Activation of glycogen synthase kinase-3 (GSK-3) can cause memory deficits as seen in Alzheimer disease (AD),the most common age-associated dementia,but the mechanism is not understood.Here,we found that activation of GSK-3 by wortmannin or transient overexpression of wild type GSK-3β (wtGSK-3β) could suppress the induction of long term potentiation (LTP) in rat hippocampus,while simultaneous inhibition of GSK-3 by lithium or SB216763 or transient expression of a dominant negative GSK-3β mutant (dnGSK-3β) preserved the LTP.After high frequency stimulation (HFS),the presynaptic release of glutamate and the expression/clustering of synapsin Ⅰ,a synaptic vesicle protein playing an important role in neurotmnsmitter release,decreased markedly upon upregulation of GSK-3.