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      Distinct Contributions of Rod, Cone, and Melanopsin Photoreceptors to Encoding Irradiance

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          Summary

          Photoreceptive, melanopsin-expressing retinal ganglion cells (mRGCs) encode ambient light (irradiance) for the circadian clock, the pupillomotor system, and other influential behavioral/physiological responses. mRGCs are activated both by their intrinsic phototransduction cascade and by the rods and cones. However, the individual contribution of each photoreceptor class to irradiance responses remains unclear. We address this deficit using mice expressing human red cone opsin, in which rod-, cone-, and melanopsin-dependent responses can be identified by their distinct spectral sensitivity. Our data reveal an unexpectedly important role for rods. These photoreceptors define circadian responses at very dim “scotopic” light levels but also at irradiances at which pattern vision relies heavily on cones. By contrast, cone input to irradiance responses dissipates following light adaptation to the extent that these receptors make a very limited contribution to circadian and pupillary light responses under these conditions. Our data provide new insight into retinal circuitry upstream of mRGCs and optimal stimuli for eliciting irradiance responses.

          Highlights

          ► Red cone knockin ( Opn1mw R ) mice reveal rod, cone, and melanopsin phases to NIF vision ► Rods drive circadian responses to very low irradiances (scotopic threshold) ► Circadian responses to light in the photopic range can be rod driven ► Light adaptation limits the influence of cones on NIF vision

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          Most cited references64

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          Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN.

          Human vision starts with the activation of rod photoreceptors in dim light and short (S)-, medium (M)-, and long (L)- wavelength-sensitive cone photoreceptors in daylight. Recently a parallel, non-rod, non-cone photoreceptive pathway, arising from a population of retinal ganglion cells, was discovered in nocturnal rodents. These ganglion cells express the putative photopigment melanopsin and by signalling gross changes in light intensity serve the subconscious, 'non-image-forming' functions of circadian photoentrainment and pupil constriction. Here we show an anatomically distinct population of 'giant', melanopsin-expressing ganglion cells in the primate retina that, in addition to being intrinsically photosensitive, are strongly activated by rods and cones, and display a rare, S-Off, (L + M)-On type of colour-opponent receptive field. The intrinsic, rod and (L + M) cone-derived light responses combine in these giant cells to signal irradiance over the full dynamic range of human vision. In accordance with cone-based colour opponency, the giant cells project to the lateral geniculate nucleus, the thalamic relay to primary visual cortex. Thus, in the diurnal trichromatic primate, 'non-image-forming' and conventional 'image-forming' retinal pathways are merged, and the melanopsin-based signal might contribute to conscious visual perception.
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            Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice.

            In the mammalian retina, besides the conventional rod-cone system, a melanopsin-associated photoreceptive system exists that conveys photic information for accessory visual functions such as pupillary light reflex and circadian photo-entrainment. On ablation of the melanopsin gene, retinal ganglion cells that normally express melanopsin are no longer intrinsically photosensitive. Furthermore, pupil reflex, light-induced phase delays of the circadian clock and period lengthening of the circadian rhythm in constant light are all partially impaired. Here, we investigated whether additional photoreceptive systems participate in these responses. Using mice lacking rods and cones, we measured the action spectrum for phase-shifting the circadian rhythm of locomotor behaviour. This spectrum matches that for the pupillary light reflex in mice of the same genotype, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells. We have also generated mice lacking melanopsin coupled with disabled rod and cone phototransduction mechanisms. These animals have an intact retina but fail to show any significant pupil reflex, to entrain to light/dark cycles, and to show any masking response to light. Thus, the rod-cone and melanopsin systems together seem to provide all of the photic input for these accessory visual functions.
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              Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice.

              In the mammalian retina, a small subset of retinal ganglion cells (RGCs) are intrinsically photosensitive, express the opsin-like protein melanopsin, and project to brain nuclei involved in non-image-forming visual functions such as pupillary light reflex and circadian photoentrainment. We report that in mice with the melanopsin gene ablated, RGCs retrograde-labeled from the suprachiasmatic nuclei were no longer intrinsically photosensitive, although their number, morphology, and projections were unchanged. These animals showed a pupillary light reflex indistinguishable from that of the wild type at low irradiances, but at high irradiances the reflex was incomplete, a pattern that suggests that the melanopsin-associated system and the classical rod/cone system are complementary in function.
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                Author and article information

                Contributors
                Journal
                Neuron
                Neuron
                Neuron
                Cell Press
                0896-6273
                1097-4199
                13 May 2010
                13 May 2010
                : 66
                : 3
                : 417-428
                Affiliations
                [1 ]Faculty of Life Sciences, AV Hill Building, University of Manchester, Manchester M13 9PT, UK
                [2 ]Department of Computer Science, Regent Court, 211 Portobello, University of Sheffield, Sheffield S1 4DP, UK
                [3 ]Departments of Biology and Neuroscience (JHMI), 227 Mudd Hall/3400 North Charles Street, Johns Hopkins University, Baltimore, MD 21218, USA
                [4 ]Nuffield Laboratory of Ophthalmology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
                Author notes
                []Corresponding author robert.lucas@ 123456manchester.ac.uk
                [5]

                Present address: Medway School of Pharmacy, University of Kent, Chatham ME4 4TB, UK

                [6]

                Present address: Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK

                [7]

                Present address: Warwick Systems Biology Centre, University of Warwick, Coventry CV4 7AL, UK; and Warwick HRI, University of Warwick, Wellesbourne, Warwick CV35 9EF, UK

                Article
                NEURON10233
                10.1016/j.neuron.2010.04.037
                2875410
                20471354
                911e9870-cab2-4a13-b9de-9f8a52af535a
                © 2010 ELL & Excerpta Medica.

                This document may be redistributed and reused, subject to certain conditions.

                History
                : 19 April 2010
                Categories
                Article

                Neurosciences
                cellbio,sysneuro
                Neurosciences
                cellbio, sysneuro

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