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

Nature volume 491, pages 594–598 (2012)Cite this article

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Abstract

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.

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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.

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Acknowledgements

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.

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Author notes

  1. Tara A. LeGates and Cara M. Altimus: These authors contributed equally to the work.

Authors and Affiliations

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

    Tara A. LeGates, Cara M. Altimus, Haiqing Zhao & Samer Hattar

  2. Department of Neuroscience, Johns Hopkins University, Baltimore, 21218, Maryland, USA

    Hui Wang, Hey-Kyoung Lee, Sunggu Yang, Alfredo Kirkwood & Samer Hattar

  3. Department of Biology, Rider University, Lawrenceville, 08648, New Jersey, USA

    E. Todd Weber

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  1. Tara A. LeGates
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Contributions

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.

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Correspondence to Samer Hattar.

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The authors declare no competing financial interests.

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LeGates, T., Altimus, C., Wang, H. et al. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 491, 594–598 (2012). https://doi.org/10.1038/nature11673

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