The acute light-induction of sleep is mediated by OPN4-based photoreception

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Abstract

Sleep is regulated by both homeostatic and circadian mechanisms. The latter, termed 'process c', helps synchronize sleep-wake patterns to the appropriate time of the day. However, in the absence of a circadian clock, overall sleep-wake rhythmicity is preserved and remains synchronized to the external light-dark cycle, indicating that there is an additional, clock-independent photic input to sleep. We found that the direct photic regulation of sleep in mice is predominantly mediated by melanopsin (OPN4)-based photoreception of photosensitive retinal ganglion cells (pRGCs). Moreover, OPN4-dependent sleep regulation was correlated with the activation of sleep-promoting neurons in the ventrolateral preoptic area and the superior colliculus. Collectively, our findings describe a previously unknown pathway in sleep regulation and identify the pRGC/OPN4 signaling system as a potentially new pharmacological target for the selective manipulation of sleep and arousal states.

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Figure 1: Rods/cones alone or pRGCs alone are sufficient to entrain the circadian clock and sleep-wake rhythms.
Figure 2: OPN4, but not rods and cones, regulates the acute light-induced sleep response in mice.
Figure 3: Masking responses to light are preserved in Opn4−/− mice.
Figure 4: Light-induced Fos transcription is abolished in the VLPO and superior colliculus of Opn4−/−.

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Acknowledgements

We thank S. Hattar (Johns Hopkins University) for generously donating the Opn4−/− mice, N. Naujokat for technical assistance and S.N. Peirson for helpful comments on this manuscript. This work was supported by a Wellcome Trust Program grant and a European Commission grant (EuClock) to R.G.F. H.O. was supported by an Otto Hahn fellowship of the Max Planck Society and an Emmy Noether fellowship of the Deutsche Forschungsgemeinschaft.

Author information

R.G.F. conceived the project. D.L. conducted the sleep and immunohistochemical analyses. H.O. undertook the wheel running, the in situ and the qPCR analyses. S.T. set up and contributed to the sleep experiments. R.G.F., H.O. and D.L. wrote the paper, with advice from S.T.

Correspondence to Russell G Foster.

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Lupi, D., Oster, H., Thompson, S. et al. The acute light-induction of sleep is mediated by OPN4-based photoreception. Nat Neurosci 11, 1068–1073 (2008) doi:10.1038/nn.2179

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