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Journal ArticleDOI

Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain?

01 Jun 2007-European Journal of Neuroscience (John Wiley & Sons Ltd)-Vol. 25, Iss: 11, pp 3195-3216
TL;DR: This review examines the evidence for extra‐SCN circadian oscillators in the mammalian brain and highlights some of the essential properties and key differences between brain oscillators.
Abstract: The suprachiasmatic nucleus of the hypothalamus (SCN) is the master circadian pacemaker or clock in the mammalian brain. Canonical theory holds that the output from this single, dominant clock is responsible for driving most daily rhythms in physiology and behaviour. However, important recent findings challenge this uniclock model and reveal clock-like activities in many neural and non-neural tissues. Thus, in addition to the SCN, a number of areas of the mammalian brain including the olfactory bulb, amygdala, lateral habenula and a variety of nuclei in the hypothalamus, express circadian rhythms in core clock gene expression, hormone output and electrical activity. This review examines the evidence for extra-SCN circadian oscillators in the mammalian brain and highlights some of the essential properties and key differences between brain oscillators. The demonstration of neural pacemakers outside the SCN has wide-ranging implications for models of the circadian system at a whole-organism level.
Citations
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Journal ArticleDOI
TL;DR: This work discusses knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system and some of the SCN output pathways serve as input pathways for peripheral tissues.
Abstract: Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system.

1,984 citations

Journal ArticleDOI
TL;DR: 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.
Abstract: 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.

1,045 citations


Cites background from "Challenging the omnipotence of the ..."

  • ...As a master pacemaker, the SCN synchronizes other oscillators throughout the brain (50) and peripheral tissues (10)....

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  • ...The SCN also generates pronounced circadian rhythms in frequency of spontaneous neuronal firing when physically isolated, either in vivo (46) or in vitro (47–49), although recent data indicate this may not be a unique property (50)....

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Journal ArticleDOI
TL;DR: The habenula, a highly conserved structure in the brain, provides a fundamental mechanism for both survival and decision-making through its effects on neuromodulator systems, in particular the dopamine and serotonin systems.
Abstract: Surviving in a world with hidden rewards and dangers requires choosing the appropriate behaviours. Recent discoveries indicate that the habenula plays a prominent part in such behavioural choice through its effects on neuromodulator systems, in particular the dopamine and serotonin systems. By inhibiting dopamine-releasing neurons, habenula activation leads to the suppression of motor behaviour when an animal fails to obtain a reward or anticipates an aversive outcome. Moreover, the habenula is involved in behavioural responses to pain, stress, anxiety, sleep and reward, and its dysfunction is associated with depression, schizophrenia and drug-induced psychosis. As a highly conserved structure in the brain, the habenula provides a fundamental mechanism for both survival and decision-making.

805 citations

Journal ArticleDOI
26 Apr 2012-Neuron
TL;DR: This review will highlight the relationship between clocks and metabolism, and describe how cues such as light, food, and reward mediate entrainment of the circadian system.

682 citations


Cites background from "Challenging the omnipotence of the ..."

  • ...However, KLF10 is implicated in circadian lipid and cholesterol homeostasis in females (Guillaumond et al., 2010)....

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  • ...Interestingly, Tieg1/Klf10 is regulated by BMAL1/ CLOCK and thus appears to be part of a feedback loop involving the circadian clock and glucose levels (Guillaumond et al., 2010) (Figure 4)....

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Journal ArticleDOI
TL;DR: Differences between master and the peripheral clocks suggest that coupling‐induced rigidity in the SCN filters environmental noise to create a robust circadian system.
Abstract: Circadian clocks are endogenous oscillators driving daily rhythms in physiology and behavior. Synchronization of these timers to environmental light–dark cycles (‘entrainment’) is crucial for an organism’s fitness. Little is known about which oscillator qualities determine entrainment, i.e., entrainment range, phase and amplitude. In a systematic theoretical and experimental study, we uncovered these qualities for circadian oscillators in the suprachiasmatic nucleus (SCN—the master clock in mammals) and the lung (a peripheral clock): (i) the ratio between stimulus (zeitgeber) strength and oscillator amplitude and (ii) the rigidity of the oscillatory system (relaxation rate upon perturbation) determine entrainment properties. Coupling among oscillators affects both qualities resulting in increased amplitude and rigidity. These principles explain our experimental findings that lung clocks entrain to extreme zeitgeber cycles, whereas SCN clocks do not. We confirmed our theoretical predictions by showing that pharmacological inhibition of coupling in the SCN leads to larger ranges of entrainment. These differences between master and the peripheral clocks suggest that coupling-induced rigidity in the SCN filters environmental noise to create a robust circadian system.

305 citations


Cites background or methods from "Challenging the omnipotence of the ..."

  • ...Proceeding in general terms, we assume the oscillator can be characterized by its amplitude, its intrinsic period and its stability with respect to amplitude perturbations (amplitude relaxation rate or Floquet exponent (Guckenheimer and Holmes, 1983))....

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  • ...We find that increasing coupling strength leads to a drastic increase of the amplitude most pronounced for small values of g, the relaxation rate of the individual oscillators (Figure 5A)—a well-known resonance phenomenon (Guckenheimer and Holmes, 1983)....

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  • ...Our results for the generic Poincaré oscillator also hold for other oscillator models, such as the standard Hopf oscillator (Guckenheimer and Holmes, 1983) or the more realistic biophysical circadian clock Becker-Weimann–Bernard model (Becker-Weimann et al, 2004; Bernard et al, 2007) (see…...

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References
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Journal ArticleDOI
TL;DR: It is shown here how the response of the immune system to repeated exposure to high-energy radiation affects its ability to discriminate between healthy and diseased tissue.

11,002 citations


"Challenging the omnipotence of the ..." refers methods in this paper

  • ...Schematic sections are adapted from the rat brain atlas of Paxinos & Watson (1998)....

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Journal ArticleDOI
29 Aug 2002-Nature
TL;DR: Circadian rhythms are generated by one of the most ubiquitous and well-studied timing systems and are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.
Abstract: Time in the biological sense is measured by cycles that range from milliseconds to years. Circadian rhythms, which measure time on a scale of 24 h, are generated by one of the most ubiquitous and well-studied timing systems. At the core of this timing mechanism is an intricate molecular mechanism that ticks away in many different tissues throughout the body. However, these independent rhythms are tamed by a master clock in the brain, which coordinates tissue-specific rhythms according to light input it receives from the outside world.

3,962 citations


"Challenging the omnipotence of the ..." refers background in this paper

  • ...The mechanism has been extensively reviewed (Dunlap, 1999; Hastings & Maywood, 2000; Piggins, 2002; Reppert & Weaver, 2002; Albrecht, 2004; Ko & Takahashi, 2006) and, it is postulated, functions as follows: basic helix–loop–helix transcription factors Bmal1 and Clock provide the positive drive to…...

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  • ...…ª Federation of European Neuroscience Societies and Blackwell Publishing Ltd European Journal of Neuroscience, 25, 3195–3216 lags between transcription, translation and translocation of proteins from the cytoplasm to the nucleus (Lee et al., 2001; Reppert & Weaver, 2002; Lee et al., 2004)....

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  • ...Mutations of these genes result in various behavioural phenotypes indicative of altered clock function, such as arrhythmicity or changes in period length (for a review see Reppert & Weaver, 2002)....

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Journal ArticleDOI
20 Oct 2005-Neuron
TL;DR: Five major research topics are highlighted that illustrate parallel roles for the amygdala in humans and other animals, including implicit emotional learning and memory, emotional modulation of memory,otional influences on attention and perception, emotion and social behavior, and emotion inhibition and regulation.

2,799 citations

Journal ArticleDOI
Jay C. Dunlap1
22 Jan 1999-Cell
TL;DR: It used to be that research in chronobiology moved biochemical functions [transcriptional activators], the along at a gentlemanly pace, but by mid 1997 the word in determining what the authors perceive as time was PASWCCLK.

2,723 citations


"Challenging the omnipotence of the ..." refers background in this paper

  • ...The mechanism has been extensively reviewed (Dunlap, 1999; Hastings & Maywood, 2000; Piggins, 2002; Reppert & Weaver, 2002; Albrecht, 2004; Ko & Takahashi, 2006) and, it is postulated, functions as follows: basic helix–loop–helix transcription factors Bmal1 and Clock provide the positive drive to…...

    [...]

Journal ArticleDOI
TL;DR: Findings from animal and human studies indicate that the amygdala mediates the memory-modulating effects of adrenal stress hormones and several classes of neurotransmitters and plays a key role in enabling emotionally significant experiences to be well remembered.
Abstract: Converging findings of animal and human studies provide compelling evidence that the amygdala is critically involved in enabling us to acquire and retain lasting memories of emotional experiences. This review focuses primarily on the findings of research investigating the role of the amygdala in modulating the consolidation of long-term memories. Considerable evidence from animal studies investigating the effects of posttraining systemic or intra-amygdala infusions of hormones and drugs, as well as selective lesions of specific amygdala nuclei, indicates that (a) the amygdala mediates the memory-modulating effects of adrenal stress hormones and several classes of neurotransmitters; (b) the effects are selectively mediated by the basolateral complex of the amygdala (BLA); (c) the influences involve interactions of several neuromodulatory systems within the BLA that converge in influencing noradrenergic and muscarinic cholinergic activation; (d) the BLA modulates memory consolidation via efferents to other brain regions, including the caudate nucleus, nucleus accumbens, and cortex; and (e) the BLA modulates the consolidation of memory of many different kinds of information. The findings of human brain imaging studies are consistent with those of animal studies in suggesting that activation of the amygdala influences the consolidation of long-term memory; the degree of activation of the amygdala by emotional arousal during encoding of emotionally arousing material (either pleasant or unpleasant) correlates highly with subsequent recall. The activation of neuromodulatory systems affecting the BLA and its projections to other brain regions involved in processing different kinds of information plays a key role in enabling emotionally significant experiences to be well remembered.

2,107 citations


"Challenging the omnipotence of the ..." refers background in this paper

  • ...It functions to integrate emotion, cognition and autonomic signals and is crucial to the perception of and responses to fear, stress and drugs of abuse (Gallagher & Chiba, 1996; Maren & Fanselow, 1996; Rasia-Filho et al., 2000; LeDoux, 2003; See et al., 2003; McGaugh, 2004; Phelps & LeDoux, 2005)....

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