The sleeping zebrafish can offer clues about the origins of sleep

It took about ten years of work – and probably a few sleepless nights – but for the first time, researchers have identified sleeping patterns in the brains of small zebrafish, and these patterns look remarkably like activity. brain in sleeping humans.

As scientists report today in the newspaper Naturethe presence of similar sleep patterns in fish and mammals may provide clues to sleep patterns in our common ancestors, which may also help us better understand the biological function of drowsiness.

"Sleep is a huge mystery in neuroscience," says William Joiner, a biologist at the University of California at San Diego, who studies sleep in fruit flies, but does not participate in this research. A lot of work has asked why we do it, and "people have not really picked a good answer."

For the new study, the team used advanced imaging techniques to observe zebrafish sleep and found that the tiny cycle of fish between sleep states was similar to what we have in humans: rapid eye movements or paradoxical sleep. This pattern has already been observed in many mammals, birds and lizards, but this is the first time it has been observed in a fish.

Based on our understanding of the evolving relationships between fish and mammals, the team suggests that REM-like sleep states evolved over 450 million years ago, making this type of sleep a deeply rooted biological phenomenon.

"We share a spine, but we share much more than that," says co-author of the study, Philippe Mourrain, neuroscientist at Stanford University. "It makes it easier to understand sleep and what it does for us."

Other experts claim that the methods used by the authors have set a new standard in the study of sleep. Joiner called the document a "technological feat". But not everyone is convinced that it reveals a lot of information about the evolution of sleep.

"I doubt that you can trace a direct line of fish through mice, birds, reptiles and humans," says Paul Franken, neuroscientist at the University of Lausanne in Switzerland, who studies sleep among mouse.

Scientists already knew that zebrafish could sleep just by watching their behavior. But the gold standard for studying sleep uses physiology, says Franken.

Lead author, Louis C. Leung, neuroscientist at Stanford University, built the microscope responsible for the complex imaging performed for the study. Most body activities are choreographed by a complex network of nerve cells, or neurons. When the neurons are active, the calcium levels increase inside, so the researchers genetically modified the zebrafish to include a protein that flashes in fluorescent green when it detects calcium, indicating that 39, an area of ​​the body is active.

Then the real work started. The team focused on the zebrafish that was only two weeks old, because the fish is transparent at this age. This allowed the researchers to observe the brain and other activities inside the body without cutting the animal or implanting electrodes, Leung said.

They immobilized the tiny fish by immersing it in a gelatin-like substance under a microscope, and then began to examine the key physiological components: brain activity, heart rate, muscle activity, and eye movement.

Almost immediately, active and non-active neural patterns began to differentiate, revealing a "fingerprint" of activity similar to that of slow, non-REM sleep cycles.

"It almost took my breath away," says Leung.

To confirm that the activity patterns were really sleepy, the researchers then prevented the fish from "napping", creating a very sleepy fish. When they tested the fish deprived of sleep, they found the same neural patterns, but several of them. In addition, when the fish was in a state other than REM, his heart rate was reduced by half and the muscles of his body relaxed.

Compared with sleepy states, the awake brain in zebrafish was very noisy, with chaotic blinking neurons, Leung said.

For many organisms, environmental factors such as temperature influence the duration and intensity of sleep – humans sleep longer in cold weather. Mammals need to thermoregulate, adjusting their body temperature to stay warm or cool, and thermoregulation has long been associated with sleep. But because the zebrafish's sleep state is similar to ours, this suggests that this type of sleep existed before thermoregulation increased, according to the team.

However, it is difficult to link the results of this study to mammals because there is so much time between them and the fish, says Jerry Siegel, a sleep scientist at the University of California, Los Angeles. Sleep is almost ubiquitous in animals, he admits, but it varies a lot in mammals.

"You can not just say that sleep is sleep," he says. Among mammals, the amount of sleep required varies from three to 20 hours per day. REM sleep may be non-existent, as in many cetaceans. It can also be a major part of sleep, lasting up to 8 hours in mammals such as platypus.

In addition, sleep signatures have been found in very young fish, says Siegel, and these results do not necessarily apply to adults. Throughout the animal kingdom, babies sleep differently from their parents.

Other experts are more optimistic, especially with regard to the techniques used in the document. The neural signatures "did not need to be present in fish, but he found them," says Paul Shaw, sleep scientist at Washington University in St. Louis, who was not involved in the study . "I think it's surprising. It's super cool! "

Shaw and others praise the extensive imagery used to observe sleep on such a scale.

"Seeing is believing, and that's what I really like about this technology," says Shaw. "You do not have to deduce from sleep [in this study]. "

This breakthrough could be particularly useful for health professionals seeking to design new drugs to combat the growing epidemic of sleep deprivation in many countries. Sleep-improving drugs may help those who have difficulty drifting. By implementing these techniques in the future, we can potentially better screen drugs to determine if they are activating the right cells, so that patients wake up refreshed, Leung says.

"It's amazing to see the individual neurons of a living animal and see how it reacts to different drugs," Franken says. "It's a big step forward."