Hostname: page-component-78c5997874-s2hrs Total loading time: 0 Render date: 2024-11-15T07:29:19.311Z Has data issue: false hasContentIssue false
  • English
  • Français

Immunohistochemical localization of GABAA receptors in the retina of the new world primate Saimiri sciureus

Published online by Cambridge University Press:  02 June 2009

Thomas E. Hughes ,
Russell G. Carey ,
Javier Vitorica ,
Angel L. de Blas  and
Harvey J. Karten
Thomas E. Hughes
Affiliation:
Department of Neurosciences, University of California, San Diego
Russell G. Carey
Affiliation:
Division of Neurobiology, St. Joseph's Hospital and Medical Center, Barrow Neurological Institute, Phoenix
Javier Vitorica
Affiliation:
Department of Neurobiology and Behavior, State University of New York at Stony Brook
Angel L. de Blas
Affiliation:
Department of Neurobiology and Behavior, State University of New York at Stony Brook
Harvey J. Karten
Affiliation:
Department of Neurosciences, University of California, San Diego
Get access Rights & Permissions [Opens in a new window]

Abstract

A large population of amacrine cells in the retina are thought to use GABA as an inhibitory neurotransmitter in their synaptic interactions within the inner plexiform layer. However, little is known about their synaptic targets; the neurons that express the receptors for GABA have not been clearly identified. Recently, the GABAA receptor has been isolated and antibodies have been raised against it. These antibodies have proven useful for the immunocytochemical localization of the receptor, and two brief reports describing the distribution of GABAA receptor immunoreactivity in the retina have appeared (Richards et al., 1987; Mariani et al., 1987). We used a monoclonal antibody (62–3G1) against the GABAA receptor to study the retina of the New World primate Saimiri sciureus.

Labeled somata were found in the inner nuclear layer (INL) and ganglion cell layer (GCL). The staining was confined to what appeared to be the cell's plasmalemma and small cytoplasmic granules. Most of the labeled neurons in the INL had small somata (5–7 μm in diameter) located at the vitreal edge of the layer. They arborized in two laminae (approximately 2 and 4) of inner plexiform layer (IPL). Ventral to the optic disc (2.5 mm) they comprised 29% of the cells present. A few of the labeled neurons appeared to be interplexiform cells or flat bipolar cells, with labeled processes that extended into both the IPL and the inner half of the outer plexiform layer. In the GCL, the labeled somata were among the largest present (13–20 μm in diameter), and 2.5 mm ventral to the optic disc they made up 15% of the cells present. Experiments in which immunoreactive somata were retrogradely labeled following the injection of fluorescent tracers into the optic tract provided a conclusive demonstration that some of the immunoreactive somata were ganglion cells. The antibody often labeled their axons in the optic fiber layer. This suggests that the GABAA receptors are transported anterogradely to the retinal terminal fields. The dendrites of the immunoreactive ganglion cells extended into the 2 laminae of labeled processes in the IPL, and their primary dendritic arbors were, at any given eccentricity, quite similar in appearance. This homogeneity suggests that they comprise a particular subset of the ganglion cells.

Sections simultaneously labeled with the monoclonal antibody against the GABAA receptor and antisera against either L-glutamic acid decarboxylase (GAD) or GABA revealed that the GAD/GABA was distributed much more widely in the IPL than the GABAA receptor. This variance may reflect either the presence of other, perhaps GABAB, receptors in the IPL or GABA in portions of the IPL where it is ineffective as a neurotransmitter.

Keywords

GABAGABAA receptorAmacrine cellsGanglion cellsRetinaPrimate
Type
Research Article
Information
Visual Neuroscience , Volume 2 , Issue 6 , June 1989 , pp. 565 - 581
Copyright
Copyright © Cambridge University Press 1989

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Agardh, E., Bruun, A., Ehinger, B., Ekström, P., Van Veen, T. & Wu, J.Y. (1987 a). Gamma-aminobutyric acid- and glutamic acid de-carboxylase-immunoreactive neurons in the retina of different vertebrates. Journal of Comparative Neurology 258, 622–630.Google Scholar
Agardh, E., Bruun, A., Ehinger, B. & Storm-Mathisen, J. (1986). Gaba immunoreactivity in the retina. Investigative Ophthalmology and Visual Science 27, 674–678.Google Scholar
Agardh, E., Ehinger, B. & Wu, J.Y. (1987 b). Gaba and Gad-like immunoreactivity in the primate retina. Histochemistry 86, 485–490.Google Scholar
Alstein, M., Dudai, Y. & Vogel, Z. (1981). Benzodiazepine receptors in chick retina: development and cellular localization. Brain Research 206, 198–202.Google Scholar
Ariel, M. & Adolph, A.R. (1985). Neurotransmitter inputs to directionally sensitive turtle retinal ganglion cells. Journal of Neurophysiology 54, 1123–1143.CrossRefGoogle ScholarPubMed
Ariel, M. & Daw, N.W. (1982). Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells. Journal of Physiology (London) 324, 161–185.Google Scholar
Ball, A.K. (1987). Immunocytochemical and autoradiographic localization of GABAergic neurons in the goldfish retina. Journal of Comparative Neurology 255, 317–325.Google Scholar
Bai, S.-H. & Slaughter, M.M. (1989). Baclofen enhances transient responses of retinal neurons through two mechanisms. Journal of Neurophysiology (in press).Google Scholar
Barnard, E.A., Darlison, M.G. & Seeburg, P. (1987). Molecular biology of the GABAA receptor: the receptor/channel superfamily. Trends in Neuroscience 10, 502–509.CrossRefGoogle Scholar
Belgum, J.H., Dvorak, D.R. & McReynolds, J.S. (1984). Strychnine blocks transient but not sustained inhibition in mudpuppy retinal ganglion cells. Journal of Physiology (London) 354, 273–286.Google Scholar
Bolz, J., Frumkes, T., Voigt, T. & Wässle, H. (1985). Action and localization of gamma-aminobutyric acid in the cat retina. Journal of Physiology (London) 362, 369–393.Google Scholar
Bonaventure, N. & Wioland, N. (1981). Involvement of GABA in ganglion cell receptive-field organization in the frog retina. Vision Research 21, 1653–1655.Google Scholar
Bonaventure, N., Wioland, N. & Jardon, B. (1986). Anisotropic inhibition in the receptive field surround of the frog retinal ganglion cells, evidenced by bicuculline and SR 95103, a new GABA antagonist. European Journal of Pharmacology 121, 327–336.Google Scholar
Borman, J. (1988). Electrophysiology of GABAA and GABAB receptor subtypes. Trends in Neuroscience 11, 112–116.CrossRefGoogle Scholar
Boycott, B.B. & Dowling, J.E. (1969). Organization of the primate retina: light microscopy. Philosophical Transactions of the Royal Society B (London) 255, 109–184.Google Scholar
Boycott, B.B., Dowling, J.E., Fisher, S.K., Kolb, H. & LAties, A.M. (1975). Interplexiform cells of the mammalian retina and their comparison with catecholamine-containing retinal cells. Proceedings of the Royal Society B (London) 191, 353–368.Google ScholarPubMed
Brandon, C. (1985). Retinal GABA neurons: localization in vertebrate species using an antiserum to rabbit brain glutamate decarboxylase. Brain Research 344, 286–295.CrossRefGoogle ScholarPubMed
Brecha, N. (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., Francis, A. & Schechter, N. (1979). Rapid loss of nicotine-cholinergic receptor binding activity in the deafferented avian optic lobe. Brain Research 167, 273–280.CrossRefGoogle ScholarPubMed
Bunt, A.H., Hendrickson, A.E., Lund, J.S., Lund, R.D. & Fuchs, A.F. (1975). Monkey retinal ganglion cells: morphometric analysis and tracing of axonal projections with a consideration of the peroxidase technique. Journal of Comparative Neurology 164, 265–286.Google Scholar
Caldwell, J.H. & Daw, N.W. (1978). Effects of picrotoxin and strychnine on rabbit retinal ganglion cells: changes in centre surround receptive fields. Journal of Physiology 276, 299–310.Google Scholar
Cohen, J.L. (1985). Effects of glycine and GABA on the ganglion cells of the retina of the skate (Raja erinacea). Brain Research 332, 169–173.Google Scholar
Daw, N.W. & Ariel, M. (1981). Effect of synaptic transmitter drugs on receptive fields of rabbit retinal ganglion cells. Vision Research 21, 1643–1647.Google Scholar
de Blas, A.L., Vitorica, J. & Friedrich, P. (1988). Localization of the GABAA receptor in the rat brain with a monoclonal antibody to the 57,000 Mr peptide of the GABAA receptor/benzodiazepine receptor/CL-channel complex. Journal of Neuroscience 8, 602–614.CrossRefGoogle Scholar
Dowling, J.E. (1987). The Retina: An Approachable Part of the Brain. Cambridge, Massachusetts: Harvard University Press.Google Scholar
Enna, S.J. & Snyder, S.H. (1976). Gamma-aminobutyric acid (GABA) receptor binding in mammalian retina. Brain Research 115, 174–179.CrossRefGoogle ScholarPubMed
Frumkes, T.E., Miller, R.F., Slaughter, M. & Dacheux, R.F. (1981). Physiological and pharmacological basis of GABA and glycine action on neurons of mudpuppy retina. III. Amacrine-mediated inhibitory influences on ganglion cell receptive-field organization: a model. Journal of Neurophysiology 45, 783–804.CrossRefGoogle ScholarPubMed
Gläsener, G., Himstedt, W., Weiler, R., Matute, C. (1988). Putative neurotransmitters in the retinae of three urodele species (Triturus alpestris, Salamandra salamandra, Pleurodeles waltli). Cell and Tissue Research 252, 317–328.Google Scholar
Glickman, R.D., Adolph, A.R. & Dowling, J.E. (1982). Inner plexiform circuits in the carp retina: effects of cholinergic agonists, GABA, and substance P on the ganglion cells. Brain Research 234, 81–99.CrossRefGoogle ScholarPubMed
Hendrickson, A., Ryan, M., Noble, B. & Wu, J.-Y. (1985). Colo-calization of [3H]muscimol and antisera to GABA and glutamic acid decarboxylase within the same neurons in monkey retina. Brain Research 348, 391–396.Google Scholar
Henley, J.M., Lindstrom, J.M. & Oswald, R.E. (1986). Acetylcho-Iine receptor synthesis in retina and transport to optic tectum in goldfish. Science 232, 1627–1629.CrossRefGoogle ScholarPubMed
Houser, C.R., Olsen, R.W., Richards, J.G. & Möhler, H. (1988). Immunohistochemical localization of benzodiazepine/GABAA receptors in the human hippocampal formation. Journal of Neuroscience 8, 1370–1383.Google Scholar
Howells, R.D. & Simon, E.J. (1980). Benzodiazepine binding in chicken retina and its interaction with gamma-aminobutyric acid. European Journal of Pharmacology 67, 133–137.Google Scholar
Ikeda, H. & Sheardown, M.J. (1983). Transmitters mediating inhibition of ganglion cells in the cat retina: iontophorectic studies in vivo. Neuroscience 8, 837–853.Google Scholar
Jäger, J. & Wässle, H. (1987). Localization of glycine uptake and receptors in the cat retina. Neuroscience Letters 75, 147–151.CrossRefGoogle ScholarPubMed
Kaneko, A. & Tachibana, M. (1986). Effects of gamma-aminobutyric acid on isolated cone photoreceptors of the turtle retina. Journal of Physiology (London) 373, 443–461.Google Scholar
Keyser, K.T., Hughes, T.E., Whiting, P.J., Lindstrom, J.M. & Kar-Ten, H.J. (1988). Cholinoceptive neurons in the retina of the chick: an immunohistochemical study of the nicotinic acetylcholine receptors. Visual Neuroscience 1, 349–366.Google Scholar
Kirby, A.W. (1979). The effect of strychnine, bicuculline, and picro-toxin on X and Y cells in the cat retina. Journal of General Physiology 74, 71–84.Google Scholar
Kirby, A.W. & Enroth-Cugell, C. (1976). The involvement of gamma-aminobutyric acid in the organization of cat retinal ganglion cell receptive fields. Journal of General Physiology 68, 465–484.CrossRefGoogle ScholarPubMed
Kirby, A.W. & Schweitzer-Tong, D.E. (1981). Gaba-antagonists and spatial summation in Y-type cat retinal ganglion cells. Journal of Physiology (London) 312, 335–344.Google Scholar
Kojima, K., Mizuno, K. & Miyazaki, M. (1958). Gamma-aminobutyric acid in ocular tissue. Nature 181, 1200–1201.Google Scholar
Koontz, M.A. & Hendrickson, A.E. (1987). Stratified distribution of synapses in the inner plexiform layer of primate retina. Journal of Comparative Neurology 263, 581–592.Google Scholar
Koontz, M.A., Hendrickson, A.E. & Ryan, M.K. (1989). GABA-immunoreactive synaptic plexus in the nerve fiber layer of primate retina. Visual Neuroscience 2, 19–25.CrossRefGoogle ScholarPubMed
Lasater, E.M. & Lam, D.M. (1984 a). The indentification and some functions of GABAergic neurons in the distal catfish retina. Vision Research 24, 497–506.CrossRefGoogle Scholar
Lasater, E.M. & Lam, D.M. (1984 b). The identification and some functions of GABAergic neurons in the proximal retina of the catfish. Vision Research 24, 875–881.CrossRefGoogle ScholarPubMed
Leventhal, A.G., Rodieck, R.W. & Dreher, B. (1981). Retinal ganglion cell classes in cat and Old-World monkey: morphology and central projections. Science 213, 1139–1142.Google Scholar
Levitan, E.S., Schofield, P.R., 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.H. (1988). Structural and functional basis for GABAA receptor heterogeneity. Nature 355, 76–79.Google Scholar
Lin, C.T., Song, G.X. & Wu, J.Y. (1985). Ultrastructural demonstration of L-glutamate decarboxylase and cysteinesulfinic acid decar-boxylase in rat retina by immunocytochemistry. Brain Research 331, 71–80.Google Scholar
Mamalaki, C., Stephenson, R.A. & Barnard, E.A. (1987). The GABA/benzodiazepine receptor is a heterotetramer of homologous α and β subunits. The EMBO Journal 6, 561–565.Google Scholar
Marc, R.E. (1986). Neurochemical stratification in the inner plexiform layer of the vertebrate retina. Vision Research 26, 223–238.Google Scholar
Mariani, A.P. (1984). The neuronal organization of the outer plexiform layer of the primate retina. International Review of Cytology 86, 285–320.Google Scholar
Mariani, A.P. & Caserta, M.T. (1986). Electron microscopy of glu-tamate decarboxylase (GAD) immunoreactivity in the inner plexiform layer of the rhesus monkey retina. Journal of Neurocytology 15, 645–655.Google Scholar
Mariani, A.P., Cosenza-Murphy, D. & Barker, J.L. (1987). GABAergic synapses and benzodiazepine receptors are not identically distributed in the primate retina. Brain Research 415, 152–157.Google Scholar
McGuire, B.A., Stevens, J.K. & Sterling, P. (1986). Microcircuitry of Beta ganglion cells in cat retina. Journal of Neuroscience 6, 907–918.Google Scholar
Miller, R.F., Frumkes, T.E., Slaughter, M. & Dacheux, R.F. (1981 a). Physiological and pharmacological basis of GABA and glycine action on neurons of mudpuppy retina. I. Receptors, horizontal cells, bipolars, and G-cells. Journal of Neurophysiology 45, 743–763.Google Scholar
Miller, R.F., Frumkes, T.E., Slaughter, M. & Dacheux, R.F. (1981 b). Physiological and pharmacological basis of GABA and glycine action on neurons of mudpuppy retina. II. Amacrine and ganglion cells. Journal of Neurophysiology 45, 764–782.Google Scholar
Mosinger, J.L., Yazulla, S. & Studholme, K.M. (1986). GABA-like immunoreactivity in the vertebrate retina: a species comparison. Experimental Eye Research 42, 631–644.Google Scholar
Negishi, K., Teranishi, T. & Kato, S. (1983). A GABA antagonist, bicuculline, exerts its uncoupling action on external horizontal cells through dopamine cells in carp retina. Neuroscience Letters 37, 261–266.CrossRefGoogle ScholarPubMed
Nishtmura, Y., Schwartz, M.L. & Rakic, P. (1985). Localization of gamma-aminobutyric acid and glutamic acid decarboxylase in rhesus monkey retina. Brain Research 359, 351–355.Google Scholar
O'Connor, P., Dorison, S.J., Watltng, K.J. & Dowling, J.E. (1986). Factors affecting release of 3H-dopamine from perfused carp retina. Journal of Neuroscience 6, 1857–1865.Google Scholar
Paul, S.M., Zatz, M. & Skolnick, P. (1980). Demonstration of brain-specific benzodiazepine receptors in rat retina. Brain Research 187, 243–246.Google Scholar
Perry, V.H., Oehler, R. & Cowey, A. (1984). Retinal ganglion cells that project to the dorsal lateral geniculate nucleus in the Macaque monkey. Neuroscience 12, 1101–1123.Google Scholar
Perry, V.H. & Cowey, A. (1984). Retinal ganglion cells that project to the superior colliculus and pretectum in the Macaque monkey. Neuroscience 12, 1125–1137.Google Scholar
Pessac, B., Towle, A.C., Geffard, M. & Wu, J.Y. (1987). The presence of glutamic acid decarboxylase and gamma-aminobutyric acid immunoreactivity in photoreceptors of hatching quail retina. Brain Research 4283, 156–159.CrossRefGoogle Scholar
Ramón, Y Cajal S. (1972). The Structure of the Retina. Springfield, Illinois: Charles C. Thomas, Publisher.Google Scholar
Regan, J.W., Roeske, W.R. & Yamamura, H.I. (1980). 3H-Flunitrazepam binding to bovine retina and the affect of GABA thereon. Neuropharmacology 19, 413–415.Google 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.Google Scholar
Saito, H. (1981). The effects of strychnine and bicuculline on the responses of X- and Y-cells of the isolated eye-cup preparation of the cat. Brain Research 212, 243–248.Google Scholar
Saito, H. (1983). Pharmacological and morphological differences between X- and Y-type ganglion cells in the cat's retina. Vision Research 23, 1299–1308.CrossRefGoogle ScholarPubMed
Sargent, P.B., Pike, S.H., Nadel, D.B. & Lindstrom, J.M. (1989). Nicotinic acetylcholine receptor-like molecules in the retina, retinotectal pathway, and optic tectum of the frog. The Journal of Neuroscience, 9, 565–573.Google Scholar
Schoch, P., Häring, P., Takacs, B., Stähli, C. & Möhler, H. (1984). A GABA/benzodiazepine receptor complex from bovine brain: Purification, reconstitution and immunological characterization. Journal of Receptor Research 4, 189–200.CrossRefGoogle ScholarPubMed
Sigel, E., Stephenson, F.A., Mamalaki, C. & Barnard, E.A. (1983). A γ-aminobutyric acid/benzodiazepine receptor complex of bovine cerebral cortex: purification and partial characterization. Journal of Biological Chemistry 258, 6965–6971.Google Scholar
Sigel, E. & Barnard, E.A. (1984). A γ-aminobutyric acid/benzodiazepine receptor complex from bovine cerebral cortex. Improved purification with preservation of regulatory sites and their interactions. Journal of Biological Chemistry 259, 7219–7223.Google Scholar
Slaughter, M.M. & Bai, S.-H. (1989). Differential effects of baclofen on sustained and transient responses of retinal neurons. Journal of Neurophysiology (in press).Google Scholar
Stevens, J.K., McGuire, B.A. & Sterling, P. (1980). Toward a functional architecture of the retina: serial reconstruction of adjacent ganglion cells. Science 207, 317–319.Google Scholar
Stone, J. & Johnston, E. (1981). The topography of primate retina: a study of the human, bushbaby, and New and Old World monkeys. Journal of Comparative Neurology 196, 205–223.CrossRefGoogle ScholarPubMed
Stone, J. (1983). Parallel Processing in the Visual System. New York: Plenum Press.Google Scholar
Storm-Mathisen, J., Liknes, A.K., Bore, A.T., Vaaland, J.L., Edminson, P., Haug, M.S. & Ottersen, O.P. (1983). First visualization of glutamate and GABA in neurons by immunocytochemistry. Nature 301, 517–520.Google Scholar
Straschtll, M. (1968). Actions of drugs on single neurons in the cat's retina. Vision Research 8, 35–47.Google Scholar
Straschill, M. & Perwein, J. (1969). The inhibition of retinal ganglion cells by catecholeamines and γ-aminobutyric acid. Pflügers Archiv, European Journal of Physiology 312, 45–54.Google Scholar
Straus, W. (1982). Imidazole increases the sensitivity of the cytochemical reaction for peroxidase with diaminobenzidine at a neutral pH. Journal of Histochemistry and Cytochemistry 30, 491–493.Google Scholar
Swanson, L.W., Simmons, D.M., Whiting, P.J. & Lindstrom, J. (1987). Immunohistochemical localization of neuronal nicotinic receptors in the rodent central nervous system. Journal of Neuroscience 7, 334–342.Google Scholar
Tachibana, M. & Kaneko, A. (1987). Gamma-Aminobutyric acid exerts a local inhibitory action on the axon terminal of bipolar cells: evidence for negative feedback from amacrine cells. Proceedings of the National Academy of Sciences of the U.S.A. 84, 3501–3505.Google Scholar
Triller, A., Cluzeaud, F., Pfeiffer, F., Betz, H. & Korn, H. (1985). Distribution of glycine receptors at central synapses: an immunoelectron microscopy study. Journal of Cell Biology 101, 683–688.Google Scholar
van den Pol, A.N. & Gorcs, T. (1988). Glycine and glycine receptor immunoreactivity in brain and spinal cord. Journal of Neuroscience 8, 472–492.Google Scholar
Vaughn, J.E., Famiglietti, E.V. Jr, 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.Google Scholar
Vitorica, J., Park, D., Chin, G. & de Blas, A.L. (1988). Monoclonal antibodies and conventional antisera to the GABAA receptor/benzodiazepine receptor/Cl- channel complex. Journal of Neuroscience 8, 615–622.Google Scholar
Wässle, H. & Chun, M.H. (1988). Dopaminergic and Indoleamine-accumulating amacrine cells express GABA-like immunoreactivity in the cat retina. Journal of Neuroscience 8, 3383–3394.Google Scholar
Yazulla, S. & Brecha, N. (1980). Binding and uptake of the GABA analogue, 3H-muscimol, in the retinas of goldfish and chicken. Investigative Ophthalmology and Visual Science 19, 1415–1426.Google Scholar
Yazulla, S. & Brecha, N. (1981). Localized binding of [3H] muscimol to synapses in chicken retina. Proceedings of the National Academy of Sciences of the U.S.A. 78, 643–647.CrossRefGoogle ScholarPubMed
Yazulla, S., Studholme, K.M., Vitorica, J. & de Blas, A.L. (1989). Immunocytochemical localization of GABAA receptors in goldfish and chicken retinas. Journal of Comparative Neurology 280, 15–26.Google Scholar
Zarbin, M.A., Wamsley, J.K., Palacios, J.M. & Kuhar, M.J. (1986). Autoradiographic localization of high-affinity GABA, Benzodiazepine, Dopaminergic, Adrenergic, and Muscarinic Cholinergic receptors in the Rat, Monkey, and Human retina. Brain Research 374, 75–92.CrossRefGoogle ScholarPubMed