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Neuroscience. 2011 Dec 29;199:213-24. doi: 10.1016/j.neuroscience.2011.09.057. Epub 2011 Oct 4.

Separation of function for classical and ganglion cell photoreceptors with respect to circadian rhythm entrainment and induction of photosomnolence.

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Department of Psychiatry, Stony Brook University Medical Center, Stony Brook, NY, USA.


Four studies were performed to further clarify the contribution of rod/cone and intrinsically photoreceptive retinal ganglion cells to measures of entrainment, dark preference, light-induced locomotor suppression and photosomnolence. Wild type (WT), retinally degenerate (rd/rd), and melanopsin-less (OPN4⁻/⁻) mouse strains were compared. In Experiment 1, mice were exposed to a graded photoperiod in which approximately 0.26 μW/cm² irradiance diminished to dark over a 6-h interval. This method enabled "phase angle titration," with individual animals assuming activity onsets according to their sensitivity to light. WT and OPN4⁻/⁻ animals entrained with identical phase angles (effective irradiance=0.078 μW/cm²), but rd/rd mice required a more intense irradiance (0.161 μW/cm²) and entrainment occurred about 2.5 h earlier. In Experiment 2, all three strains preferred the dark side of a divided light-dark chamber until the irradiance dropped to 0.5 μW/cm² at which point, rd/rd mice no longer showed a preference. Experiments 3 and 4 determined that WT and rd/rd mice showed equivalent light-induced locomotor suppression, but the response was greatly impaired in OPN4⁻/⁻ mice. Closer examination of open field locomotion using infrared video-based methods and Any-maze(tm) software revealed two opposing effects of light. Locomotor suppression was equivalent in WT and rd/rd mice. Responses by OPN4⁻/⁻ mice varied from being absent (n=17) to normal (similar to WT and rd/rd mice; n=8). Light onset was associated with a significant, but brief, locomotion increase in WT and OPN4⁻/⁻ mice, but not in rd/rd mice. Any-maze(tm) analysis supports the view that light-induced locomotor quiescence is followed by behavioral sleep (photosomnolence), a fact that was visually validated from the raw video files. The data show that (a) classical photoreceptors, most likely rods, allow mice to prefer and entrain to very dim light such as found in natural twilight; (b) the presence of melanopsin photopigment enables light-induced locomotor suppression and photosomnolence;

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