesundheit und Verbraucherschutz" in SaarbrÃ1/4cken/Germany (animal license number 72/2010).
Copyright
© 2016, Perea et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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