Skip to main content
SpringerLink
Log in

Melanopsin in the circadian timing system

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

In mammals, circadian rhythms are generated by a light-entrainable oscillator located in the hypothalamic suprachiasmatic nucleus (SCN). Light signals reach the SCN via a dedicated retinal pathway, the retinohypothalamic tract (RHT). One question that continues to elude scientists is whether the circadian system has its own dedicated photoreceptor or photoreceptors. It is well established that conventional photoreceptors, rods and cones, are not required for circadian photoreception, suggesting that the inner retinal layer might contribute to circadian photoreception. Melanopsin, a novel photo pigment expressed in retinal ganglion cells (RGCs), has been proposed recently as a candidate circadian photoreceptor. Melanopsin-containing RGCs are intrinsically photosensitive, form part of the RHT, and contain neurotransmitters known to play a critical role in the circadian response to light. Furthermore, melanopsin-containing RGCs do not depend on inputs from rods and cones to transmit light signals to the SCN. However, based on a review of the available information about melanopsin and on new data from our laboratory, we propose that melanopsin, in itself, is not necessary for circadian photoreception. In fact, it appears that of the known photoreceptor systems, none, in and of itself, is necessary for circadian photoreception. Instead, it appears that within the photoreceptive systems there is some degree of redundancy, each contributing in some way to photic entrainment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Adams M. D., Kerlavage A. R., Fleischmann R. D., Fuldner R. A., Bult C. J., Lee N. H., et al. (1995) Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence. Nature 377, 3–174.

    PubMed  CAS  Google Scholar 

  • Ahmad M. and Cashmore A. R. (1993) HY4 gene of A. thaliana encodes a protein with characteristics of a blue-light photoreceptor. Nature 366, 162–166.

    Article  PubMed  CAS  Google Scholar 

  • Beaulé C. and Amir S. (2001) Photic regulation of circadian rhythms and the expression of p75 neurotrophin receptor immunoreactivity in the suprachiasmatic nucleus in rats. Brain Res. 894, 301–306.

    Article  PubMed  Google Scholar 

  • Berson D. M., Dunn F. A., and Takao M. (2002). Phototransduction by retinal ganglion cells that set the circadian clock. Science 295, 1070–1073.

    Article  PubMed  CAS  Google Scholar 

  • Brainard G. C., Hanifin J. P., Greeson J. M., Byrne B., Glickman G., Gerner E., and Rollag M. D. (2001) Action spectrum for melatonin regulation in humans: evidence for a novel circadian photoreceptor. J. Neurosci. 21, 6405–6412.

    PubMed  CAS  Google Scholar 

  • Cashmore A. R., Jarillo J. A., Wu Y. J., and Liu D. (1999) Cryptochromes: blue light receptors for plants and animals. Science 284, 760–765.

    Article  PubMed  CAS  Google Scholar 

  • Chambille I. (1998) Retinal ganglion cells expressing the FOS protein after light stimulation in the Syrian hamster are relatively insensitive to neonatal treatment with monosodium glutamate. J. Comp. Neurol. 392, 458–467.

    Article  PubMed  CAS  Google Scholar 

  • Chambille I. and Serviere J. (1993) Neurotoxic effects of neonatal injections of monosodium L-glutamate (L- MSG) on the retinal ganglion cell layer of the golden hamster: anatomical and functional consequences on the circadian system. J. Comp. Neurol. 338, 67–82.

    Article  PubMed  CAS  Google Scholar 

  • Czeisler C. A., Shanahan T. L., Klerman E. B., Martens H., Brotman D. J., Emens J. S., et al. (1995) Suppression of melatonin secretion in some blind patients by exposure to bright light. N. Engl. J. Med. 332, 6–11.

    Article  PubMed  CAS  Google Scholar 

  • Ebling F. J. (1996) The role of glutamate in the photic regulation of the suprachiasmatic nucleus. Prog. Neurobiol. 50, 109–132.

    Article  PubMed  CAS  Google Scholar 

  • Edelstein K. and Amir S. (1996) Constant light induces persistent Fos expression in rat intergeniculate leaflet. Brain Res. 731, 221–225.

    Article  PubMed  CAS  Google Scholar 

  • Edelstein K. and Amir S. (1999) The intergeniculate leaflet does not mediate the disruptive effects of constant light on circadian rhythms in the rat. Neuroscience 90, 1093–1101.

    Article  PubMed  CAS  Google Scholar 

  • Edelstein K., Pfaus J. G., Rusak B., and Amir S. (1995) Neonatal monosodium glutamate treatment prevents effects of constant light on circadian temperature rhythms of adult rats. Brain Res. 675, 135–142.

    Article  PubMed  CAS  Google Scholar 

  • Freedman M. S., Lucas R. J., Soni B., von Schantz M., Munoz M., David-Gray Z., and Foster R. (1999) Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284, 502–504.

    Article  PubMed  CAS  Google Scholar 

  • Groos G. (1982) The comparative physiology of extraocular photoreception. Experientia 38, 989–991.

    Article  PubMed  CAS  Google Scholar 

  • Hall J. C. (2000) Cryptochromes: sensory reception, transduction, and clock functions subserving circadian systems. Curr. Opin. Neurobiol. 10, 456–466.

    Article  PubMed  CAS  Google Scholar 

  • Hannibal J., Vrang N., Card J. P., and Fahrenkrug J. (2001) Light-dependent induction of cFos during subjective day and night in PACAP-containing ganglion cells of the retinohypothalamic tract. J. Biol. Rhythms 16, 457–470.

    Article  PubMed  CAS  Google Scholar 

  • Hannibal J., Hindersson P., Knudsen S. M., Georg B., Fahrenkrug J. (2002) The photopigment melanopsin is exclusively present in pituitary adenylate cyclase-activating polypeptide-containing retinal ganglion cells of the retinohypothalamic tract. J. Neurosci. 22, RC191.

    Google Scholar 

  • Hannibal J., Ding J. M., Chen D., Fahrenkrug J., Larsen P. J., Gillette M. U., and Mikkelsen J. D. (1997) Pituitary adenylate cyclase-activating peptide (PACAP) in the retinohypothalamic tract: a potential daytime regulator of the biological clock. J. Neurosci. 17, 2637–2644.

    PubMed  CAS  Google Scholar 

  • Hattar S., Liao H. W., Takao M., Berson D. M., and Yau K. W. (2002) Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295, 1065–1070.

    Article  PubMed  CAS  Google Scholar 

  • Johnson R. F., Morin L. P., and Moore R. Y. (1988) Retinohypothalamic projections in the hamster and rat demonstrated using cholera toxin. Brain Res. 462, 301–312.

    Article  PubMed  CAS  Google Scholar 

  • Klein D., Moore R. Y., and Reppert S. M., eds (1991) Suprachiasmatic Nucleus: The Mind’s Clock. Oxford: Oxford University Press.

    Google Scholar 

  • Lucas R. J., Douglas R. H., and Foster R. G. (2001) Characterization of an ocular photopigment capable of driving pupillary constriction in mice. Nat. Neurosci. 4, 621–626.

    Article  PubMed  CAS  Google Scholar 

  • Lucas R. J., Hattar S., Takao M., Berson D. M., Foster R. G., and Yau K. W. (2003) Diminished pupillary light reflex at high irradian ces in melanopsin-knockout mice. Science 299, 245–247.

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto Y. and Sancar A. (1998) Vitamin B2-based blue-light photoreceptors in the retinohypothalamic tract as the photoactive pigments for setting the circadian clock in mammals. Proc. Natl. Acad. Sci. U. S. A. 95, 6097–6102.

    Article  PubMed  CAS  Google Scholar 

  • Miyamoto Y. and Sancar A. (1999) Circadian regulation of cryptochrome genes in the mouse. Brain Res. Mol. Brain Res. 71, 238–243.

    Article  PubMed  CAS  Google Scholar 

  • Moore R. Y. and Lenn N. J. (1972) A retinohypothalmic projection in the rat. J. Comp. Neurol. 146, 1–14.

    Article  PubMed  CAS  Google Scholar 

  • Panda S., Sato T. K., Castrucci A. M., et al. (2002) Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science 298, 2213–2216.

    Article  PubMed  CAS  Google Scholar 

  • Perry V. H. (1979) The ganglion cell layer of the retina of the rat: a Golgi study. Proc. R. Soc. Lond. B. Biol. Sci. 204, 363–375.

    Article  PubMed  CAS  Google Scholar 

  • Pickard G. E., Turek F. W., Lamperti A. A., and Silverman A. J. (1982) The effect of neonatally administered monosodium glutamate (MSG) on the development of retinofugal projections and entrainment of circadian locomotor activity. Behav. Neural. Biol. 34, 433–444.

    Article  PubMed  CAS  Google Scholar 

  • Provencio I. and Foster R. G. (1995) Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics. Brain Res. 694, 183–190.

    Article  PubMed  CAS  Google Scholar 

  • Provencio I., Jiang G., De Grip W. J., Hayes W. P., and Rollag M. D. (1998) Melanopsin: an opsin in melanophores, brain, and eye. Proc. Natl. Acad. Sci. U. S. A. 95, 340–345.

    Article  PubMed  CAS  Google Scholar 

  • Provencio I., Rodriguez I. R., Jiang G., Hayes W. P., Moreira E. F., and Rollag M. D. (2000) A novel human opsin in the inner retina. J. Neurosci. 20, 600–605.

    PubMed  CAS  Google Scholar 

  • Provencio I., Rollag M. D., and Castrucci A. M. (2002) Photoreceptive net in the mammalian retina. This mesh of cells may explain how some blind mice can still tell day from night. Nature 415, 493.

    Article  PubMed  CAS  Google Scholar 

  • Ruby N. F., Brennan T. J., Xie X., Cao V., Franken P., Heller H. C., and O’Hara B. F. (2002) Role of melanopsin in circadian responses to light. Science 298, 2211–2213.

    Article  PubMed  CAS  Google Scholar 

  • Sancar A. (2000) Cryptochrome: the second photoactive pigment in the eye and its role in circadian photoreception. Annu. Rev. Biochem. 69, 31–67.

    Article  PubMed  CAS  Google Scholar 

  • Selby C. P., Thompson C., Schmitz T. M., Van Gelder R. N., and Sancar A. (2000) Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice. Proc. Natl. Acad. Sci. U. S. A. 97, 14697–14702.

    Article  PubMed  CAS  Google Scholar 

  • Sollars P. J., Smeraski C. A., Kaufman J. D., Ogilvie M. D., Provencio I., Morin L. P., and Pickard G. E. (2002) Melanopsin and non-melanopsin expressing retinal ganglion cells innervate the suprachiasmatic nucleus. Soc. Neurosci. Abstr.

  • Soni B. G., Philp A. R., Foster R. G., and Knox B. E. (1998) Novel retinal photoreceptors. Nature 394, 27–28.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi J. S., DeCoursey P. J., Bauman L., and Menaker M. (1984) Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms. Nature 308, 186–188.

    Article  PubMed  CAS  Google Scholar 

  • Thompson C. L., Blaner W. S., Van Gelder R. N., Lai K., Quadro L., Colantuoni V., et al. (2001) Preservation of light signaling to the suprachiasmatic nucleus in vitamin A-deficient mice. Proc. Natl. Acad. Sci. U. S. A. 98, 11708–11713.

    Article  PubMed  CAS  Google Scholar 

  • Thresher R. J., Vitaterna M. H., Miyamoto Y., Kazantsev A., Hsu D. S., Petit C., et al. (1998) Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses. Science 282, 1490–1494.

    Article  PubMed  CAS  Google Scholar 

  • Todo T. (1999) Functional diversity of the DNA photolyase/blue light receptor family. Mutat. Res. 434, 89–97.

    PubMed  CAS  Google Scholar 

  • van der Horst G. T., Muijtjens M., Kobayashi K., Takano R., Kanno S., Takao M., et al. (1999) Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature 398, 627–630.

    Article  PubMed  Google Scholar 

  • Williams J. A. and Sehgal A. (2001) Molecular components of the circadian system in Drosophila. Annu. Rev. Physiol. 63, 729–755.

    Article  PubMed  CAS  Google Scholar 

  • Young M. W. (2000) Life’s 24-hour clock: molecular control of circadian rhythms in animal cells. Trends Biochem. Sci. 25, 601–606.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, H3G 1M8, Montréal, QC, Canada

    Christian Beaulé, Barry Robinson, Elaine Waddington Lamont & Shimon Amir

Authors
  1. Christian Beaulé
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Barry Robinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elaine Waddington Lamont
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shimon Amir
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shimon Amir.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beaulé, C., Robinson, B., Lamont, E.W. et al. Melanopsin in the circadian timing system. J Mol Neurosci 21, 73–89 (2003). https://doi.org/10.1385/JMN:21:1:73

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1385/JMN:21:1:73

Index Entries

Search

Navigation