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Article ; Online: Synchronization and maintenance of circadian timing in the mammalian clockwork.

Maywood, Elizabeth S

2018 Volume 51, Issue 1, Page(s) 229–240

Abstract: The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian pacemaker in mammals. Cells in the SCN contain cell-autonomous transcriptional-translational feedback loops, which are synchronised to each other and thereby provide a coherent ... ...

Abstract	The hypothalamic suprachiasmatic nucleus (SCN) is the principal circadian pacemaker in mammals. Cells in the SCN contain cell-autonomous transcriptional-translational feedback loops, which are synchronised to each other and thereby provide a coherent output to direct synchrony of peripheral clocks located in the brain and body. A major difference between these peripheral clocks and the SCN is the requirement for intercellular coupling mechanisms, which confer robustness, stability and amplitude to the system. There has been remarkable progress to our understanding of the intra- and inter-cellular mechanisms of the SCN circuitry over the last ~20 years, which has come hand-in-hand with the development of new technologies to measure and manipulate the clock.
MeSH term(s)	Animals ; Circadian Clocks ; Circadian Rhythm ; Mammals ; Protein Processing, Post-Translational ; Suprachiasmatic Nucleus
Language	English
Publishing date	2018-12-05
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.14279
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Article: The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker.

Hastings, Michael H / Maywood, Elizabeth S / Brancaccio, Marco

Biology

2019 Volume 8, Issue 1

Abstract: The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria ( ...

Abstract	The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria (
Language	English
Publishing date	2019-03-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology8010013
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Article ; Online: The Cell-Autonomous Clock of VIP Receptor VPAC2 Cells Regulates Period and Coherence of Circadian Behavior.

Hamnett, Ryan / Chesham, Johanna E / Maywood, Elizabeth S / Hastings, Michael H

The Journal of neuroscience : the official journal of the Society for Neuroscience

2020 Volume 41, Issue 3, Page(s) 502–512

Abstract: Circadian (approximately daily) rhythms pervade mammalian behavior. They are generated by cell-autonomous, transcriptional/translational feedback loops (TTFLs), active in all tissues. This distributed clock network is coordinated by the principal ... ...

Abstract	Circadian (approximately daily) rhythms pervade mammalian behavior. They are generated by cell-autonomous, transcriptional/translational feedback loops (TTFLs), active in all tissues. This distributed clock network is coordinated by the principal circadian pacemaker, the hypothalamic suprachiasmatic nucleus (SCN). Its robust and accurate time-keeping arises from circuit-level interactions that bind its individual cellular clocks into a coherent time-keeper. Cells that express the neuropeptide vasoactive intestinal peptide (VIP) mediate retinal entrainment of the SCN; and in the absence of VIP, or its cognate receptor VPAC2, circadian behavior is compromised because SCN cells cannot synchronize. The contributions to pace-making of other cell types, including VPAC2-expressing target cells of VIP, are, however, not understood. We therefore used intersectional genetics to manipulate the cell-autonomous TTFLs of VPAC2-expressing cells. Measuring circadian behavioral and SCN rhythmicity in these temporally chimeric male mice thus enabled us to determine the contribution of VPAC2-expressing cells (∼35% of SCN cells) to SCN time-keeping. Lengthening of the intrinsic TTFL period of VPAC2 cells by deletion of the
MeSH term(s)	ARNTL Transcription Factors/genetics ; ARNTL Transcription Factors/physiology ; Animals ; Behavior, Animal/physiology ; Circadian Rhythm/genetics ; Circadian Rhythm/physiology ; Feedback, Physiological ; Male ; Mice ; Mice, Knockout ; Motor Activity/physiology ; Mutant Chimeric Proteins/genetics ; Periodicity ; Receptors, Vasoactive Intestinal Peptide/genetics ; Receptors, Vasoactive Intestinal Peptide/physiology ; Receptors, Vasoactive Intestinal Peptide, Type II/genetics ; Receptors, Vasoactive Intestinal Peptide, Type II/physiology ; Suprachiasmatic Nucleus/physiology
Chemical Substances	ARNTL Transcription Factors ; Bmal1 protein, mouse ; Mutant Chimeric Proteins ; Receptors, Vasoactive Intestinal Peptide ; Receptors, Vasoactive Intestinal Peptide, Type II
Language	English
Publishing date	2020-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.2015-20.2020
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Zs.A 1668: Show issues

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Article ; Online: Restoring the Molecular Clockwork within the Suprachiasmatic Hypothalamus of an Otherwise Clockless Mouse Enables Circadian Phasing and Stabilization of Sleep-Wake Cycles and Reverses Memory Deficits.

Maywood, Elizabeth S / Chesham, Johanna E / Winsky-Sommerer, Raphaelle / Hastings, Michael H

The Journal of neuroscience : the official journal of the Society for Neuroscience

2021 Volume 41, Issue 41, Page(s) 8562–8576

Abstract: ... To determine the specific contribution(s) of the SCN, we used virally mediated genetic complementation ...

Abstract	The timing and quality of sleep-wake cycles are regulated by interacting circadian and homeostatic mechanisms. Although the suprachiasmatic nucleus (SCN) is the principal clock, circadian clocks are active across the brain and the respective sleep-regulatory roles of SCN and local clocks are unclear. To determine the specific contribution(s) of the SCN, we used virally mediated genetic complementation, expressing Cryptochrome1 (Cry1) to establish circadian molecular competence in the suprachiasmatic hypothalamus of globally clockless, arrhythmic male
MeSH term(s)	Animals ; Circadian Clocks/physiology ; Circadian Rhythm/physiology ; Cryptochromes/biosynthesis ; Cryptochromes/genetics ; Electroencephalography/methods ; Electromyography/methods ; Male ; Memory Disorders ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Sleep/physiology ; Suprachiasmatic Nucleus/metabolism ; Wakefulness/physiology
Chemical Substances	Cry1 protein, mouse ; Cry2 protein, mouse ; Cryptochromes
Language	English
Publishing date	2021-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.3141-20.2021
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Article ; Online: Cryptochrome 1 as a state variable of the circadian clockwork of the suprachiasmatic nucleus: Evidence from translational switching.

McManus, David / Polidarova, Lenka / Smyllie, Nicola J / Patton, Andrew P / Chesham, Johanna E / Maywood, Elizabeth S / Chin, Jason W / Hastings, Michael H

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 34, Page(s) e2203563119

Abstract: The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal clock driving circadian rhythms of physiology and behavior that adapt mammals to environmental cycles. Disruption of SCN-dependent rhythms compromises health, and so understanding SCN ...

Abstract	The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal clock driving circadian rhythms of physiology and behavior that adapt mammals to environmental cycles. Disruption of SCN-dependent rhythms compromises health, and so understanding SCN time keeping will inform management of diseases associated with modern lifestyles. SCN time keeping is a self-sustaining transcriptional/translational delayed feedback loop (TTFL), whereby negative regulators inhibit their own transcription. Formally, the SCN clock is viewed as a limit-cycle oscillator, the simplest being a trajectory of successive phases that progresses through two-dimensional space defined by two state variables mapped along their respective axes. The TTFL motif is readily compatible with limit-cycle models, and in
MeSH term(s)	Animals ; Circadian Clocks ; Circadian Rhythm ; Cryptochromes/metabolism ; Drosophila melanogaster ; Neurospora ; Protein Transport ; Suprachiasmatic Nucleus/metabolism
Chemical Substances	Cryptochromes
Language	English
Publishing date	2022-08-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2203563119
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Zs.A 1148: Show issues

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Article ; Online: Generation of circadian rhythms in the suprachiasmatic nucleus.

Hastings, Michael H / Maywood, Elizabeth S / Brancaccio, Marco

Nature reviews. Neuroscience

2018 Volume 19, Issue 8, Page(s) 453–469

Abstract: The suprachiasmatic nucleus (SCN) of the hypothalamus is remarkable. Despite numbering only about 10,000 neurons on each side of the third ventricle, the SCN is our principal circadian clock, directing the daily cycles of behaviour and physiology that ... ...

Abstract	The suprachiasmatic nucleus (SCN) of the hypothalamus is remarkable. Despite numbering only about 10,000 neurons on each side of the third ventricle, the SCN is our principal circadian clock, directing the daily cycles of behaviour and physiology that set the tempo of our lives. When this nucleus is isolated in organotypic culture, its autonomous timing mechanism can persist indefinitely, with precision and robustness. The discovery of the cell-autonomous transcriptional and post-translational feedback loops that drive circadian activity in the SCN provided a powerful exemplar of the genetic specification of complex mammalian behaviours. However, the analysis of circadian time-keeping is moving beyond single cells. Technical and conceptual advances, including intersectional genetics, multidimensional imaging and network theory, are beginning to uncover the circuit-level mechanisms and emergent properties that make the SCN a uniquely precise and robust clock. However, much remains unknown about the SCN, not least the intrinsic properties of SCN neurons, its circuit topology and the neuronal computations that these circuits support. Moreover, the convention that the SCN is a neuronal clock has been overturned by the discovery that astrocytes are an integral part of the timepiece. As a test bed for examining the relationships between genes, cells and circuits in sculpting complex behaviours, the SCN continues to offer powerful lessons and opportunities for contemporary neuroscience.
MeSH term(s)	Animals ; Astrocytes/physiology ; Circadian Clocks ; Circadian Rhythm ; Humans ; Neurons/physiology ; Signal Transduction ; Suprachiasmatic Nucleus/physiology
Language	English
Publishing date	2018-06-22
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2034150-7
ISSN	1471-0048 ; 1471-0048 ; 1471-003X
ISSN (online)	1471-0048
ISSN	1471-0048 ; 1471-003X
DOI	10.1038/s41583-018-0026-z
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Zs.A 5473: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 47: Show issues

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Article ; Online: The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker

Michael H. Hastings / Elizabeth S. Maywood / Marco Brancaccio

Biology, Vol 8, Iss 1, p

2019 Volume 13

Abstract	The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria (Synechococcus), fungi (Neurospora), higher plants (Arabidopsis), insects (Drosophila) and mammals (mouse and humans), a common mechanistic motif of delayed negative feedback has emerged as the Deus ex machina for the cellular definition of ca. 24 h cycles. This review will consider, briefly, comparative circadian clock biology and will then focus on the mammalian circadian system, considering its molecular genetic basis, the properties of the suprachiasmatic nucleus (SCN) as the principal circadian clock in mammals and its role in synchronising a distributed peripheral circadian clock network. Finally, it will consider new directions in analysing the cell-autonomous and circuit-level SCN clockwork and will highlight the surprising discovery of a central role for SCN astrocytes as well as SCN neurons in controlling circadian behaviour.
Keywords	astrocytes ; entrainment ; photoperiod ; suprachiasmatic ; period ; cryptochrome ; sleep ; clock ; Bmal1 ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mechanisms and physiological function of daily haemoglobin oxidation rhythms in red blood cells.

Beale, Andrew D / Hayter, Edward A / Crosby, Priya / Valekunja, Utham K / Edgar, Rachel S / Chesham, Johanna E / Maywood, Elizabeth S / Labeed, Fatima H / Reddy, Akhilesh B / Wright, Kenneth P / Lilley, Kathryn S / Bechtold, David A / Hastings, Michael H / O'Neill, John S

The EMBO journal

2023 Volume 42, Issue 19, Page(s) e114164

Abstract: Cellular circadian rhythms confer temporal organisation upon physiology that is fundamental to human health. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body, but their physiological function is poorly understood. ... ...

Abstract	Cellular circadian rhythms confer temporal organisation upon physiology that is fundamental to human health. Rhythms are present in red blood cells (RBCs), the most abundant cell type in the body, but their physiological function is poorly understood. Here, we present a novel biochemical assay for haemoglobin (Hb) oxidation status which relies on a redox-sensitive covalent haem-Hb linkage that forms during SDS-mediated cell lysis. Formation of this linkage is lowest when ferrous Hb is oxidised, in the form of ferric metHb. Daily haemoglobin oxidation rhythms are observed in mouse and human RBCs cultured in vitro, or taken from humans in vivo, and are unaffected by mutations that affect circadian rhythms in nucleated cells. These rhythms correlate with daily rhythms in core body temperature, with temperature lowest when metHb levels are highest. Raising metHb levels with dietary sodium nitrite can further decrease daytime core body temperature in mice via nitric oxide (NO) signalling. These results extend our molecular understanding of RBC circadian rhythms and suggest they contribute to the regulation of body temperature.
MeSH term(s)	Humans ; Mice ; Animals ; Erythrocytes/metabolism ; Hemoglobins/metabolism ; Oxidation-Reduction ; Heme/metabolism ; Circadian Rhythm
Chemical Substances	Hemoglobins ; Heme (42VZT0U6YR)
Language	English
Publishing date	2023-08-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2023114164
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Zs.A 1808: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 100: Show issues

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Article ; Online: Zfhx3-mediated genetic ablation of the SCN abolishes light entrainable circadian activity while sparing food anticipatory activity.

Wilcox, Ashleigh G / Bains, R Sonia / Williams, Debbie / Joynson, Elizabeth / Vizor, Lucie / Oliver, Peter L / Maywood, Elizabeth S / Hastings, Michael H / Banks, Gareth / Nolan, Patrick M

iScience

2021 Volume 24, Issue 10, Page(s) 103142

Abstract: Circadian rhythms persist in almost all organisms and are crucial for maintaining appropriate timing in physiology and behaviour. Here, we describe a mouse mutant where the central mammalian pacemaker, the suprachiasmatic nucleus (SCN), has been ... ...

Abstract	Circadian rhythms persist in almost all organisms and are crucial for maintaining appropriate timing in physiology and behaviour. Here, we describe a mouse mutant where the central mammalian pacemaker, the suprachiasmatic nucleus (SCN), has been genetically ablated by conditional deletion of the transcription factor
Language	English
Publishing date	2021-09-16
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2021.103142
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker

Hastings, Michael H / Maywood, Elizabeth S / Brancaccio, Marco

Biology. 2019 Mar. 11, v. 8, no. 1

2019

Abstract	The past twenty years have witnessed the most remarkable breakthroughs in our understanding of the molecular and cellular mechanisms that underpin circadian (approximately one day) time-keeping. Across model organisms in diverse taxa: cyanobacteria (Synechococcus), fungi (Neurospora), higher plants (Arabidopsis), insects (Drosophila) and mammals (mouse and humans), a common mechanistic motif of delayed negative feedback has emerged as the Deus ex machina for the cellular definition of ca. 24 h cycles. This review will consider, briefly, comparative circadian clock biology and will then focus on the mammalian circadian system, considering its molecular genetic basis, the properties of the suprachiasmatic nucleus (SCN) as the principal circadian clock in mammals and its role in synchronising a distributed peripheral circadian clock network. Finally, it will consider new directions in analysing the cell-autonomous and circuit-level SCN clockwork and will highlight the surprising discovery of a central role for SCN astrocytes as well as SCN neurons in controlling circadian behaviour.
Keywords	Arabidopsis ; Drosophila ; Neurospora ; Synechococcus ; astrocytes ; circadian clocks ; circadian rhythm ; fungi ; humans ; insects ; mice ; models ; neurons
Language	English
Dates of publication	2019-0311
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology8010013
Database	NAL-Catalogue (AGRICOLA)

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