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Discovery clarifies role of peptide in biological clock

d. "The mice showed multiple rhythms, getting up both earlier and earlier and later and later on subsequent days so that their daily activity patterns were splitting apart."

Herzog and Aton recorded neuron activity from the SCN using a multielectrode array with 60 electrodes upon which they place SCN cells, a "clock in a dish." This enabled them to record data from many cells for many days.

"We found that the VIP mutants, indeed, can generate circadian rhythms, but the neurons can't synchronize to each other," Herzog said. "We showed that we could restore rhythms to the arrhythmic neurons and synchrony to the SCN by providing VIP once a day."

The SCN is a part of the hypothalamus that can be found on the bottom of the brain just above the roof of your mouth where your optic nerves cross. There are roughly 10,000 neurons in this nucleus on either side of your brain. The timekeeping mechanism in these cells depends on daily cycles in gene activity.

Herzog found in his latest study that the percentage of rhythmic cells in the mutant SCN was very low, and he believes these rhythmic neurons are specialized circadian pacemakers.

"We suspect that at least some of the pace making cells in the SCN are VIP cells, and one of the things we'll try to do next is confirm this. We will also try to understand better how VIP synchronizes pacemakers," he said.

It is surprising that the process is regulated by a peptide, usually a slow signaling agent, rather than a neurotransmitter, associated with fast events, Herzog said.

"We're trying to understand the mechanics of how the system synchronizes and the secondary messenger systems as well," Herzog said. "We're getting closer to the heart and soul of circadian rhythmicity by uncoupling the (biological) clock."


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Source:Washington University in St. Louis


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