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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

09/2008

Volume

11

Pages

1068 - 1073

Keywords

Analysis of Variance, Animals, Circadian Rhythm, Electroencephalography, Electromyography, Eye Proteins, Galanin, Gene Expression Regulation, Light, Light Signal Transduction, Male, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Mutant Strains, Motor Activity, Neural Pathways, Oncogene Proteins v-fos, Photoreceptor Cells, Vertebrate, Retinal Ganglion Cells, Rod Opsins, Sleep