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

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]  M. Menaker,et al.  Circadian photoreception in the retinally degenerate mouse (rd/rd) , 1991, Journal of Comparative Physiology A.

[2]  K. Gardner,et al.  White Collar-1, a DNA Binding Transcription Factor and a Light Sensor , 2002, Science.

[3]  J. Dunlap,et al.  White Collar-1, a Circadian Blue Light Photoreceptor, Binding to the frequency Promoter , 2002, Science.

[4]  K. Yau,et al.  Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity , 2002, Science.

[5]  D. Berson,et al.  Phototransduction by Retinal Ganglion Cells That Set the Circadian Clock , 2002, Science.

[6]  M. Rollag,et al.  Anatomy: Photoreceptive net in the mammalian retina , 2002, Nature.

[7]  Jun Lu,et al.  Melanopsin in cells of origin of the retinohypothalamic tract , 2001, Nature Neuroscience.

[8]  J. P. Card,et al.  Light-Dependent Induction of cFos during Subjective Day and Night in PACAP-Containing Ganglion Cells of the Retinohypothalamic Tract , 2001, Journal of biological rhythms.

[9]  Jeffrey C. Hall,et al.  The Circadian Clock of Fruit Flies Is Blind after Elimination of All Known Photoreceptors , 2001, Neuron.

[10]  J. Hannibal,et al.  Pituitary adenylate cyclase-activating polypeptide induces period1 and period2 gene expression in the rat suprachiasmatic nucleus during late night , 2001, Neuroscience.

[11]  R. V. Van Gelder,et al.  Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  M. Yanovsky,et al.  A quadruple photoreceptor mutant still keeps track of time , 2000, Current Biology.

[13]  W. P. Hayes,et al.  A Novel Human Opsin in the Inner Retina , 2000, The Journal of Neuroscience.

[14]  N Mrosovsky,et al.  Masking: history, definitions, and measurement. , 1999, Chronobiology international.

[15]  R. Foster,et al.  Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. , 1999, Science.

[16]  H. Fong,et al.  The Endogenous Chromophore of Retinal G Protein-coupled Receptor Opsin from the Pigment Epithelium* , 1999, The Journal of Biological Chemistry.

[17]  J. Ashby.  References and Notes , 1999 .

[18]  Jeffrey C. Hall,et al.  The cryb Mutation Identifies Cryptochrome as a Circadian Photoreceptor in Drosophila , 1998, Cell.

[19]  D. E. Somers,et al.  Phytochromes and cryptochromes in the entrainment of the Arabidopsis circadian clock. , 1998, Science.

[20]  J. Rizzo,et al.  Suppression of melatonin secretion in some blind patients by exposure to bright light. , 1995, The New England journal of medicine.

[21]  G. E. Pickard.  Intergeniculate leaflet ablation alters circadian rhythms in the mouse , 1994, Neuroreport.

[22]  J. Takahashi,et al.  Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms , 1984, Nature.

[23]  J Cairns,et al.  Cold Spring Harbor Symposia. , 1968, Science.