Humans have evolved to do stuff during the day and sleep at night, but international travel or shift work can throw off that natural rhythm. Finding ways to reset this circadian clock could be key, and now researchers at Washington University in St Louis have isolated a small cluster of "grandmother" neurons that tell the rest of the brain when to go to bed, and found that stimulating those could help combat jet lag.
Your biological clock manages bodily functions on a roughly 24-hour schedule, and it's regulated through changes in light. Messing with this cycle, be it through flying into new timezones or working the graveyard shift, can lead to a whole range of unpleasant physical side effects.
But sometimes these interruptions are unavoidable, so scientists are trying to dream up ways to reset the clock. Everything from synthetic molecules to light-up glasses to glowing pillows have been floated as possible remedies, while other studies have explored the biology behind the system, uncovering the "bicycle mechanism" that drives the brain in and out of sleep, and the role of the retinas in the process.
The brain's master clock has long been known to reside in the suprachiasmatic nucleus (SCN), a small bundle of neurons at the base of the brain. Past research has found that stimulating this region with pulses of light can help mice adjust their rhythm back to normal.
For the new study, the Washington researchers discovered that you don't need to stimulate the whole SCN. Only about 2,000 of the 20,000 neurons in that part of the brain seem to play an active role, by producing a compound called vasoactive intestinal peptide (VIP), which neurons use to communicate with each other and sync up their schedules.
"We hypothesized that VIP neurons are like the grandmothers who are in charge of telling everyone what to do," says Erik Herzog, an author of the study.
To test out whether these nanna neurons really are bossy enough to restart the cycle, the researchers first messed up the circadian rhythm of mice by keeping them in total darkness 24 hours a day. Then, they used optogenetics techniques to trigger the VIP neurons at the same time every day, to simulate a new "timezone" of sorts.
Interestingly, the researchers found that different patterns of stimulation had different effects on the mice. Those that had their neurons fired in irregular patterns seemed to adjust to the new schedule much faster than those that received more steady signals.
"We found the irregular pattern causes VIP neurons to release VIP," says Herzog. "VIP, we think, is the juice that is capable of shifting the clock faster. We are really starting to understand how the timing system in the brain is wired together, and found that the code used by VIP neurons is really key to setting our daily schedule."
We still have a long way to go before shift workers are stimulating their own grandmother neurons to get themselves back in sync, but discovering this mechanism is at least the first step towards that goal.
The research was published in the journal Neuron.
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