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Tuning the body clock
August 2, 2018, 5:24 pm

International travel on airplanes often brings with it the trails of jet lag. Now researchers at Washington University in the US say they have unlocked a cure for jet lag in mice by activating a small subset of the neurons associated with setting their daily rhythms.

All essential body functions are highly synchronized with local time by the body's daily, or circadian clock. A small spot at the very bottom of the brain, close to the roof of the mouth, reminds us to wake up and go to sleep at a regular time each day. This master clock is referred to as the suprachiasmatic nucleus, or SCN.

When this system is disturbed, for example by shift work or crossing time zones, the 20,000 or so neurons in the SCN struggle to adjust the body to the new schedule. Stimulating just 10 percent of these neurons to fire with the right pattern of electrical activity caused mice to rapidly shift to the new daily schedule, the researchers found.

The study showed the involvement of a small subset of SCN neurons that produces vasoactive intestinal polypeptide or VIP — an essential compound that neurons use to communicate and synchronize their daily rhythms with one another. Researchers identified two classes of VIP neurons: Tonic VIP neurons, which fired at a steady pace with equally spaced intervals between each firing episode, and VIP irregular neurons, which fired in doublets or triplets with equally spaced intervals after each doublet or triplet.

To conduct the experiment, researchers kept mice in total darkness all day and all night with no environmental clues about what time it was. Using a tool called optogenetics, they activated only the VIP neurons at the same time every day, a procedure that mimicked flying to a new time zone.

Testing the different firing patterns of VIP neurons, researchers found that mice got over jet lag faster when VIP neurons were activated to fire irregularly. The mice were slower to adjust to the new local time when their VIP neurons were excited with tonic patterns.

The team found that the irregular pattern caused VIP neurons to release VIP, which the study found to be responsible for shifting the clock faster. In the future, the researchers hope to learn ways to encourage VIP neurons to release their VIP to pick the clock's lock and reduce jet lag for human travelers and shift workers.


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