Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-24T13:20:56.112Z Has data issue: false hasContentIssue false
  • English
  • Français

The role of NMDA and non-NMDA excitatory amino acid receptors in the functional organization of primate retinal ganglion cells

Published online by Cambridge University Press:  02 June 2009

Ethan D. Cohen  and
Robert F. Miller
Ethan D. Cohen
Affiliation:
Department of Physiology, University of Minnesota Medical School, Minneapolis
Robert F. Miller
Affiliation:
Department of Physiology, University of Minnesota Medical School, Minneapolis
Get access Rights & Permissions [Opens in a new window]

Abstract

The role of excitatory amino acid (EAA) receptors in primate retinal ganglion cell function was analyzed in a superfused retina-eyecup preparation using single-unit, extracellular recording techniques. The effects of bath applied L-2–amino-4–phosphonobutyrate (APB), N-methyl-D-aspartate (NMDA), and non-NMDA EAA receptor agonists and antagonists were examined on the light-evoked responses and resting firing rates of ganglion cells. APB (30–100 μM) reduced or blocked the light-evoked responses and resting firing rates of all ON-center ganglion cells; higher doses of APB (100 μM) were required to block the light-evoked responses of ON-transient cells. In contrast, an increase in resting firing rates was observed when L-APB was applied to some OFF-center ganglion cells. The EAA agonists kainate (KA) (10–20 μM) and NMDA (200–350 μM) increased the firing rate of virtually all ganglion cells examined. Quisqualate (10–20 μM) increased firing in most cells, but occasionally (4/13 cases) produced inhibition. The NMDA antagonist D-amino-phosphono-heptanoic acid (D-AP7) (200–250 μM) reduced the light-evoked responses of ganglion cells by an average of 12% from control levels, while resting firing rates declined 37%. In the presence of D-AP7, the basic receptive-field characteristics of cells were not significantly altered. In contrast, two non-NMDA receptor antagonists, NBQX (2,3–Dihydroxy-6–nitro-7–sulfamoyl-benzo-(F)-quinoxalinedione) and DNQX (6,7–dinitro-quinoxaline-2,3–dione), produced substantial reductions in the light-evoked responses (82%) and resting firing rates (87%) of all ganglion cell classes. A striking observation in some neurons was the recovery of a persistent transient light-evoked response in the presence of NBQX. This NBQX-insensitive, light-evoked response was always blocked by adding D-AP7. Thus, neurotransmission from bipolar to ganglion cells in primates is mediated predominantly by non-NMDA EAA receptors, with NMDA receptors forming a minor component of the light-evoked response.

Keywords

Primate retinaExcitatory amino acid receptorsQuinoxalinesGanglion cells
Type
Research Articles
Information
Visual Neuroscience , Volume 11 , Issue 2 , March 1994 , pp. 317 - 332
Copyright
Copyright © Cambridge University Press 1994

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

Aizenman, E., Frosch, M.P. & Lipton, S.A. (1988). Responses mediated by excitatory amino acid receptors in solitary retinal ganglion cells from rat. Journal of Physiology 396, 75–91.CrossRefGoogle ScholarPubMed
Ames, A. & Nesbett, F.B. (1981). In vitro retina as experimental model of the central nervous system. Journal of Neurochemistry 37, 867–877.CrossRefGoogle ScholarPubMed
Anis, N.A., Berry, S.C., Burton, N.R. & Lodge, D. (1983). The dissociative anesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl aspartate. British Journal of Pharmacology 79, 565–575.CrossRefGoogle ScholarPubMed
Arkin, M.S. & Miller, R.F. (1987). Subtle actions of 2–amino-4–phosphonobutyrate (APB) on the OFF pathway in the mudpuppy retina. Brain Research 426, 142–148.CrossRefGoogle ScholarPubMed
Ascher, P. & Nowak, L. (1988). The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurons in culture. Journal of Physiology 396, 75–91.Google Scholar
Birch, P.J., Grossman, C.J. & Hayes, A.G. (1988). Kynurenate and FG9041 have both competitive and non-competitive antagonist actions at excitatory amino acid receptors. European Journal of Pharmacology 151, 313–315.CrossRefGoogle ScholarPubMed
Boos, R., Muller, F. & Wassle, H. (1990). Actions of excitatory amino acids on brisk ganglion cells in the cat retina. Journal of Neurophysiology 65, 1368–1379.CrossRefGoogle Scholar
Chen, L. & Huang, L.-Y. (1992). Protein kinase C reduces Mg2+ block of NMDA-receptor channels as a mechanism of modulation. Nature 356, 521–523.CrossRefGoogle ScholarPubMed
Cohen, E.D. & Miller, R. F. (1990). The role of NMDA receptors in ganglion cell excitability in the primate retina. Investigative Ophthalmology and Visual Science (Suppl.) 32, p. 114.Google Scholar
Cohen, E.D. & Miller, R.F. (1991). NBQX reveals a prominent NMDA response in the rabbit retina. Society for Neuroscience (Abstract) 17, 403.1.Google Scholar
Cohen, E.D. & Sterling, P. (1992). Parallel circuits from cones to the on-beta ganglion cell. European Journal of Neuroscience 4, 506–520.CrossRefGoogle Scholar
Coleman, P. & Miller, R.F. (1988). Do N-Methyl-D-aspartate receptors mediate synaptic responses in the mudpuppy retina? Journal of Neuroscience 8, 4728–4733.CrossRefGoogle ScholarPubMed
Coleman, P., Yu, W.-F. & Miller, R. (1991). NBQX reveals an NMDA mediated EPSP in the retina of the mudpuppy. Society for Neuroscience (Abstract) 17, 107.8.Google Scholar
Copenhagen, D. R. & Jahr, C. (1989). Release of endogenous excitatory amino acids from turtle photoreceptors. Nature 341, 536–539.CrossRefGoogle ScholarPubMed
Dacheux, R.F. & Raviola, E. (1990). Physiology of H1 horizontal cells in the primate retina. Proceedings of the Royal Society B 239, 213–230.Google Scholar
Demonasterio, F.M. & Gouras, P. (1975). Functional properties of ganglion cells of the rhesus retina. Journal of Physiology 251, 167–195.CrossRefGoogle Scholar
Dixon, D.B. & Copenhagen, D.R. (1992). Two types of glutamate receptors differentially excite amacrine cells in the tiger salamander retina. Journal of Physiology 449, 589–606.CrossRefGoogle ScholarPubMed
Dolan, R.P. & Schiller, P.H. (1989). Evidence for only depolarizing rod bipolar cells in the primate retina. Visual Neuroscience 2, 421–424.CrossRefGoogle ScholarPubMed
Ehinger, B., Otterson, P., Storm-Mathisen, J. & Dowling, J. (1988). Bipolar cells in the turtle retina are strongly immunoreactive for glutamate. Proceedings of the National Academy of Sciences of the U.S.A. 85, 8321–8325.CrossRefGoogle ScholarPubMed
Freed, M.A. & Sterling, P. (1988). The on-alpha ganglion cell of the cat retina and its presynaptic cell types. Journal of Neuroscience 8, 2303–2320.CrossRefGoogle ScholarPubMed
Gottesman, J. & Miller, R.F. (1992). Pharmacology properties of N-Methyl-D-Aspartate receptors on ganglion cells in an amphibian retina. Journal of Neurophysiology 68, 596–604.CrossRefGoogle Scholar
Gouras, P. (1968). Identification of cone mechanisms in ganglion cells. Journal of Physiology 199, 533–547.CrossRefGoogle ScholarPubMed
HonorÉ, T., Davies, T., Drejer, J., Fletcher, E.J., Jacobsen, P., Lodge, D. & Nielsen, F.E. (1988). Quinoxalinediones: Potent competitive non-NMDA glutamate receptor antagonists. Science 241, 701–703.CrossRefGoogle ScholarPubMed
Hughes, T.E., Hermans-Borgmeyer, I. & Heinemann, S. (1992). Differential expression of glutamate receptor genes (GluR1–5) in the rat retina. Visual Neuroscience 8, 49–55.CrossRefGoogle ScholarPubMed
Kaplan, E. & Shapley, R.M. (1986). The primate retina contains 2 types of ganglion cells with high and low contrast sensitivity. Proceedings of the National Academy of Sciences of the U.S.A. 83, 2755–2757.CrossRefGoogle Scholar
Karschin, A., Aizenman, E. & Lipton, S. (1988). The interactions of agonists and non-competitive antagonists at the excitatory amino acid receptors in rat retinal ganglion cells in vitro. Journal of Neuroscience 8, 2895–2906.CrossRefGoogle Scholar
Kay, C. & Ikeda, H. (1989). Quinoxalinediones antagonize the visual firing of sustained retinal ganglion cells. European Journal of Pharmacology 164, 381–384.CrossRefGoogle Scholar
Kelso, S.R., Nelson, T.E. & Leonard, J.P. (1992). Protein kinase C enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes. Journal of Physiology 449, 705–718.CrossRefGoogle ScholarPubMed
Kessler, M., Baudry, M. & Lynch, G. (1989). Quinoxaline derivatives are high-affinity antagonists of the NMDA receptor-associated glycine sites. Brain Research 489, 377–382.CrossRefGoogle ScholarPubMed
Knapp, A.G. & Schiller, P.H. (1984). The contribution of ON-bipolar cells to the electroretinogram of rabbit and monkey. Vision Research 24, 1841–1846.CrossRefGoogle Scholar
Kolb, H. (1979). The inner plexiform layer in the retina of the cat: Electron-microscopic observations. Journal of Neurocytology 8, 295–329.CrossRefGoogle ScholarPubMed
Kolb, H. & Dekorver, L. (1991). Midget ganglion cells of the parafovea of the human retina: A study by electron microscopy and serial section reconstructions. Journal of Comparative Neurology 303, 617–636.CrossRefGoogle ScholarPubMed
Leventhal, A.G., Rodiek, R.W. & Dreher, B. (1981). Retinal ganglion cell classes in the Old World: Morphology and central projections. Science 213, 1139–1142.CrossRefGoogle ScholarPubMed
Levick, W.R. (1972). Another tungsten microelectrode. Medical and Biological Engineering 10, 510–515.CrossRefGoogle ScholarPubMed
Liman, E.R., Knapp, A.G. & Dowling, J.E. (1989). Enhancement of kainate-gated currents in retinal horizontal cells by cyclic AMP-dependent protein kinase. Brain Research 481, 399–402.CrossRefGoogle ScholarPubMed
Marc, R.E., Liu, W.L., Kalliontis, M., Raiguel, S.F. & Vanjaesendonck, E. (1990). Patterns of glutamate immunoreactivity in the goldfish retina. Journal of Neuroscience 10, 4006–4034.CrossRefGoogle ScholarPubMed
Massey, S.C., Redburn, D.A. & Crawford, M.J. (1983). The effects of 2–amino-4–phosphonobutyric acid (APB) on the ERG and ganglion cell discharge of rabbit retina. Vision Research 23, 1607–1613.CrossRefGoogle ScholarPubMed
Massey, S.C. (1990). Cell types using glutamate as a neurotransmitter. In Progress in Retinal Research, Vol. 10, ed. Osborne, N. & Chader, G., pp. 399–425. Oxford, England: Pergamon Press.Google Scholar
Massey, S.C. & Miller, R.F. (1987). Excitatory amino acid receptors of rod- and cone-driven horizontal cells in the rabbit retina. Journal of Neurophysiology 57, 645–659.CrossRefGoogle ScholarPubMed
Massey, S.C. & Miller, R.F. (1988). Glutamate receptors of ganglion cells in the rabbit retina: Evidence for glutamate as a bipolar transmitter. Journal of Physiology 405, 635–655.CrossRefGoogle ScholarPubMed
Massey, S.C. & Miller, R.F. (1990). N-Methyl-D-aspartate receptors on ganglion cells in the rabbit retina. Journal of Neurophysiology 63, 16–30.CrossRefGoogle ScholarPubMed
Mayer, M.L. & Westbrook, G.L. (1987). The physiology of excitatory amino acids in the vertebrate central nervous system. Progress in Neurobiology 28, 197–276.CrossRefGoogle ScholarPubMed
Mcguire, B.A., Smith, R.G. & Sterling, P. (1986). Microcircuitry of beta ganglion cells in the cat retina. Journal of Neuroscience 6, 907–918.CrossRefGoogle ScholarPubMed
Miller, B.M., Sarantis, M., Traynellis, S.F. & Atwell, D. (1992). Potentiation of NMDA receptor currents by arachidonic acid. Nature 355, 722–725.CrossRefGoogle ScholarPubMed
Miller, R.F. & Dacheux, R.F. (1976). Synaptic organization and ionic basis of on and off channels in mudpuppy retina. I. Intracellular analysis of chloride-sensitive electrogenic properties of receptors, horizontal cells, bipolar cells, and amacrine cells. Journal of General Physiology 67, 639–659.CrossRefGoogle Scholar
Miller, R.F. & Slaughter, M.M. (1986). Excitatory amino acid receptors of the retina: Diversity of subtypes and conductance mechanisms. Trends in Neurosciences 9, 211–218.CrossRefGoogle Scholar
Miller, R.F., Zalutsky, R.A. & Massey, S.C. (1986). A perfused retina preparation suitable for pharmacological studies. Journal of Neuroscience Methods 16, 309–322.CrossRefGoogle ScholarPubMed
Mittman, S., Taylor, W.R. & Copenhagen, D.R. (1990). Concomitant activation of two types of glutamate receptor mediates excitation of salamander retinal ganglion cells. Journal of Physiology 428, 175–197.CrossRefGoogle ScholarPubMed
Monyer, H., Sprengel, R., Schoepfer, R., Herb, A., Higuchi, M., Lomeli, H., Burnashev, N., Sakmann, B. & Seeburg, P.H. (1992). Heteromeric NMDA receptors: Molecular and functional distinction of subtypes. Science 256, 1217–1221.CrossRefGoogle ScholarPubMed
Moriyoshi, K., Masu, M., Ishii, T., Shigemoto, R., Mizuno, N. & Nakanishi, S. (1991). Molecular cloning and characterization of the rat NMDA receptor. Nature 354, 31–37.CrossRefGoogle ScholarPubMed
Muller, F., Wassle, H. & Voigt, T. (1988). Pharmacological modulation of the rod pathway in the cat retina. Journal of Neurophysiology 59, 1657–1672.CrossRefGoogle ScholarPubMed
Murakami, M., Ohtsuka, T. & Shimazaki, H. (1975). Effects of aspartate and glutamate on the bipolar cells in the carp retina. Vision Research 15, 456–458.CrossRefGoogle ScholarPubMed
Nawy, S. & Jahr, C.E. (1990). Suppression of glutamate of cGMP conductance in retinal bipolar cells. Nature 346, 269–271.CrossRefGoogle ScholarPubMed
Nowak, L., Bregestovski, P., Ascher, P., Herbert, A. & Prochlantz, A. (1984). Magnesium gates glutamate-activated channels in mouse central neurones. Nature 307, 462–465.CrossRefGoogle ScholarPubMed
O’Dell, T.J. & Christensen, B.N. (1989). Horizontal cells isolated from catfish retina contain two types of excitatory amino acid receptors. Journal of Neurophysiology 61, 1097–1109.CrossRefGoogle ScholarPubMed
Perry, V.H. & Cowey, A. (1984). Retinal ganglion cells that project to the superior colliculus and pretectum in the macacque monkey. Neuroscience 12, 1125–1137.CrossRefGoogle Scholar
Perry, V.H., Oehler, R. & Cowey, A. (1984). Retinal ganglion cells that project to the dorsal lateral geniculate nucleus in the macacque monkey. Neuroscience 12, 1101–1123.CrossRefGoogle Scholar
Sah, P., Hestrin, S. & Nicoll, R.A. (1989). Tonic activation of NMDA receptors by ambient glutamate enhances excitability of neurons. Science 246, 815–818.CrossRefGoogle ScholarPubMed
Schiller, P.H. (1982). Central connections of the retinal ON and OFF pathways. Nature 297, 580–583.CrossRefGoogle ScholarPubMed
Schiller, P. (1984). The connections of the retinal ON and OFF pathways to the lateral geniculate nucleus of the monkey. Vision Research 24, 923–932.CrossRefGoogle Scholar
Schiller, P.H., Sandell, J.H. & Maunsell, J.H.R. (1986). Functions of the ON and OFF channels in the visual system. Nature 322, 824–825.CrossRefGoogle ScholarPubMed
Sheardown, M.J., Nielson, E.O., Hansen, A.J., Jacobsen, P. & Honoré, T. (1990). 2.3–Dihydroxy-6–nitro-7–sulfamoyl-benzo(F)quinoxaline: A neuroprotectant for cerebral ischemia. Science 247, 571–574.CrossRefGoogle ScholarPubMed
Shiells, R.A., Falk, G. & Naghshineh, S. (1981). Action of glutamate and aspartate analogues on rod horizontal and bipolar cells. Nature 294, 592–594.CrossRefGoogle ScholarPubMed
Slaughter, M. & Miller, R.F. (1981). 2–Amino-4–phosphonobutyric acid: A new pharmacological tool for retinal research. Science 211, 182–185.CrossRefGoogle Scholar
Slaughter, M. & Miller, R.F. (1983 a). Bipolar cells in the mudpuppy use an excitatory amino acid neurotransmitter. Nature 303, 537–538.CrossRefGoogle ScholarPubMed
Slaughter, M. & Miller, R.F. (1983 b). An excitatory amino acid antagonist block cone input to sign-conserving second-order retinal neurons. Science 219, 1230–1232.CrossRefGoogle ScholarPubMed
Slaughter, M. & Miller, R.F. (1983 c). The role of excitatory amino acid transmitters in the mudpuppy retina: An analysis with kainic acid and N-methyl aspartate. Journal of Neuroscience 3, 1701–1711.CrossRefGoogle ScholarPubMed
Stockton, R.A. & Slaughter, M.M. (1989). B-wave of the electroretinogram. A reflection of ON-bipolar cell activity. Journal of General Physiology 93, 101–122.CrossRefGoogle ScholarPubMed
Tachibana, M. & Okada, T. (1991). Release of endogenous excitatory amino acids from ON-type bipolar cells isolated from the goldfish retina. Journal of Neuroscience 11, 2199–2208.CrossRefGoogle ScholarPubMed
Tang, C.M., Dichter, M. & Morad, M. (1989). Quisqualate activates a rapidly inactivating high conductance ionic channel in hippocampal neurons. Science 243, 1474–1477.CrossRefGoogle ScholarPubMed
Thompson, A.M., West, D.C. & Lodge, D. (1985). An N-methyl-aspartate receptor-mediated synapse in rat cerebral cortex: A site of action of ketamine? Nature 313, 479–481.CrossRefGoogle Scholar
Trussell, L.O. & Fischbach, G.D. (1989). Glutamate receptor desensitization and its role in synaptic transmission. Neuron 3, 209–218.CrossRefGoogle ScholarPubMed
Wang, L.-Y., Salter, M.W. & Macdonald, J.F. (1991). Regulation of kainate receptors by cAMP-dependent protein kinase and phosphatases. Science 253, 1132–1138.CrossRefGoogle ScholarPubMed
Wassle, H., Schafer-Trenkler, I. & Voigt, T. (1986). Analysis of a glycinergic inhibitory pathway in the cat retina. Journal of Neuroscience 6, 594–604.CrossRefGoogle ScholarPubMed
Watkins, J.C., Krogsgaard-Larsen, P. & Honoré, T. (1991). Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. In The Pharmacology of Excitatory Amino Acids: A Trends in Pharmacological Sciences Special Report, ed. Lodge, D. & Collingridge, G., pp. 4–12, Amsterdam: Elsevier.Google Scholar
Watkins, J.C. & Evans, R.H. (1981). Excitatory amino acid neurotransmitters. Annual Review of Pharmacology and Toxicology 21, 165–204.CrossRefGoogle Scholar
Yamashita, M. & Wassle, H. (1991). Responses of rod bipolar cells isolated from the rat retina to the glutamate agonist 2–amino-phosphonobutyric acid (APB). Journal of Neuroscience 11, 2372–2382.CrossRefGoogle Scholar
Yazejian, B. & Fain, G.L. (1992). Excitatory amino acid receptors on isolated retinal ganglion cells from the goldfish. Journal of Neurophysiology 67, 94–107.CrossRefGoogle ScholarPubMed