Functional Composition Change Of Nmda Receptor Activity - Dependent Role In The Regulation Of Synaptic Plasticity

N-methyl-D-aspartate(NMDA) ionotropic glutamate receptors are ligand-activated cation channels concentrated in the postsynaptic density (PSD), which play a critical role in synaptic transmission and plasticity in the central nervous system. Activation of NMDA receptors is not only critical for the inductions of long-term potentiation (LTP) and long-term depression (LTD) at diverse sets of synapses, but also involves in some forms of homeostatic plasticity. Functional importance of NMDA receptors in mediating synaptic plasticity is that they can act as a coincidence detector and allow influx of calcium, which can activate a variety of signaling cascades. Because of their key role in increasing the postsynaptic Ca2+ concentration, subtle alterations in NMDA receptors activation can result in modifying the threshold level of activity for the induction of LTP or LTD. In primary visual cortex, some excellent experiments showed that sensory deprivation, such as dark-rearing, reduced the developmental shift in NR2A/NR2B ratio. Then light exposure(1h) rapidly raised NR2A protein levels, which were correlated with subsequent modifications of synaptic plasticity. In detail, dark-rearing favored LTP over LTD, while LTD-LTP crossover point(θLTP/LTD) sliding to the left, and vice verse. Another experiment found that after LTP induction, NR2A-contained NMDA receptors increased. As a result, NR2A/NR2B ratio elevated. The improvement of NR2A/NR2B ratio following LTP induction eliminated after depotentiation. However, it is still unclear that the relationship between NR2A/NR2B ratio and theθLTP/LTD sliding. At hippocampal Schaffer collateral-CA1 synapses, we first examined whether a recent history of neuronal activity could affect subsequent synaptic plasticity through its actions on NMDAR subunit components. We found that prior activity history produced by priming stimulations (PSs) across a wide range of frequencies (1-100 Hz) could induce bidirectional changes in the NR2A/NR2B ratio. Simultaneous, the threshold for subsequent LTP/LTD is modified. The changes of NR2A/NR2B ratio are correlate withθLTP/LTD. Manipulating the NR2A/NR2B ratio through partial NR2 subunit blockade mimicked or reversed the PSs regulation of LTP/LTD threshold. Our results demonstrate that activity-dependent changes in NR2A/NR2B ratio can be critical factors in metaplastic regulation of the LTP/LTD threshold.