Melanopsin-Based Brightness Discrimination in Mice and Humans

Abstract

SummaryPhotoreception in the mammalian retina is not restricted to rods and cones but extends to a small number of intrinsically photoreceptive retinal ganglion cells (ipRGCs), expressing the photopigment melanopsin [1–4]. ipRGCs are known to support various accessory visual functions including circadian photoentrainment and pupillary reflexes. However, despite anatomical and physiological evidence that they contribute to the thalamocortical visual projection [5–7], no aspect of visual discrimination has been shown to rely upon ipRGCs. Based on their currently known roles, we hypothesized that ipRGCs may contribute to distinguishing brightness. This percept is related to an object's luminance—a photometric measure of light intensity relevant for cone photoreceptors. However, the perceived brightness of different sources is not always predicted by their respective luminance [8–12]. Here, we used parallel behavioral and electrophysiological experiments to first show that melanopsin contributes to brightness discrimination in both retinally degenerate and fully sighted mice. We continued to use comparable paradigms in psychophysical experiments to provide evidence for a similar role in healthy human subjects. These data represent the first direct evidence that an aspect of visual discrimination in normally sighted subjects can be supported by inner retinal photoreceptors.

Human trichromacy revisited

“…There are only a few studies that attempt to isolate the effect of melanopsin in healthy humans, and these are inconclusive about the role of melanopsin-initiated signals for visual perception (8). We describe the human measurements next.…”

“…The inhomogeneity of absorptions arising from the macular pigment distribution requires different spectral power distributions for metameric blacks in the fovea and periphery. In related work, Brown et al (8) used a very large field, spanning both the fovea and the periphery, and concluded that melanopsin contrast influences brightness perception; using an annular spatial configuration that masked the central 5°, they Fig. 3A. (B) Estimated S1 cone responses to the peripheral invisible stimuli at 10% modulation in 3D LMS space.…”

“…And a class of mRGCs in macaques projects to the lateral geniculate nucleus, the thalamic relay to primary visual cortex (3). Finally, it appears that melanopsininitiated signals influence brightness discrimination, although these results leave open the possibility that subjects fail to perceive signals arising from mRGCs (8). We describe direct tests of the hypothesis that sensitivity depends on absorptions in four receptor classes (tetrasensitivity).…”

Signalling by melanopsin (OPN4) expressing photosensitive retinal ganglion cells

“…There is, however, some data concerning the potential roles performed by M4-type pRGCs. The nature and properties of light responses recorded from cells within the dLGN have suggested a role for melanopsin in encoding changes in background [18][19][20] and the modulation of visual responses, with melanopsin reportedly driving adaptation of visual responses, modulating visual feature selectivity and facilitating a more reliable encoding of complex visual signals. 22,23 Based on retrograde labelling studies, it would seem that M4-type pRGCs project almost exclusively to the dLGN, 39 and would, therefore, seem to be predominantly tasked with providing input to visual pathways.…”

“…17 More recently it has become clear that melanopsin contributes not only to a range of NIF pathways but also performs multiple roles in image forming visual pathways. Melanopsin provides visual centres with information regarding overall levels of environmental light, and performs roles in irradiance coding and brightness discrimination, [18][19][20] contrast detection, 21 and adaptation of visual responses. 22 Melanopsin also acts as an irradiance detector for the retina, 22,23 providing measures of overall illuminance and facilitating the adaptation of cone photoresponses under bright-light conditions.…”