Clock controls circadian period in isolated suprachiasmatic nucleus neurons (original) (raw)
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Genetics of Circadian Rhythms in Mammalian Model Organisms
Genetics of Circadian Rhythms, 2011
The mammalian circadian system is a complex hierarchical temporal network which is organized around an ensemble of uniquely coupled cells comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus. This central pacemaker is entrained each day by the environmental light/dark cycle and transmits synchronizing cues to cell-autonomous oscillators in tissues throughout the body. Within cells of the central pacemaker and the peripheral tissues, the underlying molecular mechanism by which oscillations in gene expression occur involves interconnected feedback loops of transcription and translation. Over the past 10 years we have learned much regarding the genetics of this system, including how it is particularly resilient when challenged by single-gene mutations, how accessory transcriptional loops enhance the robustness of oscillations, how epigenetic mechanisms contribute to the control of circadian gene expression, and how, from coupled neuronal networks, emergent clock properties arise. Here we will explore the genetics of the mammalian circadian system from cell-autonomous molecular oscillations, to interactions among central and peripheral oscillators and ultimately, to the daily rhythms of behavior observed in the animal.
The mammalian circadian clock shop
Seminars in Cell & Developmental Biology, 2001
In mammals, a master circadian pacemaker driving daily rhythms in behavior and physiology resides in the suprachiasmatic nucleus (SCN). The SCN contains multiple circadian oscillators that synchronize to environmental cycles and to each other in vivo. Rhythm production, an intracellular event, depends on more than eight identified genes. The period of the rhythms within the SCN also depends upon intercellular communication. Many other tissues also retain the ability to generate near 24-h periodicities although their place in the organization of circadian timing is still unclear. This paper focuses on the tissue-, cellular-and molecularlevel events that generate and entrain circadian rhythms in behavior in mammals and emphasizes the apparent differences between the SCN and peripheral oscillators.
Molecular components of the mammalian circadian clock
Human Molecular Genetics, 2006
Circadian rhythms are 24-h oscillations in behavior and physiology, which are internally generated and function to anticipate the environmental changes associated with the solar day. A conserved transcriptional -translational autoregulatory loop generates molecular oscillations of 'clock genes' at the cellular level. In mammals, the circadian system is organized in a hierarchical manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN) regulates downstream oscillators in peripheral tissues. Recent findings have revealed that the clock is cell-autonomous and self-sustained not only in a central pacemaker, the SCN, but also in peripheral tissues and in dissociated cultured cells. It is becoming evident that specific contribution of each clock component and interactions among the components vary in a tissue-specific manner. Here, we review the general mechanisms of the circadian clockwork, describe recent findings that elucidate tissue-specific expression patterns of the clock genes and address the importance of circadian regulation in peripheral tissues for an organism's overall well-being.
The Journal of Physiological Sciences
The circadian nature of physiology and behavior is regulated by a circadian clock that generates intrinsic rhythms with a periodicity of approximately 24 h. The mammalian circadian system is composed of a hierarchical multi-oscillator structure, with the central clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus regulating the peripheral clocks found throughout the body. In the past two decades, key clock genes have been discovered in mammals and shown to be interlocked in transcriptional and translational feedback loops. At the cellular level, each cell is governed by its own independent clock; and yet, these cellular circadian clocks in the SCN form regional oscillators that are further coupled to one another to generate a single rhythm for the tissue. The oscillatory coupling within and between the regional oscillators appears to be critical for the extraordinary stability and the wide range of adaptability of the circadian clock, the mechanism of which is now being elucidated with newly advanced molecular tools.
Cell, 2001
observe how they interact . Confrontation analysis has been applied to study the physiology behind circadian behavior in the form of SCN tissue transplantation, using the tau mutation, to show that the circadian period of activity rhythms always reflects the genotype of the SCN (Ralph et al., 1990). Furthermore, when SCN tissue of a contrasting tau genotype was introduced into hamsters with disrupted SCN function, behavior was organized into two concurrent but distinct Summary circadian rhythmic components that did not interact (Vogelbaum and Menaker, 1992; Hurd et al., 1995). An intri-The Clock mutation lengthens periodicity and reduces amplitude of circadian rhythms in mice. The effects of cate network of connections and feedback underlies the generation and expression of circadian locomotor Clock are cell intrinsic and can be observed at the level of single neurons in the suprachiasmatic nucleus.