Increase in synaptic vesicle proteins accompanies long-term potentiation in the dentate gyrus

Maintenance of long-term potentiation in synapses formed by the perforant path on to granule cells of the dentate gyrus is accompanied by a sustained increase in the extracellular concentration of glutamate, the presumed transmitter at this excitatory hippocampal pathway. Quantal analysis indicates that, at least in the first hour of induction, this reflects an increase in transmitter release rather than a decrease in glutamate uptake, while biochemical studies have suggested that the increase in release persists for several hours. Morphological studies have described early but persistent increases in the spine number and area. Increases in the number of segmented/perforated synapses persisting for at least 1 h after induction of long-term potentiation, have also been reported. These morphological changes suggest both presynaptic and postsynaptic modifications. Increases in synaptic vesicle number and distribution lasting for at least 1 h specifically indicate presynaptic changes. To explore further the role of the presynaptic terminal in long-term potentiation, we have investigated changes in three synaptic vesicle proteins, synapsin, synaptotagmin and synaptophysin, in control tissue and in tissue prepared from potentiated dentate gyrus 45 min and 3 h after induction of long-term potentiation. We found that there was an increase in the concentration of the three proteins 3 h after induction of long-term potentiation. No such increase was observed 45 min after induction or in tissue prepared from animals in which an intraventricular injection of the N-methyl-D-aspartate receptor antagonist, D(-)-2-amino-5-phosphonopentanoic acid, blocked induction of long-term potentiation.