Nitric oxide (NO), produced by repetitive activation of the cerebellar parallel fiber (PF), induces long-term potentiation (LTP) of synaptic transmission between PF- Purkinje cell (PC) synapse. Underlying mechanism of this LTP is known to be increase in density of surface expressed AMPA type glutamate receptors (AMPA-Rs), mediated by receptor exocytosis (1). NO directly S-nitrosylates N-Ethylmaleimide Sensitive Factor (NSF) and this S-nytrosylated NSF increase its affinity to GluA2 carboxy-terminus (CT) region, and interaction of NSF – GluA2-CT enhances insertion of AMPA-Rs into the synaptic membrane (2). However, whether actually NO enhanced AMPA-Rs exocytosis or suppress endocytic elimination from the synaptic membrane remained elusive. Here, we quantitatively analyzed interaction between constitutive endocytosis and NO-induced LTP with an aid of data-driven kinetic model of AMPA-R trafficking. Slice of cerebellar cortex was prepared from rat (P19-23) cerebellum ectomized after decapitation during deep anesthesia with ethyl ether. EPSC evoked by electrical stimulation of the molecular layer was recorded from PC by means of a whole-cell recording method. In basal condition, NO-donor (NOR3 30microM) itself enhanced PF-PC EPSC amplitude to 170% of the basal amplitude (LTP) in rat cerebellar slice. When constitutive endocytosis was blocked by dynamin inhibitor, similar amount of increase in EPSC-amplitude through a constitutive exocytosis of AMPA-R was observed. Because LTP occluded with the constitutive exocytosis of AMPA-Rs, both pathways had to share common mechanism. When EPSC amplitude was reduced to the minimum steady state level by tetanus toxin (TeTx) infusion through a whole-cell patch-pipette (3), NOR3 had no effect on EPSC amplitude. However, when NOR3 was applied early phase of TeTx-action, NO intermitted constitutive endocytic reduction of EPSC amplitude with a slight rebound. By using our kinetic model of AMPA-R trafficking, I successfully reconstituted this time course including a slight rebound of EPSC amplitude by assuming that AMPA-R endocytosis was blocked, but not that exocytosis was enhanced, by NO. Because NSF and AP-2, an adaptor protein required for clathrin dependent endocytosis, compete binding to the overlapping NSF/AP-2 domain at GluA2-CT, S-nitrosylated NSF would competitively inhibit binding of AP-2 to this domain, and consequently suppress endocytosis of GluA2. We conclude that NO induces LTP by blocking GluA2 endocytosis at PF-PC synapse.