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The Journal of Neuroscience, December 15, 1998, 18(24):10389-10397
CREB in the Mouse SCN: A Molecular Interface Coding the Phase-Adjusting Stimuli Light, Glutamate, PACAP, and Melatonin for Clockwork Access
Charlotte von Gall1, Giles E. Duffield2, Michael H. Hastings2, Michael D. A. Kopp1, 3, Faramarz Dehghani1, Horst-Werner Korf1, and Jörg H. Stehle1 1 Dr. Senckenbergische Anatomie, Anatomisches Institut II, Johann Wolfgang Goethe-Universität, D-60590 Frankfurt, Germany, 2 Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom, and 3 Max-Planck-Institut für Physiologische und Klinische Forschung, W. G. Kerckhoff-Institut, D-61231 Bad Nauheim, Germany
The suprachiasmatic nucleus (SCN) is a central pacemaker in mammals, driving many endogenous circadian rhythms. An important pacemaker target is the regulation of a hormonal message for darkness, the circadian rhythm in melatonin synthesis. The endogenous clock within the SCN is synchronized to environmental light/dark cycles by photic information conveyed via the retinohypothalamic tract (RHT) and by the nocturnal melatonin signal that acts within a feedback loop. We investigated how melatonin intersects with the temporally gated resetting actions of two RHT transmitters, pituitary adenylate cyclase-activating polypeptide (PACAP) and glutamate. We analyzed immunocytochemically the inducible phosphorylation of the transcription factor Ca2+/cAMP response element-binding protein (CREB) in the SCN of a melatonin-proficient (C3H) and a melatonin-deficient (C57BL) mouse strain. In vivo, light-induced phase shifts in locomotor activity were consistently accompanied by CREB phosphorylation in the SCN of both strains. However, in the middle of subjective nighttime, light induced larger phase delays in C57BL than in C3H mice. In vitro, PACAP and glutamate induced CREB phosphorylation in the SCN of both mouse strains, with PACAP being more effective during late subjective daytime and glutamate being more effective during subjective nighttime. Melatonin suppressed PACAP- but not glutamate-induced phosphorylation of CREB. The distinct temporal domains during which glutamate and PACAP induce CREB phosphorylation imply that during the light/dark transition the SCN switches sensitivity between these two RHT transmitters. Because these temporal domains are not different between C3H and C57BL mice, the sensitivity windows are set independently of the rhythmic melatonin signal.
Key words: suprachiasmatic nucleus; circadian; phase shifts; mice; brain slice; CREB (Ca2+/cAMP response element-binding protein); glutamate; PACAP (pituitary adenylate cyclase-activating polypeptide); melatonin
Copyright © 1998 Society for Neuroscience 0270-6474/98/182410389-09$05.00/0
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