Nonsynaptic Mechanisms and Interictal-Ictal Transitions in the Mammalian Hippocampus

  • Yoel Yaari
  • Morten S. Jensen


Interictal-ictal transition is the process by which an epileptic neuronal organization, whose abnormality manifests itself only in brief and spatially restricted synchronized bursts (the so-called interictal „spikes“ in the electroencephalogram), detonates into a hyperexcitable ictal state of intense, highly synchronous, self-sustained neuronal discharge. The ictal episode, or simply seizure, may last from several seconds to a minute or more. It tends to spread through the neuronal aggregate, and to propagate over projection pathways to remote neuronal and peripheral structures. Consequently, it may involve large brain areas and in the intact man or animal, may manifest itself in overt behavioral signs (1).


Pyramidal Cell Hippocampal Slice Population Spike Extracellular Potassium Tonic Seizure 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ajmone-Marsan, C. Acute effects of topical agents. In: Jasper, H., Ward, A., Jr., Pope, A. (eds). Basic Mechanisms of the Epilepsies. Boston: Little Brown and Co., pp. 229 - 328, 1969.Google Scholar
  2. 2.
    Alger, B. Hippocampus: electrophysiological studies of epileptiform activity in vitro. In: Dingledine, R. (ed.) Brain Slices. New York: Plenum Press, pp. 155 - 193, 1984.CrossRefGoogle Scholar
  3. 3.
    Alger, B. and Nicoll, R. Ammonia does not selectively block IPSPs in rat hippocampal pyramidal cells. J. Neurophysiol. 49: 1381 - 1390.Google Scholar
  4. 4.
    Alger, B. and Nicoll, R Epileptiform burst afterhyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science 210: 1122 - 1125.Google Scholar
  5. 5.
    Alger, B. and Nicoll, R. Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studied in vitro. J. Physiol. 328: 105 - 123, 1982.PubMedGoogle Scholar
  6. 6.
    Alkon, D. and Grosman, Y. Evidence for nonsynaptic neuronal interaction. J. Neurophysiol. 41: 640 - 653.Google Scholar
  7. 7.
    Andrew, R., Taylor, C., Snow, R., Dudek, F. Coupling in rat hippocampal slices: dye transfer between CAl pyramidal cells. Brain Res. Bull. 8: 211 - 222, 1982.Google Scholar
  8. 8.
    Ayala, G., Dichter, M., Gumnit, R., Matsumoto, H., and Spencer, W. Genesis of epi- leptic interictal spikes. New knowledge of cortical feedback systems suggests a neurophysiological explanation of brief paroxysms. Brain Res. 52: 1 - 17, 1973.PubMedCrossRefGoogle Scholar
  9. 9.
    Ayala, G., Matsumoto, H.,Gumnit, R. Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. J. Neurophysiol. 33: 73 - 85, 1970.Google Scholar
  10. 10.
    Balestrino, M., Aitkin, P., Somjen, G. The effects of moderate changes of extracellular K and Ca on synaptic and neural function in the CAl region of the hippocampal slice. Brain Res. 377: 229 - 239, 1986.PubMedCrossRefGoogle Scholar
  11. 11.
    Ben-Ari, Y., Krnjevic, K., Reinhardt, W. Hippocampal seizures and failure of inhibition. Can. J. Physiol. Pharmacol. 57: 1462 - 1466, 1979.CrossRefGoogle Scholar
  12. 12.
    Bennet, M. and Goodenough, D. Gap junctions, electrotonic coupling and intracellular communication. Neurosci. Res. Prog. Bull. 16: 373 - 486.Google Scholar
  13. 13.
    Benninger, C., Kadis, J., Prince, D. Extracellular calcium and potassium changes in hippocampal slices. Brain Res. 180: 165 - 182, 1982.Google Scholar
  14. 14.
    Dichter, M., Herman, C., Selzer, M. Silent cells during interictal discharges and seizures in hippocampal penicillin foci: Evidence for the role of extracellular K in the transition from interictal state to seizure. Brain Res. 48: 173 - 183, 1972.PubMedCrossRefGoogle Scholar
  15. 15.
    Dietzel, I., Heinemann, U., Hofmeier, G., Lux, H. Transient changes in the size of the extracellular space in the sensorimotor cortex of cats in relation to stimulus induced changes in potassium concentration. Exp. Brain Res. 40: 432 - 439, 1980.PubMedCrossRefGoogle Scholar
  16. 16.
    Dudek, F., Snow, R., Taylor, C. Role of electrical interactions in synchronization of epileptiform bursts. In: Delgado-Escueta, A., Ward, A., Woodbury, D., Porter, R. (eds). Advances in Neurology, Vol. 44, New York Raven Press, pp. 593 - 617, 1986.Google Scholar
  17. 17.
    Fertziger, A., Ranck, J., Jr. Potassium accumulation in interstitial space during epileptiform seizures. Exp. Neurol. 26: 571 - 585, 1970.PubMedCrossRefGoogle Scholar
  18. 18.
    Fisher, R., Pedley, T., Moody, W. and Prince, D. The role of extracellular potassium in hippocampal epilepsy. Arch. Neurol. 33: 76 - 83, 1976.PubMedCrossRefGoogle Scholar
  19. 19.
    Frankenhaeuser, B. and Hodgkin, A. The action of calcium on the electrical properties of the squid axons. J. Physiol. 137: 218 - 224, 1957.PubMedGoogle Scholar
  20. 20.
    Gardner-Medwin, A. A study of the mechanisms by which potassium moves through brain tissue in the rat. J. Physiol. 335: 353 - 374, 1983.Google Scholar
  21. 21.
    Gloor, P., Sperti, L., Vera, C. A consideration of feedback mechanisms in the genesis and maintenance of hippocampal seizure activity. Epilepsia 5: 213 - 238, 1964.PubMedCrossRefGoogle Scholar
  22. 22.
    Green, J. The hippocampus. Physiol. Rev. 44: 561 - 608, 1969.Google Scholar
  23. 23.
    Green, J. and Maxwell, D. Hippocampal electrical activity. I. Morphologic aspects. Electroenceph. Clin. Neurophysiol. 13: 854 - 867, 1961.Google Scholar
  24. 24.
    Haas, H. and Jeffreys, J. Low-calcium field burst discharges of CAl pyramidal neurones in rat hippocampal slices. J. Physiol. 354: 185 - 201, 1984.PubMedGoogle Scholar
  25. 25.
    Hablitz, J. Picrotoxin-induced epileptiform activity in hippocampus: Role of endogenous versus synaptic factors. J. Neurophysiol. 51: 1011 - 1027, 1984.Google Scholar
  26. 26.
    Hablitz, J. and Lundervold, A. Hippocampal excitability and changes in extracellular potassium. Exper. Neurol. 71: 410 - 420, 1981.CrossRefGoogle Scholar
  27. 27.
    Heinemann, U. and Dietzel, I. Extracellular potassium concentration in chronic alumina cream foci of cats. J. Neurophysiol. 52: 421 - 434, 1984.PubMedGoogle Scholar
  28. 28.
    Heinemann, U., Franseschetti, S., Hamon, B., et al. Effects of anticonvulsants on spontaneous epileptiform activity which develops in the absence of chemical synaptic transmission in hippocampal slices. Brain Res. 325: 349 - 352, 1985.PubMedCrossRefGoogle Scholar
  29. 29.
    Heinemann, U. and Gutnick, M. Relation between extracellular potassium concentration and neuronal activities in cat thalamus (VPL) during projection of cortical epileptiform discharge. Electroenceph. Clin. Neurophysiol. 47: 345 - 357, 1979.PubMedCrossRefGoogle Scholar
  30. 30.
    Heinemann, U. and Lux, H. Ceiling of stimulus induced rises in extracellular potassium concentration in the cerebral cortex of cat. Brain Res. 120: 231 - 249, 1977.PubMedCrossRefGoogle Scholar
  31. 31.
    Heinemann, U., Lux, H., and Gutnick, M. Extracellular free calcium and potassium during paroxysmal activity in cerebral cortex of the cat. Exp. Brain Res. 27: 237243, 1977.Google Scholar
  32. 32.
    Heinemann, U., Neuhaus, S. and Dietzel, I. Aspects of K regulation in normal and gliotic brain tissue. In: Baldy, M., Moulinier, D., Ingvar, Meldrum, B. (eds). Cerebral Blood Flow, Metabolism and Epilepsy, London: John Libbey, pp. 271 - 278, 1983.Google Scholar
  33. 33.
    Hotson, J. and Prince, D. A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons. J. Neurophysiol. 43: 409 - 419, 1980.PubMedGoogle Scholar
  34. 34.
    Hotson, J., Sypert, G., Ward, A. Extracellular potassium concentration changes during propagated seizures in neocortex. Exp. Neurol. 38: 20 - 26, 1973.PubMedCrossRefGoogle Scholar
  35. 35.
    Hounsgaard, J. and Nicholson, C. Potassium accumulation around individual Purkinje cells in cerebellar slices from the guinea-pig. J. Physiol. 340: 359 - 388, 1983.PubMedGoogle Scholar
  36. 36.
    Izquierdo, I., Nasello, A., Marichich, E. Effects of potassium on rat hippocampus: The dependence of hippocampal evoked and seizure activity on extracellular potassium levels. Arch. Int. Pharmacodyn. Ther. 187: 318 - 328, 1951.Google Scholar
  37. 37.
    Jeffreys, J. and Hass, H. Synchronized bursting of CA1 hippocampal pyramidal cells in the absence of synaptic transmission. Nature 300: 448 - 450, 1982.CrossRefGoogle Scholar
  38. 38.
    Johnston, D. and Brown, T. The synaptic nature of the paroxysmal depolarizing shift in hippocampal neurons. Ann. Neurol. Suppl. 16: S65 - S71, 1984.CrossRefGoogle Scholar
  39. 39.
    Kandel, E. and Spencer, W. Excitation and inhibition on pyramidal cells during hippocampal seizure. Exp. Neurol. 4: 162 - 179, 1961.PubMedCrossRefGoogle Scholar
  40. 40.
    Katz, B. and Miledi, R. An endplate potential due to potassium released by motor nerve impulse. Proc. R. Soc. Lond. B. 216: 497 - 506, 1982.CrossRefGoogle Scholar
  41. 41.
    Knowles, W., Funch, P., and Schwartzkroin, P. Electrotonic and dye coupling in hippocampal CA1 pyramidal cells in vitro. Neurosci. 7: 1713 - 1722, 1982.CrossRefGoogle Scholar
  42. 42.
    Koike, H., Mano, N., Okada, Y., Oshima, T. Activities of the sodium pump in cat pyradmical tract cells investigated with intracellular injection of sodium ions. Exp. Brain Res. 14: 489 - 503, 1972.CrossRefGoogle Scholar
  43. 43.
    Konnerth, A., Heinemann, U., Yaari, Y. Slow transmission of neural activity in hippocampal area CA1 in absence of active chemical synapses. Nature 307: 69 - 71, 1984.PubMedCrossRefGoogle Scholar
  44. 44.
    Konnerth, A., Heinemann, U.,Yaari, Y. Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. I. Development of seizure like activity in low extracellular calcium. J. Neurophysiol. 56: 409 - 423, 1986.Google Scholar
  45. 45.
    Korn, H. and Faber, D. Electrical field effect interactions in the vertebrate brain. Trends Neurosci. 3: 6 - 9, 1980.Google Scholar
  46. 46.
    Kosaka, T. Gap junctions between nonpyramidal cell dendrites in the rat hippo-campus (CA1 and CA3 regions). Brain Res. 271: 157 - 161, 1983.PubMedCrossRefGoogle Scholar
  47. 47.
    Krnjevic, K., Morris, M., Reinffenstein, R. Changes in extracellular Ca and K activity accompanying hippocampal discharges. Can. J. Physiol. Pharmac. 58: 579 - 583, 1980.Google Scholar
  48. 48.
    Lebovitz, R., Dichter, M., Spencer, W. Recurrent excitation in the CA3 region of cat hippocampus. Int. J. Neurosci. 2: 99 - 108, 1971.PubMedCrossRefGoogle Scholar
  49. 49.
    Lorente de No R. Studies on the structure of the cerebral cortex. II. Continuation of the structure of the ammonic system. J. Psychol. Neurol. 46: 225 - 242, 1934.Google Scholar
  50. 50.
    Lux, H., Heinemann, U., Deitzel, I. Ionic changes and alterations in the size of the extracellular space during epileptic activity. In: Delgado-Escueta, A., Ward, A., Woodbury, D. and Porter, R. (eds). Advances in Neurology, Vol 44, New York: Raven Press, pp. 619 - 639, 1986.Google Scholar
  51. 51.
    Lux, H. and Neher, E. The equilibration time course of [K] in cat cortex. Exp. Brain Res. 17: 190 - 205, 1973.PubMedCrossRefGoogle Scholar
  52. 52.
    MacVicar, B. and Dudek, F. Dye-coupling between CA3 pyramidal cells and slices of rat hippocampus. Brain Res. 196: 494 - 497, 1980.PubMedCrossRefGoogle Scholar
  53. 53.
    MacVicar, B. and Dudek, F. Electronic coupling between pyramidal cells: A direct demonstration in hippocampal slices. Science 213: 782 - 785, 1981.PubMedCrossRefGoogle Scholar
  54. 54.
    Madison, D. and Nicoll, R. Control of the repetitive discharge of rat CAl pyramidal neurones in vitro. J. Physiol. 354: 319 - 331, 1984.PubMedGoogle Scholar
  55. 55.
    Malenka, R., Kocsis, J., Ransom, B., Waxman, S. Modulation of parallel fiber excitability by postsynaptically mediated changes in extracellular potassium. Science 214: 339 - 341, 1981.PubMedCrossRefGoogle Scholar
  56. 56.
    Masukawa, L., Bernardo, L., Prince, D. Variations in electrophysiological properties of hippocampal neurons in different subfields. Brain Res. 242: 341 - 344, 1982.PubMedCrossRefGoogle Scholar
  57. 57.
    Matsumoto, H. and Ajmone-Marsan, C. Cortical cellular phenomena in experimental epilepsy: ictal manifestations. Exp. Neurol. 9: 305 - 326, 1964.PubMedCrossRefGoogle Scholar
  58. 58.
    Miles, R. and Wong, R. Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus. J. Physiol. 373: 397 - 418.Google Scholar
  59. 59.
    Moody, W., Jr., Futamachi, K., Prince, D. Extracellular potassium activity during epileptogenesis. Exp. Neurol. 42: 246 - 263, 1974.CrossRefGoogle Scholar
  60. 60.
    Connor, M. and Lewis, D. Recurrent seizures induced by potassium in the penicillin treated hippocampus. Electroenceph. Clin. Neurophysiol. 36: 337 - 345, 1974.Google Scholar
  61. 61.
    Ogata, N., Hovi, N., Katsuda, N. The correlation between extracellular potassium concentration and hippocampal epileptic activity in vitro. Brain Res. 110: 371 - 375, 1976.PubMedCrossRefGoogle Scholar
  62. 62.
    Orkand, R., Nicholls, J., Kuffler, S. Effect of nerve impulses on the membrane potential of glial cells in the central nervous system of amphibia. J. Neurophysiol. 29: 788 - 806, 1966.PubMedGoogle Scholar
  63. 63.
    Prince, D. Contribution of Ca-mediated events to epileptogenesis. Exp. Brain Res. Ser. 14, 318 - 324, 1986.Google Scholar
  64. 64.
    Prince, D. and Connors, B. Mechanisms of interictal epileptogenesis. In: DelgadoEscueta, A., Ward, A., Woodbury, D. and Porter, R. (eds). Advances in Neurology, Vol. 44, New York: Raven Press, pp. 275 - 299, 1986.Google Scholar
  65. 65.
    Prince, D., Connors, B., Bernardo, L. Mechanisms underlying interictal-ictal transitions. In: Delgado-Escueta, A., Wasterlain, C., Treiman, D. and Porter, R. (eds). Advances in Neurology, Vol. 34, New York: Raven Press, pp. 179 - 189, 1982.Google Scholar
  66. 66.
    Prince, D. and Schwartzkroin, P. Nonsynaptic mechanisms in epileptogenesis. In: Chalazonitis, N. and Boisson, M. (eds). Abnormal Neuronal Discharges, New York: Raven Press, pp. 1 - 12, 1978.Google Scholar
  67. 67.
    Rang, H. and Ritchie, J. On the electrogenic sodium pump in mammalian nonmyelinated nerve fibres and its activation by various external cations. J. Physiol. 196: 183 - 221.Google Scholar
  68. 68.
    Roberts, E. Failure of GABAergic inhibition: A key to local and global seizures. In: Delgado-Escueta, A., Ward, A., Woodbury, D. and Porter, R. (eds). Advances in Neurology, Vol 44, New York: Raven Press, pp. 319 - 342, 1986.Google Scholar
  69. 69.
    Rutecki, P., Lebeda, F., Johnston, D. Epileptiform activity induced by changes in extracellular potassium in hippocampus. J. Neurophysiol. 54: 1363 - 1374, 1985.PubMedGoogle Scholar
  70. 70.
    Somjen, G. Interstitial Ion Concentration and the Role of Neuroglia in Seizures. In: Wheal, H. and Schwartzkroin, P. (eds). Electrophysiology of Epilepsy, London: Academic Press, pp. 303 - 341, 1984.Google Scholar
  71. 71.
    Somjen, G., Aitken, P., Giacchino, J., McNamara, J. Interstitial ion concentrations and paroxysmal discharges in hippocampal formation and spinal cord. In: Delgado-Escueta, A., Ward, A., Woodbury, D. and Porter, R. (eds). Advances in Neurology, Vol 44, New York: Raven Press, pp. 663 - 680, 1986.Google Scholar
  72. 72.
    Spencer, W. and Kandel, E. Synaptic Inhibition in Seizures. In: Jasper, H., Ward, A. and Pope, A. (eds). Basic Mechanisms of the Epilepsies. Boston: Little, Brown, pp. 575 - 603, 1969.Google Scholar
  73. 73.
    Spira, M., Yarom, Y., Zeldes, D. Neuronal interactions mediated by neurally evoked changes in the extracellular potassium concentration. J. Exp. Biol. 112: 179 - 197, 1984.PubMedGoogle Scholar
  74. 74.
    Sypert, G. and Ward, A. Changes in extracellular potassium activity during neo-cortical propagated seizures. Exp. Neurol. 45: 19 - 41, 1974.PubMedCrossRefGoogle Scholar
  75. 75.
    Taylor, C. and Dudek, F. A physiological test for electrotonic coupling between CAl pyramidal cells in rat hippocampal slices. Brain Res. 235: 351 - 357, 1982.PubMedCrossRefGoogle Scholar
  76. 76.
    Taylor, C. and Dudek, F. Excitation of hippocampal pyramidal cells by an electrical field effect. J. Neurophysiol. 52: 126 - 142, 1984.PubMedGoogle Scholar
  77. 77.
    Taylor, C. and Dudek, F. Synchronization without active chemical synapses during hippocampal afterdischarges. J. Neurophysiol. 52: 143 - 155, 1984.PubMedGoogle Scholar
  78. 78.
    Taylor, C., Krnjevic, K., Ropert, N. Facilitation of CA3 pyramidal cell firing by electrical fields generated antidromically. Neurosci. 11: 101 - 109, 1984.CrossRefGoogle Scholar
  79. 79.
    Traub, R., Dudek, F., Taylor, C., Knowles, W. Simulation of hippocampal after-discharges synchronized by electrical interactions. Neurosci. 14: 1033 - 1038.Google Scholar
  80. 80.
    Wong, R. and Prince, D. Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res. 159: 385 - 390, 1978.PubMedCrossRefGoogle Scholar
  81. 81.
    Wong, R. and Traub, R. Synchronized burst discharge in disinhibited hippocampal slice. I. Initiation in CA2-CA3 region. J. Neurophysiol. 49: 442 - 458, 1983.PubMedGoogle Scholar
  82. 82.
    Yaari, Y. and Konnerth, A. Epileptogenesis in low extracellular calcium. Exp. Brain Res. Ser. 14: 353 - 365, 1986.Google Scholar
  83. 83.
    Yaari, Y., Konnerth, A., Heinemann, U. Spontaneous epileptiform activity of CAl hippocampal neurons in low extracellular calcium solutions. Exp. Brain Res. 51: 153 - 156, 1983.PubMedCrossRefGoogle Scholar
  84. 84.
    Yaari, Y., Konnerth, A., Heinemann, U. Nonsynaptic epileptogenesis at the mammalian hippocampus in vitro. II. Role of extracellular potassium. J. Neurophysiol. 56: 424 - 438, 1986.PubMedGoogle Scholar
  85. 85.
    Yarom, Y. and Spira, M. Extracellular potassium ions mediate specific neuronal interaction. Science 216: 80 - 82, 1982.PubMedCrossRefGoogle Scholar
  86. 86.
    Yim, C., Krnjevic, K., Dalkara, T. Ephaptically generated potentials in CAl neurons of rats hippocampus in situ. J. Neurophysiol. 56: 99 - 122.Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Yoel Yaari
    • 1
  • Morten S. Jensen
    • 2
  1. 1.Department of PhysiologyHebrew University-Hadassah School of MedicineJerusalemIsrael
  2. 2.Institute of PhysiologyUniversity of AarhusAarhus CDenmark

Personalised recommendations