Abstracts

Rationale: Modification of existing synaptic connections following synchronous neural network activity likely plays a key role in epileptogenesis and subsequent seizure initiation and propagation. Here we report persistent depression of spontaneous network activity following longer lasting, seizure-like activity in the highly recurrent CA3 pyramidal cell network in organotypic hippocampal cultures. Methods: Somatic whole-cell recordings of CA3 pyramidal cells were performed in organotypic hippocampal cultures from P8-P10 Wistar rat pups after 14-24 DIV. Following baseline recordings of spontaneous excitatory postsynaptic currents (sEPSCs) in standard ACSF, seizure-activity was induced by wash-in of modified ACSF with 1.3 mM Ca2+, 0.9 mM Mg2+, 3.3 mM K+, picrotoxin (GABAA receptor antagonist, 0.1 mM) and CGP-55845 (GABAB receptor antagonist, 0.001 mM) followed by a return to standard ACSF. Results: Dual whole-cell recordings revealed synchronized discharges with durations of up to 35 seconds following wash-in of low Mg2+ and GABAergic antagonists. After only few (2-4) periods of discharges, the amplitudes sEPSCs were increased in CA3 pyramidal cells experiencing shorter duration (<10 second) discharges, but decreased in cells experiencing prolonged (>20 second) discharges. These effects persisted for more than 15 minutes following wash-out of antagonists. Conclusions: These findings suggest, perhaps surprisingly, that longer duration, seizure-like activity can lead to a lasting depression of spontaneous network activity, while shorter discharges lead to potentiation as previously reported for recurrent bursting (Ben-Ari & Gho, 1988; Bains et al., 1999).