Circadian Photoentrainment in Mice and Humans

Abstract

Light around twilight provides the primary entrainment signal for circadian rhythms. Here we review the mechanisms and responses of the mouse and human circadian systems to light. Both utilize a network of photosensitive retinal ganglion cells (pRGCs) expressing the photopigment melanopsin (OPN4). In both species action spectra and functional expression of OPN4 in vitro show that melanopsin has a λmax close to 480 nm. Anatomical findings demonstrate that there are multiple pRGC sub-types, with some evidence in mice, but little in humans, regarding their roles in regulating physiology and behavior. Studies in mice, non-human primates and humans, show that rods and cones project to and can modulate the light responses of pRGCs. Such an integration of signals enables the rods to detect dim light, the cones to detect higher light intensities and the integration of intermittent light exposure, whilst melanopsin measures bright light over extended periods of time. Although photoreceptor mechanisms are similar, sensitivity thresholds differ markedly between mice and humans. Mice can entrain to light at approximately 1 lux for a few minutes, whilst humans require light at high irradiance (>100’s lux) and of a long duration (>30 min). The basis for this difference remains unclear. As our retinal light exposure is highly dynamic, and because photoreceptor interactions are complex and difficult to model, attempts to develop evidence-based lighting to enhance human circadian entrainment are very challenging. A way forward will be to define human circadian responses to artificial and natural light in the “real world” where light intensity, duration, spectral quality, time of day, light history and age can each be assessed.

The circadian clock and metabolic homeostasis: entangled networks

“…OPN4 was shown to participate, together with cone and rod photoreceptors, in the synchronization of the SCN to the environmental light-dark cycle [14,15]. Two isoforms of OPN4 are expressed in a subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) [12,16,17] and are further subdivided into five categories [16][17][18]. OPN4 not only serves as a regulator of circadian rhythms, but it also controls several other light-responsive biological processes such as pupil constriction, melatonin synthesis, glaucoma development, migraine photophobia, and sleep [19].…”

Naturalistic Intensities of Light at Night: A Review of the Potent Effects of Very Dim Light on Circadian Responses and Considerations for Translational Research

“…To properly assess how relevant the summarized research on nLAN in model organisms is for human circadian rhythms, in this section we compare the pertinent neurobiology across species. First, the mammalian circadian system is very well-conserved ( 76 , 125 ), including fundamental properties of the primary oscillators. While the main body of mechanistic basic research involved nocturnal rodents (mice, rats, hamsters), circadian rhythms have been well-described in diurnal rodent species, including grass rats, degus and squirrels as well as larger mammals, including sheep and several species of non-human primates [e.g., baboon ( 126 )].…”

Circadian Biology in Obstructive Sleep Apnea

“…In humans, circadian rhythms are maintained through a natural cycle of 24 h light and dark. Intrinsically photosensitive retinal ganglion cells (IPRGCs) in the human eye receive light and pass this information to the central oscillator (suprachiasmatic nuclei) located in the hypothalamus [27,28]. This information serves to entrain, or synchronize, the circadian system to the environment.…”