INCREASE IN SYNAPTIC VESICLE PROTEINS ACCOMPANIES LONG-TERM POTENTIATION IN THE DENTATE GYRUS

Maintenance of long-term potentiation in synapses formed by the perfor ant path on to granule cells of the dentate gyrus is accompanied by a sustained increase in the extracellular concentration of glutamate,(34 ) the presumed transmitter at this excitatory hippocampal pathway. Qua ntal analysis(2,12,13,19,27) indicates that, at least in the first hou r of induction, this reflects an increase in transmitter release rathe r than a decrease in glutamate uptake, while biochemical studies(4,17, 18) have suggested that the increase in release persists for several h ours. Morphological studies have described early but persistent increa ses in the spine number(5,14) and area.(28) Increases in the number of segmented/perforated synapses persisting for at least 1 h after induc tion of long-term potentiation, have also been reported.(9,24) These m orphological changes suggest both presynaptic and postsynaptic modific ations.(15) Increases in synaptic vesicle number(20) and distribution( 1) 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 p roteins, synapsin, synaptotagmin and synaptophysin, in control tissue and in tissue prepared from potentiated dentate gyrus 45 min and 3 h a fter induction of long-term potentiation. We found that there was an i ncrease 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 intraventric ular injection of the N-methyl-D-aspartate receptor antagonist, D(-)-2 -amino-5-phosphonopentanoic acid, blocked induction of long-term poten tiation. This finding demonstrates an increased expression of synaptic vesicle proteins in long-term potentiation and implies the existence of distinct temporal phases of long-term potentiation during which dif ferent synaptic mechanisms for increased transmitter release are engag ed.