title: The acute light-induction of sleep is mediated by OPN4-based photoreception.
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.
authors.affiliation: 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.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lupi
authors.forename: Henrik
authors.initials: H
authors.lastname: Oster
authors.forename: Stewart
authors.initials: S
authors.lastname: Thompson
authors.forename: Russell G
authors.initials: RG
authors.lastname: Foster
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D019004:Galanin / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics / Q000528:radiation effects; D008027:Light; D055537:Light Signal Transduction / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000235:genetics; D009434:Neural Pathways / Q000502:physiology; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology* / Q000528:radiation effects; D012165:Retinal Ganglion Cells / Q000502:physiology; D017299:Rod Opsins / Q000172:deficiency / Q000378:metabolism*; D012890:Sleep / Q000235:genetics / Q000502:physiology*; D000099210:Melanopsin
chemical_list: D005136:Eye Proteins; D019004:Galanin; D016761:Oncogene Proteins v-fos; D017299:Rod Opsins; D000099210:Melanopsin