Experiment overview. (A) There are several classes of melanopsin-containing ipRGCs, which vary in their central projections, function, and extent to which they receive input from cones. The ipRGCs project to the somatosensory thalamus and the lateral geniculate nucleus, where their signals may contribute to light sensitivity. Other ipRGCs project to the pretectal nuclei to control the size of the pupil. Not shown are numerous, additional subcortical projection targets of the ipRGCs (e.g., the suprachiasmatic nucleus). RGC, retinal ganglion cell. (B) The spectral sensitivity functions of the relevant photoreceptors under daylight conditions. S, M, and L refer to the short-, medium-, and long-wavelength sensitive cones, respectively. (C) Shown are pairs of spectra (background: black; stimulus: red) that differ in excitation for the targeted photoreceptors. In Left, Center, and Right, the stimuli produce equal contrast on the cones and melanopsin (termed light flux), contrast only on melanopsin, and equal contrast across all three classes of cones but no contrast on melanopsin, respectively. (D) Each trial featured a 4-s period during which the stimulus transitioned from the background to the stimulation spectrum and back. Twelve seconds after stimulus offset, the subject provided a discomfort rating. There was an intertrial interval that varied between 1.5 and 2.5 s. (E) The light from a digital spectral integrator was presented to the pharmacologically dilated right eye of the subject through an artificial pupil. The consensual pupillary light response of left eye was recorded with an infrared camera. (F) The stimulus spectra were presented in an eyepiece with a 27.5°-diameter field, with the central 5° obscured to minimize macular stimulation.