 Neurophysiologist David Rector ponders the inner workings of the brain.
According to fellow sleep researcher James Krueger, Rector “changed
sleep research forever, . . . because he identified what it is that
sleeps.”
Piece by Piece
Another intriguing bit of information came out of Belenky’s
sleep deprivation studies: as a PVT test goes on, performance
drops. Well-rested people do a bit worse after three or four
minutes of the test. Sleep-deprived people do a lot worse after
just one minute. This is the “time-on-task” effect—the longer we do
one thing, the more fatigued we get, and the more mistakes we make.
Sleep deprivation accentuates it.
Belenky thinks the drop in performance happens because the brain
cells responsible for doing the task enter a sleep-like state after
they’ve been used a lot. That’s why a person can feel tired after
working for a long time on one task, but perk up by switching to a
different activity that uses different sets of cells.
That fit nicely with Krueger and Obal’s hypothesis. Still,
direct evidence that that’s how sleep happens remained elusive.
Electroencephalograms (EEGs) of humans couldn’t give fine enough
resolution to see what specific neuronal groups were doing. Studies
with animals offered more detail, but few ways of measuring
performance. There was no PVT test for lab rats.
Amazingly, says David Rector, there wasn’t even any way of
knowing whether neurons were “asleep” or “awake.”
“So far the sleep community has only had one definition of
sleep, and that is if you’re lying down, or in some particular
posture, and you’re not responding to external stimuli,” he says.
“It’s not a very useful definition”—especially if you’re looking at
brain cells rather than a whole animal.
In a warren of small rooms crowded with workbenches and
electrical equipment, Rector combined EEGs and a standard
behavioral test with new brain-mapping techniques to create a new
way of asking the question.
“You should see how hard these experiments are,” says Krueger.
“He has to train the animals for months.”
First, Rector trained lab rats to be comfortable hanging out in
a hammock for a couple of hours, dozing intermittently while having
a whisker twitched and brain activity recorded. The hammock was
needed to keep the rats from curling up in a ball when they napped,
which would have made the whisker work impossible.
Then, using a specially-designed electrode array, Rector mapped
the area on the surface of the brain that contained the neurons
connected to the whiskers. Once he found the column of cells
“belonging” to a particular whisker, he twitched that whisker with
a mechanical device. The size of the neuronal response told him
whether the column was asleep or awake.
While the whisker was being twitched, EEGs showed when the whole
animal was awake and asleep. Most of the time, the column’s state
matched that of the whole animal; but sometimes, the rat was awake,
but those particular cells had zoned out. The harder the cells had
been required to work—the longer the whisker had been twitched—the
more often the column entered the sleep state.
Rector had discovered the basic biological unit that sleeps: not
the whole brain, and not individual cells, but groups of cells
related by function. That was already a huge breakthrough, but
Rector went even further. He taught his rats a skill. They learned
to lick when a particular whisker was twitched, and to refrain from
licking when a different whisker was twitched. This behavior had
been used in studies with rats before, but not in conjunction with
the sleep-wake assessment. It became, in essence, the world’s first
PVT test for rats.
Once a rat was adept at its new skill, Rector twitched one
whisker repeatedly, to “tire out” the neurons connected to it. Lo
and behold, when the column went to sleep, the rat’s score on the
lick test dropped—just like Belenky’s human subjects several
minutes into a PVT.
Last fall, Lynn Churchill added another piece of the puzzle. She
found that after a prolonged period of whisker twitching, the
worked column produced TNF, the chemical Krueger had earlier shown
is related to sleepiness.
Rector had put the pieces together. Krueger and Obal were right.
Different parts of the brain can be asleep at different times. When
enough groups enter the sleep state, the whole animal goes to
sleep. There’s no central control, no on-off switch. Sleep emerges
from the individual clusters of neurons that work together on some
task. As they work, they accumulate TNF and other chemicals, and
eventually they tune out.
What sleep does for the neuronal groups remains an open
question. Krueger & Co. have ideas about it—but that’s a story
for another day.
It’s Better in a Group
Rector presented his whisker-twitch results at the national
Sleep Research Society meetings in Denver last summer.
“He changed sleep research forever,” says Krueger. “I think
David’s paper on this will probably be the single most important
paper ever published in sleep research, because he identified what
it is that sleeps.”
After the symposium, all the members of the team, plus Van
Dongen, who was not yet at WSU, and another scientist who visits
Krueger’s lab yearly, got together for a lunch that became a
brainstorming session.
“That was such a treat,” says Krueger. Their discussion brought
out ideas that culminated in a grant proposal, currently under
review by the National Institutes of Health, to look at chronic
fatigue syndrome as a disorder of the sleep-regulation system.
Krueger says that’s just one example of how a group of people
working in the same area can make headway where a lone investigator
would struggle.
“Having isolated individuals working on their areas by
themselves doesn’t work,” he says. “It’s so hard for them to
compete nationally and internationally.”
He’s especially pleased that the WSU team spans two generations
of researchers.
“Our strength is in David and Hans,” says Krueger. “They’re
young, and they are the very best. Just watching these guys
interact, already it’s just spectacular. Harvard doesn’t have
anybody that age group that’s even close to these guys. The
future’s with us.”
To learn more about sleep, sleep
deprivation, and your own sleep health, check the Web site of the
National Sleep Foundation, www.sleepfoundation.org.
Page
1
2
3
Washington State Magazine Home
|
