Synaptic plasticity is cellular basis for learning and memory, and regulation of polarity of the synaptic plasticity (long-term potentiation (LTP) or long-term depression (LTD)) is critical for rational behavior and danger avoidance. However, regulatory mechanism for the polarity of synaptic plasticity has not been fully understood. Both LTD and LTP are demonstrated in parallel fiber (PF) to Purkinje cell (PC) synapse in the cerebellum (PF synapse). PF-LTP is induced by repetitive stimulation of PF, whereas PF-LTD is elicited by the repetitive PF stimulation in combination with CF stimulation. Therefore, LTD-inducing stimulation is indicated to activate LTP-inducing signals. However, LTD-inducing stimulus does not induce LTP when signals specifically involved in LTD are inhibited. The results suggest LTD-inducing stimulus impairs LTP-inducing signals. Protein S-nitrosylation by nitric oxide (NO) is necessary for LTP induction, and reactive oxygen species (ROS)/8-nitro-cGMP signals is recently suggested to be involved in LTD induction. Because thiol residue (R-SH) in cysteine is possible targets for both NO and ROS/8-nitro-cGMP signals, it is possible that protein S-nitrosylation and PF-LTP are impaired by ROS/8-nitro-cGMP signals. In this talk, our studies examining this hypothesis will be presented.