title: Rev-Erbα modulates retinal visual processing and behavioral responses to light.
abstract: The circadian clock is thought to adjust retinal sensitivity to ambient light levels, yet the involvement of specific clock genes is poorly understood. We explored the potential role of the nuclear receptor subfamily 1, group D, member 1 (REV-ERBα; or NR1D1) in this respect. In light-evoked behavioral tests, compared with wild-type littermates, Rev-Erbα-/-mice showed enhanced negative masking at low light levels (0.1 lx). Rev-Erbα-/-mouse retinas displayed significantly higher numbers of intrinsically photosensitive retinal ganglion cells (ipRGCs; 62% more compared with wild-type) and more intense melanopsin immunostaining of individual ipRGCs. In agreement with a pivotal role for melanopsin, negative masking at low light intensities was abolished in Rev-Erbα-/-Opn4-/-(melanopsin gene) double-null mice. Rev-Erbα-/-mice showed shortened latencies of both a and b electroretinogram waves, modified scotopic and photopic b-wave and scotopic threshold responses, and increased pupillary constriction, all of which suggested increased light sensitivity. However, wild-type and Rev-Erbα-/-mice displayed no detectable differences by in vivo fundus imaging, retinal histology, or expression of cell type-specific markers for major retinal cell populations. We conclude that REV-ERBα plays a major role in retinal information processing, and we speculate that REV-ERBα and melanopsin set sensitivity levels of the rod-mediated ipRGC pathway to coordinate activity with ambient light.-Ait-Hmyed Hakkari, O., Acar, N., Savier, E., Spinnhirny, P., Bennis, M., Felder-Schmittbuhl, M.-P., Mendoza, J., Hicks, D. Rev-Erbα modulates retinal visual processing and behavioral responses to light.
authors.affiliation: Department of Neurobiology of Rhythms, Centre National de la Recherche Scientifique, Unités Propres de Recherche 3212, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.|Université Cadi Ayad, Département de Biologie, Laboratoire de Pharmacologie, Neurobiologie et Comportement, Marrakech, Morocco.
authors.forename: Ouafa
authors.initials: O
authors.lastname: Ait-Hmyed Hakkari
authors.affiliation: Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 6265, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.|Institut National de la Recherche Agronomique, Unités Mixtes de Recherche 324, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.|Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, Dijon, France.
authors.forename: Niyazi
authors.initials: N
authors.lastname: Acar
authors.affiliation: Department of Neurobiology of Rhythms, Centre National de la Recherche Scientifique, Unités Propres de Recherche 3212, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
authors.forename: Elise
authors.initials: E
authors.lastname: Savier
authors.affiliation: Department of Neurobiology of Rhythms, Centre National de la Recherche Scientifique, Unités Propres de Recherche 3212, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
authors.forename: Perrine
authors.initials: P
authors.lastname: Spinnhirny
authors.affiliation: Université Cadi Ayad, Département de Biologie, Laboratoire de Pharmacologie, Neurobiologie et Comportement, Marrakech, Morocco.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bennis
authors.affiliation: Department of Neurobiology of Rhythms, Centre National de la Recherche Scientifique, Unités Propres de Recherche 3212, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Felder-Schmittbuhl
authors.affiliation: Department of Neurobiology of Rhythms, Centre National de la Recherche Scientifique, Unités Propres de Recherche 3212, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
authors.forename: Jorge
authors.initials: J
authors.lastname: Mendoza
authors.affiliation: Department of Neurobiology of Rhythms, Centre National de la Recherche Scientifique, Unités Propres de Recherche 3212, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France; photoreceptor67@hotmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Hicks
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology; D008027:Light; D018345:Mice, Knockout; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000172:deficiency / Q000378:metabolism*; D010775:Photic Stimulation / Q000379:methods; D012160:Retina / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; D017299:Rod Opsins; D000099210:Melanopsin; C498262:Nr1d1 protein, mouse
keywords: circadian clock; electroretinogram; ipRGCs; negative masking; photoreceptors