Kindling 4 pp 75-92 | Cite as

Alterations of Synaptic Ultrastructure Induced by Hippocampal Kindling

  • Yuri Geinisman
  • Frank Morrell
  • Leyla deToledo-Morrell
Part of the Advances in Behavioral Biology book series (ABBI, volume 37)


Kindling, first discovered by the late Graham Goddard1, is widely regarded as a dramatic, reliable and robust form of neural plasticity2–6. One of the most remarkable features of kindling is that it induces a virtually permanent change in brain function. Synaptic responsiveness of the circuit stimulated during kindling undergoes an augmentation which persists, without further reinforcement, for many months5–9. This exceptionally enduring enhancement of synaptic efficacy caused by kindling and the dependence of the process on protein synthesis10,11 and axonal transport12,13 imply an underlying structural modification of the synapse itself.


Dentate Gyrus Perforant Path Medial Entorhinal Cortex Mossy Fiber Synapse Synaptic Morphology 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    G. V. Goddard, Development of epileptic seizures through brain stimulation of low intensity, Nature 214: 1020 (1967).PubMedCrossRefGoogle Scholar
  2. 2.
    G. V. Goddard and R. M. Douglas, Does the engram of kindling model the engram of normal long term memory?, Can. J. Neurol. Sci. 2: 385 (1975).PubMedGoogle Scholar
  3. 3.
    R. Racine, L. Tuff, and J. Zaide, Kindling, unit discharge and neural plasticity, Can. J. Neurol. Sci. 2: 395 (1975).PubMedGoogle Scholar
  4. 4.
    R. Racine, Kindling: the first decade, Neurosurgery 3: 234 (1978).PubMedCrossRefGoogle Scholar
  5. 5.
    G. V. Goddard, The kindling model of epilepsy, Trends Neurosci. 6: 275 (1983).CrossRefGoogle Scholar
  6. 6.
    F. Morrell and L. deToledo-Morrell, Kindling as a model of neuronal plasticity, in: “Kindling 3”, J. A. Wada, ed., Raven, New York (1986).Google Scholar
  7. 7.
    G. V. Goddard, D. C. McIntyre, and C. K. Leech, A permanent change in brain function resulting from daily electrical stimulation, Exp. Neurol. 25: 295 (1969).PubMedCrossRefGoogle Scholar
  8. 8.
    J. A. Wada and M. Sato, Generalized convulsive seizures induced by daily electrical stimulation of the amygdala in cats: correlative electrgraphic and behavioral seizures, Neurology (Minneap.) 24: 565 (1974).Google Scholar
  9. 9.
    F. Morrell, Goddard’s kindling phenomenon, in: “Chemical Modulation of Brain Function”, H. C. Sabelli, ed., Raven, New York (1973).Google Scholar
  10. 10.
    F. Morrell, N. Tsuru, T. J. Hoeppner, D. Morgan, and W. H. Harrison, Secondary epileptogenesis in frog forebrain: effect of inhibition of protein synthesis, Can. J. Neurol. Sci. 2: 407 (1975).PubMedGoogle Scholar
  11. 11.
    V. Jonec and C. G. Wasterlain, Effects of inhibitors of protein synthesis on the development of kindled seizures in rats, Exp. Neurol. 66: 524 (1979).PubMedCrossRefGoogle Scholar
  12. 12.
    F. Morrell, Biochemical alterations in secondary epileptogenic lesions, in: “Secondary Epileptogenesis”, A. Mayersdorf and R. P. Schmidt, eds., Raven, New York (1982).Google Scholar
  13. 13.
    F. Morrell, Callosal mechanisms in epileptogenesis, in: “Epilepsy and the Corpus Callosum”, A. Reeves, ed., Plenum, New York (1985).Google Scholar
  14. 14.
    R. Racine and J. Zaide, A further investigation into the mechanisms underlying the kindling phenomenon, in: “Limbic Mechanisms”, K. L. Livingston and O. Hornykiewicz, eds., Plenum, New York (1978).Google Scholar
  15. 15.
    M. Langmeier and J. Mares, Changes in some ultrastructural parameters of cortical synapses in the initial phases of kindling, Physiol. Bohemoslov. 33: 367 (1984).PubMedGoogle Scholar
  16. 16.
    A. J. Cronin, T. P. Sutula, and N. L. Desmond, Morphological changes in the hippocampal dentate gyrus accompany kindling of the entorhinal cortex, Soc. Neurosci. Abstr. 13: 947 (1987).Google Scholar
  17. 17.
    N. Hawrylak, F.-L. Chang, D. Treacy, K. R. Isaaks, and W. T. Greenough, Synaptogenesis in kindling, Soc. Neurosci. Abstr. 14: 881 (1988).Google Scholar
  18. 18.
    T. Sutula, H. Xiao-Xian, J. Cavazos and G. Scott, Synaptic reorganization in the hippocampus induced by abnormal functional activity, Science 239: 1147 (1988).PubMedCrossRefGoogle Scholar
  19. 19.
    H. J. G. Gundersen, Stereology of arbitrary particles, J. Microsc. 143: 3 (1986).PubMedCrossRefGoogle Scholar
  20. 20.
    H. Brændgaard and H. J. G. Gundersen, The impact of recent stereological advances on quantitative studies of the nervous system, J. Neurosci. Meth. 18: 39 (1986).CrossRefGoogle Scholar
  21. 21.
    C. A. Curcio and J. W. Hinds, Stability of synaptic density and spine volume in dentate gyrus of aged rats, Neurobiol. Aging 4: 77 (1983).PubMedCrossRefGoogle Scholar
  22. 22.
    D. C. Sterio, The unbiased estimation of number and sizes of arbitrary particles using the disector, J. Microsc. 134: 127 (1984).PubMedCrossRefGoogle Scholar
  23. 23.
    Y. Geinisman, F. Morrell, and L. deToledo-Morrell, Remodeling of synaptic architecture during hippocampal kindling, Proc. Natl. Acad. Sci. U.S.A. 85: 3260 (1988).CrossRefGoogle Scholar
  24. 24.
    A. Hjorth-Simonsen, Projection of the lateral part of the entorhinal area to the hippocampus and fascia dentata, J. Comp. Neurol. 146: 219 (1972).PubMedCrossRefGoogle Scholar
  25. 25.
    A. Hjorth-Simonsen and B. Jeune, Origin and termination of the hippocampal perforant path in the rat studied by silver impregnation, J. Comp. Neurol. 144: 215 (1972).PubMedCrossRefGoogle Scholar
  26. 26.
    O. Steward, Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat, J. Comp. Neurol. 167: 285 (1976).PubMedCrossRefGoogle Scholar
  27. 27.
    D. L. Rosene and G. W. Van Hoesen, The hippocampal formation of the primate brain, in: “Cerebral Cortex”, Vol. 6, E. G. Jones and A. Peters, eds., Plenum, New York (1987).Google Scholar
  28. 28.
    M. Nieto-Sampedro, S. F. Hoff, and C. W. Cotman, Perforated postsynaptic densities: probable intermediates in synapse turnover, Proc. Natl. Acad. Sci. U.S.A. 79: 5718 (1982).PubMedCrossRefGoogle Scholar
  29. 29.
    Y. Y. Geinisman, V. N. Larina, and V. N. Mats, Changes of neurones dimensions as a possible morphological correlate of their increased functional activity, Brain Res. 26: 247 (1971).Google Scholar
  30. 30.
    Y. Geinisman, L. deToledo-Morrell, and F. Morrell, Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory, Brain Res. 398: 266 (1986).PubMedCrossRefGoogle Scholar
  31. 31.
    H. J. G. Gundersen, Notes on the estimation of the numerical density of arbitrary profiles: the edge effect, J. Microsc. 111: 219 (1987).CrossRefGoogle Scholar
  32. 32.
    D. A. Matthews, C. Cotman, and G. Lynch, An electron microscopic study of lesion-induced synaptogenesis in the dentate gyrus of the adult rat. I. Magnitude and time course of degeneration, Brain Res. 115: 1 (1986).CrossRefGoogle Scholar
  33. 33.
    J. O. McNamara, M. Byrne, R. Danshieff, and J. Fitz, The kindling model of epilepsy: a review, Prog. Neurobiol. 15: 139 (1980).PubMedCrossRefGoogle Scholar
  34. 34.
    C. E. Ribak, R. M. Bradburne, and A. B. Harris, A preferential loss of gabaergic symmetric synapses in epileptic foci: a quantitative ultrastructural analysis of monkey neocortex, J. Neurosci. 2: 1725 (1982).PubMedGoogle Scholar
  35. 35.
    R. S. Sloviter, decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy, Science 235: 73 (1987).PubMedCrossRefGoogle Scholar
  36. 36.
    L. P. Tuff, R. J. Racine, and R. Adamec, The effects of kindling on GABA-mediated inhibition in the dentate gyrus of the rat. I. Paired pulse depression, Brain Res. 277: 79 (1983).PubMedCrossRefGoogle Scholar
  37. 37.
    G. V. Goddard and E. Maru, Forces for and against the kindled state as revealed by EEG and field potential analysis in the hippocampal dentate area of perforant path kindled rats, la: “Kindling 3”, J. A. Wada, ed., Raven, New York (1986).Google Scholar
  38. 38.
    P. Andersen, B. Holmquist, and P. E. Voorhoeve, Entorhinal activation of dentate granule cells, Acta Physiol. Scand. 66: 448 (1966).PubMedCrossRefGoogle Scholar
  39. 39.
    T. Loma, Patterns of activation in a monosynaptic cortical pathway: the perforant path input to the dentate area of the hippocampal formation, Exp. Brain Res. 12: 18 (1971).Google Scholar
  40. 40.
    A. Peters and I. R. Kaiserman-Abramof, The small pyramidal neuron of the rat cerebral cortex. The synapses upon dendritic spines, Z. Zelifosch. 100: 487 (1969).CrossRefGoogle Scholar
  41. 41.
    A. M. Sirevaag and W. T. Greenough, Differential rearing effects on rat visual cortex synapses. II. Synaptic morphometry, Dev. Brain Res. 19: 215 (1985).CrossRefGoogle Scholar
  42. 42.
    S. E. Dyson and D. G. Jones, Quantitation of terminal parameters and their interrelationships in maturing central synapses: a perspective for experimental studies, Brain Res. 183: 43 (1980).PubMedCrossRefGoogle Scholar
  43. 43.
    C. J. Wilson, P. M. Groves, S. T. Kitai, and J. C. Linder, Three-dimensional structure of dendritic spines in the rat neostriatum, J. Neurosci. 3: 383 (1983).PubMedGoogle Scholar
  44. 44.
    K. M. Harris and J. K. Stevens, Dendritic spines of rat cerebellar Purkinje cells: serial electron microscopy with reference to their biophysical characteristics, J. Neurosci. 8: 4455 (1988).PubMedGoogle Scholar
  45. 45.
    Y. Geinisman, F. Morrell, and L. deToledo-Morrell, Axospinous synapses with segmented postsynaptic densities: a morphologically distinct synaptic subtype contributing to the number of profiles of “perforated” synapses visualized in random sections, Brain Res. 423: 179 (1987).PubMedCrossRefGoogle Scholar
  46. 46.
    D. M. G. De Groot, Comparison of methods for the estimation of the thickness of ultrathin tissue sections, J. Microsc. 151: 23 (1988).PubMedCrossRefGoogle Scholar
  47. 47.
    C. W. Cotman and P. T. Kelly, Macromolecular architecture of CNS synapses, in: “The Cell Surface and Neuronal Function”, C. W. Cotman, G. Poste, and G. L. Nocolson, eds., Elsevier, Amsterdam (1980).Google Scholar
  48. 48.
    P. Siekevitz, The postsynaptic density: a possible role in long-lasting effects in the central nervous system, Proc. Natl. Acad. Sci. U.S.A. 82: 3494 (1985).PubMedCrossRefGoogle Scholar
  49. 49.
    A. A. Herrera, A. D. Grinnell, and B. Wolowske, Ultrastructural correlates of naturally occurring differences in transmitter release efficacy in frog motor nerve terminals, J. Neurocytol. 14: 193 (1985).PubMedCrossRefGoogle Scholar
  50. 50.
    P. K. Carlin and P. Siekevitz, Plasticity in the central nervous system: do synapses divide?, Proc. Natl. Acad. Sci. U.S.A. 80: 3517 (1983).PubMedCrossRefGoogle Scholar
  51. 51.
    S. E. Dyson and D. G. Jones, Synaptic remodelling during development and maturation: junction differentiation and splitting as a mechanism of modifying connectivity, Dey. Brain Res. 13: 125 (1984).CrossRefGoogle Scholar
  52. 52.
    T. V. P. Bliss and A. R. Gardner-Medwin, Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetized rabbit following stimulation of the perforant path, J. Physiol (Lond.) 232: 357 (1973).Google Scholar
  53. 53.
    T. Sutula and O. Steward, Quantitative analysis of synaptic potentiation during kindling of the perforant path, J. Neurophysiol. 56: 732 (1986).PubMedGoogle Scholar
  54. 54.
    T. Sutula and O. Steward, Facilitation of kindling by prior induction of long-term potentiation in the perforant path, Brain Res. 420: 109 (1987).PubMedCrossRefGoogle Scholar
  55. 55.
    N. L. Desmond and W. B. Levy, Changes in the numerical density of synaptic contacts with long-term potentiation in the hippocampal dentate gyrus, J. Comp. Neurol. 253: 466 (1986).PubMedCrossRefGoogle Scholar
  56. 56.
    N. L. Desmond and W. B. Levy, Changes in the postsynaptic density with long-term potentiation in the dentate gyrus, J. Comp. Neurol. 253: 476 (1986).PubMedCrossRefGoogle Scholar
  57. 57.
    G. Vrensen and J. Nunes Cardozo, Changes in size and shape of synaptic connections after visual training: an ultrastructural approach of synaptic plasticity, Brain Res. 218: 79 (1981).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Yuri Geinisman
    • 1
  • Frank Morrell
    • 2
  • Leyla deToledo-Morrell
    • 2
    • 3
  1. 1.Department of Cell Biology and AnatomyNorthwestern University Medical SchoolChicagoUSA
  2. 2.Departments of Neurological SciencesRush Medical CollegeChicagoUSA
  3. 3.Departments of PsychologyRush Medical CollegeChicagoUSA

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