SummaryExposure to even moderately bright short-wavelength light in the evening can strongly suppress the production of melatonin and delay our circadian rhythm. These effects are mediated by the retinohypothalamic pathway, connecting a subset of retinal ganglion cells to the circadian pacemaker in the suprachiasmatic nucleus (SCN) in the brain. These retinal ganglion cells express the photosensitive protein melanopsin, rendering them intrinsically photosensitive (ipRGCs). But ipRGCs also receive input from the classical photoreceptors — the cones and rods. Here, in human participants, we examined whether the short-wavelength-sensitive (S) cones contribute to the neuroendocrine response to light by using stimuli which differed exclusively in the amount of S cone excitation by almost two orders of magnitude (ratio 1:83), but not in the excitation of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones, rods, and melanopsin. We specifically examined the S cones since the previously published action spectra for melatonin suppression [1,2] pointed to a possible role of S cones in addition to melanopsin. We find no evidence for a role of S cones in the acute alerting and melatonin-supressing response to evening light exposure.

Exposure to even moderately bright, short-wavelength light in the evening can strongly suppress the production of melatonin and can delay our circadian rhythm. These effects are mediated by the retinohypothalamic pathway, connecting a subset of retinal ganglion cells to the circadian pacemaker in the suprachiasmatic nucleus (SCN) in the brain. These retinal ganglion cells directly express the photosensitive protein melanopsin, rendering them intrinsically photosensitive (ipRGCs). But ipRGCs also receive input from the classical photoreceptors — the cones and rods. Here, we examined whether the short-wavelength-sensitive (S) cones contribute to circadian photoreception by using lights which differed exclusively in the amount of S cone excitation by almost two orders of magnitude (ratio 1:83), but not in the excitation of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones, rods, and melanopsin. We find no evidence for a role of S cones in the acute alerting and melatonin supressing response to evening light exposure, pointing to an exclusive role of melanopsin in driving circadian responses.