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Model of frequent, recurrent, and spontaneous seizures in the intact mouse hippocampus
Author(s) -
Derchansky M.,
Shahar E.,
Wennberg R.A.,
Samoilova M.,
Jahromi S.S.,
Abdelmalik P.A.,
Zhang L.,
Carlen P.L.
Publication year - 2004
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20007
Subject(s) - hippocampus , neuroscience , psychology , epilepsy
Abstract This study presents a model of chronic, recurrent, spontaneous seizures in the intact isolated hippocampal preparation from mice aged P8–P25. Field activity from the CA1 pyramidal cell layer was recorded and recurrent, spontaneous seizure‐like events (SLEs) were observed in the presence of low Mg 2+ (0.25 mM) artificial cerebrospinal fluid (ACSF). Hippocampi also showed interictal epileptiform discharges (IEDs) of 0.9–4.2 Hz occurring between seizures. No age‐specific differences were found in SLE occurrence (2 SLEs per 10 min, on average), duration, and corresponding frequencies. After long exposure to low Mg 2+ ACSF (>3 h), SLEs were completely reversible within minutes with the application of normal (2 mM Mg 2+ ) ACSF. The AMPA antagonist, CNQX, blocked all epileptiform activity, whereas the NMDA antagonist, APV, did not. The γ‐aminobutyric acid (GABA) A antagonist, bicuculline, attenuated and fragmented SLEs, implicating interneurons in SLE generation. The L‐type Ca 2+ blocker, nifedipine, enhanced epileptiform activity. Analysis of dual site recordings along the septotemporal hippocampus demonstrated that epileptiform activity began first in the temporal pole of the hippocampus, as illustrated by disconnection experiments. Once an SLE had been established, however, the septal hippocampus was sometimes seen to lead the epileptiform activity. The whole hippocampus with intact local circuitry, treated with low Mg 2+ , provides a realistic model of recurrent spontaneous seizures, which may be used, in normal and genetically modified mice, to study the dynamics of seizures and seizure evolution, as well as the mechanisms of action of anti‐epileptic drugs and other therapeutic modalities. © 2004 Wiley‐Liss, Inc.