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The Journal of Neuroscience, April 18, 2007, 27(16):4351-4358; doi:10.1523/JNEUROSCI.4843-06.2007

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Behavioral/Systems/Cognitive
Entrainment to Feeding but Not to Light: Circadian Phenotype of VPAC₂ Receptor-Null Mice

W. John Sheward,^1,2 Elizabeth S. Maywood,³ Karen L. French,² Jacqueline M. Horn,^1,2 Michael H. Hastings,³ Jonathan R. Seckl,² Megan C. Holmes,^1,2 and Anthony J. Harmar^1,2

¹Centre for Neuroscience Research, School of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom, ²Centre for Cardiovascular Science, University of Edinburgh, Queen's Medical Research Institute, Edinburgh EH16 4TJ, United Kingdom, and ³Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, United Kingdom

Correspondence should be addressed to Anthony J. Harmar, Centre for Neuroscience Research, School of Biomedical Sciences, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK. Email: tony.harmar{at}ed.ac.uk

The master clock driving mammalian circadian rhythms is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and entrained by daily light/dark cycles. SCN lesions abolish circadian rhythms of behavior and result in a loss of synchronized circadian rhythms of clock gene expression in peripheral organs (e.g., the liver) and of hormone secretion (e.g., corticosterone). We examined rhythms of behavior, hepatic clock gene expression, and corticosterone secretion in VPAC₂ receptor-null (Vipr2^–/–) mice, which lack a functional SCN clock. Unexpectedly, although Vipr2^–/– mice lacked robust circadian rhythms of wheel-running activity and corticosterone secretion, hepatic clock gene expression was strongly rhythmic, but advanced in phase compared with that in wild-type mice. The timing of food availability is thought to be an important entrainment signal for circadian clocks outside the SCN. Vipr2^–/– mice consumed food significantly earlier in the 24 h cycle than wild-type mice, consistent with the observed timing of peripheral rhythms of circadian gene expression. When restricted to feeding only during the daytime (RF), mice develop rhythms of activity and of corticosterone secretion in anticipation of feeding time, thought to be driven by a food-entrainable circadian oscillator, located outside the SCN. Under RF, mice of both genotypes developed food-anticipatory rhythms of activity and corticosterone secretion, and hepatic gene expression rhythms also became synchronized to the RF stimulus. Thus, food intake is an effective zeitgeber capable of coordinating circadian rhythms of behavior, peripheral clock gene expression, and hormone secretion, even in the absence of a functional SCN clock.

Key words: circadian rhythms; corticosterone; entrainment; feeding; HPA axis; liver; VIP

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Received Nov. 7, 2006; revised Feb. 28, 2007; accepted March 5, 2007.

Correspondence should be addressed to Anthony J. Harmar, Centre for Neuroscience Research, School of Biomedical Sciences, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK. Email: tony.harmar{at}ed.ac.uk

This article has been cited by other articles:

				D. A. Bechtold, T. M. Brown, S. M. Luckman, and H. D. Piggins Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R344 - R351. [Abstract] [Full Text] [PDF]

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