Differential subcellular targeting of glutamate receptor subtypes during homeostatic synaptic plasticity
Open accessAbstract
Homeostatic processes are believed to contribute to the stability of neuronal networks that are perpetually influenced by Hebbian forms of synaptic plasticity. Whereas the rules governing the targeting and trafficking of AMPA and NMDA subtypes of glutamate receptors during rapid Hebbian LTP have been extensively studied, those that are operant during homeostatic forms of synaptic strengthening are less well understood. Here, we used biochemical, biophysical, and pharmacological approaches to investigate glutamate receptor regulation during homeostatic synaptic plasticity. We show in rat organotypic hippocampal slices that prolonged network silencing induced a robust surface upregulation of GluA2-lacking AMPARs, not only at synapses, but also at extrasynaptic dendritic and somatic regions of CA1 pyramidal neurons. We also detected a shift in NMDAR subunit composition that, in contrast to the cell-wide surface delivery of GluA2-lacking AMPARs, occurred exclusively at synapses. The subunit composition and subcellular distribution of AMPARs and NMDARs are therefore distinctly regulated during homeostatic synaptic plasticity. Thus, because subunit composition dictates key channel properties, such as agonist affinity, gating kinetics, and calcium permeability, the homeostatic synaptic process transcends the simple modulation of synaptic strength by also regulating the signaling and integrative properties of central synapses.
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TTX-induced homeostatic scaling-up in cultured neurons increases GluA1 protein expression as well as surface and synaptic levels of CP-AMPARs (GluA1 homomers) and GluA1/2 heteromers, but not GluA3-containing AMPARs.
“TTX-induced homeostatic scaling-up in cultured neurons increases GluA1 protein expression as well as surface and synaptic levels of CP-AMPARs (GluA1 homomers) and GluA1/2 heteromers but not in GluA3-containing AMPARs (Figure 3) (Diering et al., 2014, Soares et al., 2013, Tan et al., 2015, Kim and Ziff, 2014, Hu et al., 2010).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Soares et al., 2013
In “Homeostatic upregulation of synaptic GluA2-lacking AMPARs” (page unavailable), the paper reports increased total and surface GluA1 after TTX treatment and evidence of synaptic GluA2-lacking AMPARs in organotypic hippocampal slices. It does not establish that these receptors are specifically GluA1 homomers, that GluA1/2 heteromers increase, or that GluA3-containing AMPARs do not increase. The claim also describes cultured neurons more broadly than the slice preparation studied. (LLM, conf=0.88)
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Cites
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- Authors
- Soares, C., Lee, K. F. H., Nassrallah, W., & Béïque, J.-C.
- Affiliations
- University of Ottawa (CA)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-08-14
- Volume
- 33
- Issue
- 33
- Pages
- 13547-13559
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6705149
- OpenAlex
- W2078166071
- Cited by
- 80
- References
- 10
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 2 · 2021: 5 · 2020: 8 · 2019: 5 · 2018: 12 · 2017: 9 · 2016: 8 · 2015: 6 · 2014: 7 · 2013: 1
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Heart and Stroke Foundation of Canada
- Canadian Institutes of Health Research
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- homeostatic plasticity, glutamate receptors, AMPA receptors, NMDA receptor, subcellular targeting, receptor trafficking, extrasynaptic receptors, CA1 pyramidal neurons, hippocampus, NMDA receptor subunit composition, synaptic homeostasis
- MeSH terms
- Animals, Female, Hippocampus, Homeostasis, Male, Neuronal Plasticity, Organ Culture Techniques, Synapses, Blotting, Western, Rats, Sprague-Dawley, Receptors, AMPA, Patch-Clamp Techniques, Excitatory Postsynaptic Potentials, Protein Transport, Rats
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