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.
| Original language | English |
|---|---|
| Journal | Nature Neuroscience |
| Volume | 11 |
| Issue number | 9 |
| Pages (from-to) | 1068-1073 |
| Number of pages | 6 |
| ISSN | 1097-6256 |
| DOIs | |
| Publication status | Published - 01.09.2008 |
Funding
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.
Research Areas and Centers
- Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)
