Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus
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TLDR
Circadian pacemaking in the SCN provides an unrivalled context in which to understand how a complex, adaptive behaviour can be organised by the dynamic activity of a relatively few gene products, operating in a clearly defined neuronal circuit, with both cell‐autonomous and emergent, circuit‐level properties.Abstract:
The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker of the brain. It co-ordinates the daily rhythms of sleep and wakefulness, as well as physiology and behaviour, that set the tempo to our lives. Disturbance of this daily pattern, most acutely with jet-lag but more insidiously with rotational shift-work, can have severely deleterious effects for mental function and long-term health. The present review considers recent developments in our understanding of the properties of the SCN that make it a robust circadian time-keeper. It first focuses on the intracellular transcriptional/ translational feedback loops (TTFL) that constitute the cellular clockwork of the SCN neurone. Daily timing by these loops pivots around the negative regulation of the Period (Per) and Cryptochrome (Cry) genes by their protein products. The period of the circadian cycle is set by the relative stability of Per and Cry proteins, and this can be controlled by both genetic and pharmacological interventions. It then considers the function of these feedback loops in the context of cytosolic signalling by cAMP and intracellular calcium ([Ca(2+) ]i ), which are both outputs from, and inputs to, the TTFL, as well as the critical role of vasoactive intestinal peptide (VIP) signalling in synchronising cellular clocks across the SCN. Synchronisation by VIP in the SCN is paracrine, operating over an unconventionally long time frame (i.e. 24 h) and wide spatial domain, mediated via the cytosolic pathways upstream of the TTFL. Finally, we show how intersectional pharmacogenetics can be used to control G-protein-coupled signalling in individual SCN neurones, and how manipulation of Gq/[Ca(2+) ]i -signalling in VIP neurones can re-programme the circuit-level encoding of circadian time. Circadian pacemaking in the SCN therefore provides an unrivalled context in which to understand how a complex, adaptive behaviour can be organised by the dynamic activity of a relatively few gene products, operating in a clearly defined neuronal circuit, with both cell-autonomous and emergent, circuit-level properties.read more
Citations
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Journal ArticleDOI
Generation of circadian rhythms in the suprachiasmatic nucleus.
TL;DR: The molecular, cellular and circuit mechanisms underlying time-keeping in the SCN are examined, which act as the principal pacemaker for circadian rhythms, which are powerful regulators of physiology and behaviour in mammals.
Journal ArticleDOI
Astrocytes Control Circadian Timekeeping in the Suprachiasmatic Nucleus via Glutamatergic Signaling
Marco Brancaccio,Andrew P. Patton,Johanna E. Chesham,Elizabeth S. Maywood,Michael H. Hastings +4 more
TL;DR: It is shown that neurons constitute only one “half” of the SCN clock, the one metabolically active during circadian daytime, when they suppress the activity of SCN neurons by regulating extracellular glutamate levels, and somatic genetic re-programming of intracellular clocks in SCN astrocytes was capable of remodeling circadian behavioral rhythms in adult mice.
Journal ArticleDOI
GWAS of 89,283 individuals identifies genetic variants associated with self-reporting of being a morning person
TL;DR: A genome-wide association analysis of self-reported morningness is conducted, followed by analyses of biological pathways and related phenotypes that reinforce current understanding of circadian biology and will guide future studies.
Journal ArticleDOI
Light and Cognition: Roles for Circadian Rhythms, Sleep, and Arousal.
Angus S. Fisk,Tam Ske.,Laurence A. Brown,Vladyslav V. Vyazovskiy,David M. Bannerman,Stuart N. Peirson +5 more
TL;DR: It is proposed that studies addressing the effects of different lighting conditions on cognitive processes must also account for their effects on circadian rhythms, sleep, and arousal if they are to fully understand the physiological basis of these responses.
Journal ArticleDOI
The Circadian System: A Regulatory Feedback Network of Periphery and Brain
Frederik N Buijs,Luis León-Mercado,Mara A. Guzmán-Ruiz,Natalí N. Guerrero-Vargas,Francisco Romo-Nava,Ruud M. Buijs +5 more
TL;DR: Evidence that chronic diseases like diabetes, hypertension, cancer, and psychiatric disorders stem from the need of the SCN for peripheral feedback to fine-tune its output and adjust physiological processes to the requirements of the moment is evaluated.
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Entrainment of the Circadian Clock in the Liver by Feeding
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