Seizure-like activity in the disinhibited CA1 minislice of adult guinea-pigs

1. Spontaneous activity was monitored during pharmacological blockade of GABA(A) receptor function in the CA1 minislice (CA3 was cut off). Synaptic inhibition was blocked by competitive GABA(A) antagonists bicuculline-methiodide (Bic) or GABAZINE (GBZ) and the chloride channel blocker picrotoxin (PTX). Extra- and intracellular recordings using sharp electrodes were carried out in stratum radiatum and pyramidale. 2. At low antagonist concentrations (Bic, GBZ: 1-10 muM; PTX: < 100 <mu>M), synchronized bursts (< 500 ms in duration, interictal activity) were seen as described previously. However, in the presence of high concentrations (Bic, GBZ: 50-100 <mu>M; PTX: 100-200 muM), seizure-like, ictal events (duration 4-17 s) ware observed in 67 of 88 slices. No other experimental measures to increase excitability were applied: cation concentrations ([Ca2+](o) = 2 mM, [Mg2+](o) = 1.7 mM, [K+](o) = 3 mM) and recording temperature (30-32 degreesC) were standard and GABA(B)-mediated inhibition was intact. 3. In whole-slice recordings prominent interictal activity, but fewer ictal events were observed. A reduced ictal activity was also observed when interictal-like responses were evoked by afferent stimulation. 4. Ictal activity was reversibly blocked by antagonists of excitatory transmission, CNQX (40 muM) or D-AP5 (50 muM). 5. Disinhibition-induced ictal development did not rely on group I mGluR activation as it was not prevented in the presence of group I mGluR antagonists (AIDB or 4CPG). 6. (RS)-3,5-DHPG prevented the induction and reversed the tertiary component of the ictal event through a group I mGluR-independent mechanism.