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. 1990 Dec;101(4):847–852. doi: 10.1111/j.1476-5381.1990.tb14169.x

Sensitivity of hippocampal neurones to kainic acid, and antagonism by kynurenate.

T W Stone 1
PMCID: PMC1917822  PMID: 1964821

Abstract

1. The sensitivity to kainic acid of neurones in the CA1 and CA3 regions of rat hippocampal slices has been examined by microiontophoresis and by superfusion methods. 2. When the iontophoretic currents needed to produce comparable plateaux of firing were compared, neurones in the pyramidal cell layer of the CA3 region were approximately 5 times more sensitive than cells in the CA1 region. No difference was noted in sensitivity to N-methyl-D-aspartate (NMDA) or quisqualate. 3. When kainate was superfused at known concentrations, the threshold for eliciting excitation in CA1 was 2.1 microM. The threshold concentration in CA3 was 0.24 microM. 4. Two weeks after the stereotaxic intrahippocampal injection of colchicine, the granule cells of the dentate gyrus and thus the mossy fibre projections to CA3 were destroyed. In slices prepared from animals thus treated the threshold concentration of kainate for eliciting excitation had risen to 1.64 microM. 5. Kainate was less effective in promoting the development of epileptiform bursts of neuronal firing in colchicine-treated slices than in controls. 6. Kynurenic acid antagonized the excitation of CA1 neurones elicited by kainate, NMDA or quisqualate. In the CA3 region kynurenate antagonized selectively responses to microiontophoretic NMDA, with little effect on responses to kainate or quisqualate. 7. In slices taken from colchicine-treated rats kynurenate was able to block responses to kainate in the CA3 area in parallel with responses to NMDA. 8. Taken together the results suggest that the excitatory responses to kainate in the CA3 region may be partly due to a presynaptic action on mossy fibre terminals to release endogenous amino acids.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Birch P. J., Grossman C. J., Hayes A. G. Kynurenic acid antagonises responses to NMDA via an action at the strychnine-insensitive glycine receptor. Eur J Pharmacol. 1988 Sep 1;154(1):85–87. doi: 10.1016/0014-2999(88)90367-6. [DOI] [PubMed] [Google Scholar]
  2. Collins G. G., Anson J., Surtees L. Presynaptic kainate and N-methyl-D-aspartate receptors regulate excitatory amino acid release in the olfactory cortex. Brain Res. 1983 Apr 11;265(1):157–159. doi: 10.1016/0006-8993(83)91348-3. [DOI] [PubMed] [Google Scholar]
  3. Connick J. H., Stone T. W. Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo. Br J Pharmacol. 1988 Apr;93(4):868–876. doi: 10.1111/j.1476-5381.1988.tb11474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Danysz W., Fadda E., Wroblewski J. T., Costa E. Kynurenate and 2-amino-5-phosphonovalerate interact with multiple binding sites of the N-methyl-D-aspartate-sensitive glutamate receptor domain. Neurosci Lett. 1989 Jan 30;96(3):340–344. doi: 10.1016/0304-3940(89)90402-3. [DOI] [PubMed] [Google Scholar]
  5. Dodd J., Kelly J. S. The actions of cholecystokinin and related peptides on pyramidal neurones of the mammalian hippocampus. Brain Res. 1981 Feb 2;205(2):337–350. doi: 10.1016/0006-8993(81)90344-9. [DOI] [PubMed] [Google Scholar]
  6. Elmslie K. S., Yoshikami D. Effects of kynurenate on root potentials evoked by synaptic activity and amino acids in the frog spinal cord. Brain Res. 1985 Mar 25;330(2):265–272. doi: 10.1016/0006-8993(85)90685-7. [DOI] [PubMed] [Google Scholar]
  7. Evans R. H., Evans S. J., Pook P. C., Sunter D. C. A comparison of excitatory amino acid antagonists acting at primary afferent C fibres and motoneurones of the isolated spinal cord of the rat. Br J Pharmacol. 1987 Jul;91(3):531–537. doi: 10.1111/j.1476-5381.1987.tb11246.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ferkany J. W., Coyle J. T. Kainic acid selectively stimulates the release of endogenous excitatory acidic amino acids. J Pharmacol Exp Ther. 1983 May;225(2):399–406. [PubMed] [Google Scholar]
  9. Fisher R. S., Alger B. E. Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. J Neurosci. 1984 May;4(5):1312–1323. doi: 10.1523/JNEUROSCI.04-05-01312.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Foster A. C., Mena E. E., Monaghan D. T., Cotman C. W. Synaptic localization of kainic acid binding sites. Nature. 1981 Jan 1;289(5793):73–75. doi: 10.1038/289073a0. [DOI] [PubMed] [Google Scholar]
  11. Gallo V., Giovannini C., Levi G. Quisqualic acid modulates kainate responses in cultured cerebellar granule cells. J Neurochem. 1989 Jan;52(1):10–16. doi: 10.1111/j.1471-4159.1989.tb10891.x. [DOI] [PubMed] [Google Scholar]
  12. Gallo V., Suergiu R., Levi G. Functional evaluation of glutamate receptor subtypes in cultured cerebellar neurones and astrocytes. Eur J Pharmacol. 1987 Jun 19;138(2):293–297. doi: 10.1016/0014-2999(87)90448-1. [DOI] [PubMed] [Google Scholar]
  13. Ganong A. H., Cotman C. W. Kynurenic acid and quinolinic acid act at N-methyl-D-aspartate receptors in the rat hippocampus. J Pharmacol Exp Ther. 1986 Jan;236(1):293–299. [PubMed] [Google Scholar]
  14. Ganong A. H., Lanthorn T. H., Cotman C. W. Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res. 1983 Aug 22;273(1):170–174. doi: 10.1016/0006-8993(83)91108-3. [DOI] [PubMed] [Google Scholar]
  15. Goldschmidt R. B., Steward O. Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. Proc Natl Acad Sci U S A. 1980 May;77(5):3047–3051. doi: 10.1073/pnas.77.5.3047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Greenamyre J. T., Olson J. M., Penney J. B., Jr, Young A. B. Autoradiographic characterization of N-methyl-D-aspartate-, quisqualate- and kainate-sensitive glutamate binding sites. J Pharmacol Exp Ther. 1985 Apr;233(1):254–263. [PubMed] [Google Scholar]
  17. Herrling P. L. Pharmacology of the corticocaudate excitatory postsynaptic potential in the cat: evidence for its mediation by quisqualate- or kainate-receptors. Neuroscience. 1985 Feb;14(2):417–426. doi: 10.1016/0306-4522(85)90301-x. [DOI] [PubMed] [Google Scholar]
  18. Innis R. B., Corrêa F. M., Uhl G. R., Schneider B., Snyder S. H. Cholecystokinin octapeptide-like immunoreactivity: histochemical localization in rat brain. Proc Natl Acad Sci U S A. 1979 Jan;76(1):521–525. doi: 10.1073/pnas.76.1.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leone C., Gordon F. J. Is L-glutamate a neurotransmitter of baroreceptor information in the nucleus of the tractus solitarius? J Pharmacol Exp Ther. 1989 Sep;250(3):953–962. [PubMed] [Google Scholar]
  20. London E. D., Klemm N., Coyle J. T. Phylogenetic distribution of [3H]kainic acid receptor binding sites in neuronal tissue. Brain Res. 1980 Jun 23;192(2):463–476. doi: 10.1016/0006-8993(80)90897-5. [DOI] [PubMed] [Google Scholar]
  21. Mayer M. L., Westbrook G. L., Vyklický L., Jr Sites of antagonist action on N-methyl-D-aspartic acid receptors studied using fluctuation analysis and a rapid perfusion technique. J Neurophysiol. 1988 Aug;60(2):645–663. doi: 10.1152/jn.1988.60.2.645. [DOI] [PubMed] [Google Scholar]
  22. Monaghan D. T., Yao D., Cotman C. W. L-[3H]Glutamate binds to kainate-, NMDA- and AMPA-sensitive binding sites: an autoradiographic analysis. Brain Res. 1985 Aug 12;340(2):378–383. doi: 10.1016/0006-8993(85)90936-9. [DOI] [PubMed] [Google Scholar]
  23. Neuman R. S., Ben-Ari Y., Cherubini E. Antagonism of spontaneous and evoked bursts by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the CA3 region of the in vitro hippocampus. Brain Res. 1988 Nov 22;474(1):201–203. doi: 10.1016/0006-8993(88)90686-5. [DOI] [PubMed] [Google Scholar]
  24. Okazaki M. M., Aitken P. G., Nadler J. V. Mossy fiber lesion reduces the probability that kainic acid will provoke CA3 hippocampal pyramidal cell bursting. Brain Res. 1988 Feb 9;440(2):352–356. doi: 10.1016/0006-8993(88)91006-2. [DOI] [PubMed] [Google Scholar]
  25. Okazaki M. M., Nadler J. V. Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration. Neuroscience. 1988 Sep;26(3):763–781. doi: 10.1016/0306-4522(88)90097-8. [DOI] [PubMed] [Google Scholar]
  26. Perkins M. N., Stone T. W. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 1982 Sep 9;247(1):184–187. doi: 10.1016/0006-8993(82)91048-4. [DOI] [PubMed] [Google Scholar]
  27. Potashner S. J., Gerard D. Kainate-enhanced release of D-[3H]aspartate from cerebral cortex and striatum: reversal by baclofen and pentobarbital. J Neurochem. 1983 Jun;40(6):1548–1557. doi: 10.1111/j.1471-4159.1983.tb08125.x. [DOI] [PubMed] [Google Scholar]
  28. Represa A., Tremblay E., Ben-Ari Y. Kainate binding sites in the hippocampal mossy fibers: localization and plasticity. Neuroscience. 1987 Mar;20(3):739–748. doi: 10.1016/0306-4522(87)90237-5. [DOI] [PubMed] [Google Scholar]
  29. Robinson J. H., Deadwyler S. A. Kainic acid produces depolarization of CA3 pyramidal cells in the vitro hippocampal slice. Brain Res. 1981 Sep 21;221(1):117–127. doi: 10.1016/0006-8993(81)91067-2. [DOI] [PubMed] [Google Scholar]
  30. Sawada S., Higashima M., Yamamoto C. Kainic acid induces long-lasting depolarizations in hippocampal neurons only when applied to stratum lucidum. Exp Brain Res. 1988;72(1):135–140. doi: 10.1007/BF00248508. [DOI] [PubMed] [Google Scholar]
  31. Sawada S., Yamamoto C. Fast and slow depolarizing potentials induced by short pulses of kainic acid in hippocampal neurons. Brain Res. 1984 Dec 24;324(2):279–287. doi: 10.1016/0006-8993(84)90038-6. [DOI] [PubMed] [Google Scholar]
  32. Stone T. W., Burton N. R. NMDA receptors and ligands in the vertebrate CNS. Prog Neurobiol. 1988;30(4):333–368. doi: 10.1016/0301-0082(88)90027-5. [DOI] [PubMed] [Google Scholar]
  33. Surtees L., Collins G. G. Receptor types mediating the excitatory actions of exogenous L-aspartate and L-glutamate in rat olfactory cortex. Brain Res. 1985 May 20;334(2):287–295. doi: 10.1016/0006-8993(85)90220-3. [DOI] [PubMed] [Google Scholar]
  34. Unnerstall J. R., Wamsley J. K. Autoradiographic localization of high-affinity [3H]kainic acid binding sites in the rat forebrain. Eur J Pharmacol. 1983 Jan 21;86(3-4):361–371. doi: 10.1016/0014-2999(83)90185-1. [DOI] [PubMed] [Google Scholar]
  35. Vanderhaeghen J. J., Lotstra F., De Mey J., Gilles C. Immunohistochemical localization of cholecystokinin- and gastrin-like peptides in the brain and hypophysis of the rat. Proc Natl Acad Sci U S A. 1980 Feb;77(2):1190–1194. doi: 10.1073/pnas.77.2.1190. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. 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]
  37. Westbrook G. L., Lothman E. W. Cellular and synaptic basis of kainic acid-induced hippocampal epileptiform activity. Brain Res. 1983 Aug 22;273(1):97–109. doi: 10.1016/0006-8993(83)91098-3. [DOI] [PubMed] [Google Scholar]
  38. Young A. M., Crowder J. M., Bradford H. F. Potentiation by kainate of excitatory amino acid release in striatum: complementary in vivo and in vitro experiments. J Neurochem. 1988 Feb;50(2):337–345. doi: 10.1111/j.1471-4159.1988.tb02918.x. [DOI] [PubMed] [Google Scholar]
  39. Zarbin M. A., Innis R. B., Wamsley J. K., Snyder S. H., Kuhar M. J. Autoradiographic localization of cholecystokinin receptors in rodent brain. J Neurosci. 1983 Apr;3(4):877–906. doi: 10.1523/JNEUROSCI.03-04-00877.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. de Montigny C., Tardif D. Differential excitatory effects of kainic acid on CA3 and CA1 hippocampal pyramidal neurons: further evidence for the excitotoxic hypothesis and for a receptor-mediated action. Life Sci. 1981 Nov 16;29(20):2103–2111. doi: 10.1016/0024-3205(81)90667-6. [DOI] [PubMed] [Google Scholar]
  41. de Montigny C., Weiss M., Ouellette J. Reduced excitatory effect of kainic acid on rat CA3 hippocampal pyramidal neurons following destruction of the mossy projection with colchicine. Exp Brain Res. 1987;65(3):605–613. doi: 10.1007/BF00235983. [DOI] [PubMed] [Google Scholar]

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