title: Decrease of neocortical paired-pulse depression in GAERS and possible implication of gap junctions.
abstract: Thalamocortical slices are widely used to study thalamocortical relationships and absence epilepsy. However, it is still not known whether (1) intracortical synaptic transmission, in particular neocortical paired-pulse depression (PPD), is maintained in these slices and (2) whether PPD is altered in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS, a model of absence epilepsy for which cortico-thalamic loops are involved). Furthermore, while the involvement of gap junctions (GJ) in the mechanisms leading to epileptiform discharges has been intensively studied, little is known about their effect on intracortical transmission. We first studied intracortical connection efficacy and PPD in thalamocortical slices from GAERS and non-epileptic rats (NER). We then investigated the effects of GJ blockers (carbenoxolone and quinidine) on intracortical response following single or paired-pulse stimulations in coronal slices from Wistar rats. We show that the efficacy of intracortical connections is not impaired in GAERS. We also show that neocortical PPD is preserved in thalamocortical slices of NER, but that its efficacy is strongly decreased in GAERS. Moreover, a NMDA antagonist strongly reduced the PPD in NER but had no effect in GAERS. Cortical responses to white matter stimulation were not modified by quinidine or carbenoxolone in coronal slices of Wistar rats. PPD was recorded in these slices and was decreased by carbenoxolone but not by quinidine. We hypothesize that the decrease of PPD observed in GAERS might be due to a decrease in function of (1) NMDA receptors and/or (2) astrocytic GJ's.
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France; University Paris Descartes, Sorbonne Paris Cité; CEA, Gif sur Yvette, France. Electronic address: s.gigout@leeds.ac.uk.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Gigout
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France; University Paris Descartes, Sorbonne Paris Cité; CEA, Gif sur Yvette, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Louvel
authors.affiliation: INSERM U1129 "Infantile Epilepsies and Brain Plasticity", Paris, France; University Paris Descartes, Sorbonne Paris Cité; CEA, Gif sur Yvette, France.
authors.forename: René
authors.initials: R
authors.lastname: Pumain
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002229:Carbenoxolone / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004832:Epilepsy, Absence / Q000235:genetics; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D011802:Quinidine / Q000494:pharmacology; D017208:Rats, Wistar; D013045:Species Specificity; D009435:Synaptic Transmission
chemical_list: D000927:Anticonvulsants; D011802:Quinidine; D002229:Carbenoxolone
keywords: Absence epilepsy; Carbenoxolone; Gap junctions; Paired-pulse protocol; Quinidine; Thalamocortical slices