Abstract

Input-dependent left-right asymmetry of NMDA receptor ϵ2 (NR2B) subunit allocation was discovered in hippocampal Schaffer collateral (Sch) and commissural fiber pyramidal cell synapses (Kawakami et al., 2003). To investigate whether this asymmetricalϵ2 allocation is also related to the types of the postsynaptic cells, we compared postembedding immunogold labeling for ϵ2 in left and right Sch synapses on pyramidal cells and interneurons. To facilitate the detection of ϵ2 density difference, we used ϵ1 (NR2A) knock-out (KO) mice, which have a simplified NMDA receptor subunit composition.

The labeling density for ϵ2 but not ζ1 (NR1) and subtype 2/3 glutamate receptor (GluR2/3) in Sch-CA1 pyramidal cell synapses was significantly different between the left and right hippocampus with opposite directions in strata oriens and radiatum; the left to right ratio ofϵ2 labeling density was 1:1.50 in stratum oriens and 1.44:1 in stratum radiatum. No significant difference, however, was detected in CA1 stratum radiatum between the left and right Sch-GluR4-positive (mostly parvalbumin-positive) and Sch-GluR4-negative interneuron synapses. Consistent with the anatomical asymmetry, the amplitude ratio of NMDA EPSCs to non-NMDA EPSCs in pyramidal cells was approximately two times larger in right than left stratum radiatum and vice versa in stratum oriens of ϵ1 KO mice. Moreover, the amplitude of long-term potentiation in the Sch-CA1 synapses of left stratum radiatum was significantly larger than that in the right corresponding synapses. These results indicate that the asymmetry of ϵ2 distribution is target cell specific, resulting in the left-right difference in NMDA receptor content and plasticity in Sch-CA1 pyramidal cell synapses in ϵ1 KO mice.