TY - JOUR
T1 - The spectral sensitivity of human circadian phase resetting and melatonin suppression to light changes dynamically with light duration
AU - St Hilaire, Melissa A.
AU - Ámundadóttir, María L.
AU - Rahman, Shadab A.
AU - Rajaratnam, Shantha M.W.
AU - Rüger, Melanie
AU - Brainard, George C.
AU - Czeisler, Charles A.
AU - Andersen, Marilyne
AU - Gooley, Joshua J.
AU - Lockley, Steven W.
N1 - Funding Information:
We thank research volunteers, recruiters, and research staff at the Division of Sleep and Circadian Disorders, Brigham and Women's Hospital (BWH); the technical, dietary, nursing, and medical staff at the Center for Clinical Investigation at BWH in partnership with the Harvard Catalyst, Jonathan Williams MD, for medical supervision; Ralph Todesco (BWH) for administrative support; Joseph M. Ronda, M.A.S. (BWH) for technical support; John Hanifin, Ph.D. and William Coyle (Thomas Jefferson University) and Ron Kovak and Jon Cooke (Photon Technology International, Inc.) for technical support for the generation of monochromatic light; Vincent Ricchiuti, Ph.D. and the Core Laboratory staff (BWH) for melatonin assays. This study was supported by National Institutes of Health grants T32-HL007901 (MSH, J.J.G.), R01-MH045130 (C.A.C.), R01-NS036590 (G.C.B.), and R01-AT002129 (S.W.L.); Ecole Polytechnique Fédérale de Lausanne (M.L.A., M.A.); Swiss National Science Foundation grant CR13I2_153018 (M.L.A.); and National Space Biomedical Research Institute grants NBPF02001 (M.R., S.W.L.), HPF00001 (G.C.B., S.W.L.), HPF01605 (G.C.B.), HPF01701 (G.C.B.), HFP01601 (C.A.C.), and HPF01301 (S.W.L.) through NASA NCC 9–58. The project described was conducted through the Harvard Clinical and Translational Science Center from the National Center for Research Resources, which was supported by National Institutes of Health grants M01-RR01066 and 1UL1-RR025758. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Center for Advancing Translational Science or the National Institutes of Health.
Funding Information:
ACKNOWLEDGMENTS. We thank research volunteers, recruiters, and research staff at the Division of Sleep and Circadian Disorders, Brigham and Women's Hospital (BWH); the technical, dietary, nursing, and medical staff at the Center for Clinical Investigation at BWH in partnership with the Harvard Catalyst, Jonathan Williams MD, for medical supervision; Ralph Todesco (BWH) for administrative support; Joseph M. Ronda, M.A.S. (BWH) for technical support; John Hanifin, Ph.D. and William Coyle (Thomas Jefferson University) and Ron Kovak and Jon Cooke (Photon Technology International, Inc.) for technical support for the generation of monochromatic light; Vincent Ricchiuti, Ph.D. and the Core Laboratory staff (BWH) for melatonin assays. This study was supported by National Institutes of Health grants T32-HL007901 (MSH, J.J.G.), R01-MH045130 (C.A.C.), R01-NS036590 (G.C.B.), and R01-AT002129 (S.W.L.); Ecole Polytechnique Fédérale de Lausanne (M.L.A., M.A.); Swiss National Science Foundation grant CR13I2_153018 (M.L.A.); and National Space Biomedical Research Institute grants NBPF02001 (M.R., S.W.L.), HPF00001 (G.C.B., S.W.L.), HPF01605 (G.C.B.), HPF01701 (G.C.B.), HFP01601 (C.A.C.), and HPF01301 (S.W.L.) through NASA NCC 9–58. The project described was conducted through the Harvard Clinical and Translational Science Center from the National Center for Research Resources, which was supported by National Institutes of Health grants M01-RR01066 and 1UL1-RR025758. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources, the National Center for Advancing Translational Science or the National Institutes of Health.
Publisher Copyright:
Copyright © 2022 the Author(s). Published by PNAS.
PY - 2022/12/20
Y1 - 2022/12/20
N2 - Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambdamax at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambdamax was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambdamax was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambdamax ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.
AB - Human circadian, neuroendocrine, and neurobehavioral responses to light are mediated primarily by melanopsin-containing intrinsically-photosensitive retinal ganglion cells (ipRGCs) but they also receive input from visual photoreceptors. Relative photoreceptor contributions are irradiance- and duration-dependent but results for long-duration light exposures are limited. We constructed irradiance-response curves and action spectra for melatonin suppression and circadian resetting responses in participants exposed to 6.5-h monochromatic 420, 460, 480, 507, 555, or 620 nm light exposures initiated near the onset of nocturnal melatonin secretion. Melatonin suppression and phase resetting action spectra were best fit by a single-opsin template with lambdamax at 481 and 483 nm, respectively. Linear combinations of melanopsin (ipRGC), short-wavelength (S) cone, and combined long- and medium-wavelength (L+M) cone functions were also fit and compared. For melatonin suppression, lambdamax was 441 nm in the first quarter of the 6.5-h exposure with a second peak at 550 nm, suggesting strong initial S and L+M cone contribution. This contribution decayed over time; lambdamax was 485 nm in the final quarter of light exposure, consistent with a predominant melanopsin contribution. Similarly, for circadian resetting, lambdamax ranged from 445 nm (all three functions) to 487 nm (L+M-cone and melanopsin functions only), suggesting significant S-cone contribution, consistent with recent model findings that the first few minutes of a light exposure drive the majority of the phase resetting response. These findings suggest a possible initial strong cone contribution in driving melatonin suppression and phase resetting, followed by a dominant melanopsin contribution over longer duration light exposures.
KW - circadian phase resetting
KW - circadian rhythms
KW - light
KW - melanopsin
KW - melatonin suppression
UR - http://www.scopus.com/inward/record.url?scp=85144365669&partnerID=8YFLogxK
U2 - 10.1073/pnas.2205301119
DO - 10.1073/pnas.2205301119
M3 - Article
C2 - 36508661
AN - SCOPUS:85144365669
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 51
M1 - e2205301119
ER -