Taken together, this suggests that overexpression of NR2B subunit indeed contributes to the enhanced LTP, which is consistent with findings from hippocampus area of transgenic NR2B mice. In addition, we found that antagonist of NR2A and NR2B subunit reduced the Norgestimate prefrontal cortex LTP in both Tg and Wt slices. This result reconciled with the proposition that both NR2A and NR2B subunits were required for prefrontal cortex LTP. Interestingly, Philpot reported that overexpression of NR2B in forebrain did not alter LTP in visual cortex. One explanation for the diverse results is that expression of NR2B subunits were not increased in synaptosome of visual cortex in NR2B transgenic mice. In contrast with the above result, our western blot data reveal that the synaptic expression of the NR2B protein was significantly increased in prefrontal cortex of NR2B transgenic mice. The increased expression of NR2B protein provides the molecular basis for the enhancement of NMDAdependent LTP in the prefrontal cortex. Working memory is a trial-unique-specific memory, which enables the temporary holding of CGP36742 information for the purposes of processing, playing a critical role in many cognitive tasks. Lesions restricted to PFC have been shown to impair performance on delayed-response tasks which reflect working memory ability. Furthermore, antagonists of NMDA receptors impaired prefrontal cortex-dependent working memory, suggesting NMDAR have been implicated in working memory. Based on all knowledge, we assume that overexpression of NR2B protein may enhance prefrontal-related working memory by up-regulating NMDA receptor function. Consistent with our speculation, NR2B transgenic mice exhibited super performance in comparision to Wt mice in T-maze and working-memory version of water maze tasks, suggesting NR2B overexpression can enhance spatial working memory. Both hippocampus and prefrontal cortex play a role in spatial working memory, moreover overexpression of NR2B gene is throughout the forebrain including hippocampus and prefrontal cortex in transgenic mice.