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Modulation of Inhibition and the Transition to Seizures

  • Marc A. Dichter

Abstract

Understanding the mechanisms which underlie the transition between interictal and ictal activity is one of the most critical issues in the study of epilepsy. In all forms of epilepsy, the electrical activity in most parts of the brain is normal most of the time. A seizure occurs when neurons in many parts of the brain, including those parts which are normal, develop synchronized activity. In primary generalized epilepsy, the transition between interictal and ictal activity occurs abruptly and without obvious behavioral or electrophysiological warning. In focal epilepsy, the transition appears to occur first in a focal area of abnormality and then spreads to both adjacent and distant areas of normal brain. The phenomena which occur at the cellular level during such transitions have not been well characterized in either the human epilepsies or in most animal models of epilepsy, and therefore relatively few hypotheses have been developed to explain the transition to seizure.

Keywords

Cortical Neuron Epileptiform Activity Inhibitory Synapse Focal Epilepsy Repetitive Activation 
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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References

  1. 1.
    Alger, B. Characteristics of slow hyperpolarizing synaptic potentials in rat hippocampal pyramidal cells in vitro. J. Neurophysiol. 52: 892–910, 1984.PubMedGoogle Scholar
  2. 2.
    Alger, B. and Nicoll, R. Epileptiform burst afterhyperpolarization. calcium dependent potassium potential in hippocampal CAl pyramidal cells. Science 210: 1122–1124, 1980.PubMedCrossRefGoogle Scholar
  3. 3.
    Andersen, P. and Lomo, T. Counteraction of powerful recurrent inhibition in hippocampal pyramidal cells by frequency potentiation of excitatory synapses. In C. Von Euler, S. Skoglund, and U. Soderberg (eds). Structure and Function of Inhibitory Neuronal Mechanisms, Oxford: UK, Pergamon, pp. 335–342, 1968.Google Scholar
  4. 4.
    Ayala, G., Dichter, M., Gummit, R., Matsumoto, H., Spencer, W. Genesis of epileptic interictal spikes. Brain Res. 52: 1–17, 1973.PubMedCrossRefGoogle Scholar
  5. 5.
    Ayala, G., Matsumoto, M., Gumnit, R. Excitability changes and inhibitory mechanism in neocortical neurons during seizures. J. Neurophysiol. 33: 73–85, 1970.PubMedGoogle Scholar
  6. 6.
    Ayala, G. and Vasconetto, C. Role of recurrent excitatory pathways in epileptogenesis. EEG Clin. Neurophysiol. 33: 96–98, 1972.CrossRefGoogle Scholar
  7. 7.
    Barnes, D. and Dichter, M. Development of inhibitory mechanisms in dissociated cultures of rat hippocampus. Neurosci. Abst. 10, 1984.Google Scholar
  8. 8.
    Ben-Ari, Y., Krnjevic, K., Reinhardt, W. Hippocampal seizures and failure of inhibition. Can J. Physiol. Pharmacol. 57: 1462–1466, 1979.CrossRefGoogle Scholar
  9. 9.
    Bernardo, L. and Prince, D. Ionic mechanisms of cholinergic excitation in mammalian hippocampal pyramidal cells. Brain Res: 249: 333–344, 1982.CrossRefGoogle Scholar
  10. 10.
    Brown, D., Adams, P., Constanti, A. Voltage-sensitive K-currents in sympathetic neurons and their modulation by neurotransmitters. J. Autonom. Nerv. Sys. 6: 23–35, 1982.CrossRefGoogle Scholar
  11. 11.
    Buchhalter, J. and Dichter, M. Blockers of GABA uptake diminish spontaneous IPSP size in mammalian dissociated cell culture. Neurosci. Abst. 11, 1985.Google Scholar
  12. 12.
    Cole, A. and Nicoll, R. Acetylcholine mediates a slow synaptic potential in hippocampal pyramidal cells. Science 221: 1299–1301, 1983.PubMedCrossRefGoogle Scholar
  13. 13.
    Cole, A. and Nicoll, R. Characterization of slow cholinergic postsynaptic potential recorded in vitro from hippocampal pyramidal cells. J. Physiol. 352: 173–188, 1984.PubMedGoogle Scholar
  14. 14.
    Croucher, M., Collins, J., Meldrum, B. Anticonvulsant action of excitatory amino acid antagonists. Science 216: 899–901, 1982.PubMedCrossRefGoogle Scholar
  15. 15.
    Delfs, J. and Dichter, M. Effects of somatostatin on cortical neurons in culture. J. Neuroscience 3: 1176–1188, 1983.Google Scholar
  16. 16.
    Dichter, M. Physiological identification of GABA as the inhibitory transmitter between cortical neurons in culture. Brain Res. 190: 111–121, 1981.CrossRefGoogle Scholar
  17. 17.
    Dichter, M. (Ed) Mechansims of Epileptogenesis: The Transition to Seizure. New York: Plenum Press, 1988.Google Scholar
  18. 18.
    Dichter, M. and Ayala, G. Cellular Mechanisms of Epilepsy: A Status Report. Science 237: 157–164, 1987.PubMedCrossRefGoogle Scholar
  19. 19.
    Dichter, M. and Delfs, J. In: Neurosecretion and Brain Peptides, J. Martin, S. Reichlin and K. Bick, (eds). New York: Raven Press, 1981.Google Scholar
  20. 20.
    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 seizures. Brain Res. 48: 173–183, 1972.PubMedCrossRefGoogle Scholar
  21. 21.
    Dichter, M., Herman, C., Selzer, M. Extracellular unit analysis of the hippocampal penicillin foci. EEG Clin Neurophysiol. 34: 619–629, 1973.CrossRefGoogle Scholar
  22. 22.
    Dichter, M., Lisak, J., Biales, B. Action potential mechanism of rat cortical neurons in cell culture. Brain Research 289: 99–107, 1983.PubMedCrossRefGoogle Scholar
  23. 23.
    Dichter, M. and Spencer, W. Penicillin induced interictal discharges from cat hippocampus. I. Characteristics and topographical features. J. Neurophysiol. 32: 649–662, 1969.PubMedGoogle Scholar
  24. 24.
    Dichter, M. and Spencer, W. Penicillin induced interictal discharges from cat hippocampus. II. Mechanisms underlying origin and restriction. J. Neurophysiol. 32: 663–687, 1969.PubMedGoogle Scholar
  25. 25.
    Dingledine, R. N-methyl aspartate activates voltage-dependent calcium conductances in rat hippocampal pyramidal cells. J. Physiol. 343: 385–405, 1983.PubMedGoogle Scholar
  26. 26.
    Dingledine, R. and Gjerstad, L. Reduced inhibition during epileptiform activity in the in vitro hippocampal slice. J. Physiol. 305: 297–313, 1980.PubMedGoogle Scholar
  27. 27.
    Dingledine, R., Hynes, M., King, G. Involvement of N-methyl-D-aspartate receptors in epileptiform bursting in the rat hippocampal slice. J. Physiol. 380: 175–189, 1986.PubMedGoogle Scholar
  28. 28.
    Dingledine, R. and Korn, S. GABA uptake and the termination of inhibitory synaptic potentials in the rat hippocampal slice. J. Physiol. 366: 387–409, 1985.PubMedGoogle Scholar
  29. 29.
    Fertziger, A. and Ranck, J. Potassium accumulation in interstitial space during epileptiform seizures. Exp. Neurol. 26: 571–585, 1970.PubMedCrossRefGoogle Scholar
  30. 30.
    Frosch, M., Lipton, S., Dichter, M. Desensitization and resensitization of GABA activated current and channels in cultured cortical neurons. In preparation.Google Scholar
  31. 31.
    Hablitz, J. Effects of intracellular injections of chloride and EGTA on postepileptiform-burst hyperpolarizations in hippocampal neurons. Neurosci. Lett. 22: 159–163, 1981.PubMedCrossRefGoogle Scholar
  32. 32.
    Hendry, S., Jones, E., DeFelipe, J., Schmechel, D., Brandon, C., Emson, P. Neuropeptide containing neurons of the cerebral cortex are also GAB Aergic. Proc. Natl. Acad. Sci. USA 81: 6526–6530, 1984.PubMedCrossRefGoogle Scholar
  33. 33.
    Herron, C., Williamson, R., Collingridge, G. A selective N-methyl-D-aspartate antagonist depresses epileptiform activity in rat hippocampal slices. Neurosci. Lett. 61: 255–260, 1985.PubMedCrossRefGoogle Scholar
  34. 34.
    Hille, B. Ionic Channels of Excitable Membranes. Sinauer Associates, Inc., Sunderland, Massachusetts, 1984.Google Scholar
  35. 35.
    Hotson, J., Prince, D., Schwartzkroin, P. Anomalous inward rectification in hippocampual neurons. J. Neurophysiol. 42: 889–895, 1979.PubMedGoogle Scholar
  36. 36.
    Huguenard, J. and Alger, B. Whole cell voltage clamp study of the fading of GABA activated currents in acutely dissociated hippocampal neurons. J. Neurophysiol. 56: 1–18, 1986.PubMedGoogle Scholar
  37. 37.
    Johnston, D. and Brown, T. The giant synaptic potential hypothesis for epileptiform activity. Science 211: 294–297, 1981.PubMedCrossRefGoogle Scholar
  38. 38.
    Korn, H., Faber, D., Burnod, Y., Triller, A. Regulation of efficacy at central synapses. J. Neurosci. 4: 125–130, 1984.PubMedGoogle Scholar
  39. 39.
    Krnjevic, K. Loss of synaptic inhibiton as a cause of hippocampal seizures. In: Klee, M., Lux, D., Speckman, E. Physiology and Pharmacology of Epileptogenic Phenomena, New York: Raven Press, pp. 123–130, 1982.Google Scholar
  40. 40.
    Lebovitz, R., Dichter, M., Spencer, W. Recurrent excitation in the CA3 region of cat hippocampus. Intern J. Neuroscience 2: 99–108, 1971.Google Scholar
  41. 41.
    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
  42. 42.
    Madison, D., Malenka, R., Nicoll, R. Phorbol esters block a voltage-sensitive chloride current in hippocampal pyramidal cells. Nature 321: 695–697, 1986.PubMedCrossRefGoogle Scholar
  43. 43.
    Malenka, R., Madison, D., Andrade, R., Nicoll, R. Phorbol esters mimic some cholinergic actions in hippocampal pyramidal neurons. J. Neurosci. 6: 475–480, 1986.PubMedGoogle Scholar
  44. 44.
    Matsumoto, H. and Ajmone Marsan, C. C.rtical cellular phenomena in experimental epilepsy. I. Interictal manifestations. Exp. Neurol. 9: 286–304, 1964.PubMedCrossRefGoogle Scholar
  45. 45.
    Matsumoto H and Ajmone Marsan C. Cortical cellular phenomena in experimental epilepsy. II. Ictal manifestations. Exp. Neurol. 9: 305–31, 1964.PubMedCrossRefGoogle Scholar
  46. 46.
    Matsumoto, H., Ayala, G., Gumnit, R. Neuronal behavior and triggering mechanisms in cortical epileptic focus. J. Neurophysiol. 32: 688–703, 1969.PubMedGoogle Scholar
  47. 47.
    Mayer, M. A calcium activated chloride current generates the after-depolarization of rat sensory neurones in culture. J. Physiol. 364: 217–239, 1985.PubMedGoogle Scholar
  48. 48.
    Mayer, M. and Westbrook, G. The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture. J. Physiol. (London) 361: 65–90, 1985.Google Scholar
  49. 49.
    Meech, R. Calcium dependent potassium activation in nervous tissue. Ann. Rev. Biophys. Bioeng. 7: 1–18, 1978.CrossRefGoogle Scholar
  50. 50.
    Miles, R. and Wong, R. Unitary inhibitory synaptic potentials in the guinea pig hippocampus in vitro. J. Physiol. 356: 97–113, 1984.PubMedGoogle Scholar
  51. 51.
    Miles, R. and Wong, R. Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus. J. Physiol. 373: 397–418, 1986.PubMedGoogle Scholar
  52. 52.
    Miles, R. and Wong, R. Inhibitory control of local excitatory circuits in the guinea-pig hippocampus. J. Physiol. 388: 611–629, 1987.PubMedGoogle Scholar
  53. 53.
    Nicoll, R. and Alger, B. Synaptic excitation may activate a calcium dependent potassium conductance in hippocampal pyramidal cells. Science 212: 957–959, 1981.PubMedCrossRefGoogle Scholar
  54. 54.
    Numann, R. and Wong, R. Voltage clamp study on GABA response desensitization in single pyramidal cells dissociated from the hippocampus of adult guinea pigs. Neurosci. Lettr. 47: 289–294, 1984.CrossRefGoogle Scholar
  55. 55.
    Olsen, R. GABA-benzodiazepine-barbiturate receptor interactions. J. Neurochem. 37: 1–13, 1981.PubMedCrossRefGoogle Scholar
  56. 56.
    Owen, D., Segal, M., Barker, J. A Ca-dependent chloride conductance in cultured mouse spinal cord neurons. Nature 311: 657–570, 1984.CrossRefGoogle Scholar
  57. 57.
    Prince, D. Electrophysiology of “epileptic neurons.” EEG Clin. Neurophysiol. 23: 83–84, 1967.Google Scholar
  58. 58.
    Prince, D. Electrophysiology of “epileptic neurons:” spike generation. EEG Clin. Neurophysiol. 26: 476–487, 1969.Google Scholar
  59. 59.
    Prince, D. Neurophysiology of epilepsy. Ann. Rev. Neurosci. 1: 395–415, 1978.CrossRefGoogle Scholar
  60. 60.
    Prince, D. Physiological mechanisms of focal epileptogenesis. Epilepsia 26: S3 - S14, 1985.PubMedCrossRefGoogle Scholar
  61. 61.
    Prince, D. Cellular mechanisms of interictal-ictal transitions. In: Mechanisms of Epileptogenesis: The Transition to Seizure, M. Dichter, (ed). New York: Plenum Press, 1988.Google Scholar
  62. 62.
    Prince, D. and Connors, B. Mechanisms of interictal epileptogenesis. Adv. Neurol. 44: 275–299, 1986.PubMedGoogle Scholar
  63. 63.
    Prince, D. and Futamachi, K. Intracellular recording in chronic focal epilepsy. Brain Res. 11: 681–684, 1968.PubMedCrossRefGoogle Scholar
  64. 64.
    Prince, D. and Futamachi, K. Intracellular recording from chronic focal epileptogenic foci in the monkey. EEG Clin. Neurophysiol. 2: 496–510, 1970.CrossRefGoogle Scholar
  65. 65.
    Prince, D. and Wilder, B. Cortical mechanisms in cortical epileptogenic foci–surround inhibition. Arch. Neurol. 16: 194–202, 1967.PubMedCrossRefGoogle Scholar
  66. 66.
    Ralston, B. The mechanism of transition of interictal spiking foci into ictal seizure discharge. EEG Clin. Neurophysiol. 10: 217–232, 1958.Google Scholar
  67. 67.
    Schwartzkroin, P. and Mathers, L. Physiological and morphological identification of a nonpyramidal hippocampal cell type. Brain Res. 157: 1–10, 1978.PubMedCrossRefGoogle Scholar
  68. 68.
    Schwartzkroin, P. and Stafstrom, C. Effects of EGTA on the calcium activated afterhyperpolarization in hippocampal CA3 pyramidal cells. Science 210: 1125 1126, 1981.Google Scholar
  69. 69.
    Somogyi, P., Hodgson, A., Smith, A., Nunzi, M., Gorio, A., Wu, J. Different populations of GAB Aergic neurons in the visual cortex and hippocampus of cat contain somatostatin or cholecystokinin-immunoreacti“-° material. J. Neurosci. 4: 2590–2603, 1984.PubMedGoogle Scholar
  70. 70.
    Takahashi, K., Kubota, K., Uno, M. Recurrent facilitation in cat pyramidal tract cells. J. Neurophysiol. 30: 22–34, 1967.Google Scholar
  71. 71.
    Thalmann, R., Peck, E., Ayala, G. Biphasic response of hippocampal pyramidal neurons to GABA. Neurosci Lett. 212: 319–324, 1981.CrossRefGoogle Scholar
  72. 72.
    Wong, R. and Prince, D. Participation of Ca spikes during intrinsic burst firing in hippocampal neurons. Brain Res. 159: 385–390, 1978.PubMedCrossRefGoogle Scholar
  73. 73.
    Wong, R., Prince, D., Basbaum, A. Intradendritic recordings in hippocampal neurons. Proc. Natl. Acad. Sci. 76: 986–990, 1979.PubMedCrossRefGoogle Scholar
  74. 74.
    Wong, R. and Watkins, D. Cellular factors influencing GABA response in hippocampal pyramidal cells. J. Neurophysiol. 48: 938–951, 1982.PubMedGoogle Scholar
  75. 75.
    Yaari, Y. and Jensen, M. Nonsynaptic mechanisms and interictal ictal transitions in the mammalian hippocampus. In: Dichter, M. (Ed). Mechansims of Epileptogenesis: The Transition to Seizure. New York: Plenum Press, 1988.Google Scholar
  76. 76.
    Yaari, Y., Selzer, M., Pincus, J. Phenytoin: mechanisms of its anticonvulsant action. Ann. Neurol. 20: 171–184, 1986.PubMedCrossRefGoogle Scholar
  77. 77.
    Yamamoto, C., Matsumoto, K., Takagi, M. Potentiation of excitatory postsynaptic potentials during and after repetitive stimulation in thin hippocampal sections. Exp. Brain Res. 38: 469–477, 1980.PubMedCrossRefGoogle Scholar
  78. 78.
    Zucker, R. Frequencey dependent changes in excitatory synaptic efficacy. In: Dichter M. (Ed). Mechansims of Epileptogenesis: The Transition to Seizure. New York: Plenum Press, 1988.Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Marc A. Dichter
    • 1
  1. 1.Department of NeurologyThe Graduate Hospital and The University of PennsylvaniaPhiladelphiaUSA

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