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Brain
connections strengthen during waking hours,
weaken during sleep
Newswise — Most people know it from
experience: After so many hours of being
awake, your brain feels unable to absorb any
more-and several hours of sleep will refresh
it.
Now new research from the University of
Wisconsin School of Medicine and Public
Health clarifies this phenomenon, supporting
the idea that sleep plays a critical role in
the brain's ability to change in response to
its environment. This ability, called
plasticity, is at the heart of learning.
Reporting in the Jan. 20, 2008, online
version of Nature Neuroscience, the
UW-Madison scientists showed by several
measures that synapses - nerve cell
connections central to brain plasticity -
were very strong when rodents had been awake
and weak when they had been asleep.
The new findings reinforce the UW-Madison
researchers' highly-debated hypothesis about
the role of sleep. They believe that people
sleep so that their synapses can downsize
and prepare for a new day and the next round
of learning and synaptic strengthening.
The human brain expends up to 80 percent of
its energy on synaptic activity, constantly
adding and strengthening connections in
response to all kinds of stimulation,
explains study author Chiara Cirelli,
associate professor of psychiatry.
Given that each of the millions of neurons
in the human brain contains thousands of
synapses, this energy expenditure "is huge
and can't be sustained."
"We need an off-line period, when we are not
exposed to the environment, to take synapses
down," Cirelli say. "We believe that's why
humans and all living organisms sleep.
Without sleep, the brain reaches a
saturation point that taxes its energy
budget, its store of supplies and its
ability to learn further."
To test the theory, researchers conducted
both molecular and electro-physiological
studies in rats to evaluate synaptic
potentiation, or strengthening, and
depression, or weakening, following sleeping
and waking times. In one set of experiments,
they looked at brain slices to measure the
number of specific receptors, or binding
sites, that had moved to synapses.
"Recent research has shown that as synaptic
activity increases, more of these
glutamatergic receptors enter the synapse
and make it bigger and stronger," explains
Cirelli.
The Wisconsin group was surprised to find
that rats had an almost 50 percent receptor
increase after a period of wakefulness
compared to rats that had been asleep.
In a second molecular experiment, the
scientists examined how many of the
receptors underwent phosphorylation, another
indicator of synaptic potentiation. They
found phosphorylation levels were much
higher during waking than sleeping. The
results were the same when they measured
other enzymes that are typically active
during synaptic potentiation.
To strengthen their case, Cirelli and
colleagues also performed studies in live
rats to evaluate electrical signals
reflecting synaptic changes at different
times. This involved stimulating one side of
each rat's brain with an electrode following
waking and sleeping and then measuring the
"evoked response," which is similar to an
EEG, on another side.
The studies again showed that, for the same
levels of stimulation, responses were
stronger following a long period of waking
and weaker after sleep, suggesting that
synapses must have grown stronger.
"Taken together, these molecular and
electro-physiological measures fit nicely
with the idea that our brain circuits get
progressively stronger during wakefulness
and that sleep helps to recalibrate them to
a sustainable baseline," says Cirelli.
The theory she and collaborator Dr. Giulio
Tononi, professor of psychiatry, have
developed, called the synaptic homeostasis
hypothesis, runs against the grain of what
many scientists currently think about how
sleep affects learning. The most popular
notion these days, says Cirelli, is that
during sleep synapses are hard at work
replaying the information acquired during
the previous waking hours, consolidating
that information by becoming even stronger.
"That's different from what we think," she
says. "We believe that learning occurs only
when we are awake, and sleep's main function
is to keep our brains and all its synapses
lean and efficient."