Melanopsin And Sleep Modulation: A Bright Future For Light Therapy?

The light reaching our eyes sends two types of information to our brains. Firstly, visual information is mainly relayed by the retina cells known as rods and cones. Secondly, non visual information from light intensity is detected in the eye and transmitted to the brain, notably by melanopsin. The discovery of this photosensitive protein, less than ten years ago, and its major role in the mediation of light effects, have stimulated a great deal of research.

The two principal mechanisms of sleep regulation are known as circadian and homeostatic. The circadian rhythm (from the Latin circa dies: around a day) lasts 24 hours. It is determined by the internal biological clock (located in the hypothalamus of the brain) and synchronised by light (this is what causes jet lag, for example). Light detected by the eye influences the circadian mechanism by aligning the waking/sleeping cycle onto the light-dark regime. Sleep homeostasis can be defined as sleep pressure, which increases with duration of waking time (accumulation of the need for sleep). Although the effects of light and melanopsin on the circadian clock are well established, non circadian light effects are poorly understood and considered minor.

However, the research team seem to have demonstrated that melanopsin and non circadian light effects play a broader role than previously believed. The group studied the sleep and encephalograms (EEG) of mice genetically-modified to be melanopsin-deficient, under different conditions of light and dark. In these nocturnal animals, light induces sleep: the opposite effect to that found in man. Mice deprived of melanopsin make a perfect model for studies on non circadian non visual light effects on sleep. The researchers observed that non circadian light effects varied over the course of the day. In fact, flashes of light and dark throughout the day showed that while melanopsin acts during the circadian dark phase, rods and cones work equally during the circadian light phase.

The study also revealed that in the absence of melanopsin, the mice slept one hour less each day during the light phase. This demonstrates the non circadian influence of light on long periods and not only in response to flashes of light. Furthermore, in these modified mice, the alteration of certain EEG oscillations shows that the level of alertness induced by darkness is reduced and the mice have a lower quality of wakefulness as a result. These melanopsin-deprived mice, which slept an hour less, should have a greater tendency to sleep than the controls but instead showed a trend of decreasing sleep (notably in response to sleep deprivation), proving that the absence of a photopigment such as melanopsin could alter sleep homeostasis.

From another perspective, by identifying the neural networks involved, the researchers have shown that light works by activating the ‘sleep-active' neurons of the anterior hypothalamus.

Together, these results confirm that light does not only affect vision. This is the first time that direct effects of light and dark have been shown to interact with circadian and homeostatic sleep regulation to determine the duration and quality of wakefulness and sleep. If these observations are confirmed in man they will have important implications for the clinical use of light therapy and society's use of light in general.