Synaptic plasticity through activation of GluA3-containing AMPA-receptors
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.
Article and author information
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.
Metrics
-
- 3,647
- views
-
- 718
- downloads
-
- 56
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Determining the presence and frequency of neural oscillations is essential to understanding dynamic brain function. Traditional methods that detect peaks over 1/f noise within the power spectrum fail to distinguish between the fundamental frequency and harmonics of often highly non-sinusoidal neural oscillations. To overcome this limitation, we define fundamental criteria that characterize neural oscillations and introduce the cyclic homogeneous oscillation (CHO) detection method. We implemented these criteria based on an autocorrelation approach to determine an oscillation’s fundamental frequency. We evaluated CHO by verifying its performance on simulated non-sinusoidal oscillatory bursts and validated its ability to determine the fundamental frequency of neural oscillations in electrocorticographic (ECoG), electroencephalographic (EEG), and stereoelectroencephalographic (SEEG) signals recorded from 27 human subjects. Our results demonstrate that CHO outperforms conventional techniques in accurately detecting oscillations. In summary, CHO demonstrates high precision and specificity in detecting neural oscillations in time and frequency domains. The method’s specificity enables the detailed study of non-sinusoidal characteristics of oscillations, such as the degree of asymmetry and waveform of an oscillation. Furthermore, CHO can be applied to identify how neural oscillations govern interactions throughout the brain and to determine oscillatory biomarkers that index abnormal brain function.
-
- Neuroscience
Female sexual receptivity is essential for reproduction of a species. Neuropeptides play the main role in regulating female receptivity. However, whether neuropeptides regulate female sexual receptivity during the neurodevelopment is unknown. Here, we found the peptide hormone prothoracicotropic hormone (PTTH), which belongs to the insect PG (prothoracic gland) axis, negatively regulated virgin female receptivity through ecdysone during neurodevelopment in Drosophila melanogaster. We identified PTTH neurons as doublesex-positive neurons, they regulated virgin female receptivity before the metamorphosis during the third-instar larval stage. PTTH deletion resulted in the increased EcR-A expression in the whole newly formed prepupae. Furthermore, the ecdysone receptor EcR-A in pC1 neurons positively regulated virgin female receptivity during metamorphosis. The decreased EcR-A in pC1 neurons induced abnormal morphological development of pC1 neurons without changing neural activity. Among all subtypes of pC1 neurons, the function of EcR-A in pC1b neurons was necessary for virgin female copulation rate. These suggested that the changes of synaptic connections between pC1b and other neurons decreased female copulation rate. Moreover, female receptivity significantly decreased when the expression of PTTH receptor Torso was reduced in pC1 neurons. This suggested that PTTH not only regulates female receptivity through ecdysone but also through affecting female receptivity associated neurons directly. The PG axis has similar functional strategy as the hypothalamic–pituitary–gonadal axis in mammals to trigger the juvenile–adult transition. Our work suggests a general mechanism underlying which the neurodevelopment during maturation regulates female sexual receptivity.