Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision

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Abstract

Rod and cone photoreceptors detect light and relay this information through a multisynaptic pathway to the brain by means of retinal ganglion cells (RGCs)1. These retinal outputs support not only pattern vision but also non-image-forming (NIF) functions, which include circadian photoentrainment and pupillary light reflex (PLR). In mammals, NIF functions are mediated by rods, cones and the melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs)2,3. Rod–cone photoreceptors and ipRGCs are complementary in signalling light intensity for NIF functions4,5,6,7,8,9,10,11,12. The ipRGCs, in addition to being directly photosensitive, also receive synaptic input from rod–cone networks13,14. To determine how the ipRGCs relay rod–cone light information for both image-forming and non-image-forming functions, we genetically ablated ipRGCs in mice. Here we show that animals lacking ipRGCs retain pattern vision but have deficits in both PLR and circadian photoentrainment that are more extensive than those observed in melanopsin knockouts8,10,11. The defects in PLR and photoentrainment resemble those observed in animals that lack phototransduction in all three photoreceptor classes6. These results indicate that light signals for irradiance detection are dissociated from pattern vision at the retinal ganglion cell level, and animals that cannot detect light for NIF functions are still capable of image formation.

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Figure 1: Elimination of ipRGCs in mouse retina.
Figure 2: The ipRGC fibres in the brain decrease in aDTA mice.
Figure 3: Opn4 aDTA mice have deficits in PLR.
Figure 4: Opn4 aDTA / aDTA mice do not photoentrain or mask.

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Acknowledgements

We thank J. Mackes and G. Harrison for help in genotyping the animals; R. Kuruvilla, M. Van Doren, B. Wendland, M. Halpern, M. Caterina, C.-Y. Su, J. Bradley and laboratory members in the Biology Department at the Johns Hopkins University for scientific discussions and comments on the manuscript. This work was supported by grants from the National Institutes of Health (to S. Hattar and K.-W.Y.), the Biotechnology and Biological Sciences Research Council (to R.J.L.) and the David and Lucile Packard and Alfred P. Sloan Foundations (to S. Hattar).

Author Contributions A.D.G. and S. Hattar wrote the paper. J.L.E., R.J.L., D.M.B. and T.C.B. gave helpful comments on the manuscript. A.D.G., J.L.E. and C.M.A. in S. Hattar’s laboratory performed all the behavioural studies on the aDTA homozygous animals, as well as the X-gal staining of the Opn4aDTA/tau-LacZ and Opn4tau-LacZ/+ animals, the morphology of the retina, the cholera toxin injections, the water maze and the optomotor studies. D.M.B. helped in analysing the brains of the Opn4aDTA/tau-lacZ and the cholera-toxin-injected animals. G.S.L. and A.R.B. in R.J.L.’s laboratory conducted all the behavioural studies on the aDTA heterozygous animals, and the electroretinogram studies. T.C.B. provided the construct and suggestions for the aDTA targeting strategy. H.C. made the optokinetic nystagmus recordings. H.-W.L. in K.-W.Y.’s laboratory performed the melanopsin immunostaining on aDTA heterozygous mice. Animals were first conceived in K.-W.Y.’s laboratory and produced by S. Hattar and S. Haq to the chimeric stage. Germline transmission was obtained independently in the laboratories of S. Hattar (with help from H.Z.) and K.-W.Y. All other authors helped in the planning, technical support and discussions of experiments.

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Correspondence to Robert J. Lucas or Samer Hattar.

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Güler, A., Ecker, J., Lall, G. et al. Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision. Nature 453, 102–105 (2008) doi:10.1038/nature06829

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