title: Circadian organization of the rodent retina involves strongly coupled, layer-specific oscillators.
abstract: Rhythmic physiology is central to retinal function and survival and adapts vision to daily light intensity changes. Mammalian retina rhythmically releases melatonin when cultured under constant conditions, and the occurrence of clock gene [e.g., Period (Per)] expression has been shown for most cellular layers. However, contribution of the distinct layers to genesis of circadian rhythms within the retina is still debated. To characterize their endogenous oscillatory capacity and their communication at the whole-tissue level, we used a vibratome-based method to isolate individual or paired retina cellular layers from the mPer2(Luc) mouse and Per1-luciferase (Per1-Luc) rat, and real-time recorded bioluminescence. We report that each layer of the mouse retina harbors a self-sustained oscillator whose period is significantly longer (∼ 26 hours) than in whole-retina explants (∼ 22.9 hours), indicating that the period is correlated with the degree of coupling. Accordingly, the maximal period (∼ 29 hours) is reached upon complete enzymatic dissociation of the retina. By using pharmacological approaches, we demonstrate that connection between retina oscillators involves gap junctions but only minor contribution from the main retina neurochemicals. Taken together with results from Per1-Luc rats, these data show that mammalian retina consists of a network of layer-specific oscillators whose period is determined by their connectivity.
authors.affiliation: *Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neurosciences, National Center for Scientific Research UPR3212; and Unit of Mathematics and Computer Science, University of Strasbourg, Strasbourg, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Jaeger
authors.affiliation: *Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neurosciences, National Center for Scientific Research UPR3212; and Unit of Mathematics and Computer Science, University of Strasbourg, Strasbourg, France.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sandu
authors.affiliation: *Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neurosciences, National Center for Scientific Research UPR3212; and Unit of Mathematics and Computer Science, University of Strasbourg, Strasbourg, France.
authors.forename: André
authors.initials: A
authors.lastname: Malan
authors.affiliation: *Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neurosciences, National Center for Scientific Research UPR3212; and Unit of Mathematics and Computer Science, University of Strasbourg, Strasbourg, France.
authors.forename: Katell
authors.initials: K
authors.lastname: Mellac
authors.affiliation: *Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neurosciences, National Center for Scientific Research UPR3212; and Unit of Mathematics and Computer Science, University of Strasbourg, Strasbourg, France.
authors.forename: David
authors.initials: D
authors.lastname: Hicks
authors.affiliation: *Department of Neurobiology of Rhythms, Institute for Cellular and Integrative Neurosciences, National Center for Scientific Research UPR3212; and Unit of Mathematics and Computer Science, University of Strasbourg, Strasbourg, France feldermp@inci-cnrs.unistra.fr.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Felder-Schmittbuhl
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D056950:Period Circadian Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C539024:Per1 protein, rat; C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D011993:Recombinant Fusion Proteins; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D008156:Luciferases; D005998:Glycine
keywords: bioluminescence; circadian rhythms; clock; period