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Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.

Abstract
Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure.
AuthorsLaura Uva, Gian Luca Breschi, Vadym Gnatkovsky, Stefano Taverna, Marco de Curtis
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 35 Issue 7 Pg. 3048-55 (Feb 18 2015) ISSN: 1529-2401 [Electronic] United States
PMID25698742 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 the authors 0270-6474/15/353048-08$15.00/0.
Chemical References
  • Convulsants
  • Excitatory Amino Acid Antagonists
  • Potassium Channel Blockers
  • Quinoxalines
  • bicuculline methiodide
  • FG 9041
  • 4-Aminopyridine
  • Bicuculline
Topics
  • 4-Aminopyridine (pharmacology)
  • Action Potentials (drug effects, physiology)
  • Animals
  • Bicuculline (analogs & derivatives, toxicity)
  • Computer Simulation
  • Convulsants (toxicity)
  • Disease Models, Animal
  • Electric Stimulation (adverse effects)
  • Entorhinal Cortex (physiopathology)
  • Excitatory Amino Acid Antagonists (pharmacology)
  • Excitatory Postsynaptic Potentials (drug effects)
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Models, Biological
  • Neural Inhibition (drug effects, physiology)
  • Potassium Channel Blockers (pharmacology)
  • Quinoxalines (pharmacology)
  • Seizures (chemically induced, pathology)

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