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Localization of GABAA receptors in the rat retina

Published online by Cambridge University Press:  02 June 2009

Ursula Greferath ,
Frank Müller ,
Heinz Wässle ,
Brenda Shivers  and
Peter Seeburg
Ursula Greferath
Affiliation:
Max-Planck-Institut für Hirnforschung, Neuroanatomische Abteilung, Deutschordenstrasse 46, 6000 Frankfurt 71, Germany
Frank Müller
Affiliation:
Max-Planck-Institut für Hirnforschung, Neuroanatomische Abteilung, Deutschordenstrasse 46, 6000 Frankfurt 71, Germany
Heinz Wässle
Affiliation:
Max-Planck-Institut für Hirnforschung, Neuroanatomische Abteilung, Deutschordenstrasse 46, 6000 Frankfurt 71, Germany
Brenda Shivers
Affiliation:
Laboratorium für Molekulare Neuroendokrinologie, ZMBH, Universitat Heidelberg, Im Neuenheimer Feld 282, 6900 Heidelberg, Germany
Peter Seeburg
Affiliation:
Laboratorium für Molekulare Neuroendokrinologie, ZMBH, Universitat Heidelberg, Im Neuenheimer Feld 282, 6900 Heidelberg, Germany
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Abstract

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian retina. The present paper describes the localization of GABAA receptors in the rat retina as revealed by in situ hybridization and immunocytochemistry.

In situ hybridization with probes against various a subunits revealed a marked differential expression pattern. The αl subunit gene is expressed mainly in the bipolar and horizontal cell layer, the α2 gene in the amacrine and ganglion cell layer, and the α4 gene in a subpopulation of amacrine cells. β subunit mRNA is present diffusely throughout the entire inner nuclear layer and in the ganglion cell layer.

The monoclonal antibody bd 17 (against β2/β3 subunits) stained subpopulations of GABAergic and glycinergic amacrine cells as well as some ganglion cells and bipolar cells. Immunoreactivity was not restricted to synaptic input sites. In the outer plexiform layer bipolar cell dendrites were immunoreactive; in the inner plexiform layer mainly amacrine and ganglion cell processes were labeled, and bipolar cell axons appeared unstained. The results demonstrate a strong heterogeneity of GABAA receptors in the retina.

Keywords

GABAGABAA receptorsIn situ hybridizationImmunocytochemistry
Type
Articles
Information
Visual Neuroscience , Volume 10 , Issue 3 , May 1993 , pp. 551 - 561
Copyright
Copyright © Cambridge University Press 1993

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References

Agardh, E., Ehinger, B. & Wu, J.Y. (1987). GABA- and GAD-like immunoreactivity in the primate retina. Histochemistry 86, 485–490.CrossRefGoogle ScholarPubMed
Bolz, J., Frumkes, T., Voigt, T. & Wässle, H. (1985). Action and localization of γ-aminobutyric acid in the cat retina. Journal of Physiology 362, 369–393.CrossRefGoogle ScholarPubMed
Bormann, J. (1988). Electrophysiology of GABAA and GABAB receptor subtypes. Trends in Neuroscience Abstracts 11, 112–116.CrossRefGoogle ScholarPubMed
Bowery, N. (1989). GABAB receptors and their significance in mammalian pharmacology. Trends in Pharmacology 10, 401–407.CrossRefGoogle ScholarPubMed
Brecha, N.C. (1983). Retinal neurotransmitters: Histochemical and biochemical studies. In Chemical Neuroanatomy, ed. Emson, P.C., pp. 85–129. New York: Raven Press.Google Scholar
Brecha, N., Lai, M. & Sternini, C. (1990). Differential expression of GABAA αl and α2 receptor mRNAs in the rat retina. Investigative Ophthalmology and Visual Science (Suppl.) 31, 330.Google Scholar
Brecha, N.C., Sternini, C. & Humphrey, M.F. (1991). Cellular distribution of L-glutamate decarboxylase (GAD) and γ-aminobutyric acidA (GABAA) receptor mRNAs in the retina. Cellular and Molecular Neurobiology 11, 497–509.CrossRefGoogle ScholarPubMed
Brecha, N.C. (1992). Expression of GABAA receptors in the vertebrate retina. Progress in Brain Research 90, 3–28.CrossRefGoogle ScholarPubMed
Chun, M.H. & Wässle, H. (1989). GABA-like immunoreactivity in the cat retina. Electron microscopy. Journal of Comparative Neurology 279, 55–67.CrossRefGoogle ScholarPubMed
Cutting, G.R., Lu, L., O’Hara, B.F., Kasch, L.M., Montrose-Rafizadeh, C., Donovan, D.M., Shimada, S., Antonarakis, S.E., Guggino, W.B., Uhl, G.R. & Kazazian, H.H. (1991). Cloning of the γ-aminobutyric acid (GABA) ρ1 cDNA: A GABA receptor sub-unit highly expressed in the retina. Proceedings of the National Academy of Sciences of the U.S.A. 88, 2673–2677.CrossRefGoogle Scholar
Ewert, M., De Blas, A.L., Mohler, H. & Seeburg, P. (1992). A prominent epitope on GABAA receptors is recognized by two different monoclonal antibodies. Brain Research 569, 57–62.CrossRefGoogle ScholarPubMed
Friedmann, D.L. & Redburn, D.A. (1990). Evidence for functionally distinct subclasses of γ-aminobutyric acid receptors in rabbit retina. Journal of Neurochemistry 55, 1189–1199.CrossRefGoogle Scholar
Fritschy, J.-M., Benke, D., Mertens, S., Oertel, W.H., Bachi, T. & Möhler, H. (1992). Five subtypes of type A γ-aminobutyric acid receptors identified in neurons by double and triple immunofluo-rescence staining with subunit-specific antibodies. Proceedings of the National Academy of Sciences of the U.S.A. 89, 6726–6730.CrossRefGoogle Scholar
Greferath, U., Grünert, U. & Wässle, H. (1990). Rod bipolar cells in the mammalian retina show protein kinase C-like immunoreactivity. Journal of Comparative Neurology 301, 433–442.CrossRefGoogle ScholarPubMed
Grünert, U. & Wässle, H. (1990). GABA-like immunoreactivity in the macaque monkey retina: A light- and electron-microscopic study. Journal of Comparative Neurology 297, 509–534.CrossRefGoogle ScholarPubMed
Hsu, S.M., Raine, L. & Fanger, H. (1981). Use of avidin-biotin peroxidase complex (ABC) in immunoperoxidase techniques. Journal of Histochemistry and Cytochemistry 29, 577–580.CrossRefGoogle ScholarPubMed
Hughes, T.E., Carey, R.G., Vitorica, J., De Blas, A.L. & Karten, H.J. (1989). Immunohistochemical localization of GABAA receptors in the retina of the New World primate (Saimiri sciureus). Visual Neuroscience 2, 565–581.CrossRefGoogle ScholarPubMed
Hughes, T.E., Grünert, U. & Karten, H.J. (1991). GABAA receptors in the retina of the cat: An immunohistochemical study of wholemounts, sections, and dissociated cells. Visual Neuroscience 6, 229–238.CrossRefGoogle Scholar
Ishida, A.T. (1992). The physiology of GABAA receptors in retinal neurons. Progress in Brain Research 90, 29–45.CrossRefGoogle ScholarPubMed
Kaneko, A. & Tachtbana, M. (1987). GABA mediates the negative feedback from amacrine to bipolar cells. Neuroscience Research (Suppl.) 6, 239–252.Google ScholarPubMed
Karschin, A. & Wässle, H. (1990). Voltage- and transmitter-gated currents in isolated rod bipolar cells of rat retina. Journal of Neurophysiology 63, 860–876.CrossRefGoogle ScholarPubMed
Koontz, M.A. & Hendrickson, A.E. (1990). Distribution of GABA-immunoreactive amacrine cell synapses in the inner plexiform layer of macaque monkey retina. Visual Neuroscience 5, 17–28.CrossRefGoogle ScholarPubMed
Laurie, D.J., Seeburg, P.H. & Wisden, W. (1992). The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. 2. Olfactory bulb and Cerebellum. Journal of Neuroscience 12, 1063–1078.CrossRefGoogle ScholarPubMed
Levitan, E.S., Schofteld, D.R.B., Burt, D.R., Rhee, L.M., Wisden, W., Köhler, M., Fujita, N., Rodriguez, H.F., Stephenson, A., Darlison, M.G., Barnard, E.A. & Seeburg, P. (1988). Structural and functional basis for GABAA receptor heterogeneity. Nature 335, 76–79.CrossRefGoogle ScholarPubMed
Lipton, S.A. (1989). GABA-activated single channel currents in out-side-out membrane patches from rat retinal ganglion cells. Visual Neuroscience 3, 275–279.CrossRefGoogle Scholar
Massey, S.C. & Redburn, D.A. (1987). Transmitter circuits in the vertebrate retina. Progress in Neurobiology 28, 55–96.CrossRefGoogle ScholarPubMed
Mosinoer, J.L., Yazulla, S. & Studholme, K.M. (1986). GABA-like immunoreactivity in the vertebrate retina: A species comparison. Experimental Eye Research 41, 631–644.CrossRefGoogle Scholar
Müller, F., Boos, R. & Wässle, H. (1992). Actions of GABAergic ligands on brisk ganglion cells in the cat retina. Visual Neuroscience 9, 415–425.CrossRefGoogle ScholarPubMed
Nakamura, Y., McGutre, B.A. & Sterling, P. (1980). Interplexiform cell in cat retina: Identification by uptake of γ-[3H]aminobutyric acid and serial reconstruction. Proceedings of the National Academy of Sciences of the U.S.A. 77, 658–661.CrossRefGoogle ScholarPubMed
Nishimura, Y., Schwartz, M.L. & Rakic, P. (1986). GABA and GAD immunoreactivity of photoreceptor terminals in primate retina. Nature 320, 753–756.CrossRefGoogle ScholarPubMed
Pourcho, R.G. & Owczarzak, M.T. (1989). Distribution of GABA immunoreactivity in the cat retina: A light- and electron-microscopic study. Visual Neuroscience 2, 425–435.CrossRefGoogle ScholarPubMed
Pourcho, R.G. & Owczarzak, M.T. (1991). Glycine receptor immunoreactivity is localized at amacrine synapses in the cat retina. Visual Neuroscience 7, 611–618.CrossRefGoogle ScholarPubMed
Pritchett, D.B., Lüddens, H. & Seeburg, P.H. (1989). Type I and type II GABAA benzodiazepine receptors produced in transfected cells. Science 246, 1389–1392.CrossRefGoogle Scholar
Richards, J.G., Schoch, P., Häring, P., Takacs, B. & Möhler, H. (1987). Resolving GABAA/benzodiazepine receptors: Cellular and subcellular localization in the CNS with monoclonal antibodies. Journal of Neuroscience 7, 1866–1886.CrossRefGoogle ScholarPubMed
Röhrenbeck, J. (1990). Immunzytochemische Untersuchungen an der Retina von Primaten. Ph.D. Thesis. Mainz: Gutenberg-Universität.Google Scholar
Seeburg, P., Wisden, W., Verdoorn, T.A., Pritchett, D.B., Werner, P., Herb, A., Lüddens, H., Sprengel, R. & Sakmann, B. (1990). The GABAA receptor family: Molecular and functional diversity. Cold Spring Harbour Symposia on Quantitative Biology 55, 29–40.CrossRefGoogle ScholarPubMed
Shivers, B.D., Killisch, I., Sprengel, R., Sontheimer, H., Köhler, M., Schofield, P.R. & Seeburg, P.H. (1989). Two novel GABAA receptor subunits exist in distinct neuronal subpopulations. Neuron 3, 327–337.CrossRefGoogle ScholarPubMed
Sigel, E., Baur, P., Trube, G., Möhler, H. & Malherbe, P. (1990). The effect of subunit composition of rat brain GABAA receptors on channel function. Neuron 5, 703–711.CrossRefGoogle ScholarPubMed
Soltesz, I., Roberts, J.D.B., Takagi, H., Richards, J.G., Möhler, H. & Somogyi, p. (1990). Synaptic and nonsynaptic localization of benzodiazepine/GABAA receptor/Cl-channel complex using monoclonal antibodies in the dorsal lateral geniculate nucleus of the cat. European Journal of Neuroscience 2, 414–429.CrossRefGoogle ScholarPubMed
Somogyi, P., Takagi, H., Richards, J.G. & Möhler, H. (1989). Subcellular localization of benzodiazepine/GABAA receptors in the cerebellum of rat, cat, and monkey using monoclonal antibodies. Journal of Neuroscience 9, 2197–2209.CrossRefGoogle Scholar
Suzuki, S., Tachibana, M. & Kaneko, A. (1990). Effects of glycine and GABA on isolated bipolar cells of the mouse retina. Journal of Physiology 412, 645–662.CrossRefGoogle Scholar
Tachibana, M. & Kaneko, A. (1988). Retinal bipolar cells receive negative feedback input from GABAergic amacrine cells. Visual Neuroscience 1, 297–305.CrossRefGoogle ScholarPubMed
Tauck, D.L., Frosch, M.P. & Lipton, S.A. (1988). Characterization of GABA- and glycine-induced currents of solitary rodent retinal ganglion cells in culture. Neuroscience 11, 193–203.CrossRefGoogle Scholar
Triller, A., Cluzeaud, F., Pfeiffer, F., Betz, H. & Korn, K. (1985). Distribution of gycine receptors at central synapses: An electron-microscopy study. Journal of Cell Biology 101, 683–688.CrossRefGoogle Scholar
Triller, A., Cluzeaud, F. & Korn, K. (1987). Gamma-aminobutyric acid-containing terminals can be apposed to glycine receptors at central synapses. Journal of Cell Biology 104, 947–956.CrossRefGoogle ScholarPubMed
Uhl, G.R., Cutting, G.R., Shimada, S., O’Hara, B., Donovan, D. & Kitayama, S. (1991). GABA C receptors& Sterling, P. (1992). Immunoreactivity to GABAA receptor in outer plexiform layer of the cat retina. Journal of Comparative Neurology 320, 394–397.Google Scholar
Vaughn, J.E., Famiglietti, E.V., Barber, R.P., Saito, K., Roberts, E. & Ribak, C.E. (1981). GABAergic amacrine cells in rat retina: Immunocytochemical identification and synaptic connectivity. Journal of Comparative Neurology 197, 113–127.CrossRefGoogle ScholarPubMed
Verdoorn, T.A., Draguhn, A., Ymer, S., Seeburg, P. & Sakmann, B. (1990). Functional properties of recombinant rat GABAA receptors depend upon subunit composition. Neuron 4, 919–928.CrossRefGoogle ScholarPubMed
Wässle, H. & Chun, M.H. (1989). GABA-like immunoreactivity in the cat retina: Light microscopy. Journal of Comparative Neurology 279, 43–54.CrossRefGoogle ScholarPubMed
Wässle, H. & Boycott, B.B. (1991). Functional architecture of the mammalian retina. Physiological Reviews 71, 447–480.CrossRefGoogle ScholarPubMed
Wisden, W., Morris, B.J., Darlison, M.G., Hunt, S.P. & Barnard, E.A. (1988). Distinct GABAA receptor α subunit mRNAs show differential patterns of expression in bovine brain. Neuron 1, 937–947.CrossRefGoogle ScholarPubMed
Wisden, W., Morris, B.J. & Hunt, S.P. (1991 a). In situ hybridization with synthetic DNA probes. In Molecular Neurobiology–A Practical Approach, ed. Chad, J. & Wheal, H., pp. 205–225. Oxford: IRL Press/Oxford University Press.CrossRefGoogle Scholar
Wisden, W., Herb, A., Wieland, H., Keinänen, K., Lüddens, H. & Seeburg, P.H. (1991 b). Cloning and pharmacological characteristics and expression pattern of the rat GABAA receptor α4 subunit. Federation of European Biochemical Societies Letters 289, 227–230.CrossRefGoogle Scholar
Wisden, W., Laurie, D.J., Monyer, H. & Seeburg, P.H. (1992). The distribution of 13 GABAA receptor subunits mRNAs in the rat brain. 1. Telencephalon, diencephalon, mesencephalon. Journal of Neuroscience 12, 1040–1062.CrossRefGoogle ScholarPubMed
Yamashita, M. & Wässle, H. (1991). Responses of rod bipolar cells isolated from the rat retina to the glutamate agonist 2-amino-4-phos-phono-butyric acid (APB). Journal of Neuroscience 11, 2372–2382.CrossRefGoogle Scholar
Yazulla, S. (1986). GABAergic mechanisms in the retina. In Progress in Retinal Research, Vol. 5, ed. Osborne, N.N. & Chader, G.J., pp. 1–52. Oxford: Pergamon Press.Google Scholar
Yazulla, S., Studholme, K.M., Victoria, J. & De Blas, A.L. (1989). Immunocytochemical localization of GABAA receptors in goldfish and chicken retinas. Journal of Comparative Neurology 280, 15–26.CrossRefGoogle ScholarPubMed
Yeh, H.H., Lee, M.B. & Cheun, J.F. (1990). Properties of GABA-activated whole-cell currents in bipolar cells of the rat retina. Visual Neuroscience 4, 349–357.CrossRefGoogle ScholarPubMed
Yu, B.C.-Y., Watt, C.B., Lam, D.M.K. & Fry, K.R. (1988). GABAergic ganglion cells in the rabbit retina. Brain Research 439, 376–382.CrossRefGoogle ScholarPubMed