Study: Brain connections strengthen during waking hours, weaken during
sleep

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."

Source: University of Wisconsin-Madison
http://www.physorg.com/news120059987.html