Synaptic Change in the Limbic System; Evidence from Studies Using Electrical Stimulation with and without Seizure Activity

  • G. V. Goddard
  • B. L. McNaughton
  • R. M. Douglas
  • C. A. Barnes


Agents with the potential to induce seizure-like discharge in the limbic system also have the potential to induce permanent alteration in that system. The most dramatic set of alterations have been called, collectively, the kindling effect (Goddard, McIntyre & Leech, 1969). Kindling is observed when an agent is applied mildly, repeatedly, usually once per day, and the response to that agent progressively changes until it includes a major clinical convulsion. If the treatments are discontinued, the system does not return to normal, but remains in a state of readiness even for a year or more. It will respond with convulsions to unusually low doses or gentle application of a wide range of the known epileptogenic agents (Pinel & Van Oot, 1976). When sufficient time is allowed between treatments, the sensitivity of the convulsive response may continue to increase; and, in some cases after many repetitions, the convulsions may recur spontaneously (Wada, Sato & Corcoran, 1974; Wada, Osawa & Mizoguchi, 1976; Pinel, Mucha & Phillips, 1975).


Spike Train Seizure Activity Limbic System Perforant Path Synaptic Change 
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. ADAMEC, R. Behavioral and epileptic determinants of predatory attack behavior in the cat. In: J.A. Wada (Ed.), Kindling, Raven Press, New York, 1976, 135–154.Google Scholar
  2. ALGER, B.E. & TEYLER, T.J. Long-term and short-term plasticity in the CA1, CA3 and dentate regions of the rat hippocampal slice. Brain Research, 1976, 110, 463–480.PubMedCrossRefGoogle Scholar
  3. ANDERSEN, P., SUNDBERG, S.H. & SVEEN, O. Specific long-lasting potentiation of synaptic transmission in hippocampal slices. Nature 1977, 266 736–737.Google Scholar
  4. BARNES, C.A. Memory deficits associated with senescence: A neuro-physiological and behavioral study in the rat, Unpublished Doctoral Dissertation, Carleton University, 1977.Google Scholar
  5. BLISS, T.V.P. & GARDNER-MEDWIN, A.R. Long-lasting potentiation of synaptic transmission in the dentate area of unanesthetized rabbit following stimulation of the perforant path. Journal of Physiology, 1973, 232, 357–374.PubMedGoogle Scholar
  6. BLISS, T.V.P. & LOMO, T. Long-lasting potentiation of synaptic transmission on the dentate area of the anaesthetized rabbit following stimulation of the perforant path. Journal of Physiology, 1973, 232, 331–356.PubMedGoogle Scholar
  7. BURNHAM, W.M. Primary and “transfer” seizure development in the kindled rat. In: J.A. Wada (Ed.), Kindling, Raven Press, New York, 1976, 61–84.Google Scholar
  8. CALVIN, W.H. & SYPERT, G.W. Cerebral cortex neurons with extra spikes: A normal substrate for epileptic discharges? Brain Research 1975, 83, 498–503.Google Scholar
  9. DEADWYLER, S.A., DUDEK, F.E., COTMAN, C.W. & LYNCH, G. Intracellular responses of rat dentate granule cells in vitro: Post-tetanic potentiation to perforant path stimulation. Brain Research, 1975, 88, 80–85.Google Scholar
  10. DOUGLAS, R.M. Long-lasting synaptic potentiation in the rat dentate gyrus following brief high frequency stimulation. Brain Research, 1977, 126, 361–365.PubMedCrossRefGoogle Scholar
  11. DOUGLAS, R.M. & GODDARD, G.V. Long-term potentiation of the perforant path-granule cell synapse in the rat hippocampus. Brain Research, 1975, 86, 205–215.PubMedCrossRefGoogle Scholar
  12. DUDEK, F.E, DEADWYLER, S., COTMAN, C.E1 LYNCH, G. Intracellular responses from granule cell layer in slices of rat hippocampus: siology, 1976, 39,Perforant path synapse. Journal of Neuroph 384–393.Google Scholar
  13. GODDARD, G.V. Development of epileptic seizures through brain stimulation at low intensity. Nature 1967, 214 1020–1021Google Scholar
  14. GODDARD, G.V. & DOUGLAS, R.M. Does the engram of kindling model the engram of normal long term memory? In: J.A. Wada (Ed.), Kindling Raven Press, New York, 1976, 1–18Google Scholar
  15. GODDARD, G.V. & MCINTYRE, D.C. Some properties of a lasting epilep-togenic trace kindled by repeated electrical stimulation of the amygdala in mammals. In: L.V. Laitinen and K.E. Livingston (Eds.), Surgical Apsroaches in Psychiatry, University Park Press, Baltimore, 1972, 109–115.Google Scholar
  16. GODDARD, G.V., MCINTYRE, D.C. E1 LEECH, C.K. A permanent change in brain function resulting from daily electrical stimulation. Experimental Neurology, 1969, 25, 295–330.PubMedCrossRefGoogle Scholar
  17. HEBB, D.O. The Organization of Behavior, a Neuropsychological Theory. John Wiley & Sons, New York, 1949.Google Scholar
  18. HJORTH-SIMONSEN, A. Projection of the lateral part of the entorhinal area to the hippocampus and fascia dentata. Journal of Comparative Neurology, 1972, 146, 219–232.CrossRefGoogle Scholar
  19. KANDEL, E.R. & SPENCER, W.A. Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing. Journal of Neurophysiology, 1961, 24, 243–259.PubMedGoogle Scholar
  20. LEECH, C.K. Rate of development of electrically kindled convulsions compared to audiogenic seizures and learning ability in six inbred mouse strains. Unpublished Doctoral Dissertation, The University of Waterloo, 1972.Google Scholar
  21. LOMO, T. Patterns of activation in a monosynaptic cortical pathway. The perforant path input to the dentate area of the hippocampal formation. Experimental Brain Research 1971, 12, 18–45Google Scholar
  22. MAGLEBY, K. & ZENGEL, J. A quantitative description of tetanic and post-tetanic potentiation of transmitter release at the frog neuromuscular junction. Journal of Physiology, 1975, 245, 183–208.PubMedGoogle Scholar
  23. MAGLEBY, K.L. & ZENGEL, J.E. Augmentation: A process that acts to increase transmitter release at the frog neuromuscular junction. Journal of Physiology, 1976, 257, 449–470.PubMedGoogle Scholar
  24. MASON, C.R. & COOPER, R.M. A permanent change in convulsive threshold in normal and brain-damaged rats with repeated small doses of pentylenetetrazol. Epilepsia 1972, 13, 663–674Google Scholar
  25. MCINTYRE, D.C. 8 MOLINO, A. Amygdala lesions and CER learning: Long-term effect of kindling. Physiology and Behavior, 1972, 8, 1055–1058.PubMedCrossRefGoogle Scholar
  26. MCNAUGHTON, B.L. Dissociation of short-and long-lasting modifica-tion of synaptic efficacy at the terminals of the perforant path. Seventh Annual Meeting of the Society for Neuroscience, Anaheim, California, 1977. ( Abstract).Google Scholar
  27. MCNAUGHTON, B. & BARNES, C. Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat. Journal of Comparative Neurology, 1977, 175, 439–454.PubMedCrossRefGoogle Scholar
  28. MCNAUGHTON, B.L., DOUGLAS, R.M. 8 GODDARD, G.V. Synaptic enhancement in fascia dentata: Cooperativity among co-active afferents. Under editorial review for publication, 1978Google Scholar
  29. MORRELL, F. Goddard’s kindling phenomenon: A new model of the “mirror focus”. In: H.C. Sabelli (Ed.), Chemical Modulation of Brain Function Raven Press, New York, 1973, 207–223Google Scholar
  30. MORRELL, F., TSURU, N., HOEPPNER, T.J., MORGAN, D. & HARRISON, W.H. Secondary epileptogenesis in frog forebrain: Effect of inhi-bition of protein synthesis. In: J.A. Wada (Ed.), Kindling, Raven Press, New York, 1976, 41–60.Google Scholar
  31. O’KEEFE, J. & NADEL, L. The Hippocampus as a Cognitive Map Oxford University Press, in press, 1978.Google Scholar
  32. PINEL, J.P.J., MUCHA, R.F. 8 PHILLIPS, A.G. Spontaneous seizures generated in rats by kindling: a preliminary report. Physiological Psychology, 1975, Vol. 3, 127–129.CrossRefGoogle Scholar
  33. PINEL, J.P.J. & VAN 00T, P.H. Generality of the kindling phenomenon: Some clinical implications. In: J.A. Wada (Ed.), Kindling, 1976, 155–171.Google Scholar
  34. POST, R.M., KOPANDA, R.T. & BLACK, K.E. Progressive effects of cocaine on behavior and central amine metabolism in rhesus-monkeys–relationship to kindling and psychosis. Biological Psychiatry, 1976, 11, 403–419.Google Scholar
  35. RACINE, R.J. Modification of seizure activity by electrical stimulation: I. After-discharge threshold. Electroencephalography and Clinical Neurophysiology, 1972(a), 32, 269–279.Google Scholar
  36. RACINE, R.J. Modification of seizure activity by electrical stimulation: II. Motor seizure. Electroencephalography and Clinical Neurophysiology, 1972(b), 32, 281–294.Google Scholar
  37. RACINE, R.J. Modification of seizure activity by electrical stimulation: Cortical areas. Electroencephalography and Clinical Neurophysiology, 1975, 38, 1–12.CrossRefGoogle Scholar
  38. RACINE, R., GARTNER, J. 6 BURNHAM, W. Epileptiform activity and neural plasticity in limbic structures. Brain Research 1972, Vol. 47, 262–268.PubMedCrossRefGoogle Scholar
  39. RACINE, R., NEWBERRY, F. 6 BURNHAM, W.M. Post-activation potentiation and kindling phenomenon. Electroencephalography and Clinical Neurophysiology, 1975, 39, 261–271.PubMedCrossRefGoogle Scholar
  40. RACINE, R. 6 ?AIDE, J. A further investigation into the mechanisms underlying the kindling phenomenon (this volume).Google Scholar
  41. RANCK, J.13., Jr. Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. Part 1. Behavioural correlates and firing repertories. Experimental Neurology, 1973, 41, 461–531.Google Scholar
  42. SINGER, W., TRETTER, F. & CYNADER, M. The effect of reticular stim-ulation on spontaneous and evoked activity in the cat visual cortex. Brain Research 1976, 102 71–90Google Scholar
  43. STEWARD, O. 6 SCOVILLE, S.A. Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat. Journal of Comparative Neurology 1976, 169 347–370Google Scholar
  44. TANAKA, A. Progressive changes of behavioral and electroencephalo-graphic responses to daily amygdaloid stimulation in rabbits. Fukuoka Acta Medica 1972, 63, 152–164Google Scholar
  45. TANAKA, T., LANGE, H. 6 NAQUET, R. Sleep, subcortical stimulation and kindling in the cat. In: J.A. Wada (Ed_), Kindling, Raven Press, New York, 1976, 117–133.Google Scholar
  46. VAN HARREVELD, A. 6 FIFKOVA, E. Swelling of dendritic spines in the fascia dentata after stimulation of the perforant fibers as a mechanism of post-tetanic potentiation. Experimental Neurology, 1975, 49, 736–749.Google Scholar
  47. VOSU, H. 6 WISE, R.A. Cholinergic seizure kindling in the rat: Comparison of caudate, amygdala and hippocamous. Behavioral Biology, 1975, 13, 491–495.PubMedCrossRefGoogle Scholar
  48. WADA, J.A., OSAWA, T. & MIZOGUCHI, T. Recurrent spontaneous seizure state induced by prefrontal kindling in Seregalese baboons, Papio papio. In: J.A. Wada (Ed.), Kindling, Raven Press, New York, 1976, 173–202.Google Scholar
  49. WADA, J.A. E1 SATO, M. Generalized convulsive seizure induced by daily electrical stimulation of the amygdala in cats: Correlative electrographic and behavioral features. Neurology, 1974, 24, 565–574.PubMedCrossRefGoogle Scholar
  50. WADA, J.A. & SATO, M. The generalized convulsive seizure state induced by daily electrical stimulation of the amygdala in split brain cats. Epilepsia, 1975, 16, 417–430.PubMedCrossRefGoogle Scholar
  51. WALTERS, D.J. Sporadic interictal discharges in kindled epilepto-genic foci. Unpublished M.A. Thesis, Dalhousie University, 1970.Google Scholar
  52. WARD, A.A., Jr. The epileptic neuron: Chronic foci in animals and man. In: H. Jasper, A. Ward and A. Pope (Eds.), Basic Mechanisms of the Epilepsies, Little, Brown and Company, Boston, 1969, 263–288.Google Scholar

Copyright information

© Springer Science+Business Media New York 1978

Authors and Affiliations

  • G. V. Goddard
  • B. L. McNaughton
  • R. M. Douglas
  • C. A. Barnes

There are no affiliations available

Personalised recommendations