NMDA Receptor Content of Synapses in Stratum Radiatum of the Hippocampal CA1 Area
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Glutamate receptors activated by NMDA (NMDARs) or AMPA (AMPARs) are clustered on dendritic spines of pyramidal cells. Both the AMPAR-mediated postsynaptic responses and the synaptic AMPAR immunoreactivity show a large intersynapse variability. Postsynaptic responses mediated by NMDARs show less variability. To assess the variability in NMDAR content and the extent of their coexistence with AMPARs in Schaffer collateral–commissural synapses of adult rat CA1 pyramidal cells, electron microscopic immunogold localization of receptors has been used. Immunoreactivity of NMDARs was detected in virtually all synapses on spines, but AMPARs were undetectable, on average, in 12% of synapses. A proportion of synapses had a very high AMPAR content relative to the mean content, resulting in a distribution more skewed toward larger values than that of NMDARs. The variability of synaptic NMDAR content [coefficient of variation (CV), 0.64–0.70] was much lower than that of the AMPAR content (CV, 1.17–1.45). Unlike the AMPAR content, the NMDAR content showed only a weak correlation with synapse size. As reported previously for AMPARs, the immunoreactivity of NMDARs was also associated with the spine apparatus within spines. The results demonstrate that the majority of the synapses made by CA3 pyramidal cells onto spines of CA1 pyramids express both NMDARs and AMPARs, but with variable ratios. A less-variable NMDAR content is accompanied by a wide variability of AMPAR content, indicating that the regulation of expression of the two receptors is not closely linked. These findings support reports that fast excitatory transmission at some of these synapses is mediated by activation mainly of NMDARs.
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NMDARs tend to be concentrated in the middle of the PSD with little overlap with AMPARs.
“NMDARs tend to be concentrated in the middle of the PSD with little overlap with AMPARs (253–255).”
From Synaptic memory and CaMKII (2023) · cites this paper as [254]
The 'Tangential distribution of NMDARs across the postsynaptic density' section (page unavailable) finds NMDAR labeling more frequent in the middle of the PSD. The 'Tangential distribution of AMPARs and NMDARs' section (page unavailable) describes AMPARs as more evenly distributed and proposes segregated microclusters, but does not establish that the receptors have little spatial overlap; it describes NMDAR clusters as interspersed among AMPARs in larger synapses. (LLM, conf=0.84)
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- Authors
- Racca, C., Stephenson, F. A., Streit, P., Roberts, J. D. B., & Somogyi, P.
- Affiliations
- University of Oxford (GB)
- University of London (GB)
- University of Zurich (CH)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2000-04-01
- Volume
- 20
- Issue
- 7
- Pages
- 2512-2522
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6772245
- OpenAlex
- W2144874949
- Cited by
- 304
- References
- 59
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 14 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 10 · 2019: 8 · 2018: 9 · 2017: 5 · 2016: 10 · 2015: 10 · 2014: 6 · 2013: 6 · 2012: 14
- FWCI
- 8.02
- 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)
- UCL Discovery (University College London) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- National Institutes of Health
- National Institute on Deafness and Other Communication Disorders
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- NMDA receptor, AMPA receptors, Schaffer collateral synapses, CA1 pyramidal neurons, CA3 pyramidal cells, dendritic spines, spine apparatus, synapse size, hippocampus
- MeSH terms
- Animals, Cell Line, Dendrites, Humans, Immunohistochemistry, Synapses, Receptors, N-Methyl-D-Aspartate, Rats, Wistar, Pyramidal Cells, Receptors, AMPA, Rats
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