title: Activation of specific neuronal networks leads to different seizure onset types.
abstract: OBJECTIVE
  Ictal events occurring in temporal lobe epilepsy patients and in experimental models mimicking this neurological disorder can be classified, based on their onset pattern, into low-voltage, fast versus hypersynchronous onset seizures. It has been suggested that the low-voltage, fast onset pattern is mainly contributed by interneuronal (γ-aminobutyric acidergic) signaling, whereas the hypersynchronous onset involves the activation of principal (glutamatergic) cells.
  
  
  METHODS
  Here, we tested this hypothesis using the optogenetic control of parvalbumin-positive or somatostatin-positive interneurons and of calmodulin-dependent, protein kinase-positive, principal cells in the mouse entorhinal cortex in the in vitro 4-aminopyridine model of epileptiform synchronization.
  
  
  RESULTS
  We found that during 4-aminopyridine application, both spontaneous seizure-like events and those induced by optogenetic activation of interneurons displayed low-voltage, fast onset patterns that were associated with a higher occurrence of ripples than of fast ripples. In contrast, seizures induced by the optogenetic activation of principal cells had a hypersynchronous onset pattern with fast ripple rates that were higher than those of ripples.
  
  
  CONCLUSIONS
  Our results firmly establish that under a similar experimental condition (ie, bath application of 4-aminopyridine), the initiation of low-voltage, fast and of hypersynchronous onset seizures in the entorhinal cortex depends on the preponderant involvement of interneuronal and principal cell networks, respectively.
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, and Department of Physiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Shiri
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Manseau
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, and Department of Physiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Lévesque
authors.affiliation: Douglas Mental Health University Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Williams
authors.affiliation: Montreal Neurological Institute, Department of Neurology and Neurosurgery, and Department of Physiology, McGill University, Montreal, Quebec, Canada.
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D015761:4-Aminopyridine; D000818:Animals; D003344:Cortical Synchronization; D018728:Entorhinal Cortex / Q000187:drug effects / Q000503:physiopathology*; D007395:Interneurons; D051379:Mice; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D062308:Optogenetics / Q000379:methods*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D015761:4-Aminopyridine