Skip to main content
NCBI home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1990 Oct;429:1–16. doi: 10.1113/jphysiol.1990.sp018240

Presynaptic glutamate receptors depress excitatory monosynaptic transmission between mouse hippocampal neurones.

I D Forsythe 1, J D Clements 1
PMCID: PMC1181683  PMID: 2177502

Abstract

1. Whole-cell patch-clamp techniques were used to record the excitatory postsynaptic current (EPSC) in a cultured mouse hippocampal neurone that resulted from electrical stimulation of another neurone in the cell culture. 2. L-Glutamate (less than 1 microM) reversibly depressed the EPSC amplitude in 67% of the synapses tested. The average amplitude reduction was 40%. The depression by glutamate was not blocked by extracellular magnesium (0.8 mM) or 2-amino-5-phosphonovaleric acid (AP5, 100 microM), indicating that N-methyl-D-aspartate (NMDA) receptors were not involved. 3. The phosphonic derivative of glutamate, L-2-amino-4-phosphonobutyrate (L-AP4), also depressed the EPSC amplitude. Neither glutamate nor L-AP4 induced any detectable inward current at concentrations which produced a potent depression of the EPSC. Statistical analysis of the amplitude fluctuations of evoked synaptic currents showed that the depression induced by both glutamate and L-AP4 was due to a decrease in the probability of synaptic release, confirming a presynaptic site of action. 4. Kainate and quisqualate also depressed excitatory synaptic transmission, but this action was related to the postsynaptic inward current that they induced. Statistical analysis showed that this action was consistent with a purely postsynaptic site of action. 5. Paired EPSCs separated by 20 ms showed either depression or potentiation of the second synaptic response. There was a strong correlation between those EPSCs which exhibited paired pulse depression and those depressed by glutamate application. 6. gamma-Aminobutyric acid (GABA) and baclofen also depressed excitatory synaptic transmission. This depression was not blocked by picrotoxin (100 microM). GABA (10 microM) was effective in 85% of cell pairs tested, while baclofen (5 microM) depressed every EPSC tested. A presynaptic site of action for both substances was indicated by the statistical analysis. 7. The results indicate that both glutamate and GABA suppress excitatory synaptic transmission by an action at presynaptic sites. The glutamate-induced depression may result from activation of a distinct excitatory amino acid receptor for which L-AP4 is a specific agonist.

Full text

PDF
1

Selected References

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

  1. Bliss T. V., Douglas R. M., Errington M. L., Lynch M. A. Correlation between long-term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats. J Physiol. 1986 Aug;377:391–408. doi: 10.1113/jphysiol.1986.sp016193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bridges R. J., Hearn T. J., Monaghan D. T., Cotman C. W. A comparison of 2-amino-4-phosphonobutyric acid (AP4) receptors and [3H]AP4 binding sites in the rat brain. Brain Res. 1986 Jun 4;375(1):204–209. doi: 10.1016/0006-8993(86)90977-7. [DOI] [PubMed] [Google Scholar]
  3. Butcher S. P., Collins J. F., Roberts P. J. Characterization of the binding of DL-[3H]-2-amino-4-phosphonobutyrate to L-glutamate-sensitive sites on rat brain synaptic membranes. Br J Pharmacol. 1983 Oct;80(2):355–364. doi: 10.1111/j.1476-5381.1983.tb10041.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Clements J. D. A statistical test for demonstrating a presynaptic site of action for a modulator of synaptic amplitude. J Neurosci Methods. 1990 Jan;31(1):75–88. doi: 10.1016/0165-0270(90)90012-5. [DOI] [PubMed] [Google Scholar]
  5. Clements J. D., Forsythe I. D., Redman S. J. Presynaptic inhibition of synaptic potentials evoked in cat spinal motoneurones by impulses in single group Ia axons. J Physiol. 1987 Feb;383:153–169. doi: 10.1113/jphysiol.1987.sp016402. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cotman C. W., Flatman J. A., Ganong A. H., Perkins M. N. Effects of excitatory amino acid antagonists on evoked and spontaneous excitatory potentials in guinea-pig hippocampus. J Physiol. 1986 Sep;378:403–415. doi: 10.1113/jphysiol.1986.sp016227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Crunelli V., Forda S., Kelly J. S. Blockade of amino acid-induced depolarizations and inhibition of excitatory post-synaptic potentials in rat dentate gyrus. J Physiol. 1983 Aug;341:627–640. doi: 10.1113/jphysiol.1983.sp014829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Curtis D. R., Lodge D. The depolarization of feline ventral horn group Ia spinal afferent terminations by GABA. Exp Brain Res. 1982;46(2):215–233. doi: 10.1007/BF00237180. [DOI] [PubMed] [Google Scholar]
  9. Davies J., Watkins J. C. Actions of D and L forms of 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate in the cat spinal cord. Brain Res. 1982 Mar 11;235(2):378–386. doi: 10.1016/0006-8993(82)91017-4. [DOI] [PubMed] [Google Scholar]
  10. Dunwiddie T., Lynch G. Long-term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency. J Physiol. 1978 Mar;276:353–367. doi: 10.1113/jphysiol.1978.sp012239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Edwards F. R., Redman S. J., Walmsley B. Statistical fluctuations in charge transfer at Ia synapses on spinal motoneurones. J Physiol. 1976 Aug;259(3):665–688. doi: 10.1113/jphysiol.1976.sp011488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fagg G. E., Foster A. C., Mena E. E., Cotman C. W. Chloride and calcium ions reveal a pharmacologically distinct population of L-glutamate binding sites in synaptic membranes: correspondence between biochemical and electrophysiological data. J Neurosci. 1982 Jul;2(7):958–965. doi: 10.1523/JNEUROSCI.02-07-00958.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Forsythe I. D., Coates R. T. A chamber for electrophysiological recording from cultured neurones allowing perfusion and temperature control. J Neurosci Methods. 1988 Aug;25(1):19–27. doi: 10.1016/0165-0270(88)90116-1. [DOI] [PubMed] [Google Scholar]
  14. Forsythe I. D., Westbrook G. L., Mayer M. L. Modulation of excitatory synaptic transmission by glycine and zinc in cultures of mouse hippocampal neurons. J Neurosci. 1988 Oct;8(10):3733–3741. doi: 10.1523/JNEUROSCI.08-10-03733.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Gannon R. L., Baty L. T., Terrian D. M. L(+)-2-amino-4-phosphonobutyrate inhibits the release of both glutamate and dynorphin from guinea pig but not rat hippocampal mossy fiber synaptosomes. Brain Res. 1989 Aug 21;495(1):151–155. doi: 10.1016/0006-8993(89)91229-8. [DOI] [PubMed] [Google Scholar]
  17. Gähwiler B. H., Brown D. A. GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1558–1562. doi: 10.1073/pnas.82.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harrison N. L., Lange G. D., Barker J. L. (-)-Baclofen activates presynaptic GABAB receptors on GABAergic inhibitory neurons from embryonic rat hippocampus. Neurosci Lett. 1988 Feb 15;85(1):105–109. doi: 10.1016/0304-3940(88)90437-5. [DOI] [PubMed] [Google Scholar]
  19. Jack J. J., Redman S. J., Wong K. The components of synaptic potentials evoked in cat spinal motoneurones by impulses in single group Ia afferents. J Physiol. 1981 Dec;321:65–96. doi: 10.1113/jphysiol.1981.sp013972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Johnson J. W., Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987 Feb 5;325(6104):529–531. doi: 10.1038/325529a0. [DOI] [PubMed] [Google Scholar]
  21. Koerner J. F., Cotman C. W. Micromolar L-2-amino-4-phosphonobutyric acid selectively inhibits perforant path synapses from lateral entorhinal cortex. Brain Res. 1981 Jul 6;216(1):192–198. doi: 10.1016/0006-8993(81)91288-9. [DOI] [PubMed] [Google Scholar]
  22. Ling L., Tolhurst D. J. Recovering the parameters of finite mixtures of normal distributions from a noisy record: an empirical comparison of different estimating procedures. J Neurosci Methods. 1983 Aug;8(4):309–333. doi: 10.1016/0165-0270(83)90090-0. [DOI] [PubMed] [Google Scholar]
  23. Mayer M. L., Vyklicky L., Jr, Clements J. Regulation of NMDA receptor desensitization in mouse hippocampal neurons by glycine. Nature. 1989 Mar 30;338(6214):425–427. doi: 10.1038/338425a0. [DOI] [PubMed] [Google Scholar]
  24. Mayer M. L., Vyklicky L., Jr Concanavalin A selectively reduces desensitization of mammalian neuronal quisqualate receptors. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1411–1415. doi: 10.1073/pnas.86.4.1411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Mayer M. L., Westbrook G. L. The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol. 1987;28(3):197–276. doi: 10.1016/0301-0082(87)90011-6. [DOI] [PubMed] [Google Scholar]
  27. Monaghan D. T., McMills M. C., Chamberlin A. R., Cotman C. W. Synthesis of [3H]2-amino-4-phosphonobutyric acid and characterization of its binding to rat brain membranes: a selective ligand for the chloride/calcium-dependent class of L-glutamate binding sites. Brain Res. 1983 Nov 14;278(1-2):137–144. doi: 10.1016/0006-8993(83)90232-9. [DOI] [PubMed] [Google Scholar]
  28. Newberry N. R., Nicoll R. A. Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. 1984 Mar 29-Apr 4Nature. 308(5958):450–452. doi: 10.1038/308450a0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. 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]
  31. Pin J. P., Bockaert J., Recasesn M. The Ca2+/C1- dependent L-[3H]glutamate binding: a new receptor or a particular transport process? FEBS Lett. 1984 Sep 17;175(1):31–36. doi: 10.1016/0014-5793(84)80563-3. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Starke K. Presynaptic receptors. Annu Rev Pharmacol Toxicol. 1981;21:7–30. doi: 10.1146/annurev.pa.21.040181.000255. [DOI] [PubMed] [Google Scholar]
  34. Watkins J. C., Evans R. H. Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol. 1981;21:165–204. doi: 10.1146/annurev.pa.21.040181.001121. [DOI] [PubMed] [Google Scholar]

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

RESOURCES