How does an Animal’s Biological Clock Wakes it up in the Morning and puts it to sleep at Night?

Sleeping mouse (stock image). “What is amazing is finding the same mechanism for sleep-wake cycle control in an insect and a mammal,” said Matthieu Flourakis, the lead author of the study. “Mice are nocturnal, and flies are diurnal, or active during the day, but their sleep-wake cycles are controlled in the same way.” Credit: © Iosif Szasz-Fabian / Fotolia

In studies of fruit flies and mice and the brain circadian neurons governing the daily sleep-wake cycle’s timing, the researchers found that high sodium channel activity in these neurons during the day turn the cells on and ultimately awaken an animal, and high potassium channel activity at night turn them off, allowing the animal to sleep.

“This suggests the underlying mechanism controlling our sleep-wake cycle is ancient,” said Professor Allada. “This oscillation mechanism appears to be conserved across several hundred million years of evolution. And if it’s in the mouse, it is likely in humans, too.” Better understanding of this mechanism could lead to new drug targets to address sleep-wake trouble related to jet lag, shift work and other clock-induced problems. Eventually, it might be possible to reset a person’s internal clock to suit his or her situation.

The researchers call this a “bicycle” mechanism: 2 pedals that go up and down across a 24-hour day, conveying important time information to the neurons. That the researchers found the 2 pedals – a Na+ current and K+ currents – active in both the simple fruit fly and the more complex mouse was unexpected. “Mice are nocturnal, and flies are diurnal, or active during the day, but their sleep-wake cycles are controlled in the same way.” The balance between sodium and potassium currents controls the animal’s circadian rhythms.

•Rhythmic sodium leak conductance depolarizes Drosophila circadian pacemaker neurons •NCA localization factor 1 links the molecular clock to sodium leak channel activity •Antiphase cycles in resting K+ and Na+ conductances drive membrane potential rhythms •This “bicycle” mechanism is conserved in master clock neurons between flies and mice

They studied a small region of the mouse brain that controls the animal’s circadian rhythms – the suprachiasmatic nucleus, made up of 20,000 neurons – and found the same mechanism there. “Our starting point for this research was mutant flies missing a sodium channel who walked in a halting manner and had poor circadian rhythms,” Allada said.
“Now, of course, we have more questions about what’s regulating this sleep-wake pathway, so there is more work to be done,” he said. http://www.eurekalert.org/pub_releases/2015-08/nu-sdw081315.php