Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons

Nakamura, Wataru; Honma, Sato; Shirakawa, Tetsuo; Honma, Ken‐ichi

doi:10.1038/nn843

Cited by 128 publications

(88 citation statements)

References 9 publications

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“…Coronal brain slices of 200 mm thickness were obtained from 2-to 5-day-old pups using a tissue chopper. An SCN slice was placed on a collagen precoated MED and cultured as previously described 32 . Half of the culture medium was exchanged every day for the first several days of culturing and then every second day thereafter.…”

Section: Methodsmentioning

confidence: 99%

Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus

2013

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Cryptochrome (Cry) 1 and Cry2 are regarded as critical components for circadian rhythm generation in mammals. Nevertheless, cultured suprachiasmatic nucleus (SCN) of neonatal Cry double deficient (Cry1 À / À /Cry2 À / À ) mice exhibit circadian rhythms that damp out in several cycles. Here, by combining bioluminescence imaging of Per1-luc and PER2::LUC with multielectrode recording, we show developmental changes in SCN circadian rhythms in Cry1 À / À /Cry2 À / À mice. At the tissue level, circadian rhythms are found in neonatal but not in adult SCN, whereas at the cellular level, rhythms are detected in both SCN. Cellular circadian rhythms are synchronized in neonates, but not in adults, indicating a loss of rhythm synchrony in the course of development. Synchronized circadian rhythms in adult Cry1 À / À / Cry2 À / À SCN are restored by coculture of neonatal, but not of juvenile, SCN. These findings indicate that CRY1 and CRY2 are necessary for the development of intercellular networks that subserve coherent rhythm expression in adult SCN.

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Section: Methodsmentioning

confidence: 99%

Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus

2013

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“…SCN slices were cultured in air at 37°C with 130 l of DMEM (Invitrogen) supplemented with 10 mM Hepes/2.74 mM NaHCO 3 /0.1 mM D-Luciferin K salt and serum-free growth supplements described in ref. 33. Bioluminescence from each SCN slice was measured by a microplate luminometer equipped with PMTs (Lumicycle; Actimetrics) for 1 min at 9-min intervals for 5 successive days.…”

Section: Methodsmentioning

confidence: 99%

Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity

Inagaki

Honma

Ono

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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248

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The pattern of circadian behavioral rhythms is photoperioddependent, highlighted by the conservation of a phase relation between the behavioral rhythm and photoperiod. A model of two separate, but mutually coupled, circadian oscillators has been proposed to explain photoperiodic responses of behavioral rhythm in nocturnal rodents: an evening oscillator, which drives the activity onset and entrains to dusk, and a morning oscillator, which drives the end of activity and entrains to dawn. Continuous measurement of circadian rhythms in clock gene Per1 expression by a bioluminescence reporter enabled us to identify the separate oscillating cell groups in the mouse suprachiasmatic nucleus (SCN), which composed circadian oscillations of different phases and responded to photoperiods differentially. The circadian oscillation in the posterior SCN was phase-locked to the end of activity under three photoperiods examined. On the other hand, the oscillation in the anterior SCN was phase-locked to the onset of activity but showed a bimodal pattern under a long photoperiod [light-dark cycle (LD)18:6]. The bimodality in the anterior SCN reflected two circadian oscillatory cell groups of early and late phases. The anterior oscillation was unimodal under intermediate (LD12:12) and short (LD6:18) photoperiods, which was always phase-lagged behind the posterior oscillation when the late phase in LD18:6 was taken. The phase difference was largest in LD18:6 and smallest in LD6:18. These findings indicate that three oscillating cell groups in the SCN constitute regionally specific circadian oscillations, and at least two of them are involved in photoperiodic response of behavioral rhythm.bioluminescence reporter ͉ circadian rhythm ͉ clock gene ͉ photoperiod ͉ behavioral rhythm A daptation to seasonal changes in environment is critical to the survival of many organisms. Photoperiodic time measurement by the circadian clock is one of the strategies by which they conserve the phase relation between behavioral events such as the activity onset and dawn or dusk (1). A dramatic change induced by photoperiod is in the length of an activity band, the duration of activity in behavioral rhythms. Nocturnal rodents such as rats and mice exhibit compressed activity bands in long photoperiods and decompressed bands in short photoperiods. A long-standing hypothesis for the photoperiodic time measurement assumes two separate, but mutually coupled, circadian oscillators that drive the activity onset and end of activity, respectively, and respond to dawn and dusk differentially. Therefore, their phase-relationship encodes day lengths and changes the length of an activity band (1).The circadian clock in mammals is located in the suprachiasmatic nucleus (SCN) of the hypothalamus; it entrains to a light-dark cycle (LD) and determines the phases of overt circadian rhythms in behavior and physiology (2). Over the last decade, our understanding of the circadian clock in the SCN has advanced tremendously (3-5). The SCN consists of a number of oscillating cel...

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“…90) Displays mania-like behavior, including Shows normal spontaneous firing rhythms of SCN hyperactivity, decreased sleep, lowered neurons, suggesting that loss of circadian rhythmicity depression-like behavior, and lower may be due to uncoupling of oscillators. 91) anxiety. 94) CLOCK KO Knockout mutation.…”

Section: Possible Crosstalk Between the Circadian Clock And Cellular mentioning

confidence: 99%

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

Uchida

Hirayama

Nishina

2010

Biological & Pharmaceutical Bulletin

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INTRODUCTIONFrom bacteria to humans, almost all organisms can adapt the timing of their physiology to the cyclic changes of their environment, thanks to a naturally-selected intrinsic timekeeping system called the circadian clock. 1) The circadian clock enhances the physiological efficiency and survival of an organism by organizing its behavior and body functions. 2,3) During the circadian day, the organism's physiology is given over to catabolic processes, whereas the anabolic functions of growth, repair and consolidation occur at night. To achieve this schedule in mammals, the circadian clock regulates a number of physiological functions, including sleep and wakefulness, food intake, body temperature, cardiovascular and renal activity, hormone production, hepatic metabolism and immune responses. 4,5) Accordingly, disruption of the circadian clock in humans has been linked to profound effects on health, including insomnia, stomach ailments, depression and cancer. 4,5) In most organisms, the molecular mechanisms underlying the establishment and maintenance of biological rhythms comprise interconnected transcription-translation feedback loops in which some clock factors repress their own transcription once they have attained critical levels. 2,3) These oscillators have the property of being endogenous and cellautonomous systems that maintain their rhythm in the absence of external time cues. 6) Both vertebrates and invertebrates have circadian oscillators scattered throughout their bodies. 7,8) In mammals, the circadian system is composed of both central and peripheral oscillators. 7) The mammalian central clock is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus of the brain. 9) This central clock acts as a coordinator and provides time signals via both neural and humoral routes that entrain independent peripheral clocks. Dysfunction of the central clock does not inactivate the peripheral clocks but instead causes individual peripheral oscillators to become temporally uncoupled. [10][11][12] To guarantee that an organism's behavior remains tied to the rhythms of its environment, the circadian clock must be able to reset itself in response to environmental cues. 9,13,14) The main environmental stimulus for organisms is light, which is provided in day-night cycles. Mammals have no photoreceptors in peripheral tissues, 15) so that the effect of light on peripheral clocks is indirect. 13) For the mammalian clock, the SCN integrates photic cues from the retina and uses neural and humoral signals to transmit this information to peripheral clocks, synchronizing them. [16][17][18] This communication between the central and peripheral clocks results in the seamless regulation of fundamental physiological functions. 4,8) Interestingly, peripheral clocks can also respond directly to SCN-independent signals such as feeding and temperature change. 19,20) However, the physiological role of SCN-independent responses of peripheral clocks is not yet fully understood. A recent study has reported that ...

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Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons

Cited by 128 publications

References 9 publications

Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus

Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus

Separate oscillating cell groups in mouse suprachiasmatic nucleus couple photoperiodically to the onset and end of daily activity

A Common Origin: Signaling Similarities in the Regulation of the Circadian Clock and DNA Damage Responses

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