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

Nat Neurosci. 2008 Sep;11(9):1068-73. doi: 10.1038/nn.2179.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Eye Proteins
  • Oncogene Proteins v-fos
  • Rod Opsins
  • melanopsin
  • Galanin