Light-Dependent Regulation of Sleep and Wake States

Lights Out: The Neural Association between Sleep and Light

Humans are animals that are diurnal in nature, that is, we sleep during the night time and are awake and active during the day, as a result of light partly available or completely absent. It has been observed that light indirectly affects sleep by altering the length of our circadian rhythms a bit, quickly and directly due to an occurrence called as masking. But while a lot of information is available about how the circadian rhythms are affected by light, there is very little knowledge about the how light affects sleep directly: Why does one’s sleep gets disturbed if the lights are switched on in the middle of the night? Why does being in d dark enable us to sleep better?

Caltech researchers in Professor of Biology David Prober’s laboratory said that they have discovered the answer partly: a particular protein in the brain that is responsive to light and its absence sets and maintains the accurate balance between sleep and alertness. Prober also added that earlier, researchers had recognized the photoreceptors present in the eye to be essential for the direct outcome of light on sleep and wakefulness but how the brain uses this ocular data to induce and control sleep was unknown.

Zebrafish was used as a model organism for observing the sleeping pattern at the Prober laboratory. These organisms are visually transparent, which allows for non-invasive recording of their neurons through images. They also have diurnal sleep and wake patterns similar to like that of humans.

To study and observe in their experiment, how their sleep is responsive to the availability or absence of light, a former graduate in Prober's lab, Wendy Chen, directed the studies where they examined a specific protein present in the zebrafish brain called prokineticin 2 (Prok2).

Chen genetically engineered zebrafish to excessively produce Prok2, which resulted in the availability of the protein in a large quantity. She observed that in comparison to normal zebrafish, these animals were more liable to fall asleep during the day and stay awake at night.

Amazingly, the effects did not rely on the engineered fish's typical circadian sleep/wake cycle but to a certain extent depended only on whether the lights were switched on or off in their surroundings. These studies put forward that a surplus of Prok2 restrains both the natural awakening result of light and the sedating outcome of darkness.

Chen then produced zebrafish with metamorphosed structures of Prok2 and its receptor, and studied the sleep defects in these animals that were dependent on light. For instance, Chen found that a zebrafish with an altered Prok2 receptor were more alert and active in the presence of light and less active in the absence of it, which was quite the contrary of what she had noticed in the animals that over expressed Prok2 and had Prok2 receptors that were functional.

Prober stated his observations saying that although diurnal animals like zebrafish for example, spend their nights sleeping and are awake during the day, they also take small naps during the course of the day and sometimes wake up at night which is very similar to what humans do.

He also added that their experiment’s results put forward that levels of Prok2 play a very vital role in maintaining the accurate balance between wakefulness and sleep during both the course of the day and night.

In their next step, the researchers wanted to observe and study how Prok2 was adapting the effect of light on sleep. To find out the answer to this question, they decided to observe whether other proteins present in the brain that affect sleep, were needed for of Prok2 to have an effect on sleep behaviour.

They found that that the sleep-inducing effect of Prok2 over expression in light requires galanin, which is a protein that promotes sleep. They also observed that Prok2 over expression enhanced the level of galanin expression in the key sleep-promoting centre of the brain, the anterior hypothalamus. But in the animals that were engineered to be deficient in galanin, over expression of Prok2 did not enhance sleep.

These conclusions offer the foremost insights into how light interrelates with the brain to affect sleep and provide a foundation for scientists to start discovering the genes and neurons that trigger the occurrence. However, additional work is required to understand fully describe how light and dark directly impact sleeping and waking, and to establish whether Prok2 has a function akin to humans. If it does, these studies will ultimately result in new drugs that promote sleep and wake.

The title of this paper is based on regulation of sleep/wake states dependent on light with the help of prokineticin 2 in zebrafish. Postdoctoral scholars Chanpreet Singh and Grigorios Oikonomou are other Caltech co-authors.

Sabine Reichert and Jason Rihel of University College London also made contributions to this study. The National Institutes of Health; the Edward Mallinckrodt, Jr. Foundation; the Rita Allen Foundation; and the Brain & Behavior Research Foundation funded the work.