title: Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy.
abstract: Low-voltage 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 LVF- or 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.
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery and of Physiology, McGill University, Montréal, Québec, Canada; Facoltà di Medicina e Odontoiatria, Sapienza Università di Roma, Rome, Italy; massimo.avoli@mcgill.ca.
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
authors.affiliation: Epilepsy Unit, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy;
authors.forename: Marco
authors.initials: M
authors.lastname: de Curtis
authors.affiliation: Epilepsy Unit, Fondazione Istituto Neurologico Carlo Besta, Milan, Italy;
authors.forename: Vadym
authors.initials: V
authors.lastname: Gnatkovsky
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery and of Physiology, McGill University, Montréal, Québec, Canada;
authors.forename: Jean
authors.initials: J
authors.lastname: Gotman
authors.affiliation: Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, Rostock, Germany; and.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery and of Physiology, McGill University, Montréal, Québec, Canada;
authors.forename: Maxime
authors.initials: M
authors.lastname: Lévesque
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Manseau
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery and of Physiology, McGill University, Montréal, Québec, Canada;
authors.forename: Zahra
authors.initials: Z
authors.lastname: Shiri
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Williams
mesh_terms: D058256:Brain Waves / Q000502:physiology*; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D009433:Neural Inhibition / Q000502:physiology*; D012640:Seizures / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology*; D055366:Synaptic Potentials / Q000502:physiology*
keywords: high-frequency oscillations; hypersynchronous onset; low voltage fast onset; seizures