Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 298 (5601): 2213-2216

Copyright © 2002 by the American Association for the Advancement of Science

Melanopsin (Opn4) Requirement for Normal Light-Induced Circadian Phase Shifting

Satchidananda Panda,12 Trey K. Sato,12 Ana Maria Castrucci,34 Mark D. Rollag,3 Willem J. DeGrip,5 John B. Hogenesch,1 Ignacio Provencio,3* Steve A. Kay12*

The master circadian oscillator in the hypothalamic suprachiasmatic nucleus is entrained to the day/night cycle by retinal photoreceptors. Melanopsin (Opn4), an opsin-based photopigment, is a primary candidate for photoreceptor-mediated entrainment. To investigate the functional role of melanopsin in light resetting of the oscillator, we generated melanopsin-null mice (Opn4-/-). These mice entrain to a light/dark cycle and do not exhibit any overt defect in circadian activity rhythms under constant darkness. However, they display severely attenuated phase resetting in response to brief pulses of monochromatic light, highlighting the critical role of melanopsin in circadian photoentrainment in mammals.

1 Genomics Institute of the Novartis Research Foundation, 10675 John J. Hopkins Drive, San Diego, CA 92121, USA.
2 Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, San Diego, CA 92037, USA.
3 Department of Anatomy, Physiology, & Genetics, Uniformed Services University, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
4 Department of Physiology, University of Saõ Paolo, Post Office Box 11176, Saõ Paolo 05422, Brazil.
5 Department of Biochemistry, University of Nijmegen, Post Office Box 9101, 6500 HB Nijmegen, The Netherlands.
*   To whom correspondence should be addressed. E-mail: stevek{at}scripps.edu, provenci{at}bob.usuhs.mil



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Minutes, days and years: molecular interactions among different scales of biological timing.
D. A. Golombek, I. L. Bussi, and P. V. Agostino (2014)
Phil Trans R Soc B 369, 20120465
   Abstract »    Full Text »    PDF »
Irradiance encoding in the suprachiasmatic nuclei by rod and cone photoreceptors.
H. C. van Diepen, A. Ramkisoensing, S. N. Peirson, R. G. Foster, and J. H. Meijer (2013)
FASEB J 27, 4204-4212
   Abstract »    Full Text »    PDF »
Impairment of Intrinsically Photosensitive Retinal Ganglion Cells Associated With Late Stages of Retinal Degeneration.
G. Esquiva, P. Lax, and N. Cuenca (2013)
Invest. Ophthalmol. Vis. Sci. 54, 4605-4618
   Abstract »    Full Text »    PDF »
Human melanopsin forms a pigment maximally sensitive to blue light ({lambda}max {approx} 479 nm) supporting activation of Gq/11 and Gi/o signalling cascades.
H. J. Bailes and R. J. Lucas (2013)
Proc R Soc B 280, 20122987
   Abstract »    Full Text »    PDF »
Aberrant Development of the Suprachiasmatic Nucleus and Circadian Rhythms in Mice Lacking the Homeodomain Protein Six6.
D. D. Clark, M. R. Gorman, M. Hatori, J. D. Meadows, S. Panda, and P. L. Mellon (2013)
J Biol Rhythms 28, 15-25
   Abstract »    Full Text »    PDF »
Human phase response curve to a single 6.5 h pulse of short-wavelength light.
M. Ruger, M. A. St Hilaire, G. C. Brainard, S.-B. S. Khalsa, R. E. Kronauer, C. A. Czeisler, and S. W. Lockley (2013)
J. Physiol. 591, 353-363
   Abstract »    Full Text »    PDF »
Melanopsin Is Highly Resistant to Light and Chemical Bleaching in Vivo.
T. J. Sexton, M. Golczak, K. Palczewski, and R. N. Van Gelder (2012)
J. Biol. Chem. 287, 20888-20897
   Abstract »    Full Text »    PDF »
Melanopsin and Mechanisms of Non-visual Ocular Photoreception.
T. Sexton, E. Buhr, and R. N. Van Gelder (2012)
J. Biol. Chem. 287, 1649-1656
   Abstract »    Full Text »    PDF »
Melanopsin-Positive Intrinsically Photosensitive Retinal Ganglion Cells: From Form to Function.
T. M. Schmidt, M. T. H. Do, D. Dacey, R. Lucas, S. Hattar, and A. Matynia (2011)
J. Neurosci. 31, 16094-16101
   Abstract »    Full Text »    PDF »
Light enhances learned fear.
D. M. Warthen, B. J. Wiltgen, and I. Provencio (2011)
PNAS 108, 13788-13793
   Abstract »    Full Text »    PDF »
Early Onset and Differential Temporospatial Expression of Melanopsin Isoforms in the Developing Chicken Retina.
D. M. Verra, M. A. Contin, D. Hicks, and M. E. Guido (2011)
Invest. Ophthalmol. Vis. Sci. 52, 5111-5120
   Abstract »    Full Text »    PDF »
Multiple hypothalamic cell populations encoding distinct visual information.
T. M. Brown, J. Wynne, H. D. Piggins, and R. J. Lucas (2011)
J. Physiol. 589, 1173-1194
   Abstract »    Full Text »    PDF »
Light Activation of the Phosphoinositide Cycle in Intrinsically Photosensitive Chicken Retinal Ganglion Cells.
M. A. Contin, D. M. Verra, G. Salvador, M. Ilincheta, N. M. Giusto, and M. E. Guido (2010)
Invest. Ophthalmol. Vis. Sci. 51, 5491-5498
   Abstract »    Full Text »    PDF »
Intrinsically Photosensitive Retinal Ganglion Cells.
M. T. H. Do and K.-W. Yau (2010)
Physiol Rev 90, 1547-1581
   Abstract »    Full Text »    PDF »
Postnatal Development and Functional Adaptations of the Melanopsin Photoreceptive System in the Albino Mouse Retina.
I. Gonzalez-Menendez, F. Contreras, R. Cernuda-Cernuda, I. Provencio, and J. M. Garcia-Fernandez (2010)
Invest. Ophthalmol. Vis. Sci. 51, 4840-4847
   Abstract »    Full Text »    PDF »
Contribution of human melanopsin retinal ganglion cells to steady-state pupil responses.
S.-i. Tsujimura, K. Ukai, D. Ohama, A. Nuruki, and K. Yunokuchi (2010)
Proc R Soc B 277, 2485-2492
   Abstract »    Full Text »    PDF »
Physiology of Circadian Entrainment.
D. A. Golombek and R. E. Rosenstein (2010)
Physiol Rev 90, 1063-1102
   Abstract »    Full Text »    PDF »
Spectral Responses of the Human Circadian System Depend on the Irradiance and Duration of Exposure to Light.
J. J. Gooley, S. M. W. Rajaratnam, G. C. Brainard, R. E. Kronauer, C. A. Czeisler, and S. W. Lockley (2010)
Science Translational Medicine 2, 31ra33
   Abstract »    Full Text »    PDF »
Light-Dependent Behavioral Phenotypes in PER3-Deficient Mice.
D. R. van der Veen and S. N. Archer (2010)
J Biol Rhythms 25, 3-8
   Abstract »    PDF »
Circadian clock in Ciona intestinalis revealed by microarray analysis and oxygen consumption.
T. Minamoto, S. Hanai, K. Kadota, K. Oishi, H. Matsumae, M. Fujie, K. Azumi, N. Satoh, M. Satake, and N. Ishida (2010)
J. Biochem. 147, 175-184
   Abstract »    Full Text »    PDF »
Profile of Steve Kay.
B. Trivedi (2009)
PNAS 106, 18051-18053
   Full Text »    PDF »
The evolution of irradiance detection: melanopsin and the non-visual opsins.
S. N. Peirson, S. Halford, and R. G. Foster (2009)
Phil Trans R Soc B 364, 2849-2865
   Abstract »    Full Text »    PDF »
Circadian Modulation of Melanopsin-Driven Light Response in Rat Ganglion-Cell Photoreceptors.
S. Weng, K. Y. Wong, and D. M. Berson (2009)
J Biol Rhythms 24, 391-402
   Abstract »    PDF »
Differential Expression of Two Distinct Functional Isoforms of Melanopsin (Opn4) in the Mammalian Retina.
S. S. Pires, S. Hughes, M. Turton, Z. Melyan, S. N. Peirson, L. Zheng, M. Kosmaoglou, J. Bellingham, M. E. Cheetham, R. J. Lucas, et al. (2009)
J. Neurosci. 29, 12332-12342
   Abstract »    Full Text »    PDF »
Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation.
C. M. Altimus, A. D. Guler, K. L. Villa, D. S. McNeill, T. A. LeGates, and S. Hattar (2008)
PNAS 105, 19998-20003
   Abstract »    Full Text »    PDF »
Sensitivity of the Human Circadian System to Short-Wavelength (420-nm) Light.
G. C. Brainard, D. Sliney, J. P. Hanifin, G. Glickman, B. Byrne, J. M. Greeson, S. Jasser, E. Gerner, and M. D. Rollag (2008)
J Biol Rhythms 23, 379-386
   Abstract »    PDF »
A Computational Approach to the Functional Clustering of Periodic Gene-Expression Profiles.
B.-R. Kim, L. Zhang, A. Berg, J. Fan, and R. Wu (2008)
Genetics 180, 821-834
   Abstract »    Full Text »    PDF »
Intraretinal signaling by ganglion cell photoreceptors to dopaminergic amacrine neurons.
D.-Q. Zhang, K. Y. Wong, P. J. Sollars, D. M. Berson, G. E. Pickard, and D. G. McMahon (2008)
PNAS 105, 14181-14186
   Abstract »    Full Text »    PDF »
Retina-clock relations dictate nocturnal to diurnal behaviors.
D. S. McNeill, C. M. Altimus, and S. Hattar (2008)
PNAS 105, 12645-12646
   Full Text »    PDF »
Photochemistry of retinal chromophore in mouse melanopsin.
M. T. Walker, R. L. Brown, T. W. Cronin, and P. R. Robinson (2008)
PNAS 105, 8861-8865
   Abstract »    Full Text »    PDF »
Divergent Phenotypes of Vision and Accessory Visual Function in Mice with Visual Cycle Dysfunction (Rpe65rd12) or Retinal Degeneration (rd/rd).
S. Thompson, R. F. Mullins, A. R. Philp, E. M. Stone, and N. Mrosovsky (2008)
Invest. Ophthalmol. Vis. Sci. 49, 2737-2742
   Abstract »    Full Text »    PDF »
Photic Sensitivity Ranges of Hamster Pupillary and Circadian Phase Responses Do Not Overlap.
R. A. Hut, M. Oklejewicz, C. Rieux, and H. M. Cooper (2008)
J Biol Rhythms 23, 37-48
   Abstract »    PDF »
Responses of Suprachiasmatic Nucleus Neurons to Light and Dark Adaptation: Relative Contributions of Melanopsin and Rod Cone Inputs.
E. Drouyer, C. Rieux, R. A. Hut, and H. M. Cooper (2007)
J. Neurosci. 27, 9623-9631
   Abstract »    Full Text »    PDF »
Synaptic Contact between Melanopsin-Containing Retinal Ganglion Cells and Rod Bipolar Cells.
J. Ostergaard, J. Hannibal, and J. Fahrenkrug (2007)
Invest. Ophthalmol. Vis. Sci. 48, 3812-3820
   Abstract »    Full Text »    PDF »
Synaptic influences on rat ganglion-cell photoreceptors.
K. Y. Wong, F. A. Dunn, D. M. Graham, and D. M. Berson (2007)
J. Physiol. 582, 279-296
   Abstract »    Full Text »    PDF »
2-Aminoethoxydiphenylborane Is an Acute Inhibitor of Directly Photosensitive Retinal Ganglion Cell Activity In Vitro and In Vivo.
S. Sekaran, G. S. Lall, K. L. Ralphs, A. J. Wolstenholme, R. J. Lucas, R. G. Foster, and M. W. Hankins (2007)
J. Neurosci. 27, 3981-3986
   Abstract »    Full Text »    PDF »
Absence of Normal Photic Integration in the Circadian Visual System: Response to Millisecond Light Flashes.
L. Vidal and L. P. Morin (2007)
J. Neurosci. 27, 3375-3382
   Abstract »    Full Text »    PDF »
Melanopsin-Dependent Persistence and Photopotentiation of Murine Pupillary Light Responses.
Y. Zhu, D. C. Tu, D. Denner, T. Shane, C. M. Fitzgerald, and R. N. Van Gelder (2007)
Invest. Ophthalmol. Vis. Sci. 48, 1268-1275
   Abstract »    Full Text »    PDF »
Circadian Photoreception in Vertebrates.
S. Doyle and M. Menaker (2007)
Cold Spring Harb Symp Quant Biol 72, 499-508
   Abstract »    PDF »
Multiple Photoreceptors Contribute to Nonimage-forming Visual Functions Predominantly through Melanopsin-containing Retinal Ganglion Cells.
A.D. Guler, C.M. Altimus, J.L. Ecker, and S. Hattar (2007)
Cold Spring Harb Symp Quant Biol 72, 509-515
   Abstract »    PDF »
Dim Light Adaptation Attenuates Acute Melatonin Suppression in Humans.
S. A. Jasser, J. P. Hanifin, M. D. Rollag, and G. C. Brainard (2006)
J Biol Rhythms 21, 394-404
   Abstract »    PDF »
Inner retinal photoreception independent of the visual retinoid cycle.
D. C. Tu, L. A. Owens, L. Anderson, M. Golczak, S. E. Doyle, M. McCall, M. Menaker, K. Palczewski, and R. N. Van Gelder (2006)
PNAS 103, 10426-10431
   Abstract »    Full Text »    PDF »
Nonvisual light responses in the Rpe65 knockout mouse: Rod loss restores sensitivity to the melanopsin system.
S. E. Doyle, A. M. Castrucci, M. McCall, I. Provencio, and M. Menaker (2006)
PNAS 103, 10432-10437
   Abstract »    Full Text »    PDF »
Immunohistochemical evidence of a melanopsin cone in human retina..
O. Dkhissi-Benyahya, C. Rieux, R. A. Hut, and H. M. Cooper (2006)
Invest. Ophthalmol. Vis. Sci. 47, 1636-1641
   Abstract »    Full Text »    PDF »
Photons, Clocks, and Consciousness.
G. C. Brainard and J. P. Hanifin (2005)
J Biol Rhythms 20, 314-325
   Abstract »    PDF »
Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin.
Y. Fu, H. Zhong, M.-H. H. Wang, D.-G. Luo, H.-W. Liao, H. Maeda, S. Hattar, L. J. Frishman, and K.-W. Yau (2005)
PNAS 102, 10339-10344
   Abstract »    Full Text »    PDF »
Loss of Circadian Photoentrainment and Abnormal Retinal Electrophysiology in Math5 Mutant Mice.
J. A. Brzezinski IV, N. L. Brown, A. Tanikawa, R. A. Bush, P. A. Sieving, M. H. Vitaterna, J. S. Takahashi, and T. Glaser (2005)
Invest. Ophthalmol. Vis. Sci. 46, 2540-2551
   Abstract »    Full Text »    PDF »
Rhodopsin Formation in Drosophila Is Dependent on the PINTA Retinoid-Binding Protein.
T. Wang and C. Montell (2005)
J. Neurosci. 25, 5187-5194
   Abstract »    Full Text »    PDF »
PSEUDO-RESPONSE REGULATOR 7 and 9 Are Partially Redundant Genes Essential for the Temperature Responsiveness of the Arabidopsis Circadian Clock.
P. A. Salome and C. R. McClung (2005)
PLANT CELL 17, 791-803
   Abstract »    Full Text »    PDF »
Scotopic Illumination Enhances Entrainment of Circadian Rhythms to Lengthening Light:Dark Cycles.
M. R. Gorman, M. Kendall, and J. A. Elliott (2005)
J Biol Rhythms 20, 38-48
   Abstract »    PDF »
Nasal versus Temporal Illumination of the Human Retina: Effects on Core Body Temperature, Melatonin, and Circadian Phase.
M. Ruger, M. C. M. Gordijn, D. G. M. Beersma, B. de Vries, and S. Daan (2005)
J Biol Rhythms 20, 60-70
   Abstract »    PDF »
Illumination of the Melanopsin Signaling Pathway.
S. Panda, S. K. Nayak, B. Campo, J. R. Walker, J. B. Hogenesch, and T. Jegla (2005)
Science 307, 600-604
   Abstract »    Full Text »    PDF »
Rhabdomeric phototransduction initiated by the vertebrate photopigment melanopsin.
M. C. Isoldi, M. D. Rollag, A. M. d. L. Castrucci, and I. Provencio (2005)
PNAS 102, 1217-1221
   Abstract »    Full Text »    PDF »
Retinal Ganglion Cells Are Autonomous Circadian Oscillators Synthesizing N-Acetylserotonin during the Day.
E. Garbarino-Pico, A. R. Carpentieri, M. A. Contin, M. I. K. Sarmiento, M. A. Brocco, P. Panzetta, R. E. Rosenstein, B. L. Caputto, and M. E. Guido (2004)
J. Biol. Chem. 279, 51172-51181
   Abstract »    Full Text »    PDF »
Effect of Vitamin A Depletion on Nonvisual Phototransduction Pathways in Cryptochromeless Mice.
C. L. Thompson, C. P. Selby, R. N. Van Gelder, W. S. Blaner, J. Lee, L. Quadro, K. Lai, M. E. Gottesman, and A. Sancar (2004)
J Biol Rhythms 19, 504-517
   Abstract »    PDF »
Selective deficits in the circadian light response in mice lacking PACAP.
C. S. Colwell, S. Michel, J. Itri, W. Rodriguez, J. Tam, V. Lelievre, Z. Hu, and J. A. Waschek (2004)
Am J Physiol Regulatory Integrative Comp Physiol 287, R1194-R1201
   Abstract »    Full Text »    PDF »
Classical Photoreceptors Regulate Melanopsin mRNA Levels in the Rat Retina.
K. Sakamoto, C. Liu, and G. Tosini (2004)
J. Neurosci. 24, 9693-9697
   Abstract »    Full Text »    PDF »
Regulation of the Mammalian Circadian Clock by Cryptochrome.
A. Sancar (2004)
J. Biol. Chem. 279, 34079-34082
   Full Text »    PDF »
Light Pulses Do Not Induce C-Fos or Per1 in the SCN of Hamsters That Fail to Reentrain to the Photocycle.
M. T. Barakat, B. F. O'Hara, V. H. Cao, J. E. Larkin, H. C. Heller, and N. F. Ruby (2004)
J Biol Rhythms 19, 287-296
   Abstract »    PDF »
High Potassium Treatment Resets the Circadian Oscillator in Xenopus Retinal Photoreceptors.
M. Hasegawa and G. M. Cahill (2004)
J Biol Rhythms 19, 208-215
   Abstract »    PDF »
Molecular Mechanism of Mammalian Circadian Clock.
Y. Isojima, N. Okumura, and K. Nagai (2003)
J. Biochem. 134, 777-784
   Abstract »    Full Text »    PDF »
Seeing More Clearly: Recent Advances in Understanding Retinal Circuitry.
S. He, W. Dong, Q. Deng, S. Weng, and W. Sun (2003)
Science 302, 408-411
   Abstract »    Full Text »    PDF »
Cryptochrome, Compound Eyes, Hofbauer-Buchner Eyelets, and Ocelli Play Different Roles in the Entrainment and Masking Pathway of the Locomotor Activity Rhythm in the Fruit Fly Drosophila Melanogaster.
D. Rieger, R. Stanewsky, and C. Helfrich-Forster (2003)
J Biol Rhythms 18, 377-391
   Abstract »    PDF »
Expression of the Blue-Light Receptor Cryptochrome in the Human Retina.
C. L. Thompson, C. B. Rickman, S. J. Shaw, J. N. Ebright, U. Kelly, A. Sancar, and D. W. Rickman (2003)
Invest. Ophthalmol. Vis. Sci. 44, 4515-4521
   Abstract »    Full Text »    PDF »
Clocks, genes and sleep.
M. von Schantz and S. N. Archer (2003)
Journal of the Royal Society of Medicine 96, 486-489
   Full Text »    PDF »
A Broad Role for Melanopsin in Nonvisual Photoreception.
J. J. Gooley, J. Lu, D. Fischer, and C. B. Saper (2003)
J. Neurosci. 23, 7093-7106
   Abstract »    Full Text »    PDF »
Melanopsin Is Required for Non-Image-Forming Photic Responses in Blind Mice.
S. Panda, I. Provencio, D. C. Tu, S. S. Pires, M. D. Rollag, A. M. Castrucci, M. T. Pletcher, T. K. Sato, T. Wiltshire, M. Andahazy, et al. (2003)
Science 301, 525-527
   Abstract »    Full Text »    PDF »
Melanopsin, Ganglion-Cell Photoreceptors, and Mammalian Photoentrainment.
M. D. Rollag, D. M. Berson, and I. Provencio (2003)
J Biol Rhythms 18, 227-234
   Abstract »    PDF »
Loss of circadian rhythmicity in aging mPer1-/-mCry2-/- mutant mice.
H. Oster, S. Baeriswyl, G. T.J. van der Horst, and U. Albrecht (2003)
Genes & Dev. 17, 1366-1379
   Abstract »    Full Text »    PDF »
CIRCADIAN RHYTHMS: Circadian Photoreception.
M. Menaker (2003)
Science 299, 213-214
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882