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Science 9 December 1994:
Vol. 266. no. 5191, pp. 1713 - 1717
DOI: 10.1126/science.7527589
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Articles

Science, Vol 266, Issue 5191, 1713-1717
Copyright © 1994 by American Association for the Advancement of Science

articles

Resetting the biological clock: mediation of nocturnal circadian shifts by glutamate and NO

JM Ding, D Chen, ET Weber, LE Faiman, MA Rea, and MU Gillette

Department of Cell and Structural Biology, University of Illinois, Urbana 61801.

Circadian rhythms of mammals are timed by an endogenous clock with a period of about 24 hours located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Light synchronizes this clock to the external environment by daily adjustments in the phase of the circadian oscillation. The mechanism has been thought to involve the release of excitatory amino acids from retinal afferents to the SCN. Brief treatment of rat SCN in vitro with glutamate (Glu), N-methyl-D-aspartate (NMDA), or nitric oxide (NO) generators produced lightlike phase shifts of circadian rhythms. The SCN exhibited calcium-dependent nitric oxide synthase (NOS) activity. Antagonists of NMDA or NOS pathways blocked Glu effects in vitro, and intracerebroventricular injection of a NOS inhibitor in vivo blocked the light-induced resetting of behavioral rhythms. Together, these data indicate that Glu release, NMDA receptor activation, NOS stimulation, and NO production link light activation of the retina to cellular changes within the SCN mediating the phase resetting of the biological clock.


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Extraocular Circadian Phototransduction in Humans.
S. S. Campbell and P. J. Murphy (1998)
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Regulation of Circadian Photic Responses by Nitric Oxide.
L. Melo, D. A. Golombek, and M. R. Ralph (1997)
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J. Hannibal, J. M. Ding, D. Chen, J. Fahrenkrug, P. J. Larsen, M. U. Gillette, and J. D. Mikkelsen (1997)
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J. Neurosci. 17, 1302-1319
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Melatonin Action and Signal Transduction in the Rat Suprachiasmatic Circadian Clock: Activation of Protein Kinase C at Dusk and Dawn.
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Coupling of Muscarinic Cholinergic Receptors and cGMP in Nocturnal Regulation of the Suprachiasmatic Circadian Clock.
C. Liu, J. M. Ding, L. E. Faiman, and M. U. Gillette (1997)
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   Abstract »    PDF »
A cell-based system that recapitulates the dynamic light-dependent regulation of the vertebrate clock.
M. P. Pando, A. B. Pinchak, N. Cermakian, and P. Sassone-Corsi (2001)
PNAS 98, 10178-10183
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The Photopigment Melanopsin Is Exclusively Present in Pituitary Adenylate Cyclase-Activating Polypeptide-Containing Retinal Ganglion Cells of the Retinohypothalamic Tract.
J. Hannibal, P. Hindersson, S. M. Knudsen, B. Georg, and J. Fahrenkrug (2002)
J. Neurosci. 22, RC191
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Science. ISSN 0036-8075 (print), 1095-9203 (online)