Summary
Rats were injected unilaterally with colchicine in the dentate gyrus of the dorsal hippocampus. Two weeks later, under urethane anesthesia, extracellular recordings were obtained on both sides from pyramidal neurons of the CA1 and of the CA3 regions of the dorsal hippocampus. Microiontophoresis was used to assess the responsiveness of these neurons to kainate, glutamate and ibotenate. The colchicine injection produced a nearly complete destruction of the granule cells of the ipsilateral dentate gyrus and of their mossy fiber projections to CA3 without apparently affecting other hippocampal neurons. On the lesioned side, the potency of kainate in activating CA3 pyramidal neurons was reduced by 94% compared to the same neurons on the intact side. However, the excitatory effect of glutamate was unchanged and that of ibotenate only slightly reduced. Kainate was 80 times more potent in activating CA3 than CA1 pyramidal neurons on the intact side, whereas this ratio had dropped to 2.6 on the lesioned side. The selective decrease of the effectiveness of kainate in activating CA3 pyramidal neurons following the colchicine lesion suggests that this amino acid, but not glutamate and ibotenate, produces most of its excitatory effect in the intact CA3 region by releasing (an) excitatory neurotransmitter(s) from mossy fibers terminals, the nature of which remains to be identified.
Similar content being viewed by others
References
Amaral DG, Dent JA (1981) Development of the mossy fibers of the dentate gyrus. I. A light and electron microscopic study of the mossy fibers and their expansions. J Comp Neurol 195: 51–86
Ben-Ari Y, Tremblay E, Berger M, Nitecka L (1984) Kainic acid seizure syndrome and binding sites in developing rats. Develop Brain Res 14: 284–288
Ben-Ari Y, Tremblay E, 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
Blackstad TW, Brink K, Hem J, Jenne B (1970) Distribution of hippocampal mossy fibers in the rat: an experimental study with silver impregnation methods. J Comp Neurol 138: 433–450
Chavkin C, Bakhit C, Bloom FE (1983) Evidence for dynorphin-A as a neurotransmitter in rat hippocampus. Life Sci 33: 13–16
Coyle JT, Schwarcz R (1976) Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea. Nature (Lond) 263: 244–246
Crawford IL, Connor JD (1973) Localization and release of glutamic acid in relation to the hippocampal mossy fiber pathway. Nature (Lond) 244: 442–443
Danscher G, Zimmer J (1978) An improved Timm sulphide silver method for light and electron microscopic localization of heavy metals in biological tissues. Histochemistry 55: 27–40
de Montigny C, Tardif D (1981) Differential excitatory effects of kainic acid on CA1 and CA3 hippocampal pyramidal neurons: further evidence for the excitotoxic hypothesis and for a receptor-mediated action. Life Sci 29: 2103–2111
Evans RH, Watkins JC (1981) Excitatory amino acid transmitters. Ann Rev Pharmacol 21: 165–204
Fagni L, Baudry M, Lynch G (1983) Classification and properties of acidic amino acid receptors in hippocampus. I. Electrophysiological studies of an apparent desensitization and interactions with drugs which block transmission. J Neurosci 3: 1538–1546
Ferkany JW, Coyle JT (1983) Kainic acid selectively stimulates the release of endogenous excitatory acidic amino acids. J Pharmacol Exp Ther 225: 399–406
Fisher RS, Alger BE (1984) Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. J Neurosci 4: 1312–1323
Foster AC, Fagg GE (1984) Acidic amino acid binding in mammalian neuronal membranes: their characteristics and relationship to synaptic receptors. Brain Res Rev 7: 103–164
Foster AC, Mena EE, Monaghan DT, Cotman CW (1981) Synaptic localization of kainic acid binding sites. Nature (Lond) 289: 73–75
Franck JE, Schwartzkroin PA (1984) Immature rabbit hippocampus is damaged by systemic but not intraventricular kainic acid. Develop Brain Res 13: 219–227
Fuller TA, Olney JW (1979) Effects of morphine or naloxone on kainic acid neurotoxicity. Life Sci 24: 1793–1798
Goldschmidt RB, Steward O (1980) Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat. Proc Natl Acad Sci USA 77: 3047–3051
Haigler HJ, Aghajanian GK (1974) Lysergic acid diethylamide and serotonin: a comparison of effects on serotonergic neurons and neurons receiving a serotonergic input. J Pharmacol Exp Ther 168: 688–699
Hoffman DW (1984) Effects of chemical and surgical lesions on levels of chromatographically identified enkephalin-like peptides in rat hippocampus. Brain Res 310: 7–12
Kandel ER, Spencer WA (1961) Electrophysiology of hippocampal neurons. II. After potentials and repetitive firing. J Neurophysiol 24: 245–259
Kehl SJ, McLennan H, Collingridge GL (1984) Effects of folic and kainic acids on synaptic responses of hippocampal neurones. Neuroscience 11: 111–124
Kohler C, Schwarcz R (1983) Comparison of ibotenate and kainate neurotoxicity in rat brain: a histological study. Neuroscience 8: 819–835
Lehman A, Isacsson H, Hamberger A (1983) Effects of in vivo administration of kainic acid on the extracellular amino acid pool in the rabbit hippocampus. J Neurochem 40: 1314–1320
Lorente de Nó R (1934) Studies on the structure of the cerebral cortex. II. Continuation of the study of the ammonic system. J Psychol Neurol 46: 113–117
Lothman EW, Collins RC, Ferrendelli JA (1981) Kainic acid-induced limbic seizures: electrophysiologic studies. Neurology 31: 806–812
McGinty JF, Henriksen SJ, Goldstein A, Terenius L, Bloom FE (1983) Dynorphin is contained within hippocampal mossy fibers: immunochemical alterations after kainic acid administration and colchicine induced neurotoxicity. Proc Natl Acad Sci USA 80: 589–593
McLennan H, Lodge D (1979) The antagonism of amino acid-induced excitation of spinal neurones in the cat. Brain Res 169: 83–90
Mason ST, Sanberg PR, Fibiger HC (1978) Kainic acid lesions of the stratium dissociate amphetamine and apomorphine stereotypy: similarities to Hutington's chorea. Science 201: 352–355
Monagan DT, Cotman CW (1982) The distribution of [3H]kainic acid binding sites in rats CNS as determined by autoradiography. Brain Res 252: 91–100
Nadler JV, Evenson DA, Smith EM (1981) Evidence from lesion studies of epileptogenic and non-epileptogenic neurotoxic interactions between kainic acid and excitatory innervation. Brain Res 205: 405–410
Nadler JV, Perry BW, Cotman CW (1978) Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature (Lond) 271: 676–677
Olney JW, Fuller T, De Gubareff T (1979) Acute dendrotoxic changes in the hippocampus of kainate treated rats. Brain Res 176: 91–100
Obata HL, Kubo S, Kinoshita H, Murabe Y, Ibata Y (1981) The effect of small doses of kainic acid on the area CA3 of hippocampal formation. An electron microscopic study. Arch Histol Jpn 44: 135–149
Okazaki MM, Nadler JV (1985) Protective effects of mossy fiber lesions against kainic acid-induced seizures and neuronal degeneration. Neuroscience Abstr 11: 385.12
Pastuszko A, Wilson DF, Erecinska F (1984) Effects of kainic acid in rat brain synaptosomes: the involvement of calcium. J Neurochem 43: 747–754
Perkins MN, Collins JF, Stone JW (1982) Isomers of 2-amino-7-phosphonoheptanoic acid as antagonist of neuronal excitants. Neurosci Lett 32: 65–68
Poli A, Contestabile A, Migani P, Rossi L, Rondelli C, Virgili M, Bissoli R, Barnabeio O (1985) Kainic acid differentially affects the synaptosomal release of endogenous and exogenous amino acidic neurotransmitters. J Neurochem 45: 1677–1686
Robinson JH, Deadwyler SA (1981) Kainic acid produces depolarization of CA3 pyramidal cells in the in vitro hippocampal slice. Brain Res 221: 117–127
Simmonds MA (1974) Quantitative evaluation of responses to microiontophoretically applied drugs. Neuropharmacology 13: 401–406
Stegaard-Pedersen K, Fredens K, Larsspn LI (1981) Enkephalin and zinc on the hippocampal mossy fiber system. Brain Res 212: 230–233
Storm-Mathisen J, Iversen LL (1979) Uptake of [3H] glutamic acid in excitatory nerve endings: light and electron microscopic observations in the hippocampal formation of the rat. Neuroscience 4: 1237–1253
Storm-Mathisen J, Leknes AK, Bore AT, Vaaland JL, Edminson P, Hang FMS, Ottersen PO (1983) First visualization of glutamate and gaba in neurones by immunochemistry. Nature (Lond) 301: 517–520
Timm F (1958) Zur Histochemie des Ammonshorngebietes. Z Zellforsch 48: 458–555
Unnerstall JR, Wamsley JK (1983) Autoradiographic localization of high-affinity [3H]kainic acid binding sites in the rat forebrain. Eur J Pharmacol 86: 361–371
Westbrook GL, Lothman EW (1983) Cellular and synaptic basis of kainic acid-induced hippocampal epileptiform activity. Brain Res 273: 97–109
Wolf G, Keilhoff G (1984) Kainate and glutamate neurotoxicity in dependence on the postnatal development with special reference to hippocampal neurons. Develop Brain Res 14: 15–21
Zimmer J (1978) Development of the hippocampus and fascia dentata: morphological and histochemical aspects. In: Corner MA, Baker RE, Van de Poll NE, Waab DF, Vylings HB (eds) Maturation of the nervous system. Elsevier, Amsterdam, pp 171–189
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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 65, 605–613 (1987). https://doi.org/10.1007/BF00235983
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00235983