INPUT-SELECTIVE SORTING OF THE NMDA RECEPTOR SUBUNITS IN MOUSE HIPPOCAMPAL PYRAMIDAL NEURONS.

Recently，by examining the effects of targeted disruption of the GluR ei D2ε文件D2(NR2A)and GluR文件D2(NR2B)subunits on NMDA receptor activities，we have shown that NMDA receptors operating at different CA3 pyramidal cell synapses might have different subunit compositions.In this project，we confirmed our previous observation by pharmacological analyses using Ro 25-6981 and ifenprodil，the GluR ei D2ε-D2 subunit selective NMDA receptor antagonists.Next，we examined the effects of the GluR ei D2εii D2 1subunit disruption on NMDA receptor-mediated currents in response to glutamate applied iontophoretically.NMDA receptor-mediated currents of the GluR ei D2ε文件D2 1mutant mice were reduced to one-half that of the wild-type mice both in the apical dendrite and in the basal dendrite of CA3pyramidal neurons.We also examined the postnatal developments of the long-term potentiation(LTP)in the CA3region。The development of LTP at the CA3 stratum radiatum synapses closely followed the development of the GluR Ii D2εIED2 1subunit，and the GluR Ii D2εIee D2 1mutation strongly suppressed this LTP。The LTP at the CA3 stratum oriens synapses was not affected significantly by the mutation at all ages.Then，we examined the effects of the GluR ei D2εii D2 1subunit disruption on NMDA EPSCs at two types of synapses on the basal dendrites of CA3pyramidal neurons.The GluR-D2ε-D2 1subunit disruption resulted in a significant reduction of NMDA EPSCs in the commissural/associational-CA3 synapse，whereas NMDA EPSCs in the commissural-CA3 synapse were apparently unaffected.Our data indicate that synapse-selective sorting of the GluR I D2εii subunits is also found in the wild-type mice and that this targeted distribution is dependent on the types of synaptic input but not on the cell polarity.

Recently, by examining the effects of targeted disruption of the GluR ィイD2εィエD2 1(NR2A)and GluR ィイD2εィエD2 2(NR2B)subunits on NMDA receptor activities, we have shown that NMDA receptors operating at different CA3 pyramidal cell synapses might have different subunit compositions. In this project, we confirmed our previous observation by pharmacological analyses using Ro 25-6981 and ifenprodil, the GluR ィイD2εィエD2 2 subunit selective NMDA receptor antagonists. Next, we examined the effects of the GluR ィイD2εィエD2 1 subunit disruption on NMDA receptor-mediated currents in response to glutamate applied iontophoretically. NMDA receptor-mediated currents of the GluR ィイD2εィエD2 1 mutant mice were reduced to one-half that of the wild-type mice both in the apical dendrite and in the basal dendrite of CA3 pyramidal neurons. We also examined the postnatal developments of the long-term potentiation(LTP)in the CA3 region. The development of LTP at the CA3 stratum radiatum synapses closely followed the development of the GluR ィイD2εィエD2 1 subunit, and the GluR ィイD2εィエD2 1 mutation strongly suppressed this LTP. The LTP at the CA3 stratum oriens synapses was not affected significantly by the mutation at all ages. Then, we examined the effects of the GluR ィイD2εィエD2 1 subunit disruption on NMDA EPSCs at two types of synapses on the basal dendrites of CA3 pyramidal neurons. The GluR ィイD2εィエD2 1 subunit disruption resulted in a significant reduction of NMDA EPSCs in the commissural/associational-CA3 synapse, whereas NMDA EPSCs in the commissural-CA3 synapse were apparently unaffected. Our data indicate that synapse-selective sorting of the GluR ィイD2εィエD2 subunits is also found in the wild-type mice and that this targeted distribution is dependent on the types of synaptic input but not on the cell polarity.