Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons
Open accessAbstract
The AMPA receptor, which is involved in most fast glutamatergic transmission in the mammalian brain and is expressed in most neurons, is made up of four subunits, GluR1–4. In situ hybridzation, immunocytochemistry studies, and single-cell PCR analyses show that the number and type of AMPA receptor subunits expressed vary among neuronal populations and that two to four subunits usually are expressed in each neuron. Neurons that express two or more subunits theoretically could produce multiple pentameric receptor complexes that differ in their subunit compositions, and these complexes could be targeted to different synaptic populations. To determine whether a single neuronal population produces multiple AMPA receptor complexes, we used a preparation of CA1/CA2 hippocampal pyramidal neurons and immunoprecipitation with subunit-specific antibodies to characterize the receptor complexes. The CA1/CA2 pyramidal neurons express high levels of GluR1–3 and receive multiple excitatory inputs, offering the possibility that distinct receptor complexes may be assembled and expressed selectively at different synaptic populations. Our results suggest the presence of two major populations of AMPA receptor complexes: those made up of GluR1 and GluR2 and those made up of GluR2 and GluR3. Very few complexes contained both GluR1 and GluR3, whereas approximately 8% of the total AMPA receptor complexes was homomeric GluR1. The integrity of the receptor complex was verified by measuring [3H]AMPA binding activity in the immunoprecipitated fractions. These results show that AMPA receptor complexes with different subunit compositions are present in CA1/CA2 pyramidal neurons and suggest an additional mechanism to regulate receptor expression in neurons.
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Most AMPARs in CA1 hippocampal pyramidal cells are tetraheteromeric assemblies of either GluA1/GluA2 or GluA2/GluA3 subunits, with a preponderance of GluA1/GluA2.
“Most AMPARs in CA1 hippocampal pyramidal cells are tetraheteromeric assemblies of either GluA1/GluA2 subunits or GluA2/GluA3 subunits with a preponderance of GluA1/GluA2 subunits (264–266).”
From Synaptic memory and CaMKII (2023) · cites this paper as [266]
The immunoprecipitation results report that most complexes in the CA1/CA2 pyramidal-neuron preparation contain GluR1/GluR2 or GluR2/GluR3. Our copy does not establish a four-subunit assembly for those complexes or a clear preponderance of GluR1/GluR2 over GluR2/GluR3, and the preparation includes CA2 as well as CA1 (pages unavailable in the indexed copy). (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn hippocampal CA1 neurons the majority of AMPARs are made up from GluA1/2 and GluA2/3 subunit combinations, with a small contribution of GluA1 homomers.
“In hippocampal CA1 neurons the majority of AMPARs are made up from GluA1/2 and GluA2/3 subunit combinations, with a small contribution of GluA1 homomers (Wenthold et al., 1996).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Wenthold et al., 1996
The majority of these GluA1-containing receptors are likely to be GluA1/2 heteromers.
“The majority of these GluA1-containing receptors are likely to be GluA1/2 heteromers (Wenthold et al., 1996, Lu et al., 2009).”
From The AMPA Receptor Code of Synaptic Plasticity (2018) · cites this paper as Wenthold et al., 1996
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- Authors
- Wenthold, R., Petralia, R., Blahos J, II, & Niedzielski, A.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1996-03-15
- Volume
- 16
- Issue
- 6
- Pages
- 1982-1989
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6578515
- OpenAlex
- W2169578249
- Cited by
- 850
- References
- 0
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 25 · 2023: 25 · 2022: 22 · 2021: 34 · 2020: 23 · 2019: 19 · 2018: 41 · 2017: 35 · 2016: 25 · 2015: 29 · 2014: 45 · 2013: 23 · 2012: 25
- FWCI
- 9.85
- 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)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- AMPA receptors, GluR1, GluR2, GluR3, receptor subunit composition, heteromeric receptors, glutamatergic neurotransmission
- MeSH terms
- Animals, Antibody Specificity, Detergents, Hippocampus, Immunohistochemistry, Male, Neurons, Precipitin Tests, Synapses, Blotting, Western, Rats, Sprague-Dawley, Pyramidal Cells, Receptors, AMPA, Rats
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