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Research starring brain cells known as astrocytes uncovers a pathway that allows mental acuity to lie alongside sleep deprivation.
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In the late 1980s, researchers subjected rats to prolonged sleep deprivation by keeping them on never-stopping conveyor belts, recorded their fluctuating body temperatures, noted a drastic drop in weight, then watched them fall over dead.

We've written previously about the health consequences that can accompany sleep loss. And despite controversy regarding how essential sleep is, few will dispute that the sleep urge, the feeling that the eyelids are obliged to close, is a strong desire.

New research, a collaboration between laboratories at Tufts University School of Medicine and the University of Pennsylvania, has introduced mice that are less prone to sleepiness, resistant to sleep deprivation and — get this —maintain their sharp wit despite reduced sleep.

The report, largely the work of first author Michael Halassa and published in Neuron, shows that “sleep pressure,” as researchers term the desire to sleep, is regulated by a special class of stars — astrocytes.

These star-shaped cells — shown twinkling with green fluorescence in the Tufts laboratory of Philip Haydon — are reminiscent and yet distinct from neurons. They don't have the same electrical reputation as neurons, with wild action potentials and the capacity to propagate signals. Described in the 1800s as “cement” in the brain, astrocytes are still widely referred to as “support” cells, since they, in part, frame or couch neurons. But neuroscientists in the 2000s now emphasize that astrocytes are more than mere furniture and play significant roles in many brain processes; this new research is the first report implicating them directly in any sort of behavior.

Enter caffeine, a much indulged, ever-so-popular, sleep-countering stimulator. “Caffeine can promote wakefulness, we know that too well,” said Haydon. It does this by essentially disabling receptors for adenosine, a neurotransmitter that accumulates between brain cells as wake time increases, driving sleepiness.

High adenosine equates to high sleep need, which in turn is associated with deep (or slow-wave) sleep. In the sleep deprived, slow-wave activity increases in intensity when sleep is finally permitted.
Adenosine is also, circuitously, provided by astrocytes.

Haydon's team engineered mice astrocytes to be able to turn on and off the release of adenosine. Turn out the stars and look, the mice are still spry. In fact, once the sleep-deprived mice are allowed to sleep, their slow-wave activity does not increase as it would for those with functioning astrocytes. Their need for make-up sleep is reduced. (Variability in this system may help explain the diversity in sleep requirements among individuals.)

And when the mice with disabled astrocytes were sleep deprived, their memory performance remained unimpaired. Since many studies show a link between cognitive function and sleep, this is a striking find.

Using different compounds (including caffeine), the researchers dissected the receptors involved with sleepiness, which demonstrated that sleep regulation “acts critically” through the adenosine A1 receptor, Haydon explained. Manipulating the adenosine pathway, particularly the A1 receptor, is one way medications make you drowsy or keep you up. (Caffeine, by the way, carries most of its might through a different receptor.)

Haydon's group is going on to investigate how neurons hold up during chronic sleep restriction. Currently the mice are in cages with a slow-moving conveyor belt preventing them from nodding off.

While it's unclear what will happen when these modified mice endure days (for the aforementioned rats it was weeks) ofprolonged sleep deprivation conditions, this study gives those inclined to understanding how and why sleep is regulated a new star to reach for.

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