Article | Published:

Photon capture and signalling by melanopsin retinal ganglion cells

Nature volume 457, pages 281287 (15 January 2009) | Download Citation

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Abstract

A subset of retinal ganglion cells has recently been discovered to be intrinsically photosensitive, with melanopsin as the pigment. These cells project primarily to brain centres for non-image-forming visual functions such as the pupillary light reflex and circadian photoentrainment. How well they signal intrinsic light absorption to drive behaviour remains unclear. Here we report fundamental parameters governing their intrinsic light responses and associated spike generation. The membrane density of melanopsin is 104-fold lower than that of rod and cone pigments, resulting in a very low photon catch and a phototransducing role only in relatively bright light. Nonetheless, each captured photon elicits a large and extraordinarily prolonged response, with a unique shape among known photoreceptors. Notably, like rods, these cells are capable of signalling single-photon absorption. A flash causing a few hundred isomerized melanopsin molecules in a retina is sufficient for reaching threshold for the pupillary light reflex.

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Acknowledgements

Supported by an NRSA fellowship and a VNTP Training Grant to M.T.H.D., and NIH grants to K.-W.Y. and D.E.B. We thank Y. Koutalos, V. Bhandawat, D.-G. Luo, V. Kefalov, D. Liu, G. Maimon and C.-Y. Su for discussions, and Y. Wang, J. Hsieh and N. Nishiyama for technical assistance. We also thank J. Nathans and R. Reeves for suggestions on transgenic lines, J. Nathans and H. Cahill for the Gnat1-/- cl mouse line, and T. Shelley for machining. We dedicate this work to the Champalimaud Foundation, Portugal.

Author Contributions M.T.H.D. and K.-W.Y. designed the experiments and wrote the paper. All experiments were performed by M.T.H.D., except for pupil measurements, which were done by T.X. and M.T.H.D. The melanopsin-tdTomato BAC-transgenic mouse was generated by S.H.K. in the laboratory of D.E.B. Important early observations of the intensity–response relationship and kinetics were made by H.Z. using animals retrograde-labelled by H.-W.L.

Author information

Author notes

    • Haining Zhong
    •  & Hsi-Wen Liao

    Present addresses: Janelia Farm Research Campus, HHMI, Ashburn, Virginia 20147, USA (H.Z.); Department of Neurobiology, Children’s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA (H.-W.L.).

Affiliations

  1. Solomon H. Snyder Department of Neuroscience,

    • Michael Tri H. Do
    • , Shin H. Kang
    • , Tian Xue
    • , Haining Zhong
    • , Hsi-Wen Liao
    • , Dwight E. Bergles
    •  & King-Wai Yau
  2. Department of Ophthalmology, and,

    • King-Wai Yau
  3. Center for Sensory Biology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA

    • Michael Tri H. Do
    • , Tian Xue
    •  & King-Wai Yau

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Corresponding authors

Correspondence to Michael Tri H. Do or King-Wai Yau.

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https://doi.org/10.1038/nature07682

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