Spatial training and high-frequency stimulation engage a common pathway to enhance glutamate release in the hippocampus.

We have measured depolarization-induced release of endogenous glutamate in synaptosomes prepared from the dentate gyrus after the induction of LTP by high-frequency stimulation in anesthetized rats, and after training in the water maze. Both spatial training and LTP in untrained rats were accompanied by an increase in glutamate release from dentate synaptosomes. The enhancement of synaptosomal glutamate release induced by high-frequency stimulation was abolished in well-trained rats, and was reduced in partially trained rats and in rats trained in a nonspatial task. However, the magnitude of LTP was similar in well-trained and untrained groups. These results indicate that spatial training activates a glutamate release pathway that converges with that activated in LTP, and demonstrate an unexpected dissociation between increased glutamate release and LTP.