Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light.
In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.
Gooley
Joshua J
JJ
Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Rajaratnam
Shantha M W
SM
Brainard
George C
GC
Kronauer
Richard E
RE
Czeisler
Charles A
CA
Lockley
Steven W
SW
D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008027:Light; D008550:Melatonin / Q000378:metabolism; D017440:Photoperiod; D010789:Phototherapy; D012160:Retina / Q000502:physiology / Q000528:radiation effects; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology / Q000528:radiation effects; D012165:Retinal Ganglion Cells / Q000502:physiology / Q000528:radiation effects; D017299:Rod Opsins / Q000502:physiology; D055815:Young Adult; D000099210:Melanopsin
D008550:Melatonin; D017299:Rod Opsins; D000099210:Melanopsin
J Comp Physiol A. 1996 Jun;178(6):797-802
8667293
Biol Psychiatry. 2006 Mar 15;59(6):502-7
16165105
Nat Neurosci. 2001 Jun;4(6):621-6
11369943
Science. 2002 Feb 8;295(5557):1070-3
11834835
Sleep. 2005 May;28(5):616-23
16171276
Science. 1999 Apr 16;284(5413):505-7
10205062
Nat Neurosci. 2001 Dec;4(12):1165
11713469
Brain Res. 1995 Oct 2;694(1-2):183-90
8974643
Chronobiol Int. 2009 May;26(4):709-25
19444751
JAMA. 2008 Jun 11;299(22):2642-55
18544724
Vision Res. 1995 Nov;35(22):3083-91
8533344
Nature. 2003 Jul 3;424(6944):76-81
12808468
J Physiol. 2000 Aug 1;526 Pt 3:695-702
10922269
Science. 1999 Apr 16;284(5413):502-4
10205061
Scand J Work Environ Health. 2008 Aug;34(4):297-306
18815716
Nature. 2005 Feb 17;433(7027):741-5
15674244
Nature. 2008 May 1;453(7191):102-5
18432195
J Clin Endocrinol Metab. 2005 Mar;90(3):1311-6
15585546
J Physiol. 2007 Jul 1;582(Pt 1):279-96
17510182
J Pineal Res. 1993 Sep;15(2):88-103
8283389
Curr Biol. 2005 Jun 7;15(11):1065-9
15936279
J Comp Neurol. 2003 Jun 2;460(3):380-93
12692856
J Clin Endocrinol Metab. 2004 Jul;89(7):3610-4
15240654
J Biol Rhythms. 2002 Feb;17(1):4-13
11837947
Neuron. 2007 Mar 1;53(5):677-87
17329208
J Physiol. 2003 Jun 15;549(Pt 3):945-52
12717008
Neurosci Lett. 2008 Jun 20;438(2):242-5
18479818
Science. 2003 Jan 10;299(5604):245-7
12522249
J Affect Disord. 1990 Dec;20(4):209-16
2149726
Chronobiol Int. 2003 Nov;20(6):989-99
14680139
N Engl J Med. 1995 Jan 5;332(1):6-11
7990870
Science. 2002 Dec 13;298(5601):2211-3
12481140
J Neurosci. 2000 Jan 15;20(2):600-5
10632589
J Neurosci. 2001 Aug 15;21(16):6405-12
11487664
J Physiol. 2000 Feb 15;523 Pt 1:211-22
10673556
Acta Psychiatr Scand. 2009 Sep;120(3):203-12
19207131
Chronobiol Int. 2007;24(6):1125-37
18075803
J Clin Endocrinol Metab. 1996 Aug;81(8):2980-5
8768862
Science. 2005 Jan 28;307(5709):600-4
15681390
J Physiol. 2001 Aug 15;535(Pt 1):261-7
11507175
Science. 2002 Dec 13;298(5601):2213-6
12481141
Nature. 2005 Feb 17;433(7027):749-54
15716953
Vision Res. 2007 Mar;47(7):946-54
17320141
Curr Biol. 2007 Dec 18;17(24):2122-8
18082405
Neuron. 2005 Dec 22;48(6):1001-10
16364903
J Clin Endocrinol Metab. 2005 May;90(5):2755-61
15713707
Sleep. 1990 Aug;13(4):354-61
2267478
Sleep Med. 2009 Mar;10(3):287-94
18805055
Nature. 1984 Mar 8-14;308(5955):186-8
6700721
J Physiol. 1966 Aug;185(3):536-55
5918058
Neurosci Lett. 1997 Sep 5;232(3):135-8
9310298
J Biol Rhythms. 2002 Dec;17(6):548-55
12465888
Sleep. 2006 Feb;29(2):161-8
16494083
Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):14181-6
18779590
Science. 2003 Jul 25;301(5632):525-7
12829787
Neuro Endocrinol Lett. 2005 Oct;26(5):493-8
16264413
Proc Natl Acad Sci U S A. 2008 Jul 1;105(26):8861-5
18579788
J Clin Endocrinol Metab. 2003 Sep;88(9):4502-5
12970330
J Biol Rhythms. 2007 Oct;22(5):411-24
17876062