Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks
- Instituto Cajal, Spain
- University of Minnesota, United States
- University of Castilla-La Mancha, Spain
- University of Saarland, Germany
- Ruhr University Bochum, Germany
- Universidad de Valparaíso, Chile
- Johns Hopkins School of Medicine, United States
- University of Basel, Switzerland
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.
Article and author information
Author details
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.
Reviewing Editor
- Marlene Bartos, Albert-Ludwigs-Universität Freiburg, Germany
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).
Version history
- Received: August 5, 2016
- Accepted: December 23, 2016
- Accepted Manuscript published: December 24, 2016 (version 1)
- Version of Record published: January 12, 2017 (version 2)
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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Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks
eLife 5:e20362.
https://doi.org/10.7554/eLife.20362
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Probing memory of a complex visual image within a few hundred milliseconds after its disappearance reveals significantly greater fidelity of recall than if the probe is delayed by as little as a second. Classically interpreted, the former taps into a detailed but rapidly decaying visual sensory or ‘iconic’ memory (IM), while the latter relies on capacity-limited but comparatively stable visual working memory (VWM). While iconic decay and VWM capacity have been extensively studied independently, currently no single framework quantitatively accounts for the dynamics of memory fidelity over these time scales. Here, we extend a stationary neural population model of VWM with a temporal dimension, incorporating rapid sensory-driven accumulation of activity encoding each visual feature in memory, and a slower accumulation of internal error that causes memorized features to randomly drift over time. Instead of facilitating read-out from an independent sensory store, an early cue benefits recall by lifting the effective limit on VWM signal strength imposed when multiple items compete for representation, allowing memory for the cued item to be supplemented with information from the decaying sensory trace. Empirical measurements of human recall dynamics validate these predictions while excluding alternative model architectures. A key conclusion is that differences in capacity classically thought to distinguish IM and VWM are in fact contingent upon a single resource-limited WM store.
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Our ability to recall details from a remembered image depends on a single mechanism that is engaged from the very moment the image disappears from view.
