Hostname: page-component-8448b6f56d-c4f8m Total loading time: 0 Render date: 2024-04-19T21:51:39.983Z Has data issue: false hasContentIssue false
  • English
  • Français

Push–pull model of the primate photopic electroretinogram: A role for hyperpolarizing neurons in shaping the b-wave

Published online by Cambridge University Press:  02 June 2009

Paul A. Sieving ,
Koichiro Murayama  and
Franklin Naarendorp
Paul A. Sieving
Affiliation:
Department of Ophthalmology and the Neuroscience and Bioengineering Programs, University of Michigan, Ann Arbor
Koichiro Murayama
Affiliation:
Department of Ophthalmology and the Neuroscience and Bioengineering Programs, University of Michigan, Ann Arbor
Franklin Naarendorp
Affiliation:
Department of Ophthalmology and the Neuroscience and Bioengineering Programs, University of Michigan, Ann Arbor
Get access Rights & Permissions [Opens in a new window]

Abstract

Existing models of the primate photopic electroretinogram (ERG) attribute the light-adapted b–wave to activity of depolarizing bipolar cells (DBCs), mediated through a release of potassium that is monitored by Müller cells. However, possible ERG contributions from OFF-bipolar cells (HBCs) and horizontal cells (HzCs) have not been explored. We examined the contribution of these hyperpolarizing second-order retinal cells to the photopic ERG of monkey by applying glutamate analogs to suppress photoreceptor transmission selectively to HBC/HzCs vs. DBCs.

ERGs of Macaca monkeys were recorded at the cornea before and after intravitreal injection of drugs. Photopic responses were elicited by bright 200–220 ms flashes on a steady background of 3.3 log scotopic troland to suppress rod ERG components.

2–amino-4–phosphonobutyric acid (APB), which blocks DBC light responses, abolished the photopic b–wave and indicated that DBC activity is requisite for photopic b–wave production.

However, applying cis–2,3–piperidine dicarboxylic acid (PDA) and kynurenic acid (KYN), to suppress HBCs/HzCs and third-order neurons, revealed a novel ERG response that was entirely positive and was sustained for the duration of the flash. The normally phasic b–wave was subsumed into this new response. Applying n–methyl-dl-aspartate (NMA) did not replicate the PDA+KYN effect, indicating that third-order retinal cells are not involved. This suggests that HBC/HzC activity is critical for shaping the phasic b–wave.

Components attributable to depolarizing vs. hyperpolarizing cells were separated by subtracting waveforms after each drug from responses immediately before. This analysis indicated that DBCs and HBC/HzCs each can produce large but opposing field potentials that nearly cancel and that normally leave only the residual phasic b–wave response in the photopic ERG.

Latency of the DBC component was 5–9 ms slower than the HBC/HzC component. However, once activated, the DBC component had a steeper slope. This resembles properties known for the two types of cone synapses in lower species, in which the sign-preserving HBC/HzC synapse has faster kinetics but probably lower gain than the slower sign-inverting G-protein coupled DBC synapse.

A human patient with “unilateral cone dystrophy” was found to have a positive and sustained ERG that mimicked the monkey ERG after PDA+KYN, indicating that these novel positive photopic responses can occur naturally even without drug application.

These results demonstrate that hyperpolarizing second-order neurons are important for the primate photopic ERG. A “Push-Pull Model” is proposed in which DBC activity is requisite for b–wave production but in which HBC/HzC activity limits the amplitude and controls the shape of the primate photopic b–wave.

Keywords

Primate photopic electroretinogramCone photoreceptor cellRetinal bipolar cell2-amino-4-phosphonobutyric acidcis-2,3-piperidine dicarboxylic acid
Type
Research Articles
Information
Visual Neuroscience , Volume 11 , Issue 3 , May 1994 , pp. 519 - 532
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

Aguilar, M. & Stiles, W. S. (1954). Saturation of the rod mechanism of the retina at high levels of stimulation. Optica Acta (London) 1, 59–65.CrossRefGoogle Scholar
Ashmore, J. F. & Copenhagen, D. R. (1980). Different postsynaptic events in two types of retinal bipolar cell. Nature 288, 84–86.Google Scholar
Ashmore, J. F. & Copenhagen, D. R. (1983). An analysis of transmission from cones to hyperpolarizing bipolar cells in the retina of the turtle. Journal of Physiology 340, 569–597.CrossRefGoogle ScholarPubMed
Ashmore, J. F. & Falk, G. J. (1980). Responses of rod bipolar cells in the dark-adapted retina of the dogfish, Scyliorhinus canicula. Journal of Physiology 300, 115–150.CrossRefGoogle ScholarPubMed
Baylor, D. A., Fuortes, M. G. F. & O’Bryan, P. M. (1971). Receptive fields of single cones in the retina of the turtle. Journal of Physiology 214, 256–294.Google Scholar
Baylor, D. A. & Fetttplace, R. (1977 a). Transmission from photoreceptors to ganglion cells in turtle retina. Journal of Physiology 271, 391–424.CrossRefGoogle ScholarPubMed
Baylor, D. A. & Fetttplace, R. (1977 b). Kinetics of synaptic transfer from receptors to ganglion cells in turtle retina. Journal of Physiology 271, 425–448.CrossRefGoogle ScholarPubMed
Blake, J. F., Brown, M. W. & Collingridge, G. L. (1988). CNQX blocks acidic amino acid induced depolarizations and synaptic components mediated by non-NMDA receptors in rat hippocampal slices. Neuroscience Letters 89, 182–186.CrossRefGoogle ScholarPubMed
Brew, H., Gray, P. T. A., Mobbs, P. & Attwell, D. (1986). Endfeet of retinal glial cells have higher densities of ion channels that mediate K+ buffering. Nature 324, 466–468.CrossRefGoogle ScholarPubMed
Brigell, M. & Celesia, G. G. (1992). Electrophysiological evaluation of the neuro-ophthalmology patient: An algorithm for clinical use. Seminars in Ophthalmology 7, 65–78.CrossRefGoogle ScholarPubMed
Bush, R. A. & Sieving, P. A. (1994). A proximal retinal contribution to the primate photopic a–wave. Investigative Ophthalmology and Visual Science 35, 635–645.Google Scholar
Cervetto, L. & Piccolino, M. (1974). Synaptic transmission between photoreceptors and horizontal cells in the turtle retina. Science 183, 417–418.CrossRefGoogle ScholarPubMed
Coleman, P. A., Massey, S. C. & Miller, R. F. (1986). Kynurenic acid distinguishes kainate and quisqualate receptors in the vertebrate retina. Brain Research 381, 172–175.CrossRefGoogle ScholarPubMed
Copenhagen, D. R., Ashmore, J. F. & Schnapf, J. K. (1983). Kinetics of synaptic transmission from photoreceptors to horizontal and bipolar cells in turtle retina. Vision Research 23, 363–369.CrossRefGoogle ScholarPubMed
Dacheux, R. F. & Miller, R. F. (1976). Photoreceptor-bipolar cell transmission in the perfused retina eyecup of the mudpuppy. Science 191, 963–964.CrossRefGoogle ScholarPubMed
Daw, N. W., Jensen, R. J. & Bruken, W. J. (1990). Rod pathways in mammalian retinae. Trends in Neuroscience 13, 110–115.CrossRefGoogle ScholarPubMed
DeMarco, P. J. & Powers, M. K. (1989). Sensitivity of ERG components from dark-adapted goldfish retina treated with APB. Brain Research 482, 317–323.Google Scholar
deMonasterio, F. M., Gouras, P. & Tolhurst, D. J. (1975). Trichromatic color opponency in ganglion cells of the rhesus monkey retina. Journal of Physiology 251, 197–216.Google Scholar
Dick, E., Miller, R. F. (1978). Light-evoked potassium activity in mud-puppy retina: Its relationship to the b–wave of the electroretinogram. Brain Research 154, 388–394.Google Scholar
Dick, E. & Miller, R. F. & Bloomfield, S. (1985). Extracellular K+ activity changes related to electroretinogram components: II. Rabbit (E-type) retinas. Journal of General Physiology 85, 911–931.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
Evers, H. U. & Gouras, P. (1986). Three cone mechanisms in the primate electroretinogram: two with, one without off-center bipolar responses. Vision Research 26, 245–254.CrossRefGoogle ScholarPubMed
Faber, D. S. (1969). Analysis of slow transretinal potential in response to light. Ph.D. Dissertation, State University of New York at Buffalo.Google Scholar
Falk, G. & Shiells, R. A. (1986). Do horizontal cell responses contribute to the electroretinogram (ERG) in dogfish? Journal of Physiology 381, 113P.Google Scholar
Frishman, L. J. & Steinberg, R. H. (1989). Light-evoked changes in (K+)0 in proximal portion of the dark-adapted cat retina. Journal of Neurophysiology 61, 1233–1243.CrossRefGoogle Scholar
Frishman, L. J., Yamamoto, F, Bogucka, J. & Steinberg, R. H. (1992). Light-evoked changes in (K+)0 in proximal portion of light-adapted cat retina. Journal of Neurophysiology 67, 1201–1212.Google Scholar
Gallemore, R. P. & Steinberg, R. H. (1991). Cobalt increases photoreceptor-dependent responses of the chick retinal pigment epithelium. Investigative Ophthalmology and Visual Science 32, 3041–3052.Google ScholarPubMed
Granit, R. (1947). Sensory Mechanisms of the Retina. Oxford University Press, London.Google Scholar
Heynen, H., Wachtmeister, L. & VanNorren, D. (1985). Origin of the oscillatory potentials in the primate retina. Vision Research 25, 1365–1374.CrossRefGoogle ScholarPubMed
Honore, T., Davies, S. N., 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
Houchin, K. W., Purple, R. L. & Wirtschafter, J. D. (1991). X-linked congenital stationary night-blindness and depolarizing bipolar system dysfunction (ARVO Abstract). Investigative Ophthalmology and Visual Science 32, 1229.Google Scholar
Jardon, B., Yucel, H. & Bonaventure, N. (1989). Glutamatergic separation of ON and OFF retinal channels: Possible modulation by glycine and acetylcholine. European Journal of Pharmacology 162, 215–224.CrossRefGoogle Scholar
Kaneko, A., Pinto, L. H. & Tachibana, M. (1989). Transient calcium current of retinal bipolar cells of the mouse. Journal of Physiology 410, 613–629.Google Scholar
Kaneko, A. & Shimazaki, H. (1976). Synaptic transmission from photoreceptors to bipolar and horizontal cells in the carp retina. Cold Spring Harbor Symposium on Quantitative Biology 40, 537–546.Google Scholar
Kaneko, A. & Tachibana, M. (1985). A voltage-clamp analysis of membrane currents in solitary bipolar cells dissociated from Carassius auratus. Journal of Physiology 358, 131–152.Google Scholar
Karschin, A. & Wassle, H. (1990). Voltage- and transmitter-gated currents in isolated rod bipolar cells of rat retina. Journal of Neurophysiology 63, 860–876.CrossRefGoogle ScholarPubMed
Karwoski, C. J. & Proenza, L. M. (1977). Relationship between Müller cell responses, a local transretinal potential, and potassium flux. Journal of Neurophysiology 40, 244–259.Google Scholar
Katz, B. J., Wen, R., Zheng, J. B., Xu, Z. A. & Oakley, B. (1991). M-wave of the toad electroretinogram. Journal of Neurophysiology 66, 1927–1940.CrossRefGoogle ScholarPubMed
Klein, R. P., Ripps, H. & Dowling, J. E. (1978). Generation of b–wave currents in the skate retina. Proceedings of the National Academy of Sciences of the U.S.A. 75, 5727–5731.CrossRefGoogle Scholar
Kleinschmidt, J. & Dowling, J. E. (1975). Intracellular recordings from gecko photoreceptors during light and dark adaptation. Journal of General Physiology 66, 617–648.Google Scholar
Knapp, A. G. & Schiller, P. H. (1984). The contribution of ON-bipolar cells to the electroretinogram of rabbits and monkeys. Vision Research 24, 1841–1846.CrossRefGoogle Scholar
Kuffler, J. G. & Nichols, J. G. (1966). The physiology of neuroglial cells. Ergebnisse der Physiologic Biologischen Chemie und Experi-mentellen Pharmakologie 57, 1–90.Google ScholarPubMed
Lasater, E. (1988). Membrane currents of retinal bipolar cells in culture. Journal of Neurophysiology 60, 1460–1480.CrossRefGoogle ScholarPubMed
Malpeli, S. W. & Schiller, P. H. (1978). Lack of blue OFF-center cells in the visual system of the monkey. Brain Research 141, 385–389.CrossRefGoogle ScholarPubMed
Marc, R. E., Stell, W. K., Bok, D. & Lam, DM-K. (1978). GABA-ergic pathways in the goldfish retina. Journal of Comparative Neurology 182, 221–246.CrossRefGoogle ScholarPubMed
Mariani, A. P. (1984 a). Bipolar cells in monkey retina selective for cones likely to be blue sensitive. Nature 308, 184–186.CrossRefGoogle ScholarPubMed
Mariani, A. P. (1984 b). The neuronal organization of the outer plexi-form layer of the primate retina. International Reviews of Cytology 86, 285–320.CrossRefGoogle Scholar
Massey, S. C. (1990). Cell types using glutamate as a neurotransmitter in the vertebrate retina. Progress in Retinal Research 10, 399–426.Google Scholar
Massey, S. C, Redburn, D. A. & Crawford, M. L. 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
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
Miller, R. F. (1973). Role of K+ in generation of b–wave of electroretinogram. Journal of Neurophysiology 36, 28–38.CrossRefGoogle ScholarPubMed
Miller, R. F. & Dowling, J. E. (1970). Intracellular responses of the Müller (glial) cells of mudpuppy retina: Their relation to the b–wave of the electroretinogram. Journal of Neurophysiology 33, 323–341.CrossRefGoogle Scholar
Miyake, Y., Yagasaki, K., Horiguchi, M. & Kawase, Y. (1987). ON- and OFF-responses in photopic electroretinogram in complete and incomplete types of congenital stationary night blindness. Japanese Journal of Ophthalmology 31, 81–87.Google ScholarPubMed
Muller, F., Wässle, H. & Voigt, T. (1988). Pharmacological modulation of the rod pathway in the cat retina. Journal of Neurophysiology 59, 1657–1672.Google Scholar
Naarendorp, F. & Sieving, P. A. (1991). The scotopic threshold response of the cat ERG is suppressed selectively by GABA and glycine. Vision Research 31, 1–15.Google Scholar
Nawy, S. & Copenhagen, D. R. (1987). Multiple classes of glutamate receptor on depolarizing bipolar cells in retina. Nature 325, 56–58.CrossRefGoogle ScholarPubMed
Nawy, S. & Jahr, C. E. (1990). Suppression by glutamate of cGMP-activated conductance in retinal bipolar cells. Nature 346, 269–271.Google Scholar
Nawy, S., Sie, A. & Copenhagen, D. R. (1989). The glutamate analog 2–amino-4–phosphonobutyrate antagonizes synaptic transmission from cones to horizontal cells in the goldfish retina. Proceedings of the National Academy of Sciences of the U.S.A. 86, 1726–1730.Google Scholar
Newman, E. A. (1985). Voltage-dependent calcium and potassium channels in retinal glial cells. Nature 317, 809–811.CrossRefGoogle ScholarPubMed
Newman, E. A. & Odette, L. L. (1984). Model of electroretinogram b–wave generation: A test of the K+ hypothesis. Journal of Neurophysiology 51, 164–182.CrossRefGoogle ScholarPubMed
Nilius, B. & Reichenbach, A. (1988). Efficient K+ buffering by mammalian retinal glial cells is due to cooperation of specialized ion channels. European Journal of Physiology 411, 654–660.Google Scholar
Noell, W. K. (1953). The origin of the electroretinogram. American Journal of Ophthalmology 28, 78–90.Google Scholar
Oakley, B. II, Flaming, D.G. & Brown, K.T. (1979). Effects of the rod receptor potential upon retinal extracellular potassium concentration. Journal of General Physiology 74, 713–737.Google Scholar
Oakley, B. & Green, D. G. (1976). Correlation of light-induced changes in retinal extracellular potassium concentration with the c–wave of the electroretinogram. Journal of Neurophysiology 39, 1117–1133.CrossRefGoogle ScholarPubMed
Ogden, T. E. (1973). The oscillatory waves of the primate electroretinogram. Vision Research 13, 1059–1074.CrossRefGoogle ScholarPubMed
Penn, R. D. & Hagins, W. A. (1969). Signal transmission along retinal rods and the origin of the electroretinogram a–wave. Nature 223, 201–204.Google Scholar
Porciatti, V., Bagnoli, P. & Alesci, R. (1987). ON- and OFF-activityin the retinal and tectal responses to focal stimulation with uniform or patterned stimuli. Clinical Vision Sciences 2, 93–102.Google Scholar
Sarantis, M., Everett, K. & Attwell, D. (1988). A presynaptic action of glutamate at the cone output synapse. Nature 322, 451–453.Google Scholar
Shiells, R. A. & Falk, G. (1990). Glutamate receptors of rod bipolar cells are linked to a cyclic GMP cascade via a G-protein. Proceedings of the Royal Society B (London) 242, 91–94.Google Scholar
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
Shingai, R. & Quandt, F. N. (1986). Single inward rectifier channels in horizontal cells. Brain Research 369, 65–74.CrossRefGoogle ScholarPubMed
Sieving, P. A. (1993). AOS Thesis: Photopic ON- and OFF-pathway abnormalities in retinal dystrophies. Transactions of the American Ophthalmological Society LXXXXI, 701–773.Google 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 ScholarPubMed
Slaughter, M. M. & Miller, R. F. (1983 a). Bipolar cells in the mud-puppy retina use an excitatory amino acid neurotransmitter. Nature 303, 537–538.Google Scholar
Slaughter, M. M. & Miller, R. F. (1983 b). An excitatory amino acid antagonist blocks cone input to sign-conserving second-order retinal neurons. Science 219, 1230–1232.Google Scholar
Slaughter, M. 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.Google Scholar
Slaughter, M. M. & Miller, R. F. (1985). Identification of a distinct synaptic glutamate receptor on horizontal cells in mudpuppy retina. Nature 314, 96–97.Google Scholar
Smith, R. G., Freed, M. & Sterling, P. (1986). Microcircuitry of the dark-adapted cat retina: Functional architecture of the rod-cone network. Journal of Neurophysiology 6, 3505–3517.Google ScholarPubMed
IIISmith, E. L., Harwerth, R. S., Crawford, M. L. J & Duncan, G. C. (1989). Contribution of the retinal ON channels to scotopic and photopic spectral sensitivity. Visual Neuroscience 3, 225–239.CrossRefGoogle ScholarPubMed
Sperling, H. G. & Mills, S. L. (1991). Red-green interactions in the spectral sensitivity of primates as derived from ERG and behavioral data. Visual Neuroscience 7, 75–86.Google Scholar
Sterling, P., Freed, M. A. & Smith, R. G. (1986). Microcircuitry and functional architecture of the cat retina. Trends in Neuroscience 9, 186–192.CrossRefGoogle Scholar
Sterling, P., Freed, M. A. & Smith, R. G. (1988). Architecture of rod and cone circuits to the ON-beta ganglion cell. Journal of Neurophysiology 8, 623–642.Google Scholar
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.Google Scholar
Tachibana, M. & Kaneko, A. (1984). GABA acts at the axon terminals of turtle photoreceptors: Differences in sensitivity among cell types. Proceedings of the National Academy of Sciences of the U.S.A. 85, 5315–5319.CrossRefGoogle Scholar
Wakabayashi, K., Gieser, J. & Sieving, P. A. (1988). Aspartate separation of the scotopic threshold response (STR) from the photo-receptor a–wave of the cat and monkey ERG. Investigative Ophthalmology and Visual Science 29, 1615–1622.Google Scholar
Wassle, H., Yamashita, M., Greferath, U., Grunert, U. & Müller, F. (1991). The rod bipolar cell of the mammalian retina. Visual Neuroscience 7, 99–112.CrossRefGoogle ScholarPubMed
Wen, R. & Oakley, B. (1990). K(+)-evoked Müller cell depolarization generates b–wave of electroretinogram in toad retina. Proceedings of the National Academy of Sciences of the U.S.A. 87, 2117–2121.CrossRefGoogle ScholarPubMed
Witkovsky, P., Dudek, F. E. & Ripps, H. (1975). Slow PIII component of the carp electroretinogram. Journal of General Physiology 65, 119–134.CrossRefGoogle ScholarPubMed
Witkovsky, P., Stone, S. & Ripps, H. (1985). Pharmacological modification of the light-induced responses of Müuller (glial) cells in the amphibian retina. Brain Research 328, 111–120.CrossRefGoogle Scholar
Wu, S. M. (1991). Input-output relations of the feedback synapse between horizontal cells and cones in the tiger salamander retina. Journal of Neurophysiology 65, 1197–1206.CrossRefGoogle ScholarPubMed
Xu, X. & Karwoski, C. J. (1993). Current sources and sinks associated with the ERG b–wave. Investigative Ophthalmology and Visual Science (ARVO Abstract #2807), 34, 1272.Google Scholar
Xu, X., Xu, J., Huang, B., Livsey, C. T. & Karwoski, C. J. (1991). Comparison of pharmacological agents (aspartate vs. aminophos-phonobutyric + kyurenic acids) to block synaptic transmission from retinal photoreceptors in frog. Experimental Eye Research 52, 691–698.Google Scholar
Yamashita, M. & Wassle, H. (1991). Responses of rod bipolar cells isolated from the rat retina to the glutamate agonist 2–amino-4–phosphonobutyric acid (APB). Journal of Neuroscience 11(8), 2372–2382.Google Scholar
Yang, X.-L. & Wu, S. M. (1989). Effects of CNQX, APB, PDA, and kynurenate on horizontal cells of the tiger salamander retina. Visual Neuroscience 3, 207–212.CrossRefGoogle ScholarPubMed
Young, R. S. L. (1991). Low-frequency component of the photopic ERG in patients with X-linked congenital stationary night blindness. Clinical Vision Sciences 4, 309–315.Google Scholar
Zervas, J. P. & Smith, J. L. (1987). Neuro-ophthalmic presentation of cone dysfunction syndromes in the adult. Journal of Clinical Neuro-Ophthalmology 7, 202–218.Google Scholar