Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons

被引：598
作者：
Aton, SJ
Colwell, CS
Harmar, AJ
Waschek, J
Herzog, ED
机构：
[1] Washington Univ, Dept Biol, St Louis, MO 63130 USA
[2] Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA
[3] Univ Edinburgh, Div Neurosci, Edinburgh EH8 9JZ, Midlothian, Scotland
[4] Univ Edinburgh, Neurosci Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland
来源：
NATURE NEUROSCIENCE | 2005年 / 8卷 / 04期
关键词：
D O I：
10.1038/nn1419
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
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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收藏
页码：476 / 483
页数：8
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