The Roles Of NR2A And NR2B Subunits Of NMDA Receptor In Hippocampal Long-Term Potentiation And Metaplasticity

There has been an increasing understanding of the properties and mechanisms underlying long-term potentiation (LTP) and long-term depression (LTD) of synaptic efficacy, putative learning and memory mechanisms in the mammalian brain. It has been demonstrated by several groups that activation of NMDA receptors is required for both induction of LTP and LTD. Although several reports have indicated the different roles of NR2A- and NR2B-containing NMDA receptors in an induction of long-term potentiation (LTP), the underlying mechanisms remain largely unclear. In this experiment, we have tested and compared the effects of selective antagonists for NR2A and NR2B on low-frequency stimulation (LFS) and high-frequency stimulation (HFS) evoked LTP inductions, respectively, in hippocampal CA1 pyramidal neurons. The selective antagonists for NR2B subunit promoted LFS-induced LTP but failed to influence HFS-induced LTP. On the other hand, a selective antagonist for NR2A subunit completely blocked both LFS- and HFS- induced LTP. These results demonstrated that the NR2A-containing NMDA receptors are required for LTP induction while the NR2B-containing NMDA receptors negatively contribute to LTP by increasing the induction threshold.In addition, we have examined the effects of above antagonists on metaplasticity, a higher order-form of plasticity. Applying selective antagonists for NR2B but not an antagonist for NR2A after a conditioning LFS stimulation, called priming stimulation, resulted in disinhibition of subsequent HFS-induced LTP, indicating that activation of NR2B-containing NMDA receptors is involved in induction of metaplasticity.