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ARTICLE, Behavioral/Systems

Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor

George C. Brainard, John P. Hanifin, Jeffrey M. Greeson, Brenda Byrne, Gena Glickman, Edward Gerner and Mark D. Rollag
Journal of Neuroscience 15 August 2001, 21 (16) 6405-6412; DOI: https://doi.org/10.1523/JNEUROSCI.21-16-06405.2001
George C. Brainard
1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and
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John P. Hanifin
1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and
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Jeffrey M. Greeson
1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and
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Brenda Byrne
1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and
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Gena Glickman
1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and
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Edward Gerner
1Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, and
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Mark D. Rollag
2Department of Anatomy, Physiology and Genetics, Uniformed Services University of Health Sciences, Bethesda, Maryland 20814
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  • Fig. 1.
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    Fig. 1.

    This diagram illustrates the experimental electronic, optic, and ganzfeld dome exposure array. This apparatus provides a uniform, patternless stimulus that encompasses the subject's entire visual field. For clarity, the subject's head is shown slightly withdrawn from the opening of the ganzfeld dome. During all light exposures, the subjects' bony orbits are completely enclosed in the dome walls, providing complete exposure of their visual fields.

  • Fig. 2.
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    Fig. 2.

    In the top two graphs, thebars represent group mean + SEM values of plasma melatonin relative to 460 nm monochromatic light exposure at different irradiances in one group of eight healthy subjects. Thetop shows plasma melatonin values before and after light exposure. There were no significant differences (F= 0.70; p = 0.69) across preexposure mean melatonin values. Light irradiances at or above 3.1 μW/cm2elicited significant melatonin suppression. The middleillustrates the subjects' plasma melatonin percent control-adjusted change scores. Progressively higher irradiance exposures at 460 nm produce progressively greater plasma melatonin percent control-adjusted change scores (p < 0.0001). Thebottom demonstrates the best-fit fluence–response curve for 460 nm exposures and percent control-adjusted melatonin suppression (R2 = 0.97). Each data point represents one group mean ± SEM.

  • Fig. 3.
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    Fig. 3.

    This figure illustrates the fitted univariant fluence–response curves for monochromatic light exposures and percent control-adjusted melatonin suppression for eight wavelengths of visible light. Each fluence–response curve is derived from eight healthy volunteers who participated in a complete, within-subjects experimental design. In each graph, the data points represent group means ± SEM. Each curve has a high coefficient of correlation (0.95–0.81).

  • Fig. 4.
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    Fig. 4.

    In this graph, the bars represent group mean ± SEM plasma melatonin values before and after exposure to 31.8 μW/cm2 monochromatic light at 420 nm in eight healthy subjects. This light irradiance induced a significant melatonin suppression (p < 0.003).

  • Fig. 5.
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    Fig. 5.

    This graph demonstrates the action spectrum for percent control-adjusted melatonin suppression in 72 healthy human subjects. The filled circles represent the half-saturation constants of eight wavelengths from 440 to 600 nm that were normalized to the maximum response and plotted as log relative sensitivity. The open circle represents the estimated half-saturation constant derived from the 420 nm data. The solid curve portrays the best-fit template for vitamin A1 retinaldehyde photopigments, which predicts a maximal spectral absorbance (λmax) of 464 nm (Partridge and De Grip, 1991). There is a high coefficient of correlation for fitting this opsin template to the melatonin suppression data (R2 = 0.91).

  • Fig. 6.
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    Fig. 6.

    This figure illustrates a comparison of the melatonin suppression and visual action spectra. The maximal spectral response and long wavelength limb of the melatonin suppression template is plotted along with the maximal spectral response and long wavelength limbs of the human rods and cones that support vision (Stockman and Sharpe, 1999). The shaded area around the 464 nm template represents ±SD from the data presented above.

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The Journal of Neuroscience: 21 (16)
Journal of Neuroscience
Vol. 21, Issue 16
15 Aug 2001
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Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor
George C. Brainard, John P. Hanifin, Jeffrey M. Greeson, Brenda Byrne, Gena Glickman, Edward Gerner, Mark D. Rollag
Journal of Neuroscience 15 August 2001, 21 (16) 6405-6412; DOI: 10.1523/JNEUROSCI.21-16-06405.2001

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Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor
George C. Brainard, John P. Hanifin, Jeffrey M. Greeson, Brenda Byrne, Gena Glickman, Edward Gerner, Mark D. Rollag
Journal of Neuroscience 15 August 2001, 21 (16) 6405-6412; DOI: 10.1523/JNEUROSCI.21-16-06405.2001
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Keywords

  • melatonin
  • action spectrum
  • circadian
  • wavelength
  • light
  • pineal gland
  • neuroendocrine
  • photoreception
  • photopigment
  • human

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  • Developing the family of curves for the Human Melatonin Action Spectrum
    Alan C. Haungs
    Published on: 10 December 2015
  • Published on: (10 December 2015)
    Page navigation anchor for Developing the family of curves for the Human Melatonin Action Spectrum
    Developing the family of curves for the Human Melatonin Action Spectrum
    • Alan C. Haungs, Inventor Owner

    The original experiment for plotting the melatonin action spectrum involved instantaneous purified wavelengths.

    This is not typical light that enters the eye.

    I suggest superimposing white light on top of each purified wavelength and develop the family of curves as purified colors will likely have the left most peak action wavelength, but purified color + increasing amounts of white will move the peak ac...

    Show More

    The original experiment for plotting the melatonin action spectrum involved instantaneous purified wavelengths.

    This is not typical light that enters the eye.

    I suggest superimposing white light on top of each purified wavelength and develop the family of curves as purified colors will likely have the left most peak action wavelength, but purified color + increasing amounts of white will move the peak action wavelength to the right, due to how the L and M cones constructively enhance the ipRGC signal during day- light adaptation.

    I would also hope to see such a family of curves for values of intensity that fit under the night-adaptation category.

    Such a family of curves would have utility from a circadian driver point of view when incorporating white light into the human living space, to defeat morning/mid-day SAD issues or evening circadian disruption issues.

    Conflict of Interest:

    I am an electrical engineer working on solutions to circadian disruption

    Show Less
    Competing Interests: None declared.

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