Synaptic plasticity through activation of GluA3-containing AMPA-receptors
- The Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Netherlands
Abstract
Excitatory synaptic transmission is mediated by AMPA-type glutamate receptors (AMPARs). In CA1 pyramidal neurons of the hippocampus two types of AMPARs predominate: those that contain subunits GluA1 and GluA2 (GluA1/2), and those that contain GluA2 and GluA3 (GluA2/3). Whereas subunits GluA1 and GluA2 have been extensively studied, the contribution of GluA3 to synapse physiology has remained unclear. Here we show in mice that GluA2/3s are in a low-conductance state under basal conditions, and although present at synapses they contribute little to synaptic currents. When intracellular cyclic AMP (cAMP) levels rise, GluA2/3 channels shift to a high-conductance state, leading to synaptic potentiation. This cAMP-driven synaptic potentiation requires the activation of both protein kinase A (PKA) and the GTPase Ras, and is induced upon the activation of β-adrenergic receptors. Together, these experiments reveal a novel type of plasticity at CA1 hippocampal synapses that is expressed by the activation of GluA3-containing AMPARs.
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Author details
Funding
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (821.02.016)
- Helmut W Kessels
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (864.11.014)
- Helmut W Kessels
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 experiments were conducted in line with the European guidelines for the care and use of laboratory animals (Council Directive 86/6009/EEC). The experimental protocol was approved by the Animal Experiment Committee of the Royal Netherlands Academy of Arts and Sciences (KNAW).
Copyright
© 2017, Renner 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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Synaptic plasticity through activation of GluA3-containing AMPA-receptors
eLife 6:e25462.
https://doi.org/10.7554/eLife.25462
