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

recently,by examining the effects of targeted disruption of the GluR D2ε e D2 1(NR2A)and GluR D2ε e D2（NR2B）subunits on NMDA receptor activities我们应该在NMDA receptors operating at different CA3 pyramidal cell synapses mightdifferent subunit compositions. In this project，我们已经确认了我们之前的药物分析使用Ro 25-6981 and ifenprodil，the GluR D2ε e D2 2 subunit selective NMDA receptor antagonists. Next，we examined the effects of the GluR D2ε e D2 1 subunit disruption on NMDA receptor-mediatedcurrents in response to glutamate applied iontophoretically. NMDA receptor-mediated currents of theGluR D2ε e D2 1 mutant mice were reduced to one-half that of the wild-type mice both in the apicaldendrite and in the basal dendrite of CA3 pyramidal neurons. We also examined the postnataldevelopments of the long-term potentiation in the CA3 region. the development of LTP at the CA3stratum radiatum synapses closely followed the development of the GluR i - D2ε - D2 1 subunit，and the GluR D2ε e D2 1 mutation strongly suppressed this LTP. the LTP at the CA3 stratum orienssynapses not affected significantly by the mutation at all ages. Then，we examined the effects of the GluR e - D2ε e - D2 1 subunit disruption on NMDA EPSCs at two types ofsynapses on the basal dendrites of CA3 pyramidal neurons. the GluR D2ε e D2 1 subunit disruptionresulted in a significant reduction of nmda epscs in the commissural / associational - ca 3 synapse,NMDA EPSCs in the commissural-CA3 synapse是apparently unaffected. Our data indicate thatsynapse-selective sorting of the GluR D2ε e D2 subunits is also found in the wild-type mice andthis targeted distribution is dependent on the types of synaptic input，但not on the cellpolarity。

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.