title: Synchronous inhibitory potentials precede seizure-like events in acute models of focal limbic seizures.
abstract: Interictal spikes in models of focal seizures and epilepsies are sustained by the synchronous activation of glutamatergic and GABAergic networks. The nature of population spikes associated with seizure initiation (pre-ictal spikes; PSs) is still undetermined. We analyzed the networks involved in the generation of both interictal and PSs in acute models of limbic cortex ictogenesis induced by pharmacological manipulations. Simultaneous extracellular and intracellular recordings from both principal cells and interneurons were performed in the medial entorhinal cortex of the in vitro isolated guinea pig brain during focal interictal and ictal discharges induced in the limbic network by intracortical and brief arterial infusions of either bicuculline methiodide (BMI) or 4-aminopyridine (4AP). Local application of BMI in the entorhinal cortex did not induce seizure-like events (SLEs), but did generate periodic interictal spikes sensitive to the glutamatergic non-NMDA receptor antagonist DNQX. Unlike local applications, arterial perfusion of either BMI or 4AP induced focal limbic SLEs. PSs just ahead of SLE were associated with hyperpolarizing potentials coupled with a complete blockade of firing in principal cells and burst discharges in putative interneurons. Interictal population spikes recorded from principal neurons between two SLEs correlated with a depolarizing potential. We demonstrate in two models of acute limbic SLE that PS events are different from interictal spikes and are sustained by synchronous activation of inhibitory networks. Our findings support a prominent role of synchronous network inhibition in the initiation of a focal seizure.
authors.affiliation: Unit of Epileptology and Experimental Neurophysiology, Fondazione Istituto Neurologico Carlo Besta, 20133 Milano, Italy, and.
authors.forename: Laura
authors.initials: L
authors.lastname: Uva
authors.affiliation: Department of Neuroscience and Brain Technologies, Italian Institute of Technology, 16163 Genova, Italy.
authors.forename: Gian Luca
authors.initials: GL
authors.lastname: Breschi
authors.affiliation: Unit of Epileptology and Experimental Neurophysiology, Fondazione Istituto Neurologico Carlo Besta, 20133 Milano, Italy, and.
authors.forename: Vadym
authors.initials: V
authors.lastname: Gnatkovsky
authors.affiliation: Department of Neuroscience and Brain Technologies, Italian Institute of Technology, 16163 Genova, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Taverna
authors.affiliation: Unit of Epileptology and Experimental Neurophysiology, Fondazione Istituto Neurologico Carlo Besta, 20133 Milano, Italy, and decurtis@istituto-besta.it.
authors.forename: Marco
authors.initials: M
authors.lastname: de Curtis
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001640:Bicuculline / Q000031:analogs & derivatives / Q000633:toxicity; D003198:Computer Simulation; D003292:Convulsants / Q000633:toxicity; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D018728:Entorhinal Cortex / Q000503:physiopathology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008954:Models, Biological; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000473:pathology*
chemical_list: D003292:Convulsants; D018691:Excitatory Amino Acid Antagonists; D026902:Potassium Channel Blockers; D011810:Quinoxalines; C017069:bicuculline methiodide; C056723:FG 9041; D015761:4-Aminopyridine; D001640:Bicuculline
keywords: acute seizure model; entorhinal cortex; focal seizures; in vitro guinea pig brain; interictal spikes; pre-ictal spikes