Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity
Open accessAbstract
Synaptic activity regulates the postsynaptic accumulation of AMPA receptors over timescales ranging from minutes to days. Indeed, the regulated trafficking and mobility of GluR1 AMPA receptors underlies many forms of synaptic potentiation at glutamatergic synapses throughout the brain. However, the basis for synapse-specific accumulation of GluR1 is unknown. Here we report that synaptic activity locally immobilizes GluR1 AMPA receptors at individual synapses. Using single-molecule tracking together with the silencing of individual presynaptic boutons, we demonstrate that local synaptic activity reduces diffusional exchange of GluR1 between synaptic and extraynaptic domains, resulting in postsynaptic accumulation of GluR1. At neighboring inactive synapses, GluR1 is highly mobile with individual receptors frequently escaping the synapse. Within the synapse, spontaneous activity confines the diffusional movement of GluR1 to restricted subregions of the postsynaptic membrane. Thus, local activity restricts GluR1 mobility on a submicron scale, defining an input-specific mechanism for regulating AMPA receptor composition and abundance.
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AMPA receptors tagged with QDs selectively reduce their mobility at active synapses while freely diffusing through non-active synapses.
“AMPA receptors tagged with QDs were reported to selectively reduce their mobility at active synapse while they freely diffused through non-active synapses (Ehlers et al., 2007).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Ehlers et al., 2007
Exchange of single receptor molecules between spines is reduced during stimulation.
“The same study observed reduced exchange of single receptor molecules between spines during stimulation.”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Ehlers et al., 2007
Glutamate receptors localize to submicron scale clusters within the synaptic membrane.
“In addition, recent studies have shown that glutamate receptors localize to submicron scale clusters within the synaptic membrane as shown by various techniques ranging from EM to PALM microscopy (Ehlers et al., 2007; MacGillavry et al., 2013; Nair et al., 2013).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Ehlers et al., 2007
Mushroom shaped spines retain AMPA receptors in the vicinity of the synapse for an increased period of time.
“Mushroom shaped spines were found to retain AMPA receptors in the vicinity of the synapse for an increased period of time (Ashby et al., 2006; Ehlers et al., 2007; Opazo and Choquet, 2011, see Figure 3A).”
From Barriers in the brain: resolving dendritic spine morphology and compartmentalization (2014) · cites this paper as Ehlers et al., 2007
Three other studies failed to observe local enhancement of AMPAR accumulation at inactivated synapses.
“In contrast, three other studies failed to observe such a local enhancement of AMPAR accumulation at inactivated synapses.”
From Homeostatic Synaptic Plasticity: Local and Global Mechanisms for Stabilizing Neuronal Function (2012) · cites this paper as Ehlers et al. 2007
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References 127 · Cited by 300
- Authors
- Ehlers, M. D., Heine, M., Groc, L., Lee, M.-C., & Choquet, D.
- Affiliations
- Howard Hughes Medical Institute (US)
- Centre National de la Recherche Scientifique (FR)
- Duke Medical Center (US)
- Corresponding author
- Ehlers, Michael D.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-05
- Volume
- 54
- Issue
- 3
- Pages
- 447-460
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC1993808
- OpenAlex
- W2084627891
- Cited by
- 300
- References
- 127
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 4 · 2022: 6 · 2021: 11 · 2020: 10 · 2019: 8 · 2018: 19 · 2017: 15 · 2016: 11 · 2015: 8 · 2014: 24 · 2013: 33 · 2012: 27
- FWCI
- 12.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2269 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG024492, R01AG024492)
- National Institute of Mental Health (R01MH064748, MH046478)
- National Institute of Neurological Disorders and Stroke (NS047574, R01NS047574, R01NS039402)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- synaptic activity, receptor mobility, synaptic potentiation, glutamatergic synapses, single-molecule tracking, spontaneous synaptic activity, receptor trafficking
- MeSH terms
- Animals, Carrier Proteins, Cells, Cultured, Embryo, Mammalian, Hippocampus, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Synapses, Time Factors, Transduction, Genetic, Patch-Clamp Techniques, Protein Transport, Intracellular Signaling Peptides and Proteins, Green Fluorescent Proteins, Rats
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