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 language | English (US) |
|---|---|
| Article number | e20362 |
| Journal | eLife |
| Volume | 5 |
| Issue number | DECEMBER2016 |
| DOIs | |
| State | Published - Dec 24 2016 |
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ASJC Scopus subject areas
- Neuroscience(all)
- Medicine(all)
- Immunology and Microbiology(all)
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Activity-dependent switch of gabaergic inhibition into glutamatergic excitation in astrocyte-neuron networks
AU - Perea, Gertrudis
AU - Gómez, Ricardo
AU - Mederos, Sara
AU - Covelo, Ana
AU - Ballesteros, Jesús J.
AU - Schlosser, Laura
AU - Hernández-Vivanco, Alicia
AU - Martín-Fernández, Mario
AU - Quintana, Ruth
AU - Rayan, Abdelrahman
AU - Díez, Adolfo
AU - Fuenzalida, Marco
AU - Agarwal, Amit
AU - Bergles, Dwight E
AU - Bettler, Bernhard
AU - Manahan-Vaughan, Denise
AU - Martín, Eduardo D.
AU - Kirchhoff, Frank
AU - Araque, Alfonso
PY - 2016/12/24
Y1 - 2016/12/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85010644425&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85010644425&partnerID=8YFLogxK
U2 - 10.7554/eLife.20362
DO - 10.7554/eLife.20362
M3 - Article
C2 - 28012274
AN - SCOPUS:85010644425
VL - 5
JO - eLife
JF - eLife
SN - 2050-084X
IS - DECEMBER2016
M1 - e20362
ER -