Persistent ictal-like activity in rat entorhinal/perirhinal cortex following washout of 4-aminopyridine.

Abstract:

:Application of 4-aminopyridine (4-AP, 100μM) in a solution containing 0.6mM Mg(2+) and 1.2mM Ca(2+) to hippocampal-entorhinal-perirhinal slices of adult rat brain induced ictal-like epileptiform activity in entorhinal and perirhinal cortices as revealed by electrophysiological field potential recordings. The ictal-like activity persisted after washing out the 4-AP. This persistence indicated that a change had occurred in the slice so that it was now "epileptic" in the absence of the convulsant 4-AP. Induction of persistent ictal-like activity was dependent upon the concentration of divalent cations during 4-AP exposure; that is, although 4-AP caused ictal-like activity in approximately half the slices in solution containing 1.6mM Mg(2+) and 2.0mM Ca(2+), this ictal-like activity did not persist upon washout of the 4-AP. Expression of the persistent ictal-like epileptiform activity required ionotropic glutamate-mediated synaptic transmission: application of the AMPA/kainate receptor antagonist NBQX after 4-AP washout reduced persistent ictal-like activity, and the combined application of NBQX and the NMDA receptor antagonist d-AP5 completely blocked it. In order to investigate the mechanism of induction of persistent ictal-like activity, several agents were applied before the introduction of 4-AP. Application of d-AP5 did not block the onset of ictal-like activity upon introduction of 4-AP but did prevent the persistence of the ictal-like activity upon washout of the 4-AP. In contrast, induction of persistent ictal-like activity was not prevented by simultaneous application of the group I metabotropic glutamate receptor (mGluR) antagonists LY 367385 and MPEP or by application of the protein synthesis inhibitor cycloheximide. In conclusion, we have characterized a new in vitro model of epileptogenesis in which induction of ictal-like activity is dependent upon NMDA receptor activation but not upon group I mGluR activation or protein synthesis.

journal_name

Epilepsy Res

journal_title

Epilepsy research

authors

Salah A,Perkins KL

doi

10.1016/j.eplepsyres.2011.01.017

subject

Has Abstract

pub_date

2011-05-01 00:00:00

pages

163-76

issue

3

eissn

0920-1211

issn

1872-6844

pii

S0920-1211(11)00036-2

journal_volume

94

pub_type

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