Advertisement

Cellular Mechanisms of Interictal-Ictal Transitions

  • David A. Prince

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).

Keywords

Gaba Receptor Gaba Release Epileptiform Discharge Extracellular Potassium Ictal Episode 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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.Google Scholar
  2. 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.PubMedGoogle Scholar
  3. 3.
    Traub, R. and Wong, R. Synchronized burst discharge in disinhibited hippocampal slice. II. Model of cellular mechanism. J. Neurophysiol. 49: 459–471, 1983.PubMedGoogle Scholar
  4. 4.
    Miles, R., Wong, R., Traub, R. Synchronized afterdischarges in the hippocampus: contribution of local synaptic interactions. Neuroscience 12: 1179–1189, 1984.PubMedCrossRefGoogle Scholar
  5. 5.
    McCarren, M. and Alger, B. Use-dependent depression of Ipsps in rat hippocampal pyramidal cells in vitro. J. Neurophysiol. 53: 557–571, 1985.PubMedGoogle Scholar
  6. 6.
    Deisz, R. and Prince, D. Presynaptic GABA feedback causes frequency dependent depression of Ipsps in neocortical neurons. Neurosci. Abstr. 12: 19, 1986Google Scholar
  7. 7.
    Satou, M., Mori, K., Tazawa, Y., Takagi, S. Long-lasting disinhibition in pyriform cortex of the rabbit. J. Neurophysiol. 48: 1157–1163, 1982.PubMedGoogle Scholar
  8. 8.
    Ben-Ari, Y., Krnjevic, K., Reinhardt, W. Hippocampal seizures and failure of inhibition. Can. J. Physiol. Pharmac. 57:1462–1466, 1979.CrossRefGoogle Scholar
  9. 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. 10.
    Cole, A. and Nicoll, R. Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science 221: 1299–1301, 1983.PubMedCrossRefGoogle Scholar
  11. 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.Google Scholar
  12. 12.
    Benardo, L. and Prince, D. Cholinergic excitation of mammalian hippocampal pyramidal cells. Brain Res. 249: 315–331, 1982.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.Google Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 17.
    Taylor, C., Krnjevic, K., Ropert, N. Facilitation of hippocampal CA3 pyramidal cell firing by electrical fields generated antidromically. Neuroscience 11: 101–109, 1984.PubMedCrossRefGoogle Scholar
  18. 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.Google Scholar
  19. 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. 20.
    Alger, B. and Nicoll, R. Epileptiform burst afterhyperpolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science 210: 1122–1124, 1980.PubMedCrossRefGoogle Scholar
  21. 21.
    Hotson, J. and Prince, D. A calcium-activated hyperpolarization follows repetitive firing in hippocampal neurons. J. Neurophysiol. 43: 409–419, 1980.PubMedGoogle Scholar
  22. 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.PubMedGoogle Scholar
  23. 23.
    Ayala, G., Matsumoto, H., Gumnit, R. Excitability changes and inhibitory mechanisms in neocortical neurons during seizures. J. Neurophysiol. 33: 73–85, 1970.PubMedGoogle Scholar
  24. 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.Google Scholar
  25. 25.
    Newberry, N. and Nicoll, R. Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308: 450–452, 1984.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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. 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. 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. 30.
    Prince, D., Lux, H., Neher, E. Measurement of extracellular potassium activity in cat cortex. Brain Res. 50: 489–495, 1973.PubMedCrossRefGoogle Scholar
  31. 31.
    Moody, W., Futamachi, K., Prince, D. Extracellular potassium activity during epileptogenesis. Exp. Neurol. 42: 248–263, 1974.PubMedCrossRefGoogle Scholar
  32. 32.
    Fisher, R., Pedley, T., Moody, W., Jr., Prince, D. The role of extracellular potassium in hippocampal epilepsy. Arch. Neurol. 33: 76–83, 1976.PubMedCrossRefGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.PubMedCrossRefGoogle Scholar
  35. 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. 36.
    Rutecki, P., Lebeda, F., Johnston, D. Epileptiform activity induced by changes in extracellular potassium in hippocampus. J. Neurophysiol. 54: 1363–1374, 1985.PubMedGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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. 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. 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.Google Scholar
  41. 41.
    McCormick, D. and Prince, D. Neurotransmitter modulation of thalamic neuronal firing pattern. J. Mind & Behay. 18: 573–590, 1987.Google Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 43.
    Levitan, I. Phosphorylation of ion channels. J. Membrane Biol. 87: 177–190, 1985.CrossRefGoogle Scholar
  44. 44.
    Katz, B. and Miledi, R. A study of synaptic transmission in the absence of nerve impulses. J. Physiol. (London) 192: 407–436, 1967.Google Scholar
  45. 45.
    Gutnick, M. and Prince, D. Thalamocortical relay neurons: antidromic invasion of spikes from cortical epileptogenic focus. Science 176: 424–426, 1972.PubMedCrossRefGoogle Scholar
  46. 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. 47.
    Noebels, J. and Prince, D. Development of focal seizures in cerebral cortex: role of axon terminal bursting. J. Neurophysiol. 41: 1267–1281, 1978.PubMedGoogle Scholar
  48. 48.
    Noebels, J. and Prince, D. Excitability changes in thalamocortical relay neurons during synchronous discharges in cat neocortex. J. Neurophysiol. 41: 1282–1296, 1978.PubMedGoogle Scholar
  49. 49.
    Gabor, A. and Scobey, R. Spatial limits of epileptogenic cortex: its relationship to ectopic spike generation. J. Neurophysiol. 38: 395–404, 1975.PubMedGoogle Scholar
  50. 50.
    Pinault, D. and Pumain, R. Ectopic action potential generation: its occurrence in a chronic epileptogenic focus. Exp. Brain Res. 60: 599–602, 1985.PubMedCrossRefGoogle Scholar
  51. 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.PubMedCrossRefGoogle Scholar
  52. 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.PubMedGoogle Scholar
  53. 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. 54.
    Taylor, C. and Dudek, F. Synchronous neural afterdischarges in rat hippocampal slices without active chemical synapses. Science 218: 810–812, 1982.PubMedCrossRefGoogle Scholar
  55. 55.
    Rasminsky, M. Ephaptic transmission between single nerve fibers in the spinal nerve root of dystrophic mice. J. Physiol. (London) 305: 151–169, 1980.Google Scholar
  56. 56.
    Traub, R., Dudek, F., Taylor, C., Knowles, W. Simulation of hippocampal after-discharges synchronized by electrical interactions. Neurosci. 14: 1033–1038, 1985.CrossRefGoogle Scholar
  57. 57.
    Wong, R. and Watkins, D. Cellular factors influencing GABA response in hippocampal pyramidal cells. J. Neurophysiol. 48: 938–951, 1982.PubMedGoogle Scholar
  58. 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.PubMedCrossRefGoogle Scholar
  59. 59.
    Connors, B., Gutnick, M., Prince, D. Electrophysiological properties of neocortical neurons in vitro. J. Neurophysiol. 48: 1302–1320, 1982.PubMedGoogle Scholar
  60. 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. 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. 62.
    Newberry, N. and Nicoll, R. A bicuculline-resistant inhibitory postsynaptic potential in rat hippocampal pyramidal cells. J. Physiol. (London) 348: 239–254, 1984.Google Scholar
  63. 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. 64.
    Futamachi, K., Mutani, R., Prince, D. Potassium activity in rabbit cortex. Brain Res. 75: 5–25, 1974.PubMedCrossRefGoogle Scholar
  65. 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. 66.
    Krnjevic, K. Desensitization of GABA receptors. Adv. Biochem. Psychopharmacol. 26: 111–120, 1981.PubMedGoogle Scholar
  67. 67.
    Miles, R. and Wong, R. Latent synaptic pathways revealed after tetanic stimulation in the hippocampus. Nature 329: 724–726, 1987.PubMedCrossRefGoogle Scholar
  68. 68.
    Kupfermann, I. Modulatory actions of neurotransmitters. Ann. Rev. Neurosci. 2: 447–465, 1979.PubMedCrossRefGoogle Scholar
  69. 69.
    Brown, D. and Adams, P. Muscarinic suppression of a novel voltage-sensitive K current in a vertebrate neurone. Nature 283: 673–676, 1980.PubMedCrossRefGoogle Scholar
  70. 70.
    Halliwell, J. and Adams, P. Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 250: 71–92, 1982.PubMedCrossRefGoogle Scholar
  71. 71.
    Madison, D. and Nicoll, R. Control of repetitive discharge of rat cerebral CA1 neurones in vitro. J. Physiol. (London) 354: 319–331, 1984.Google Scholar
  72. 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.PubMedCrossRefGoogle Scholar
  73. 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.Google Scholar
  74. 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.Google Scholar
  75. 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.PubMedCrossRefGoogle Scholar
  76. 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.Google Scholar
  77. 77.
    Mayer, M., Westbrook, G., Guthrie, P. Voltage-dependent block by Mg of NMDA responses in spinal cord neurones. Nature 309: 261–263, 1984.PubMedCrossRefGoogle Scholar
  78. 78.
    Dingledine, R. N-methyl aspartate activates voltage-dependent calcium conductance in rat hippocampal pyramidal cells. J. Physiol. (London) 343: 385–405, 1983.Google Scholar
  79. 79.
    Croucher, M., Coffins, J., Meldrum, B. Anticonvulsant action of excitatory amino acids antagonists. Science 216: 899–901, 1982.PubMedCrossRefGoogle Scholar
  80. 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.PubMedGoogle Scholar
  81. 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.Google Scholar
  82. 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.CrossRefGoogle Scholar
  83. 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. 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. 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.PubMedCrossRefGoogle Scholar
  86. 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.Google Scholar
  87. 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. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • David A. Prince
    • 1
  1. 1.Department of NeurologyStanford University School of Medicine StanfordUSA

Personalised recommendations