Selective clustering of glutamate and gamma-aminobutyric acid receptors opposite terminals releasing the corresponding neurotransmitters.
Open accessAbstract
Several immunocytochemical and physiological studies have demonstrated a concentration of neurotransmitter receptors at postsynaptic sites on neurons, but an overall picture of receptor distribution has not emerged. In particular, it has not been clear whether receptor clusters are selectively localized opposite terminals that release the corresponding neurotransmitter. By using antibodies against the excitatory glutamate receptor subunit GluR1 and the inhibitory type A gamma-aminobutyric acid (GABA) receptor beta 2/3 subunits, we show that these different receptor types cluster at distinct postsynaptic sites on cultured rat hippocampal neurons. The GABAA receptor beta 2/3 subunits clustered on cell bodies and dendritic shafts opposite GABAergic terminals, whereas GluR1 clustered mainly on dendritic spines and was associated with glutamatergic synapses. Chronic blockade of evoked transmitter release did not block receptor clustering at postsynaptic sites. These results suggest that complex mechanisms involving nerve terminal-specific signals are required to allow different postsynaptic receptor types to cluster opposite only appropriate presynaptic terminals.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Cultured hippocampal pyramidal neurons possess both spinous and nonspinous synapses, the latter often representing GABAergic synapses.
“Cultured hippocampal pyramidal neurons possess both spinous and nonspinous synapses (Bartlett and Banker, 1984), the latter often representing GABAergic synapses that are present together with glutamatergic synapses along the dendrites (Craig et al., 1994).”
From Regulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin (1998) · cites this paper as Craig et al., 1994
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Rat hippocampal neurons in dispersed cell culture.
Banker, G. A., & Cowan, W. M. (1977) · Brain Research · doi:10.1016/0006-8993(77)90594-7 · Cited by 1,110 · see citing works
Self-citationReist, N. E., Werle, M. J., & McMahan, U. J. (1992) · Neuron · doi:10.1016/0896-6273(92)90200-w · Cited by 237 · see citing works
Flagged first, then by citations
Research works printed but not linked: 41
- Aoki C., Joh T. H., Pickel V. M. Ultrastructural localization of beta-adrenergic receptor-like immunoreactivity in the cortex and neostriatum of rat brain. Brain Res. 1987 Dec 29;437(2):264–282. doi: 10.1016/0006-8993(87)91642-8. [DOI] [PubMed] [Google Scholar] · DOI
- Baude A., Nusser Z., Roberts J. D., Mulvihill E., McIlhinney R. A., Somogyi P. The metabotropic glutamate receptor (mGluR1 alpha) is concentrated at perisynaptic membrane of neuronal subpopulations as detected by immunogold reaction. Neuron. 1993 Oct;11(4):771–787. doi: 10.1016/0896-6273(93)90086-7. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- Baude A., Sequier J. M., McKernan R. M., Olivier K. R., Somogyi P. Differential subcellular distribution of the alpha 6 subunit versus the alpha 1 and beta 2/3 subunits of the GABAA/benzodiazepine receptor complex in granule cells of the cerebellar cortex. Neuroscience. 1992 Dec;51(4):739–748. doi: 10.1016/0306-4522(92)90513-2. [DOI] [PubMed] [Google Scholar] · DOI
- Bekkers J. M., Stevens C. F. NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus. Nature. 1989 Sep 21;341(6239):230–233. doi: 10.1038/341230a0. [DOI] [PubMed] [Google Scholar] · DOI
- Bergey G. K., Fitzgerald S. C., Schrier B. K., Nelson P. G. Neuronal maturation in mammalian cell culture is dependent on spontaneous electrical activity. Brain Res. 1981 Feb 23;207(1):49–58. doi: 10.1016/0006-8993(81)90678-8. [DOI] [PubMed] [Google Scholar] · DOI
- Blackstone C. D., Moss S. J., Martin L. J., Levey A. I., Price D. L., Huganir R. L. Biochemical characterization and localization of a non-N-methyl-D-aspartate glutamate receptor in rat brain. J Neurochem. 1992 Mar;58(3):1118–1126. doi: 10.1111/j.1471-4159.1992.tb09370.x. [DOI] [PubMed] [Google Scholar] · DOI
- Buckley K., Kelly R. B. Identification of a transmembrane glycoprotein specific for secretory vesicles of neural and endocrine cells. J Cell Biol. 1985 Apr;100(4):1284–1294. doi: 10.1083/jcb.100.4.1284. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Chang Y. C., Gottlieb D. I. Characterization of the proteins purified with monoclonal antibodies to glutamic acid decarboxylase. J Neurosci. 1988 Jun;8(6):2123–2130. doi: 10.1523/JNEUROSCI.08-06-02123.1988. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Choi D. W., Fischbach G. D. GABA conductance of chick spinal cord and dorsal root ganglion neurons in cell culture. J Neurophysiol. 1981 Apr;45(4):605–620. doi: 10.1152/jn.1981.45.4.605. [DOI] [PubMed] [Google Scholar] · DOI
- Craig A. M., Blackstone C. D., Huganir R. L., Banker G. The distribution of glutamate receptors in cultured rat hippocampal neurons: postsynaptic clustering of AMPA-selective subunits. Neuron. 1993 Jun;10(6):1055–1068. doi: 10.1016/0896-6273(93)90054-u. [DOI] [PubMed] [Google Scholar] · DOI
- De Camilli P., Cameron R., Greengard P. Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections. J Cell Biol. 1983 May;96(5):1337–1354. doi: 10.1083/jcb.96.5.1337. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Eshhar N., Petralia R. S., Winters C. A., Niedzielski A. S., Wenthold R. J. The segregation and expression of glutamate receptor subunits in cultured hippocampal neurons. Neuroscience. 1993 Dec;57(4):943–964. doi: 10.1016/0306-4522(93)90040-m. [DOI] [PubMed] [Google Scholar] · DOI
- Ewert M., Shivers B. D., Lüddens H., Möhler H., Seeburg P. H. Subunit selectivity and epitope characterization of mAbs directed against the GABAA/benzodiazepine receptor. J Cell Biol. 1990 Jun;110(6):2043–2048. doi: 10.1083/jcb.110.6.2043. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Fertuck H. C., Salpeter M. M. Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after 125I-alpha-bungarotoxin binding at mouse neuromuscular junctions. J Cell Biol. 1976 Apr;69(1):144–158. doi: 10.1083/jcb.69.1.144. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Froehner S. C. Neurobiology. Anchoring glycine receptors. Nature. 1993 Dec 23;366(6457):719–719. doi: 10.1038/366719a0. [DOI] [PubMed] [Google Scholar] · DOI
- Frosch M. P., Dichter M. A. Non-uniform distribution of GABA activated chloride channels in cultured cortical neurons. Neurosci Lett. 1992 Apr 13;138(1):59–62. doi: 10.1016/0304-3940(92)90472-j. [DOI] [PubMed] [Google Scholar] · DOI
- Gottlieb D. I., Cowan W. M. On the distribution of axonal terminals containing spheroidal and flattened synaptic vesicles in the hippocampus and dentate gyrus of the rat and cat. Z Zellforsch Mikrosk Anat. 1972;129(3):413–429. doi: 10.1007/BF00307297. [DOI] [PubMed] [Google Scholar] · DOI
- Hall Z. W., Sanes J. R. Synaptic structure and development: the neuromuscular junction. Cell. 1993 Jan;72 (Suppl):99–121. doi: 10.1016/s0092-8674(05)80031-5. [DOI] [PubMed] [Google Scholar] · DOI
- Hepler J. R., Toomim C. S., McCarthy K. D., Conti F., Battaglia G., Rustioni A., Petrusz P. Characterization of antisera to glutamate and aspartate. J Histochem Cytochem. 1988 Jan;36(1):13–22. doi: 10.1177/36.1.2891743. [DOI] [PubMed] [Google Scholar] · DOI
- Jacob M. H., Berg D. K., Lindstrom J. M. Shared antigenic determinant between the Electrophorus acetylcholine receptor and a synaptic component on chicken ciliary ganglion neurons. Proc Natl Acad Sci U S A. 1984 May;81(10):3223–3227. doi: 10.1073/pnas.81.10.3223. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Jacob M. H., Berg D. K. The ultrastructural localization of alpha-bungarotoxin binding sites in relation to synapses on chick ciliary ganglion neurons. J Neurosci. 1983 Feb;3(2):260–271. doi: 10.1523/JNEUROSCI.03-02-00260.1983. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Janka Z., Jones D. G. Junctions in rat neocortical explants cultured in TTX-, GABA-, and Mg++-environments. Brain Res Bull. 1982 Mar;8(3):273–278. doi: 10.1016/0361-9230(82)90059-4. [DOI] [PubMed] [Google Scholar] · DOI
- Jones K. A., Baughman R. W. Both NMDA and non-NMDA subtypes of glutamate receptors are concentrated at synapses on cerebral cortical neurons in culture. Neuron. 1991 Oct;7(4):593–603. doi: 10.1016/0896-6273(91)90372-7. [DOI] [PubMed] [Google Scholar] · DOI
- Kaufman D. L., Houser C. R., Tobin A. J. Two forms of the gamma-aminobutyric acid synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J Neurochem. 1991 Feb;56(2):720–723. doi: 10.1111/j.1471-4159.1991.tb08211.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Killisch I., Dotti C. G., Laurie D. J., Lüddens H., Seeburg P. H. Expression patterns of GABAA receptor subtypes in developing hippocampal neurons. Neuron. 1991 Dec;7(6):927–936. doi: 10.1016/0896-6273(91)90338-z. [DOI] [PubMed] [Google Scholar] · DOI
- Kirsch J., Wolters I., Triller A., Betz H. Gephyrin antisense oligonucleotides prevent glycine receptor clustering in spinal neurons. Nature. 1993 Dec 23;366(6457):745–748. doi: 10.1038/366745a0. [DOI] [PubMed] [Google Scholar] · DOI
- Martin L. J., Blackstone C. D., Levey A. I., Huganir R. L., Price D. L. AMPA glutamate receptor subunits are differentially distributed in rat brain. Neuroscience. 1993 Mar;53(2):327–358. doi: 10.1016/0306-4522(93)90199-p. [DOI] [PubMed] [Google Scholar] · DOI
- Molnár E., Baude A., Richmond S. A., Patel P. B., Somogyi P., McIlhinney R. A. Biochemical and immunocytochemical characterization of antipeptide antibodies to a cloned GluR1 glutamate receptor subunit: cellular and subcellular distribution in the rat forebrain. Neuroscience. 1993 Mar;53(2):307–326. doi: 10.1016/0306-4522(93)90198-o. [DOI] [PubMed] [Google Scholar] · DOI
- Nicola M. A., Becker C. M., Triller A. Development of glycine receptor alpha subunit in cultivated rat spinal neurons: an immunocytochemical study. Neurosci Lett. 1992 Apr 13;138(1):173–178. doi: 10.1016/0304-3940(92)90499-w. [DOI] [PubMed] [Google Scholar] · DOI
- Ottersen O. P., Storm-Mathisen J., Somogyi P. Colocalization of glycine-like and GABA-like immunoreactivities in Golgi cell terminals in the rat cerebellum: a postembedding light and electron microscopic study. Brain Res. 1988 May 31;450(1-2):342–353. doi: 10.1016/0006-8993(88)91573-9. [DOI] [PubMed] [Google Scholar] · DOI
- Petralia R. S., Wenthold R. J. Light and electron immunocytochemical localization of AMPA-selective glutamate receptors in the rat brain. J Comp Neurol. 1992 Apr 15;318(3):329–354. doi: 10.1002/cne.903180309. [DOI] [PubMed] [Google Scholar] · DOI
- Sargent P. B., Pang D. Z. Acetylcholine receptor-like molecules are found in both synaptic and extrasynaptic clusters on the surface of neurons in the frog cardiac ganglion. J Neurosci. 1989 Mar;9(3):1062–1072. doi: 10.1523/JNEUROSCI.09-03-01062.1989. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Sealock R., Froehner S. C. Dystrophin-associated proteins and synapse formation: is alpha-dystroglycan the agrin receptor? Cell. 1994 Jun 3;77(5):617–619. doi: 10.1016/0092-8674(94)90045-0. [DOI] [PubMed] [Google Scholar] · DOI
- Segal M., Barker J. L. Rat hippocampal neurons in culture: properties of GABA-activated Cl- ion conductance. J Neurophysiol. 1984 Mar;51(3):500–515. doi: 10.1152/jn.1984.51.3.500. [DOI] [PubMed] [Google Scholar] · DOI
- Seitanidou T., Nicola M. A., Triller A., Korn H. Partial glycinergic denervation induces transient changes in the distribution of a glycine receptor-associated protein in a central neuron. J Neurosci. 1992 Jan;12(1):116–131. doi: 10.1523/JNEUROSCI.12-01-00116.1992. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Somogyi P., Takagi H., Richards J. G., Mohler H. Subcellular localization of benzodiazepine/GABAA receptors in the cerebellum of rat, cat, and monkey using monoclonal antibodies. J Neurosci. 1989 Jun;9(6):2197–2209. doi: 10.1523/JNEUROSCI.09-06-02197.1989. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Todd A. J., Sullivan A. C. Light microscope study of the coexistence of GABA-like and glycine-like immunoreactivities in the spinal cord of the rat. J Comp Neurol. 1990 Jun 15;296(3):496–505. doi: 10.1002/cne.902960312. [DOI] [PubMed] [Google Scholar] · DOI
- Triller A., Cluzeaud F., Korn H. gamma-Aminobutyric acid-containing terminals can be apposed to glycine receptors at central synapses. J Cell Biol. 1987 Apr;104(4):947–956. doi: 10.1083/jcb.104.4.947. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Triller A., Cluzeaud F., Pfeiffer F., Betz H., Korn H. Distribution of glycine receptors at central synapses: an immunoelectron microscopy study. J Cell Biol. 1985 Aug;101(2):683–688. doi: 10.1083/jcb.101.2.683. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- Vernallis A. B., Conroy W. G., Berg D. K. Neurons assemble acetylcholine receptors with as many as three kinds of subunits while maintaining subunit segregation among receptor subtypes. Neuron. 1993 Mar;10(3):451–464. doi: 10.1016/0896-6273(93)90333-m. [DOI] [PubMed] [Google Scholar] · DOI
- van Huizen F., Romijn H. J., Habets A. M. Synaptogenesis in rat cerebral cortex cultures is affected during chronic blockade of spontaneous bioelectric activity by tetrodotoxin. Brain Res. 1985 Mar;351(1):67–80. doi: 10.1016/0165-3806(85)90232-9. [DOI] [PubMed] [Google Scholar] · DOI
Cited by
Sorted by citations
Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors
Farrant, M., & Nusser, Z. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1625 · Cited by 2,081 · see citing works
Cell Type and Pathway Dependence of Synaptic AMPA Receptor Number and Variability in the Hippocampus
Nusser, Z., Lujan, R., Laube, G., Roberts, J. D. B., Molnar, E., & Somogyi, P. (1998) · Neuron · doi:10.1016/s0896-6273(00)80565-6 · Cited by 804 · see citing works
Retinal waves and visual system development
Wong, R. O. L. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.29 · Cited by 544 · see citing works
Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product narp.
O’Brien, R. J., Xu, D., Petralia, R. S., Steward, O., Huganir, R. L., & Worley, P. (1999) · Neuron · doi:10.1016/s0896-6273(00)80782-5 · Cited by 471 · see citing works
Self-citationRegulation of F-Actin Stability in Dendritic Spines by Glutamate Receptors and Calcineurin
Halpain, S., Hipolito, A., & Saffer, L. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-23-09835.1998 · Cited by 408 · see citing works
“Cultured hippocampal pyramidal neurons possess both spinous and nonspinous synapses (Bartlett and Banker, 1984), the latter often representing GABAergic synapses that are present together with glutamatergic synapses along the dendrites (Craig et al., 1994).”
BackgroundXu, D., Hopf, C., Reddy, R., Cho, R. W., Guo, L., Lanahan, A., Petralia, R. S., Wenthold, R. J., O'Brien, R. J., & Worley, P. (2003) · Neuron · doi:10.1016/s0896-6273(03)00463-x · Cited by 265 · see citing works
Allison, D. W., Chervin, A. S., Gelfand, V. I., & Craig, A. M. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04545.2000 · Cited by 245 · see citing works
Self-citationMHCI negatively regulates synapse density during the establishment of cortical connections
Glynn, M. W., Elmer, B. M., Garay, P. A., Liu, X.-B., Needleman, L. A., El-Sabeawy, F., & McAllister, A. K. (2011) · Nature Neuroscience · doi:10.1038/nn.2764 · Cited by 198 · see citing works
Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus
Zhang, W., Vazquez, L., Apperson, M., & Kennedy, M. B. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-01-00096.1999 · Cited by 190 · see citing works
GABAA Receptors in Normal Development and Seizures: Friends or Foes?
Galanopoulou, A. (2008) · Current Neuropharmacology · doi:10.2174/157015908783769653 · Cited by 156 · see citing works
Target‐specific expression of pre‐ and postsynaptic mechanisms
Tóth, K., & McBain, C. J. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.00041.x · Cited by 91 · see citing works
- Authors
- Craig, A. M., Blackstone, C. D., Huganir, R. L., & Banker, G.
- Affiliations
- University of Virginia (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-12-20
- Volume
- 91
- Issue
- 26
- Pages
- 12373-12377
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC45440
- OpenAlex
- W2087045924
- Cited by
- 237
- References
- 2
- Citations by year
- 2021: 2 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 4 · 2014: 1 · 2013: 4 · 2012: 3
- FWCI
- 4.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (NS 17112, R01NS017112)
- 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
- glutamate receptors, GABA receptors, receptor clustering, postsynaptic localization, GluR1, hippocampal neurons, dendritic spines, glutamatergic synapses, GABAergic synapses, presynaptic terminals, neurotransmitter release
- MeSH terms
- Action Potentials, Animals, Evoked Potentials, Fluorescent Antibody Technique, gamma-Aminobutyric Acid, Glutamates, Hippocampus, Receptor Aggregation, Synaptic Membranes, Tetrodotoxin, Receptors, Glutamate, Receptors, GABA, Neurotransmitter Agents, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review