Mice that have a particular brain chemical switched off become
hyperactive and sleep for just 65 per cent of their normal
time.
This discovery could help researchers to develop new drugs that
promote better sleep, or control hyperactivity in people with the
medical condition mania.
Scientists altered the neurochemistry of mice to help
investigate why we need to sleep, what controls our wakefulness,
and how a balance between these two states influences brain
functions like concentration and memory and our general health.
The chemicals they studied, histamine and GABA, are produced in
a primitive part of the brain that is highly similar in mice and
humans.
The team of scientists was led by Dr Stephen Brickley, Professor
Nick Franks and Professor Bill Wisden of Imperial College
London.
Professor Wisden said, "Sleep is essential for health. We have
to do it every day. But nobody yet knows why."
Scientists already know the chemical histamine sends signals to
the brain to make it awake, which is why antihistamines are
associated with drowsiness. The new research suggests that the
chemical GABA acts against histamine, like a chemical 'brake'
preventing wakefulness being too intense.
The researchers found that GABA and histamine are made in the
same brain cells, called histamine neurons, which led the
scientists to question its function. They altered the levels of the
GABA produced by the mice's brains and measured what changes this
had on their brain activity over the day and night.
Mice without the GABA chemical developed characteristics similar
to a medical condition called mania, in which patients experience
restlessness and sleeplessness. In humans these are often also
symptoms of bipolar disorder, which affects around 2.4 million
people in the UK.
"Wakefulness stimulated by histamine may be too much of a good
thing, and so the brain has a built in brake on histamine's
wake-inducing actions," said Dr Brickley.
The scientists found that compared with normal mice, those
without GABA ran twice as far and twice as fast, and maintained or
even increased their overall activity over a 30 minute period.
The mice also stayed awake much longer in the day, when they
would otherwise be asleep. When they did sleep, the mice
experienced just 65 per cent of the normal amount of non-REM (Rapid
Eye Movement) sleep, a heavy sleep state with no
dreaming.
"What particularly surprised us was how little the mice were
affected by sleep deprivation," said Professor Franks.
"Normally mice that lose 5 hours of sleep would sleep for longer
following this deprivation, and we would see a much lower level of
activity. These mice kept up their hyperactive state over the
following 16 hours they were awake. They didn't appear to need any
recovery sleep at all."
The scientists have begun new work with mice to investigate the
link between lack of sleep and memory loss. They hope this will
lead to a better understanding of the link between poor sleep and
mental health issues in humans.
The paper, Wakefulness
Is Governed by GABA and Histamine Cotransmission, is published
in Neuron.