@misc{oai:ir.soken.ac.jp:00001153,
 author = {WU, Yue and ウ, ユェ and WU, Yue},
 month = {2016-02-17, 2016-02-17},
 note = {N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission and activity-dependent changes in synaptic efficacy in the central nervous system and play an important role in learning and memory. NMDA receptors are composed of seven known subunits- GluRζ1 (NR1), GluRε1-4 (NR2A-2D) and GluRχ1-2 (NR3A-3B), and functional activities of the NMDA receptor channel require the heteromeric assemblies of obligatory GluRζ1 with one or more other subunits.<br />　　　In the hippocampal CA1 area, pyramidal cells and GABAergic interneurons receive excitatory inputs from Schaffer collaterals (Sch) arising from the ipsilateral CA3 pyramidal neurons and commissural fibers (com) arising from the contralateral CA3 pyramidal neurons (Ishizuka et al., 1990). The fast excitatory synaptic transmission from these inputs is mostly mediated by NMDA and AMPA type glutamate receptors. The NMDA receptors in the Sch and com fiber synapses on pyramidal cells contain ζ1, ε1, and ε2 subunits in adult rodents (Monyer et al., 1994; Fritschy et al., 1998; Takumi et al., 1999; Racca et al., 2000). Some interneurons in the hippocampus also express ε4 subunit as well as ζ1, ε1, and ε2 subunits (Monyer et al., 1994; Standaert et al., 1996; Standaert et al., 1999).<br />　　　The asymmetrical allocation of NMDA receptor ε2 (NR2B) subunits was discovered in the Sch-CA1 pyramidal cell synapses between the left and right hippocampus and between the apical and basal dendrites of single neurons (Kawakami et al., 2003). Direction of this asymmetry depends on inputs; com-pyramidal cell synapses have a mirror-image asymmetry to that for Sch-pyramidal cell synapses (Kawakami et al., 2003). Although electrophysiological and morphological studies have suggested differential localization of glutamate receptors depending on target-cell types as well as on input pathways (Shigemoto et al., 1996; Nusser et al., l998b; Gottmann et al., 1997; Ito et al., 2000), it is not clear whether the asymmetry in ε2 allocation is also related to the types of the postsynaptic cells. In the present study, to examine the asymmetrical ε2 distribution in distinct postsynaptic target cells, I utilized quantitative postembedding immunogold labeling method in the left and right CA1 areas. I used ε1 knock-out (KO) mice to facilitate the detection of difference in the ε2 immunoparticle density.<br />　　　In na&iuml;ve ε1 KO mice, I found no significant difference in labeling density for ε2 in pyramidal cell synapses, which are made by both Schaffer collateral and commissural fibers. However, in ε1 KO mice operated for ventral hippocampal commissure transection (VHCT) to examine Schaffer collateral synapses selectively, labeling density for ε2 but not ζ1 and GluR2/3 in Sch-CA1 pyramidal cell synapses was significantly different (P<0.05) between the left and right hippocampus. The ratio of ε2 labeling density in the left to right was about 1:1.5 in the stratum oriens and about 1.6:1 in the stratum radiatum. Moreover, labeling density for ε2 in Sch-CA1 pyramidal cell synapses was significantly different (P<0.05) between basal and apical dendrites. The ratio of ε2 labeling density in the basal to apical dendrites was about 1:1.4 in the left hippocampus and about 1.5:1 in the right hippocampus. This result is consistent with the asymmetry in ε2 allocation previously detected with electrophysiology and immunoblot analysis in wild type mice. On the other hand, the ε2 labeling density was not significantly different (P>0.05) in interneuron synapses between the left and right. Interneurons were grouped into GluR4-immunopositive and GluR4-immunonegative subpopulations in the stratum radiatum. Double immunofluorescence results showed that 88.7% of GluR4-immunopositive interneurons were palvalbumin immunoreactive and 11.1% of GluR4-immunopositive interneurons were mGluR1α immunoreactive. None of GluR4-immunopositive interneurons showed immunoreactivity for calretinin or calbindin. In addition, immunoreactivity for GluR4 was not colocalized with that for ε4 in the CA1 area, indicating that NMDA receptors in GluR4-immunopositive interneuron synapses are composed of ζ1 and ε2 similar to those in the pyramidal cell synapses. The density ratio of ε2 labeling in the left to right was 0.88:1 in Sch-GluR4 immunopositive interneuron synapses and 1.14:1 in Sch-GluR4 immunonegative interneuron synapses.<br />　　　Consistent with the anatomical asymmetry in the ε2 distribution in Sch-CA1 pyramidal cell synapses, amplitude of evoked NMDA EPSCs relative to that of non-NMDA EPSCs was different between the left and right CA1 area in VHCT- operated ε1 KO mice. The amplitude ratio of AP5-sensitive EPSCs to DNQX-sensitive EPSCs was larger in the right than left stratum oriens (left, 21.6%±2.64, n = 5 from 5 animals; right, 40.2％±3.40, n = 5, from 5 animals; P<0.01, t-test,). By contrast, the ratio in the stratum radiatum showed a mirror-image asymmetry to that found in the stratum oriens (left, 39.3％±3.40, n = 6, from 6 animals; right, 16.4％±3.11, n = 5, from 5 animals; P<0.01, t-test). Moreover, the asymmetrical ε2 content was directly reflected in different amplitudes of long-term potentiation (LTP) in the left and right stratum radiatum in VHCT-operated ε1 KO mice: in the left Sch-CA1 synapses, the amplitude of LTP was higher than that in the right Sch-CA1 synapses (left, 138％±2.76, n =7, from 7 animals; right, 104％ ±2.77, n = 6, from 6 animals, P<0.05, t-test).<br />　　　The present results indicate that the target-cell-specific left-right asymmetry of ε2 distribution results in the left-right difference in NMDA receptor content in Sch-CA1 pyramidal cell synapses in ε1 KO mice., application/pdf, 総研大甲第818号},
 title = {Target-cell-specific Left-Right Asymmetry of NMDA Receptor Content in Schaffer Collateral Synapses in e1 Knock-out Mice},
 year = {}
}