To discover the point of sleep, scientists breed flies that nod off on demand

By Ed Yong | June 26, 2011 12:00 pm

The good news for all new parents is that scientists have found a way of sending individuals straight to sleep by turning up the thermostat. The bad news is that it only works in flies. Alas, this technique is not going to solve anyone’s sleepless nights, but it could tell us something about why we sleep at all.

Every animal, or at least every one with a brain, needs to sleep, but it’s still not entirely clear why. William Dement, who has been studying sleep for six decades, once said, “As far as I know, the only reason we need to sleep that is really, really solid is because we get sleepy.” As Daniel Bushey from the University of Wisconsin writes, “Sleep is perhaps the only major behaviour still in search of a function.”

Traditionally, scientists have tried to deduce the role of sleep by looking at what happens when animals don’t get enough of it. But sleep deprivation wreaks wide-ranging havoc on the body and it’s a blunt instrument for understanding the function of sleep. Jeffrey Donlea from Washington University has taken a more refined approach. He has bred flies that can be sent to sleep on demand, and he used them to show how sleep boosts our ability to form lasting memories.

Donlea worked with gate-like proteins called sodium channels, and tweaked them so they would always be open. When he implanted these gates into fly neurons, they started to constantly fire, and Donlea noticed that some of the flies fell asleep far longer than their peers. By studying the brains of these heavy sleepers, he saw that the open gates had clustered around a small group of neurons within an area called the dorsal fan-shaped body. It appeared to be a control centre for sleep.

Donlea then used a slightly different sodium channel that only opens at a fixed temperature of 31 degrees Celsius. He implanted these heat-sensitive gates into the fan-shaped bodies, and when he turned up the heat, his flies went to sleep (see the right tube in the video below)  They stopped moving and they were unresponsive. They could be roused by a bright pulse of light or a firm shake, and they took longer to fall asleep if they’d had a dose of caffeine.

The dorsal fan-shaped body is involved in movement and memory, so Donlea wanted to see if he could improve the memories of his flies by sending them to sleep after bouts of learning. As flies (or humans) go through the waking day, their neurons respond to new experiences by creating connections (synapses) between one another. This is how they (and we) learn.

But there are limits. Every new synapse takes up more space and more energy. There comes a time when the barrage of experiences saturates the brain’s ability to create new synapses. The fly simply cannot learn any more. For example, Donlea showed that rich social environments – like being stuck in a group of 90 flies – can take the brain to saturation more quickly than being in isolation.

But there’s a way for flies to cope with this ceiling of learning – sleep. According to a couple of popular hypothesis, sleep gives the brain time to replay the events of the day before, integrating new pieces of information with old ones, and producing better long-term memories. The sleeping brain also has a chance to prune away any newborn synpases, keeping only those that are most useful. Like a sculptor adding lumps of clay and then moulding them into shape, the brain builds up scores of synapses when we’re awake and then pares them down when we’re asleep.

This means that the more an animal learns, the more it needs to sleep and the greater the benefits when it wakes. Some scientists have found as much by studying sleep patterns in normal flies. Indira Ganguly-Fitzgerald found that the amount of time that flies spend asleep increases with the amount of experience they acquire while awake. Social flies sleep for twice as long as those kept in solitary confinement, and they learn more information.

Now, Donlea has confirmed these results with his sleep-on-demand insects. He exposed male flies to other males that had been modified to smell like females. The males are driven to mate with the impostors but after a few rejections, they soon learn not to bother. If Donlea put his flies through this courtship training, after housing them in overwhelming groups of 90, he found that they soon forgot their lessons. However, if he sent them to sleep for a few hours after their training, they remembered what they had learned.

This supports the idea that sleep allows the brain to cope with synaptic saturation, by pruning away the excesses of an intense waking experience. A second group of scientists led by Daniel Bushey found something similar. They showed that fly neurons do indeed develop more synapses when the insects are awake, and that number only falls when they’re allowed to sleep.

Donlea also tested his flies with light bursts of courtship training. Normally, these only produce short-term memories, which fade after a few hours. But if the flies had a nap after their training, they developed long-term memories for the weird-smelling males that lasted for days. This supports the idea that sleep helps to consolidate memories.

This is just the beginning. By allowing scientists to control the timing and length of sleep, Donlea’s flies should open the way for all sorts of fascinating new experiments.

Reference: Donlea, Thimgan, Suzuki, Gottschalk & Shaw. 2011. Inducing Sleep by Remote Control Facilitates Memory Consolidation in Drosophila. Science. http://dx.doi.org/10.1126/science.1202249

More on sleep:

Comments (9)

  1. Leah Drake

    Hi Ed,

    I love your blog! Thanks for writing!

    This piece was very interesting, and reminded me of a childhood memory. My mother was a middle school math teacher (and now I’m a high school science teacher), and she gave me the following study advice: reread all of your study notes as the last thing you do before you go to bed at night, and it will help you remember in the morning. I found it extremely helpful for memorizing as well as making creative connections. This research you posted supports this advice.

    I will continue to read your blog with interest!
    Leah

  2. Just a clarification: Donlea didn’t “tweak” the ion channels he used in his experiments. Both the temperature-insensitive and temperature-sensitive ion channel reagents were developed by other scientists in other labs, and have been used extensively in a wide variety of published work.

    Donlea’s innovations in Paul Shaw’s lab are twofold:

    (1) He used these well-established reagents to identify and control a population of neurons that–when activated–induce sleep.

    (2) He exploited this new ability to acutely induce sleep to demonstrate that sleep allows a short-term memory that would otherwise have not have been to be consolidated into a long-term memory.

  3. Thanks PP – I’ve amended the sentence accordingly.

  4. Torbjörn Larsson, OM

    Ah, finally a theory that seems to go somewhere! Those social vs solitary flies sleeping times are suggestive.

    @ Leah Drake:

    Nothing in the article supports a connection between timing of learning and sleeping and the amount of consolidated memories. That is you reading something into this that simply isn’t there.

    [Or you read it out of the paper, in which case I would be interested of where exactly; it would indeed be neat.]

    If anything, the article suggests naively that unless you adjust your sleeping time rereading can be a waste of time. =D

  5. vinoy

    This is a fascinating paper! Thanks for the great writeup and bringing attention to this paper.
    One small point – I do believe that the TRPA1 channel that they used are part of the TRP family of ion channels that are thought to be calcium channels and not sodium channels (to the best of my knowledge).

  6. Leah Drake

    @Torbjörn Larsson, OM: “Nothing in the article supports a connection between timing of learning and sleeping and the amount of consolidated memories. That is you reading something into this that simply isn’t there.”

    I agree I took more out of the article than the direct implications. Not the least of which I am using the flies’ results to make an inference about my own human life. I simply thought the possible connection was interesting.

    Here is my reasoning:

    This article suggests that a function of sleep is to trim away extra synapses. It seems logical to me that if you fire synapses to create short term memories right before this process, this would make them more enforced, more likely to survive the paring down and more likely to become long term memories.

    The following quote from the blog post also shows a connection between timing of learning and sleeping and the amount of consolidated memories.

    “Donlea also tested his flies with light bursts of courtship training. Normally, these only produce short-term memories, which fade after a few hours. *But if the flies had a nap after their training, they developed long-term memories* for the weird-smelling males that lasted for days. This supports the idea that sleep helps to consolidate memories.” (emphasis mine)

    I can see a parallel between this test and my original non-scientifically-rigorous anecdote about studying in the evening before a good night’s rest.

  7. Tony

    Hmm! Intersting!

    Has anyone ever thought to further this study to possibly help those who suffer from Alzheimer’s? If you can tell one to sleep by manipulation in this manner, and sleep increases memory capabilities; is it possible to munipulate the brain to produce the effects of sleep without actually sleeping? Perhaps this would, if not defeat it, at least help fight the degratory effects of Alzheimer’s.

  8. Kandeda Trefil

    My father, who suffered from severe bipolar disorder (He died of it at age 41, before the FDA approved lithium as a medicine.) was an ambitious, extremely hard-working farmer (On his own he amassed ownership of over 800 acres in 10 years). The bottom land he farmed had steep hills on the side and a creek that ran down the middle of most fields. In a manic phase he got about 2 hours of sleep per night…BED sleep, that is.

    Riding behind him on the tractor I’ve observed his doing this:

    Cultivating a straight row, he’d fall asleep almost immediately, but he’d wake up very shortly before he reached the creek, turn, and immediately fall asleep again. When he was within seconds of reaching the steep hill that signaled the row’s opposite end…BAM!…He was awake and he’d turn once more…again and again.

  9. skeptic

    The Donlea-Shaw paper’s explanation is not convincing. How do we know the authors are really looking at increased sleep? Do the flies recover quickly after the foreign channels are turned off? Do the flies stop moving for other reasons – e.g. are they in pain? How do we know that the neurons they say are responsible normally regulate sleep? Exactly what are the foreign channels doing to the neurons? They are not sodium channels as you say but calcium channels, and calcium does many things to cells. Do the effects of sustained excess calcium replicate the normal roles of these cells? Can the authors get the opposite effect – increased waking – by turning off the neurons in which they express the foreign channels?

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