Nature Neuroscience8, 476 - 483 (2005)
Published online: 6 March 2005; | doi:10.1038/nn1419
Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons
Sara J Aton1, Christopher S Colwell2, Anthony J Harmar3, James Waschek2
& Erik D Herzog1
1
Department of Biology, One Brookings Drive, Washington University, St. Louis, Missouri 63130, USA.
2
Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, 10920 Wilshire Blvd., Suite 1200, Los Angeles, California 90024, USA.
3
Division of Neuroscience and Centre for Neuroscience Research, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.
Correspondence should be addressed to Erik D Herzog herzog@wustl.edu
The mammalian suprachiasmatic nucleus (SCN) is a master circadian pacemaker. It is not known which SCN neurons are autonomous pacemakers or how they synchronize their daily firing rhythms to coordinate circadian behavior. Vasoactive intestinal polypeptide (VIP) and the VIP receptor VPAC2 (encoded by the gene Vipr2) may mediate rhythms in individual SCN neurons, synchrony between neurons, or both. We found that Vip-/- and Vipr2-/- mice showed two daily bouts of activity in a skeleton photoperiod and multiple circadian periods in constant darkness. Loss of VIP or VPAC2 also abolished circadian firing rhythms in approximately half of all SCN neurons and disrupted synchrony between rhythmic neurons. Critically, daily application of a VPAC2 agonist restored rhythmicity and synchrony to VIP-/- SCN neurons, but not to Vipr2-/- neurons. We conclude that VIP coordinates daily rhythms in the SCN and behavior by synchronizing a small population of pacemaking neurons and maintaining rhythmicity in a larger subset of neurons.
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