The Purpose of Sleep? To Forget, Scientists Say
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.
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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.
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.
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