Skip to main content
The Journal of Physiology logoLink to The Journal of Physiology
. 1990 Sep;428:175–197. doi: 10.1113/jphysiol.1990.sp018206

Concomitant activation of two types of glutamate receptor mediates excitation of salamander retinal ganglion cells.

S Mittman 1, W R Taylor 1, D R Copenhagen 1
PMCID: PMC1181641  PMID: 2172521

Abstract

1. Cells in the ganglion cell layer of salamander retinal slices were voltage clamped using patch pipettes. Light elicited transient excitatory postsynaptic currents (EPSCs) in on-off ganglion cells and sustained EPSCs in on ganglion cells. Light-evoked inhibitory postsynaptic currents in these cells could be blocked by 100 microM-bicuculline methobromide and 500 nM-strychnine. 2. In the presence of external Cd2+, at a concentration that blocked light-evoked synaptic inputs, N-methyl-D-aspartate (NMDA) and the non-NMDA-receptor agonists, quisqualate and kainate, gated conductances in both on-off and on ganglion cells. The current-voltage (I-V) curve for the conductance elicited by NMDA had a negative slope between -40 and -70 mV and a reversal potential near 0 mV. The I-V curves for the non-NMDA-receptor-mediated conductances were nearly linear and also had reversal potentials near 0 mV. 3. I-V curves were measured at an early time point near the peak of transient EPSCs and at a later time point during the decay phase of the responses. The late I-V curve had a negative slope below -40 mV. The early I-V curve had a positive slope over the entire voltage range but the slope was greater at positive than at negative potentials. The evoked current reversed near 0 mV at both time points. 4. The region of negative slope of the late I-V curve was eliminated when Mg2+ was removed from the external saline. A slowly decaying component of transient EPSCs was eliminated in 20 microM-DL-2-amino-7-phosphonoheptanoate (AP7), an NMDA-receptor antagonist. 5. Application of 1 microM-6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA-receptor antagonist at this concentration, blocked a fast component of transient EPSCs. 6. Our results demonstrate that the synaptic inputs to on-off ganglion cells have two components: a slower NMDA-receptor-mediated component having a time-to-peak of 110 +/- 45 ms and an e-fold decay time of 209 +/- 35 ms at -31 mV (mean +/- S.D., n = 5), and a faster non-NMDA-receptor-mediated component having a time-to-peak of 28 +/- 10 ms and an e-fold decay time of 43 +/- 20 ms at -31 mV (n = 8). 7. A similar analysis of sustained EPSCs of on ganglion cells showed that these currents resulted from sustained activation of both NMDA and non-NMDA receptors.

Full text

PDF
180

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aizenman E., Frosch M. P., Lipton S. A. Responses mediated by excitatory amino acid receptors in solitary retinal ganglion cells from rat. J Physiol. 1988 Feb;396:75–91. doi: 10.1113/jphysiol.1988.sp016951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ascher P., Nowak L. The role of divalent cations in the N-methyl-D-aspartate responses of mouse central neurones in culture. J Physiol. 1988 May;399:247–266. doi: 10.1113/jphysiol.1988.sp017078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ball A. K., Dickson D. H. Displaced amacrine and ganglion cells in the newt retina. Exp Eye Res. 1983 Feb;36(2):199–213. doi: 10.1016/0014-4835(83)90006-4. [DOI] [PubMed] [Google Scholar]
  4. Bekkers J. M., Stevens C. F. NMDA and non-NMDA receptors are co-localized at individual excitatory synapses in cultured rat hippocampus. Nature. 1989 Sep 21;341(6239):230–233. doi: 10.1038/341230a0. [DOI] [PubMed] [Google Scholar]
  5. Belgum J. H., Dvorak D. R., McReynolds J. S. Strychnine blocks transient but not sustained inhibition in mudpuppy retinal ganglion cells. J Physiol. 1984 Sep;354:273–286. doi: 10.1113/jphysiol.1984.sp015375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coleman P. A., Massey S. C., Miller R. F. Kynurenic acid distinguishes kainate and quisqualate receptors in the vertebrate retina. Brain Res. 1986 Aug 27;381(1):172–175. doi: 10.1016/0006-8993(86)90708-0. [DOI] [PubMed] [Google Scholar]
  7. Coleman P. A., Miller R. F. Do N-methyl-D-aspartate receptors mediate synaptic responses in the mudpuppy retina? J Neurosci. 1988 Dec;8(12):4728–4733. doi: 10.1523/JNEUROSCI.08-12-04728.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coleman P. A., Miller R. F. Kainate receptor-mediated synaptic currents in mudpuppy inner retinal neurons reduced by D-O-phosphoserine. J Neurophysiol. 1989 Aug;62(2):495–500. doi: 10.1152/jn.1989.62.2.495. [DOI] [PubMed] [Google Scholar]
  9. Dale N., Roberts A. Dual-component amino-acid-mediated synaptic potentials: excitatory drive for swimming in Xenopus embryos. J Physiol. 1985 Jun;363:35–59. doi: 10.1113/jphysiol.1985.sp015694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Forsythe I. D., Westbrook G. L. Slow excitatory postsynaptic currents mediated by N-methyl-D-aspartate receptors on cultured mouse central neurones. J Physiol. 1988 Feb;396:515–533. doi: 10.1113/jphysiol.1988.sp016975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Frumkes T. E., Miller R. F., Slaughter M., Dacheux R. F. 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. J Neurophysiol. 1981 Apr;45(4):783–804. doi: 10.1152/jn.1981.45.4.783. [DOI] [PubMed] [Google Scholar]
  12. Hoffman R., Gross L. The modulation contrast microscope. Nature. 1975 Apr 17;254(5501):586–588. doi: 10.1038/254586a0. [DOI] [PubMed] [Google Scholar]
  13. Honoré T., Davies S. N., Drejer J., Fletcher E. J., Jacobsen P., Lodge D., Nielsen F. E. Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists. Science. 1988 Aug 5;241(4866):701–703. doi: 10.1126/science.2899909. [DOI] [PubMed] [Google Scholar]
  14. Lukasiewicz P. D., McReynolds J. S. Synaptic transmission at N-methyl-D-aspartate receptors in the proximal retina of the mudpuppy. J Physiol. 1985 Oct;367:99–115. doi: 10.1113/jphysiol.1985.sp015816. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lukasiewicz P., Werblin F. A slowly inactivating potassium current truncates spike activity in ganglion cells of the tiger salamander retina. J Neurosci. 1988 Dec;8(12):4470–4481. doi: 10.1523/JNEUROSCI.08-12-04470.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Maguire G., Lukasiewicz P., Werblin F. Amacrine cell interactions underlying the response to change in the tiger salamander retina. J Neurosci. 1989 Feb;9(2):726–735. doi: 10.1523/JNEUROSCI.09-02-00726.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Marchiafava P. L., Torre V. The responses of amacrine cells to light and intracellularly applied currents. J Physiol. 1978 Mar;276:83–102. doi: 10.1113/jphysiol.1978.sp012221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Massey S. C., Miller R. F. Glutamate receptors of ganglion cells in the rabbit retina: evidence for glutamate as a bipolar cell transmitter. J Physiol. 1988 Nov;405:635–655. doi: 10.1113/jphysiol.1988.sp017353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mayer M. L., Vyklicky L., Jr, Westbrook G. L. Modulation of excitatory amino acid receptors by group IIB metal cations in cultured mouse hippocampal neurones. J Physiol. 1989 Aug;415:329–350. doi: 10.1113/jphysiol.1989.sp017724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Mayer M. L., Westbrook G. L., Guthrie P. B. Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones. Nature. 1984 May 17;309(5965):261–263. doi: 10.1038/309261a0. [DOI] [PubMed] [Google Scholar]
  21. Mayer M. L., Westbrook G. L. Mixed-agonist action of excitatory amino acids on mouse spinal cord neurones under voltage clamp. J Physiol. 1984 Sep;354:29–53. doi: 10.1113/jphysiol.1984.sp015360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mayer M. L., Westbrook G. L. Permeation and block of N-methyl-D-aspartic acid receptor channels by divalent cations in mouse cultured central neurones. J Physiol. 1987 Dec;394:501–527. doi: 10.1113/jphysiol.1987.sp016883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mayer M. L., Westbrook G. L. The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture. J Physiol. 1985 Apr;361:65–90. doi: 10.1113/jphysiol.1985.sp015633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Miller R. F., Dacheux R. F., Frumkes T. E. Amacrine cells in Necturus retina: evidence for independent gamma-aminobutyric acid- and glycine-releasing neurons. Science. 1977 Nov 18;198(4318):748–750. doi: 10.1126/science.910159. [DOI] [PubMed] [Google Scholar]
  25. Miller R. F., Frumkes T. E., Slaughter M., Dacheux R. F. Physiological and pharmacological basis of GABA and glycine action on neurons of mudpuppy retina. II. Amacrine and ganglion cells. J Neurophysiol. 1981 Apr;45(4):764–782. doi: 10.1152/jn.1981.45.4.764. [DOI] [PubMed] [Google Scholar]
  26. Mittman S., Flaming D. G., Copenhagen D. R., Belgum J. H. Bubble pressure measurement of micropipet tip outer diameter. J Neurosci Methods. 1987 Dec;22(2):161–166. doi: 10.1016/0165-0270(87)90010-0. [DOI] [PubMed] [Google Scholar]
  27. Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
  28. Olverman H. J., Jones A. W., Watkins J. C. L-glutamate has higher affinity than other amino acids for [3H]-D-AP5 binding sites in rat brain membranes. Nature. 1984 Feb 2;307(5950):460–462. doi: 10.1038/307460a0. [DOI] [PubMed] [Google Scholar]
  29. Perry V. H. The ganglion cell layer of the retina of the rat: a Golgi study. Proc R Soc Lond B Biol Sci. 1979 May 23;204(1156):363–375. doi: 10.1098/rspb.1979.0033. [DOI] [PubMed] [Google Scholar]
  30. Shiells R. A., Falk G., Naghshineh S. Action of glutamate and aspartate analogues on rod horizontal and bipolar cells. Nature. 1981 Dec 10;294(5841):592–594. doi: 10.1038/294592a0. [DOI] [PubMed] [Google Scholar]
  31. Slaughter M. M., Miller R. F. 2-amino-4-phosphonobutyric acid: a new pharmacological tool for retina research. Science. 1981 Jan 9;211(4478):182–185. doi: 10.1126/science.6255566. [DOI] [PubMed] [Google Scholar]
  32. Slaughter M. M., Miller R. F. Bipolar cells in the mudpuppy retina use an excitatory amino acid neurotransmitter. Nature. 1983 Jun 9;303(5917):537–538. doi: 10.1038/303537a0. [DOI] [PubMed] [Google Scholar]
  33. Slaughter M. M., Miller R. F. The role of excitatory amino acid transmitters in the mudpuppy retina: an analysis with kainic acid and N-methyl aspartate. J Neurosci. 1983 Aug;3(8):1701–1711. doi: 10.1523/JNEUROSCI.03-08-01701.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Turner J. E., Delaney R. K., Powell R. E. Retinal ganglion cell response to axotomy in the regenerating visual system of the newt (Triturus viridescens): an ultrastructural morphometric analysis. Exp Neurol. 1978 Nov;62(2):444–462. doi: 10.1016/0014-4886(78)90067-5. [DOI] [PubMed] [Google Scholar]
  35. Werblin F. S. Transmission along and between rods in the tiger salamander retina. J Physiol. 1978 Jul;280:449–470. doi: 10.1113/jphysiol.1978.sp012394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Wigström H., Gustafsson B., Huang Y. Y. A synaptic potential following single volleys in the hippocampal CA1 region possibly involved in the induction of long-lasting potentiation. Acta Physiol Scand. 1985 Jul;124(3):475–478. doi: 10.1111/j.1748-1716.1985.tb07685.x. [DOI] [PubMed] [Google Scholar]
  37. Wu S. M. Synaptic connections between neurons in living slices of the larval tiger salamander retina. J Neurosci Methods. 1987 Jun;20(2):139–149. doi: 10.1016/0165-0270(87)90046-x. [DOI] [PubMed] [Google Scholar]
  38. Wunk D. F., Werblin F. S. Synaptic inputs to the ganglion cells in the tiger salamander retina. J Gen Physiol. 1979 Mar;73(3):265–286. doi: 10.1085/jgp.73.3.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yamada K. A., Dubinsky J. M., Rothman S. M. Quantitative physiological characterization of a quinoxalinedione non-NMDA receptor antagonist. J Neurosci. 1989 Sep;9(9):3230–3236. doi: 10.1523/JNEUROSCI.09-09-03230.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES