Sprouting of Mossy Fibers in the Hippocampus of Epileptic Human and Rat

  • Alfonso Represa
  • Evelyne Tremblay
  • Yehezkel Ben-Ari
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 268)


Epilepsy is a neurological disorder characterized by the presence of recurrent seizures and during the interictal periods, synchronous activation of a neuronal cell group. Numerous reports have suggested that there is common underlying mechanisms with long term potentiation; i.e. the kindling model of epilepsy induced by stimulation of the entorhinal cortex is associated with a synaptic potentiation at the perforant pathway-granule cell synapse (Goddard et al. 1969); moreover, as in LTP induction, these synaptic potentiation involves the activation of NMDA receptors (Mody and Heinemann 1987; Ben-Ari and Gho 1987). The hypothesis that the morphological substrate of epilepsy resides in the establishment of new aberrant connections has been frequently considered. Morphological evidence has recently been obtained for the hippocampal mossy fibers which originate in the dentate granule cells and project to the giant pyramidal neurons of CA3 area. Thus, mossy fibers sprout and establish aberrant connections both in kindling epilepsy (Sutula et al. 1988, Represa et al 1989) and in childhood epilepsy (Represa et al 1989 b).


Mossy Fiber Kainic Acid Childhood Epilepsy Synaptic Potentiation Epileptic Child 
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  1. Ben-Ari Y. (1985) Limbic seizures and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience 14: 375–403.PubMedCrossRefGoogle Scholar
  2. Ben-Ari Y. and Gho M. (1988) Long-lasting modification of the synaptic properties of rat CA3 hippocampal neurones induced by kainic acid. J. Physiol. 404: 365–384.PubMedGoogle Scholar
  3. Berger M. and Ben-Ari Y. (1983) Autoradiographic visualization of [3H] kainic acid receptor subtypes in the rat hippocampus. Neurosci. Lett. 39: 237–242.CrossRefGoogle Scholar
  4. Fisher R.S. and Alger B.E. (1984) Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. J. Neurosci. 4: 1312–1323.PubMedGoogle Scholar
  5. Frotscher M. and Zimmer J. (1983) Lesion induced mossy fibers to the molecular layer of the rat fascia dentata; identification of postsynaptic granule cells by the golgi-EM technique. J.Comp.Neurol. 215: 299–311.PubMedCrossRefGoogle Scholar
  6. Gho M., King A.E., Ben-Ari Y. and Cherubini E. (1986) Kainate reduces two voltage dependent potassium conductances in rat hippocampal neurons in vitro. Brain Res. 385: 411–414.PubMedCrossRefGoogle Scholar
  7. Goddard G.V., McIntyre D.C. and Leech C.K. (1969) A permanent change in brain function resulting from daily electric stimulation. Exp. Neurol. 25: 295–330.Google Scholar
  8. Haug F.M.S. (1967) Electron microscopical localization of the zinc in the hippocampal mossy fibre synapses by a modified sulfide silver procedure. Histochemie 8: 355–368.PubMedCrossRefGoogle Scholar
  9. Hauser, C.R., J.E. Miyashiro, B.E., Swartz, G.O., J.R. Rich and A.V. Delgado-Escueta (1990) Altered patterns of dynorphin immunoreactivity suggest mossy fiber reorganization in human hippocampal epilepsy. J. Neurosci. In press.Google Scholar
  10. Lanerolle N.C., Kim J.H., Robbins R.J. and Spencer D.D. (1989) Hippocampal interneuron loss and plasticity in human temporal lobe epilepsy. Brain Res. 495: 387–395.PubMedCrossRefGoogle Scholar
  11. Nadler J.V. (1981) Kainic acid as a tool for the study of temporal lobe epilepsy. Life Sci. 29: 2031–2042.PubMedCrossRefGoogle Scholar
  12. Represa A. Tremblay E. and Ben-Ari Y. (1987) Kainate binding sites in the hippocampal mossy fibers: localization and plasticity. Neurosci. 20: 739–748.CrossRefGoogle Scholar
  13. Represa A. Le Gall La Salle G. and Ben-Ari Y. (1989a) Hippocampal plasticity in the kindling model of epilepsy in rats. Neurosci. Lett. 99: 345–350.Google Scholar
  14. Represa A., Robain O., Tremblay E. and Ben-Ari Y. (1989b) Hippocampal plasticity in childhood epilepsy. Neurosci. Lett. 99: 351–355.PubMedCrossRefGoogle Scholar
  15. Robinson J.H. and Deadwyler S.A. (1981) Kainic acid produces depolarization of CA3 pyramydal cells in the in vitro hippocampal slice. Brain Res. 221: 117–127.PubMedCrossRefGoogle Scholar
  16. Rovira C., Gho M. and Ben-Ari Y. (1989) Block of GABAB -activated K+ conductance by kainate and quisqualate in rat CA3 hippocampal pyramidal neurones. Eur. J. Physiol. in press.Google Scholar
  17. Sutula T. Xiao-Xian H., Cavazos J. and Scott G. (1988) Synaptic reorganization in the hippocampus induced by abnormal functional activity. Science 239: 1147–1150.PubMedCrossRefGoogle Scholar
  18. Tauck D.L. and Nadler J.V. (1985) Evidence for functional mossy fiber sprouting in hippocampal formation of kainic acid treated rats. J.Neurosci. 5: 1016–1022.PubMedGoogle Scholar
  19. Tremblay E., Represa A. and Ben-Ari Y. (1985) Autoradiographic localization of kainic acid binding sites in the human hippocampus. Brain Res. 343: 378–382.PubMedCrossRefGoogle Scholar
  20. Unnerstall J.R. and Wamsley J.K. (1983) Autoradiographic localization of high-affinity [3H] kainic acid binding sites in the rat forebrain. Eur. J. Pharmacol. 86: 361–371.PubMedCrossRefGoogle Scholar
  21. Westbrook G.L. and Lothman E.W. (1983) Cellular and synaptic basis of kainic acid-induced hippocampal epileptiform activity. Brain Res. 273: 97–109.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Alfonso Represa
    • 1
  • Evelyne Tremblay
    • 1
  • Yehezkel Ben-Ari
    • 1
  1. 1.INSERM U29ParisFrance

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