Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy

Massimo Avoli, Marco De Curtis, Vadym Gnatkovsky, Jean Gotman, Rüdiger Köhling, Maxime Lévesque, Frédéric Manseau, Zahra Shiri, Sylvain Williams

Research output: Contribution to journalArticle

Abstract

Lowvoltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTLE in vivo and in vitro, and these studies have highlighted the predominant involvement of distinct neuronal network/neurotransmitter receptor signaling in each of them. First, LVF-onset seizures in epileptic rodents can originate from several limbic structures, frequently spread, and are associated with high-frequency oscillations in the ripple band (80-200 Hz), whereas HYP onset seizures initiate in the hippocampus and tend to remain focal with predominant fast ripples (250-500 Hz). Second, in vitro intracellular recordings from principal cells in limbic areas indicate that pharmacologically induced seizure-like discharges with LVF onset are initiated by a synchronous inhibitory event or by a hyperpolarizing inhibitory postsynaptic potential barrage; in contrast, HYP onset is associated with a progressive impairment of inhibition and concomitant unrestrained enhancement of excitation. Finally, in vitro optogenetic experiments show that, under comparable experimental conditions (i.e., 4-aminopyridine application), the initiation of LVFor HYP-onset seizures depends on the preponderant involvement of interneuronal or principal cell networks, respectively. Overall, these data may provide insight to delineate better therapeutic targets in the treatment of patients presenting with MTLE and, perhaps, with other epileptic disorders as well.

Original languageEnglish
Pages (from-to)3229-3237
Number of pages9
JournalJournal of Neurophysiology
Volume115
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Keywords

  • High-frequency oscillations
  • Hypersynchronous onset
  • Low voltage fast onset
  • Seizures

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Medicine(all)

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  • Cite this

    Avoli, M., De Curtis, M., Gnatkovsky, V., Gotman, J., Köhling, R., Lévesque, M., Manseau, F., Shiri, Z., & Williams, S. (2016). Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy. Journal of Neurophysiology, 115(6), 3229-3237. https://doi.org/10.1152/jn.01128.2015