Daily exposure to environmental light-dark cycles is fundamental for the regulation of circadian sleep-wake rhythms, alertness levels and cognitive performance. These non-image forming effects (NIF) of light are mediated in part by the photopigment melanopsin, located in intrinsically photosensitive retinal ganglion cells (ipRGCs) in the retina. The spectral sensitivity of the ipRGCs is distinct from any aspect of conventional vision and peaks around 480nm, which coincides with the widely used LED spectral characteristics of visual displays in our days. Altering irradiance in the blue range (460-480nm) does indeed impact NIF responses under laboratory and more natural conditions, but such manipulations currently also change colour (e.g. “Night Shift” on iOS). We have pioneered more sophisticated approaches involving custom-made metameric light sources for displays and general illumination. Those recently patented and patent pending technical approaches allow for selective modulation of melanopsin without impacting visual appearance. This represents a powerful new tool to understand the importance of melanopsin for NIF responses and a potential intervention to control these effects in the real world.Overall objective:We will test the effects of a melanopic-display, a new technology that has the potential to regulate the NIF impact of visual displays without affecting their visual appearance, human sleep.Specific aims:We hypothesize that visual contents presented via the melanopic-display in a low melanopic (LM) mode in the evening will not aversively affect sleep, while those presented in a high melanopic mode (HM) will attenuate the evening increase in melatonin, lengthen sleep onset and reduce the proportion of electroencephalographic (EEG) deep sleep in the night following exposure. If the data support our hypothesis, this will allow using LM displays and light sources in the evening, which fulfil optimal condition for vision without affecting sleep. We hypothesize that controlling melanopic irradiance allows an opportunity to control sleep and related NIF responses independent of any effect on the activity of photopic, cone-based vision. The outcome of these studies will allow to determine the utility of modulating melanopic irradiance, which is currently recommended by the international commission on illumination (CIE) and Deutsches Institut für Normung e.V. (DIN), and also define the effectiveness of this strategy compared to the traditional approach of regulating ‘visual brightness’ (photopic lux).A parallel set of experiments in animals will establish the mechanism behind such an effect. Greater responses to HM vs LM would imply a dominant influence of melanopsin. However, in humans it is not possible to exclude the alternative possibility that they reflect residual differences in cone or rod activity between the two conditions. We will be able to distinguish these alternatives in mice by asking whether differences in response to HM and LM stimuli are absent in melanopsin knockout (Opn4-/-) mice. Methods: This work relies upon a visual Display, developed by Robert Lucas, University of Manchester, in which we will be able to independently modulate the effective irradiance for cones vs. melanopsin. Healthy volunteers will undergo a 17-h laboratory study under different lighting conditions and intensive physiological (polysomnography), endocrinological and neurocognitive measurements. We will consider the two routes via which light can impact sleep onset time: adjustments in circadian phase and direct effects on behavioural state. We will be able to use versions of the melanopic display designed according to the characteristics of the mouse visual system to present HM and LM stimuli in wild type and Opn4-/- mice in established paradigms testing circadian phase resetting and control of sleep.Expected results: If the melanopic-device approach has the expected effects, light induced changes in circadian phase and sleep/arousal will be higher in HM vs LM conditions in humans and wild type mice, but not Opn4-/- animals.Impact: It would, for the first time, answer the question whether sleep-wake cycles exclusively respond to spectral components of light mediated by melanopsin or not and whether melanopic-displays could be applied to minimise their negative effects on alertness and sleep, and beneficially affect sleep instead. As such, we expect a considerable impact of the project not only on science but also society given that more than 90% of human beings are exposed to artificial light sources in the evening and at night.