Although epileptic seizures are characterized by excessive excitation, the role of excitatory synaptic transmission in the induction and expression of epilepsy remains unclear. Here, we show that epileptiform activity strengthens excitatory hippocampal synapses by increasing the number of functional (RS)--amino- 3hydroxy-5methyl-4-isoxadepropionate (AMPA)-type glutamate receptors in CA3-CA1 synapses. This form of synaptic strengthening occludes long-term potentiation (LTP) and enhances long-term depression (LTD), processes involved in learning and memory. These changes in synaptic transmission and plasticity, which are fully blocked with N-methyl-D-aspartate (NMDA) receptor- antagonists, may underlie epilepsy induction and seizure- associated memory deficits.