Hostname: page-component-8448b6f56d-cfpbc Total loading time: 0 Render date: 2024-04-18T20:07:19.680Z Has data issue: false hasContentIssue false
  • English
  • Français

Glycine receptors of A-type ganglion cells of the mouse retina

Published online by Cambridge University Press:  29 May 2007

SRIPARNA MAJUMDAR ,
LIANE HEINZE ,
SILKE HAVERKAMP ,
ELENA IVANOVA  and
HEINZ WÄSSLE
SRIPARNA MAJUMDAR
Affiliation:
Department of Neuroanatomy, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany
LIANE HEINZE
Affiliation:
Department of Neuroanatomy, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany
SILKE HAVERKAMP
Affiliation:
Department of Neuroanatomy, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany
ELENA IVANOVA
Affiliation:
Department of Neuroanatomy, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany
HEINZ WÄSSLE
Affiliation:
Department of Neuroanatomy, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany
Get access Rights & Permissions [Opens in a new window]

Abstract

A-type ganglion cells of the mouse retina represent the visual channel that transfers temporal changes of the outside world very fast and with high fidelity. In this study we combined anatomical and physiological methods in order to study the glycinergic, inhibitory input of A-type ganglion cells. Immunocytochemical studies were performed in a transgenic mouse line whose ganglion cells express green fluorescent protein (GFP). The cells were double labeled for GFP and the four α subunits of the glycine receptor (GlyR). It was found that most of the glycinergic input of A-type cells is through fast, α1-expressing synapses. Whole-cell currents were recorded from A-type ganglion cells in retinal whole mounts. The response to exogenous application of glycine and spontaneous inhibitory postsynaptic currents (sIPSCs) were measured. By comparing glycinergic currents recorded in wildtype mice and in mice with specific deletions of GlyRα subunits (Glra1spd-ot, Glra2−/−, Glra3−/−), the subunit composition of GlyRs of A-type ganglion cells could be further defined. Glycinergic sIPSCs of A-type ganglion cells have fast kinetics (decay time constant τ = 3.9 ± 2.5 ms, mean ± SD). Glycinergic sIPSCs recorded in Glra2−/− and Glra3−/− mice did not differ from those of wildtype mice. However, the number of glycinergic sIPSCs was significantly reduced in Glra1spd-ot mice and the remaining sIPSCs had slower kinetics than in wildtype mice. The results show that A-type ganglion cells receive preferentially kinetically fast glycinergic inputs, mediated by GlyRs composed of α1 and β subunits.

Keywords

Glycine receptorsRetinaGlycinergic sIPSCsA-type ganglion cellsMouseGlra1spd-ot MouseGlra2−/− MouseGlra3−/− Mouse
Type
Research Article
Information
Visual Neuroscience , Volume 24 , Issue 4 , July 2007 , pp. 471 - 487
Copyright
© 2007 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

Badea, T.C. & Nathans, J. (2004). Quantitative analysis of neuronal morphologies in the mouse retina visualized by using a genetically directed reporter. Journal of Comparative Neurology 480, 331–351.CrossRefGoogle Scholar
Barry, P.H. (1994). JPCalc, a software package for calculating liquid junction potential corrections in patch-clamp, intracellular, epithelial and bilayer measurements and for correcting junction potential measurements. Journal of Neuroscience Methods 51, 107–116.CrossRefGoogle Scholar
Becker, C.-M., Hoch, W. & Betz, H. (1988). Glycine receptor heterogeneity in rat spinal-cord during postnatal-development. EMBO Journal 7, 3717–3726.Google Scholar
Betz, H. & Laube, B. (2006). Glycine receptors: recent insights into their structural organization and functional diversity. Journal of Neurochemistry 97, 1600–1610.CrossRefGoogle Scholar
Bolz, J., Thier, P., Voigt, T. & Wässle, H. (1985). Action and localization of glycine and taurine in the cat retina. Journal of Physiology (London) 362, 395–413.CrossRefGoogle Scholar
Buckwalter, M.S., Cook, S.A., Davisson, M.T., White, W.F. & Camper, S.A. (1994). A frameshift mutation in the mouse alpha 1 glycine receptor gene (Glra1) results in progressive neurological symptoms and juvenile death. Human Molecular Genetics 3, 2025–2030.CrossRefGoogle Scholar
Bunt, A.H. (1976). Ramification patterns of ganglion cell dendrites in the retina of the albino rat. Brain Research 103, 1–8.CrossRefGoogle Scholar
Cohen, E.D., Zhou, Z.J. & Fain, G.L. (1994). Ligand-gated currents of alpha and beta ganglion cells in the cat retinal slice. Journal of Neurophysiology 72, 1260–1269.Google Scholar
Coombs, J., van der List, D., Wang, G.Y. & Chalupa, L.M. (2006). Morphological properties of mouse retinal ganglion cells. Neuroscience 140, 123–136.CrossRefGoogle Scholar
Cui, J., Ma, Y.-P., Lipton, S.A. & Pan Z.-H. (2003). Glycine receptors and glycinergic synaptic input at the axon terminals of mammalian retinal rod bipolar cells. Journal of Physiology 553, 895–909.CrossRefGoogle Scholar
Dacey, D.M. (1999). Primate retina: Cell types, circuits and color opponency. In Progress in Retinal and Eye Research, eds. Osborne, N.N. & Chader, G.J., pp. 737–763. Oxford, UK: Pergamon Press.CrossRef
Demb, J.B., Zaghloul, K. & Sterling, P. (2001). Cellular basis for the response to second-order motion cues in Y retinal ganglion cells. Neuron 32, 711–721.CrossRefGoogle Scholar
Dodt, H.U. & Zieglgänsberger, W. (1990). Visualizing unstained neurons in living brain slices by infrared DIC-videomicroscopy. Brain Research 537, 333–336.CrossRefGoogle Scholar
Dräger, U.C. & Olsen, J.F. (1981). Ganglion cell distribution in the retina of the mouse. Investigative Ophthalmology & Visual Science 20, 285–293.Google Scholar
Eggers, E.D. & Lukasiewicz, P.D. (2006). Receptor and transmitter release properties set the time course of retinal inhibition. Journal of Neuroscience 26, 9413–9425.CrossRefGoogle Scholar
Famiglietti, E.V. & Kolb, H. (1975). A bistratified amacrine cell and synaptic circuitry in the inner plexiform layer of the retina. Brain Research 84, 293–300.CrossRefGoogle Scholar
Feng, G., Mellor, R.H., Bernstein, M., Keller-Peck, C., Nguyen, Q.T., Wallace, M., Nerbonne, J.M., Lichtman, J.W. & Sanes, J.R. (2000). Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28, 41–51.CrossRefGoogle Scholar
Fischer, F., Kneussel, M., Tintrup, H., Haverkamp, S., Rauen, T., Betz, H. & Wässle, H. (2000). Reduced synaptic clustering of GABA and glycine receptors in the retina of the gephyrin null mutant mouse. Journal of Comparative Neurology 427, 634–648.3.0.CO;2-X>CrossRefGoogle Scholar
Flores-Herr, N., Protti, D.A. & Wässle, H. (2001). Synaptic currents generating the inhibitory surround of ganglion cells in the mammalian retina. Journal of Neuroscience 21, 4852–4863.Google Scholar
Frech, M.J., Perez-Leon, J., Wässle, H. & Backus, K.H. (2001). Characterization of the spontaneous synaptic activity of amacrine cells in the mouse retina. Journal of Neurophysiology 86, 1632–1643.Google Scholar
Gill, S.B., Veruki, M.L. & Harveit, E. (2006). Functional properties of spontaneous IPSCs and glycine receptors in rod amacrine (AII) cells in the rat retina. Journal of Physiology 575, 739–759.CrossRefGoogle Scholar
Grudzinska, J., Schemm, R., Haeger, S., Nicke, A., Schmalzing, G., Betz, H. & Laube, B. (2005). The beta subunit determines the ligand binding properties of synaptic glycine receptors. Neuron 45, 727–739.CrossRefGoogle Scholar
Grünert, U. & Wässle, H. (1993). Immunocytochemical localization of glycine receptors in the mammalian retina. Journal of Comparative Neurology 335, 523–537.CrossRefGoogle Scholar
Han, Y., Li, P. & Slaughter, M.M. (2003). Selective antagonism of rat inhibitory glycine receptor subunits. Journal of Physiology 554, 649–658.Google Scholar
Harvey, R.J. & Betz, H. (2000). Structure, diversity, pharmacology, and pathology of glycine receptor chloride channels. In Pharmacology of Ionic Channel Function: Activators and Inhibitors, Handbook of Experimental Pharmacology, Vol. 147, eds. Endo, M., Kurachi, Y. & Mishina, M., pp. 479–497. Berlin, Heidelberg, Germany: Springer Verlag.CrossRef
Harvey, R.J., Schmieden, V., von Holst, A., Laube, B., Rohrer, H. & Betz, H. (2000). Glycine receptors containing the α4 subunit in the embryonic sympathetic nervous system, spinal cord and male genital ridge. European Journal of Neuroscience 12, 994–1001.CrossRefGoogle Scholar
Harvey, R.J., Depner, U.B., Wässle, H., Ahmadi, S., Heindl, C., Reinold, H., Smart, T.G., Harvey, K., Schütz, B., Abo-Salem, O.M., Zimmer, A., Poisbeau, P., Welzl, H., Wolfer, D.P., Betz, H., Zeilhofer, H.U. & Müller, U. (2004). GlyR alpha 3: An essential target for spinal PGE(2)-mediated inflammatory pain sensitization. Science 304, 884–887.CrossRefGoogle Scholar
Haverkamp, S., Müller, U., Harvey, K., Harvey, R.J., Betz, H. & Wässle, H. (2003). Diversity of glycine receptors in the mouse retina: Localization of the α3 subunit. Journal of Comparative Neurology 465, 524–539.CrossRefGoogle Scholar
Haverkamp, S., Müller, U., Zeilhofer, H.U., Harvey, R.J. & Wässle, H. (2004). Diversity of glycine receptors in the mouse retina: Localization of the α2 subunit. Journal of Comparative Neurology 477, 399–411.CrossRefGoogle Scholar
Heinze, L., Harvey, R.J., Haverkamp, S. & Wässle, H. (2007). Diversity of glycine receptors in the mouse retina: Localization of the α4 subunit. Journal of Comparative Neurology 500, 693–707.CrossRefGoogle Scholar
Hidaka, S., Akahori, Y. & Kurosawa, Y. (2004). Dendrodendritic electrical synapses between mammalian retinal ganglion cells. Journal of Neuroscience 24, 10553–10567.CrossRefGoogle Scholar
Hu, E.H. & Bloomfield, S.A. (2003). Gap junctional coupling underlies the short-latency spike synchrony of retinal α ganglion cells. Journal of Neuroscience 23, 6768–6777.Google Scholar
Huxlin, K.R. & Goodchild, A.K. (1997). Retinal ganglion cells in the albino rat: Revised morphological classification. Journal of Comparative Neurology 385, 309–323.3.0.CO;2-5>CrossRefGoogle Scholar
Isayama, T., Berson, D.M. & Pu, M. (2000). Theta ganglion cell type of cat retina. Journal of Comparative Neurology 417, 32–48.3.0.CO;2-S>CrossRefGoogle Scholar
Ivanova, E., Müller, U. & Wässle, H. (2006). Characterization of the glycinergic input to bipolar cells of the mouse retina. European Journal of Neuroscience 23, 350–364.CrossRefGoogle Scholar
Kling, C., Koch, M., Saul, B. & Becker, C.M. (1997). The frameshift mutation oscillator (Glra1 (spd-ot)) produces a complete loss of glycine receptor alpha1-polypeptide in mouse central nervous system. Journal of Neuroscience 78, 411–417.CrossRefGoogle Scholar
Kolb, H. & Famiglietti, E.V. (1974). Rod and cone pathways in the inner plexiform layer of the cat retina. Science 186, 47–49.CrossRefGoogle Scholar
Kong, J.H., Fish, D.R., Rockhill, R.L. & Masland, R.H. (2005). Diversity of ganglion cells in the mouse retina: Unsupervised morphological classification and its limits. Journal of Comparative Neurology 489, 293–310.CrossRefGoogle Scholar
Koulen, P., Sassoè-Pognetto, M., Grünert, U. & Wässle, H. (1996). Selective clustering of GABAA and glycine receptors in the mammalian retina. Journal of Neuroscience 16, 2127–2140.Google Scholar
Legendre, P. (1997). Pharmacological evidence for two types of postsynaptic glycinergic receptors on the Mauthner cell of 52-h-old zebrafish larvae. Journal of Neurophysiology 77, 2400–2415.Google Scholar
Legendre, P. (2001). The glycinergic inhibitory synapse. Cellular and Molecular Life Sciences: CMLS 58, 760–793.CrossRefGoogle Scholar
Levick, W.R. (1996). Receptive fields of cat retinal ganglion cells with special reference to the alpha cells. Progress in Retinal and Eye Research 15, 457–500.CrossRefGoogle Scholar
Lynch, J.W. (2004). Molecular structure and function of the glycine receptor chloride channel. Physiological Reviews 84, 1051–1095.CrossRefGoogle Scholar
Malosio, M.-L., Marqueze-Pouey, B., Kuhse, J. & Betz, H. (1991). Widespread expression of glycine receptor subunit mRNAs in the adult and developing rat brain. EMBO Journal 10, 2401–2409.Google Scholar
Marc, R.E. & Jones, B.W. (2002). Molecular phenotyping of retinal ganglion cells. Journal of Neuroscience 22, 413–427.Google Scholar
Masland, R.H. (2001). The fundamental plan of the retina. Nature Neuroscience 4, 877–886.CrossRefGoogle Scholar
Murphy, G.J. & Rieke, F. (2006). Network variability limits stimulus-evoked spike timing precision in retinal ganglion cells. Neuron 52, 511–524.CrossRefGoogle Scholar
Nikolic, Z., Laube, B., Weber, R.G., Lichter, P., Kioschis, P., Poustka, A., Mülhardt, C. & Becker, C.-M. (1998). The human glycine receptor subunit α3. Journal of Biological Chemistry 273, 19708–19714.CrossRefGoogle Scholar
O'Brien, B.J., Isayama, T., Richardson, R. & Berson, D.M. (2002). Intrinsic physiological properties of cat retinal ganglion cells. Journal of Physiology 538, 787–802.CrossRefGoogle Scholar
O'Brien, B.J., Richardson, R.C. & Berson, D.M. (2003). Inhibitory network properties shaping the light evoked responses of cat alpha retinal ganglion cells. Visual Neuroscience 20, 351–361.CrossRefGoogle Scholar
Pang, J.-J., Gao, F. & Wu, S.M. (2002). Relative contributions of bipolar cell and amacrine cell inputs to light responses on ON, OFF and ON-OFF retinal ganglion cells. Vision Research 42, 19–27.CrossRefGoogle Scholar
Pang, J.-J., Gao, F. & Wu, S.M. (2003). Light-evoked excitatory and inhibitory synaptic inputs to ON and OFF α ganglion cells. Journal of Neuroscience 23, 6063–6073.Google Scholar
Peichl, L. (1989). Alpha and delta ganglion cells in the rat retina. Journal of Comparative Neurology 286, 120–139.CrossRefGoogle Scholar
Pérez-León, J., Frech, M.J., Schröder, J.E., Fischer, F., Kneussel, M., Wässle, H. & Backus, K.H. (2003). Spontaneous synaptic activity in an organotypic culture of the mouse retina. Investigative Ophthalmology & Visual Science 44, 1376–1387.CrossRefGoogle Scholar
Perry, V.H. (1979). The ganglion cell layer of the retina of the rat: a Golgi study. Proceedings of the Royal Society B (London) 204, 363–375.CrossRefGoogle Scholar
Pfeiffer, F., Simler, R., Grenningloh, G. & Betz, H. (1984). Monoclonal antibodies and peptides mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord. Proceedings of the National Academy of Sciences USA 81, 7224–7227.CrossRefGoogle Scholar
Pinto, L.H., Grünert, U., Studholme, K., Yazulla, S., Kirsch, J. & Becker, C.M. (1994). Glycine receptors in the retinas of normal and spastic mutant mice. Investigative Ophthalmology & Visual Science 35, 3633–3639.Google Scholar
Pribilla, I., Takagi, T., Langosch, D., Bormann, J. & Betz, H. (1992). The atypical M2 segment of the β subunit confers picrotoxinin resistance to inhibitory glycine receptor channels. EMBO Journal 11, 4305–4311.Google Scholar
Protti, D.A., Gerschenfeld, H.M. & Llano, I. (1997). GABAergic and glycinergic IPSCs in ganglion cells of rat retinal slices. Journal of Neuroscience 17, 6075–6085.Google Scholar
Rockhill, R.L., Daly, F.J., MacNeil, M.A., Brown, S.P. & Masland, R.H. (2002). The diversity of ganglion cells in a mammalian retina. Journal of Neuroscience 22, 3831–3843.Google Scholar
Roska, B., Molnar, A. & Werblin, F.S. (2006). Parallel processing in retinal ganglion cells: How integration of space-time patterns of excitation and inhibition form the spiking output. Journal of Neurophysiology 95, 3810–3822.CrossRefGoogle Scholar
Rotolo, T.C. & Dacheux, R.F. (2003a). Evidence for glycine, GABAA, and GABAB receptors on rabbit OFF-alpha ganglion cells. Visual Neuroscience 20, 285–296.Google Scholar
Rotolo, T.C. & Dacheux, R.F. (2003b). Two neuropharmacological types of rabbit ON-alpha ganglion cells express GABAC receptors. Visual Neuroscience 20, 373–384.Google Scholar
Sassoè-Pognetto, M., Wässle, H. & Grünert, U. (1994). Glycinergic synapses in the rod pathway of the rat retina: cone bipolar cells express the α1 subunit of the glycine receptor. Journal of Neuroscience 14, 5131–5146.Google Scholar
Schmitt, B., Knaus, P., Becker, C.M. & Betz, H. (1987). The Mr 93,000 polypeptide of the postsynaptic glycine receptor complex is a peripheral membrane protein. Biochemistry 26, 805–811.CrossRefGoogle Scholar
Schröder, S., Hoch, W., Becker, C.M., Grenningloh, G. & Betz, H. (1991). Mapping of antigenic epitopes on the α1 subunit of the inhibitory glycine receptor. Biochemistry 30, 42–47.CrossRefGoogle Scholar
Schubert, T., Maxeiner, S., Krüger, O., Willecke, K. & Weiler, R. (2005). Connexin45 mediates gap junctional coupling of bistratified ganglion cells in the mouse retina. Journal of Comparative Neurology 490, 29–39.CrossRefGoogle Scholar
Singer, J.H., Talley, E.M., Bayliss, D.A. & Berger, A.J. (1998). Development of glycinergic synaptic transmission to rat brain stem motoneurons. Journal of Neurophysiology 80, 2608–2620.Google Scholar
Smith, A.J., Owens, S. & Forsythe, I.D. (2000). Characterisation of inhibitory and excitatory postsynaptic currents of the rat medial superior olive. Journal of Physiology 529, 681–698.CrossRefGoogle Scholar
Stone, C. & Pinto, L.H. (1992). Receptive field organization of retinal ganglion cells in the spastic mutant mouse. Journal of Physiology 456, 125–142.CrossRefGoogle Scholar
Sun, W., Li, N. & He, S. (2002a). Large-scale morphological survey of mouse retinal ganglion cells. Journal of Comparative Neurology 451, 115–126.Google Scholar
Sun, W., Li, N. & He, S. (2002b). Large-scale morphological survey of rat retinal ganglion cells. Visual Neuroscience 19, 483–493.Google Scholar
Takahashi, T., Momiyama, A., Hirai, K., Hishinuma, F. & Akagi, H. (1992). Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels. Neuron 9, 1155–1161.CrossRefGoogle Scholar
Tauchi, M., Morigiwa, K. & Fukuda, Y. (1992). Morphological comparisons between outer and inner ramifying alpha cells of the albino rat retina. Experimental Brain Research 88, 67–77.CrossRefGoogle Scholar
Tian, N., Hwang, T.N. & Copenhagen, D.R. (1998). Analysis of excitatory and inhibitory spontaneous synaptic activity in mouse retinal ganglion cells. Journal of Neurophysiology 80, 1327–1340.Google Scholar
Vannier, C. & Triller, A. (1997). Biology of the postsynaptic glycine receptor. International Review of Cytology 176, 201–244.CrossRefGoogle Scholar
Völgyi, B., Abrams, J., Paul, D.L. & Bloomfield, S.A. (2005). Morphology and tracer coupling pattern of alpha ganglion cells in the mouse retina. Journal of Comparative Neurology 492, 66–77.CrossRefGoogle Scholar
Wässle, H. (1988). Dendritic maturation of retinal ganglion cells. Trends in Neurosciences 11, 87–89.CrossRefGoogle Scholar
Wässle, H. (2004). Parallel processing in the mammalian retina. Nature Neuroscience 5, 747–757.CrossRefGoogle Scholar
Wässle, H., Koulen, P., Brandstätter, J.H., Fletcher, E.L. & Becker, C.M. (1998). Glycine and GABA receptors in the mammalian retina. Vision Research 38, 1411–1430.CrossRefGoogle Scholar
Weiss, J., O'Sullivan, G., Heinze, L., Chen, N.-H., Betz, H. & Wässle, H. (2007). Glycinergic input of small field amacrine cells in the retina of wildtype and glycine receptor-deficient mice (submitted).
Young-Pearse, T.L., Ivic, L., Kriegstein, A.R. & Cepko, C.L. (2006). Characterization of mice with targeted deletion of glycine receptor alpha 2. Molecular and Cellular Biology 26, 5728–5734.CrossRefGoogle Scholar