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 enables us to generate images of our environment. However, light - through intrinsically photosensitive retinal ganglion cells (ipRGCs) - also influences behaviours that are essential for our health and quality of life but are independent of image formation. These include the synchronization of the circadian clock to the solar day, tracking of seasonal changes and the 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 affect mood and learning without producing major disruptions in circadian rhythms and sleep. In this Review, we 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.

Figure 1. Model of the direct and indirect influences light on mood and cognition

Light can regulate mood and learning secondarily by first modulating sleep and circadian rhythms (indirect pathway), or light can directly affect mood without disrupting sleep or causing circadian arrhythmicity (direct pathway). The effects of light on circadian rhythms, sleep and mood are mediated by ipRGCs.

Figure 2. Retinal and brain circuits underlying the effects of light on non-image forming visual functions

A. Schematic view of the retina showing the organization of different neuronal populations and their synaptic connections. Rods and cones are confined to the photoreceptor layer. Light detected by rods and cones is processed and signaled to retinal ganglion cells (RGCs) through horizontal, amacrine and bipolar cells. RGCs are the only output neurons from the retina to the brain. A subset of RGCs (2–5% of the total number of RCGs) are intrinisically photosensitive RGCs (ipRGCs). There are at least 5 subtypes of ipRGCs (M1–M5) with different morphological and electrophysiological properties, which show widespread projection patterns throughout the brain. B. ipRGCs project to numerous brain regions, including many that have a role in driving light-mediated behaviors, including circadian photoentrainment and sleep. In addition, ipRGCs also innervate nuclei involved in depression and/or anxiety, such as the MA, LHb and SPZ (highlighted in green) indicating a possible direct role of light on mood. C. Several of the ipRGCs targets (blue), including the SPZ, VLPO, LH and LHb also receive innervation from the SCN, raising the possibility that in addition to its pacemaker function, the SCN can also act as a conduit for light information. Interestingly, the MA and the LHb are also brain peripheral clocks that receive direct retinal innervation. Areas involved in mood regulation (VTA and raphe) and cognition (LH) can be influenced by light either via the SCN or in parallel via the MA and LHb. LHb: lateral habenula; MA: medial amygdala; SCN: suprachiasmatic nucleus; SPZ: subparaventricular zone; VLPO: ventrolateral preoptic area; VTA: ventral tegmental area; HC: hippocampus; LH: lateral hypothalamus; LC: locus coeruleus.