Selective Allocation of GABAA Receptors Containing the α1 Subunit to Neurochemically Distinct Subpopulations of Rat Hippocampal Interneurons
Abstract
The identification of a large variety of GABAA receptor subunits by molecular cloning suggests the existence of multiple receptor subtypes differing in localization and functional properties. In the present study we analysed immunohistochemically the cellular distribution of GABAA receptors containing the alpha 1 subunit in the rat hippocampus with a subunit-specific antiserum. Prominent staining of numerous interneurons was evident in Ammon's horn and the dentate gyrus, which contrasted with moderate and diffuse immunoreactivity in the dendritic layers of pyramidal and granule cells. Double immunofluorescence staining with antibodies to GABA revealed that a subset of GABAergic neurons in the hippocampus were immunoreactive for the alpha 1 subunit. To determine whether these cells represent distinct subpopulations of interneurons, we analysed the co-localization of the GABAA receptor alpha 1 subunit with selective markers of hippocampal interneurons (selected calcium-binding proteins and neuropeptides). In both Ammon's horn and the dentate gyrus, all parvalbumin-positive neurons and 50% of calretinin-positive neurons were double-labelled, whereas interneurons containing calbindin-D28k were devoid of alpha 1 subunit staining. Similarly, most neurons positive for neuropeptide Y and a subset of somatostatin-positive cells were double-labelled, in contrast to cholecystokinin- and vasoactive intestinal peptide-containing cells, which lacked the alpha 1 subunit staining. These results demonstrate cell-specific expression of GABAA receptors containing the alpha 1 subunit among subsets of hippocampal interneurons, pointing to a pronounced functional specialization of these cells. Furthermore, the prominent expression of GABAA receptors by interneurons suggests that disinhibition may be of major functional relevance in regulating the balance between excitation and inhibition in hippocampal circuits.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
All PV+ interneurons in CA1, CA3 and DG express α1GABAARs.
“All PV+ interneurons in CA1, CA3 and DG express the α1 GABAARs [86]; Fig. 2).”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [86]
Cites
Wisden, W., Laurie, D. J., Monyer, H., & Seeburg, P. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-03-01040.1992 · Cited by 1,543 · see citing works
GABA-containing neurons in the septum control inhibitory interneurons in the hippocampus
Freund, T. F., & Antal, M. (1988) · Nature · doi:10.1038/336170a0 · Cited by 1,283 · see citing works
Somogyi, P., Hodgson, A., Smith, A. D., Nunzi, M. G., Gorio, A., & Wu, J. (1984) · Journal of Neuroscience · doi:10.1523/jneurosci.04-10-02590.1984 · Cited by 731 · see citing works
Type I and Type II GABA A -Benzodiazepine Receptors Produced in Transfected Cells
Pritchett, D. B., Lüddens, H., & Seeburg, P. H. (1989) · Science · doi:10.1126/science.2551039 · Cited by 718 · see citing works
Sloviter, R. S. (1989) · The Journal of Comparative Neurology · doi:10.1002/cne.902800203 · Cited by 686 · see citing works
Laurie, D., Seeburg, P., & Wisden, W. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-03-01063.1992 · Cited by 668 · see citing works
Kosaka, T., Katsumaru, H., Hama, K., Wu, J.-Y., & Heizmann, C. W. (1987) · Brain Research · doi:10.1016/0006-8993(87)90575-0 · Cited by 536 · see citing works
GABA A receptor subtypes: from pharmacology to molecular biology
Burt, D. R., & Kamatchi, G. L. (1991) · The FASEB Journal · doi:10.1096/fasebj.5.14.1661244 · Cited by 425 · see citing works
Monoclonal antibodies directed against the calcium binding protein parvalbumin
Celio, M. R., Baier, W. K., Schärer, L., de Viragh, P. A., & Gerday, C. (1988) · Cell Calcium · doi:10.1016/0143-4160(88)90027-9 · Cited by 423 · see citing works
Sloviter, R. S., & Nilaver, G. (1987) · The Journal of Comparative Neurology · doi:10.1002/cne.902560105 · Cited by 392 · see citing works
Lacaille, J., Mueller, A., Kunkel, D., & Schwartzkroin, P. (1987) · The Journal of Neuroscience · doi:10.1523/jneurosci.07-07-01979.1987 · Cited by 388 · see citing works
Comparative molecular neuroanatomy of cloned GABAA receptor subunits in the rat CNS
Persohn, E., Malherbe, P., & Richards, J. (1992) · The Journal of comparative neurology · doi:10.1002/cne.903260204 · Cited by 365 · see citing works
Serotonergic control of the hippocampus via local inhibitory interneurons.
Freund, T. F., Gulyás, A. I., Acsády, L., Görcs, T. J., & Tóth, K. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8501 · Cited by 360 · see citing works
Fritschy, J., Benke, D., Mertens, S., Oertel, W., Bächi, T., & Möhler, H. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.15.6726 · Cited by 344 · see citing works
Self-citationKosaka, T., Kosaka, K., Tateishi, K., Hamaoka, Y., Yanaihara, N., Wu, J., & Hama, K. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902390408 · Cited by 324 · see citing works
Richards, J., Schoch, P., Häring, P., Takács, B., & Möhler, H. (1987) · Journal of Neuroscience · doi:10.1523/jneurosci.07-06-01866.1987 · Cited by 296 · see citing works
Monoclonal antibodies directed against the calcium binding protein Calbindin D-28k
Celio, M. R., Baier, W. K., Schärer, L., Gregersen, H.-J., de Viragh, P. A., & Norman, A. W. (1990) · Cell Calcium · doi:10.1016/0143-4160(90)90014-l · Cited by 273 · see citing works
Lacaille, J., & Schwartzkroin, P. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-04-01400.1988 · Cited by 272 · see citing works
Lacaille, J., & Schwartzkroin, P. (1988) · The Journal of Neuroscience · doi:10.1523/jneurosci.08-04-01411.1988 · Cited by 270 · see citing works
Tóth, K., & Freund, T. F. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90357-8 · Cited by 260 · see citing works
Schwaller, B., Buchwald, P., Blümcke, I., Celio, M. R., & Hunziker, W. H. (1993) · Cell Calcium · doi:10.1016/0143-4160(93)90089-o · Cited by 255 · see citing works
Katsumaru, H., Kosaka, T., Heizmann, C. W., & Hama, K. (1988) · Experimental Brain Research · doi:10.1007/bf00250256 · Cited by 249 · see citing works
Neurohistochemistry, Modern Methods and Applications
LESLIE, R. A. (1987) · Neurochemistry International · doi:10.1016/0197-0186(87)90019-2 · Cited by 235 · see citing works
Somogyi, P., Takagi, H., Richards, J. G., & Möhler, H. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-06-02197.1989 · Cited by 234 · see citing works
Innervation of different peptide-containing neurons in the hippocampus by gabaergic septal afferents
Gulyás, A. I., Görcs, T. J., & Freund, T. F. (1990) · Neuroscience · doi:10.1016/0306-4522(90)90189-b · Cited by 234 · see citing works
Multiple benzodiazepine receptors: no reason for anxiety
Doble, A., & Martin, I. L. (1992) · Trends in Pharmacological Sciences · doi:10.1016/0165-6147(92)90027-4 · Cited by 232 · see citing works
Kosaka, T., Wu, J., & Benoit, R. (1988) · Experimental Brain Research · doi:10.1007/bf00247498 · Cited by 218 · see citing works
GABAA receptors display association of γ2-subunit with α1- and β2/3-subunits
Benke, D., Mertens, S., Trzeciak, A. M., Gillessen, D., & Möhler, H. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)64347-2 · Cited by 216 · see citing works
Miettinen, R. A., Gulyás, A. I., Baimbridge, K. G., Jacobowitz, D. M., & Freund, T. F. (1992) · Neuroscience · doi:10.1016/0306-4522(92)90335-y · Cited by 215 · see citing works
Gao, B., Fritschy, J., Benke, D., & Möhler, H. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90582-z · Cited by 214 · see citing works
Self-citationMcKernan, R. M., Quirk, K., Prince, R. J., Cox, P. A., Gillard, N. P., RAGAN, C. I., & Whiting, P. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90379-e · Cited by 194 · see citing works
Neuropeptide Y innervation of the hippocampal region in the rat and monkey brain
Köhler, C., Eriksson, L. G., Davies, S. W., & Chan‐Palay, V. (1986) · The Journal of Comparative Neurology · doi:10.1002/cne.902440310 · Cited by 192 · see citing works
The GABAA Receptor Family: Molecular and Functional DiversityPreprint
Seeburg, P. H., Wisden, W., Verdoorn, T. A., Pritchett, D. B., Werner, P., Herb, A., Lüddens, H., Sprengel, R., & Sakmann, B. J. (1990) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1990.055.01.006 · Cited by 191 · see citing works
Gulyás, A. I., Tóth, K., Dános, P., & Freund, T. F. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903120305 · Cited by 180 · see citing works
Mertens, S., Benke, D., & Möhler, H. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53413-x · Cited by 176 · see citing works
Léránth, C., Malcolm, A. J., & Frotscher, M. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.902950110 · Cited by 170 · see citing works
Deller, T., & Leranth, C. (1990) · The Journal of Comparative Neurology · doi:10.1002/cne.903000312 · Cited by 165 · see citing works
Hökfelt, T. G. M., Herrera‐Marschitz, M., Seroogy, K. B., et al. (1989) · PubMed · Cited by 150 · see citing works
Nunzi, M. G., Gorio, A., Milán, F. J., Freund, T. F., Somogyi, P., & Smith, A. D. (1985) · The Journal of Comparative Neurology · doi:10.1002/cne.902370406 · Cited by 149 · see citing works
Postsynaptic-gabaergic inhibition of non-pyramidal neurons in the guinea-pig hippocampus
Misgeld, U., & Frotscher, M. (1986) · Neuroscience · doi:10.1016/0306-4522(86)90015-1 · Cited by 140 · see citing works
Bohlhalter, S., Möhler, H., & Fritschy, J. (1994) · Brain Research · doi:10.1016/0006-8993(94)90905-9 · Cited by 140 · see citing works
Self-citationA GABAergic axo-axonic cell in the fascia dentata controls the main excitatory hippocampal pathway
Soriano, E., & Frotscher, M. (1989) · Brain Research · doi:10.1016/0006-8993(89)91722-8 · Cited by 130 · see citing works
Benke, D., Mertens, S., Trzeciak, A. M., Gillessen, D., & Möhler, H. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)80573-l · Cited by 107 · see citing works
Houser, C. R., Rw, O., Richards, J. G., & Möhler, H. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-04-01370.1988 · Cited by 100 · see citing works
Biochemical evidence for the existence of gamma-aminobutyrateA receptor iso-oligomers.
Duggan, M. J., & Stephenson, F. A. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39669-3 · Cited by 99 · see citing works
Kawaguchi, Y., & Hama, K. (1987) · Brain Research · doi:10.1016/0006-8993(87)90700-1 · Cited by 99 · see citing works
Hornung, J., & Celio, M. R. (1992) · The Journal of Comparative Neurology · doi:10.1002/cne.903200404 · Cited by 94 · see citing works
Immunohistochemical localization of the α1, α2 and α3 subunit of the GABAA receptor in the rat brain
Zimprich, F., Zezula, J., Sieghart, W., & Lassmann, H. (1991) · Neuroscience Letters · doi:10.1016/0304-3940(91)90910-l · Cited by 93 · see citing works
Mapping of GABAA receptor α5 and α6 subunit-like immunoreactivity in rat brain
Thompson, C. L., Bodewitz, G., Stephenson, F. A., et al. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90714-i · Cited by 79 · see citing works
Marksitzer, R., Benke, D., Fritschy, J., et al. (1993) · Journal of Receptor Research · doi:10.3109/10799899309073673 · Cited by 76 · see citing works
Self-citationMiettinen, R. A., & Freund, T. F. (1992) · Brain Research · doi:10.1016/0006-8993(92)91133-y · Cited by 69 · see citing works
Soltész, I., Roberts, J. D. B., Takagi, H., Richards, J. G., Möhler, H., & Somogyi, P. (1990) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1990.tb00434.x · Cited by 66 · see citing works
Antibodies Specific for α‐Subunit Subtypes of GABAA Receptors Reveal Brain Regional Heterogeneity
Endo, S., & Olsen, R. W. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03300.x · Cited by 60 · see citing works
Isolation of type I and type II GABAA‐benzodiazepine receptors by immunoaffinity chromatography
Zezula, J., & Sieghart, W. (1991) · FEBS Letters · doi:10.1016/0014-5793(91)80750-w · Cited by 47 · see citing works
Miettinen, R. A., & Freund, T. F. (1992) · Neuropeptides · doi:10.1016/0143-4179(92)90161-o · Cited by 41 · see citing works
Dános, P., Frotscher, M., & Freund, T. ́. F. (1991) · Brain Research · doi:10.1016/0006-8993(91)91481-f · Cited by 39 · see citing works
Local circuitry of GABAergic basket cells in the dentate gyrus.
Ribak, C. E. (1992) · PubMed · Cited by 30 · see citing works
GABAA-receptor immunoreactivity in the rat dorsal thalamus: An ultrastructural investigation
Spreafico, R., Biasi, S. D., Amadeo, A., et al. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90272-m · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks
Bartos, M., Vida, I., & Jonas, P. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2044 · Cited by 2,070 · see citing works
Fritschy, J., & Mohler, H. (1995) · Journal of Comparative Neurology · doi:10.1002/cne.903590111 · Cited by 1,244 · see citing works
Self-citationKatona, I., Sperlágh, B., Sı́k, A., Käfalvi, A., Vizi, E. S., Mackie, K., & Freund, T. F. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-11-04544.1999 · Cited by 1,218 · see citing works
Which GABAA-receptor subtypes really occur in the brain?
McKernan, R. M., & Whiting, P. J. (1996) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)80023-3 · Cited by 1,222 · see citing works
Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889 · see citing works
Sugiyama, S., Di Nardo, A. A., Aizawa, S., Matsuo, I., Volovitch, M., Prochiantz, A., & Hensch, T. K. (2008) · Cell · doi:10.1016/j.cell.2008.05.054 · Cited by 491 · see citing works
Rapid Signaling at Inhibitory Synapses in a Dentate Gyrus Interneuron Network
Bartos, M., Vida, I., Frotscher, M., Geiger, J. R. P., & Jonas, P. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-08-02687.2001 · Cited by 325 · see citing works
An emerging circuit pharmacology of GABAA receptors
Engin, E., Benham, R. S., & Rudolph, U. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.04.003 · Cited by 225 · see citing works
Regulation of GABAA Receptor Subunit Expression by Pharmacological Agents
Uusi-Oukari, M., & Korpi, E. R. (2010) · Pharmacological Reviews · doi:10.1124/pr.109.002063 · Cited by 213 · see citing works
Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons
Földy, C., Darmanis, S., Aoto, J., Malenka, R. C., Quake, S. R., & Südhof, T. C. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1610155113 · Cited by 179 · see citing works
Cobb, S. R., Halasy, K., Vida, I., Nyı́ri, G., Tamás, G., Buhl, E. H., & Somogyi, P. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00055-9 · Cited by 188 · see citing works
Inhibitory control of hippocampal inhibitory neurons
Chamberland, S., & Topolnik, L. (2012) · Frontiers in Neuroscience · doi:10.3389/fnins.2012.00165 · Cited by 134 · see citing works
Baude, A., Bleasdale, C., Dalezios, Y., Somogyi, P., & Klausberger, T. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhl117 · Cited by 137 · see citing works
Hájos, N., & Mody, I. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-21-08427.1997 · Cited by 131 · see citing works
A precritical period for plasticity in visual cortex
Feller, M. B., & Scanziani, M. (2005) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2005.01.012 · Cited by 92 · see citing works
Milenkovic, I., Vasiljevic, M., Maurer, D., Höger, H., Klausberger, T., & Sieghart, W. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.09.019 · Cited by 62 · see citing works
Ferando, I., & Mody, I. (2013) · Frontiers in Neural Circuits · doi:10.3389/fncir.2013.00144 · Cited by 52 · see citing works
GABA<sub>B</sub>-Receptor–Mediated Currents in Interneurons of the Dentate-Hilus Border
Mott, D. D., Li, Q., Okazaki, M. M., Turner, D. A., & Lewis, D. V. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.82.3.1438 · Cited by 46 · see citing works
- Authors
- Gao, B., & Fritschy, J. M.
- Affiliations
- University of Zurich (CH)
- Corresponding author
- Fritschy, J. M.
- ORCID
- Fritschy, J. M.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 1994-05
- Volume
- 6
- Issue
- 5
- Pages
- 837-853
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2139756898
- Cited by
- 147
- References
- 58
- Citations by year
- 2026: 1 · 2024: 1 · 2022: 2 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 8 · 2012: 1
- FWCI
- 4.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Bern
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- GABAA receptor, alpha1 subunit, hippocampal interneurons, parvalbumin, calretinin, calbindin-D28k, neuropeptide Y, somatostatin, cholecystokinin, vasoactive intestinal peptide, GABAergic neurons, disinhibition, excitation-inhibition balance, dentate gyrus, Ammon's horn, calcium-binding proteins
- MeSH terms
- Animals, Brain Mapping, Fluorescent Antibody Technique, Hippocampus, Immunoenzyme Techniques, Interneurons, Male, Nerve Tissue Proteins, Rats, Sprague-Dawley, Receptors, GABA, 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