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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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.
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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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