title: Architecture of retinal projections to the central circadian pacemaker.
abstract: The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218;
authors.forename: Diego Carlos
authors.initials: DC
authors.lastname: Fernandez
authors.affiliation: Department of Life Science, National Taiwan University, Taipei 10617, Taiwan;
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Chang
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218; Department of Neuroscience, Johns Hopkins University, Baltimore, MD 21218;
authors.forename: Samer
authors.identifier: 0000-0002-3124-9525
authors.initials: S
authors.lastname: Hattar
authors.affiliation: Department of Life Science, National Taiwan University, Taipei 10617, Taiwan; Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 10617, Taiwan alenskchen@ntu.edu.tw.
authors.forename: Shih-Kuo
authors.identifier: 0000-0002-7921-1358
authors.initials: SK
authors.lastname: Chen
mesh_terms: D000818:Animals; D057906:Circadian Clocks / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D014785:Vision, Ocular / Q000502:physiology*
keywords: circadian; ipRGCs; melanopsin; non-image–forming functions; suprachiasmatic nucleus