Scientists unlocked a cure for jet lag in mice by activating a small subset of the neurons involved in setting daily rhythms. The mammalian suprachiasmatic nucleus (SCN) functions as a master circadian pacemaker, integrating environmental input to align physiological and behavioral rhythms to local time cues. The study was published in the journal Neuron.

Approximately 10% of SCN neurons express vasoactive intestinal polypeptide (VIP); however, it is unknown how the firing activity of VIP neurons releases VIP to entrain circadian rhythms. To identify physiologically relevant firing patterns, they optically tagged VIP neurons and characterized spontaneous firing over 3 days.  VIP neurons had circadian rhythms in firing rate and exhibited two classes of instantaneous firing activity.

Body's Clock

All essential body functions are highly synchronized with local time by the 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 by shift work or crossing time zones. Stimulating just 10% of these neurons to fire with the right pattern of electrical activity caused mice to rapidly shift to the new daily schedule.

They hypothesized that VIP neurons are like the grandmothers who are in charge of telling everyone what to do. There are only about 2,000 VIP neurons in the SCN of people and mice. They developed a way to characterize the normal daily firing patterns of VIP neurons.

Recording the millisecond-long action potentials from a set of neurons, they were able to identify two classes of VIP neurons. Tonic VIP neurons fired at a steady pace with equally spaced intervals between each firing episode and VIP irregular neurons fired in doublets or triplets with equally spaced intervals after each doublet or triplet.

Activation Of VIP Neurons

The researchers then tested whether activation of VIP neurons would shift the daily schedule of the SCN and the mice. 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.

This was an important step to understand how the SCN keeps organisms synced to their local light schedule. Testing the different firing patterns of VIP neurons, researchers found that mice got over jet lag faster when VIP neurons were activated to irregularly fire. The mice were slower to adjust to the new local time when their VIP neurons were excited with tonic patterns.

They found the irregular pattern causes VIP neurons to release VIP. VIP, they think, is the juice that is capable of shifting the clock faster. They are starting to understand how the timing system in the brain is wired together and found that the code used by VIP neurons is key to setting our daily schedule.

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.