Long-term Potentiation Reversal Developmentally Regulated By NMDA Receptors Of Dentate Granule Cells

Background: Activity-dependent synaptic plasticity – long-term potentiation(LTP),long-term depression(LTD)and LTP reversal – are generally thought to be the cellular mechanism underlying learning and memory in the mature brain,in which NMDA receptors and neurogenesis play important roles.LTP reversal may be the mechanism of forgetting and mediate many psychiatric disorders such an schizophrenia,but the specific mechanisms about them are still unclear.It's reported that LTP reversal can be induced in adult but not in young animals,which may be related to the relative expressions of NMDA receptor subtypes NR2 A and NR2 B,but their particular mechanisms remain to be further studied.In the schizophrenia model mice,abnormalities in adult neurogenesis are accompanied by LTP reversal deficiency.However,LTP reversal during the development of adult-born dentate granule cells(DGCs)remain unknown.So we will explore the changes and possible mechanisms of LTP reversal with the development of individuals and adult-born DGCs,which might help us to make these problems clear.Objective and Methods: We first used whole-cell patch-clamp to observe the LTP and LTP reversal during development of individuals and maturation of adult-born DGCs.Adult-born DGCs were labeled with retrovirus to detect the neonatal time of them to observe the changes of synaptic plasticity during development.We then used real-time PCR to quantify the mRNA expression levels of NMDA receptor subtypes NR2 A and NR2 B during maturation of adult newborn(adult-born 3 weeks and adult-born 6 weeks)DGCs and during development of individuals(adult and young mice)DG regions.Third,we used patch clamp to record the EPSC of these groups and perfused NR2 A and NR2 B blockers to observe their effects on NMDA-EPSC.Finally,we tested the changes of LTP and LTP reversal after perfusing NMDA receptors blockers.In conclusion,we wanted to explore the changes of NMDA receptor subtypes and the characteristics of LTP reversal during individuals and adult-born DGCs and the relationship between them.Result: 1.LTP reversal was induced by subsequent stimulation in the DGCs of adult mice.2.LTP reversal could be induced by subsequent stimulation in the adult-born 6 weeks DGCs in the hippocampus.3.The NR2 A mRNA expression of adult-born 6 weeks DGCs was significantly higher than that of adult-born 6 weeks DGCs in the hippocampus.And its electrophysiological characteristics were consistent with the above.4.LTP reversal could be induced in adult mice and NR2 A expression was higher than juvenile mice during postnatal development.5.NR2 A blocker and NMDA blocker inhibited LTP reversal,but NR2 B blocker did not.Conclusions: The susceptibility of LTP reversal progressively increases during development of postnatal individuals and maturation of adult-born neurons,in which coupled with NMDA receptor subunit NR2 A expression augment and NR2 A mediated the reversal of LTP.