Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1993 Jan 1;90(1):257–261. doi: 10.1073/pnas.90.1.257

Reversible loss of dendritic spines and altered excitability after chronic epilepsy in hippocampal slice cultures.

M Müller 1, B H Gähwiler 1, L Rietschin 1, S M Thompson 1
PMCID: PMC45639  PMID: 8093558

Abstract

The morphological and functional consequences of epileptic activity were investigated by applying the convulsants bicuculline and/or picrotoxin to mature rat hippocampal slice cultures. After 3 days, some cells in all hippocampal subfields showed signs of degeneration, including swollen somata, vacuolation, and dendritic deformities, whereas others displayed only a massive reduction in the number of their dendritic spines. Intracellular recordings from CA3 pyramidal cells revealed a decrease in the amplitude of evoked excitatory synaptic potentials. gamma-Aminobutyric acid-releasing interneurons and inhibitory synaptic potentials were unaffected. Seven days after withdrawal of convulsants, remaining cells possessed a normal number of dendritic spines, thus demonstrating a considerable capacity for recovery. The pathological changes induced by convulsants are similar to those found in the hippocampi of human epileptics, suggesting that they are a consequence, rather than a cause, of epilepsy.

Full text

PDF
257

Images in this article

258Image
on p.258
259Image
on p.259
260Image
on p.260

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Babb T. L., Pretorius J. K., Kupfer W. R., Crandall P. H. Glutamate decarboxylase-immunoreactive neurons are preserved in human epileptic hippocampus. J Neurosci. 1989 Jul;9(7):2562–2574. doi: 10.1523/JNEUROSCI.09-07-02562.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Calverley R. K., Jones D. G. Contributions of dendritic spines and perforated synapses to synaptic plasticity. Brain Res Brain Res Rev. 1990 Sep-Dec;15(3):215–249. doi: 10.1016/0165-0173(90)90002-6. [DOI] [PubMed] [Google Scholar]
  3. Choi D. W., Rothman S. M. The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci. 1990;13:171–182. doi: 10.1146/annurev.ne.13.030190.001131. [DOI] [PubMed] [Google Scholar]
  4. Corsellis J. A., Bruton C. J. Neuropathology of status epilepticus in humans. Adv Neurol. 1983;34:129–139. [PubMed] [Google Scholar]
  5. Davies C. H., Davies S. N., Collingridge G. L. Paired-pulse depression of monosynaptic GABA-mediated inhibitory postsynaptic responses in rat hippocampus. J Physiol. 1990 May;424:513–531. doi: 10.1113/jphysiol.1990.sp018080. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dichter M. A., Ayala G. F. Cellular mechanisms of epilepsy: a status report. Science. 1987 Jul 10;237(4811):157–164. doi: 10.1126/science.3037700. [DOI] [PubMed] [Google Scholar]
  7. Franck J. E., Kunkel D. D., Baskin D. G., Schwartzkroin P. A. Inhibition in kainate-lesioned hyperexcitable hippocampi: physiologic, autoradiographic, and immunocytochemical observations. J Neurosci. 1988 Jun;8(6):1991–2002. doi: 10.1523/JNEUROSCI.08-06-01991.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frotscher M., Gähwiler B. H. Synaptic organization of intracellularly stained CA3 pyramidal neurons in slice cultures of rat hippocampus. Neuroscience. 1988 Feb;24(2):541–551. doi: 10.1016/0306-4522(88)90348-x. [DOI] [PubMed] [Google Scholar]
  9. Geinisman Y., Morrell F., deToledo-Morrell L. Increase in the relative proportion of perforated axospinous synapses following hippocampal kindling is specific for the synaptic field of stimulated axons. Brain Res. 1990 Jan 22;507(2):325–331. doi: 10.1016/0006-8993(90)90291-i. [DOI] [PubMed] [Google Scholar]
  10. Gähwiler B. H. Development of the hippocampus in vitro: cell types, synapses and receptors. Neuroscience. 1984 Apr;11(4):751–760. doi: 10.1016/0306-4522(84)90192-1. [DOI] [PubMed] [Google Scholar]
  11. Isokawa M., Levesque M. F. Increased NMDA responses and dendritic degeneration in human epileptic hippocampal neurons in slices. Neurosci Lett. 1991 Nov 11;132(2):212–216. doi: 10.1016/0304-3940(91)90304-c. [DOI] [PubMed] [Google Scholar]
  12. Kamphuis W., Wadman W. J., Buijs R. M., Lopes da Silva F. H. Decrease in number of hippocampal gamma-aminobutyric acid (GABA) immunoreactive cells in the rat kindling model of epilepsy. Exp Brain Res. 1986;64(3):491–495. doi: 10.1007/BF00340486. [DOI] [PubMed] [Google Scholar]
  13. Kapur J., Stringer J. L., Lothman E. W. Evidence that repetitive seizures in the hippocampus cause a lasting reduction of GABAergic inhibition. J Neurophysiol. 1989 Feb;61(2):417–426. doi: 10.1152/jn.1989.61.2.417. [DOI] [PubMed] [Google Scholar]
  14. Mattson M. P., Dou P., Kater S. B. Outgrowth-regulating actions of glutamate in isolated hippocampal pyramidal neurons. J Neurosci. 1988 Jun;8(6):2087–2100. doi: 10.1523/JNEUROSCI.08-06-02087.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Meldrum B. Possible therapeutic applications of antagonists of excitatory amino acid neurotransmitters. Clin Sci (Lond) 1985 Feb;68(2):113–122. doi: 10.1042/cs0680113. [DOI] [PubMed] [Google Scholar]
  16. Paul L. A., Scheibel A. B. Structural substrates of epilepsy. Adv Neurol. 1986;44:775–786. [PubMed] [Google Scholar]
  17. Popov V. I., Bocharova L. S., Bragin A. G. Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation. Neuroscience. 1992;48(1):45–51. doi: 10.1016/0306-4522(92)90336-z. [DOI] [PubMed] [Google Scholar]
  18. Ribak C. E., Bradburne R. M., Harris A. B. A preferential loss of GABAergic, symmetric synapses in epileptic foci: a quantitative ultrastructural analysis of monkey neocortex. J Neurosci. 1982 Dec;2(12):1725–1735. doi: 10.1523/JNEUROSCI.02-12-01725.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ribak C. E., Reiffenstein R. J. Selective inhibitory synapse loss in chronic cortical slabs: a morphological basis for epileptic susceptibility. Can J Physiol Pharmacol. 1982 Jun;60(6):864–870. doi: 10.1139/y82-122. [DOI] [PubMed] [Google Scholar]
  20. Scheibel M. E., Crandall P. H., Scheibel A. B. The hippocampal-dentate complex in temporal lobe epilepsy. A Golgi study. Epilepsia. 1974 Mar;15(1):55–80. doi: 10.1111/j.1528-1157.1974.tb03997.x. [DOI] [PubMed] [Google Scholar]
  21. Sloviter R. S. Decreased hippocampal inhibition and a selective loss of interneurons in experimental epilepsy. Science. 1987 Jan 2;235(4784):73–76. doi: 10.1126/science.2879352. [DOI] [PubMed] [Google Scholar]
  22. Sloviter R. S. Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the "dormant basket cell" hypothesis and its possible relevance to temporal lobe epilepsy. Hippocampus. 1991 Jan;1(1):41–66. doi: 10.1002/hipo.450010106. [DOI] [PubMed] [Google Scholar]
  23. Stelzer A., Slater N. T., ten Bruggencate G. Activation of NMDA receptors blocks GABAergic inhibition in an in vitro model of epilepsy. Nature. 1987 Apr 16;326(6114):698–701. doi: 10.1038/326698a0. [DOI] [PubMed] [Google Scholar]
  24. Streit Peter, Thompson Scott M., Gähwiler Beat H. Anatomical and Physiological Properties of GABAergic Neurotransmission in Organotypic Slice Cultures of Rat Hippocampus. Eur J Neurosci. 1989 Jan;1(6):603–615. doi: 10.1111/j.1460-9568.1989.tb00366.x. [DOI] [PubMed] [Google Scholar]
  25. Thompson S. M., Gähwiler B. H. Comparison of the actions of baclofen at pre- and postsynaptic receptors in the rat hippocampus in vitro. J Physiol. 1992;451:329–345. doi: 10.1113/jphysiol.1992.sp019167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Valverde F. Rate and extent of recovery from dark rearing in the visual cortex of the mouse. Brain Res. 1971 Oct 8;33(1):1–11. doi: 10.1016/0006-8993(71)90302-7. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES