Neurochemical Research

, Volume 16, Issue 3, pp 251–262 | Cite as

Electrophysiology of GABA-mediated synaptic transmission and possible roles in epilepsy

  • Jeffrey G. Tasker
  • F. Edward Dudek
Original Articles

Abstract

Epileptogenic conditions come about from a disequilibrium between excitatory and inhibitory mechanisms, creating a state of neuronal hypersynchrony. From experimental studies in animal models of epilepsy it appears that several mechanisms, alone or in combination, could be responsible for this imbalance. An alteration of GABA-mediated inhibition has long been considered to be one of the most likely candidates. We review recent data on the synaptic physiology of GABA-mediated inhibition, with emphasis on GABAA and GABAB receptors and their conductances. We describe the integrative role of GABAergic local-circuit neurons in the normal control of recurrent excitation. We then discuss possible alterations in GABAA-mediated inhibition in two chronic animal models of epilepsy, the kindled rat and the kainate-treated rat. Finally, we review studies on GABA inhibition in human epileptic cortex resected for the treatment of intractable epilepsy.

Key Words

Seizure burst inhibition hippocampus neocortex slice preparation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Roberts, E. 1986. Failure of GABAergic inhibition: a key to local and global seizures. Pages 319–341,in Delgado-Escueta, A. V., Ward, A. A., Jr., Woodbury, D. M. and Porter, R. J. (eds.), Basic Mechanisms of the Epilepsies: Molecular and Cellular Approaches, in the series Advances in Neurology, Raven Press, New York.Google Scholar
  2. 2.
    Dichter, M. A. and Ayala, G. F. 1987. Cellular mechanisms of epilepsy: a status report. Science 237:157–164.PubMedGoogle Scholar
  3. 3.
    Dudek, F. E., Snow, R. W., and Taylor, C. P. 1986. Role of electrical interactions in synchronization of epileptiform bursts. Pages 593–617,in Delgado-Escueta, A. V., Ward, A. A., Jr., Woodbury, D. M. and Porter, R. J. (eds.), Basic Mechanisms of the Epilepsies: Molecular and Cellular Approaches, in the series Advances in Neurology, Raven Press, New York.Google Scholar
  4. 4.
    Avoli, M. 1988. GABAergic mechanisms and epileptic discharges. Pages 187–205,in Avoli, M., Reader, T. A., Dykes, R. W. and Gloor, P. A. (eds.), Neurotransmitters and Cortical Function: From Molecules to Mind, Plenum Press, New York.Google Scholar
  5. 5.
    Taylor, C. P. 1988. How do seizures begin? Clues from hippocampal slices. Trends in Neurosciences 11:375–378.PubMedGoogle Scholar
  6. 6.
    Jefferys, J. G. R. 1990. Basic mechanisms of focal epilepsies. Exp. Physiol. 75:127–162.PubMedGoogle Scholar
  7. 7.
    Nicoll, R. A. 1988. The coupling of neurotransmitter receptors to ion channels in the brain. Science 241:545–551.PubMedGoogle Scholar
  8. 8.
    Nicoll, R. A., Malenka, R. C., and Kauer, J. A. 1990. Functional comparison of neurotransmitter receptor subtypes in mammalian central nervous system. Physiol. Rev. 70:513–565.PubMedGoogle Scholar
  9. 9.
    Alger, B. E., and Nicoll, R. A. 1982. Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studiedin vitro. J. Physiol. 328:125–141.PubMedGoogle Scholar
  10. 10.
    Alger, B. E., and Nicoll, R. A. 1982. Feed-forward dendritic inhibition in rat hippocampal pyramidal cells studiedin vitro. J. Physiol. 328:105–123.PubMedGoogle Scholar
  11. 11.
    Connors, B. W., Malenka, R. C., and Silva, L. R. 1988. Two inhibitory postsynaptic potentials, and GABAA and GABAB receptor-mediated responses in neocortex of rat and cat. J. Physiol. 406:443–468.PubMedGoogle Scholar
  12. 12.
    Dingledine, R., and Gjerstad, L. 1980. Reduced inhibition during epileptiform activity in the in vitro hippocampal slice. J. Physiol. 305:297–313.PubMedGoogle Scholar
  13. 13.
    Rutecki, P. A., Lebeda, F. J., and Johnston, D. 1987. 4-Aminopyridine produces epileptiform activity in hippocampus and enhances synaptic excitation and inhibition. J. Neurophysiol. 57:1911–1924.PubMedGoogle Scholar
  14. 14.
    Perreault, P., and Avoli, M. 1989. Effects of low concentrations of 4-aminopyridine on CA1 pyramidal cells of the hippocampus. J. Neurophysiol. 61:953–970.PubMedGoogle Scholar
  15. 15.
    Houser, C. R. 1991. GABA neurons in seizure disorders: a review of immunocytochemical studies. Neurochem. Res. 16:295–308.PubMedGoogle Scholar
  16. 16.
    MacVicar, B. A., and Dudek, F. E. 1980. Local synaptic circuits in rat hippocampus: interactions between pyramidal cells. Brain Res. 184:220–223.PubMedGoogle Scholar
  17. 17.
    Knowles, W. D., and Schwartzkroin, P. A. 1981. Local circuit synaptic interactions in hippocampal brain slices. J. Neurosci. 1:318–322.PubMedGoogle Scholar
  18. 18.
    Miles, R. and Wong, R. K. S. 1984. Unitary inhibitory synaptic potentials in the guinea-pig hippocampusin vitro. J. Physiol. 356:97–113.PubMedGoogle Scholar
  19. 19.
    Miles, R. and Wong, R. K. S. 1986. Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus. J. Physiol. 373:397–418.PubMedGoogle Scholar
  20. 20.
    Thomson, A. M., Girdlestone, D., and West, D. C. 1988. Voltage-dependent currents prolong single-axon postsynaptic potentials in layer III pyramidal neurons in rat neocortical slices. J. Neurophysiol. 60:1896–1907.PubMedGoogle Scholar
  21. 21.
    Miles, R., and Wong, R. K. S. 1987. Inhibitory control of local excitatory circuits in the guinea-pig hippocampus. J. Physiol. 388:611–629.PubMedGoogle Scholar
  22. 22.
    Christian, E. P., and Dudek, F. E. 1988. Characteristics of local excitatory circuits studied with glutamate microapplication in the CA3 area of rat hippocampal slices. J. Neurophysiol. 59:90–109.PubMedGoogle Scholar
  23. 23.
    Traub, R. D., and Wong, R. K. S. 1982. Cellular mechanism of neuronal synchronization in epilepsy. Science 216:745–747.PubMedGoogle Scholar
  24. 24.
    Schwartzkroin, P. A., and Prince, D. A. 1980. Changes in excitatory and inhibitory synaptic potentials leading to epileptogenic activity. Brain Res. 183:61–76.PubMedGoogle Scholar
  25. 25.
    Johnston, D., and Brown, T. H. 1981. Giant synaptic potential hypothesis for epileptiform activity. Science 211:294–297.PubMedGoogle Scholar
  26. 26.
    Chagnac-Amitai, Y., and Connors, B. W. 1989. Horizontal spread of synchronized activity in neocortex and its control by GABA-mediated inhibition. J. Neurophysiol. 61:747–758.PubMedGoogle Scholar
  27. 27.
    Chagnac-Amitai, Y., and Connors, B. W. 1989. Synchronized excitation and inhibition driven by intrinsically bursting neurons in neocortex. J. Neurophysiol. 62:1149–1162.PubMedGoogle Scholar
  28. 28.
    Chervin, R. D., Pierce, P. A., and Connors, B. W. 1988. Periodicity and directionality in the propagation of epileptiform discharges across neocortex. J. Neurophysiol. 60:1695–1713.PubMedGoogle Scholar
  29. 29.
    Huguenard, J. R., and Alger, B. E. 1986. Whole-cell voltageclamp study of the fading of GABA-activated currents in acutely dissociated hippocampal neurons. J. Neurophysiol. 56:1–18.PubMedGoogle Scholar
  30. 30.
    Stelzer, A., Slater, N. T., and Bruggencate, G. T. 1987. Activation of NMDA receptors blocks GABAergic inhibition in anin vitro model of epilepsy. Nature 326:698–701.PubMedGoogle Scholar
  31. 31.
    Oliver, M. W., and Miller, J. J. 1985. Alteration of inhibitory processes in the dentate gyrus following kindling-induced epilepsy. Exp. Brain Res. 57:443–447.PubMedGoogle Scholar
  32. 32.
    King, G. L., Dingledine, R., Giacchino, J. L., and McNamara, J. O. 1985. Abnormal neuronal excitability in hippocampal slices from kindled rats. J. Neurophysiol. 54:1295–1304.PubMedGoogle Scholar
  33. 33.
    Maru, E., and Goddard, G. V. 1987. Alteration in dentate neuronal activities associated with perforant path kindling. III. Enhancement of synaptic inhibition. Exp. Neurol. 96:46–60.PubMedGoogle Scholar
  34. 34.
    Kapur, J., Michelson, H. B., Buterbaugh, G. G., and Lothman, E. W. 1989. Evidence for a chronic loss of inhibition in the hippocampus after kindling: electrophysiological studies. Epilepsy. Res. 4:90–99.PubMedGoogle Scholar
  35. 35.
    Fisher, R. S., and Alger, B. E. 1984. Electrophysiological mechanisms of kainic acid-induced epileptiform activity in the rat hippocampal slice. J. Neurosci. 4:1312–1323.PubMedGoogle Scholar
  36. 36.
    Ben-Ari, Y., and Gho, M. 1988. Long-lasting modification of the synaptic properties of rat CA3 hippocampal neurones induced by kainic acid. J. Physiol. 404:365–384.PubMedGoogle Scholar
  37. 37.
    Franck, J. E., and Schwartzkroin, P. A. 1985. Do kainate-lesioned hippocampi become epileptogenic?. Brain Res. 329:309–313.PubMedGoogle Scholar
  38. 38.
    Ashwood, T. J., and Wheal, H. V. 1986. Loss of inhibition in the CA1 region of the kainic acid lesioned hippocampus is not associated with changes in postsynaptic responses to GABA. Brain Res. 367:390–394.PubMedGoogle Scholar
  39. 39.
    McCormick, D. A. 1989. GABA as an inhibitory neurotransmitter in human cerebral cortex. J. Neurophysiol. 62:1018–1027.PubMedGoogle Scholar
  40. 40.
    Tasker, J. G., Cronin, J., Peacock, W. J., and Dudek, F. E. 1989. Local circuits and the spread of epileptiform activity in neocortical slices from pediatric patients with intractable epilepsy. Epilepsia 30:680.Google Scholar
  41. 41.
    Wuarin, J.-P., Kim, Y. I., Cepeda, C., Tasker, J. G., Walsh, J. P., Peacock, W. J., Buchwald, N. A., and Dudek, F. E. 1990 Synaptic transmission in human neocortex removed for treatment of intractable pediatric epilepsy. Ann. Neurol. 28:503–511.PubMedGoogle Scholar
  42. 42.
    Lloyd, K. G., Bossi, L., Morselli, P. L., Munari, C., Rougier, M., and Loiseau, H. 1986. Alterations of GABA-mediated synaptic transmission in human epilepsy. Pages 1033–1044,in Delgado-Escueta, A. V., Ward, A. A., Jr., Woodbury, D.M. and Porter, R.J. (eds.), Basic Mechanisms of the Epilepsies: Molecular and Cellular Approaches, in the series Advances in Neurology, Raven Press, New York.Google Scholar
  43. 43.
    Babb, T. L., Pretorius, J. K., Kupfer, W. R., and Crandall, P. H. 1989. Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus. J. Neurosci. 9:2562–2574.PubMedGoogle Scholar
  44. 44.
    Isokawa-Akesson, M., Wilson, C. L., and Babb, T. L. 1989. Inhibition in synchronously firing human hippocampal neurons. Epilepsy. Res. 3:236–247.PubMedGoogle Scholar
  45. 45.
    Prince, D. A., and Wong, R. K. S. 1981. Human epileptic neurons studied in vitro. Brain Res. 210:323–333.PubMedGoogle Scholar
  46. 46.
    Prince, D. A. 1983. Chronic epileptogenesis studied in vitro. Ann. Neurol. 14:595.PubMedGoogle Scholar
  47. 47.
    Schwartzkroin, P. A. 1983. Chronic epileptogenesis studied in vitro: reply. Ann. Neurol. 14:596.PubMedGoogle Scholar
  48. 48.
    Schwartzkorin, P. A., Turner, D. A., Knowles, W. D., and Wyler, A. R. 1983. Studies of human and monkey “epileptic” neocortex in the in vitro slice preparation. Ann. Neurol. 13:249–257.PubMedGoogle Scholar
  49. 49.
    Schwartzkroin, P. A., and Knowles, W. D. 1984. Intracellular study of human epileptic cortex: in vitro maintenance of epileptiform activity? Science 223:709–712.PubMedGoogle Scholar
  50. 50.
    Schwartzkroin, P. A., and Haglund, M. M. 1986. Spontaneous rhythmic synchronous activity in epileptic human and normal monkey temporal lobe. Epilepsia 27:523–533.PubMedGoogle Scholar
  51. 51.
    Reid, S. A., and Palovcik, R. A. 1989. Spontaneous epileptiform discharges in isolated human cortical slices from epileptic patients. Neurosci. Lett. 98:200–204.PubMedGoogle Scholar
  52. 52.
    Masukawa, L. M., Higashima, M., Kim, J. H., and Spencer, D. D. 1989. Epileptiform discharges evoked in hippocampal brain slices from epileptic patients. Brain Res. 493:168–174.PubMedGoogle Scholar
  53. 53.
    Avoli, M., and Oliver, A. 1989. Electrophysiological properties and synaptic responses in the deep layers of the human epileptogenic neocortex in vitro. J. Neurophysiol. 61:589–606.PubMedGoogle Scholar
  54. 54.
    Strowbridge, B. W., Masukawa, L. M., Spencer, D. D., and Shepherd, G. M. Hyperexcitability associated with localizable lesions in epileptic patients. Brain Res. (in press)Google Scholar
  55. 55.
    Tasker, J. G., Obenaus, A., Peacock, W. J., and Dudek, F. E. 1990. Analysis of synaptic inhibition in neocortical slices from pediatric patients with intractable epilepsy. Epilepsia 31:691.Google Scholar
  56. 56.
    Dudek, F. E., and Christian, E. P. 1987. Inhibition, local excitatory interactions and synchronization of epileptiform activity in hippocampal slices. J. Mind Behav. 8:619–634.Google Scholar
  57. 57.
    Miles, R., Traub, R. D., and Wong, R. K. S. 1988. Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus. J. Neurophysiol. 60:1481–1496.PubMedGoogle Scholar
  58. 58.
    Ashwood, T. J., and Wheal, H. V. 1987. The expression of N-methyl-D-aspartate-receptor-mediated component during epileptiform synaptic activity in the hippocampus. Br. J. Pharmac. 91:815–822.Google Scholar

Copyright information

© Plenum Publishing Corporation 1991

Authors and Affiliations

  • Jeffrey G. Tasker
    • 1
  • F. Edward Dudek
    • 1
  1. 1.Mental Retardation Research Center and Brain Research InstituteUCLA School of MedicineLos Angeles

Personalised recommendations