GABA A receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex

M. D'Antuono, J. Louvel, R. Köhling, D. Mattia, A. Bernasconi, A. Olivier, B. Turak, A. Devaux, R. Pumain, M. Avoli

Research output: Contribution to journalArticle

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Abstract

Patients with Taylor's type focal cortical dysplasia (FCD) present with seizures that are often medically intractable. Here, we attempted to identify the cellular and pharmacological mechanisms responsible for this epileptogenic state by using field potential and K +-selective recordings in neocortical slices obtained from epileptic patients with FCD and, for purposes of comparison, with mesial temporal lobe epilepsy (MTLE), an epileptic disorder that, at least in the neocortex, is not characterized by any obvious structural aberration of neuronal networks. Spontaneous epileptiform activity was induced in vitro by applying 4-aminopyridine (4AP)-containing medium. Under these conditions, we could identify in FCD slices a close temporal relationship between ictal activity onset and the occurrence of slow interictal-like events that were mainly contributed by GABA A receptor activation. We also found that in FCD slices, pharmacological procedures capable of decreasing or increasing GABA A receptor function abolished or potentiated ictal discharges, respectively. In addition, the initiation of ictal events in FCD tissue coincided with the occurrence of GABA A receptor-dependent interictal events leading to [K +] o elevations that were larger than those seen during the interictal period. Finally, by testing the effects induced by baclofen on epileptiform events generated by FCD and MTLE slices, we discovered that the function of GABA B receptors (presumably located at presynaptic inhibitory terminals) was markedly decreased in FCD tissue. Thus, epileptiform synchronization leading to in vitro ictal activity in the human FCD tissue is initiated by a synchronizing mechanism that paradoxically relies on GABA A receptor activation causing sizeable increases in [K +] o. This mechanism may be facilitated by the decreased ability of GABA B receptors to control GABA release from interneuron terminals.

Original languageEnglish
Pages (from-to)1626-1640
Number of pages15
JournalBrain
Volume127
Issue number7
DOIs
Publication statusPublished - Jul 2004

Fingerprint

Malformations of Cortical Development
GABA-A Receptors
Stroke
GABA-B Receptors
Temporal Lobe Epilepsy
Pharmacology
4-Aminopyridine
Baclofen
Neocortex
Presynaptic Terminals
Interneurons
Human Activities
gamma-Aminobutyric Acid
Seizures

Keywords

  • [K ] homeostasis
  • Baclofen
  • Epileptiform synchronization
  • Focal cortical dysplasia
  • GABA receptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

D'Antuono, M., Louvel, J., Köhling, R., Mattia, D., Bernasconi, A., Olivier, A., ... Avoli, M. (2004). GABA A receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex. Brain, 127(7), 1626-1640. https://doi.org/10.1093/brain/awh181

GABA A receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex. / D'Antuono, M.; Louvel, J.; Köhling, R.; Mattia, D.; Bernasconi, A.; Olivier, A.; Turak, B.; Devaux, A.; Pumain, R.; Avoli, M.

In: Brain, Vol. 127, No. 7, 07.2004, p. 1626-1640.

Research output: Contribution to journalArticle

D'Antuono, M, Louvel, J, Köhling, R, Mattia, D, Bernasconi, A, Olivier, A, Turak, B, Devaux, A, Pumain, R & Avoli, M 2004, 'GABA A receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex', Brain, vol. 127, no. 7, pp. 1626-1640. https://doi.org/10.1093/brain/awh181
D'Antuono M, Louvel J, Köhling R, Mattia D, Bernasconi A, Olivier A et al. GABA A receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex. Brain. 2004 Jul;127(7):1626-1640. https://doi.org/10.1093/brain/awh181
D'Antuono, M. ; Louvel, J. ; Köhling, R. ; Mattia, D. ; Bernasconi, A. ; Olivier, A. ; Turak, B. ; Devaux, A. ; Pumain, R. ; Avoli, M. / GABA A receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex. In: Brain. 2004 ; Vol. 127, No. 7. pp. 1626-1640.
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abstract = "Patients with Taylor's type focal cortical dysplasia (FCD) present with seizures that are often medically intractable. Here, we attempted to identify the cellular and pharmacological mechanisms responsible for this epileptogenic state by using field potential and K +-selective recordings in neocortical slices obtained from epileptic patients with FCD and, for purposes of comparison, with mesial temporal lobe epilepsy (MTLE), an epileptic disorder that, at least in the neocortex, is not characterized by any obvious structural aberration of neuronal networks. Spontaneous epileptiform activity was induced in vitro by applying 4-aminopyridine (4AP)-containing medium. Under these conditions, we could identify in FCD slices a close temporal relationship between ictal activity onset and the occurrence of slow interictal-like events that were mainly contributed by GABA A receptor activation. We also found that in FCD slices, pharmacological procedures capable of decreasing or increasing GABA A receptor function abolished or potentiated ictal discharges, respectively. In addition, the initiation of ictal events in FCD tissue coincided with the occurrence of GABA A receptor-dependent interictal events leading to [K +] o elevations that were larger than those seen during the interictal period. Finally, by testing the effects induced by baclofen on epileptiform events generated by FCD and MTLE slices, we discovered that the function of GABA B receptors (presumably located at presynaptic inhibitory terminals) was markedly decreased in FCD tissue. Thus, epileptiform synchronization leading to in vitro ictal activity in the human FCD tissue is initiated by a synchronizing mechanism that paradoxically relies on GABA A receptor activation causing sizeable increases in [K +] o. This mechanism may be facilitated by the decreased ability of GABA B receptors to control GABA release from interneuron terminals.",
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AU - Bernasconi, A.

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