Fly on the Wall

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Tag: sleep

Valentine’s Day Special: Drosophila in lust

Valentine’s Day is quickly approaching, which means that men (and women) all over the U.S. are performing courtship rituals to woo a companion. But while we humans often have trouble figuring out the right moves to attract a potential mate, fruit flies have it down to a science. And incredibly, researchers can study fruit fly courtship to gain a better understanding of our own brains.

Fly courtshipThe fruit fly courtship ritual has a set of specific steps. Image modified from Greenspan and Ferveur, 2000.

In polite fruit fly society, males have the responsibility of wooing a female. The mating behavior is composed of several specific steps (see figure), which the males perform in repetition until the female responds (or until the male gives up trying). This courtship behavior is very well understood by researchers, due in part because the courtship ritual is so stereotyped and predictable. Courtship is a complex innate behavior, which means that all flies are born with the knowledge of how to do it. Successful mating means passing your genes on to the next generation, so the networks of neurons responsible for this behavior are critical for survival and therefore consistent among flies. This consistency provides a perfect system for studying how neurons interact to give rise to a behavior.

Fly researchers have made great progress in unraveling the anatomy underlying courtship, and found that the behavior arises from the integration of multiple sensory cues, including smell (is the female releasing “come and get me” pheromones?), vision (does the female look interested?), and touch (am I in the right spot?). The fruit fly brain has to combine all of this information to influence the fly’s decision making. Should he start the next step of the courtship ritual, or try this one again? Can he approach the female and try to mate?

“But who cares about fruit fly sex?” you might ask. The fly researchers studying courtship aren’t necessarily interested in exactly how flies get it on. They’re more interested in a general understanding of how the brain integrates multiple sensory cues to influence decisions. The fact that the “courtship circuit” is critical for survival suggests that it is also used by other important behaviors, and is shared by other species. Think about how much information needs to be integrated for you to hunt for food, drive a car, or even court another human. The complexity is amazing… how does our brain manage that?!  By first studying it in the simpler brains of fruit flies, we can gain a basic understanding that we can apply to our complex mammalian brains.

Studying courtship behavior can provide us with an understanding for how neurons communicate and integrate information to make decisions, but researchers can do even more with it. As our understanding of courtship increases, we can use it to investigate other behaviors that seem more directly related to human health, such as learning and memory, sleep, and addiction.

For example, the courtship ritual is most commonly used to study memory. Researchers have noticed that male flies tend to “give up” after too many rejections, so they’ve developed a learning experiment that exposes males to uninterested females. Normal males quickly learn to give up on trying to mate with them, but what happens if a scientist mutates a particular gene or “turns off” a certain molecule? Now researchers can use courtship to investigate the genes and molecules involved in learning and memory. If a mutant male never learns to stop courting, the gene might be involved in learning. If the mutant male initially learns to give up, but then quickly forgets the experience and tries again, the gene might be involved in long-term memory.

The predictable steps of courtship also allows researchers to easily recognize when a male is impaired in this innate behavior, providing a system for studying brain development. Last year, the Seghal lab published a study in which they used courtship behavior to show that sleep is necessary for normal brain development. They deprived young flies of sleep and found that, as adults, the flies were impaired in courtship. The impairment was due to lack of growth in a brain region important for the behavior, suggesting that sleep deprivation stunts brain development.

As a final example (and one of my favorites), in 2012 the Heberlein lab produced a paper showing that sexual rejection makes male flies turn to booze. Natural rewards such as sex activate the brain’s reward system, which is also activated by abused drugs and alcohol (did you know that flies can be alcoholics too?). Understanding how natural rewards, drugs, and rejections affect the reward system is important for treating or preventing addiction. From this study, the researchers in the Heberlein lab found that levels of neuropeptide F (NPF), a signaling chemical, rose and fell with reward and rejection. Low levels of NPF drove flies to drink, and artificially raising NPF levels prevented this behavior. Their finding that the same chemical is involved in both natural and artificial rewards directly helps research aimed at understanding a similar chemical in mammals called NPY.

In these research examples, the goal of studying courtship wasn’t to learn about fruit fly sex, it was to use what we know to answer more important questions. Because of these studies, researchers have identified dozens of genes and molecules involved in learning and memory, uncovered more reasons for why sleep is important, and progressed our understanding of how alcohol affects the brain. All of these findings have direct implications for human health because we also share those memory genes, need sleep, and use drugs and alcohol.

Flies in love

So the next time you see some flies getting it on near your bananas… swat them, because they’ll make hundreds of new nuisances for you to deal with. But afterward, you can smile knowingly to yourself and remember that scientists are studying the act to answer long-standing questions in neuroscience.

 

 

General references:

  • Pavlou H.J. and S.F. Goodwin (2013). Courtship behavior in Drosophila melanogaster: towards a ‘courtship connectome’, Current Opinion in Neurobiology, 23 (1) 76-83. DOI: http://dx.doi.org/10.1016/j.conb.2012.09.002
  • Griffith L.C. and A. Ejima (2009). Courtship learning in Drosophila melanogaster: Diverse plasticity of a reproductive behavior, Learning , 16 (12) 743-750. DOI: http://dx.doi.org/10.1101/lm.956309

Breaking Research: Fruit flies help uncover the brain’s link between sleep and memory

Researchers at Brandeis University have found that the link between sleep and memory is stronger than we thought. It is well known that sleep is important for learning and memory, and many people can attest to having a hard time focusing and remembering things after a bad night’s sleep. Students often receive advice about getting a good night’s sleep instead of late-night cramming before a test. Simply put, scientists have learned that the brain takes advantage of the quiet hours during sleep to transfer newly-learned memories into long-term storage.

But how exactly are these complex behaviors connected in the brain? Does sleep simply permit memory storage to take place, such that the part of the brain involved in memory just takes advantage of sleep whenever it can? Or are sleep and memory physically connected, and the same mechanism in the brain is involved in both? In a recent study published in eLife, researchers in the Griffith lab may have finally uncovered the answer. They found that a single pair of neurons, known as the DPM neurons, are actively involved in both sleep and memory storage in fruit flies.

Why the fly? Fruit flies may be less complex than humans, but they have similar behaviors such as sleep and memory, and their brains have a similar organization. You may have heard of the hippocampus: the seahorse-shaped brain region in mammals that is responsible for learning and memory. The hippocampus receives a lot of information from other parts of the brain, and it has been very difficult for researchers to sort it all out. Fortunately, fruit flies have a similar region called the mushroom bodies (MBs), which are also important for learning and memory. Even better, fruit fly researchers have identified many of the neurons that send information to the MBs. One such example is the DPM neurons, which are critical for long-term memory storage. If the DPM neurons (there’s just two of them!) are “turned off” so that they can’t communicate with the MBs, flies can’t form long-term memories. This gave the researchers a great place to start for studying how sleep and memory are linked in the brain.

To find out if the DPM neurons are also involved in sleep, the group manipulated the activity levels of the DPM neurons and observed whether the flies showed any changes in their sleep patterns (Click here if you want to learn more about exactly how we study sleep in flies). They found that the DPM neurons had a dramatic effect: hyper-activating them increased the amount of time the flies slept, while silencing them decreased sleep (remember that silencing them also shut down long-term memory storage). Thus, sleep doesn’t just permit memory storage. These behaviors are actually tied to the same mechanism—the same neurons!—in the fruit fly brain.

Dream WaterThe fact that DPM neurons use GABA and serotonin is another similarity to us. Those chemical promote sleep in humans too, and many sleep aids include GABA and/or serotonin supplements.

As the researchers delved further, they found that the DPM neurons were dampening part of the MBs’ activity using GABA and serotonin (both are chemical messengers that neurons use for communicating with each other). That part of the MBs was important for learning and, as it turns out, also signaling wakefulness. It’s almost as if that section of the MBs were saying “Hey, stay awake and learn this”. After a while, however, the DPM neurons may start signaling to suppress the MBs, as if to say “You’re going to need sleep if you want to remember this later”.

Finally, there was another interesting insight uncovered by this study. It is widely believed that long-term memory is stored when groups of neurons signal back and forth in an excitatory manner, progressively strengthening their connections with one another (you may have heard the adage “neurons that fire together, wire together”). Yet, the authors of this study found that the DPM neurons, which are critical for memory storage, are not actually excitatory. To the contrary, they inhibit a section of the MBs necessary for learning. What role does inhibition play in memory? This finding doesn’t answer that question, but it does demonstrate just how much work is left to be done.

 

 
Reference:

  • Haynes P.R., Christmann, B.L. & Leslie C. Griffith (2015). A single pair of neurons links sleep to memory consolidation in Drosophila melanogaster , eLife, 4 DOI: http://dx.doi.org/10.7554/elife.03868

Fly Life: Watching fruit flies sleep

Did you know that fruit flies sleep? There are actually a lot of similarities between sleep in fruit flies and sleep in humans and other mammals. For example…

Caffeinated flyImage modified from Colwell, 2007
  • Like us, fruit flies get most of their sleep at night, and they also have an afternoon slump (although unlike us, they actually give in to their sleep desires instead of running for coffee).
  • Their sleep is affected by the same drugs: caffeine, cocaine, and modafinil (an alertness drug) keep them awake, while antihistamines (allergy medication) make them drowsy just like us.
  • They sleep more at higher temperatures (think of lazy summer days)
  • If they get a bad night’s sleep, they’ll try to sleep more the next day to make up for it. In fact, sleep deprivation even affects their memory performance (have you ever noticed that your memory isn’t so great after a bad night’s sleep?)

And the comparisons don’t stop there. Over the years, fruit flies have proven to be a great animal model for studying sleep, and researchers have used them to improve our understanding of why sleep is important. In fact, earlier this year a group of researchers found that young flies need sleep for normal brain development.

But, how do fly researchers actually study sleep in these tiny flies?

DAM system

The most common method is called the Drosophila Activity Monitoring (DAM) system. Flies are loaded into individual tubes (Figures A-C) and placed in a DAM machine (Figure D). An infrared beam (marked as a red line in Figure D) crosses each fly tube, and the machine notes when the beam is blocked by the fly. If the beam isn’t broken for five or more minutes (meaning the fly hasn’t moved), it’s counted as sleep. Using this method, researchers can analyze how long a fly sleeps, how many times it goes to sleep and wakes back up (called sleep bouts) and the duration of each sleep bout.

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DAM system in incubatorClick here for a larger version of the picture

To conduct the sleep experiment, the machines are hooked up to a computer and placed in an incubator, which controls the humidity, temperature, and lights. The light cycle is usually set to lights-on for 12 hours (day) and then lights-off for 12 hours (night), and experiments often run for several days or even weeks. In this picture, a newer version of DAM machines is shown (one is circled in red).

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Sleepless dataSleepless mutants sleep much less than normal (control) flies. Image modified from Koh et al, 2008

This system allows researchers to study the sleep habits of dozens of flies at once, and it’s relatively quick and easy (compared to studying sleep in mammals). So what’s an example of a real sleep experiment? In 2008, the Seghal lab used this system to find sleep-related genes. They ran a genetic screen in which they exposed a population of flies to toxic chemicals that caused random mutations in their DNA. Then, they tested the flies to see if any had sleep abnormalities. They found that flies with a mutation in one gene (which they aptly named sleepless) slept about 80% less! Isn’t it crazy that a single gene can affect such a complex behavior so dramatically?

Sleepless dataA common way to display fly sleep habits over the day and night period for one day. The amount of sleep within 30 minute intervals (y axis) is plotted for the time of day (x axis). Note that Sleepless mutants (open circles) sleep much less than control flies (filled circles). The bar at the bottom indicates time: white = day, black = night. Image modified from Koh et al, 2008

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In another experiment that same year, the Guo lab was interested in finding out how sleep affects memory. They tested the sleeping habits of a fly mutant called amnesiac, which can’t form long-term memories. They found that amnesiac mutants had very fragmented sleep (meaning that they woke up a lot during the night). The fact that the same gene is involved in both sleep and memory provides a link that researchers can use for future studies about how these behaviors are connected.

Tracker setupA schematic of the Tracker setup. Image modified from Gilestro, 2012

Although studies have shown that the DAM system is relatively accurate for measuring fly sleep, more sophisticated methods have recently been developed for tracking fly movement. These systems (sometimes called the “Tracker” program) rely on cameras and sensitive tracking software to measure movement at a much higher resolution. As use of the Tracker program becomes more widespread, I have no doubt that we will gain yet more insights into how and why we sleep.

 
 

References:

  • Potdar S. (2013). Lessons From Sleeping Flies: Insights from Drosophila melanogaster on the Neuronal Circuitry and Importance of Sleep , Journal of Neurogenetics, 27 (1-2) 23-42. DOI: http://dx.doi.org/10.3109/01677063.2013.791692
  • Koh K., M. N. Wu, Z. Yue, C. J. Smith & A. Sehgal (2008). Identification of SLEEPLESS, a Sleep-Promoting Factor, Science, 321 (5887) 372-376. DOI: http://dx.doi.org/10.1126/science.1155942
  • Liu W., Beika Lu & Aike Guo (2008). amnesiac regulates sleep onset and maintenance in Drosophila melanogaster, Biochemical and Biophysical Research Communications, 372 (4) 798-803. DOI: http://dx.doi.org/10.1016/j.bbrc.2008.05.119
  • Donelson N., Kim E.Z., Slawson J.B., Vecsey C.G., Huber R. & Griffith L.C. (2012). High-resolution positional tracking for long-term analysis of Drosophila sleep and locomotion using the “tracker” program., PloS one, PMID: http://www.ncbi.nlm.nih.gov/pubmed/22615954
  • Gilestro G.F. (2012). Video tracking and analysis of sleep in Drosophila melanogaster, Nature Protocols, 7 (5) 995-1007. DOI: http://dx.doi.org/10.1038/nprot.2012.041

Thanksgiving Special: Uncovering the link between sleep and food

rest and digest turkey

If you ate a big Thanksgiving dinner yesterday, you probably felt drowsy and sluggish afterward, a phenomenon often referred to as a “food coma”. The belief that it’s caused by the tryptophan in turkey is a long busted myth, and in fact it can happen after any carb-heavy meal. The reasons for this post-food slump are relatively well understood from experiments in humans and other mammals. For one, big meals trigger a “rest and digest” response when the food reaches the stomach and small intestine (via activation of the parasympathetic nervous system). This diverts energy to digestion, making you feel sluggish and sleepy.  But wait, there’s more! Eating a meal full of carbs and other sugars also stimulates the release of insulin, which triggers a process to take up nutrients from the bloodstream. But a side effect of this process is an increase in the amount of serotonin and melatonin in the brain, two chemicals that are associated with drowsiness (and often happiness).

So having a full stomach makes you sleepy, but did you know that the relationship between sleep and food goes deeper than that? For example, studies in animals from fruit flies all the way to humans have shown that having an empty stomach can keep you awake. Even worse, chronic sleep deprivation stimulates appetite and can lead to weight gain. Studies in humans have uncovered strong correlations between sleep disorders like insomnia and obesity-related disorders such as diabetes and cardiovascular disease. One of the reasons for this is that sleep loss wreaks havoc on the levels of certain hormones, such as the “hunger hormone” ghrelin.

Thus, even though sleeping and eating are mutually exclusive behaviors (you can’t sleep while you’re eating), they’re also obviously connected. Both are essential for survival, so the brain may often be promoting at least one of them. But how does the brain decide which behavior is more important at any given time? When you’re hungry, it seems more important to stay awake and find food to prevent starvation, but sleep deprivation also has health consequences, so the brain needs to ensure you get enough sleep.

So how are sleep and hunger connected in the brain? Are they independent, so that hunger suppresses sleep, and sleepiness stimulates hunger? Or maybe they arise from the same mechanism, which signals in turn for either sleep or eating depending on your body’s needs. Answering this question will improve our understanding of sleep- and obesity-related disorders and how they’re linked, a necessary step before treatments can be developed.

Fruit flies make a great animal model for answering detailed questions like these, which take place on a molecular and cellular scale. Although much research has yet to be done, there have already been some informative findings. For starters, scientists have found that insulin-producing cells in the fly brain regulate both feeding and sleep, providing a cellular link between these two behaviors (remember that insulin’s activities are partially responsible for the food coma after Thanksgiving dinner). Their findings suggest that these cells integrate information from other brain regions about sleep need and hunger, and may even potentially act as a “behavioral switch” to signal which behavior is more important at any given time.

Other fruit fly researchers have found a link between eating and sleeping in a single molecule called “NPY-like short neuropeptide F” (sNPF). sNPF had already been shown to regulate food intake, but recently it was found that sNPF also promotes sleep. sNPF is similar to a mammalian chemical called “neuropeptide Y” (NPY), which also plays a little-understood role in sleep and eating in mammals. NPY has recently been studied as a possible drug target for obesity treatment in humans even though its role in other behaviors is unclear, so a better understanding of this chemical is essential to account for possible side effects such as sleep disruption.

Research in a variety of animal models (and humans) has shown us that sleep and hunger are related. Overall, the combined results of fruit fly research suggests that sleep and feeding behaviors may arise from shared mechanisms in the brain. Future studies will pin down the exact mechanisms and apply those findings to more complex mammalian systems. Hopefully, this research will lead to the development of drugs that can help with sleep- and obesity-related disorders. In the meantime, I think I’ll try drinking coffee with Thanksgiving dinner.

Happy Thanksgiving!

References:

Breaking Research: WIDE AWAKE is a newly identified gene that explains how we become sleepy at night

The body’s biological clock is responsible for keeping track of time and synchronizing behavior with the environment, so that you feel alert during daylight hours and sleepy at night. This biological clock (also called the circadian clock or circadian rhythms) consists of three major parts:

  1. The central pacemaker, which oscillates with a period of about 24 hours to keep time
  2. Inputs to the clock, such as light or temperature, that synchronize it with the environment
  3. Outputs from the clock, which signal to your body to indicate when it’s time to sleep, eat, etc

Researchers have made great progress in understanding how the central pacemaker works and how environmental cues can control the clock, but how does the clock signal to the rest of the body to control rhythmic behaviors? A recent fruit fly paper published in Neuron by the Koh and Wu labs investigated this question and discovered a new gene involved in signaling that it’s time to sleep.

How does our body know when it’s time to feel sleepy or alert? The biological clock must have an output pathway for controlling sleep, but the mechanism of exactly how that happens is poorly understood. After analyzing the sleep patterns of thousands of fruit fly colonies with different genetic mutations, the authors of this paper found a group of flies that had trouble falling asleep at night. They called the mutated gene Wide Awake (wake for short) and discovered that while the gene wasn’t necessary for accurate functioning of the circadian clock itself, it was important for signaling a transition from wake to sleep at the end of the day.

The role of WAKE in LNvsDuring the day, GABA signaling from sleep circuits in the fly brain has little effect on LNvs (the wake-promoting clock cells). At dusk, increased amounts of WAKE proteins in clock cells leads to an increase in the number of GABA receptors on the membrane, thus increasing the cells’ sensitivity to GABA. This dampens LNvs activity, allowing flies to fall asleep at night.

So how does this gene translate clock information into a feeling of sleepiness? The authors looked to “clock cells” to answer this question. Clock cells are a group of cells that make up the central pacemaker. In mammals, this pacemaker is located in the suprachiasmatic nucleus (SCN). In flies, the central pacemaker includes a small group of neurons called LNvs, which promote wakefulness. During the day, activity in the LNvs causes flies to be awake and active. But at dusk, the amount of WAKE protein from the wake gene in these cells increases. WAKE makes the cells more susceptible to inhibition from a chemical messenger called GABA, which dampens activity. As the wake-inducing LNvs become more sensitive to GABA, they become less active, which allows the sleep circuits in the brain to exert more control over behavior so the flies can fall asleep. On the other hands, flies with a mutation in the wake gene were not getting enough GABA signal to quiet the LNvs at night, keeping them agitated and awake.

The circadian clock in humans

The authors identified a gene that seems to be a messenger from the circadian clock to the brain, telling it that it’s time to shut down and go to sleep at night. But how can these fruit fly findings help us humans? They also found the same gene in the SCN in mammals, suggesting that it plays the same role in other species as well. The finding that wake mutants had difficulty falling asleep after lights-off is reminiscent of sleep-onset insomnia in humans. Currently, the most common treatment for insomnia are drugs the mimic the effects of GABA in the brain. However, these findings suggest that the effectiveness of this treatment is limited if wake-promoting neurons are not sensitive enough to GABA signaling. Thus, future research in this area may focus on manipulating the wake gene and its proteins to develop a better treatment for sleep disorders such as insomnia in humans.

For more information on circadian rhythm research in fruit flies, check out the related Translational Findings post.

Reference:

  • Liu S., Qili Liu, Masashi Tabuchi, Yong Yang, Melissa Fowler, Rajnish Bharadwaj, Julia Zhang, Joseph Bedont, Seth Blackshaw & Thomas E. Lloyd & (2014). WIDE AWAKE Mediates the Circadian Timing of Sleep Onset, Neuron, 82 (1) 151-166. DOI: http://dx.doi.org/10.1016/j.neuron.2014.01.040

Breaking research: A recent study in fruit flies suggests that sleep loss during childhood could lead to abnormal brain development

Discussions about whether schools for children should start later have been making headlines recently, highlighting the importance of getting enough sleep at night. We all know how important sleep is for day-to-day performance—you’ve likely experienced firsthand how hard it can be to think and focus after a bad night’s sleep. Luckily, these effects are reversible: just get enough sleep for the next couple of nights and you’ll feel refreshed again. But can sleep deprivation have long-term, irreversible consequences in children?

Table of sleep needs by ageTable 1. Human children require more sleep than adults. Data obtained from the National Sleep Foundation

Across multiple species, young animals need more sleep than adults. Although the purpose of sleep is not fully understood, researchers believe that the brain may use this time to repair itself, store new memories, and modify itself to stay current with recently learned skills or adapt to changes in the environment (a process known as plasticity). The brains of young animals are very plastic and are undergoing a lot of changes as they develop, and scientists have always suspected that increased sleep is necessary for normal brain development. In humans, the majority of brain growth occurs before the age of two, which is also the period of life with the highest amount of sleep. In a recent paper published in Science, the Sehgal lab studied the link between sleep and brain development using Drosophila melanogaster and found that loss of sleep in immature flies led to abnormal development in a fast-growing area of the brain and consequent behavioral problems in adult flies.

Just like humans and other mammals, fruit flies need a good night’s sleep to function normally during the day. The authors began their study by confirming that in flies, young animals also sleep more than adults. They then sleep deprived a group of flies by placing them in a shaking machine for two nights and measured their behavior three days later (a long time for a humble fruit fly!). Fly researchers prefer to study innate behaviors because they are instinctual instead of learned, suggesting that their underlying brain structure develops genetically rather than from experience (in these cases, it is thought that the “nature versus nurture scale” is tipped toward nature.) In this case, the authors studied “courtship behavior”, a measure of how well male flies can solicit female flies and successfully pass on his genes (so to speak). They found that flies that were sleep deprived when they were younger didn’t perform as well as flies that had gotten enough sleep. The authors showed that this behavioral abnormality was specifically caused by loss of sleep in young flies, because flies that were sleep deprived as adults performed normally three days later.

Table of sleep needs by ageFigure 1. Sleep is required in young flies for normal development of fast-growing brain regions. Sleep deprivation during youth causes lack of growth in the VA1v, an important region for courtship behavior. Image modified from Murakami and Keene, 2014.

What happened in the brains of young sleep-deprived flies that led to their courtship inadequacy as adults? Previous research had already located the brain regions responsible for this innate behavior, so the authors knew where to start looking. They found that one of the regions (a structure called the VA1v) had not grown as much in flies that had been sleep-deprived when they were young. The VA1v is a very fast-growing region during development, and the authors showed that loss of sleep irreversibly slowed its growth. On the other hand, structures that do not undergo fast growth during development were normal. The authors concluded that sleep deprivation in young animals impairs brain development in fast-growing areas, resulting in irreversible behavioral abnormalities.

These results demonstrate just how important it can be to get enough sleep, especially as children. Research with human children already indicate that loss of sleep can have long-term effects on behavior, and the findings from this paper suggest that the consequences may not always be reversible if developing regions of the brain are affected. But what if children have a developmental or genetic disorder—such as a pediatric sleep disorder—that causes loss of sleep during this critical time period?

The authors also figured out the difference in young fly brains that caused them to sleep more than adults. Using the impressive set of genetic tools that Drosophila are famous for, they identified a small set of dopaminergic (DA) cells that behaved differently in young versus adult flies. Dopamine is a chemical in the brain that some neurons use to communicate with each other, and is already known to be important for the “be awake!” signal in several mammalian species and humans. The authors found that this particular set of DA neurons was less active in young flies than adults, while other DA neurons had the same activity level regardless of age. The neurons communicated with a sleep-related structure known as the dorsal fan-shaped body (dFSB). The authors found that in young flies, reduced activity in these DA neurons allowed the dFSB to be more active, causing the flies to sleep more. When the authors artificially activated the DA neurons, they found that young flies were unable to sleep and had behavioral problems three days later, while adult flies did not experience any long-term effects. This result matched the one they obtained when they sleep deprived young flies by shaking them, confirming that reduced activity in these neurons was responsible for the extra sleep in young flies.

How can knowing the circuit responsible for extra sleep in young flies help us humans? Dopamine plays the same role in causing wakefulness in mammals as it does in flies, and the dFSB is similar to known mammalian sleep-related structures (such as the VLPO). Researchers can use these findings as a starting point for identifying similar DA neurons in mammals. Eventually, scientists may be able to develop a treatment that acts on these neurons in children with sleep disorders, allowing them to get more sleep and ensure normal brain development during this critical period.

Circuit underlying extra sleep in young fliesFigure 2. The circuit responsible for extra sleep in young flies. In young flies, a set of dopaminergic (DA) neurons is less active, allowing a sleep-related structure known as the dFSB to be more active and promote extra sleep. In adult flies, the DA neurons are more active and suppress dFSB activity, leading to relatively less sleep.

Original reference:

  • Kayser M.S., Yue Z. & A. Sehgal (2014). A Critical Period of Sleep for Development of Courtship Circuitry and Behavior in Drosophila, Science, 344 (6181) 269-274. DOI: http://dx.doi.org/10.1126/science.1250553

General references:

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