Let there be 'circadian' light

New study describes science behind best lights to affect sleep, mood and learning

February 20, 2020

Science Daily/University of Washington Health Sciences/UW Medicine

Researchers said the wavelengths at sunrise and sunset have the biggest impact to brain centers that regulate our circadian clock and our mood and alertness.

Their study, "A color vision circuit for non-image-forming vision in the primate retina," published in Current Biology Feb. 20, identifies a cell in the retina, which plays an important role in signaling our brain centers that regulate circadian rhythms, boost alertness, help memory and cognitive function, and elevate mood.

These effects have been attributed to a pigment in the eye called melanopsin, which is sensitive to blue light, but researchers say cone photoreceptors are a thousand times more sensitive to light than melanopsin. The cone photoreceptor inputs to the circadian circuity respond to short wavelength blue light, but they also respond strongly to long wavelength oranges and yellows and contrasting light -- the colors at sunrise and sunset. What makes good lighting, researchers discovered, is lighting capable of stimulating the cone photoreceptor inputs to specific neurons in the eye that regulate circadian rhythms.

Lead author Sara Patterson, a graduate student in neuroscience at the University of Washington School of Medicine, said how we set our internal clocks to the external light-dark cycle has been studied a lot. But how the changes in the color of light affect our brain has not.

"Color vision used for something other than color perception was the most exciting part for me," she said.

In the study, Patterson and colleagues identified a cell known as an inhibitory interneuron or amacrine cell in the retina, which signals to photosensitive ganglion cells that affect our circadian brain centers. The researchers said these amacrine cells provide "the missing component of an evolutionary ancient color vision circuit capable of setting the circadian clock by encoding the spectral content of light."

Patterson said so little is known about rare retinal circuitry that it was possible to find a new blue cone cell. She said there is a lot more to be discovered about how blue cone cells are projecting to other areas of the brain.

While sunrise lights, blue lights and seasonal affective disorder (SAD) lights have all tried to capture benefits of natural light, they haven't been that effective because they are missing key science data, said corresponding author Jay Neitz, professor of ophthalmology at the UW School of Medicine, a scientist at the UW Medicine Eye Institute, and a well-known color vision researcher. He said the science behind SAD lights, for example, is to make lights hundreds of times brighter than normal lights to stimulate melanopsin.

"This research all started because of our interest in the health benefits of having natural light that occurs at the right time of day that helps regulate our circadian clock and our mood and alertness," Neitz said.

The University of Washington has licensed technology based on this discovery to TUO (https://www.thetuolife.com/), a lighting technology company that will be selling white LED lightbulbs that will incorporate undetectable sunrise and sunset wavelengths for commercial use.

The work was supported by the National Eye Institute and Research to Prevent Blindness. Other collaborators include James A. Kuchenbecker, research scientist/biomedical engineer with the Department of Ophthalmology at the University of Washington School of Medicine; James R. Anderson, research scientist/software architect with the John A. Moran Eye Center at the University of Utah School of Medicine, and Maureen Neitz, professor of ophthalmology at the University of Washington School of Medicine.

https://www.sciencedaily.com/releases/2020/02/200220141731.htm

A timekeeper for siesta

October 7, 2019

Science Daily/University of Würzburg

External stimuli can rearrange the hierarchy of neuronal networks and influence behavior. This was demonstrated by scientists using the circadian clock of the fruit fly as an example.

Circadian clocks must be flexible and they must be able to adapt to varying environmental conditions. Otherwise, it would be impossible for living beings to change their patterns of activity when the days get shorter again as is happening now. After all, Drosophila, also known as the common fruit fly, no longer needs a long siesta in autumn to protect itself from excessive heat and predators as in the middle of summer, at least in our latitudes. At the same time, the fly must shift its evening activity peak a few hours forward if it doesn't want to end up buzzing around in the dark.

For the fruit fly to adapt to changing day-and-night rhythms, its circadian clock must be able to process external cues, so-called zeitgebers, which are used to synchronise the molecular and physiological properties of the organism. Light is the most important zeitgeber the fly uses for this.

Publication in Current Biology

Scientists from the Department of Neurobiology and Genetics at the University of Würzburg have been researching the interaction of light, photoreceptors and circadian clocks in the fruit fly for some time. Chair holder, Charlotte Förster, together with her former colleague Matthias Schlichting, who presently works at Brandeis University (Massachusetts, USA), have now figured out new and surprising details of this interaction. They present the results of their research in the current issue of Current Biology.

"In mammals, a combination of the traditional photoreceptor pathway (rods and cones of the retina) and the circadian photoreceptor melanopsin in retinal ganglion cells enables the fine-tuning of clock synchronisation," Charlotte Förster explains. She says that there is a comparable mechanism in Drosophila: "The compound eyes, the extraretinal Hofbauer-Buchner eyelets and the circadian photoreceptor cryptochrome all work together in the light synchronisation process," the professor summarises the central result of the recently published study.

It is known from earlier studies how the photoreceptor cryptochrome works. Located in special nerve cells, the so-called clock neurons, it interacts with the timeless clock protein during light exposure, leading to the degradation of the protein. Figuratively speaking, it turns the clock back to zero. However, less is known about the exchange between the eyes of the fruit fly and the clock neurons and how the different day length is mediated.

Experiments with different day lengths

For their study, the scientists worked with different specimens of fruit flies. They used healthy flies, eyeless flies and flies lacking specific visual pigments of the eye, the so-called rhodopsins. During the laboratory experiments, the insects were exposed to different light conditions: At a constant day length of 24 hours, the researchers extended the period of light in two-hour increments from twelve to a maximum of 20 hours and observed the activity patterns of the respective fly groups.

It turned out that the activity of the insects changed with increasing length of the daylight period. When periods of light and darkness alternate regularly every twelve hours, which corresponds to a typical day at the equator, healthy flies become active twice: around the time of "sunrise" and before the simulated "sunset." As the days get longer, the evening activity is also delayed and the "siesta" -- the midday resting period -- is extended. It is striking though that as the periods of daylight increase, the activity peak in the evening deviates from the simulated sunset and is much earlier in some cases. The largest deviation occurs when the daylight period is 20 hours long, probably because the flies are never confronted with such conditions in their natural environment.

Discovery in the compound eye

While searching for the molecular and neuronal mechanisms which the fruit fly uses to "fine-tune" its circadian clock in a manner of speaking, the neurobiologists had to carry out numerous experiments. Experiments on fruit flies that lacked these eyes demonstrated that the compound eyes play a key role. Their activity peak was also delayed as the length of the daylight period increased, but much less so than in their seeing relatives. More experiments were conducted to pinpoint which receptor cell and visual pigment are responsible for this. After all, each facet of the fly's compound eye has eight receptor cells and five rhodopsins. So the scientists selectively switched off the individual cells until it was clear that receptor cell 8 and rhodopsins 5 and 6 which occur there were their targets.

The scientists next investigated how the light signal reaches the brain of the fruit fly and how it travels from there to the clock neurons. Surprisingly, they found that while the signal is transported via so-called "small lateral clock neurons" during "moderate" light periods, it travels through "large lateral clock neurons" in the 20-hour light experiments. "Although the circadian clock of the fruit fly is comparatively small with just 150 neurons, the overall system has high plasticity," Charlotte Förster recapitulates the results of the study and she explains that this neuronal plasticity is necessary to enable the animals to quickly adjust to varying conditions.

https://www.sciencedaily.com/releases/2019/10/191007103615.htm