OBJECTIVE The reagents to enhance serotonergic and GABAergic synaptic function are used to treat anxiety.Their effectiveness delay and side-effect make psychological therapies to be paid attention, in which anxiety status appears to be relieved by reward memory.Cellular and molecular mechanisms underlying such psychological therapies remain elusive.The elucidation to these issues will shed light onto finding new therapeutic approach for anxiety.METHODS AND RESULTS Food reward at the open-arm end of the elevated plusmaze was applied to train the mice for them to form working memory and challenge open arm.Glutamatergic synapses in the hippocampal dentate gyrus were analyzed by using electrophysiology and cellular imaging.The mice with reward training increase their entrances and staying in the reward open-arm versus in a neutral open-arm and two closed-arms.After the level of mouse anxiety-related behavior is reduced by this reward memory, long-term synaptic potentiation in vivo and dendritic spines in the granule cells become upregulated.This upregulated synaptic plasticity is accompanied by the expression of more protein kinase C in the dendritic spines.Protein kinase C inhibitor,chelerythrine, reduces the formation of working memory,the relief of anxiety-related behavior and the upregulation of glutamate synapses.CONCLUSION Reward-induced memory relieves the mouse anxiety-related behaviors via strengthening synaptic efficacy and protein kinase C expression in the hippocampus.