Entrainment to feeding but not to light: circadian phenotype of VPAC2 receptor-null mice.
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.
Sheward
W John
WJ
Centre for Neuroscience Research, School of Biomedical Sciences, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
Maywood
Elizabeth S
ES
French
Karen L
KL
Horn
Jacqueline M
JM
Hastings
Michael H
MH
Seckl
Jonathan R
JR
Holmes
Megan C
MC
Harmar
Anthony J
AJ
D000818:Animals; D002940:Circadian Rhythm / Q000235:genetics*; D003345:Corticosterone / Q000378:metabolism; D003463:Cues; D004435:Eating / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D015870:Gene Expression; D008027:Light; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000502:physiology
D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D003345:Corticosterone