Hostname: page-component-76fb5796d-dfsvx Total loading time: 0 Render date: 2024-04-26T00:59:18.745Z Has data issue: false hasContentIssue false
  • English
  • Français

Localization of NMDA receptor subunits and mapping NMDA drive within the mammalian retina

Published online by Cambridge University Press:  01 July 2004

MICHAEL KALLONIATIS ,
DANIEL SUN ,
LISA FOSTER ,
SILKE HAVERKAMP  and
HEINZ WÄSSLE
MICHAEL KALLONIATIS
Affiliation:
Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia
DANIEL SUN
Affiliation:
Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand
LISA FOSTER
Affiliation:
Department of Optometry and Vision Sciences, University of Melbourne, Victoria, Australia
SILKE HAVERKAMP
Affiliation:
Max-Planck-Insitut für Hirnforschung, Frankfurt/M, Germany
HEINZ WÄSSLE
Affiliation:
Max-Planck-Insitut für Hirnforschung, Frankfurt/M, Germany
Get access Rights & Permissions [Opens in a new window]

Abstract

Glutamate is a major neurotransmitter in the retina and other parts of the central nervous system, exerting its influence through ionotropic and metabotropic receptors. One ionotropic receptor, the N-methyl-D-aspartate (NMDA) receptor, is central to neural shaping, but also plays a major role during neuronal development and in disease processes. We studied the distribution pattern of different subunits of the NMDA receptor within the rat retina including quantifying the pattern of labelling for all the NR1 splice variants, the NR2A and NR2B subunits. The labelling pattern for the subunits was confined predominantly in the outer two-thirds of the inner plexiform layer. We also wanted to probe NMDA receptor function using an organic cation, agmatine (AGB); a marker for cation channel activity. Although there was an NMDA concentration-dependent increase in AGB labelling of amacrine cells and ganglion cells, we found no evidence of functional NMDA receptors on horizontal cells in the peripheral rabbit retina, nor in the visual streak where the type A horizontal cell was identified by GABA labelling. Basal AGB labelling within depolarizing bipolar cells was also noted. This basal bipolar cell AGB labelling was not modulated by NMDA and was completely abolished by the use of L-2-amino-4-phosphono-butyric acid, which is known to hyperpolarize retinal depolarizing bipolar cells. AGB is therefore not only useful as a probe of ligand-gated drive, but can also identify neurons that have constitutively open cationic channels. In combination, the NMDA receptor subunit distribution pattern and the AGB gating experiments strongly suggests that this ionotropic glutamate receptor is functional in the cone-driven pathway of the inner retina.

Keywords

GlutamateNR1NR1C2NR1C2′NR2ANR2BAgmatine; L-AP4
Type
Research Article
Information
Visual Neuroscience , Volume 21 , Issue 4 , July 2004 , pp. 587 - 597
Copyright
2004 Cambridge University Press

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

REFERENCES

Anis, N., Sherby, S., Goodnow, R., Niwa, M., Konno, K., Kallimopoulos, T., Bukownik, R., Nakanishi, K., Usherwood, P., Eldefrawi, A., & Eldefrawi, M. (1990). Structure–activity relationships of philanthotoxin analogs and polyamines on N-methyl-D-aspartate and nicotinic acetylcholine receptors. Journal of Pharmacology and Experimental Therapeutics 254, 764–773.Google Scholar
Awatramani, G.B. & Slaughter, M.M. (2001). Intensity-dependent, rapid activation of presynaptic metabotropic glutamate receptors at a central synapse. Journal of Neuroscience 21, 741–749.Google Scholar
Bloomfield, S.A. & Dowling, J.E. (1985). Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer. Journal of Neurophysiology 53, 699–713.Google Scholar
Brandstätter, J.H., Harveit, E., Sassoè-Pognetto, M., & Wässle, H. (1994). Expression of NMDA and high affinity kainate receptor subunit mRNAs in the adult rat retina. European Journal of Neuroscience, 6, 1100–1112.CrossRefGoogle Scholar
Brandstätter, J.H., Koulen, P., Kuhn, R., van der Putten, H., & Wässle, H. (1996). Compartmental localization of a metabotropic glutamate receptor (mGluR7): Two different active sites at a retinal synapse. Journal of Neuroscience 16, 4749–4756.Google Scholar
Brandstätter, J.H., Koulen, P., & Wässle, H. (1998). Diversity of glutamate receptors in the mammalian retina. Vision Research 38, 1385–1397.CrossRefGoogle Scholar
Bui, B.V., Vingrys, A.J., & Kalloniatis, M. (2003). Correlating retinal function and amino acid immunocytochemistry following post-mortem ischemia. Experimental Eye Research 77, 125–136.CrossRefGoogle Scholar
Caramelo, O.L., Santos, P.F., Carvalho, A.P., & Duarte, C.B. (1999). Metabotropic glutamate receptors modulate [(3)H]acetylcholine release from cultured amacrine-like neurons. Journal of Neuroscience Research 58, 505–514.3.0.CO;2-J>CrossRefGoogle Scholar
Choi, D.W. (1992). Excitotoxic cell death. Journal of Neurobiology 23, 1261–1276.CrossRefGoogle Scholar
Cull-Candy, S., Brickley, S., & Farrant, M. (2001). NMDA receptor subunits: Diversity, development and disease. Current Opinions in Neurobiology 11, 327–335.CrossRefGoogle Scholar
Dacheux, R.F. & Raviola, E. (1986). The rod pathway in the rabbit retina: A depolarizing bipolar and amacrine cell. Journal of Neuroscience 6, 331–345.Google Scholar
Dwyer, T.M., Adams, D.J., & Hille, B. (1980). The permeability of the endplate channel to organic cations in frog muscle. Journal of General Physiology 75, 469–492.CrossRefGoogle Scholar
Edwards, F.A., Konnerth, A., Sakmann, B., & Takahashi, T. (1989). A thin slice preparation for patch clamp recordings from neurones of the mammalian central nervous system. Pflugers Archiv-European Journal of Physiology 414, 600–612.CrossRefGoogle Scholar
Edwards, J.G. & Michel, W.C. (2002). Odor-stimulated glutamatergic neurotransmission in the zebrafish olfactory bulb. Journal of Comparative Neurology 454, 294–309.CrossRefGoogle Scholar
Edwards, J.G. & Michel, W.C. (2003). Pharmacological characterization of ionotropic glutamate receptors in the zebrafish olfactory bulb. Neuroscience 122, 1037–1047.CrossRefGoogle Scholar
Ehinger, B., Ottersen, O.P., Storm-Mathisen, S., & Dowling, J.E. (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 Scholar
Emerit, M.B., Riad, M., Fattaccini, C.M., & Hamon, M. (1993). Characteristics of [14C] guanidinium accumulation in NG 108-15 cells exposed to serotonin 5-HT3 receptor ligands and substance P. Journal of Neurochemistry 60, 2059–2067.CrossRefGoogle Scholar
Euler, T. & Wässle, H. (1995). Immunocytochemical identification of cone bipolar cells in the rat retina. Journal of Comparative Neurology 361, 461–478.CrossRefGoogle Scholar
Evans, R.J., Lewis, C., Virginio, C., Lundstrom, K., Buell, G., Surprenant, A., & North, R.A. (1996). Ionic permeability of, and divalent cation effects on, two ATP-gated cation channels (P2X receptors) expressed in mammalian cells. Journal of Physiology (London) 497, 413–422.CrossRefGoogle Scholar
Famiglietti, E.V.Jr. & Kolb, H. (1976). Structural basis for ON-and OFF-center responses in retinal ganglion cells. Science 194, 193–195.CrossRefGoogle Scholar
Fletcher, E.L. & Kalloniatis, M. (1996). Neurochemical architecture of the normal and degenerating rat retina. Journal of Comparative Neurology 376, 343–360.3.0.CO;2-2>CrossRefGoogle Scholar
Fletcher, E.L. & Kalloniatis, M. (1997a). Localisation of amino acid neurotransmitters during postnatal development of the rat retina. Journal of Comparative Neurology 380, 449–471.Google Scholar
Fletcher, E.L. & Kalloniatis, M. (1997b). Neurochemical development of the degenerating rat retina. Journal of Comparative Neurology 388, 1–22.Google Scholar
Fletcher, E.L., Hack, I., Brandstätter, J.H., & Wässle, H. (2000). Synaptic localization of NMDA receptor subunits in the rat retina. Journal of Comparative Neurology 420, 98–112.3.0.CO;2-U>CrossRefGoogle Scholar
Goebel, D.J. & Poosch, M.S. (1999). NMDA receptor subunit gene expression in the rat brain: A quantitative analysis of endogenous mRNA levels of NR1com, NR2A, NR2B, NR2C, NR2D and NR3A. Molecular Brain Research 69, 164–170.CrossRefGoogle Scholar
Goebel, D.J., Aurelia, J.L., Tai, Q., Jojich, L., & Poosch, M.S. (1998). Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina. Brain Research 808, 141–154.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 Scholar
Gründer, T., Kohler, K., Kaletta, A., & Guenther, E. (2000). The distribution and developmental regulation of NMDA receptor subunit proteins in the outer and inner retina of the rat. Journal of Neurobiology 44, 333–342.3.0.CO;2-S>CrossRefGoogle Scholar
Haberecht, M.F., Mitchell, C.K., Lo, G.J., & Redburn, D.A. (1997). N-methyl-D-aspartate-mediated glutamate toxicity in the developing rabbit retina. Journal of Neuroscience Research 47, 416–426.3.0.CO;2-H>CrossRefGoogle Scholar
Hartveit, E. (1996). Membrane currents evoked by ionotropic glutamate receptor agonists in rod bipolar cells in the rat retinal slice preparation. Journal of Neurophysiology 76, 401–422.Google Scholar
Hartveit, E., Brandstätter, J.H., Sassoè-Pognetto, M., Laurie, D.J., Seeburg, P.H., & Wässle, H. (1994). Localization and developmental expression of the NMDA receptor subunit NR2A in the mammalian retina. Journal of Comparative Neurology 348, 570–582.CrossRefGoogle Scholar
Hirano, A.A., Hack, I., Wässle, H., & Duvoisin, R.M. (2000). Cloning and immunocytochemical localization of a cyclic nucleotide-gated channel α-subunit to all cone photoreceptors in the mouse retina. Journal of Comparative Neurology 421, 80–94.3.0.CO;2-O>CrossRefGoogle Scholar
Hollmann, M., Boulter, J., Maron, C., Beasley, L., Sullivan, J., Pecht, G., & Heinemann, S. (1993). Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor. Neuron 10, 943–954.CrossRefGoogle Scholar
Ishii, T., Moriyoshi, K., Sugihara, H., Sakurada, K., Kadotani, H., Yokoi, M., Akazawa, C., Shigemoto, R., Mizuno, N., Masu, M., & Nakanishi, S. (1993). Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. Journal of Biological Chemistry 268, 2836–2843.Google Scholar
Johnson, M.A. & Vardi, N. (1998). Regional differences in GABA and GAD immunoreactivity in rabbit horizontal cells. Visual Neuroscience 15, 743–753.Google Scholar
Kalloniatis, M. & Fletcher, E.L. (1993). Immunocytochemical localization of the amino acid neurotransmitters in the chicken retina. Journal of Comparative Neurology 336, 174–193.CrossRefGoogle Scholar
Kalloniatis, M. & Napper, G.A. (1996). Glutamate metabolic pathways in displaced ganglion cells of the chicken retina. Journal of Comparative Neurology 367, 518–536.3.0.CO;2-7>CrossRefGoogle Scholar
Kalloniatis, M. & Tomisich, G. (1999). Amino acid neurochemistry of the vertebrate retina. Progress in Retinal and Eye Research 18, 811–866.CrossRefGoogle Scholar
Kalloniatis, M., Marc, R.E., & Murry, R. (1996). Amino acid signatures in the primate retina. Journal of Neuroscience 16, 6807–6829.Google Scholar
Kalloniatis, M., Tomisich, G., Wellard, J.W., & Foster, L.E. (2002). Mapping photoreceptor and post-receptoral function using a channel permeable probe during development in the normal and degenerating rat retina. Visual Neuroscience 19, 61–70.CrossRefGoogle Scholar
Kreutz, M.R., Böckers, T.M., Bockmann, J., Seidenbecher, C.I., Kracht, B., Vorwerk, C.K., Weise, J., & Sabel, B.A. (1998). Axonal injury alters alternative splicing of the retinal NR1 receptor: The preferential expression of the NR1b isoforms is crucial for retinal ganglion cell survival. Journal of Neuroscience 15, 8278–8291.Google Scholar
Kuzirian, A.M., Meyhofer, E., Hill, L., Neary, J.T., & Alkon, D.L. (1986). Autoradiographic measurement of tritiated agmatine as an indicator of physiologic activity in Hermissenda visual and vestibular neurons. Journal of Neurocytology 15, 629–643.CrossRefGoogle Scholar
Laube, B., Kuhse, J., & Betz, H. (1998). Evidence for tetrameric structure of recombinant NMDA receptors. Journal of Neuroscience 18, 2954–2961.Google Scholar
Laurie, D.J., Bartke, I., Schoepfer, R., Naujoks, K., & Seeburg, P.H. (1997). Regional, developmental and interspecies expression of the four NMDAR2 subunits, examined using monoclonal antibodies. Molecular Brain Research 51, 23–32.CrossRefGoogle Scholar
Li, G., Regunathan, S., Barrow, C.J., Eshraghi, J., Cooper, R., & Reis, D.J. (1994). Agmatine: an endogenous clonidine-displacing substance in the brain. Science 263, 966–969.CrossRefGoogle Scholar
Linn, D.M. & Massey, S.C. (1991). Acetylcholine release from the rabbit retina mediated by NMDA receptors. Journal of Neuroscience 11, 123–133.Google Scholar
Lipschitz, D.L. & Michel, W.C. (1999). Physiological evidence for the discrimination of L-Arginine from structural analogues by the zebrafish olfactory system. Journal of Neurophysiology 82, 3160–3167.Google Scholar
Lipschitz, D.L. & Michel, W.C. (2002). Amino acid odorants stimulate microvillar sensory neurons. Chemical Senses 27, 277–286.CrossRefGoogle Scholar
Lo, W., Molloy, R., & Hughes, T.E. (1998). Ionotropic glutamate receptors in the retina: Moving from molecules to circuits. Vision Research 38, 1399–1410.CrossRefGoogle Scholar
Loring, R.H. (1990). Agmatine acts as an antagonist of neuronal nicotinic receptors. British Journal of Pharmacology 99, 207–211.CrossRefGoogle Scholar
Marc, R.E. (1989). The role of glycine in the mammalian retina. Progress in Retinal and Eye Research 8, 67–107.Google Scholar
Marc, R.E. (1999a). Mapping glutamatergic drive in the vertebrate retina with a channel-permeant organic cation. Journal of Comparative Neurology 407, 47–64.Google Scholar
Marc, R.E. (1999b). Kainate activation of horizontal, bipolar, amacrine, and ganglion cells in the rabbit retina. Journal of Comparative Neurology 407, 65–76.Google Scholar
Marc, R.E. & Jones, B.W. (2002). Molecular phenotyping of retinal ganglion cells. Journal of Neuroscience 22, 413–427.Google Scholar
Marc, R.E., Liu, W.-L., Kalloniatis, M., Raiguel, S.F., & Van Haesendonck, E. (1990). Patterns of glutamate immunoreactivity in the goldfish retina. Journal of Neuroscience 10, 4006–4034.Google Scholar
Marc, R.E., Murry, R.F., & Basinger, S.F. (1995). Pattern recognition of amino acid signatures in retinal neurons. Journal of Neuroscience 15, 5106–5129.Google Scholar
Massey, S.C. (1990). Cell types using glutamate as a neurotransmitter in the vertebrate retina. Progress in Retinal Research 9, 399–425.CrossRefGoogle Scholar
Massey, S.C. & Miller, R.F. (1990). N-methyl-D-aspartate receptors of ganglion cells in the rabbit retina. Journal of Neurophysiology 63, 16–30.Google Scholar
Michel, W.C., Steullet, P., Cate, H.S., Burns, C.J., Zhainazarov, A.B., & Derby, C.D. (1999). High-resolution functional labelling of vertebrate and invertebrate olfactory receptor neurons using agmatine, a channel-permeant cation. Journal of Neuroscience Methods 90, 143–156.CrossRefGoogle Scholar
Mills, S.L. & Massey, S.C. (1994). Distribution and coverage of A- and B-type horizontal cells stained with Neurobiotin in the rabbit retina. Visual Neuroscience 11, 549–560.CrossRefGoogle Scholar
Monyer, H., Sprengel, R., Schoepfer, R., Hebb, 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 Scholar
Nakatani, K. & Yau, K.W. (1988). Calcium and magnesium fluxes across the plasma membrane of the toad rod outer segment. Journal of Physiology (London) 395, 695–729.CrossRefGoogle Scholar
Napper, G.A. & Kalloniatis, M. (1999). Neurochemical changes following post-mortem ischemia in the rat retina. Visual Neuroscience 16, 1169–1180.CrossRefGoogle Scholar
Napper, G.A., Pianta, M.J., & Kalloniatis, M. (2001). Localization of amino acid neurotransmitters following in-vitro ischemia and anoxia in the rat retina. Visual Neuroscience 18, 413–427.CrossRefGoogle Scholar
Osborne, N.N. & Herrera, A.J. (1994). The effect of experimental ischaemia and excitatory amino acid agonists on the GABA and serotonin immunoreactivities in the rabbit retina. Neuroscience 59, 1071–1081.CrossRefGoogle Scholar
Periyasamy, S., Kothapalli, M.R., & Hoss, W. (1994). Regulation of the phosophoinositide cascade by polyamines in brain. Journal of Neurochemistry 63, 1319–1327.Google Scholar
Picco, C. & Menini, A. (1993). The permeability of the cGMP-activated channel to organic cations in retinal rods of the tiger salamander. Journal of Physiology (London) 460, 741–758.CrossRefGoogle Scholar
Picones, A. & Korenbrot, J.I. (1992). Permeation and interaction of monovalent cations with the cGMP-gated channel of cone photoreceptors. Journal of General Physiology 100, 647–673.CrossRefGoogle Scholar
Picones, A. & Korenbrot, J.I. (1995). Permeability and interaction of Ca2+ with cGMP-gated ion channels differ in retinal rod and conephotoreceptors. Biophysics Journal 69, 120–127.Google Scholar
Pin, J.P. & Duvoisin, R. (1995). The metabotropic glutamate receptors: Structure and functions. Neuropharmacology 34, 1–26.CrossRefGoogle Scholar
Rang, H.P. & Ritchie, J.M. (1988). Depolarization of nonmyelinated fibers of the rat vagus nerve produced by activation of protein kinase C. Journal of Neuroscience 8, 2606–2617.Google Scholar
Romano, C., Price, M.T., & Olney, J.W. (1995). Delayed excitotoxic neurodegeneration induced by excitatory amino acid agonists in isolated retina. Journal of Neurochemistry 65, 59–67.Google Scholar
Saito, T. (1987). Physiological and morphological differences between On- and Off-center bipolar cells in the vertebrate retina. Vision Research 27, 135–142.CrossRefGoogle Scholar
Sakata, Y., Olson, J.K., & Michel, W.C. (2003). Assessment of neuronal maturation and acquisition of functional competence in the developing zebrafish olfactory system. Methods in Cell Science 25, 39–48.CrossRefGoogle Scholar
Siliprandi, R., Lipartiti, M., Fadda, E., Sautter, J., & Manev, H. (1992). Activation of the glutamate metabotropic receptor protects retina against N-methyl-D-aspartate toxicity. European Journal of Pharmacology 219, 173–174.CrossRefGoogle Scholar
Slaughter, M.M. & Miller, R.F. (1981). 2-amino-4-phosphonobutyric acid: A new pharmacological tool for retina research. Science 211, 182–185.CrossRefGoogle Scholar
Stotz, S.C. & Haynes, L.W. (1996). Block of the cGMP-gated cation channel of catfish rod and cone photoreceptors by organic cations. Biophysics Journal 71, 3136–3147.Google Scholar
Sucher, N.J., Aizenman, E., & Lipton, S.A. (1991b). N-methyl-D-aspartate antagonists prevent kainate neurotoxicity in rat retinal ganglion cells in vitro. Journal of Neuroscience 11, 966–971.Google Scholar
Sucher, N.J., Lei, S.Z., & Lipton, S.A. (1991a). Calcium channel antagonists attenuate NMDA receptor-mediated neurotoxicity of retinal ganglion cells in culture. Brain Research 551, 297–302.Google Scholar
Sun, D., Rait, J.L., & Kalloniatis, M. (2003). Inner retinal neurons display differential responses to N-methyl-D-aspartate receptor activation. Journal of Comparative Neurology 465, 3–56.Google Scholar
Thoreson, W.B. & Witkovsky, P. (1999). Glutamate receptors and circuits in the vertebrate retina. Progress in Retinal and Eye Research 18, 765–810.CrossRefGoogle Scholar
Tian, N. & Slaughter, M.M. (2003). Structure of glutamate analogs that activate the ON bipolar cell metabotropic glutamate receptor in vertebrate retina. Visual Neuroscience 20, 231–240.CrossRefGoogle Scholar
Watanabe, M., Fukaya, M., Sakimura, K., Manabe, T., Mishina, M., & Inoue, Y. (1998). Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fibre-recipient layer) of the mouse hippocampal CA3 subfield. European Journal of Neuroscience 10, 478–487.CrossRefGoogle Scholar
Yoshikami, D. (1981). Transmitter sensitivity of neurons assayed by autoradiography. Science 212, 929–930.CrossRefGoogle Scholar
Zukin, R.S. & Bennett, M.V.L. (1995). Alternatively spliced isoforms of the NMDAR1 receptor subunit. Trends in Neuroscience 18, 306–313.CrossRefGoogle Scholar