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Discovery clarifies role of peptide in biological clock

A biologist at Washington University in St. Louis is giving the VIP treatment to laboratory mice in hopes of unraveling more clues about our biological clock.

VIP is not "very important person," but vasoactive intestinal polypeptide (VIP), a neuropeptide originally found in the gut, that is also made by a specialized group of neurons in the brain.

Erik Herzog, Ph.D., Washington University assistant professor of Biology in Arts & Sciences, has discovered that VIP is needed by the brain's biological clock to coordinate daily rhythms in behavior and physiology. Neurons in the biological clock, an area called the suprachiasmatic nucleus (SCN), keep 24-hour time and are normally synchronized as a well-oiled marching band coming onto the field at half time. Herzog and graduate student, Sara Aton, found that mice lacking the gene that makes VIP or lacking the receptor molecule for VIP suffer from internal de-synchrony. When they recorded the electrical activity of SCN neurons from these mice, they found that many had lost their beat while others were cycling but unable to synch to each other.

But when Herzog and Aton added VIP to the mice cells, the synchronicity was restored, showing that VIP couples pacemaker cells and drives rhythms in slave cells.

"VIP between SCN neurons is like a rubber band between the pendulums of two grandfather clocks, helping to synchronize their timing. Some researchers had proposed that knocking out VIP or the receptor for it stopped the clock," Herzog said. "We've found that the biological clock is still running, but its internal synchrony is uncoordinated. This causes irregular patterns of sleep and wake, for example."

The study was published on-line in Nature Neuroscience on March 6, 2005. Herzog's work is funded by the National Institutes of Health.

"In a light-dark schedule, these mice looked normal, but as soon as you leave off the lights, the
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Contact: Tony Fitzpatrick
tony_fitzpatick@wustl.edu
314-935-5272
Washington University in St. Louis
6-Mar-2005


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