A brief period of epileptiform activity strengthens excitatory synapses in the rat hippocampus in vitro

Purpose: We examined here whether a very short period of epileptiform activity could produce lasting modifications of synaptic strength and network properties in the rat hippocampus in vitro. Methods: Synaptic transmission at CA3-CA1 and at CA3-CA3 pyramidal cell synapses was monitored in hippocampal slice cultures before and after a very brief episode of epileptiform activity (20-180 s) induced with bicuculline methochloride. Results: We show here that a brief period of epileptiform activity induces long-lasting potentiation of glutamatergic transmission at CA3-CA1 and at CA3-CA3 pyramidal cell synapses. This potentiation also was observed at synapses formed by pairs of monosynaptically connected neurons. It was dependent on N-methyl-D-aspartate (NMDA) receptors, occluded classic long-term potentiation, and could be depotentiated by low-frequency stimulation at 3 Hz. Recruitment of polysynaptic pathways within area CA3 was facilitated after epileptiform activity indicating that the induced potentiation enhanced overall hippocampal network excitability. Conclusions: These changes in synaptic transmission may contribute to the genesis of epilepsy and to seizure-associated memory deficits.