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Advances in Genetics 2013The mitogen-activated protein kinase (MAPK) family of genes aids cells in sensing both extracellular and intracellular stimuli, and emerging data indicate that MAPKs... (Review)
Review
The mitogen-activated protein kinase (MAPK) family of genes aids cells in sensing both extracellular and intracellular stimuli, and emerging data indicate that MAPKs have fundamental, yet diverse, roles in the circadian biological clock. In the mammalian suprachiasmatic nucleus (SCN), MAPK pathways can function as inputs allowing the endogenous clock to entrain to 24h environmental cycles. MAPKs can also interact physically and/or genetically with components of the molecular circadian oscillator, implying that MAPKs can affect the cycling of the clock. Finally, circadian rhythms in MAPK pathway activation exist in many different tissue types and in model organisms, providing a mechanism to coordinately control the expression tissue-specific target genes at the proper time of day. As such, it should probably not come as a surprise that MAPK signaling pathways and circadian clocks affect similar biological processes and defects in either pathway lead to many of the same types of human diseases, highlighting the need to better define the mechanisms that link these two fundamental pathways together.
Topics: Animals; Circadian Clocks; Humans; MAP Kinase Signaling System; Suprachiasmatic Nucleus
PubMed: 24262095
DOI: 10.1016/B978-0-12-407703-4.00001-3 -
International Journal of Molecular... Apr 2019Why do we experience the ailments of jetlag when we travel across time zones? Why is working night-shifts so detrimental to our health? In other words, why can't we... (Review)
Review
Why do we experience the ailments of jetlag when we travel across time zones? Why is working night-shifts so detrimental to our health? In other words, why can't we readily choose and stick to non-24 h rhythms? Actually, our daily behavior and physiology do not simply result from the passive reaction of our organism to the external cycle of days and nights. Instead, an internal clock drives the variations in our bodily functions with a period close to 24 h, which is supposed to enhance fitness to regular and predictable changes of our natural environment. This so-called circadian clock relies on a molecular mechanism that generates rhythmicity in virtually all of our cells. However, the robustness of the circadian clock and its resilience to phase shifts emerge from the interaction between cell-autonomous oscillators within the suprachiasmatic nuclei (SCN) of the hypothalamus. Thus, managing jetlag and other circadian disorders will undoubtedly require extensive knowledge of the functional organization of SCN cell networks. Here, we review the molecular and cellular principles of circadian timekeeping, and their integration in the multi-cellular complexity of the SCN. We propose that new, in vivo imaging techniques now enable to address these questions directly in freely moving animals.
Topics: Animals; Cells; Circadian Rhythm; Signal Transduction; Suprachiasmatic Nucleus; Temperature
PubMed: 31027315
DOI: 10.3390/ijms20082052 -
Trends in Genetics : TIG Oct 2017The circadian clock directs many aspects of metabolism, to separate in time opposing metabolic pathways and optimize metabolic efficiency. The master circadian clock of... (Review)
Review
The circadian clock directs many aspects of metabolism, to separate in time opposing metabolic pathways and optimize metabolic efficiency. The master circadian clock of the suprachiasmatic nucleus synchronizes to light, while environmental cues such as temperature and feeding, out of phase with the light schedule, may synchronize peripheral clocks. This misalignment of central and peripheral clocks may be involved in the development of disease and the acceleration of aging, possibly in a gender-specific manner. Here we discuss the interplay between the circadian clock and metabolism, the importance of the microbiome, and how they relate to aging.
Topics: Aging; Animals; Circadian Clocks; Humans; Microbiota; Suprachiasmatic Nucleus
PubMed: 28844699
DOI: 10.1016/j.tig.2017.07.010 -
Progress in Brain Research 1996
Review
Topics: Excitatory Amino Acids; Glutamic Acid; Membrane Potentials; Suprachiasmatic Nucleus; Synaptic Transmission
PubMed: 8990906
DOI: 10.1016/s0079-6123(08)60399-4 -
TRESK is a key regulator of nocturnal suprachiasmatic nucleus dynamics and light adaptive responses.Nature Communications Sep 2020The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to...
The suprachiasmatic nucleus (SCN) is a complex structure dependent upon multiple mechanisms to ensure rhythmic electrical activity that varies between day and night, to determine circadian adaptation and behaviours. SCN neurons are exposed to glutamate from multiple sources including from the retino-hypothalamic tract and from astrocytes. However, the mechanism preventing inappropriate post-synaptic glutamatergic effects is unexplored and unknown. Unexpectedly we discovered that TRESK, a calcium regulated two-pore potassium channel, plays a crucial role in this system. We propose that glutamate activates TRESK through NMDA and AMPA mediated calcium influx and calcineurin activation to then oppose further membrane depolarisation and rising intracellular calcium. Hence, in the absence of TRESK, glutamatergic activity is unregulated leading to membrane depolarisation, increased nocturnal SCN firing, inverted basal calcium levels and impaired sensitivity in light induced phase delays. Our data reveals TRESK plays an essential part in SCN regulatory mechanisms and light induced adaptive behaviours.
Topics: Adaptation, Ocular; Animals; Behavior, Animal; Calcium; Darkness; Glutamic Acid; Light; Membrane Potentials; Mice, Inbred C57BL; Potassium Channels; Signal Transduction; Suprachiasmatic Nucleus
PubMed: 32929069
DOI: 10.1038/s41467-020-17978-9 -
The Journal of Neuroscience : the... Nov 2014The transcriptional architecture of intracellular circadian clocks is similar across phyla, but in mammals interneuronal mechanisms confer a higher level of circadian... (Review)
Review
The transcriptional architecture of intracellular circadian clocks is similar across phyla, but in mammals interneuronal mechanisms confer a higher level of circadian integration. The suprachiasmatic nucleus (SCN) is a unique model to study these mechanisms, as it operates as a ∼24 h clock not only in the living animal, but also when isolated in culture. This "clock in a dish" can be used to address fundamental questions, such as how intraneuronal mechanisms are translated by SCN neurons into circuit-level emergent properties and how the circuit decodes, and responds to, light input. This review addresses recent developments in understanding the relationship between electrical activity, [Ca(2+)]i, and intracellular clocks. Furthermore, optogenetic and chemogenetic approaches to investigate the distinct roles of neurons and glial cells in circuit encoding of circadian time will be discussed, as well as the epigenetic and circuit-level mechanisms that enable the SCN to translate light input into coherent daily rhythms.
Topics: Animals; Circadian Clocks; Circadian Rhythm; Circadian Rhythm Signaling Peptides and Proteins; Gene Expression; Mammals; Neuroglia; Neurons; Photoperiod; Suprachiasmatic Nucleus; Time
PubMed: 25392488
DOI: 10.1523/JNEUROSCI.3233-14.2014 -
Cold Spring Harbor Symposia on... 2007Suprachiasmatic nucleus (SCN) neuroanatomy has been a subject of intense interest since the discovery of the SCN's function as a brain clock and subsequent studies... (Review)
Review
Suprachiasmatic nucleus (SCN) neuroanatomy has been a subject of intense interest since the discovery of the SCN's function as a brain clock and subsequent studies revealing substantial heterogeneity of its component neurons. Understanding the network organization of the SCN has become increasingly relevant in the context of studies showing that its functional circuitry, evident in the spatial and temporal expression of clock genes, can be reorganized by inputs from the internal and external environment. Although multiple mechanisms have been proposed for coupling among SCN neurons, relatively little is known of the precise pattern of SCN circuitry. To explore SCN networks, we examine responses of the SCN to various photic conditions, using in vivo and in vitro studies with associated mathematical modeling to study spatiotemporal changes in SCN activity. We find an orderly and reproducible spatiotemporal pattern of oscillatory gene expression in the SCN, which requires the presence of the ventrolateral core region. Without the SCN core region, behavioral rhythmicity is abolished in vivo, whereas low-amplitude rhythmicity can be detected in SCN slices in vitro, but with loss of normal topographic organization. These studies reveal SCN circuit properties required to signal daily time.
Topics: Animals; Circadian Rhythm; Humans; Mice; Models, Anatomic; Models, Neurological; Nerve Net; Neuropeptides; Photoperiod; Suprachiasmatic Nucleus
PubMed: 18419312
DOI: 10.1101/sqb.2007.72.037 -
Brain Research Mar 2010In this study, two circadian related centers, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) were evaluated in respect to their...
In this study, two circadian related centers, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) were evaluated in respect to their cytoarchitecture, retinal afferents and chemical content of major cells and axon terminals in the rock cavy (Kerodon rupestris), a Brazilian rodent species. The rock cavy SCN is innervated in its ventral portion by terminals from the predominantly contralateral retina. It also contains vasopressin, vasoactive intestinal polypeptide and glutamic acid decarboxilase immunoreactive cell bodies and neuropeptide Y, serotonin and enkephalin immunopositive fibers and terminals and is marked by intense glial fibrillary acidic protein immunoreactivity. The IGL receives a predominantly contralateral retinal projection, contains neuropeptide Y and nitric oxide synthase-producing neurons and enkephalin immunopositive terminals and is characterized by dense GFAP immunoreactivity. This is the first report examining the neural circadian system in a crepuscular rodent species for which circadian properties have been described. The results are discussed comparing with what has been described for other species and in the context of the functional significance of these centers.
Topics: Animals; Circadian Rhythm; Geniculate Bodies; Immunohistochemistry; Male; Neurons; Photomicrography; Retina; Rodentia; Suprachiasmatic Nucleus; Visual Pathways
PubMed: 20096673
DOI: 10.1016/j.brainres.2010.01.034 -
Methods in Enzymology 2015Circadian clocks control daily rhythms in physiology and behavior across all phyla. These rhythms are intrinsic to individual cells that must synchronize to their... (Review)
Review
Circadian clocks control daily rhythms in physiology and behavior across all phyla. These rhythms are intrinsic to individual cells that must synchronize to their environment and to each other to anticipate daily events. Recent advances in recording from large numbers of cells for many circadian cycles have enabled researchers to begin to evaluate the mechanisms and consequences of intercellular circadian synchrony. Consequently, methods have been adapted to estimate the period, phase, and amplitude of individual circadian cells and calculate synchrony between cells. Stable synchronization requires that the cells share a common period. As a result, synchronized cells maintain constant phase relationships to each (e.g., with cell 1 peaking an hour before cell 2 each cycle). This chapter reviews how circadian rhythms are recorded from single mammalian cells and details methods for measuring their period and phase synchrony. These methods have been useful, for example, in showing that specific neuropeptides are essential to maintain synchrony among circadian cells.
Topics: Animals; Circadian Rhythm; Single-Cell Analysis; Suprachiasmatic Nucleus
PubMed: 25707270
DOI: 10.1016/bs.mie.2014.10.042 -
Experimental Neurology May 2013The suprachiasmatic nucleus (SCN), site of the primary clock in the circadian rhythm system, has three major afferent connections. The most important consists of a... (Review)
Review
The suprachiasmatic nucleus (SCN), site of the primary clock in the circadian rhythm system, has three major afferent connections. The most important consists of a retinohypothalamic projection through which photic information, received by classical rod/cone photoreceptors and intrinsically photoreceptive retinal ganglion cells, gains access to the clock. This information influences phase and period of circadian rhythms. The two other robust afferent projections are the median raphe serotonergic pathway and the geniculohypothalamic (GHT), NPY-containing pathway from the thalamic intergeniculate leaflet (IGL). Beyond this simple framework, the number of anatomical routes that could theoretically be involved in rhythm regulation is enormous, with the SCN projecting to 15 regions and being directly innervated by about 35. If multisynaptic afferents to the SCN are included, the number expands to approximately brain 85 areas providing input to the SCN. The IGL, a known contributor to circadian rhythm regulation, has a still greater level of complexity. This nucleus connects abundantly throughout the brain (to approximately 100 regions) by pathways that are largely bilateral and reciprocal. Few of these sites have been evaluated for their contributions to circadian rhythm regulation, although most have a theoretical possibility of doing so via the GHT. The anatomy of IGL connections suggests that one of its functions may be regulation of eye movements during sleep. Together, neural circuits of the SCN and IGL are complex and interconnected. As yet, few have been tested with respect to their involvement in rhythm regulation.
Topics: Animals; Circadian Rhythm; Geniculate Bodies; Humans; Hypothalamus; Neural Pathways; Photoperiod; Photoreceptor Cells; Suprachiasmatic Nucleus
PubMed: 22766204
DOI: 10.1016/j.expneurol.2012.06.026