Glutamate Receptors Mediate TTX-Resistant Synchronous Activity in the Rat Hippocampus

4-Aminopyridine (4-AP) is a well known convulsant that en-hances the release of both excitatory and inhibitory neurotrans-mitters in the CNS. Low concentrations of 4-AP (;100 mM) readily induce synchronized discharges in the hippocampus that are blocked by tetrodotoxin (TTX), suggesting that they require Na1-dependent action potentials in addition to the enhanced release of neurotransmitters. However, in the present study we have found that higher concentrations of 4-AP (1 mM) in combination with 5 mM tetraethylammonium (TEA) induce spontaneous synchronized discharges in rat hippocampal slices that are resistant to blockade by TTX. These synchro-nous discharges are evident in field potential recordings, which progress from the hilus to CA1 at 0.023 6 0.002 m/sec and in intracellular recordings from the hilar mossy cells and CA3 pyramidal cells. In some slices exposed to 4-AP and TEA