Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities

Abstract

In mammals, synchronization of the circadian pacemaker in the hypothalamus is achieved through direct input from the eyes conveyed by intrinsically photosensitive retinal ganglion cells (ipRGCs). Circadian photoentrainment can be maintained by rod and cone photoreceptors, but their functional contributions and their retinal circuits that impinge on ipRGCs are not well understood. Using mice that lack functional rods or in which rods are the only functional photoreceptors, we found that rods were solely responsible for photoentrainment at scotopic light intensities. Rods were also capable of driving circadian photoentrainment at photopic intensities at which they were incapable of supporting a visually guided behavior. Using mice in which cone photoreceptors were ablated, we found that rods signal through cones at high light intensities, but not at low light intensities. Thus, rods use two distinct retinal circuits to drive ipRGC function to support circadian photoentrainment across a wide range of light intensities.

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Figure 1: Rods drive circadian photoentrainment across a wide range of light intensities.
Figure 2: The rod-cone pathway is important for mesopic light signaling.
Figure 3: Rods contribution to phase shifts and period lengthening in constant light is dependent on cone state.

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Acknowledgements

We would like to thank J. Nathans for the h.red DTA mice. We also want to thank R. Kuruvilla, H. Zhao and M. Halpern for their careful reading of the manuscript and helpful suggestions and the Johns Hopkins University Mouse Tri-Lab for its support. This work was supported by US National Institutes of Health grants GM076430 (S.H.) and EY017606 (A.P.S.), the David and Lucile Packard Foundation (S.H.), the Alfred P. Sloan Foundation (S.H.) and the McKnight Endowment Fund for Neurosciences (A.P.S.).

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The experiments were conceived and designed by C.M.A., A.D.G., A.P.S. and S.H. Wheel-running experiments were carried out by C.M.A. A.C.A. performed current-clamp recordings of retinal cells. N.M.A., C.M.A. and G.T.P. carried out virtual optomotor system experiments. C.M.A., A.D.G., A.P.S. and S.H. wrote the manuscript, which was reviewed and edited by all of the authors.

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Correspondence to Alapakkam P Sampath or Samer Hattar.

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The authors declare no competing financial interests.

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Altimus, C., Güler, A., Alam, N. et al. Rod photoreceptors drive circadian photoentrainment across a wide range of light intensities. Nat Neurosci 13, 1107–1112 (2010). https://doi.org/10.1038/nn.2617

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