Glutamatergic Pre-Ictal Discharges Emerge at the Transition to Seizure in Human Epilepsy

Nat Neurosci. 2011 May;14(5):627-34. doi: 10.1038/nn.2790. Epub 2011 Apr 3.

Abstract

The mechanisms involved in the transition to an epileptic seizure remain unclear. To examine them, we used tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability along with alkalinization or low Mg(2+). During the transition, distinct pre-ictal discharges emerged concurrently with interictal events. Intracranial recordings from the mesial temporal cortex of subjects with epilepsy revealed that similar discharges before seizures were restricted to seizure onset sites. In vitro, pre-ictal events spread faster and had larger amplitudes than interictal discharges and had a distinct initiation site. These events depended on glutamatergic mechanisms and were preceded by pyramidal cell firing, whereas interneuron firing preceded interictal events that depended on both glutamatergic and depolarizing GABAergic transmission. Once established, recurrence of these pre-ictal discharges triggered seizures. Thus, the subiculum supports seizure generation, and the transition to seizure involves an emergent glutamatergic population activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Adolescent
  • Adult
  • Analysis of Variance
  • Biophysics
  • Brain Mapping
  • Confidence Intervals
  • Electric Stimulation / methods
  • Electroencephalography / methods
  • Epilepsy, Temporal Lobe / pathology*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Female
  • Glutamic Acid / metabolism*
  • Hippocampus / physiopathology*
  • Humans
  • In Vitro Techniques
  • Magnesium / pharmacology
  • Male
  • Middle Aged
  • Nerve Net / drug effects
  • Nerve Net / physiology
  • Potassium Chloride / pharmacology
  • Quinoxalines / pharmacology
  • Valine / analogs & derivatives
  • Valine / pharmacology
  • Young Adult

Substances

  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Glutamic Acid
  • Potassium Chloride
  • 2-amino-5-phosphopentanoic acid
  • Valine
  • Magnesium