title: Hypersynchronous ictal onset in the perirhinal cortex results from dynamic weakening in inhibition.
abstract: We obtained field, K(+) selective and "sharp" intracellular recordings from the rat entorhinal (EC) and perirhinal (PC) cortices in an in vitro brain slice preparation to identify the events occurring at interictal-to-ictal transition during 4-aminopyridine application. Field recordings revealed interictal- (duration: 1.1 to 2.2s) and ictal-like (duration: 31 to 103s) activity occurring synchronously in EC and PC; in addition, interictal spiking in PC increased in frequency shortly before the onset of ictal oscillatory activity thus resembling the hypersynchronous seizure onset seen in epileptic patients and in in vivo animal models. Intracellular recordings with K-acetate+QX314-filled pipettes in PC principal cells showed that spikes at ictal onset had post-burst hyperpolarizations (presumably mediated by postsynaptic GABAA receptors), which gradually decreased in amplitude. This trend was associated with a progressive positive shift of the post-burst hyperpolarization reversal potential. Finally, the transient elevations in [K(+)]o (up to 4.4mM from a base line of 3.2mM) - which occurred with the interictal events in PC - progressively increased (up to 7.3mM) with the spike immediately preceding ictal onset. Our findings indicate that hypersynchronous seizure onset in rat PC is caused by dynamic weakening of GABAA receptor signaling presumably resulting from [K(+)]o accumulation.
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montreal, QC, H3A 2B4, Canada; Oscar-Langendorff-Institute of Physiology, Rostock University Medical Center, 18057 Rostock, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montreal, QC, H3A 2B4, Canada.
authors.forename: Margherita
authors.initials: M
authors.lastname: D'Antuono
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montreal, QC, H3A 2B4, Canada.
authors.forename: Ruba
authors.initials: R
authors.lastname: Benini
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montreal, QC, H3A 2B4, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: de Guzman
authors.affiliation: Montreal Neurological Institute and Departments of Neurology & Neurosurgery, and of Physiology, McGill University, Montreal, QC, H3A 2B4, Canada. Electronic address: massimo.avoli@mcgill.ca.
authors.forename: Massimo
authors.initials: M
authors.lastname: Avoli
mesh_terms: D015761:4-Aminopyridine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002414:Cations, Monovalent / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D010721:Phosphinic Acids / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy / Q000503:physiopathology*; D046509:Tissue Culture Techniques
chemical_list: D015761:4-Aminopyridine; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002414:Cations, Monovalent; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D010721:Phosphinic Acids; D010852:Picrotoxin; D010879:Piperazines; D011188:Potassium; D011412:Propanolamines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D016194:Receptors, N-Methyl-D-Aspartate; C085075:CGP 55845A; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
keywords: 4-Aminopyridine; Ictogenesis; Inhibition; Perirhinal cortex; Seizure onset; [K(+)](o)