Many of us have heard that going to sleep when it is dark outside is healthy, as light and darkness influence our circadian rhythm. But how exactly does light affect our sleep-wakefulness cycle? New research may have found part of the answer.

Now that summer is here, those of us who want to sleep in after 6 a.m. will need a good pair of blinds; light tends to wake us up. But why does this happen?

The majority of us know that light plays a role in regulating our circadian rhythm, but how light directly affects sleep is poorly understood. Researchers from the California Institute of Technology (Caltech) in Pasadena set out to examine the effect of light on sleep.

The lead investigator of the new research - which is published in the journal Neuron - is David Prober, a professor of Biology at Caltech.

Prof. Prober explains the motivation behind his research, saying, "Researchers had previously identified the photoreceptors in the eye that are required for the direct effect of light on wakefulness and sleep. But we wanted to know how the brain uses this visual information to affect sleep."

To get their answers, Prof. Prober and team chose to examine zebrafish, which are animals that have a sleep/wakefulness pattern similar to that of humans, and whose visual system is transparent, thus enabling researchers to take images of their neurons in a non-invasive manner.

How a protein responds to light

First author Wendy Chen conducted the experiments. She used zebrafish that were genetically modified to express a certain protein, called prokineticin 2 (Prok2), in excess.

The researchers found that the zebrafish who had over-expressed Prok2 tended to go to sleep during the day and stay up during the night.

Interestingly, this did not seem to depend on the fish's regular circadian rhythm. Instead, the effect was influenced exclusively by whether the lights were turned on or off around them.

The results of the experiments indicate that Prok2 can inhibit the waking effect that light normally has, as well as the sleep-inducing effect of darkness.

Next, the scientists induced genetic mutations in both the zebrafish's Prok2 and its receptor, to see how these would affect the light-controlled sleep-wakefulness pattern.

They found that the zebrafish developed "light-dependent sleep defects." For instance, fish with a mutated Prok2 receptor tended to be more active when the lights were on and less so when they were off - which is the opposite of what had previously been noticed in fish with excessive Prok2 but functional Prok2 receptors.

Finally, the scientists set out to investigate whether light, in order to regulate sleep, needed other sleep-inducing proteins in the brain.

The researchers found that excessive levels of Prok2 also raised the levels of galanin, which is a neuropeptide found in the brain's anterior hypothalamus (which plays a key role in regulating sleep).

More research is needed in order to understand the sleep-promoting interplay between genes and neurons in humans, as well as to investigate whether or not the Prok2 neuropeptide has the same effect in humans.

If further research determines that the proteins behave similarly in the human brain, this study could pave the way for new sleep- or wakefulness-inducing medication.

Prof. David Prober adds, "Though diurnal animals such as zebrafish spend most of their time asleep at night and awake during the day, they also take naps during the day and occasionally wake up at night, similar to many humans.

"Our study's results suggest that levels of Prok2 play a critical role in setting the correct balance between sleep and wakefulness during both the day and the night."

Prof. David Prober