Insomnia Series: The Purpose Of Sleep

NY Times Article Here

Over the years, scientists have come up with a lot of ideas about why we sleep.

Some have argued that it’s a way to save energy. Others have suggested that slumber provides an opportunity to clear away the brain’s cellular waste. Still others have proposed that sleep simply forces animals to lie still, letting them hide from predators.

A pair of papers published on Thursday in the journal Science offer evidence for another notion: We sleep to forget some of the things we learn each day.

In order to learn, we have to grow connections, or synapses, between the neurons in our brains. These connections enable neurons to send signals to one another quickly and efficiently. We store new memories in these networks.

In 2003, Giulio Tononi and Chiara Cirelli, biologists at the University of Wisconsin-Madison, proposed that synapses grew so exuberantly during the day that our brain circuits got “noisy.” When we sleep, the scientists argued, our brains pare back the connections to lift the signal over the noise.

In the years since, Dr. Tononi and Dr. Cirelli, along with other researchers, have found a great deal of indirect evidence to support the so-called synaptic homeostasis hypothesis.

It turns out, for example, that neurons can prune their synapses — at least in a dish. In laboratory experiments on clumps of neurons, scientists can give them a drug that spurs them to grow extra synapses. Afterward, the neurons pare back some of the growth.

Other evidence comes from the electric waves released by the brain. During deep sleep, the waves slow down. Dr. Tononi and Dr. Cirelli have argued that shrinking synapses produce this change.

Four years ago, Dr. Tononi and Dr. Cirelli got a chance to test their theory by looking at the synapses themselves. They acquired a kind of deli slicer for brain tissue, which they used to shave ultrathin sheets from a mouse’s brain.

How to Get a Better Night’s Sleep

How do you become a more successful sleeper? Grab a pillow, curl up and keep reading to find out.

Luisa de Vivo, an assistant scientist working in their lab, led a painstaking survey of tissue taken from mice, some awake and others asleep. She and her colleagues determined the size and shape of 6,920 synapses in total.

The synapses in the brains of sleeping mice, they found, were 18 percent smaller than in awake ones. “That there’s such a big change over all is surprising,” Dr. Tononi said.

The second study was led by Graham H. Diering, a postdoctoral researcher at Johns Hopkins University. Dr. Diering and his colleagues set out to explore the synaptic homeostasis hypothesis by studying the proteins in mouse brains. “I’m really coming at it from this nuts-and-bolts place,” Dr. Diering said.

In one experiment, Dr. Diering and his colleagues created a tiny window through which they could peer into mouse brains. Then he and his colleagues added a chemical that lit up a surface protein on brain synapses.

Looking through the window, they found that the number of surface proteins dropped during sleep. That decline is what you would expect if the synapses were shrinking.

Dr. Diering and his colleagues then searched for the molecular trigger for this change. They found that hundreds of proteins increase or decrease inside of synapses during the night. But one protein in particular, called Homer1A, stood out.

In earlier experiments on neurons in a dish, Homer1A proved to be important for paring back synapses. Dr. Diering wondered if it was important in sleep, too.

To find out, he and his colleagues studied mice genetically engineered so that they couldn’t make Homer1A proteins. These mice slept like ordinary mice, but their synapses didn’t change their proteins like the ones in ordinary mice.

Dr. Diering’s research suggests that sleepiness triggers neurons to make Homer1A and ship it into their synapses. When sleep arrives, Homer1A turns on the pruning machinery.

To see how this pruning machinery affects learning, the scientists gave regular mice a memory test. They put the animals in a room where they got a mild electric shock if they walked over one section of the floor.

That night, the scientists injected a chemical into the brains of some of the mice. The chemical had been shown to block neurons in dishes from pruning their synapses.

The next day, the scientists put all the mice back in the chamber they had been in before. Both groups of mice spent much of the time frozen, fearfully recalling the shock.

But when the researchers put the mice in a different chamber, they saw a big difference. The ordinary mice sniffed around curiously. The mice that had been prevented from pruning their brain synapses during sleep, on the other hand, froze once again.

Dr. Diering thinks that the injected mice couldn’t narrow their memories down to the particular chamber where they had gotten the shock. Without nighttime pruning, their memories ended up fuzzy.

In their own experiment, Dr. Tononi and his colleagues found that the pruning didn’t strike every neuron. A fifth of the synapses were unchanged. It’s possible that these synapses encode well-established memories that shouldn’t be tampered with.

“You can forget in a smart way,” Dr. Tononi said.

Other researchers cautioned that the new findings weren’t definitive proof of the synaptic homeostasis hypothesis.

Marcos G. Frank, a sleep researcher at Washington State University in Spokane, said that it could be hard to tell whether changes to the brain at night were caused by sleep or by the biological clock. “It’s a general problem in the field,” he said.

Markus H. Schmidt, of the Ohio Sleep Medicine Institute, said that while the brain might prune synapses during sleep, he questioned whether this was the main explanation for why sleep exists.

“The work is great,” he said of the new studies, “but the question is, is this a function of sleep or is it the function?”

Many organs, not just the brain, seem to function differently during sleep, Dr. Schmidt pointed out. The gut appears to make many new cells, for example.

Dr. Tononi said that the new findings should prompt a look at what current sleeping drugs do in the brain. While they may be good at making people sleepy, it’s also possible that they may interfere with the pruning required for forming memories.

“You may actually work against yourself,” Dr. Tononi said.

In the future, sleep medicines might precisely target the molecules involved in sleep, ensuring that synapses get properly pruned.

“Once you know a little bit of what happens at the ground-truth level, you can get a better idea of what to do for therapy,” Dr. Tononi said.

Insomnia Series: Why It Hurts to Lose Sleep

NY Times Article Here

Sleep deprivation can make your physical aches more painful. A new study begins to explain how that happens.

A subject in a sleep-disorder clinic in France. Recent research found that staying awake all night can increase a person’s sensitivity to pain the next morning by as much as 30 percent.CreditBSIP/UIG, via Getty Images

 

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A subject in a sleep-disorder clinic in France. Recent research found that staying awake all night can increase a person’s sensitivity to pain the next morning by as much as 30 percent. CreditCreditBSIP/UIG, via Getty Images

Veteran insomniacs know in their bones what science has to say about sleep deprivation and pain: that the two travel together, one fueling the other.

For instance, people who develop chronic pain often lose the ability to sleep well, and quickly point to a bad back, sciatica or arthritis as the reason. The loss of sleep, in turn, can make a bad back feel worse, and the next night’s slumber even more difficult.

Why sleep deprivation amplifies pain is not fully worked out, but it has to do with how the body responds to an injury such as a cut or turned ankle. First, it hurts, as nerves send a blast up the spinal cord and into the brain. There, a network of neural regions flares in reaction to the injury and works to manage, or blunt, the sensation.

Think of the experience as a kind of physiological dialogue between the ground unit that took the hit and the command-control center trying to contain the damage. In a new study, a team of neuroscientists has clarified the nature of the top-down portion of that exchange, and how it is affected by sleep.

In a sleep-lab experiment, the researchers found that a single night of sleep deprivation reduced a person’s pain threshold by more than 15 percent and left a clear signature in the brain’s pain-management centers.

In a separate experiment, the team determined that small deviations in the average amount of sleep from one day to another predicted the level of overall pain felt the next day.

“What’s exciting about these findings is that they will stimulate, and justify, doing more research to figure this system out,” said Michael J. Twery, director of the sleep disorders branch of the National Heart, Lung and Blood Institute, who was not involved in the new study. “Once we understand how sleep deprivation changes how these pathways function, we should be able to manage pain more effectively — all types of pain.”

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Other researchers cautioned that the study was small, and in need of larger replication. But, they said, at a time when chronic pain conditions and narcotic addiction are on the rise, the new work is a pointed reminder that the body’s own ability to manage pain can be improved without a prescription.

The study team, led by Adam J. Krause and Matthew P. Walker of the University of California, Berkeley, had 25 adults come into the lab on two occasions to measure their pain threshold for heat. Two measurements were taken from each subject, one in the morning after a full night’s sleep, and one in the morning after staying up all night. The two visits occurred at least a week apart, and included measurements in a brain-imaging machine.

The subjects judged the pain sensation of having a small, heated pad pressed against their skin, near the ankle. By gradually adjusting the temperature up and down, the researchers identified the level of pain that each person graded as 10, or “unbearable,” on a scale of 1 to 10.

Pulling an all-nighter increased everyone’s sensitivity to heat the next morning, by 15 to 30 percent on the pain scale. This wasn’t unexpected; previous research had produced similar findings, for a variety of painful sensations.

But the brain imaging added a new dimension: For each participant, activity spiked in pain perception regions, and plunged in regions thought to help manage or reduce pain. The biggest peaks were in the somatosensory cortex, a strip of neural tissue that runs across the top of the brain like a headphone band.

This is the seat of the so-called homunculus, the distorted “little man” neural map of the body; it seems to be where the perception of pain becomes a conscious “ouch.” The lowest troughs of activity occurred in deeper brain regions such as the thalamus and nucleus accumbens.

“So you have two things happening at once here,” said Dr. Walker, director of the Center for Human Sleep Science at U.C. Berkeley. “There’s ramped up sensation to pain, and a loss of natural analgesic reaction. The fact that both of them happen was surprising.”

Deliberate sleep deprivation is rare in the natural world — robins and squirrels tend not to stay up late to catch “Saturday Night Live” — so it may be that no backup systems have evolved to help restore or tune the brain’s pain management system, Dr. Walker said.

In a separate trial, the research team recruited 60 adults online who reported having daily pain. The participants rated their sleep and pain over two days, scoring the previous night’s slumber in the mornings, and their pain level in the evenings.

For each individual, poor sleep quality predicted higher ratings on the daily pain scale. The duration of sleep was not the critical factor, the study found; what mattered were alterations to deep sleep, the mostly dreamless period of rich slumber.

The implications of the new work are wide-ranging, perhaps starting with hospitals, where noise levels are high and interruptions frequent. Handing out earplugs and sleep masks, as the airlines do, would be a cheap way to speed recovery and shorten hospital stays, the study’s authors suggested.

“The good news is that it has become really clear in psychiatry and the memory field that sleep is a big player,” said Dr. Robert Stickgold, an associate professor of psychiatry at Harvard Medical School. “The bad news is that the average trickle-down time from research to practices is ten years plus.”