1. Howard Hughes Medical Institute and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
2. Department of Integrative and Molecular Neuroscience, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, Charing Cross Campus, London W6 8RF, UK
3. Departments of Zoology, Physiology and Psychology, University of Toronto, Toronto, Ontario M5S 3G5, Canada
4. Applied Vision Research Centre, Department of Optometry and Visual Science, City University, Northampton Square, London EC1V 0HB, UK
5. Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
6. Lehrstuhl Pharmakologie für Naturwissenschaften, Zentrum für Pharmaforschung, Ludwig-Maximilians Universität München, 81377 München, Germany
7. Institut für Pharmakologie und Toxikologie, Technische Universität München, 80802 München, Germany

Correspondence to: K.-W. Yau¹ Correspondence and requests for materials should be addressed to K.-W.Y. (Email: kwyau@mail.jhmi.edu).

Abstract

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^{1, 2, 3, 4, 5, 6, 7}. On ablation of the melanopsin gene, retinal ganglion cells that normally express melanopsin are no longer intrinsically photosensitive⁸. Furthermore, pupil reflex⁸, light-induced phase delays of the circadian clock^{9, 10} and period lengthening of the circadian rhythm in constant light^{9, 10} 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 genotype¹¹, and that for the intrinsic photosensitivity of the melanopsin-expressing retinal ganglion cells⁷. 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.