Third eye inside the head

Do you know the old myths about spooky creatures with a third eye on the back of their heads? Such eyes really exist in some animals, but they are hidden inside the brain. Frogs, lizards, and other non-mammal vertebrates have a structure called the parietal eye. Evolution-wise, this “eye” is quite a smart organ: although it cannot see (because the light that gets through the skull is too disperse) it can clearly tell day from night and bright summer light from dark winter days. Based on this information, the creatures can easily synchronize their behaviour with the cycle of day and night and adapt to regimes optimal for harsh winters and hot summers.

In mammals, including humans, this structure is missing. For decades, we were convinced that we could only react to light due to the cones and rods in our eyes. However, then scientists witnessed blind mice reacting to light. The mice of interest were genetically deprived of both rods and cones, so there was no room for doubt; these mice were blind and they could still clearly tell when the light in the lab was on. The researchers made sure it was not due to sound, temperature, or any other factor. Does this mean that even mammals can perceive light without eyes?

The answer is no. In cruel studies, researchers also removed the eyes of the mice and confirmed that once eye-less, they don’t perceive light at all. Only one possibility remained: there is something more in our eyes, in addition to rods and cones, that can perceive light.

During the 1990’s, researchers discovered that there is a substance in our eyes responding mostly to blue light. This unknown system projects to a brain centre called the suprachiasmatic nucleus, or SCN, which works as the central inner clock of our body. Still, they still did not know it was a chemical until 1998 when it was discovered in frogs. But before we learn the details, let’s understand the function of this sophisticated mechanism: how the light orients us in time.

The brain clock machinery

Humans and many other animals mostly act during the day – while the nocturnal creatures mostly come out at night. This requires all of us to adjust all our different bodily processes to different times of the day, for all of our organs and tissues to be ready to labour during our active periods and take a rest when appropriate. To our conscious mind, this sounds easy because, normally, we simply feel energized during the day and tired in the evening – but in fact, this means coordination of hundreds of different processes, adjusting our brain functions, heart activity, metabolism, immunity and other vital functions.

All this is guided by the central clock in our brain, in so called suprachiasmatic nucleus or simply SCN. The SCN sends hormonal signals throughout the whole body and exciting and inhibiting regions of our brain responsible for arousal. As long as SCN is well-adjusted to the environment, all of our body is, too.

The SCN is using sophisticated measures of the genetic processes within its cells to be as precise as possible estimating the time flow. But this still does not make it unmistakable. Plus, keeping the same rhythm is not always enough, for example when we need to cope with jet lag or simply adjust our rhythms to a new work schedule. Therefore, our brain keeps synchronizing itself with the environment, using information about the temperature around us and – especially – the light.

Why do we perceive sunset as if it was orange?

The light emitted by the Sun needs to travel prolonged distance through warm evening air, which reduces power of the slow-wave light we perceive as blue. In the morning, on the other hand, the atmosphere is different, and during the day the light travels only shorter distances through the air, both helping to preserve higher amounts of the blue frequencies. Throughout the evolution, our brains understood these processes and learned to rely on the quantity and quality of light to tell the time of the day.

The light input to the retina is transferred as an electrical stimulus through a nerve fiber called retinohypothalamic tract. As suggested by the name, the stimulus than arrives at hypothalamus: namely its part, the SCN. As a result, excitatory glutamate is released from the nerve terminals, together with other neuromodulators. The brain knows it is time to be awake and active!

Bright light therapy is working in the same way: mimicking the frequencies of natural light of the sun, it delivers activating signals to the brain. The basic effects are two: in terms of minutes, the excitatory substances are released, improving functioning of the brain. And in terms of days, we can manipulate and stabilise the circadian rhythm.

But how does the brain gets these signals from the retina? Finally, we are returning to the blind mice that were able to react to light and to the moment when…

…melanopsin was discovered!

The article describing melanopsin in humans was formally published in January 2000, making it the molecule of the new millennium. And, at least in the field of bright light therapy, it foreshadowed several little revelations.

First, it is this new protein which is responsible for the heightened sensitivity to blue light used in computer and phone displays. It is this blue light which can heavily disturb our circadian rhythms. Scientific experiments gradually revealed that in humans, melanopsin is most responsive to light with a wavelength of 479 nm (if you are wondering what that means, check our article on light itself). Therefore, the lamps are developed in a way to increase light in the blue spectrum.

Second, melanopsin is linked to chromosome 10q22, particularly to the gene labelled Opn4 (melanopsin is the fourth molecule from the family of opsins and is named Opsin the Fourth, in case you might be curious about the strange name). Importantly, a recent study discovered that a widespread mutation of this gene (which prevents production of melanopsin “P10L”) is exceptionally common in people suffering with the seasonal affective disorder, also called winter depression, or simply SAD.

All participants of the research who inherited this mutation from both mother and father suffered with SAD, hinting at a possible link between melanopsin and this disorder. On the other hand, only 5% of those suffering with SAD shared this genetic anomaly, thus illustrating that SAD is a much more complicated phenomenon than the result of a single mutation. Since further research also links SAD to more subtle differences in this gene, the genetics of melanopsin may explain even more.

But before we explore more the interconnection between light exposure and depression, we concentrate on sleep in the next article: