Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Effects of kainic and other amino acids on synaptic excitation in rat hippocampal slices: 1. Extracellular analysis

  • 77 Accesses

  • 31 Citations


The actions of kainic acid on excitatory synaptic responses in rat hippocampal slices have been investigated and compared with the effects of other excitatory amino acids. Kainate administered iontophoretically or via the superfusate produced a large and long lasting potentiation of the population spike evoked in the CA1 region by Schaffer collateral-commissural stimulation. This potentation was associated with a reduction in the field EPSP recorded in the dendritic region (stratum radiatum) but with no change in the presynaptic fibre volley or with any long lasting alteration in the antidromic population spike. The results suggest that one effect of kainate may be to produce dendritic depolarisation in CA1 pyramidal neurones.

Kainate in equivalent amounts elicited similar potentiations of the population spike recorded in the dentate gyrus in response to either lateral or medial perforant path stimulation. Smaller amounts of kainate than those required to affect either CA1 or dentate pathways were able to potentiate the mossy fibre-evoked population spike in the CA3 region.

Folic acid, which shares kainate's ability to produce seizures and distant brain damage when injected into the brain, elicited similar potentiations of synaptic excitation. Higher doses of folate than of kainate were required which is consistent with its weaker epileptogenic actions in vivo. In contrast, N-methyl-aspartate, ibotenate, L-glutamate and L-aspartate were unable to mimic kainate's potentiating action. In higher doses the substances depressed the population spike for long periods. These data suggest that potentiation of synaptic events may underlie the ability of kainate (and folate) to elicit seizures and distant brain damage.

This is a preview of subscription content, log in to check access.


  1. Andersen P (1960) Interhippocampal impulses. II. Apical dendritic activation of CA1 neurons. Acta Physiol Scand 48: 178–208

  2. Andersen P, Bliss TVP, Skrede KK (1971) Unit analysis of hippocampal population spikes. Exp Brain Res 13: 208–221

  3. Andersen P, Silfvenius H, Sundberg SH, Sveen O, Wigström H (1978) Functional characteristics of unmyelinated fibres in the hippocampal cortex. Brain Res 144: 11–18

  4. Auker CR, Braitman DJ, Rubinstein SL (1982) Electrophysiological action of kainic acid and folates in the vitro olfactory cortex slice. Nature 297: 538–584

  5. Ben-Ari Y, Tremblay ET, Ottersen OP, Meldrum BS (1980) The role of epileptic activity in hippocampal and ‘remote’ cerebral lesions induced by kainic acid. Brain Res 191: 79–97

  6. Biziere K, Coyle JT (1978) Influence of cortico-striatal afferents on striatal kainic acid neurotoxicity. Neurosci Lett 8: 303–310

  7. Collingridge GL, McLennan H (1981a) The effect of kainic acid on excitatory synaptic activity in the rat hippocampal slice preparation. Neurosci Lett 27: 31–36

  8. Collingridge GL, McLennan H (1981b) Alterations in synaptic transmission in the hippocampal slice produced by the iontophoretic administration of excitatory amino acids. Soc Neurosci Abstr 7: 108

  9. Collingridge GL, Kehl SJ, McLennan H (1983a) The antagonism of amino acid-induced excitations of rat hippocampal CA1 neurones in vitro. J Physiol (Lond) 334: 19–31

  10. Collingridge GL, Kehl SJ, McLennan H (1983b) Excitatory amino acids in synaptic transmission in the Schaffer collateral-commissural pathway of the rat hippocampus. J Physiol (Lond) 334: 33–46

  11. Coyle JT, Schwarcz R (1976) Lesion of striatial neurones with kainic acid provides a model for Huntington's chorea. Nature 263: 244–246

  12. Coyle JT, Zaczek R, Slevin J, Collins J (1981) Neuronal receptor sites for kainic acid: correlations with neurotoxicity. In: DiChiara G, Gessa GL (eds) Glutamate as a neurotransmitter. Raven Press, New York, pp 337–346

  13. Davies J, Watkins JC (1973) Facilitatory and direct excitatory effects of folate and folinate on single neurones of cat cerebral cortex. Biochem Pharmacol 22: 1667–1668

  14. Dingledine R, Gjerstad L (1980) Reduced inhibition during epileptiform activity in the in vitro hippocampal slice. J Physiol (Lond) 305: 297–313

  15. Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298: 757–759

  16. Foster AC, Mena EE, Monaghan DT, Cotman CW (1981) Synaptic localization of kainic acid binding sites. Nature 289: 73–75

  17. Guldin WO, Markowitsch HJ (1981) No detectable remote lesions following massive intrastriatal injections of ibotenic acid. Brain Res 225: 446–451

  18. Hjorth-Simonsen A (1973) Some intrinsic connections of the hippocampus in the rat: An experimental analysis. J Comp Neurol 147: 145–162

  19. Köhler C, Schwarcz R, Fuxe K (1978) Perforant path transactions protect hippocampal granule cells from kainate lesion. Neurosci Lett 10: 241–246

  20. Köhler C, Schwarcz R, Fuxe K (1979) Hippocampal lesions indicate differences between excitotoxic properties of acidic amino acids. Brain Res 175: 366–371

  21. Laurberg S (1979) Commissural and intrinsic connections of the rat hippocampus. J Comp Neurol 184: 685–708

  22. Lothman EW, Collins RC (1981) Kainic acid-induced limbic seizures. Metabolic, behavioural, electroencephalographic and neuropathological correlates. Brain Res 218: 299–318

  23. Lothman EW, Collins RC, Ferrendelli JA (1981) Kainic acid induced limbic seizures: Electrophysiologic studies. Neurology 31: 806–812

  24. Malthe-Sørenssen D, Skrede KK, Fonnum F (1979) Calcium-dependent release of D-(3H)aspartate evoked by selective electrical stimulation of excitatory afferent fibres to hippocampal pyramidal cells in vitro. Neuroscience 4: 1225–1263

  25. Malthe-Sørenssen D, Odden E, Walaas I (1980) Selective destruction by kainic acid of neurons innervated by putative glutaminergic afferents in septum and nucleus of the diagonal band. Brain Res 182: 461–465

  26. Mattox DE, Gulley RL, Bird SJ, Ulrich FA (1980) Effects of neuronal activity on kainic acid neurotoxicity in the ventral cochlear nucleus. Neurosci Lett 20: 153–157

  27. McGeer EG, McGeer PL (1976) Duplication of biochemical changes of Huntington's chorea by intrastriatal injections of glutamic and kainic acids. Nature 263: 517–519

  28. McGeer PL, McGeer EG, Hattori T (1978) Kainic acid as a tool in neurobiology. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 123–138

  29. McLennan H (1980) The effect of decortication on the excitatory amino acid sensitivity of striatal neurones. Neurosci Lett 18: 313–316

  30. McLennan H (1981) Excitatory amino acid receptors. In: Lombardini JB, Kenny AD (eds) The role of peptides and amino acids as neurotransmitters. Alan Liss, New York, pp 19–27

  31. McLennan H (1982) Methyltetrahydrofolate as an antagonist of excitatory amino acids on spinal neurones. Eur J Pharmacol 79: 307–310

  32. Nadler JV, Perry BW, Cotman CW (1978) Preferential vulnerability of hippocampus to intraventricular kainic acid. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 219–237

  33. Nadler JV, Evenson DA, Cuthbertson GJ (1981a) Comparative toxicity of kainic acid and other acidic amino acids toward rat hippocampal neurons. Neuroscience 6: 2505–2517

  34. Nadler JV, Evenson DA, Smith EM (1981b) Evidence from lesion studies for epileptogenic and non-epileptogenic neurotoxic interactions between kainic acid and excitatory innervation. Brain Res 205: 405–410

  35. Olney JW (1978) Neurotoxicity of excitatory amino acids. In: McGeer EG, Olney JW, McGeer PL (eds) Kainic acid as a tool in neurobiology. Raven Press, New York, pp 95–121

  36. Olney JW (1981) Kainic acid and other excitotoxins: A comparative analysis. Adv Biochem Psychopharmacol 27: 375–384

  37. Olney JW, Rhee V, Ho OL (1974) Kainic acid: a powerful neurotoxic analogue of glutamate. Brain Res 77: 507–512

  38. Olney JW, Fuller TA, Gubareff T de (1981a) Kainate-like neurotoxicity of folates. Nature 292: 165–167

  39. Olney JW, Fuller TA, Gubareff T de, Labruyere J (1981b) Intrastriatal folic acid mimics the distant but not local brain damaging properties of kainic acid. Neurosci Lett 25: 185–191

  40. Robinson JH, Deadwyler SA (1981) Kainic acid produces depolarization of CA3 pyramidal cells in the in vitro hippocampal slice. Brain Res 221: 117–127

  41. Schwarcz R, Köhler C (1980) Evidence against an exclusive role of glutamate in kainic acid toxicity. Neurosci Lett 19: 243–249

  42. Schwarcz R, Hökfelt T, Fuxe K, Jonsson G, Goldstein M, Terenius L (1979) Ibotenic acid-induced neuronal degeneration: A morphological and neurochemical study. Exp Brain Res 37: 199–216

  43. Schwartzkroin PA, Prince DA (1980) Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res 183: 61–76

  44. Shinozaki H, Konishi S (1970) Actions of several anthelminthics and insecticides on rat cortical neurones. Brain Res 24: 368–371

  45. Sloviter RS, Damiano BP (1981) On the relationship between kainic acid-induced epileptiform activity and hippocampal neuronal damage. Neuropharmacology 20: 1003–1011

  46. Storm-Mathisen J (1981) Glutamate in hippocampal pathways. In: Di Chiara G, Gessa GL (eds) Glutamate as a neurotransmitter. Raven Press, New York, pp 43–55

  47. Streit P, Stella M, Cuénod M (1980) Kainate-induced lesion in the tectum: dependency upon optic nerve afferents or glutamate. Brain Res 187: 47–57

  48. Swanson LW, Wyss JM, Cowan WM (1978) An autoradiographic study of the organization of intrahippocampal association pathways in the rat. J Comp Neurol 181: 681–716

  49. Traub RD, Llinás R (1979) Hippocampal pyramidal cells: Significance of dendritic ionic conductances for neuronal function and epileptogenesis. J Neurophysiol 42: 476–496

  50. Voneida TJ, Vardaris RM, Fish SE, Reiheid CT (1981) The origin of the hippocampal commissure in the rat. Anat Rec 201: 91–103

  51. Watkins JC, Evans RH (1981) Excitatory amino acid transmitters. Ann Rev Pharmacol Toxicol 21: 165–204

  52. Wong RKS, Prince DA (1979) Dendritic mechanisms underlying pencillin-induced epileptiform activity. Science 204: 1228–1231

  53. Wuerthele SM, Lovell KL, Jones MZ, Moore KE (1978) A histological study of kainic acid lesions in the rat brain. Brain Res 149: 489–497

Download references

Author information

Correspondence to Prof. Dr. H. McLennan.

Additional information

Supported by a grant from the Medical Research Council of Canada to H.McL.; G.L.C. is in receipt of a Killam Fellowship and S. J.K. of a Studentship of the MRC

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Collingridge, G.L., Kehl, S.J., Loo, R. et al. Effects of kainic and other amino acids on synaptic excitation in rat hippocampal slices: 1. Extracellular analysis. Exp Brain Res 52, 170–178 (1983).

Download citation

Key words

  • Kainic acid
  • Folic acid
  • Neurotoxins
  • Hippocampal slices
  • Synaptic potentiation