Changes in the state of the excitatory synaptic system in the hippocampus on prolonged exposure to excitatory amino acids and antagonists.

Prolonged exposure of hippocampal slices to L-glutamate was found to produce a biphasic effect on excitatory synaptic transmission from Schaffer collateral-commissural fibers to CA1 pyramidal neurons: an early blockade of postsynaptic responses was followed by a progressive recovery. Antagonists of N-methyl-D-aspartate (NMDA) receptors, which had no effect on the initial responses, blocked the responses which reappeared during continued exposure to L-glutamate. Furthermore, when NMDA antagonists were maintained in the presence of glutamate, excitatory transmission was again restored and the new responses were now insensitive both to 'NMDA' and 'non-NMDA' antagonists. Once elicited, the changes in synaptic transmission appear to be 'memorized' by the slice for at least tens of minutes. These phenomena suggest that the well-known plasticity of the hippocampal synapses may involve a sequence of distinct 'states', and that transitions between these states can be induced by certain pharmacological stimuli.