Skip to main content
SpringerLink
Log in
Book cover

Mechanisms of Epileptogenesis pp 57–71Cite as

Cellular Mechanisms of Interictal-Ictal Transitions

  • Chapter

Abstract

Much more is known about processes underlying development of interictal epileptiform discharge than about the mechanisms which convert such localized discharge into ictal episodes and facilitate the spread of epileptogenic activity through adjacent and distant brain regions. It seems reasonable to speculate that those mechanisms known to produce signal amplification and spread of activity in models of epileptogenesis are likely to be involved in interictal-ictal transitions. There are several prerequisites for such processes. First, some type of positive feedback sequence would be required so that increasing activity generated increases in excitability which in turn increased neuronal discharge. This might take place through augmentation of excitatory synaptic drives following use of the circuit (1); recurrent excitatory circuitry (2,3,4); a progressive depression in inhibitory electrogenesis during repetitive activation (5,6,7,8); or activation (inactivation) of membrane currents that are voltage-dependent, and may in some instances be modulated by agonists (9,10,11,12). Other potential positive feedback mechanisms include changes in extracellular microenvironment (13,14,15,16) and ephaptic interactions (17,18).

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bliss, T. and Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. (London) 232: 331–356, 1973.

    CAS  Google Scholar 

  2. Dichter, M. and Spencer, W. Penicillin-induced interictal discharges from the cat hippocampus. II. Mechanisms underlying origin and restriction. J. Neurophysiol. 32: 663–687, 1969.

    CAS  PubMed  Google Scholar 

  3. Traub, R. and Wong, R. Synchronized burst discharge in disinhibited hippocampal slice. II. Model of cellular mechanism. J. Neurophysiol. 49: 459–471, 1983.

    CAS  PubMed  Google Scholar 

  4. Miles, R., Wong, R., Traub, R. Synchronized afterdischarges in the hippocampus: contribution of local synaptic interactions. Neuroscience 12: 1179–1189, 1984.

    Article  CAS  PubMed  Google Scholar 

  5. McCarren, M. and Alger, B. Use-dependent depression of Ipsps in rat hippocampal pyramidal cells in vitro. J. Neurophysiol. 53: 557–571, 1985.

    CAS  PubMed  Google Scholar 

  6. Deisz, R. and Prince, D. Presynaptic GABA feedback causes frequency dependent depression of Ipsps in neocortical neurons. Neurosci. Abstr. 12: 19, 1986

    Google Scholar 

  7. Satou, M., Mori, K., Tazawa, Y., Takagi, S. Long-lasting disinhibition in pyriform cortex of the rabbit. J. Neurophysiol. 48: 1157–1163, 1982.

    CAS  PubMed  Google Scholar 

  8. Ben-Ari, Y., Krnjevic, K., Reinhardt, W. Hippocampal seizures and failure of inhibition. Can. J. Physiol. Pharmac. 57:1462–1466, 1979.

    Article  CAS  Google Scholar 

  9. Aldrich, R., Getting, P., Thompson, S. Inactivation of delayed outward current in molluscan neurone somata. J. Physiol. (London) 291: 507–530, 1979.

    Google Scholar 

  10. Cole, A. and Nicoll, R. Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science 221: 1299–1301, 1983.

    Article  CAS  PubMed  Google Scholar 

  11. McCormick, D. and Prince, D. Mechanisms of action of acetylcholine in the guinea-pig cerebral cortex in vitro. J. Physiol. (London) 375: 169–194, 1986.

    CAS  Google Scholar 

  12. Benardo, L. and Prince, D. Cholinergic excitation of mammalian hippocampal pyramidal cells. Brain Res. 249: 315–331, 1982.

    Article  CAS  PubMed  Google Scholar 

  13. Heinemann, Y. and Louvel, J. Changes in [Ca]o and [K]o during repetitive electrical stimulation and during pentetrazol seizure activity in the sensorimotor cortex of cats. Pflugers Arch. 398: 310–317, 1983.

    Article  CAS  PubMed  Google Scholar 

  14. Hounsgaard, J. and Nicholson, C. Potassium accumulation around individual Purkinje cells in cerebellar slices from the guinea-pig. J. Physiol. (London) 340: 359–388, 1983.

    CAS  Google Scholar 

  15. Konnerth, A., Heinemann, U., Yaari, Y. Slow transmission of neural activity in hippocampal area CAl in absence of active chemical synapses. Nature 307: 69–71, 1984.

    Article  CAS  PubMed  Google Scholar 

  16. Yaari, Y., Konnerth, A., Heinemann, U. Nonsynaptic epileptogenesis in the mammalian hippocampus in vitro. II. Role of extracellular potassium. J. Neurophysiol. 56: 424–438, 1986.

    CAS  PubMed  Google Scholar 

  17. Taylor, C., Krnjevic, K., Ropert, N. Facilitation of hippocampal CA3 pyramidal cell firing by electrical fields generated antidromically. Neuroscience 11: 101–109, 1984.

    Article  CAS  PubMed  Google Scholar 

  18. Krnjevic, K., Dalkara, T., Yim, C. Synchronization of pyramidal cell firing by ephaptic currents in hippocampus in situ. Adv. Exp Med. Biol. 203: 413–423, 1986.

    CAS  Google Scholar 

  19. Prince, D. Cellular activities in focal epilepsy. In: Brain Dysfunction in Infantile Febrile Convulsions. M. Brazier, F. Coceani (eds). New York: Raven Press, pp. 187212, 1976.

    Google Scholar 

  20. Alger, B. and Nicoll, R. Epileptiform burst afterhyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science 210: 1122–1124, 1980.

    Article  CAS  PubMed  Google Scholar 

  21. Hotson, J. and Prince, D. A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons. J. Neurophysiol. 43: 409–419, 1980.

    CAS  PubMed  Google Scholar 

  22. Thompson, S. and Prince, D. Activation of electrogenic sodium pump in hippocampal CAl neurons following glutamate-induced depolarization. J. Neurophysiol. 56: 507–522, 1986.

    CAS  PubMed  Google Scholar 

  23. Ayala, G., Matsumoto, H., Gumnit, R. Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. J. Neurophysiol. 33: 73–85, 1970.

    CAS  PubMed  Google Scholar 

  24. Alger, B. and Nicoll, R. Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studied in vitro. J. Physiol. (London.) 328: 125–141, 1982.

    CAS  Google Scholar 

  25. Newberry, N. and Nicoll, R. Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308: 450–452, 1984.

    Article  CAS  PubMed  Google Scholar 

  26. Andrade, R., Malenka, R., Nicoll, R. A G-protein couples serotonin and GABA receptors to the same channels in hippocampus. Science 234: 1261–1265, 1986.

    Article  CAS  PubMed  Google Scholar 

  27. Heinemann, U., Konnerth, A., Pumain, R., Wadman, W. Extracellular calcium and potassium concentration changes in chronic epileptic brain tissue. In: Advances in Neurology Vol. 44 Basic Mechanisms of the Epilepsies. A. Delgado-Escueta, A. Ward, Jr., D. Woodbury, R. Porter (eds). New York: Raven Press, pp. 641–661, 1986.

    Google Scholar 

  28. Dudek, E., Snow, R., Taylor, C. Role of electrical interactions and synchronization of epileptiform bursts. In: Advances in Neurology Vol. 44 Basic Mechanisms of the Epilepsies. A.Delgado-Escueta, A. Ward, jr., D. Woodbury, R. Porter (eds). New York: Raven Press, pp. 593–617, 1986.

    Google Scholar 

  29. Lux, H., Heinemann, U., Deitzel, I. Ionic changes and alterations in the size of the extracellular space during epileptic activity. In: Advances in Neurology Vol. 44 Basic Mechanisms of the Epilepsies. A. Delgado-Escueta, A. Ward, Jr., D. Woodbury, R. Porter (eds). New York: Raven Press, pp. 619–639, 1986.

    Google Scholar 

  30. Prince, D., Lux, H., Neher, E. Measurement of extracellular potassium activity in cat cortex. Brain Res. 50: 489–495, 1973.

    Article  CAS  PubMed  Google Scholar 

  31. Moody, W., Futamachi, K., Prince, D. Extracellular potassium activity during epileptogenesis. Exp. Neurol. 42: 248–263, 1974.

    Article  CAS  PubMed  Google Scholar 

  32. Fisher, R., Pedley, T., Moody, W., Jr., Prince, D. The role of extracellular potassium in hippocampal epilepsy. Arch. Neurol. 33: 76–83, 1976.

    Article  CAS  PubMed  Google Scholar 

  33. Heinemann, U., Lux, H., Gutnick, M. Extracellular free calcium and potassium during paroxysmal activity in cerebral cortex of the cat. Exp. Brain Res. 27: 237–243, 1977.

    CAS  PubMed  Google Scholar 

  34. Swann, J., Smith, K., Brady, R. Extracellular K accumulation during penicillin-induced epileptogenesis in the CA3 region of immature rat hippocampus. Brain Res. 395: 243–255, 1986.

    Article  CAS  PubMed  Google Scholar 

  35. Somjen, G. Interstitial ion concentration and the role of neuroglia in seizures. In: Electrophysiology of Epilepsy. H. Wheal, P. Schwartzkroin, (eds). London: Academic Press, pp. 303–341, 1984.

    Google Scholar 

  36. Rutecki, P., Lebeda, F., Johnston, D. Epileptiform activity induced by changes in extracellular potassium in hippocampus. J. Neurophysiol. 54: 1363–1374, 1985.

    CAS  PubMed  Google Scholar 

  37. Grossman, Y., Gutnick, M., Spira, M. Transient extracellular potassium accumulation produced prolonged depolarization during synchronized bursts in picrotoxintreated cockroach CNS. J. Neurophysiol. 48: 1089–1097, 1982.

    PubMed  Google Scholar 

  38. Prince, D. and Schwartzkroin, P. Nonsynaptic mechanisms in epileptogenesis. In: Abnormal Neuronal Discharges. N. Chalazonitis, M. Boisson, (eds). New York: Raven Press, pp. 1–12, 1978.

    Google Scholar 

  39. McCormick, D. and Prince, D. Mechanisms of ascending control of thalamic neuronal activities: Acetylcholine and norepinephrine. Neurosci. Abstr. 12: 903, 1986.

    Google Scholar 

  40. McCormick, D. and Prince, D. Actions of acetylcholine in the medial and lateral geniculate nuclei in vitro. J. Physiol. (London), 392: 147–165, 1987.

    CAS  Google Scholar 

  41. McCormick, D. and Prince, D. Neurotransmitter modulation of thalamic neuronal firing pattern. J. Mind & Behay. 18: 573–590, 1987.

    Google Scholar 

  42. Bergmann, F., Costin, A., Chaimovitz, M., Zerachia, A. Seizure activity evoked by implantation of ouabain and related drugs into cortical and subcortical regions of the rabbit brain. Neuropharmacology 9: 441–449, 1970.

    Article  CAS  PubMed  Google Scholar 

  43. Levitan, I. Phosphorylation of ion channels. J. Membrane Biol. 87: 177–190, 1985.

    Article  CAS  Google Scholar 

  44. Katz, B. and Miledi, R. A study of synaptic transmission in the absence of nerve impulses. J. Physiol. (London) 192: 407–436, 1967.

    CAS  Google Scholar 

  45. Gutnick, M. and Prince, D. Thalamocortical relay neurons: antidromic invasion of spikes from cortical epileptogenic focus. Science 176: 424–426, 1972.

    Article  CAS  PubMed  Google Scholar 

  46. Gutnick, M. and Prince, D. Effects of projected cortical epileptiform discharges on neuronal activities in cat VPL. I. Interictal discharge. J. Neurophysiol. 37: 1310 1327, 1974.

    Google Scholar 

  47. Noebels, J. and Prince, D. Development of focal seizures in cerebral cortex: role of axon terminal bursting. J. Neurophysiol. 41: 1267–1281, 1978.

    CAS  PubMed  Google Scholar 

  48. Noebels, J. and Prince, D. Excitability changes in thalamocortical relay neurons during synchronous discharges in cat neocortex. J. Neurophysiol. 41: 1282–1296, 1978.

    CAS  PubMed  Google Scholar 

  49. Gabor, A. and Scobey, R. Spatial limits of epileptogenic cortex: its relationship to ectopic spike generation. J. Neurophysiol. 38: 395–404, 1975.

    CAS  PubMed  Google Scholar 

  50. Pinault, D. and Pumain, R. Ectopic action potential generation: its occurrence in a chronic epileptogenic focus. Exp. Brain Res. 60: 599–602, 1985.

    Article  CAS  PubMed  Google Scholar 

  51. Gutnick, M. and Prince, D. Effects of projected cortical epileptiform discharges on neuronal activities in ventrobasal thalamus of the cat: ictal discharge. Exp. Neurol. 46: 418–431, 1975.

    Article  CAS  PubMed  Google Scholar 

  52. Yim, C., Krnjevic, K., Dalkara, T. Ephaptically generated potentials in CAl neurons of rat’s hippocampus in situ. J. Neurophysiol. 56: 99–122, 1986.

    CAS  PubMed  Google Scholar 

  53. Snow, R. and Dudek, F. Synchronous epileptiform bursts without chemical transmission in CA2, CA3 and dentate areas of the hippocampus. Brain Res. 298: 38 2385, 1984.

    Google Scholar 

  54. Taylor, C. and Dudek, F. Synchronous neural afterdischarges in rat hippocampal slices without active chemical synapses. Science 218: 810–812, 1982.

    Article  CAS  PubMed  Google Scholar 

  55. Rasminsky, M. Ephaptic transmission between single nerve fibers in the spinal nerve root of dystrophic mice. J. Physiol. (London) 305: 151–169, 1980.

    CAS  Google Scholar 

  56. Traub, R., Dudek, F., Taylor, C., Knowles, W. Simulation of hippocampal after-discharges synchronized by electrical interactions. Neurosci. 14: 1033–1038, 1985.

    Article  CAS  Google Scholar 

  57. Wong, R. and Watkins, D. Cellular factors influencing GABA response in hippocampal pyramidal cells. J. Neurophysiol. 48: 938–951, 1982.

    CAS  PubMed  Google Scholar 

  58. Ben-Ari, Y., Krnjevic, K., Reiffenstein, R., Reinhardt, W. Inhibitory conductance changes and action of gamma-aminobutyrate in rat hippocampus. Neuroscience 6: 2445–2463, 1981.

    Article  CAS  PubMed  Google Scholar 

  59. Connors, B., Gutnick, M., Prince, D. Electrophysiological properties of neocortical neurons in vitro. J. Neurophysiol. 48: 1302–1320, 1982.

    CAS  PubMed  Google Scholar 

  60. Thompson, S., Deisz, R., Prince, D. Identification and characterization of a Cl-extruding pump in mammalian cortical neurons. Neurosci. Abstr. 12: 19, 1986.

    Google Scholar 

  61. Ben-Ari, Krnjevic, K., Reinhardt, W., Ropert, N. Intracellular observations on the disinhibitory action of acetylcholine in the hippocampus. Neuroscience 6: 2475 2484, 1981.

    Google Scholar 

  62. Newberry, N. and Nicoll, R. A bicuculline-resistant inhibitory postsynaptic potential in rat hippocampal pyramidal cells. J. Physiol. (London) 348: 239–254, 1984.

    CAS  Google Scholar 

  63. Connors, B. and Malenka, R. Neocortical pyramidal cells: GABAA and GABAB mediated responses in two types of IPSP. Neurosci. Abstr. 11: 7, 1985.

    Google Scholar 

  64. Futamachi, K., Mutani, R., Prince, D. Potassium activity in rabbit cortex. Brain Res. 75: 5–25, 1974.

    Article  CAS  PubMed  Google Scholar 

  65. Numann, R. and Wong, R. Desensitization of the GABA receptor in hippocampal neurons isolated from the adult guinea pig. Neurosci. Abstr. 9: 736, 1983.

    Google Scholar 

  66. Krnjevic, K. Desensitization of GABA receptors. Adv. Biochem. Psychopharmacol. 26: 111–120, 1981.

    CAS  PubMed  Google Scholar 

  67. Miles, R. and Wong, R. Latent synaptic pathways revealed after tetanic stimulation in the hippocampus. Nature 329: 724–726, 1987.

    Article  CAS  PubMed  Google Scholar 

  68. Kupfermann, I. Modulatory actions of neurotransmitters. Ann. Rev. Neurosci. 2: 447–465, 1979.

    Article  CAS  PubMed  Google Scholar 

  69. Brown, D. and Adams, P. Muscarinic suppression of a novel voltage-sensitive K current in a vertebrate neurone. Nature 283: 673–676, 1980.

    Article  CAS  PubMed  Google Scholar 

  70. Halliwell, J. and Adams, P. Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 250: 71–92, 1982.

    Article  CAS  PubMed  Google Scholar 

  71. Madison, D. and Nicoll, R. Control of repetitive discharge of rat cerebral CA1 neurones in vitro. J. Physiol. (London) 354: 319–331, 1984.

    CAS  Google Scholar 

  72. Kriegstein, A., Suppes, T., Prince, D. Cholinergic enhancement of penicillin-induced epileptiform discharges in pyramidal neurons of the guinea pig hippocampus. Brain Res. 266: 137–142, 1983.

    Article  CAS  PubMed  Google Scholar 

  73. Madison, D. and Nicoll, R. Actions of noradrenaline recorded intracellularly in rat hippocampal CAl pyramidal neurones in vitro. J. Physiol. (London) 372: 221–244, 1986.

    CAS  Google Scholar 

  74. Madison, D. and Nicoll, R. Cyclic adenosine 3’,5’-monophosphate mediates [3-receptor actions of noradrenaline in rat hippocampal pyramidal cells. J. Physiol. (London) 372: 245–259, 1986.

    CAS  Google Scholar 

  75. Levitt, P. and Noebels, J. Mutant mouse tottering: selective increase of locus ceruleus axons in a defined single-locus mutation. PNAS 78: 4630–4634, 1981.

    Article  CAS  PubMed  Google Scholar 

  76. Thomson, A. A magnesium-sensitive post-synaptic potential in rat cerebral cortex resembles neuronal responses to N-methyl-aspartate. J. Physiol. (London) 370: 531–549, 1986.

    CAS  Google Scholar 

  77. Mayer, M., Westbrook, G., Guthrie, P. Voltage-dependent block by Mg of NMDA responses in spinal cord neurones. Nature 309: 261–263, 1984.

    Article  CAS  PubMed  Google Scholar 

  78. Dingledine, R. N-methyl aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells. J. Physiol. (London) 343: 385–405, 1983.

    CAS  Google Scholar 

  79. Croucher, M., Coffins, J., Meldrum, B. Anticonvulsant action of excitatory amino acids antagonists. Science 216: 899–901, 1982.

    Article  CAS  PubMed  Google Scholar 

  80. Anderson, W., Swartzwelder, H., Wilson, W. NMDA-receptor antagonist 2-amino5-phosphono-valerate blocks stimulus train-induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice. J. Neurophysiol. 57: 1–21, 1987.

    CAS  PubMed  Google Scholar 

  81. Czuczwar, S., Turski, L., Schwarz, M., Turski, W., Kleinrok, Z. Effects of excitatory amino-acid antagonists on the anticonvulsant action of phenobarbital or diphenylhydantoin in mice. Europ. J. Pharmacol. 100: 357–362, 1984.

    CAS  Google Scholar 

  82. Tortella, F. and Musacchio, J. Dextromethorphan and carbetapentane: centrally acting non-opioid antitussive agents with novel anticonvulsant properties. Brain Res. 381: 314–318, 1986.

    Article  Google Scholar 

  83. Feeser, H., Kadis, J., Wong, B., Prince, D. Anticonvulsant effects of dextromethorphan in a kindling model of epilepsy. Neurosci. Abstr. 113: 1157, 1987.

    Google Scholar 

  84. Wong, B., Coulter, D., Choi, D., Prince, D. Antitussive agents, dextrorphan and dextromethorphan antagonize N-methyl-D-aspartate and are antiepileptic. Neurosci. Abstr. 13: 1560, 1987.

    Google Scholar 

  85. Anderson, W., Lewis, D., Swartzwelder, H., Wilson, W. Magnesium free medium activates seizure-like events in rat hippocampal slice. Brain Res. 398: 215–219, 1986.

    Article  CAS  PubMed  Google Scholar 

  86. Swartzwelder, H., Lewis, D., Anderson, W., Wilson, W. Seizure-like events in brain slices: Suppression by interictal activity. Brain Res. 410: 362–366, 1987.

    CAS  Google Scholar 

  87. Prince, D., Connors, B., Benardo, L. Mechanisms underlying interictal-ictal transitions. In: Advances in Neurology Vol. 34. Status Epilepticus. Mechanisms of Brain Damage and Treatment. A. Delgado-Escueta, C. Wasterlain, D. Treiman, R. Porter (eds). New York: Raven Press, pp. 177–187, 1983.

    Google Scholar 

  88. Engel, J. and Ackerman, R. Interictal EEG spikes correlate with decreased rather than increased epileptogenicity in amygdala-kindled rats. Brain Res. 190: 543–548, 1980.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, Stanford University School of Medicine Stanford, CA, 94305, USA

    David A. Prince M.D.

Authors
  1. David A. Prince M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. The Graduate Hospital, Philadelphia, Pennsylvania, USA

    Marc A. Dichter M.D., Ph.D. (Director of the Comprehensive Epilepsy Center, Professor of Neurology) (Director of the Comprehensive Epilepsy Center, Professor of Neurology)

  2. Department of Neurology, University of Pennsylvania, Philadelphia, Philadelphia, USA

    Marc A. Dichter M.D., Ph.D. (Director of the Comprehensive Epilepsy Center, Professor of Neurology) (Director of the Comprehensive Epilepsy Center, Professor of Neurology)

Rights and permissions

Reprints and permissions

Copyright information

© 1988 Springer Science+Business Media New York

About this chapter

Cite this chapter

Prince, D.A. (1988). Cellular Mechanisms of Interictal-Ictal Transitions. In: Dichter, M.A. (eds) Mechanisms of Epileptogenesis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5556-4_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5556-4_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5558-8

  • Online ISBN: 978-1-4684-5556-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation