Non-circadian direct effects of light on sleep and alertness: lessons from transgenic mouse models

Sleep Med Rev. 2013 Dec;17(6):445-52. doi: 10.1016/j.smrv.2012.12.004. Epub 2013 Apr 17.


Light exerts a strong non-visual influence on human physiology and behavior. Additionally light is known to affect sleep indirectly through the phase shifting of circadian rhythms, and directly, promoting alertness in humans and sleep in nocturnal species. Little attention has been paid to the direct non-image-forming influence of light until recently with the discovery and emerging knowledge on melanopsin, a photopigment which is maximally sensitive to the blue spectrum of light and expressed in a subset of intrinsically photosensitive retinal ganglion cells. Indeed, the development of transgenic mouse models targeting different phototransduction pathways has allowed researchers to decipher the mechanisms by which mammals adapt sleep to their light environment. This review summarizes the novel concepts and discrepancies from recent publications relating to the non-circadian effects of light on sleep and waking. Specifically, we discuss whether darkness, in addition to light, affects their quality. Furthermore, we seek to understand whether longer sustained periods of light exposure can influence sleep, if the direct photic regulation depends on time of day, and whether this affects the homeostatic sleep process. Moreover, the neural pathways by which light exerts a direct influence on sleep will be discussed including the respective role of rods/cones and melanopsin. Finally, we suggest that light weighs on the components of the flip-flop switch model to induce respectively sleep or waking, in nocturnal and diurnal animals. Taking these data into account we therefore propose a novel model of sleep regulation based on three processes; the direct photic regulation interacting with the circadian and homeostatic drives to determine the timing and quality of sleep and waking. An outlook of promising clinical and non-clinical applications of these findings will be considered as well as directions for future animal and human research.

Keywords: Alertness; Direct non-circadian non-image-forming effects; Flip-flop switch; Light; Melanopsin; Rods/cones; SCN; Sleep regulation; Transgenic mice models; VLPO.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Circadian Rhythm / physiology
  • Circadian Rhythm / radiation effects
  • Light*
  • Mice
  • Mice, Transgenic / physiology*
  • Models, Biological
  • Rod Opsins / physiology
  • Rod Opsins / radiation effects
  • Sleep / physiology
  • Sleep / radiation effects*
  • Vision, Ocular / physiology
  • Vision, Ocular / radiation effects
  • Wakefulness / physiology
  • Wakefulness / radiation effects*


  • Rod Opsins
  • melanopsin