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Titolo:
Domoic acid-induced hippocampal CA1 hyperexcitability independent of region CA3 activity
Autore:
Sari, P; Kerr, DS;
Indirizzi:
Univ Otago, Sch Med Sci, Dept Pharmacol, Dunedin, New Zealand Univ Otago Dunedin New Zealand ci, Dept Pharmacol, Dunedin, New Zealand
Titolo Testata:
EPILEPSY RESEARCH
fascicolo: 1-2, volume: 47, anno: 2001,
pagine: 65 - 76
SICI:
0920-1211(200111)47:1-2<65:DAHCHI>2.0.ZU;2-P
Fonte:
ISI
Lingua:
ENG
Soggetto:
KAINATE RECEPTOR ACTIVATION; MONKEYS MACACA-FASCICULARIS; AMNESIC SHELLFISH TOXIN; RAT DORSAL HIPPOCAMPUS; KAINIC ACID; EPILEPTIFORM ACTIVITY; INDUCED SEIZURES; PYRAMIDAL CELLS; BINDING-SITES; AMINO-ACIDS;
Keywords:
hippocampus; domoic acid; hyperexcitability;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Kerr, DS Univ Otago, Sch Med Sci, Dept Pharmacol, POB 913, Dunedin, New Zealand Univ Otago POB 913 Dunedin New Zealand 13, Dunedin, New Zealand
Citazione:
P. Sari e D.S. Kerr, "Domoic acid-induced hippocampal CA1 hyperexcitability independent of region CA3 activity", EPILEPSY R, 47(1-2), 2001, pp. 65-76

Abstract

Domoic acid (DOM) is a potent agonist of AMPA and kainic acid (KA) receptors in the CNS and is known to produce seizures acutely, and lasting excitotoxic damage in several brain regions, While the excitotoxic effects of DOM are well documented, its seizurogenic properties are less clear. In this study, we assessed the acute effects of DOM and KA in region CA1 of intact rat hippocampal slices (CA3-on) and in slices lacking region CA3 (CA3-off). Orthodromic Schaffer collateral-evoked CA1 field potentials (population spikes and somal EPSP's) were monitored during DOM and KA (10-500 nM) administration. In CA3-off slices both KA and DOM produced immediate increases in CA1 population spike amplitude. With prolonged exposure, lasting dose-dependent reductions in spike amplitude and EPSP slope were observed, possibly dueto depolarising conduction block following excessive AMPA/KA receptor activation DOM was several-fold more potent than KA in this regard. Population spike threshold did not vary with DOM, but in CA3-on slices a dose-dependent steepening of the I/O curve and increase in maximum spike amplitude was seen. CA1 hyperexcitability, as evidenced by the appearance of prominent second and third population spikes, was equivalently increased across a range of DOM concentrations in both CA3-on and CA3-off slices and. in general, DOM-induced CA1 hyperexcitability was not enhanced by the presence of CA3 forany of the other variables assessed in this study. These findings show that DOM directly promotes neuronal hyperactivity in region CA1, presumably due to tonic AMPA and/or KA-receptor mediated depolarization, and further suggests that DOM-induced hyperactivity in the recurrently networked, AMPA/KA-receptor rich region CA3 does not contribute to the onset and spread of limbic seizures during relatively mild DOM intoxication. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 16:11:58