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N‐methyl‐D‐aspartate receptor subtype 2C is not involved in circadian oscillation or photoic entrainment of the biological clock in mice

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 Ca2+ elevations in the SCN of mutant mice using a Ca2+ imaging method. A partial reduction in Ca2+ elevation was observed in both NR2A‐/‐ and NR2C‐/‐ mice when high concentrations (100 or 300 μM) 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. J. Neurosci. Res. 61:663–673, 2000. © 2000 Wiley‐Liss, Inc.