Moriya T, Takahashi S, Ikeda M, Suzuki-Yamashita K, Asai M, Kadotani H, Okamura H, Yoshioka T, Shibata S
Advanced Research Center for Human Sciences, Waseda University, Tokorozawa, Saitama, Japan.
J Neurosci Res. 2000 Sep 15;61(6):663-73. doi: 10.1002/1097-4547(20000915)61:6<663::AID-JNR10>3.0.CO;2-M.
Ishida et al. [1994: Neurosci Lett 166: 211-215] reported the circadian change of N-methyl-D-aspartate (NMDA) receptor subtype 2C mRNA and photic induction of this receptor's mRNA in the suprachiasmatic nucleus (SCN). Therefore, we investigated the role of NMDA receptor subtypes in the biological clock using NMDA receptor 2A (NR2A)- or 2C (NR2C)-deficient mice. However, NR2C-/- mice showed normal light-dark (LD)-entrained locomotor activity rhythms and free-running rhythms under constant darkness and also exhibited normal reentrainment to 6-hr LD shifts and phase delays with single light pulses. Thus, present results demonstrated no significant NR2C contribution to circadian oscillation and photic entrainment, even though expression of NR2C mRNA was highly observed in the SCN. On the other hand, the period of the free-running activity rhythm in NR2A-/- mice but not NR2C-/- mice was slightly longer than that in wild-type mice in spite of low expression of NR2A in the SCN. Furthermore, reentrainment to an LD advance in NR2A-/- mice was slower under low-intensity light conditions. Thus, we suggest that NR2A plays a role in determining the behavioral state that affects the circadian rhythm. In order to elucidate the role of NR2A and NR2C in the SCN, we examined NMDA-induced Ca(2+) elevations in the SCN of mutant mice using a Ca(2+) imaging method. A partial reduction in Ca(2+) elevation was observed in both NR2A-/- and NR2C-/- mice when high concentrations (100 or 300 microM) of NMDA were applied. The present results suggest that NR2A plays a weak role in oscillation or entrainment of the biological clock, and that NR2C does not participate in the functions of circadian oscillation and light entrainment.
石田等人[1994年：《神经科学快报》166：211 - 215]报道了视交叉上核（SCN）中N - 甲基 - D - 天冬氨酸（NMDA）受体2C亚型mRNA的昼夜节律变化以及该受体mRNA的光诱导作用。因此，我们使用NMDA受体2A（NR2A）或2C（NR2C）缺陷小鼠研究了NMDA受体亚型在生物钟中的作用。然而，NR2C基因敲除小鼠在正常明暗（LD）条件下的运动活动节律以及在持续黑暗中的自由运行节律均正常，并且在6小时LD转换和单次光脉冲引起的相位延迟后也表现出正常的重新同步。因此，目前的结果表明，尽管在SCN中高度观察到NR2C mRNA的表达，但NR2C对昼夜节律振荡和光同步化没有显著贡献。另一方面，尽管SCN中NR2A的表达较低，但NR2A基因敲除小鼠而非NR2C基因敲除小鼠的自由运行活动节律周期比野生型小鼠略长。此外，在低强度光照条件下，NR2A基因敲除小鼠对LD提前的重新同步较慢。因此，我们认为NR2A在决定影响昼夜节律的行为状态中起作用。为了阐明NR2A和NR2C在SCN中的作用，我们使用Ca(2+)成像方法检测了突变小鼠SCN中NMDA诱导的Ca(2+)升高。当应用高浓度（100或300 microM）的NMDA时，在NR2A基因敲除小鼠和NR2C基因敲除小鼠中均观察到Ca(2+)升高的部分降低。目前的结果表明，NR2A在生物钟的振荡或同步化中起较弱的作用，而NR2C不参与昼夜节律振荡和光同步化的功能。
