Trafficking of AMPA Receptors at Plasma Membranes of Hippocampal Neurons
Open accessAbstract
The number of AMPA receptors at synapses depends on receptor cycling. Because receptors diffuse rapidly in plasma membranes, their exocytosis and endocytosis need not occur near synapses. Here, pre-embedding immunogold electron microscopy is applied to dissociated rat hippocampal cultures to provide sensitive, high-resolution snapshots of the distribution of surface AMPA receptors in spines, dendrites, and cell bodies that will be informative about trafficking of AMPA receptors. The density of the label for GluR2 varies, but is consistent throughout cell body and dendrites in each individual neuron, except at postsynaptic densities (PSDs), where it is typically higher. Glutamate receptor 2 (GluR2) labels at PSDs significantly increase after synaptic activation by glycine treatment and increase further upon depolarization by high K+. Islands of densely packed labels have consistent size and density but vary in frequency under different experimental conditions. These patches of label, which occur on plasma membranes of cell bodies and dendrites but not near PSDs, are taken to be the aftermath of exocytosis of AMPA receptors. A subpopulation of clathrin-coated pits in cell bodies and dendrites label for GluR2, and the number and amount of label in individual pits increase after NMDA treatment. Coated pits near synapses typically lack GluR2 label under basal conditions, but ∼40% of peri-PSD pits label for GluR2 after NMDA treatment. Thus, exocytosis and endocytosis of AMPA receptors occur mainly at extrasynaptic locations on cell bodies and dendrites. Receptors are not preferentially exocytosed near PSDs, but may be removed via endocytosis at peri-PSD locations after activation of NMDA receptors.
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In most cases AMPARs are inserted via exocytosis into the dendritic shaft, some distance from the synapse.
“Fourth, in most cases the AMPARs are inserted via exocytosis into the dendritic shaft, some distance from the synapse (220, 249, 250, 337).”
From Synaptic memory and CaMKII (2023) · cites this paper as [220]
The Results (page not provided) identify probable exocytosis-related patches on dendrites away from postsynaptic densities. But they also find patches on cell bodies; the paper does not establish that insertion occurs into the dendritic shaft in most cases. (LLM, conf=0.85)
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“Fourth, in most cases the AMPARs are inserted via exocytosis into the dendritic shaft, some distance from the synapse (220, 249, 250, 337).”
Background
- Authors
- Tao-Cheng, J.-H., Crocker, V. T., Winters, C. A., Azzam, R., Chludzinski, J., & Reese, T. S.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Reese, Thomas S.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-03-30
- Volume
- 31
- Issue
- 13
- Pages
- 4834-4843
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3138201
- OpenAlex
- W2160113442
- Cited by
- 82
- References
- 9
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 15 · 2020: 11 · 2019: 4 · 2018: 8 · 2017: 5 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 7 · 2012: 8
- FWCI
- 3.18
- 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
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (ZIANS003113)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- AMPA receptors, receptor trafficking, GluR2, hippocampal neurons, extrasynaptic receptors, postsynaptic density, exocytosis, endocytosis, clathrin-coated pits, NMDA receptor activation, glycine, depolarization, dendrites, dendritic spines
- MeSH terms
- Animals, Cell Membrane, Cells, Cultured, Endocytosis, Exocytosis, Female, Hippocampus, Male, Neurons, Rats, Sprague-Dawley, Receptors, AMPA, Protein Transport, Rats
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