海馬NMDA受容体のシナプス局在と左右非対称性配置

抄録

NMDA receptors play a key role in synaptic plasticity in the hippocampal CA1 pyramidal cells. Two subunits of NMDA receptors NR2A and NR2B have distinct expression patterns in development and may contribute differently to induction of long-term potentiation and depression. We discovered input-dependent left-right asymmetry of NR2B subunit allocation in Schaffer collateral (Sch)- and commissural fiber- pyramidal cell synapses. However, it has not been known if NR2B has such asymmetrical distribution in Sch-interneuron synapses, and if NR2A has also asymmetry to neutralize the NR2B asymmetry in pyramidal cell synapses. Here, we investigated distribution of NR2A and NR2B in single synapses by postembedding immunogold and SDS-digested freeze-fracture replica labeling methods. To facilitate the detection of NR2B density difference, we utilized NR2A knockout mice, which have a simplified NMDA receptor subunit composition.The labeling density for NR2B but not NR1 in Sch-CA1 pyramidal cell synapses was significantly different between the left and right hippocampus with opposite directions in strata oriens and radiatum. No significant difference in NR2B density, however, was detected in CA1 stratum radiatum between the left and right Sch-interneuron synapses. Immunoblot analysis of PSD fractions from CA1 radiatum confirmed significant difference in protein amount for NR2B but not for NR1 and NR2A between left and right hippocampus. These results indicate that the asymmetry of NR2B distribution is target-cell specific and unique to this subunit. [J Physiol Sci. 2006;56 Suppl:S23]