title: Thalamocortical oscillations in a genetic model of absence seizures.
abstract: We used field potential recordings in an in vitro thalamocortical slice preparation to compare the rhythmic oscillations generated by reciprocally connected networks of the thalamus and cerebral cortex obtained from epileptic (> 160 days old) WAG/Rij and age-matched, nonepileptic control (NEC) rats. To increase neuronal excitability, and thus to elicit spontaneous field potential activity in vitro, we applied medium containing: (i) zero [Mg2+]; (ii) high [K+] (8.25 mm); or (iii) low concentrations of the K+ channel blocker 4-aminopyridine (4AP, 0.5-1 micro m). Of these procedures, only the last was effective in triggering oscillatory activity that depended on the type of tissue. Thus, during 4AP application: (i) sequences of fast (intraburst frequency 9.5-16.1 Hz) and slower (5-8.9 Hz) field potential oscillations (FPOs) were recorded in WAG/Rij slices (n = 23), but (ii) only fast FPOs were seen in NEC slices (n = 7). Slower FPOs in WAG/Rij slices reflected a larger degree of thalamocortical synchronization than fast FPOs, and disappeared after surgical separation of cortex and thalamus (n = 5); under these conditions fast FPOs continued to occur in thalamus only. In addition, fast and slower FPOs disappeared in all areas of the WAG/Rij slice during thalamic application of the excitatory amino acid receptor antagonist kynurenic acid (n = 3), while fast FPOs continued to occur in thalamus when kynurenic acid was applied to the cortex (n = 4). Bath application of the N-methyl-D-aspartic acid (NMDA) receptor antagonist 3,3-(2-carboxypiperazine-4-yl)-propyl-1-phosphonate (CPP) abolished slower FPOs in WAG/Rij cortex and thalamus (n = 6) without infuencing fast FPOs recorded in WAG/Rij (n = 6) or NEC slices (n = 4). Moreover, cortical application of CPP (n = 6) abated slower FPOs although they persisted following CPP application to the thalamus (n = 7). Our data demonstrate that highly synchronized, slower FPOs can occur during 4AP application in WAG/Rij but not in NEC slices. This activity, which may represent an in vitro hallmark of thalamocortical epileptogenicity, requires the function of reciprocally connected thalamic and cortical networks and depends on cortical NMDA receptor-mediated mechanisms.
authors.affiliation: Montreal Neurological Institute and Department of Neurology & Neurosurgery, McGill University, 3801, University St., Montréal, QC, H3A B, Canada.
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Arcangelo
authors.forename: Margherita
authors.initials: M
authors.lastname: D'Antuono
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biagini
authors.forename: Richard
authors.initials: R
authors.lastname: Warren
authors.forename: Virginia
authors.initials: V
authors.lastname: Tancredi
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000235:genetics / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008275:Magnesium Deficiency / Q000503:physiopathology; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D016194:Receptors, N-Methyl-D-Aspartate; D015761:4-Aminopyridine; D011188:Potassium