Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Aberrant light directly impairs mood and learning through melanopsin-expressing neurons


The daily solar cycle allows organisms to synchronize their circadian rhythms and sleep–wake cycles to the correct temporal niche1. Changes in day-length, shift-work, and transmeridian travel lead to mood alterations and cognitive function deficits2. Sleep deprivation and circadian disruption underlie mood and cognitive disorders associated with irregular light schedules2. Whether irregular light schedules directly affect mood and cognitive functions in the context of normal sleep and circadian rhythms remains unclear. Here we show, using an aberrant light cycle that neither changes the amount and architecture of sleep nor causes changes in the circadian timing system, that light directly regulates mood-related behaviours and cognitive functions in mice. Animals exposed to the aberrant light cycle maintain daily corticosterone rhythms, but the overall levels of corticosterone are increased. Despite normal circadian and sleep structures, these animals show increased depression-like behaviours and impaired hippocampal long-term potentiation and learning. Administration of the antidepressant drugs fluoxetine or desipramine restores learning in mice exposed to the aberrant light cycle, suggesting that the mood deficit precedes the learning impairments. To determine the retinal circuits underlying this impairment of mood and learning, we examined the behavioural consequences of this light cycle in animals that lack intrinsically photosensitive retinal ganglion cells. In these animals, the aberrant light cycle does not impair mood and learning, despite the presence of the conventional retinal ganglion cells and the ability of these animals to detect light for image formation. These findings demonstrate the ability of light to influence cognitive and mood functions directly through intrinsically photosensitive retinal ganglion cells.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Figure 1: Aberrant light increases depression-like behaviour and corticosterone levels.
Figure 2: Aberrant light impairs hippocampal learning, LTP, and recognition memory.
Figure 3: Chronic antidepressant administration rescues learning.
Figure 4: ipRGCs mediate impairment of mood and learning by aberrant light.

Similar content being viewed by others


  1. Reppert, S. M. & Weaver, D. R. Coordination of circadian timing in mammals. Nature 418, 935–941 (2002)

    ADS  CAS  Google Scholar 

  2. Foster, R. G. & Wulff, K. The rhythm of rest and excess. Nature Rev. Neurosci. 6, 407–414 (2005)

    Article  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  CAS  Google Scholar 

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

    Article  ADS  Google Scholar 

  6. Hattar, S. et al. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J. Comp. Neurol. 497, 326–349 (2006)

    Article  Google Scholar 

  7. Altimus, C. M. 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)

    Article  ADS  CAS  Google Scholar 

  8. Lam, R. W. & Levitan, R. D. Pathophysiology of seasonal affective disorder: a review. J. Psychiatry Neurosci. 25, 469–480 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Nestler, E. J. et al. Neurobiology of depression. Neuron 34, 13–25 (2002)

    Article  CAS  Google Scholar 

  10. McEwen, B. S. Protective and damaging effects of stress mediators. N. Engl. J. Med. 338, 171–179 (1998)

    Article  CAS  Google Scholar 

  11. Cryan, J. F. & Holmes, A. The ascent of mouse: advances in modelling human depression and anxiety. Nature Rev. Drug Discov. 4, 775–790 (2005)

    Article  CAS  Google Scholar 

  12. Baldi, E., Lorenzini, C. A. & Corrado, B. Task solving by procedural strategies in the Morris water maze. Physiol. Behav. 78, 785–793 (2003)

    Article  CAS  Google Scholar 

  13. Vorhees, C. V. & Williams, M. T. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nature Protocols 1, 848–858 (2006)

    Article  Google Scholar 

  14. Bliss, T. V. & Collingridge, G. L. A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361, 31–39 (1993)

    Article  ADS  CAS  Google Scholar 

  15. McDermott, C. M. et al. Sleep deprivation causes behavioral, synaptic, and membrane excitability alterations in hippocampal neurons. J. Neurosci. 23, 9687–9695 (2003)

    Article  CAS  Google Scholar 

  16. Honey, R. C., Watt, A. & Good, M. Hippocampal lesions disrupt an associative mismatch process. J. Neurosci. 18, 2226–2230 (1998)

    Article  CAS  Google Scholar 

  17. Dulawa, S. C., Holick, K. A., Gundersen, B. & Hen, R. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 29, 1321–1330 (2004)

    Article  CAS  Google Scholar 

  18. Sprouse, J., Braselton, J. & Reynolds, L. Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. Biol. Psychiatry 60, 896–899 (2006)

    Article  CAS  Google Scholar 

  19. Lockley, S. W. 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)

    PubMed  Google Scholar 

  20. Vandewalle, G. et al. Spectral quality of light modulates emotional brain responses in humans. Proc. Natl Acad. Sci. USA 107, 19549–19554 (2010)

    Article  ADS  CAS  Google Scholar 

  21. İyilikci, O., Aydin, E. & Canbeyli, R. Blue but not red light stimulation in the dark has antidepressant effect in behavioral despair. Behav. Brain Res. 203, 65–68 (2009)

    Article  Google Scholar 

  22. Warthen, D. M., Wiltgen, B. J. & Provencio, I. Light enhances learned fear. Proc. Natl Acad. Sci. USA 108, 13788–13793 (2011)

    Article  ADS  CAS  Google Scholar 

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

    Article  Google Scholar 

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

    Article  ADS  Google Scholar 

  25. Roybal, K. et al. Mania-like behavior induced by disruption of CLOCK. Proc. Natl Acad. Sci. USA 104, 6406–6411 (2007)

    Article  ADS  CAS  Google Scholar 

  26. Tataroğlu, O., Aksoy, A., Yilmaz, A. & Canbeyli, R. Effect of lesioning the suprachiasmatic nuclei on behavioral despair in rats. Brain Res. 1001, 118–124 (2004)

    Article  Google Scholar 

  27. Lee, H. K., Min, S. S., Gallagher, M. & Kirkwood, A. NMDA receptor-independent long-term depression correlates with successful aging in rats. Nature Neurosci. 8, 1657–1659 (2005)

    Article  CAS  Google Scholar 

Download references


We would like to thank T. Gould, G. Ball and A. Sawa for their expert advice on the behavioural tests. We would like to thank R. Kuruvilla for her critical reading and advice on this manuscript. We would also like to thank the mouse tri-laboratory for suggestions and advice. This work was supported by the David and Lucile Packard Foundation grant to S.H.

Author information

Authors and Affiliations



T.A.L., C.M.A., H.Z., E.T.W. and S.H. designed experiments. T.A.L. and C.M.A. carried out experiments. H.W., H.-K.L., S.Y. and A.K. designed and performed electrophysiological experiments. T.A.L., C.M.A., H.Z., E.T.W. and S.H. wrote the paper.

Corresponding author

Correspondence to Samer Hattar.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Text, Supplementary Figures 1-13 and Supplementary References. (PDF 9371 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

LeGates, T., Altimus, C., Wang, H. et al. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 491, 594–598 (2012).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing