Light as a central modulator of circadian rhythms, sleep and affect

Abstract

Light has profoundly influenced the evolution of life on earth. As widely appreciated, light allows us to generate images of our environment. However, light, through the atypical intrinsically photosensitive retinal ganglion cells (ipRGCs; Box 1), also influences behaviors that are essential for our health and quality of life, yet are independent of image formation. These include the synchronization of the circadian clock to the solar day, tracking of seasonal changes, and regulation of sleep. Irregular light environments lead to problems in circadian rhythms and sleep, which eventually cause mood and learning deficits. Recently, it was found that irregular light can also directly impact mood and learning without producing major disruptions in circadian rhythms and sleep. Here, we will discuss the indirect and direct influence of light on mood and learning and provide a model for how light, the circadian clock, and sleep interact to influence mood and cognitive functions. Intrinsically photosensitive retinal ganglion cells (ipRGCs)Retinal photoreceptors transduce light energy into electrical signals that initiate vision. The classical photoreceptors, rods and cones, possess modified cilia that consist of stacks of membranes in which photopigments (rhodopsin and cone opsins) are concentrated. Rods are exquisitely sensitive and are able to detect even a few photons. Rods are therefore used for night vision. Cones are less sensitive than rods and are used for day and color vision. Color vision is mediated by cone photoreceptors that express cone-opsins with sensitivity peaks at different wavelengths (colors) of light. Humans have three cone types: short, mid and long wavelength sensitive cones (for simplicity, we will refer to these as blue, green and red cones, respectively). Rods and cones relay photic information through multisynaptic pathways to retinal ganglion cells (RGCs), which innervate different areas in the brain for complex visual processing13.A surprising discovery showed that a subpopulation of RGCs is intrinsically photosensitive and express the photopigment melanopsin. These cells were thus termed ipRGCs17–19. The melanopsin gene (Opn4) was originally cloned from Xenopus laevis dermal melanophores, and was shown to have orthologs in many mammalian species, including humans141. Sequence analysis shows that melanopsin shares more homology with invertebrate opsins than with vertebrate opsins, suggesting that melanopsin may use a different mechanism for light signaling than that used by the photopigments present in the rods and cones of vertebrates142. ipRGCs do not have modified membranes in which the photopigment can be concentrated: thus, melanopsin protein is expressed uniformly throughout the soma, dendrites, and the initial segment of the axon143. The lack of membrane specialization makes ipRGCs less sensitive to light than rods and cones. However, ipRGCs are able to incorporate light signals over extended period of time, resulting in an increase in their sensitivity during prolonged light stimula...

Arabian Oryx (Oryx leucoryx) Respond to Increased Ambient Temperatures with a Seasonal Shift in the Timing of Their Daily Inactivity Patterns

“…Erriksson et al, 1981;Tokura and Aschoff, 1983;Hastings et al, 1998;Pohl, 1998;Mistlberger and Skene, 2004;van Oort et al, 2007;Mircsof and Brown, 2013;El Allali et al, 2013;LeGates et al, 2014). The presence of several secondary zeitgebers (such as ambient temperature, patterns of eating and drinking, social influences and physical activity) that allow the entrainment of circadian rhythms in the absence of light is also well accepted (e.g.…”

“…Amongst many mammals, the dominant, or primary, zeitgeber for entraining circadian rhythms, including daily activity patterns, is ambient light (e.g. Daan and Aschoff, 1975;LeGates et al, 2014), but several secondary zeitgebers or modifiers of light entrained patterns (such as temperature, patterns of eating and drinking, social influences and physical activity) allow the entrainment of circadian rhythms in the absence of, or in concert with, the primary light zeitgeber (e.g. Erriksson et al, 1981;Tokura and Aschoff, 1983;Hastings et al, 1998;Pohl, 1998;Mistlberger and Skene, 2004;van Oort et al, 2007;Mircsof and Brown, 2013;El Allali et al, 2013).…”

Reconnecting Eye to Brain

“…Regeneration of certain classes of RGCs may lead to reinervation of distinct targets, which could be a problem or an opportunity. For example, in the service of circadian function, a specific class of intrinsically photosensitive RGCs (so-called M1 type of ipRGCs) preferentially innervates the suprachiasmatic nucleus, but not the dLGN or superior colliculus (SC) LeGates et al, 2014). In another remarkable example, each of three classes of direction-selective RGCs (which selectively respond to stimuli along different directional axes corresponding to the semicircular canals) project to specific nuclei in the accessory optic system (MTN, DTN, NOT) (Osterhout et al, 2015; to control eye movements that stabilize images on the retina.…”

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

“…The effect of AMD on depression is more complex as ipRGC projections to mood centres in the brain include direct innervation of the medial amygdala, lateral habenula and subparaventricular zone which are involved in depression and anxiety, as well as indirect innervation through the suprachiasmatic nucleus of the ventral tegmental area and raphe which are involved in mood regulation (LeGates, Fernandez & Hattar 2014). This is shown in rodents in which at least five ipRGC subtypes have been identified, although only two subtypes are identified in humans.…”