PLoS Biology: How do tired animals stay awake?

New research provides clues
to falling asleep quickly or being fully awake.
Through studies of fruit flies, the researchers found that brain neurons are able to help fruit flies stay awake in dangerous situations, helping them fall asleep
after a stressful day.
The findings, published in PLoS Biology at the Washington University School of Medicine in St.
Louis and the University of Missouri-Kansas City, could lead to new ways to
treat insomnia and improve people's sleep quality.

Dr.
Paul Shaw, professor of neuroscience at the University of Washington and corresponding author, said, "If you're sick, or don't get enough sleep, or you've just learned something new, you sleep more
.
" "But if there's a danger, your brain says, 'No, no, no, no
.
' It's not time
to go to bed yet.
I don't care how tired
you are.
'Neurons that regulate sleep are able to distinguish between safe sleep and dangerous sleep
.
”

The sleep habits of fruit flies are very similar
to those of humans.
Flies are active during the day, sleep at night and like to take a nap in the afternoon, especially in hot weather
.
Caffeine keeps them awake, and drugs that keep us asleep also work against
flies.

They have one key difference, though: Their brains are 1 million times smaller than ours, which makes it possible to
identify the role each neuron plays in controlling the behavior of the fly.
Shaw and co-corresponding author Stephane Dissel, Ph.
D.
, an assistant professor of biological sciences at the University of Missouri, began the project while a postdoctoral researcher at the University of Washington, focusing on 24 brain neurons
that control whether flies are asleep or awake.

These neurons receive and respond to sleep signals
from other neurons through chemical messengers called neurotransmitters.
The researchers investigated whether experiences that affect sleep behavior alter the response of these 24 neurons to dopamine, the neurotransmitter that promotes wakefulness; Glutamic acid that promotes sleep; and alastatin A, which also promotes wakefulness
.
Alastatin A plays a role
in feeding behavior.
As part of this study, the researchers showed that it also plays a role
in regulating sleep.

Sleep enhances memory and learning, and fosters creativity
.
After an intellectually challenging day, both humans and flies sleep more
.
As part of this study, the researchers showed that living in a crowded social environment or learning a new behavior triggered molecular changes in Drosophila's sleep neurons, making them less sensitive to dopamine and therefore sleepier
.

On the other hand, when the researchers regularly shake the vials they live in while the flies sleep to warn them, the flies' brains produce both alastatin A and glutamate
.
The combination of two opposing sleep signals keeps fruit flies awake in conditions of fatigue in response to what they perceive as dangerous situations
.
The sleep neurons of natural insomnia fruit flies respond abnormally to sleep neurotransmitters, suggesting that their brains have birth defects
in regulating sleep.
The insect sleeps half as
long as normal flies after hatching.

"A lot of people don't sleep well, and we don't really know why," Shaw said
.
"Our data suggest that there is a genetic predisposition
to how sleep centers in the brain interpret nerve signals.
If something goes wrong with the system, then you get these conflicting signals: you're tired, but you can't sleep
.
By understanding how these conflicting signals are generated, we can start thinking about how to design treatments
for people.
”

Interestingly, one intervention that appeared to have a lasting improvement in sleep quality was time-restricted feeding
.
Fruit flies typically eat throughout the day, but in this study, the researchers limited the flies to eating
between 8 a.
m.
and 5 p.
m.
After a week, the flies' sleep neurons became more sensitive to dopamine, and this sensitivity persisted for several days
after a return to a normal feeding schedule.
The researchers said the flies slept less, but they showed no signs of fatigue, suggesting an improvement
in their sleep quality.

"Time-restricted eating is a hot topic
right now.
" The study claims that restricting food intake to specific times of the day can help you sleep better and maintain a healthy weight
.
The evidence that this approach works in humans is mixed
.
But in flies, our data suggest that sleep quality improves
with time-restricted eating.
It's possible that there is an intersection between time-restricted feeding and sleep regulation, and we can use this to help people sleep better
.
”