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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.

Original publication

DOI

10.1038/nn.2179

Type

Journal article

Journal

Nat Neurosci

Publication Date

17/08/2008

Addresses

[1] Circadian and Visual Neuroscience Group, Nuffield Laboratory of Ophthalmology, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Headington, Oxford OX3 9DU, UK. [2] These authors contributed equally to this work.