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      Synchronization of the mammalian circadian timing system: Light can control peripheral clocks independently of the SCN clock : Alternate routes of entrainment optimize the alignment of the body's circadian clock network with external time

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          Abstract

          A vast network of cellular circadian clocks regulates 24‐hour rhythms of behavior and physiology in mammals. Complex environments are characterized by multiple, and often conflicting time signals demanding flexible mechanisms of adaptation of endogenous rhythms to external time. Traditionally this process of circadian entrainment has been conceptualized in a hierarchical scheme with a light‐reset master pacemaker residing in the hypothalamus that subsequently aligns subordinate peripheral clocks with each other and with external time. Here we review new experiments using conditional mouse genetics suggesting that resetting of the circadian system occurs in a more “federated” and tissue‐specific fashion, which allows for increased noise resistance and plasticity of circadian timekeeping under natural conditions.

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          Most cited references63

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          The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator.

          Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components of the general feedback loop. Thus, REV-ERBalpha constitutes a molecular link through which components of the negative limb drive antiphasic expression of components of the positive limb. While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation.
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            Molecular architecture of the mammalian circadian clock.

            Circadian clocks coordinate physiology and behavior with the 24h solar day to provide temporal homeostasis with the external environment. The molecular clocks that drive these intrinsic rhythmic changes are based on interlocked transcription/translation feedback loops that integrate with diverse environmental and metabolic stimuli to generate internal 24h timing. In this review we highlight recent advances in our understanding of the core molecular clock and how it utilizes diverse transcriptional and post-transcriptional mechanisms to impart temporal control onto mammalian physiology. Understanding the way in which biological rhythms are generated throughout the body may provide avenues for temporally directed therapeutics to improve health and prevent disease. Copyright © 2013 Elsevier Ltd. All rights reserved.
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              Suprachiasmatic nucleus: cell autonomy and network properties.

              The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals. Individual SCN neurons in dispersed culture can generate independent circadian oscillations of clock gene expression and neuronal firing. However, SCN rhythmicity depends on sufficient membrane depolarization and levels of intracellular calcium and cAMP. In the intact SCN, cellular oscillations are synchronized and reinforced by rhythmic synaptic input from other cells, resulting in a reproducible topographic pattern of distinct phases and amplitudes specified by SCN circuit organization. The SCN network synchronizes its component cellular oscillators, reinforces their oscillations, responds to light input by altering their phase distribution, increases their robustness to genetic perturbations, and enhances their precision. Thus, even though individual SCN neurons can be cell-autonomous circadian oscillators, neuronal network properties are integral to normal function of the SCN.
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                Author and article information

                Journal
                Bioessays
                Bioessays
                10.1002/(ISSN)1521-1878
                BIES
                Bioessays
                John Wiley and Sons Inc. (Hoboken )
                0265-9247
                1521-1878
                07 August 2015
                October 2015
                : 37
                : 10 ( doiID: 10.1002/bies.v37.10 )
                : 1119-1128
                Affiliations
                [ 1 ]Max Planck Institute for Biophysical Chemistry GöttingenGermany
                [ 2 ] Chronophysiology Group, Medical Department IUniversity of Lübeck LübeckGermany
                Author notes
                [*] [* ] Corresponding author:

                Henrik Oster

                E‐mail: henrik.oster@ 123456uksh.de

                [†]

                Present address: Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada.

                Article
                BIES201500026
                10.1002/bies.201500026
                5054915
                26252253
                1839ca55-8262-43ab-9d97-6881c291a0c2
                © 2015 The Authors. BioEssays Published by WILEY Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Page count
                Pages: 10
                Funding
                Funded by: Max Planck Society
                Categories
                Prospects & Overviews
                Problems & Paradigms
                Problems & Paradigms
                Custom metadata
                2.0
                bies201500026
                October 2015
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:07.10.2016

                Cell biology
                circadian clock,clock genes,entrainment,light,mammals,peripheral clocks,scn
                Cell biology
                circadian clock, clock genes, entrainment, light, mammals, peripheral clocks, scn

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