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

1 Spontaneous activity was monitored during pharmacological blockade of GABAA receptor function in the CA1 minislice (CA3 was cut off). Synaptic inhibition was blocked by competitive GABAA 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 μm; PTX: < 100 μm), synchronized bursts (< 500 ms in duration, interictal activity) were seen as described previously. However, in the presence of high concentrations (Bic, GBZ: 50‐100 μm; PTX: 100‐200 μm), seizure‐like, ictal events (duration 4‐17 s) were 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 °C) were standard and GABAB‐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 μm) or d‐AP5 (50 μm). 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 (AIDA 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.