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Annual Review of Neuroscience 2012The circadian system of mammals is composed of a hierarchy of oscillators that function at the cellular, tissue, and systems levels. A common molecular mechanism... (Review)
Review
The circadian system of mammals is composed of a hierarchy of oscillators that function at the cellular, tissue, and systems levels. A common molecular mechanism underlies the cell-autonomous circadian oscillator throughout the body, yet this clock system is adapted to different functional contexts. In the central suprachiasmatic nucleus (SCN) of the hypothalamus, a coupled population of neuronal circadian oscillators acts as a master pacemaker for the organism to drive rhythms in activity and rest, feeding, body temperature, and hormones. Coupling within the SCN network confers robustness to the SCN pacemaker, which in turn provides stability to the overall temporal architecture of the organism. Throughout the majority of the cells in the body, cell-autonomous circadian clocks are intimately enmeshed within metabolic pathways. Thus, an emerging view for the adaptive significance of circadian clocks is their fundamental role in orchestrating metabolism.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Feeding Behavior; Mammals; Methamphetamine; Models, Biological; Neural Pathways; Neurons; Signal Transduction; Suprachiasmatic Nucleus
PubMed: 22483041
DOI: 10.1146/annurev-neuro-060909-153128 -
Annual Review of Physiology 2010The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals. Individual SCN neurons in dispersed culture can generate independent circadian... (Review)
Review
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.
Topics: Animals; Biological Clocks; Circadian Rhythm; Drosophila; Hormones; Humans; Light; Nerve Net; Neurons; Photoperiod; Suprachiasmatic Nucleus
PubMed: 20148688
DOI: 10.1146/annurev-physiol-021909-135919 -
Frontiers in Neuroendocrinology Jan 2014Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can... (Review)
Review
Virtually every eukaryotic cell has an endogenous circadian clock and a biological sex. These cell-based clocks have been conceptualized as oscillators whose phase can be reset by internal signals such as hormones, and external cues such as light. The present review highlights the inter-relationship between circadian clocks and sex differences. In mammals, the suprachiasmatic nucleus (SCN) serves as a master clock synchronizing the phase of clocks throughout the body. Gonadal steroid receptors are expressed in almost every site that receives direct SCN input. Here we review sex differences in the circadian timing system in the hypothalamic-pituitary-gonadal axis (HPG), the hypothalamic-adrenal-pituitary (HPA) axis, and sleep-arousal systems. We also point to ways in which disruption of circadian rhythms within these systems differs in the sexes and is associated with dysfunction and disease. Understanding sex differentiated circadian timing systems can lead to improved treatment strategies for these conditions.
Topics: Animals; Circadian Rhythm; Humans; Hypothalamo-Hypophyseal System; Sex Characteristics; Sleep; Suprachiasmatic Nucleus
PubMed: 24287074
DOI: 10.1016/j.yfrne.2013.11.003 -
Neuron Oct 2021The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of...
The suprachiasmatic nucleus (SCN) is the master circadian pacemaker in mammals and is entrained by environmental light. However, the molecular basis of the response of the SCN to light is not fully understood. We used RNA/chromatin immunoprecipitation/single-nucleus sequencing with circadian behavioral assays to identify mouse SCN cell types and explore their responses to light. We identified three peptidergic cell types that responded to light in the SCN: arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), and cholecystokinin (CCK). In each cell type, light-responsive subgroups were enriched for expression of neuronal Per-Arnt-Sim (PAS) domain protein 4 (NPAS4) target genes. Further, mice lacking Npas4 had a longer circadian period under constant conditions, a damped phase response curve to light, and reduced light-induced gene expression in the SCN. Our data indicate that NPAS4 is necessary for normal transcriptional responses to light in the SCN and critical for photic phase-shifting of circadian behavior.
Topics: Animals; Arginine Vasopressin; Basic Helix-Loop-Helix Transcription Factors; Cholecystokinin; Chromatin Immunoprecipitation; Circadian Rhythm; Gene Expression Profiling; Light; Mice; Mice, Knockout; Neurons; Sequence Analysis, RNA; Single-Cell Analysis; Suprachiasmatic Nucleus; Vasoactive Intestinal Peptide
PubMed: 34416169
DOI: 10.1016/j.neuron.2021.07.026 -
Ugeskrift For Laeger Sep 2018
Topics: Circadian Clocks; Circadian Rhythm; Humans; Suprachiasmatic Nucleus
PubMed: 30187849
DOI: No ID Found -
Current Biology : CB Aug 2018Like it or not, your two suprachiasmatic nuclei (SCN) govern your life: from when you wake up and fall asleep, to when you feel hungry or can best concentrate. Each is...
Like it or not, your two suprachiasmatic nuclei (SCN) govern your life: from when you wake up and fall asleep, to when you feel hungry or can best concentrate. Each is composed of approximately 10,000 tightly interconnected neurons, and the pair sit astride the mid-line third ventricle of the hypothalamus, immediately dorsal to the optic chiasm (Figure 1A). Together, they constitute the master circadian clock of the mammalian brain. They generate an internal representation of solar time that is conveyed to every cell in our body and in this way they co-ordinate the daily cycles of physiology and behaviour that adapt us to the twenty-four hour world. The temporary discomfort associated with jetlag is a reminder of the importance of this daily programme, but there is growing recognition that its chronic disruption carries a cost for health of far greater scale. In this primer, we shall briefly review the historical identification of the SCN as the master circadian clock, and then discuss it on three different levels: the cell-autonomous SCN, the SCN as a cellular network and, finally, the SCN as circadian orchestrator. We shall focus on the intrinsic electrical and transcriptional properties of the SCN and how these properties are thought to form an input to, and an output from, its intrinsic cellular clockwork. Second, we shall describe the anatomical arrangement of the SCN, how its sub-regions are delineated by different neuropeptides, and how SCN neurons communicate with each other via these neuropeptides and the neurotransmitter γ-aminobutyric acid (GABA). Finally, we shall discuss how the SCN functions as a circadian oscillator that dictates behaviour, and how intersectional genetic approaches are being used to try to unravel the specific contributions to pacemaking of specific SCN cell populations.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Humans; Suprachiasmatic Nucleus
PubMed: 30086310
DOI: 10.1016/j.cub.2018.06.052 -
Purinergic Signalling Mar 2023Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the... (Review)
Review
Extracellular ATP is a potent signaling molecule released from various cells throughout the body and is intimately involved in the pathophysiological functions of the nervous system and immune system by activating P2 purinergic receptors. Recent increasingly studies showed that extracellular ATP exhibits circadian oscillation with an approximately 24-h periodicity, which participates in regulatory pathways of central oscillator suprachiasmatic nucleus and peripheral oscillator bladder, respectively. Oscillators modulate the protein expression of ATP release channels and ectonucleotidase activity through clock genes; indeed, real-time alterations of ATP release and degradation determine outcomes of temporal character on extracellular ATP rhythm. The regulatory pathways on extracellular ATP rhythm are different in central and peripheral systems. In this review, we summarize the circadian rhythm of extracellular ATP and discuss several circadian regulatory pathways in different organs via ATP release and degradation, to provide a new understanding for purinergic signaling in the regulatory mechanism of circadian rhythm and a potential target to research the circadian regulation of extracellular ATP in other circadian oscillators.
Topics: Circadian Rhythm; Suprachiasmatic Nucleus; Adenosine Triphosphate
PubMed: 35939197
DOI: 10.1007/s11302-022-09881-3 -
Current Biology : CB Oct 2002
Topics: Animals; Circadian Rhythm; Neurons; Rats; Suprachiasmatic Nucleus; Time Factors
PubMed: 12361580
DOI: 10.1016/s0960-9822(02)01155-7 -
International Journal of Environmental... Dec 2022The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and... (Review)
Review
The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and responds to several inputs, including food intake, light/dark cycle, sleep/wake cycle, and physical activity. The circadian timing system comprises a central clock located in the suprachiasmatic nucleus (SCN) and tissue-specific clocks in peripheral tissues. Several studies show that the desynchronization of central and peripheral clocks is associated with an increased incidence of insulin resistance (IR) and related diseases. In this review, we discuss the current knowledge of molecular and cellular mechanisms underlying the impact of circadian clock dysregulation on insulin action. We focus our attention on two possible mediators of this interaction: the phosphatases belonging to the pleckstrin homology leucine-rich repeat protein phosphatase family (PHLPP) family and the deacetylase Sirtuin1. We believe that literature data, herein summarized, suggest that a thorough change of life habits, with the return to synchronized food intake, physical activity, and rest, would doubtless halt the vicious cycle linking IR to dysregulated circadian rhythms. However, since such a comprehensive change may be incompatible with the demand of modern society, clarifying the pathways involved may, nonetheless, contribute to the identification of therapeutic targets that may be exploited to cure or prevent IR-related diseases.
Topics: Humans; Circadian Clocks; Insulin Resistance; Circadian Rhythm; Suprachiasmatic Nucleus; Photoperiod
PubMed: 36612350
DOI: 10.3390/ijerph20010029 -
Neural Plasticity 2018Seasonal changes in light exposure have profound effects on behavioral and physiological functions in many species, including effects on mood and cognitive function in... (Review)
Review
Seasonal changes in light exposure have profound effects on behavioral and physiological functions in many species, including effects on mood and cognitive function in humans. The mammalian brain's master circadian clock, the suprachiasmatic nucleus (SCN), transmits information about external light conditions to other brain regions, including some implicated in mood and cognition. Although the detailed mechanisms are not yet known, the SCN undergoes highly plastic changes at the cellular and network levels under different light conditions. We therefore propose that the SCN may be an essential mediator of the effects of seasonal changes of day length on mental health. In this review, we explore various forms of neuroplasticity that occur in the SCN and other brain regions to facilitate seasonal adaptation, particularly altered phase distribution of cellular circadian oscillators in the SCN and changes in hypothalamic neurotransmitter expression.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Humans; Nerve Net; Neuronal Plasticity; Photoperiod; Seasons; Suprachiasmatic Nucleus
PubMed: 29681926
DOI: 10.1155/2018/5147585