Cognitive, Behavioral, and Systems NeuroscienceResearch PaperSeparation of function for classical and ganglion cell photoreceptors with respect to circadian rhythm entrainment and induction of photosomnolence
Highlights
▶Entrainment and aversion to dim light utilize rod/cone, but not ipRGC photoreception. ▶Light suppression of activity is greatly disrupted in the absence of melanopsin photopigment. ▶Light acutely enhances activity by WT and OPN4−/− mice (but not rd/rd mice). ▶Light-induced “immobility” is actually light-induced sleep (“photosomnolence”). ▶Photosomnolence is normal in 1/3 of OPN4−/− mice but is absent in the remaining 2/3 of those mice.
Section snippets
Animals
Mice were C57BL/6J wild type (WT), the retinally degenerate strain, rd/rd (B6.C3-Pde6brd1 Hps4le/J) and the melanopsin null strain, OPN4−/−, in which the ipRGCs are non-functional consequent to the absence of melanopsin photopigment (Panda et al., 2002, Ruby et al., 2002). OPN4−/− breeding stock was provided courtesy of Dr. Ignacio Provencio. This congenic strain was derived from 10 successive backcrosses of the mix strain melanopsin null mice (Panda et al., 2002) onto the C57BL/6J line (
Histology
The outer nuclear layer is robustly revealed by DAPI nuclear staining in WT and OPN−/− retinas (Fig. 1). It is absent in rd/rd retina because of degeneration of rod and cone photoreceptors. BCO-IR reveals normal staining of cones in WT and OPN4−/− mice (Roberts et al., 2005), consistent with an intact classical photoreceptor layer. No BCO-IR is evident in the rd/rd retina. Although DAPI indicates the presence of the ganglion cell layer in all three strains, the melanopsin-IR is absent in
Discussion
The present studies employed strains of mice lacking the normal contingent of retinal photoreceptors to demonstrate separation of function between classical photoreceptors and ipRGCs with respect to several visually-mediated, non-image forming behaviors. In the first experiment, the adopted phase angle of circadian rhythm entrainment indicated greater sensitivity to light by mice bearing only classical photoreceptors (OPN4−/− mice) than seen in mice relying solely on melanopsin-based
Acknowledgments
Supported by NIH grant NS061804 and ARRA award NS061804-S2 to L.P.M. We thank Steven Mirabella and Max Grachev for excellent technical assistance.
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