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University of California, San Francisco
researchers are reporting direct evidence that sleep in early
life may play a crucial role in brain development.
The study indicates that sleep
dramatically enhances changes in brain connections
during a critical period of visual development in cats.
The capacity for "change," or
growth and strengthening, of connections between nerve cells
is the basis of development in the brain. The elaboration
and refinement of neural circuitry continues to a lesser extent
in the adult brain.
The process of growth, known as plasticity,
is believed to underlie the brain's capacity to control behavior,
including learning and memory. Plasticity occurs when neurons
are stimulated by events, or information, from the environment.
In their study, the researchers examined
the effect of sleep on brain plasticity after cats experienced
an environmental challenge. They determined that animals allowed
to sleep for six hours after the period of environmental stimulation
developed twice the amount
of brain change as those cats kept awake during
that time. The animals that were allowed to sleep even had
slightly more brain change than the animals whose environmental
challenge continued during the additional six hours.
The findings provide strong evidence that
a function of sleep is to help consolidate the effects of
waking experience on cortical plasticity, converting memory
into more permanent and/or enhanced forms.
This is the first direct evidence that
sleep modifies the effect of environmental stimuli on the
development of new brain connections.
While the study focused specifically on
the impact of sleep on neuronal remodeling during the critical
period for visual development in the cat, the researchers
believe the finding has broader implications, not just for
plasticity during development in
other brain structures, but for plasticity in the adult brain.
If this is shown to be the case, sleep
could prove an important part of the strategy for preparing
for such challenges as exams.
The fact that sleep provoked slightly
more plasticity than double the amount of exposure to experience
[when cats remained awake in a lit room] suggests that if
you reviewed your notes thoroughly until you were tired and
then slept, you'd achieve as much plasticity, or 'learning,'
in the brain as if you'd pulled an all-nighter repeating your
review of the material.
Significantly, the researchers determined
that the amount of plasticity in the brain depended on the
amount of sleep known as non-rapid eye movement, a deep, quiet,
slumber marked by large, slow brain waves. This is the sleep
that a person falls into when he or she first goes to sleep
and which accounts for half of sleep in animals of this age.
Non-REM sleep alternates with periods of rapid eye movement,
or so-called "dream" sleep, a period marked by rapidly
changing brain waves and rapid bursts of eye movement.
This discovery offers direction for examining
the two major hypotheses for how sleep impacts plasticity.
One theory is that patterned neuronal activity following a
period of environmental stimulation is replayed during non-REM
sleep, strengthening neuronal connection changes. The alternative
theory, which could also work in conjunction with the first,
is that powerful growth factors, such as neurotrophins, which
are known to be necessary for cortical plasticity, are released
during non-REM sleep.
Right now we don't know if these neurotrophins
are released during sleep. We do know that other growth factors
are released during sleep and we also known that these neurotrophins
play a role in learning and making the synapses of the brain
stronger and weaker.
In either case, the new evidence that
sleep appears to play a significant role in brain development
puts researchers an important step closer to solving a mystery
that has persisted for decades. Every animal sleeps - even
flies may have a state like sleep. But despite great progress
in our understanding of the regulation and neurobiology of
sleep, as well as the consequences of sleep loss on human
performance, why the brain
needs sleep has remained a mystery.
Speculation has ranged from evolutionary
theories - we need sleep to prevent us from wandering out
of our caves in the dark or sleep is just a way of keeping
us inactive for period of time when goblins or saber tooth
tigers are out - to theories having to do with the function
of neural networks.
Researchers have known that in early development
birds and mammals, including humans, sleep as much as three
times the amount as adult birds and mammals. And they have
long suspected that neuronal connections are remodeled during
sleep. Previous studies in humans have shown that
sleep and sleep loss influence learning and memory
- two processes thought to depend on neuronal plasticity.
And studies have shown that animals and
humans deprived of sleep do not perform well on memory tasks.
Other studies in rodents, birds and humans have suggested
that neuronal activity initiated while awake is reactivated
and possibly consolidated during subsequent sleep.
Other studies have shown that sleep and
sleep loss modify the expression of several genes and gene
products that may be important for synaptic plasticity; that
certain forms of long-term potentiation, a neural process
associated with the laying down of learning and memory, can
be elicited in sleep, suggesting synaptic connections are
strengthened during sleep; and that sleep amounts are very
high and undergo dramatic modifications during developmental
periods of heightened synaptogenesis and synaptic plasticity.
But while these findings together provide
strong, suggestive evidence that synaptic circuits are modified
during sleep the
current study provides the first direct evidence that sleep
and sleep loss modify experience-dependent changes in synaptic
plasticity.
The significance of our study is that
we examined a system in which we know a great deal about the
neural inputs and the outputs - we know how information gets
into the visual cortex from the two eyes, how it changes during
normal development, and we know a lot about what goes on in
the circuitry to cause plasticity in this system, and to cause
the loss of response to the eye after monocular deprivation.
Among other things, now we can begin to
examine to what extent the mechanisms inherent in sleep are
distinct from those governing cortical plasticity during wakefulness.
We should also gain general insights into plasticity.
To tease out the impact of sleep on plasticity
during early brain development, the researchers established
a model in which they measured in cats the response of neurons
of the visual cortex to an environmental challenge -vision
blocked in one eye for six hours.
The visual deprivation initiates a rapid
remodeling of neural circuitry known as ocular dominance plasticity.
The researchers then examined the impact of sleep on the long-term
effects of those changes by using brain imaging and making
electrical recordings from brain cells.
First, in one set of cats they took a
measurement of the brain change, or plasticity, immediately
following the period of visual deprivation. Then, in the other
three sets of cats, they examined the relative effects of
sleep or lack of sleep on the initial plasticity. This is
where the provocative findings were made.
The UCSF team
determined that animals allowed to sleep for six hours after
the period of visual deprivation developed twice the amount
of brain change as those cats kept awake in a dark room during
those six hours.
The animals allowed to sleep also had
twice the amount of change as the cats evaluated immediately
following the period of visual deprivation.
Finally, the cats allowed to sleep even
had slightly more brain change than those animals who were
kept awake in a light room with continued visual stimulation
through one eye and whose brains had therefore had had twice
as much time to respond to the light stimulus with just one
eye open.
Neuron April
26, 2001
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