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While rods, cones, and intrinsically photosensitive melanopsin-containing ganglion cells (ipRGCs) all drive light entrainment of the master circadian pacemaker of the suprachiasmatic nucleus, recent studies have proposed that entrainment of the mouse retinal clock is exclusively mediated by a UV-sensitive photopigment, neuropsin (OPN5). Here, we report that the retinal circadian clock can be phase shifted by short duration and relatively low-irradiance monochromatic light in the visible part of the spectrum, up to 520 nm. Phase shifts exhibit a classical photon dose-response curve. Comparing the response of mouse models that specifically lack middle-wavelength (MW) cones, melanopsin, and/or rods, we found that only the absence of rods prevented light-induced phase shifts of the retinal clock, whereas light-induced phase shifts of locomotor activity are normal. In a “rod-only” mouse model, phase shifting response of the retinal clock to light is conserved. At shorter UV wavelengths, our results also reveal additional recruitment of short-wavelength (SW) cones and/or OPN5. These findings suggest a primary role of rod photoreceptors in the light response of the retinal clock in mammals. [ABSTRACT FROM AUTHOR]

Light is a powerful stimulant for human alertness and cognition, presumably acting through a photoreception system that heavily relies on the photopigment melanopsin. In humans, evidence for melanopsin involvement in light-driven cognitive stimulation remains indirect, due to the difficulty to selectively isolate its contribution. Therefore, a role for melanopsin in human cognitive regulation remains to be established. Here, sixteen participants underwent consecutive and identical functional MRI recordings, during which they performed a simple auditory detection task and a more difficult auditory working memory task, while continuously exposed to the same test light (515 nm). We show that the impact of test light on executive brain responses depends on the wavelength of the light to which individuals were exposed prior to each recording. Test-light impact on executive responses in widespread prefrontal areas and in the pulvinar increased when the participants had been exposed to longer (589 nm), but not shorter (461 nm), wavelength light, more than 1 h before. This wavelength-dependent impact of prior light exposure is consistent with recent theories of the light-driven melanopsin dual states. Our results emphasize the critical role of light for cognitive brain responses and are, to date, the strongest evidence in favor of a cognitive role for melanopsin, which may confer a form of "photic memory" to human cognitive brain function. [ABSTRACT FROM AUTHOR]

Many nonvisual functions are regulated by light through a photoreceptive system involving melanopsin-expressing retinal ganglion cells that are maximally sensitive to blue light. Several studies have suggested that the ability of light to modulate circadian entrainment and to induce acute effects on melatonin secretion, subjective alertness, and gene expression decreases during aging, particularly for blue light. This could contribute to the documented changes in sleep and circadian regulatory processes with aging. However, age-related modification in the impact of light on steady-state pupil constriction, which regulates the amount of light reaching the retina, is not demonstrated. We measured pupil size in 16 young (22.8 ± 4 years) and 14 older (61 ± 4.4 years) healthy subjects during 45-second exposures to blue (480 nm) and green (550 nm) monochromatic lights at low (7 × 1012 photons/cm2/s), medium (3 × 1013 photons/cm2/s), and high (1014 photons/cm2/s) irradiance levels. Results showed that young subjects had consistently larger pupils than older subjects for dark adaptation and during all light exposures. Steady-state pupil constriction was greater under blue than green light exposure in both age groups and increased with increasing irradiance. Surprisingly, when expressed in relation to baseline pupil size, no significant age-related differences were observed in pupil constriction. The observed reduction in pupil size in older individuals, both in darkness and during light exposure, may reduce retinal illumination and consequently affect nonvisual responses to light. The absence of a significant difference between age groups for relative steady-state pupil constriction suggests that other factors such as tonic, sympathetic control of pupil dilation, rather than light sensitivity per se, account for the observed age difference in pupil size regulation. Compared to other nonvisual functions, the light sensitivity of steady-state pupil constriction appears to remain relatively intact and is not profoundly altered by age. [ABSTRACT FROM PUBLISHER]

In mammals, non-visual responses to light involve intrinsically photosensitive melanopsin-expressing retinal ganglion cells (ipRGCs) that receive synaptic inputs from rod and cone photoreceptors. Several studies have shown that cones also play a role in light entrainment, photic responses of the suprachiasmatic nucleus (SCN), pupil constriction, and sleep induction. These studies suggest that cones are mainly involved in the initial response to light, whereas melanopsin provides a sustained input for non-visual responses during continued light exposure. Based on this idea, we explored the effects of the absence of middle-wavelength (MW)-cones on the temporal responses of circadian behavior and clock gene expression in light. In mice lacking MW-cones, our results show a reduction in behavioral phase shifts in response to light stimulations of short duration at 480 and 530 nm, but no alteration for short-wavelength (360-nm) light exposures. Similarly, induction of the period gene mPer1 and mPer2 mRNAs in the SCN are attenuated in response to light exposures of mid to long wavelengths. Modeling of the photoresponses shows that mice lacking MW-cones have an overall reduction in sensitivity that increases with longer wavelengths. The differences in photic responsiveness are consistent with the idea that cones provide a strong initial phasic input to the circadian system at light-onset and may confer a priming effect on ipRGC responses to sub-threshold light exposures. In summary, the contribution of MW-cones is essential for the normal expression of phase shifts and clock gene induction by light in mammals. (Author correspondence: ) [ABSTRACT FROM AUTHOR]

In mammals, nonvisual responses to light have been shown to involve intrinsically photosensitive retinal ganglion cells (ipRGC) that express melanopsin and that are modulated by input from both rods and cones. Recent in vitro evidence suggests that melanopsin possesses dual photosensory and photoisomerase functions, previously thought to be a unique feature of invertebrate rhabdomeric photopigments. In cultured cells that normally do not respond to light, heterologous expression of mammalian melanopsin confers light sensitivity that can be restored by prior stimulation with appropriate wavelengths. Using three different physiological and behavioral assays, we show that this in vitro property translates to in vivo, melanopsin-dependent nonvisual responses. We find that prestimulation with long-wavelength light not only restores but enhances single-unit responses of SCN neurons to 480-nm light, whereas the long-wavelength stimulus alone fails to elicit any response. Recordings in Opn4-/- mice confirm that melanopsin provides the main photosensory input to the SCN, and furthermore, demonstrate that melanopsin is required for response enhancement, because this capacity is abolished in the knockout mouse. The efficiency of the light-enhancement effect depends on wavelength, irradiance, and duration. Prior long-wavelength light exposure also enhances short-wavelength-induced phase shifts of locomotor activity and pupillary constriction, consistent with the expression of a photoisomerase-like function in nonvisual responses to light. [ABSTRACT FROM AUTHOR]

Highlights: [•] Photoreceptive retinal ganglion cells (ipRGCs) regulate behavior and physiology. [•] ipRGCs use melanopsin-dependent intrinsic light responses and rod/cone inputs. [•] The relative contribution of each photoreceptor to evoked responses is not fully understood. [•] A method for quantifying light is presented that accounts for complex photoreceptive inputs. [•] Guidance for those designing architectural and therapeutic lighting is provided. [ABSTRACT FROM AUTHOR]