Artificial Light-dark Cycles Expose Circadian Clocks At Odds With Each Other

New research led by a University of Washington biologist demonstrates that there are at least two circadian clocks in the mammal brain, one that sticks strictly to an internal schedule and another that can be altered by external influences such as light and dark.

Typically the two clocks are synchronized so that various physical functions are in tune with each other, said Horacio de la Iglesia, a UW assistant professor of biology. But make a long plane trip or switch your 8-to-5 work schedule to begin at midnight and things can get out of kilter.

"When you travel to Europe, the rest-activity cycle will adjust relatively quickly. In two or three days you'll probably be sleeping when it's dark," de la Iglesia said. "But your temperature or hormone-release cycles might still be on Seattle time, affecting for instance how well you sleep."

A bit of brain tissue called the suprachiasmatic nucleus, a daily pacemaker that regulates rhythms such as sleep and wakefulness, has thousands of cells called neurons with synchronized circadian activities. But the neurons in the nucleus can be grouped into at least two secondary clocks that can become disconnected from one another when exposed to artificial day-night cycles.

For the study, a group of rats was exposed to artificially created 22-hour days, with 11 hours each of light and dark. With the shortened 22-hour days, the researchers found that what normally is daytime activity began to expand into the artificial night hours, and that enabled them to look at the interplay of two genes in the rats' brain clocks. One gene, called Per1, is active during the day and the other, Bmal1, is active at night.

The scientists found that when a rat behaved as expected, its suprachiasmatic nucleus contained Per1 during light periods and Bmal1 during dark. But when the daytime behavior began drifting into "night" hours, it turned out that both genes were active at the same time, Per1 in roughly the top half of the nucleus and Bmal1 in roughly the bottom half. That means the top half of the brain's main circadian clock can show a cycle of nearly 25 hours, which is normal for a rat, while the bottom half adjusts according to external signals such as light and dark.

The work is detailed in a paper published earlier this month in the journal Current Biology. Besides de la Iglesia, authors are William Schwartz of the University of Massachusetts Medical School and Trinitat Cambras and Antoni Díez-Noguera, both of the University of Barcelona in Spain.

The work adds to a growing understanding that the body contains a complex network of oscillators that regulate the body's rhythms, including peripheral, or "slave," oscillators in organs such as the liver and lungs. In turn, such research could eventually lead to a cure for jet lag, or offer help for day-shift workers switching to a midnight schedule, when it can take several days of the new routine before the body stops exerting a strong urge to sleep, de la Iglesia said.

"Many of the people employed on shift work are internally desynchronized. They have a rest-activity cycle that is out of synch with the rest of their cycle, and some can't cope with this," he said. "The same thing happens to pilots who are constantly travelling across time zones."

There has been previous evidence that human rhythms can be thrown off by external cues, de la Iglesia said. For instance, people in isolation – perhaps spelunkers spending two weeks inside a dark cave – typically believe they have been isolated for a much shorter time than they really have been. That's because, lacking the usual time cues, the body's internal clocks start cycling at different paces, one running with the normal human period and one with a much longer period that makes 33 hours feel like one day.

"We think the phenomenon might have a neural base within the brain's circadian clock itself," he said.