Objective Calciurn/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) plays an important role in synaptic plasticity, learning and memory.The α and βCaMKII are two main isoforms of CaMKⅡ in the forebrain.The roles of αCaMKⅡ in synaptic plasticity have been studied extensively; however, the information regarding that of βCaMKⅡ is rare.Therefore, we investigated the effect of βCaMKⅡ overexpression on synaptic plasticity of dentate gyrus (DG) and hippocampus-related cognition by using βCaMKⅡ-F90G transgenic mice in which the overexpression of βCaMKⅡ was restricted to the DG area.Methods In vitro electrophysiological technique and behavioral method were employed in the present study.Results (1) Western bloting analysis showed that the level of βCaMKⅡ protein in hippocampus was significantly higher in βCaMKⅡ-F90G transgenic mice than in wild type mice.(2) Low frequency stimulation (1 Hz, 15 min and 3 Hz, 5 min) failed to induce the robust long-term depression at medial perforant pathway in βCaMKⅡ-F90G transgenic slices as did in wild type slices.Furthermore, 0.5 μM NM-PP1, a specific inhibitor of βCaMKⅡ-F90G could restore the LTD deficit in the transgenic slices.(3) No significant difference was observed in paired-pulse depression curve and voltage-current response between Tg and Wt slices.(4) Passive avoidance task was utilized to test the hippocampus-related memory in βCaMKⅡ-F90G mice.The βCaMKⅡ-F90G mice exhibited impaired performances, which were reversed by oral treatment of 5 μM NM-PP1.Conclusion These results suggest that overexpression of the βCaMKⅡ may impair the long-term depression and the hippocampus-related memory without effect on the presynaptic function in DG area.