Correlative Association betweenN-Methyl-d-Aspartate Receptor-Mediated Expression of Period Genes in the Suprachiasmatic Nucleus and Phase Shifts in Behavior with Photic Entrainment of Clock in Hamsters
- 1Advanced Research Center for Human Sciences, Waseda University, Saitama, Japan (T.M); and 2Department of Pharmacology and Brain Science, School of Human Sciences, Waseda University, Saitama, Japan (K.H., M.A, S.S.)
Abstract
Because the rapid induction of Period(Per) genes is associated with the photic entrainment of the biological clock, we examined whetherN-methyl-d-aspartate (NMDA) receptors were involved in the photic induction of Pergenes in the hamster suprachiasmatic nucleus (SCN). In situ hybridization observation revealed that light during the early subjective night [circadian time (CT) 13.5] or the late subjective night (CT20) caused an induction of Per1 andPer2 but not Per3 mRNA in the SCN. Photic induction of Per mRNA at CT13.5 was observed especially in the ventrolateral SCN, whereas that at CT20 was more widespread from the ventrolateral to the dorsal SCN. A noncompetitive NMDA receptor antagonist, +MK801, dose-dependently (0.1–5.0 mg/kg) suppressed only the ventrolateral part of Per1 andPer2 mRNA induction by light at CT13.5 or CT20 in the SCN. The suppressive effects of +MK801 on Per mRNA strongly correlated with the attenuating action of this compound on phase shifts by light at both CT13.5 and CT20. A competitive NMDA receptor antagonist, d-2-amino-5-phosphonovalerate (D-APV), also exhibited inhibitory actions on light (CT20)-induced Per1 and Per2 mRNA expression in the ventrolateral SCN. Furthermore, local injection of NMDA into the SCN resulted in the induction of Per1 andPer2 mRNA in the SCN. Among NMDA receptors, NR2B and NR2C mRNA were expressed in the ventrolateral and dorsal SCN, respectively. These results suggest that the activation of NMDA receptor is a critical step for photic induction of Per1and Per2 transcripts in the SCN, which are linked to a photic behavioral entrainment.
Footnotes
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Send reprint requests to: Takahiro Moriya, Advanced Research Center for Human Sciences, Waseda University, 2-579-15 Mikajima, Tokorozawa-shi, Saitama, 359-1192, Japan. E-mail:moriya{at}human.waseda.ac.jp
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This study was partially supported by grants awarded to S.S. from the Japanese Ministry of Education, Science, Sports, and Culture (11170248, 1123207, 11145240) and the Special Coordination of Funds of the Japanese Science and Technology Agency and by a grant-in-aid for Encouragement of Young Scientists to T.M. from the Japan Society for the Promotion of Science (11771503).
- Abbreviations:
- SCN
- suprachiasmatic nucleus
- NMDA
- N-methyl-d-aspartate
- CT
- circadian time
- RHT
- retinohypothalamic tract
- Per
- Period
- LD
- light-dark
- LV
- lateral ventricle
- DD
- constant darkness
- PB
- phosphate buffer
- PFA
- paraformaldehyde
- CRE
- cAMP response element
- CREB
- CRE-binding protein
- MAPK
- mitogen-activated protein kinase
- D-APV
- d-2-amino-5-phosphonovalerate
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- Received May 23, 2000.
- Accepted August 22, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
