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We have used a glutamate-specific dialysis electrode to obtain real-time measurements of changes in the concentration of glutamate in the extracellular space of the hippocampus during low-frequency stimulation and following the induction of long-term potentiation (LTP). In the dentate gyrus, stimulation of the perforant path at 2 Hz for 2 min produced a transient increase in glutamate current relative to the basal value at control rates of stimulation (0.033 Hz). This activity-dependent glutamate current was significantly enhanced 35 and 90 min after the induction of LTP. The maximal 2 Hz signal was obtained during post-tetanic potentiation (PTP). There was also a more gradual increase in the basal level of extracellular glutamate following the induction of LTP. Both the basal and activity-dependent increases in glutamate current induced by tetanic stimulation were blocked by local infusion of the N-methyl-D-aspartate receptor antagonist D-APV. In areas CA1 and CA3 we were unable to detect a 2 Hz glutamate signal either before or after the induction of LTP, possibly owing to a more avid uptake of glutamate in the pyramidal cell fields. These results demonstrate that LTP in the dentate gyrus is associated with a greater concentration of extracellular glutamate following activation of potentiated synapses, either because potentiated synapses release more transmitter per impulse, or because of reduced uptake by glutamate transporters. We present arguments favouring increased release rather than decreased uptake.

philosophical transactions - royal society. biological sciences

Long-term potentiation in the dentate gyrus of the anaesthetized rat is accompanied by an increase in extracellular glutamate: real-time measurements using a novel dialysis electrode