title: Role of gap junctions on synchronization in human neocortical networks.
abstract: Gap junctions (GJ) have been implicated in the synchronization of epileptiform activities induced by 4-aminopyrine (4AP) in slices from human epileptogenic cortex. Previous evidence implicated glial GJ to govern the frequency of these epileptiform events. The synchrony of these events (evaluated by the phase unlocking index, PUI) in adjacent areas however was attributed to neuronal GJ. In the present study, we have investigated the effects of GAP-134, a recently developed specific activator of glial GJ, on both the PUI and the frequency of the 4AP-induced epileptiform activities in human neocortical slices of temporal lobe epilepsy tissue. To delineate the impact of GJ on spatial spread of synchronous activity we evaluated the effects of carbenoxolone (CBX, a non-selective GJ blocker) on the spread in three axes 1. vertically in a given cortical column, 2. laterally within the deep cortical layers and 3. laterally within the upper cortical layers. GAP-134 slightly increased the frequency of the 4AP-induced spontaneous epileptiform activities while leaving the PUI unaffected. CBX had no effect on the PUI within a cortical column or on the PUI in the deep cortical layers. CBX increased the PUI for long interelectrodes distances in the upper cortical layers. In conclusion we provide new arguments toward the role played by glial GJ to maintain the frequency of spontaneous activities. We show that neuronal GJ control the PUI only in upper cortical layers.
authors.affiliation: INSERM U1129 Infantile Epilepsies and Brain Plasticity, Paris, France; University Paris Descartes, Paris, France; Charité Universitätsmedizin Berlin, Centre for Anatomy, Institute for Cell Biology and Neurobiology, Berlin, Germany. Electronic address: sylvain.gigout@laposte.net.
authors.forename: S
authors.initials: S
authors.lastname: Gigout
authors.affiliation: Charité Universitätsmedizin Berlin, Centre for Anatomy, Institute for Cell Biology and Neurobiology, Berlin, Germany.
authors.forename: R A
authors.initials: RA
authors.lastname: Deisz
authors.affiliation: Epilepsy Center Berlin-Brandenburg, Königin Elisabeth Krankenhaus, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Dehnicke
authors.affiliation: Hopital Sainte-Anne, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Turak
authors.affiliation: Hopital Sainte-Anne, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Devaux
authors.affiliation: INSERM U1129 Infantile Epilepsies and Brain Plasticity, Paris, France; University Paris Descartes, Paris, France.
authors.forename: R
authors.initials: R
authors.lastname: Pumain
authors.affiliation: INSERM U1129 Infantile Epilepsies and Brain Plasticity, Paris, France; University Paris Descartes, Paris, France.
authors.forename: J
authors.initials: J
authors.lastname: Louvel
mesh_terms: D000328:Adult; D001549:Benzamides / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D003344:Cortical Synchronization / Q000187:drug effects / Q000502:physiology*; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D005260:Female; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000502:physiology; D009457:Neuroglia / Q000502:physiology; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C541429:1-(2-aminoacetyl)-4-benzamidopyrrolidine-2-carboxylic acid; D001549:Benzamides; D011392:Proline; D002229:Carbenoxolone
keywords: Carbenoxolone; Cortical slices; GAP-134; Gap junctions; Temporal lobe epilepsy