Review Article | Published:

Light as a central modulator of circadian rhythms, sleep and affect

Nature Reviews Neuroscience volume 15, pages 443454 (2014) | Download Citation

Abstract

Light has profoundly influenced the evolution of life on earth. As widely appreciated, light enables us to generate images of our environment. However, light — through intrinsically photosensitive retinal ganglion cells (ipRGCs) — also influences behaviours that are essential for our health and quality of life but are independent of image formation. These include the synchronization of the circadian clock to the solar day, tracking of seasonal changes and the regulation of sleep. Irregular light environments lead to problems in circadian rhythms and sleep, which eventually cause mood and learning deficits. Recently, it was found that irregular light can also directly affect mood and learning without producing major disruptions in circadian rhythms and sleep. In this Review, we discuss the indirect and direct influence of light on mood and learning, and provide a model for how light, the circadian clock and sleep interact to influence mood and cognitive functions.

Key points

  • Extreme light conditions, as experienced in shift-work schedules, shortened day length during winter months or transmeridian travel, can cause negative health effects, which include cognitive deficits and mood alterations.

  • Aberrant light schedules can cause circadian rhythm alterations and/or sleep disruptions, leading to mood disorders and depression-like states. This has led to a model in which the negative effects of irregular light on mood and cognitive functions are secondary to circadian and/or sleep disruptions.

  • However, light can also directly influence mood and learning without causing circadian arrhythmicity or sleep disruptions.

  • Intrinsically photosensitive retinal ganglion cells (ipRGCs) project to a wide range of brain regions, including areas that have been associated with mood and anxiety. These cells emerge as leading candidates for mediating the direct effects of irregular light on mood.

  • Rodent models have been used to define the mechanisms involved in the effects of light on circadian rhythms, sleep and mood. Several animal models and light schedules were used to recapitulate important aspects of irregular light schedules observed in humans, which cause mood and cognitive disorders.

  • A better understanding of the connections that ipRGCs form in the brain and their influence on circadian, sleep and mood controlling centres will be the first step to determine the comprehensive role of light on these complex, inter-related behaviours.

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References

  1. 1.

    Chemistry and biology of vision. J. Biol. Chem. 287, 1612–1619 (2012).

  2. 2.

    & Coordination of circadian timing in mammals. Nature 418, 935–941 (2002).

  3. 3.

    , & A clockwork web: circadian timing in brain and periphery, in health and disease. Nature Rev. Neurosci. 4, 649–661 (2003). This is a well-presented review about the interplay between central and peripheral clocks for the regulation of physiology in health and disease.

  4. 4.

    A two process model of sleep regulation. Hum. Neurobiol. 1, 195–204 (1982). A classical study on sleep regulation by both homeostatic and circadian mechanisms.

  5. 5.

    et al. Rods-cones and melanopsin detect light and dark to modulate sleep independent of image formation. Proc. Natl Acad. Sci. USA 105, 19998–20003 (2008).

  6. 6.

    et al. Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4−/− mice. PLoS Biol. 7, e1000125 (2009).

  7. 7.

    et al. Acute exposure to evening blue-enriched light impacts on human sleep. J. Sleep Res. 22, 573–580 (2013).

  8. 8.

    , & Dynamics of EEG slow-wave activity and core body temperature in human sleep after exposure to bright light. Sleep 15, 337–343 (1992).

  9. 9.

    , , & The acute light-induction of sleep is mediated by OPN4-based photoreception. Nature Neurosci. 11, 1068–1073 (2008). Together with references 5 and 6, this study shows that light can directly affect sleep and wakefulness in rodents and that the effects depend on ipRGCs. These studies also show that melanopsin signalling can affect homeostatic sleep.

  10. 10.

    , & The trouble with circadian clock dysfunction: multiple deleterious effects on the brain and body. Neurosci. Biobehav. Rev. 40, 80–101 (2014).

  11. 11.

    & Vertebrate circadian rhythms: retinal and extraretinal photoreception. Experientia 38, 1013–1021 (1982).

  12. 12.

    et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature 424, 76–81 (2003).

  13. 13.

    Parallel processing in the mammalian retina. Nature Rev. Neurosci. 5, 747–757 (2004).

  14. 14.

    , , & Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms. Nature 308, 186–188 (1984).

  15. 15.

    et al. Suppression of melatonin secretion in some blind patients by exposure to bright light. N. Engl. J. Med. 332, 6–11 (1995). A leading study in humans showing that photoreceptors other than the classical rods and cones could mediate light-dependent functions.

  16. 16.

    et al. Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. Science 284, 502–504 (1999).

  17. 17.

    et al. A novel human opsin in the inner retina. J. Neurosci. 20, 600–605 (2000).

  18. 18.

    , & Phototransduction by retinal ganglion cells that set the circadian clock. Science 295, 1070–1073 (2002).

  19. 19.

    , , , & Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295, 1065–1070 (2002). References 17–19 highlight the discovery that a subset of RGCs are photoreceptors (intrinsically photosensitive) and express the photopigment melanopsin.

  20. 20.

    et al. Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science 299, 245–247 (2003).

  21. 21.

    et al. Melanopsin (Opn4) requirement for normal light-induced circadian phase shifting. Science 298, 2213–2216 (2002).

  22. 22.

    , & Two types of melanopsin retinal ganglion cell differentially innervate the hypothalamic suprachiasmatic nucleus and the olivary pretectal nucleus. Eur. J. Neurosci. 27, 1763–1770 (2008).

  23. 23.

    , & Morphology and mosaics of melanopsin-expressing retinal ganglion cell types in mice. J. Comp. Neurol. 518, 2405–2422 (2010).

  24. 24.

    & Functional and morphological differences among intrinsically photosensitive retinal ganglion cells. J. Neurosci. 29, 476–482 (2009).

  25. 25.

    , & Intrinsic physiological properties of the five types of mouse ganglion-cell photoreceptors. J. Neurophysiol. 109, 1876–1889 (2013).

  26. 26.

    , , & Intrinsic light responses of retinal ganglion cells projecting to the circadian system. Eur. J. Neurosci. 17, 1727–1735 (2003).

  27. 27.

    et al. Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision. Neuron 67, 49–60 (2010).

  28. 28.

    & Structure and function of bistratified intrinsically photosensitive retinal ganglion cells in the mouse. J. Comp. Neurol. 519, 1492–1504 (2011).

  29. 29.

    et al. Physiologic diversity and development of intrinsically photosensitive retinal ganglion cells. Neuron 48, 987–999 (2005).

  30. 30.

    , & Intrinsically photosensitive retinal ganglion cells: many subtypes, diverse functions. Trends Neurosci. 34, 572–580 (2011).

  31. 31.

    et al. Afferents to the ventrolateral preoptic nucleus. J. Neurosci. 22, 977–990 (2002).

  32. 32.

    & Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state. Neuroscience 130, 165–183 (2005).

  33. 33.

    , , , & Afferents to the orexin neurons of the rat brain. J. Comp. Neurol. 494, 845–861 (2006).

  34. 34.

    , , , & Ventrolateral preoptic nucleus contains sleep-active, galaninergic neurons in multiple mammalian species. Neuroscience 115, 285–294 (2002).

  35. 35.

    Arousal systems. Front. Biosci. 8, S438–S451 (2003).

  36. 36.

    Hypothalamic regulation of sleep in rats. An experimental study. J. Neurophysiol. 9, 285–316 (1946).

  37. 37.

    , & The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci. 24, 726–731 (2001).

  38. 38.

    , , & Sleep–waking discharge patterns of ventrolateral preoptic/anterior hypothalamic neurons in rats. Brain Res. 803, 178–188 (1998).

  39. 39.

    & The brain reward circuitry in mood disorders. Nature Rev. Neurosci. 14, 609–625 (2013).

  40. 40.

    & Lateral habenula as a source of negative reward signals in dopamine neurons. Nature 447, 1111–1115 (2007).

  41. 41.

    Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Curr. Opin. Neurobiol. 11, 240–249 (2001).

  42. 42.

    & Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res. 916, 172–191 (2001).

  43. 43.

    & Output pathways of the mammalian suprachiasmatic nucleus: coding circadian time by transmitter selection and specific targeting. Cell Tissue Res. 309, 109–118 (2002).

  44. 44.

    & Circuit projection from suprachiasmatic nucleus to ventral tegmental area: a novel circadian output pathway. Eur. J. Neurosci. 29, 748–760 (2009).

  45. 45.

    Projections from vasopressin, oxytocin, and neurophysin neurons to neural targets in the rat and human. J. Histochem. Cytochem. 28, 475–478 (1980).

  46. 46.

    & Efferent projections of the suprachiasmatic nucleus: II. studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat. J. Comp. Neurol. 258, 230–252 (1987).

  47. 47.

    , & Efferent projections of the suprachiasmatic nucleus: I. studies using anterograde transport of Phaseolus vulgaris leucoagglutinin in the rat. J. Comp. Neurol. 258, 204–229 (1987).

  48. 48.

    , , , & Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J. Affect. Disord. 42, 209–212 (1997).

  49. 49.

    , , , & Control of sleep and wakefulness. Physiol. Rev. 92, 1087–1187 (2012).

  50. 50.

    , & REM architecture changes in bipolar and unipolar depression. Am. J. Psychiatry 136, 1424–1427 (1979).

  51. 51.

    , , , & 48-hour sleep-wake cycles in manic-depressive illness: naturalistic observations and sleep deprivation experiments. Arch. Gen. Psychiatry 39, 559–565 (1982).

  52. 52.

    et al. 24-h monitoring of plasma norepinephrine, MHPG, cortisol, growth hormone and prolactin in depression. J. Psychiatr. Res. 38, 503–511 (2004).

  53. 53.

    et al. The 24-hour profile of adrenocorticotropin and cortisol in major depressive illness. J. Clin. Endocrinol. Metab. 61, 429–438 (1985).

  54. 54.

    et al. Melatonin in mood disorders. World J. Biol. Psychiatry 7, 138–151 (2006).

  55. 55.

    et al. Seasonal affective disorder. A description of the syndrome and preliminary findings with light therapy. Arch. Gen. Psychiatry 41, 72–80 (1984).

  56. 56.

    & Melatonin and the circadian regulation of sleep initiation, consolidation, structure, and the sleep EEG. J. Biol. Rhythms 12, 627–635 (1997).

  57. 57.

    , & High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. J. Clin. Endocrinol. Metab. 88, 4502–4505 (2003).

  58. 58.

    , , & Human melatonin suppression by light is intensity dependent. J. Pineal Res. 6, 149–156 (1989).

  59. 59.

    et al. Short-wavelength sensitivity for the direct effects of light on alertness, vigilance, and the waking electroencephalogram in humans. Sleep 29, 161–168 (2006).

  60. 60.

    et al. High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light. J. Clin. Endocrinol. Metab. 90, 1311–1316 (2005).

  61. 61.

    , , , & Diurnal and seasonal variations of melatonin and serotonin in women with seasonal affective disorder. Arctic Med. Res. 53, 137–145 (1994).

  62. 62.

    , & Phase of melatonin rhythm in winter depression. Adv. Exp. Med. Biol. 460, 441–458 (1999).

  63. 63.

    et al. Evidence of a biological effect of light therapy on the retina of patients with seasonal affective disorder. Biol. Psychiatry 66, 253–258 (2009).

  64. 64.

    , & Treating phase typed chronobiologic sleep and mood disorders using appropriately timed bright artificial light. Psychopharmacol. Bull. 21, 368–372 (1985).

  65. 65.

    , , , & Winter depression and the phase-shift hypothesis for bright light's therapeutic effects: history, theory, and experimental evidence. J. Biol. Rhythms 3, 121–134 (1988).

  66. 66.

    et al. Morning versus evening light treatment for winter depression. Evidence that the therapeutic effects of light are mediated by circadian phase shifts. Arch. Gen. Psychiatry 47, 343–351 (1990).

  67. 67.

    & Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects. CNS Spectr. 10, 647–663 (2005).

  68. 68.

    , , & Circadian time of morning light administration and therapeutic response in winter depression. Arch. Gen. Psychiatry 58, 69–75 (2001).

  69. 69.

    et al. Morning or night-time melatonin is ineffective in seasonal affective disorder. J. Psychiatr. Res. 24, 129–137 (1990).

  70. 70.

    et al. Light therapy in seasonal affective disorder is independent of time of day or circadian phase. Arch. Gen. Psychiatry 50, 929–937 (1993).

  71. 71.

    Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders. J. Psychiatry Neurosci. 25, 446–458 (2000).

  72. 72.

    , , & The circadian basis of winter depression. Proc. Natl Acad. Sci. USA 103, 7414–7419 (2006).

  73. 73.

    & Manic-Depressive Illness (Oxford Univ. Press, 2012).

  74. 74.

    The relationship between mood and daily hours of sunlight in rapid cycling bipolar illness. Biol. Psychiatry 36, 422–424 (1994).

  75. 75.

    et al. Seasonal changes in clinical status in bipolar disorder: a prospective study in 1000 STEP-BD patients. Acta Psychiatr. Scand. 113, 510–517 (2006).

  76. 76.

    , & Influence of climate on the prevalence of mania. Br. J. Psychiatry 152, 820–823 (1988).

  77. 77.

    et al. Seasonal mood disorders. Patterns of seasonal recurrence in mania and depression. Arch. Gen. Psychiatry 50, 17–23 (1993).

  78. 78.

    Evolving applications of light therapy. Sleep Med. Rev. 11, 497–507 (2007).

  79. 79.

    & Rapid mood swings after unmonitored light exposure. Am. J. Psychiatry 155, 306 (1998).

  80. 80.

    Sleep loss: a preventable cause of mania and other excited states. J. Clin. Psychiatry 50 (Suppl.), 8–16 (1989).

  81. 81.

    et al. Circadian urinary 6-sulphatoxymelatonin, cortisol excretion and locomotor activity in airline pilots during transmeridian flights. J. Pineal Res. 31, 16–22 (2001).

  82. 82.

    , & Adrenal glucocorticoids have a key role in circadian resynchronization in a mouse model of jet lag. J. Clin. Invest. 120, 2600–2609 (2010).

  83. 83.

    et al. Associations between jet lag and cortisol diurnal rhythms after domestic travel. Health Psychol. 29, 117–123 (2010).

  84. 84.

    , , & Chronic jet lag produces cognitive deficits. J. Neurosci. 20, RC66 (2000).

  85. 85.

    et al. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 491, 594–598 (2012). This study shows that irregular light schedules lead to depression-like behaviours and learning deficits, which are mediated by ipRGCs.

  86. 86.

    Shift work and disturbed sleep/wakefulness. Occup. Med. (Lond.) 53, 89–94 (2003).

  87. 87.

    & The rhythm of rest and excess. Nature Rev. Neurosci. 6, 407–414 (2005).

  88. 88.

    & Sleep deprivation: impact on cognitive performance. Neuropsychiatr. Dis. Treat. 3, 553–567 (2007).

  89. 89.

    & Chronobiological therapy for mood disorders. Expert Rev. Neurother. 11, 961–970 (2011).

  90. 90.

    et al. Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4–5 hours per night. Sleep 20, 267–277 (1997).

  91. 91.

    & Chronotherapeutics (light and wake therapy) as a class of interventions for affective disorders. Handb. Clin. Neurol. 106, 697–713 (2012).

  92. 92.

    , & Effects of bright light treatment on depression- and anxiety-like behaviors of diurnal rodents maintained on a short daylight schedule. Behav. Brain Res. 201, 343–346 (2009).

  93. 93.

    , & Sand rats see the light: short photoperiod induces a depression-like response in a diurnal rodent. Behav. Brain Res. 173, 153–157 (2006). This work demonstrates that, in diurnal animals, short day length could induce depression and anxiety-like behaviours.

  94. 94.

    , , & Antidepressants reverse short-photoperiod-induced, forced swim test depression-like behavior in the diurnal fat sand rat: further support for the utilization of diurnal rodents for modeling affective disorders. Neuropsychobiology 63, 191–196 (2011).

  95. 95.

    et al. Photoperiod-mediated impairment of long-term potentiation and learning and memory in male white-footed mice. Neuroscience 175, 127–132 (2011).

  96. 96.

    , , & Short day lengths alter stress and depressive-like responses, and hippocampal morphology in Siberian hamsters. Horm. Behav. 60, 520–528 (2011).

  97. 97.

    & Measuring circadian and acute light responses in mice using wheel running activity. J. Vis. Exp. 48, e2463 (2011).

  98. 98.

    et al. An abrupt shift in the day/night cycle causes desynchrony in the mammalian circadian center. J. Neurosci. 23, 6141–6151 (2003).

  99. 99.

    , , , & Visualizing jet lag in the mouse suprachiasmatic nucleus and peripheral circadian timing system. Eur. J. Neurosci. 29, 171–180 (2009).

  100. 100.

    & Resetting the brain clock: time course and localization of mPER1 and mPER2 protein expression in suprachiasmatic nuclei during phase shifts. Eur. J. Neurosci. 19, 1105–1109 (2004).

  101. 101.

    et al. Circadian phase-shifted rats show normal acquisition but impaired long-term retention of place information in the water task. Neurobiol. Learn. Mem. 75, 51–62 (2001).

  102. 102.

    , , & Disrupting circadian rhythms in rats induces retrograde amnesia. Physiol. Behav. 34, 883–887 (1985).

  103. 103.

    , , , & Experimental 'jet lag' inhibits adult neurogenesis and produces long-term cognitive deficits in female hamsters. PLoS ONE 5, e15267 (2010).

  104. 104.

    & Phase shifting circadian rhythms produces retrograde amnesia. Science 211, 1056–1058 (1981).

  105. 105.

    et al. Rapid changes in the light/dark cycle disrupt memory of conditioned fear in mice. PLoS ONE 5, e12546 (2010).

  106. 106.

    et al. Hippocampal-dependent learning requires a functional circadian system. Proc. Natl Acad. Sci. USA 105, 15593–15598 (2008). This study shows, using an innovative light stimulation, that arrhythmicity in wild-type hamsters leads to changes in learning and memory.

  107. 107.

    , , , & Disruption of circadian clocks has ramifications for metabolism, brain, and behavior. Proc. Natl Acad. Sci. USA 108, 1657–1662 (2011). A comprehensive study on the effects of the circadian clock on several aspects of physiology besides that of psychiatric disorders.

  108. 108.

    et al. Influence of light at night on murine anxiety- and depressive-like responses. Behav. Brain Res. 205, 349–354 (2009).

  109. 109.

    et al. Mania-like behavior induced by disruption of CLOCK. Proc. Natl Acad. Sci. USA 104, 6406–6411 (2007). A direct connection links a clock gene and psychiatric diseases.

  110. 110.

    , , & Effect of lesioning the suprachiasmatic nuclei on behavioral despair in rats. Brain Res. 1001, 118–124 (2004).

  111. 111.

    , , , & Bright light effects on body temperature, alertness, EEG and behavior. Physiol. Behav. 50, 583–588 (1991).

  112. 112.

    , , & Dose-response relationship for light intensity and ocular and electroencephalographic correlates of human alertness. Behav. Brain Res. 115, 75–83 (2000).

  113. 113.

    , , & Daytime exposure to bright light, as compared to dim light, decreases sleepiness and improves psychomotor vigilance performance. Sleep 26, 695–700 (2003).

  114. 114.

    et al. Nonvisual responses to light exposure in the human brain during the circadian night. Curr. Biol. 14, 1842–1846 (2004).

  115. 115.

    , & Light as a modulator of cognitive brain function. Trends Cogn. Sci. 13, 429–438 (2009).

  116. 116.

    et al. Brain responses to violet, blue, and green monochromatic light exposures in humans: prominent role of blue light and the brainstem. PLoS ONE 2, e1247 (2007).

  117. 117.

    et al. Wavelength-dependent modulation of brain responses to a working memory task by daytime light exposure. Cereb. Cortex 17, 2788–2795 (2007).

  118. 118.

    et al. Spectral quality of light modulates emotional brain responses in humans. Proc. Natl Acad. Sci. USA 107, 19549–19554 (2010). A comprehensive study using different colours of light to implicate the melanopsin system in the modulation of the emotional responses in the human brain.

  119. 119.

    et al. Blue light stimulates cognitive brain activity in visually blind individuals. J. Cogn. Neurosci. 25, 2072–2085 (2013).

  120. 120.

    et al. Melanopsin and rod-cone photoreceptors play different roles in mediating pupillary light responses during exposure to continuous light in humans. J. Neurosci. 32, 14242–14253 (2012).

  121. 121.

    et al. Melanopsin bistability: a fly's eye technology in the human retina. PLoS ONE 4, e5991 (2009).

  122. 122.

    et al. Abnormal hypothalamic response to light in seasonal affective disorder. Biol. Psychiatry 70, 954–961 (2011).

  123. 123.

    , & Chronic dim light at night provokes reversible depression-like phenotype: possible role for TNF. Mol. Psychiatry 18, 930–936 (2013).

  124. 124.

    , , & Dim nighttime light impairs cognition and provokes depressive-like responses in a diurnal rodent. J. Biol. Rhythms 27, 319–327 (2012).

  125. 125.

    & Dim light at night increases depressive-like responses in male C3H/HeNHsd mice. Behav. Brain Res. 243, 74–78 (2013).

  126. 126.

    , , , & Dim light at night provokes depression-like behaviors and reduces CA1 dendritic spine density in female hamsters. Psychoneuroendocrinology 36, 1062–1069 (2011). A demonstration that light at night could lead to structural changes in the dendritic spines in the hippocampus, which are essential for learning and memory.

  127. 127.

    , & Blue but not red light stimulation in the dark has antidepressant effect in behavioral despair. Behav. Brain Res. 203, 65–68 (2009).

  128. 128.

    et al. A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder. J. Affect. Disord. 114, 279–285 (2009).

  129. 129.

    , & Light enhances learned fear. Proc. Natl Acad. Sci. USA 108, 13788–13793 (2011).

  130. 130.

    et al. Melanopsin cells are the principal conduits for rod-cone input to non-image-forming vision. Nature 453, 102–105 (2008).

  131. 131.

    et al. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J. Comp. Neurol. 497, 326–349 (2006). This study delineates the brain regions that are innervated by the ipRGCs.

  132. 132.

    , , & A broad role for melanopsin in nonvisual photoreception. J. Neurosci. 23, 7093–7106 (2003).

  133. 133.

    , & Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs. Nature 476, 92–95 (2011). The molecular separation of ipRGCs, based on the molecular marker BRN3B, into two major subpopulations.

  134. 134.

    et al. Daytime light exposure dynamically enhances brain responses. Curr. Biol. 16, 1616–1621 (2006).

  135. 135.

    et al. Effects of light on cognitive brain responses depend on circadian phase and sleep homeostasis. J. Biol. Rhythms 26, 249–259 (2011).

  136. 136.

    et al. Activation of suprachiasmatic nuclei and primary visual cortex depends upon time of day. Eur. J. Neurosci. 29, 399–410 (2009).

  137. 137.

    , , & Habenula: crossroad between the basal ganglia and the limbic system. J. Neurosci. 28, 11825–11829 (2008).

  138. 138.

    , , , & Lux versus wavelength in light treatment of seasonal affective disorder. Acta Psychiatr. Scand. 120, 203–212 (2009).

  139. 139.

    , , , & Light therapy for seasonal affective disorder with blue narrow-band light-emitting diodes (LEDs). Biol. Psychiatry 59, 502–507 (2006).

  140. 140.

    et al. Morning light treatment hastens the antidepressant effect of citalopram: a placebo-controlled trial. J. Clin. Psychiatry 64, 648–653 (2003).

  141. 141.

    , , , & Melanopsin: an opsin in melanophores, brain, and eye. Proc. Natl Acad. Sci. USA 95, 340–345 (1998).

  142. 142.

    et al. Evolution of melanopsin photoreceptors: discovery and characterization of a new melanopsin in nonmammalian vertebrates. PLoS Biol. 4, e254 (2006).

  143. 143.

    , & 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 (2002).

  144. 144.

    , , , & Addition of human melanopsin renders mammalian cells photoresponsive. Nature 433, 741–745 (2005).

  145. 145.

    et al. Induction of photosensitivity by heterologous expression of melanopsin. Nature 433, 745–749 (2005).

  146. 146.

    , , , & Melanopsin retinal ganglion cells receive bipolar and amacrine cell synapses. J. Comp. Neurol. 460, 380–393 (2003).

  147. 147.

    et al. Local retinal circuits of melanopsin-containing ganglion cells identified by transsynaptic viral tracing. Curr. Biol. 17, 981–988 (2007).

  148. 148.

    American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders 5th edn (American Psychiatric Association, 2013).

  149. 149.

    & The validity of animal models of predisposition to depression. Behav. Pharmacol. 13, 169–188 (2002).

  150. 150.

    et al. NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475, 91–95 (2011).

  151. 151.

    et al. Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol. Psychiatry 69, 754–761 (2011).

  152. 152.

    et al. Rapid regulation of depression-related behaviours by control of midbrain dopamine neurons. Nature 493, 532–536 (2013).

  153. 153.

    et al. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature 493, 537–541 (2013).

  154. 154.

    , , & Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Rev. Neurosci. 10, 434–445 (2009). References 152–154 reveal the power of animal models of depression to delineate the circuits and neurotransmitters that are important for understanding depression.

  155. 155.

    , & Stress and the brain: from adaptation to disease. Nature Rev. Neurosci. 6, 463–475 (2005).

  156. 156.

    Psychosocial stress and impaired sleep. Scand. J. Work Environ. Health 32, 493–501 (2006).

  157. 157.

    , & Effect of chronic mild stress on circadian rhythms in the locomotor activity in rats. Pharmacol. Biochem. Behav. 54, 229–234 (1996).

  158. 158.

    et al. Effects of controllable versus uncontrollable stress on circadian temperature rhythms. Physiol. Behav. 49, 625–630 (1991).

  159. 159.

    et al. Light at night increases body mass by shifting the time of food intake. Proc. Natl Acad. Sci. USA 107, 18664–18669 (2010).

  160. 160.

    , & Constant light desynchronizes mammalian clock neurons. Nature Neurosci. 8, 267–269 (2005).

  161. 161.

    et al. Effects of a constant light environment on hippocampal neurogenesis and memory in mice. Neurosci. Lett. 488, 41–44 (2011).

  162. 162.

    et al. Exposure to chronic constant light impairs spatial memory and influences long-term depression in rats. Neurosci. Res. 59, 224–230 (2007).

  163. 163.

    & Light deprivation damages monoamine neurons and produces a depressive behavioral phenotype in rats. Proc. Natl Acad. Sci. USA 105, 4898–4903 (2008).

  164. 164.

    , , , & Light at night alters daily patterns of cortisol and clock proteins in female Siberian hamsters. J. Neuroendocrinol. 25, 590–596 (2013).

  165. 165.

    et al. Nocturnal light exposure impairs affective responses in a wavelength-dependent manner. J. Neurosci. 33, 13081–13087 (2013).

  166. 166.

    , , & It is darkness and not light: depression-like behaviors of diurnal unstriped Nile grass rats maintained under a short photoperiod schedule. J. Neurosci. Methods 186, 165–170 (2010).

  167. 167.

    , , & Disruption of circadian rhythms due to chronic constant light leads to depressive and anxiety-like behaviors in the rat. Behav. Brain Res. 252, 1–9 (2013).

  168. 168.

    , & Continuous exposure to dim illumination uncouples temporal patterns of sleep, body temperature, locomotion and drinking behavior in the rat. Neurosci. Lett. 279, 185–189 (2000).

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Acknowledgements

The authors acknowledge H. Zhao, L. Ospri and M. Kvarta for the careful reading of and suggestions for this Review.

Author information

Author notes

    • Tara A. LeGates

    Present address: Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.

Affiliations

  1. Johns Hopkins University, Department of Biology, Baltimore, Maryland 21218, USA.

    • Tara A. LeGates
    • , Diego C. Fernandez
    •  & Samer Hattar
  2. Johns Hopkins University, Department of Neuroscience, Baltimore, Maryland 21218, USA.

    • Samer Hattar

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Samer Hattar.

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    Supplementary information S1 (figure)

    Modelling aberrant light environments in the lab using rodents.

Glossary

Non-image-forming visual functions

(NIF visual functions). Light mediated-behaviours that are not involved in detecting contrasts, colour or motion of the visual scene. These include circadian photoentrainment and sleep regulation.

Circadian photoentrainment

The synchronization of internal circadian rhythms with the solar cycle. This renders circadian rhythms physiologically relevant.

Sleep drive

The pressure to sleep. Sleep drive is driven by homeostatic and circadian mechanisms that interact to determine its strength. The higher the sleep drive, the easier it is to fall asleep.

Shift work

A work schedule that varies irrespective of the solar day–night cycles. This type of work causes sleep and circadian problems and induces major health issues.

Seasonal affective disorder

(SAD). A seasonal form of depression that occurs as a manifestation of the shorter day length of the winter months.

Circadian rhythms

Internally generated near 24-hour rhythms in biological processes that are expressed in almost all tissues throughout the body.

Suprachiasmatic nucleus

(SCN). A brain region located in the hypothalamus that houses the central circadian pacemaker. The SCN synchronizes peripheral rhythms with the solar cycle.

Glucocorticoids

Hormones produced by the adrenal cortex that are involved in carbohydrate and protein metabolism and also affect brain function. Cortisol (human) and corticosterone (rodent) are prime examples.

Jet lag

A syndrome that occurs upon crossing different time zones through transmeridian travel.

Long-term potentiation

A lasting increase in synaptic transmission in response to a strong correlated input.

Peripheral oscillators

Tissues, apart from the suprachiasmatic nucleus, that are capable of circadian rhythm generation.

Forced swim test

A test in which mice are placed in a water tank to measure depression-like states. Most depressed mice eventually develop an immobile posture, which is thought to indicate behavioural despair.

Polymorphisms

Natural variations in a gene or a particular DNA region. These genotypic differences give rise to more than one morph, evidenced as differences in the phenotype.

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DOI

https://doi.org/10.1038/nrn3743

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