title: Constant Light Desynchronizes Olfactory versus Object and Visuospatial Recognition Memory Performance.
abstract: Circadian rhythms optimize physiology and behavior to the varying demands of the 24 h day. The master circadian clock is located in the suprachiasmatic nuclei (SCN) of the hypothalamus and it regulates circadian oscillators in tissues throughout the body to prevent internal desynchrony. Here, we demonstrate for the first time that, under standard 12 h:12 h light/dark (LD) cycles, object, visuospatial, and olfactory recognition performance in C57BL/6J mice is consistently better at midday relative to midnight. However, under repeated exposure to constant light (rLL), recognition performance becomes desynchronized, with object and visuospatial performance better at subjective midday and olfactory performance better at subjective midnight. This desynchrony in behavioral performance is mirrored by changes in expression of the canonical clock genesPeriod1andPeriod2(Per1andPer2), as well as the immediate-early geneFosin the SCN, dorsal hippocampus, and olfactory bulb. UnderrLL, rhythmicPer1andFosexpression is attenuated in the SCN. In contrast, hippocampal gene expression remains rhythmic, mirroring object and visuospatial performance. Strikingly,Per1andFosexpression in the olfactory bulb is reversed, mirroring the inverted olfactory performance. Temporal desynchrony among these regions does not result in arrhythmicity because core body temperature and exploratory activity rhythms persist underrLL. Our data provide the first demonstration that abnormal lighting conditions can give rise to temporal desynchrony between autonomous circadian oscillators in different regions, with different consequences for performance across different sensory domains. Such a dispersed network of dissociable circadian oscillators may provide greater flexibility when faced with conflicting environmental signals.SIGNIFICANCE STATEMENTA master circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus regulates physiology and behavior across the 24 h day by synchronizing peripheral clocks throughout the brain and body. Without the SCN, these peripheral clocks rapidly become desynchronized. Here, we provide a unique demonstration that, under lighting conditions in which the central clock in the SCN is dampened, peripheral oscillators in the hippocampus and olfactory bulb become desynchronized, along with the behavioral processes mediated by these clocks. Multiple clocks that adopt different phase relationships may enable processes occurring in different brain regions to be optimized to specific phases of the 24 h day. Moreover, such a dispersed network of dissociable circadian clocks may provide greater flexibility when faced with conflicting environmental signals (e.g., seasonal changes in photoperiod).
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.|Department of Experimental Psychology, University of Oxford, Oxford OX1 3PH, United Kingdom, and.
authors.forename: Shu K E
authors.initials: SK
authors.lastname: Tam
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Sibah
authors.initials: S
authors.lastname: Hasan
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Harry M C
authors.identifier: 0000-0002-6113-9773
authors.initials: HM
authors.lastname: Choi
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Brown
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Aarti
authors.initials: A
authors.lastname: Jagannath
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Steven
authors.identifier: 0000-0002-1051-6428
authors.initials: S
authors.lastname: Hughes
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hankins
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Foster
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.|Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3QX, United Kingdom.
authors.forename: Vladyslav V
authors.initials: VV
authors.lastname: Vyazovskiy
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford OX1 3PH, United Kingdom, and stuart.peirson@eye.ox.ac.uk david.bannerman@psy.ox.ac.uk.
authors.forename: David M
authors.initials: DM
authors.lastname: Bannerman
authors.affiliation: Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Oxford Molecular Pathology Institute, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom, stuart.peirson@eye.ox.ac.uk david.bannerman@psy.ox.ac.uk.
authors.forename: Stuart N
authors.identifier: 0000-0003-3653-834X
authors.initials: SN
authors.lastname: Peirson
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D003344:Cortical Synchronization / Q000502:physiology; D005556:Form Perception / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D011939:Mental Recall / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010364:Pattern Recognition, Visual / Q000502:physiology; D010470:Perceptual Masking / Q000502:physiology*; D010775:Photic Stimulation / Q000379:methods; D021641:Recognition, Psychology / Q000502:physiology*; D012903:Smell / Q000502:physiology*; D065854:Spatial Navigation / Q000502:physiology*; D013647:Task Performance and Analysis
keywords: circadian; clock genes; hippocampus; internal desynchrony; olfactory bulb; suprachiasmatic nuclei