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1
Grechenko, T. N., A. N. Kharitonov, and A. V. Zhegallo. "Evolutionary paths of electric oscillators." Experimental Psychology (Russia) 8, no. 2 (2015): 105–18. http://dx.doi.org/10.17759/exppsy.2015080208.
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The endogenous electrical signals play an important role in information processes occurring in living systems. They are found in living beings of different evolutionary levels from prokaryotes to multicellular eukaryotes. We hypothesized that the presence and variety of endogenous oscillators in individual organisms are connected with the way they survive, i.e. totally dependent on the community or partially independent of it. To test the hypothesis, we recorded electrical activity from individual cells and their communities in experiments with the earliest evolutionary beings, prokaryotes: cyanobacteria Oscillatoria terebriformis, Geitlerinema sp. and Halothece sp., the unicellular eukaryotes: yeast Saccharomyces cerevisiae and ciliates Paramecium caudatum, as well as from shellfish Helix pomatia and H. lucorum. The experimental results suggest that the variety of oscillators in the individual, the properties and functions that they perform, may provide a key to understanding the individual/social organization of living systems.
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Oprisan, Sorinel A. "All Phase Resetting Curves Are Bimodal, but Some Are More Bimodal Than Others." ISRN Computational Biology 2013 (December 12, 2013): 1–11. http://dx.doi.org/10.1155/2013/230571.
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Phase resetting curves (PRCs) are phenomenological and quantitative tools that tabulate the transient changes in the firing period of endogenous neural oscillators as a result of external stimuli, for example, presynaptic inputs. A brief current perturbation can produce either a delay (positive phase resetting) or an advance (negative phase resetting) of the subsequent spike, depending on the timing of the stimulus. We showed that any planar neural oscillator has two remarkable points, which we called neutral points, where brief current perturbations produce no phase resetting and where the PRC flips its sign. Since there are only two neutral points, all PRCs of planar neural oscillators are bimodal. The degree of bimodality of a PRC, that is, the ratio between the amplitudes of the delay and advance lobes of a PRC, can be smoothly adjusted when the bifurcation scenario leading to stable oscillatory behavior combines a saddle node of invariant circle (SNIC) and an Andronov-Hopf bifurcation (HB).
3
Helfrich, Charlotte, and Wolfgang Engelmann. "Evidences for Circadian Rhythmicity in the per° Mutant of Drosophila melanogaster." Zeitschrift für Naturforschung C 42, no. 11-12 (December 1, 1987): 1335–38. http://dx.doi.org/10.1515/znc-1987-11-1231.
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per° Mutants of Drosophila melanogaster which are exposed to light-dark cycles (LD) with different Zeitgeber period (T) have a limited range of entrainment. Entrained flies show a characteristic phase relationship of activity to the LD which depends on the period of the driving cycle as expected by oscillator theory. Both facts are taken as evidence that per° possesses endogenous oscillators and that the per gene product is not concerned with central clock structures but rather might be responsible for the mutual coupling between the individual oscillators in a multioscillatory system controlling locomotor activity.
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Braun, H. A., M. T. Huber, M. Dewald, K. Schäfer, and K. Voigt. "Computer Simulations of Neuronal Signal Transduction: The Role of Nonlinear Dynamics and Noise." International Journal of Bifurcation and Chaos 08, no. 05 (May 1998): 881–89. http://dx.doi.org/10.1142/s0218127498000681.
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Nonlinear ionic interactions at the nerve cell membrane can account for oscillating membrane potentials and the generation of periodic neuronal impulse activity. In combination with noise, external modulation of the endogenous oscillations allows for continuous transitions between a variety of impulse patterns. Such "noisy oscillators" afford, thereby, an important mechanism of neuronal encoding as is demonstrated here with experimental data from peripheral cold receptors and corresponding computer simulations.
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Isorna, Esther, Nuria de Pedro, Ana I. Valenciano, Ángel L. Alonso-Gómez, and María J. Delgado. "Interplay between the endocrine and circadian systems in fishes." Journal of Endocrinology 232, no. 3 (March 2017): R141—R159. http://dx.doi.org/10.1530/joe-16-0330.
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The circadian system is responsible for the temporal organisation of physiological functions which, in part, involves daily cycles of hormonal activity. In this review, we analyse the interplay between the circadian and endocrine systems in fishes. We first describe the current model of fish circadian system organisation and the basis of the molecular clockwork that enables different tissues to act as internal pacemakers. This system consists of a net of central and peripherally located oscillators and can be synchronised by the light–darkness and feeding–fasting cycles. We then focus on two central neuroendocrine transducers (melatonin and orexin) and three peripheral hormones (leptin, ghrelin and cortisol), which are involved in the synchronisation of the circadian system in mammals and/or energy status signalling. We review the role of each of these as overt rhythms (i.e. outputs of the circadian system) and, for the first time, as key internal temporal messengers that act as inputs for other endogenous oscillators. Based on acute changes in clock gene expression, we describe the currently accepted model of endogenous oscillator entrainment by the light–darkness cycle and propose a new model for non-photic (endocrine) entrainment, highlighting the importance of the bidirectional cross-talking between the endocrine and circadian systems in fishes. The flexibility of the fish circadian system combined with the absence of a master clock makes these vertebrates a very attractive model for studying communication among oscillators to drive functionally coordinated outputs.
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O'Brien, GM. "Seasonal reproduction in flying foxes, reviewed in the context of other tropical mammals." Reproduction, Fertility and Development 5, no. 5 (1993): 499. http://dx.doi.org/10.1071/rd9930499.
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Megachiroptera inhabit the Old World tropics and most are seasonal breeders having defined times of testis growth, mating and parturition. In Pteropus scapulatus, the little red flying fox, the robust rhythm of testis cycles is resistant to modification by photoperiod. P. poliocephalus, the greyheaded flying fox, can be manipulated by photoperiod but responds slowly and incompletely. Most mammals live in the tropics, many in seasonally harsh climates, and many breed seasonally. However, few long-lived tropical mammals have been investigated for photoperiodic entrainment of annual reproductive cycles, and only animals from the edge of the tropics have responded. Thus, in long-lived tropical mammals, factors that regulate seasonal breeding have not yet been identified. Endogenous oscillators may generate circannual rhythms centrally. Downstream pathways (reproduction, metabolism, antlers, etc.) may derive their rhythm directly from the oscillator or may be modified by environmental cues. Plasticity of the circannual oscillator resolves confusion from previous contrasts between circannual rhythms and environmentally cued patterns. Plasticity may continue throughout life (species responsive to zeitgebers), but the oscillator may be 'set' in utero in some tropical species. Feedback effects from temperature, nutrition, hormones, etc. can be readily tested in this model of an oscillator generating an endogenous circannual rhythm.
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LoFaro, Thomas, Nancy Kopell, Eve Marder, and Scott L. Hooper. "Subharmonic Coordination in Networks of Neurons with Slow Conductances." Neural Computation 6, no. 1 (January 1994): 69–84. http://dx.doi.org/10.1162/neco.1994.6.1.69.
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We study the properties of a network consisting of two model neurons that are coupled by reciprocal inhibition. The study was motivated by data from a pair of cells in the crustacean stomatogastric ganglion. One of the model neurons is an endogenous burster; the other is excitable but not bursting in the absence of phasic input. We show that the presence of a hyperpolarization activated inward current (ih) in the excitable neuron allows these neurons to fire in integer subharmonics, with the excitable cell firing once for every N ≥ 1 bursts of the oscillator. The value of N depends on the amount of hyperpolarizing current injected into the excitable cell as well as the voltage activation curve of ih. For a fast synapse, these parameter changes do not affect the characteristic point in the oscillator cycle at which the excitable cell bursts; for slower synapses, such a relationship is maintained within small windows for each N. The network behavior in the current work contrasts with the activity of a pair of coupled oscillators for which the interaction is through phase differences; in the latter case, subharmonics exist if the uncoupled oscillators have near integral frequency relationships, but the phase relationships of the oscillators in general change significantly with parameters. The mechanism of this paper provides a potential means of coordinating subnetworks acting on different time scales but maintaining fixed relationships between characteristic points of the cycles.
8
Bloch, Guy, Erik D. Herzog, Joel D. Levine, and William J. Schwartz. "Socially synchronized circadian oscillators." Proceedings of the Royal Society B: Biological Sciences 280, no. 1765 (August 22, 2013): 20130035. http://dx.doi.org/10.1098/rspb.2013.0035.
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Daily rhythms of physiology and behaviour are governed by an endogenous timekeeping mechanism (a circadian ‘clock’). The alternation of environmental light and darkness synchronizes (entrains) these rhythms to the natural day–night cycle, and underlying mechanisms have been investigated using singly housed animals in the laboratory. But, most species ordinarily would not live out their lives in such seclusion; in their natural habitats, they interact with other individuals, and some live in colonies with highly developed social structures requiring temporal synchronization. Social cues may thus be critical to the adaptive function of the circadian system, but elucidating their role and the responsible mechanisms has proven elusive. Here, we highlight three model systems that are now being applied to understanding the biology of socially synchronized circadian oscillators: the fruitfly, with its powerful array of molecular genetic tools; the honeybee, with its complex natural society and clear division of labour; and, at a different level of biological organization, the rodent suprachiasmatic nucleus, site of the brain's circadian clock, with its network of mutually coupled single-cell oscillators. Analyses at the ‘group’ level of circadian organization will likely generate a more complex, but ultimately more comprehensive, view of clocks and rhythms and their contribution to fitness in nature.
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Nohales, Maria A. "Spatial Organization and Coordination of the Plant Circadian System." Genes 12, no. 3 (March 20, 2021): 442. http://dx.doi.org/10.3390/genes12030442.
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The plant circadian clock has a pervasive influence on many aspects of plant biology and is proposed to function as a developmental manager. To do so, the circadian oscillator needs to be able to integrate a multiplicity of environmental signals and coordinate an extensive and diverse repertoire of endogenous rhythms accordingly. Recent studies on tissue-specific characteristics and spatial structure of the plant circadian clock suggest that such plasticity may be achieved through the function of distinct oscillators, which sense the environment locally and are then coordinated across the plant through both intercellular coupling and long-distance communication. This review summarizes the current knowledge on tissue-specific features of the clock in plants and their spatial organization and synchronization at the organismal level.
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Mikaberidze, Guram, and Raissa M. D’Souza. "Sandpile cascades on oscillator networks: The BTW model meets Kuramoto." Chaos: An Interdisciplinary Journal of Nonlinear Science 32, no. 5 (May 2022): 053121. http://dx.doi.org/10.1063/5.0095094.
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Cascading failures abound in complex systems and the Bak–Tang–Weisenfeld (BTW) sandpile model provides a theoretical underpinning for their analysis. Yet, it does not account for the possibility of nodes having oscillatory dynamics, such as in power grids and brain networks. Here, we consider a network of Kuramoto oscillators upon which the BTW model is unfolding, enabling us to study how the feedback between the oscillatory and cascading dynamics can lead to new emergent behaviors. We assume that the more out-of-sync a node is with its neighbors, the more vulnerable it is and lower its load-carrying capacity accordingly. Also, when a node topples and sheds load, its oscillatory phase is reset at random. This leads to novel cyclic behavior at an emergent, long timescale. The system spends the bulk of its time in a synchronized state where load builds up with minimal cascades. Yet, eventually, the system reaches a tipping point where a large cascade triggers a “cascade of larger cascades,” which can be classified as a dragon king event. The system then undergoes a short transient back to the synchronous, buildup phase. The coupling between capacity and synchronization gives rise to endogenous cascade seeds in addition to the standard exogenous ones, and we show their respective roles. We establish the phenomena from numerical studies and develop the accompanying mean-field theory to locate the tipping point, calculate the load in the system, determine the frequency of the long-time oscillations, and find the distribution of cascade sizes during the buildup phase.
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Pérez-Cervera, Alberto, and Jaroslav Hlinka. "Perturbations both trigger and delay seizures due to generic properties of slow-fast relaxation oscillators." PLOS Computational Biology 17, no. 3 (March 29, 2021): e1008521. http://dx.doi.org/10.1371/journal.pcbi.1008521.
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The mechanisms underlying the emergence of seizures are one of the most important unresolved issues in epilepsy research. In this paper, we study how perturbations, exogenous or endogenous, may promote or delay seizure emergence. To this aim, due to the increasingly adopted view of epileptic dynamics in terms of slow-fast systems, we perform a theoretical analysis of the phase response of a generic relaxation oscillator. As relaxation oscillators are effectively bistable systems at the fast time scale, it is intuitive that perturbations of the non-seizing state with a suitable direction and amplitude may cause an immediate transition to seizure. By contrast, and perhaps less intuitively, smaller amplitude perturbations have been found to delay the spontaneous seizure initiation. By studying the isochrons of relaxation oscillators, we show that this is a generic phenomenon, with the size of such delay depending on the slow flow component. Therefore, depending on perturbation amplitudes, frequency and timing, a train of perturbations causes an occurrence increase, decrease or complete suppression of seizures. This dependence lends itself to analysis and mechanistic understanding through methods outlined in this paper. We illustrate this methodology by computing the isochrons, phase response curves and the response to perturbations in several epileptic models possessing different slow vector fields. While our theoretical results are applicable to any planar relaxation oscillator, in the motivating context of epilepsy they elucidate mechanisms of triggering and abating seizures, thus suggesting stimulation strategies with effects ranging from mere delaying to full suppression of seizures.
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Herzog, Erik D., and William J. Schwartz. "Invited Review: A neural clockwork for encoding circadian time." Journal of Applied Physiology 92, no. 1 (January 1, 2002): 401–8. http://dx.doi.org/10.1152/japplphysiol.00836.2001.
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10.1152/japplphysiol.00836.2001.—Many daily biological rhythms are governed by an innate timekeeping mechanism or clock. Endogenous, temperature-compensated circadian clocks have been localized to discrete sites within the nervous systems of a number of organisms. In mammals, the master circadian pacemaker is the bilaterally paired suprachiasmatic nucleus (SCN) in the anterior hypothalamus. The SCN is composed of multiple single cell oscillators that must synchronize to each other and the environmental light schedule. Other tissues, including those outside the nervous system, have also been shown to express autonomous circadian periodicities. This review examines 1) how intracellular regulatory molecules function in the oscillatory mechanism and in its entrainment to environmental cycles; 2) how individual SCN cells interact to create an integrated tissue pacemaker with coherent metabolic, electrical, and secretory rhythms; and 3) how such clock outputs are converted into temporal programs for the whole organism.
13
Rowat, P. F., and A. I. Selverston. "Modeling the gastric mill central pattern generator of the lobster with a relaxation-oscillator network." Journal of Neurophysiology 70, no. 3 (September 1, 1993): 1030–53. http://dx.doi.org/10.1152/jn.1993.70.3.1030.
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1. The gastric mill central pattern generator (CPG) controls the chewing movements of teeth in the gastric mill of the lobster. This CPG has been extensively studied, but the precise mechanism underlying pattern generation is not well understood. The goal of this research was to develop a simplified model that captures the principle, biologically significant features of this CPG. We introduce a simplified neuron model that embodies approximations of well-known membrane currents, and is able to reproduce several global characteristics of gastric mill neurons. A network built with these neurons, using graded synaptic transmission and having the synaptic connections of the biological circuit, is sufficient to explain much of the network's behavior. 2. The cell model is a generalization and extension of the Van der Pol relaxation oscillator equations. It is described by two differential equations, one for current conservation and one for slow current activation. The model has a fast current that may, by adjusting one parameter, have a region of negative resistance in its current-voltage (I-V) curve. It also has a slow current with a single gain parameter that can be regarded as the combination of slow inward and outward currents. 3. For suitable values of the fast current parameter and the slow current parameter, the isolated model neuron exhibits several different behaviors: plateau potentials, postinhibitory rebound, postburst hyperpolarization, and endogenous oscillations. When the slow current is separated into inward and outward fractions with separately adjustable gain parameters, the model neuron can fire tonically, be quiescent, or generate spontaneous voltage oscillations with varying amounts of depolarization or hyperpolarization. 4. The most common form of synaptic interaction in the gastric CPG is reciprocal inhibition. A pair of identical model cells, connected with reciprocal inhibition, oscillates in antiphase if either the isolated cells are endogenous oscillators, or they are quiescent without plateau potentials, or they have plateau potentials but the synaptic strengths are below a critical level. If the isolated cells have widely differing frequencies (or would have if the cells were made to oscillate by adjusting the fast currents), reciprocal inhibition entrains the cells to oscillate with the same frequency but with phases that are advanced or retarded relative to the phases seen when the cells have the same frequency. The frequency of the entrained pair of cells lies between the frequencies of the original cells. The relative phases can also be modified by using very unequal synaptic strengths.(ABSTRACT TRUNCATED AT 400 WORDS)
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Aviram, Rona, Vaishnavi Dandavate, Gal Manella, Marina Golik, and Gad Asher. "Ultradian rhythms of AKT phosphorylation and gene expression emerge in the absence of the circadian clock components Per1 and Per2." PLOS Biology 19, no. 12 (December 30, 2021): e3001492. http://dx.doi.org/10.1371/journal.pbio.3001492.
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Rhythmicity of biological processes can be elicited either in response to environmental cycles or driven by endogenous oscillators. In mammals, the circadian clock drives about 24-hour rhythms of multitude metabolic and physiological processes in anticipation to environmental daily oscillations. Also at the intersection of environment and metabolism is the protein kinase—AKT. It conveys extracellular signals, primarily feeding-related signals, to regulate various key cellular functions. Previous studies in mice identified rhythmicity in AKT activation (pAKT) with elevated levels in the fed state. However, it is still unknown whether rhythmic AKT activation can be driven through intrinsic mechanisms. Here, we inspected temporal changes in pAKT levels both in cultured cells and animal models. In cultured cells, pAKT levels showed circadian oscillations similar to those observed in livers of wild-type mice under free-running conditions. Unexpectedly, in livers of Per1,2−/− but not of Bmal1−/− mice we detected ultradian (about 16 hours) oscillations of pAKT levels. Importantly, the liver transcriptome of Per1,2−/− mice also showed ultradian rhythms, corresponding to pAKT rhythmicity and consisting of AKT-related genes and regulators. Overall, our findings reveal ultradian rhythms in liver gene expression and AKT phosphorylation that emerge in the absence of environmental rhythms and Per1,2−/− genes.
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Northcott, S. J., R. N. Gibson, and E. Morgan. "The persistence and modulation of endogenous circatidal rhythmicity in Lipophrys pholis (Teleostei)." Journal of the Marine Biological Association of the United Kingdom 70, no. 4 (November 1990): 815–27. http://dx.doi.org/10.1017/s0025315400059087.
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In constant conditions, freshly-collected Lipophrys pholis show an endogenous circatidal activity rhythm, the initial activity peaks of which are phased to the expected time of high tide. The rhythm usually damps out over a few days but it may re-appear spontaneously or as a result of disturbance caused by handling and transfer to the experimental apparatus. The free-running period is more variable in fish kept in non-tidal conditions for prolonged periods than in those recorded shortly after capture. The non-circatidal periodicity shown by some fish may be the result of stable coupling in antiphase of desynchronised oscillators. There is no semilunar variation of the circatidal rhythm and no influence of the slight diurnal inequality in tidal period upon the rhythm's periodicity, at least at the site studied. The activity rhythm of Lipophrys varies seasonally.
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Hatsopoulos, Nicholas G. "Coupling the Neural and Physical Dynamics in Rhythmic Movements." Neural Computation 8, no. 3 (April 1996): 567–81. http://dx.doi.org/10.1162/neco.1996.8.3.567.
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A pair of coupled oscillators simulating a central pattern generator (CPG) interacting with a pendular limb were numerically integrated. The CPG was represented as a van der Pol oscillator and the pendular limb was modeled as a linearized, hybrid spring-pendulum system. The CPG oscillator drove the pendular limb while the pendular limb modulated the frequency of the CPG. Three results were observed. First, sensory feedback influenced the oscillation frequency of the coupled system. The oscillation frequency was lower in the absence of sensory feedback. Moreover, if the muscle gain was decreased, thereby decreasing the oscillation amplitude of the pendular limb and indirectly lowering the effect of sensory feedback, the oscillation frequency decreased monotonically. This is consistent with experimental data (Williamson and Roberts 1986). Second, the CPG output usually led the angular displacement of the pendular limb by a phase of 90° regardless of the length of the limb. Third, the frequency of the coupled system tuned itself to the resonant frequency of the pendular limb. Also, the frequency of the coupled system was highly resistant to changes in the endogenous frequency of the CPG. The results of these simulations support the view that motor behavior emerges from the interaction of the neural dynamics of the nervous system and the physical dynamics of the periphery.
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Yuasa, Hideo, and Masami Ito. "Generation of Locomotive Patterns and Self-Organization." Journal of Robotics and Mechatronics 4, no. 2 (April 20, 1992): 142–47. http://dx.doi.org/10.20965/jrm.1992.p0142.
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Rhythmic movements of walking, swimming, etc. are controlled by mutually coupled endogenous neural oscillators. These rhythms coordinate one another to generate temporal and spatial moving patterns suitable for their environments and purposes. For example, a cat moves faster, the gait patterns change from “walk” to “trot”, and lastly to “gallop”. This moving pattern generator system can be regarded as one of the autonomous distributed systems which generates global patterns suitable for their environments and purposes. Using the bifurcation theory, it is possible to construct a system that suitably changes patterns discontinuously when a parameter changes continuously. This synthesis approach is applied to make a gait pattern generator system of a quadruped artificially. A gait pattern generator is constructed to couple four oscillators in which each oscillating state is regarded as each limb’s rhythmic motion. It is shown using computer simulations that the proposed system generates and changes patterns suitable for its moving speed; i.e. “walk”, “trot” and “gallop”.
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Della Torre, Sara, Andrea Biserni, Gianpaolo Rando, Giuseppina Monteleone, Paolo Ciana, Barry Komm, and Adriana Maggi. "The Conundrum of Estrogen Receptor Oscillatory Activity in the Search for an Appropriate Hormone Replacement Therapy." Endocrinology 152, no. 6 (April 19, 2011): 2256–65. http://dx.doi.org/10.1210/en.2011-0173.
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By the use of in vivo imaging, we investigated the dynamics of estrogen receptor (ER) activity in intact, ovariectomized, and hormone-replaced estrogen response element-luciferase reporter mice. The study revealed the existence of a long-paced, noncircadian oscillation of ER transcriptional activity. Among the ER-expressing organs, this oscillation was asynchronous and its amplitude and period were tissue dependent. Ovariectomy affected the amplitude but did not suppress ER oscillations, suggesting the presence of tissue endogenous oscillators. Long-term administration of raloxifene, bazedoxifene, combined estrogens alone or with basedoxifene to ovariectomized estrogen response element-luciferase mice showed that each treatment induced a distinct spatiotemporal profile of ER activity, demonstrating that the phasing of ER activity among tissues may be regulated by the chemical nature and the concentration of circulating estrogen. This points to the possibility of a hierarchical organization of the tissue-specific pacemakers. Conceivably, the rhythm of ER transcriptional activity translates locally into the activation of specific gene networks enabling ER to significantly change its physiological activity according to circulating estrogens. In reproductive and nonreproductive organs this hierarchical regulation may provide ER with the signaling plasticity necessary to drive the complex metabolic changes occurring at each female reproductive status. We propose that the tissue-specific oscillatory activity here described is an important component of ER signaling necessary for the full hormone action including the beneficial effects reported for nonreproductive organs. Thus, this mechanism needs to be taken in due consideration to develop novel, more efficacious, and safer hormone replacement therapies.
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Menger, Gus J., Kim Lu, Terry Thomas, Vincent M. Cassone, and David J. Earnest. "Circadian profiling of the transcriptome in immortalized rat SCN cells." Physiological Genomics 21, no. 3 (May 11, 2005): 370–81. http://dx.doi.org/10.1152/physiolgenomics.00224.2004.
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Endogenous oscillations in gene expression are a prevalent feature of the circadian clock in the mammalian suprachiasmatic nucleus (SCN) and similar timekeeping systems in other organisms. To determine whether immortalized cells derived from the rat SCN (SCN2.2) retain these intrinsic rhythm-generating properties, oscillatory behavior of the SCN2.2 transcriptome was analyzed and compared with that found in the rat SCN in vivo using rat U34A Affymetrix GeneChips. In SCN2.2 cells, 116 unique genes and 46 ESTs or genes of unknown function exhibited circadian fluctuations with a 1.5-fold or greater difference in their mRNA abundance for two cycles. Many (35%) of these rhythmically regulated genes in SCN2.2 cells also exhibited circadian profiles of mRNA expression in the rat SCN in vivo. Functional analyses and cartography indicate that a diverse set of cellular pathways are strategically regulated by the circadian clock in SCN2.2 cells and that the largest categories of rhythmic genes are those involved in cellular and systems-level communication or in metabolic processes like cellular respiration, fatty acid recycling, and steroid synthesis. Because many of the same genes or nodes within these functional categories were rhythmically expressed in both SCN2.2 cells and the rat SCN, the circadian regulation of these pathways may be important in modulating input to or output from the SCN clock mechanism. In summary, global expression and circadian regulation of the SCN2.2 transcriptome retain many SCN-like properties, suggesting that genes displaying rhythmic profiles in both experimental models may be integral to their function as both circadian oscillators and pacemakers.
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Mistlberger, Ralph E., and Michael C. Antle. "Entrainment of circadian clocks in mammals by arousal and food." Essays in Biochemistry 49 (June 30, 2011): 119–36. http://dx.doi.org/10.1042/bse0490119.
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Circadian rhythms in mammals are regulated by a system of endogenous circadian oscillators (clock cells) in the brain and in most peripheral organs and tissues. One group of clock cells in the hypothalamic SCN (suprachiasmatic nuclei) functions as a pacemaker for co-ordinating the timing of oscillators elsewhere in the brain and body. This master clock can be reset and entrained by daily LD (light–dark) cycles and thereby also serves to interface internal with external time, ensuring an appropriate alignment of behavioural and physiological rhythms with the solar day. Two features of the mammalian circadian system provide flexibility in circadian programming to exploit temporal regularities of social stimuli or food availability. One feature is the sensitivity of the SCN pacemaker to behavioural arousal stimulated during the usual sleep period, which can reset its phase and modulate its response to LD stimuli. Neural pathways from the brainstem and thalamus mediate these effects by releasing neurochemicals that inhibit retinal inputs to the SCN clock or that alter clock-gene expression in SCN clock cells. A second feature is the sensitivity of circadian oscillators outside of the SCN to stimuli associated with food intake, which enables animals to uncouple rhythms of behaviour and physiology from LD cycles and align these with predictable daily mealtimes. The location of oscillators necessary for food-entrained behavioural rhythms is not yet certain. Persistence of these rhythms in mice with clock-gene mutations that disable the SCN pacemaker suggests diversity in the molecular basis of light- and food-entrainable clocks.
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Lee, Yool, and Jonathan P. Wisor. "Multi-Modal Regulation of Circadian Physiology by Interactive Features of Biological Clocks." Biology 11, no. 1 (December 24, 2021): 21. http://dx.doi.org/10.3390/biology11010021.
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The circadian clock is a fundamental biological timing mechanism that generates nearly 24 h rhythms of physiology and behaviors, including sleep/wake cycles, hormone secretion, and metabolism. Evolutionarily, the endogenous clock is thought to confer living organisms, including humans, with survival benefits by adapting internal rhythms to the day and night cycles of the local environment. Mirroring the evolutionary fitness bestowed by the circadian clock, daily mismatches between the internal body clock and environmental cycles, such as irregular work (e.g., night shift work) and life schedules (e.g., jet lag, mistimed eating), have been recognized to increase the risk of cardiac, metabolic, and neurological diseases. Moreover, increasing numbers of studies with cellular and animal models have detected the presence of functional circadian oscillators at multiple levels, ranging from individual neurons and fibroblasts to brain and peripheral organs. These oscillators are tightly coupled to timely modulate cellular and bodily responses to physiological and metabolic cues. In this review, we will discuss the roles of central and peripheral clocks in physiology and diseases, highlighting the dynamic regulatory interactions between circadian timing systems and multiple metabolic factors.
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García-Allegue, R., P. Lax, A. M. Madariaga, and J. A. Madrid. "Locomotor and feeding activity rhythms in a light-entrained diurnal rodent, Octodon degus." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 277, no. 2 (August 1, 1999): R523—R531. http://dx.doi.org/10.1152/ajpregu.1999.277.2.r523.
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The wheel running (WR) and feeding activity (FA) of Octodon degus, a new laboratory rodent characterized by its diurnal habits, were recorded under different lighting conditions. Under 12:12-h light-dark (LD 12:12) cycles, WR activity exhibited a crepuscular pattern with two peaks, M and E, associated with “dawn” and “dusk,” respectively. In both cases, an anticipatory activity was patent, suggesting that, beside the masking effect of LD transitions, both peaks have an endogenous origin. This pattern, which was also observed under a skeleton photoperiod (LD 0.5:11.5), became unimodal after LD 0.5:23.5 and constant darkness (DD) exposure. Simultaneously, FA showed an arrhythmic pattern in most animals, especially under DD, when none of the animals exhibited a significant circadian rhythm. The existence of two groups of oscillators, or two oscillators, would explain most properties of the WR rhythms noted in this species. Our results show that the degu’s temporal feeding strategy seems mainly arrhythmic, whereas its WR pattern is driven by a strongly circadian bimodal rhythm.
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Prosviryakova, M. V., V. F. Storchevoy, N. G. Goryacheva, O. V. Mikhailova, G. V. Novikova, and A. V. Storchevoy. "Continuous-flow hop dryer with endogenous convection heat producers." IOP Conference Series: Earth and Environmental Science 1052, no. 1 (July 1, 2022): 012141. http://dx.doi.org/10.1088/1755-1315/1052/1/012141.
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Abstract The paper describes a KhS-400 hop dryer configuration that calls for operating conditions to be aligned for autumn conditions due to a lower moisture-absorbing capacity of ambient air, thus making consumer-oriented characteristics unstable. It seems relevant to design a continuous-flow hop dryer to provide endogenous convection drying of freshly harvested hops that reduces operating costs and maintains consumer-oriented characteristics. The innovative idea is that the hop dryer incorporates resonators with concave surfaces and ceramic perforated convex bases, and oscillators operating at close frequencies: 915 MHz, 2375 MHz, 2450 MHz. The scientific goal is to develop continuous-flow methods and equipment with microwave generators and reasonably-configured unconventional resonators for drying hops, providing electromagnetic safety with no shield. The configuration comprises concave paraboloid and concave hyperboloid resonators sequentially fitted to form a drying chamber. The shared bases of the joined resonators are dielectric convex perforated disks rigidly fixed. A conveyor belt runs along the drying chamber. A duct is attached at one side of the base to the junction of the hyperboloid resonator with the paraboloid resonator. An air outlet is attached at the other side of the base to the junction of the hyperboloid resonator with another paraboloid resonator. Generators are located along the perimeter of both paraboloid resonators and along the perimeter of a small-diameter circle of the hyperboloid resonator with an offset of 120 °. The vertices of both paraboloid resonators are truncated and have slots wide enough for letting the conveyor belt pass carrying the raw material.
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D'yakonova, T. L. "Neurochemical mechanisms of burst activity regulation in isolated snail endogenous oscillators: Role of monoamines in opoid peptides." Neurophysiology 23, no. 4 (1992): 349–56. http://dx.doi.org/10.1007/bf01052568.
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Prusik, Magdalena, and Bogdan Lewczuk. "Diurnal Rhythm of Plasma Melatonin Concentration in the Domestic Turkey and Its Regulation by Light and Endogenous Oscillators." Animals 10, no. 4 (April 13, 2020): 678. http://dx.doi.org/10.3390/ani10040678.
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The aim of this study was to characterize the diurnal rhythm of plasma melatonin (MLT) concentration and its regulation by light and endogenous oscillators in 10-week-old domestic turkeys. Three experiments were performed to examine (i) the course of daily changes in plasma MLT concentration in turkeys kept under a 12 h light: 12 h dark (12L:12D) cycle; (ii) the influence of night-time light exposure lasting 0.5, 1, 2, or 3 h on the plasma MLT level; and (iii) the occurrence of circadian fluctuations in plasma MLT levels in birds kept under continuous dim red light and the ability of turkeys to adapt their pineal secretory activity to a reversed light-dark cycle (12D:12L). The plasma MLT concentration was measured with a direct radioimmunoassay. The plasma MLT concentration in turkeys kept under a 12L:12D cycle changed significantly in a daily rhythm. It was low during the photophase and increased stepwise after the onset of darkness to achieve the maximal level in the middle of the scotophase. Next, it decreased during the second half of the night. The difference between the lowest level of MLT and the highest level was approximately 18-fold. The exposure of turkeys to light during the scotophase caused a rapid, large decrease in plasma MLT concentration. The plasma MLT concentration decreased approximately 3- and 10-fold after 0.5 and 1 h of light exposure, respectively, and reached the day-time level after 2 h of exposure. In turkeys kept under continuous darkness, the plasma MLT level was approximately 2.5-fold higher at 02:00 h than at 14:00 h. In birds kept under 12D:12L, the plasma MLT level was significantly higher at 14:00 h than at 02:00 h. The results showed that plasma MLT concentrations in 10-week-old turkeys have a prominent diurnal rhythm, which is endogenously generated and strongly influenced by environmental light.
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Yang, Ping, Jianhao Wang, Fu-Yu Huang, Songguang Yang, and Keqiang Wu. "The Plant Circadian Clock and Chromatin Modifications." Genes 9, no. 11 (November 20, 2018): 561. http://dx.doi.org/10.3390/genes9110561.
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The circadian clock is an endogenous timekeeping network that integrates environmental signals with internal cues to coordinate diverse physiological processes. The circadian function depends on the precise regulation of rhythmic gene expression at the core of the oscillators. In addition to the well-characterized transcriptional feedback regulation of several clock components, additional regulatory mechanisms, such as alternative splicing, regulation of protein stability, and chromatin modifications are beginning to emerge. In this review, we discuss recent findings in the regulation of the circadian clock function in Arabidopsis thaliana. The involvement of chromatin modifications in the regulation of the core circadian clock genes is also discussed.
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Lu, Renbin, Yufan Dong, and Jia-Da Li. "Necdin regulates BMAL1 stability and circadian clock through SGT1-HSP90 chaperone machinery." Nucleic Acids Research 48, no. 14 (July 15, 2020): 7944–57. http://dx.doi.org/10.1093/nar/gkaa601.
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Abstract Circadian clocks are endogenous oscillators that control ∼24-hour physiology and behaviors in virtually all organisms. The circadian oscillator comprises interconnected transcriptional and translational feedback loops, but also requires finely coordinated protein homeostasis including protein degradation and maturation. However, the mechanisms underlying the mammalian clock protein maturation is largely unknown. In this study, we demonstrate that necdin, one of the Prader-Willi syndrome (PWS)-causative genes, is highly expressed in the suprachiasmatic nuclei (SCN), the pacemaker of circadian clocks in mammals. Mice deficient in necdin show abnormal behaviors during an 8-hour advance jet-lag paradigm and disrupted clock gene expression in the liver. By using yeast two hybrid screening, we identified BMAL1, the core component of the circadian clock, and co-chaperone SGT1 as two necdin-interactive proteins. BMAL1 and SGT1 associated with the N-terminal and C-terminal fragments of necdin, respectively. Mechanistically, necdin enables SGT1-HSP90 chaperone machinery to stabilize BMAL1. Depletion of necdin or SGT1/HSP90 leads to degradation of BMAL1 through the ubiquitin–proteasome system, resulting in alterations in both clock gene expression and circadian rhythms. Taken together, our data identify the PWS-associated protein necdin as a novel regulator of the circadian clock, and further emphasize the critical roles of chaperone machinery in circadian clock regulation.
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Tsang, Anthony H., Johanna L. Barclay, and Henrik Oster. "Interactions between endocrine and circadian systems." Journal of Molecular Endocrinology 52, no. 1 (August 30, 2013): R1—R16. http://dx.doi.org/10.1530/jme-13-0118.
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In most species, endogenous circadian clocks regulate 24-h rhythms of behavior and physiology. Clock disruption has been associated with decreased cognitive performance and increased propensity to develop obesity, diabetes, and cancer. Many hormonal factors show robust diurnal secretion rhythms, some of which are involved in mediating clock output from the brain to peripheral tissues. In this review, we describe the mechanisms of clock–hormone interaction in mammals, the contribution of different tissue oscillators to hormonal regulation, and how changes in circadian timing impinge on endocrine signalling and downstream processes. We further summarize recent findings suggesting that hormonal signals may feed back on circadian regulation and how this crosstalk interferes with physiological and metabolic homeostasis.
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GRACE, MICHAEL S., ATSUHIKO CHIBA, and MICHAEL MENAKER. "Circadian control of photoreceptor outer segment membrane turnover in mice genetically incapable of melatonin synthesis." Visual Neuroscience 16, no. 5 (September 1999): 909–18. http://dx.doi.org/10.1017/s0952523899165106.
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Vertebrate retinal photoreceptors periodically shed membrane from their outer segment distal tips; this material is phagocytosed and degraded by the retinal pigmented epithelium. Both a circadian oscillator and the daily light–dark cycle affect disk shedding, and the effects of both may be mediated by melatonin. To clarify melatonin's role in this process, we asked whether endogenous melatonin is required for rhythmic disk shedding in mouse retina. We analyzed disk shedding in two mouse strains: C3H, which produce melatonin in retina and pineal under the control of circadian oscillators, and C57BL/6, which do not produce melatonin. In cyclic light, both strains exhibited a robust cycle of disk phagosome content in the pigmented epithelium. Peak shedding occurred just after dawn, and trough levels occurred during the middle of the dark phase. In constant darkness, mice exhibited circadian rhythms of locomotor activity, the characteristics of which were similar between strains. Both strains also exhibited rhythmic disk shedding in constant darkness, although amplitudes of the rhythms were damped. Exogenous melatonin delivered once per day failed to reestablish high-amplitude cyclic shedding in mice held in constant darkness. Our results show that, while disk shedding in cyclic light is robustly rhythmic, neither rhythmic production of melatonin nor the circadian oscillator responsible for rhythmic locomotor activity is sufficient to drive high-amplitude rhythmic shedding in constant darkness. More importantly, melatonin is required neither for cyclic changes in the rate of disk shedding in cyclic light, nor for the circadian rhythm of disk shedding in constant darkness.
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Brzezinski, Amnon, Seema Rai, Adyasha Purohit, and Seithikurippu R. Pandi-Perumal. "Melatonin, Clock Genes, and Mammalian Reproduction: What Is the Link?" International Journal of Molecular Sciences 22, no. 24 (December 8, 2021): 13240. http://dx.doi.org/10.3390/ijms222413240.
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Physiological processes and behaviors in many mammals are rhythmic. Recently there has been increasing interest in the role of circadian rhythmicity in the control of reproductive function. The circadian rhythm of the pineal hormone melatonin plays a role in synchronizing the reproductive responses of animals to environmental light conditions. There is some evidence that melatonin may have a role in the biological regulation of circadian rhythms and reproduction in humans. Moreover, circadian rhythms and clock genes appear to be involved in optimal reproductive performance. These rhythms are controlled by an endogenous molecular clock within the suprachiasmatic nucleus (SCN) in the hypothalamus, which is entrained by the light/dark cycle. The SCN synchronizes multiple subsidiary oscillators (clock genes) existing in various tissues throughout the body. The basis for maintaining the circadian rhythm is a molecular clock consisting of transcriptional/translational feedback loops. Circadian rhythms and clock genes appear to be involved in optimal reproductive performance. This mini review summarizes the current knowledge regarding the interrelationships between melatonin and the endogenous molecular clocks and their involvement in reproductive physiology (e.g., ovulation) and pathophysiology (e.g., polycystic ovarian syndrome).
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de la Iglesia, Horacio O., and William J. Schwartz. "Minireview: Timely Ovulation: Circadian Regulation of the Female Hypothalamo-Pituitary-Gonadal Axis." Endocrinology 147, no. 3 (March 1, 2006): 1148–53. http://dx.doi.org/10.1210/en.2005-1311.
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The preovulatory surge in the secretion of LH is timed by a neuroendocrine integrative mechanism that involves ovarian estradiol levels and the endogenous circadian system. Studies in female rats and hamsters have established that the clock in the hypothalamic suprachiasmatic nucleus has a preeminent role in setting the LH surge, and anatomical, physiological, and pharmacological data are revealing the responsible connections between suprachiasmatic nucleus neurons and GnRH and estradiol-receptive areas. Recent investigations show that GnRH and pituitary cells express circadian clock genes that might play a role in the release and reception of the GnRH signal. Analysis of the circadian regulation of the LH surge may provide a model for understanding how multiple neural oscillators function within other neuroendocrine axes.
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Bässler, Ulrich. "The walking-(and searching-) pattern generator of stick insects, a modular system composed of reflex chains and endogenous oscillators." Biological Cybernetics 69, no. 4 (August 1993): 305–17. http://dx.doi.org/10.1007/bf00203127.
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Li, Lei. "Circadian Vision in Zebrafish: From Molecule to Cell and from Neural Network to Behavior." Journal of Biological Rhythms 34, no. 5 (July 31, 2019): 451–62. http://dx.doi.org/10.1177/0748730419863917.
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Most visual system functions, such as opsin gene expression, retinal neural transmission, light perception, and visual sensitivity, display robust day-night rhythms. The rhythms persist in constant lighting conditions, suggesting the involvement of endogenous circadian clocks. While the circadian pacemakers that control the rhythms of animal behaviors are mostly found in the forebrain and midbrain, self-sustained circadian oscillators are also present in the neural retina, where they play important roles in the regulation of circadian vision. This review highlights some of the correlative studies of the circadian control of visual system functions in zebrafish. Because zebrafish maintain a high evolutionary proximity to mammals, the findings from zebrafish research may provide insights for a better understanding of the mechanisms of circadian vision in other vertebrate species including humans.
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van Bree, Sander, Ediz Sohoglu, Matthew H. Davis, and Benedikt Zoefel. "Sustained neural rhythms reveal endogenous oscillations supporting speech perception." PLOS Biology 19, no. 2 (February 26, 2021): e3001142. http://dx.doi.org/10.1371/journal.pbio.3001142.
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Rhythmic sensory or electrical stimulation will produce rhythmic brain responses. These rhythmic responses are often interpreted as endogenous neural oscillations aligned (or “entrained”) to the stimulus rhythm. However, stimulus-aligned brain responses can also be explained as a sequence of evoked responses, which only appear regular due to the rhythmicity of the stimulus, without necessarily involving underlying neural oscillations. To distinguish evoked responses from true oscillatory activity, we tested whether rhythmic stimulation produces oscillatory responses which continue after the end of the stimulus. Such sustained effects provide evidence for true involvement of neural oscillations. In Experiment 1, we found that rhythmic intelligible, but not unintelligible speech produces oscillatory responses in magnetoencephalography (MEG) which outlast the stimulus at parietal sensors. In Experiment 2, we found that transcranial alternating current stimulation (tACS) leads to rhythmic fluctuations in speech perception outcomes after the end of electrical stimulation. We further report that the phase relation between electroencephalography (EEG) responses and rhythmic intelligible speech can predict the tACS phase that leads to most accurate speech perception. Together, we provide fundamental results for several lines of research—including neural entrainment and tACS—and reveal endogenous neural oscillations as a key underlying principle for speech perception.
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OISHI, Katsutaka, Hidenori SHIRAI, and Norio ISHIDA. "CLOCK is involved in the circadian transactivation of peroxisome-proliferator-activated receptor α (PPARα) in mice." Biochemical Journal 386, no. 3 (March 8, 2005): 575–81. http://dx.doi.org/10.1042/bj20041150.
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PPARα (peroxisome-proliferator-activated receptor α) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that regulate the expression of genes associated with lipid metabolism. In the present study, we show that circadian expression of mouse PPARα mRNA requires the basic helix–loop–helix PAS (Per-Arnt-Sim) protein CLOCK, a core component of the negative-feedback loop that drives circadian oscillators in mammals. The circadian expression of PPARα mRNA was abolished in the liver of homozygous Clock mutant mice. Using wild-type and Clock-deficient fibroblasts derived from homozygous Clock mutant mice, we showed that the circadian expression of PPARα mRNA is regulated by the peripheral oscillators in a CLOCK-dependent manner. Transient transfection and EMSAs (electrophoretic mobility-shift assays) revealed that the CLOCK–BMAL1 (brain and muscle Arnt-like protein 1) heterodimer transactivates the PPARα gene via an E-box-rich region located in the second intron. This region contained two perfect E-boxes and four E-box-like motifs within 90 bases. ChIP (chromatin immunoprecipitation) also showed that CLOCK associates with this E-box-rich region in vivo. Circadian expression of PPARα mRNA was intact in the liver of insulin-dependent diabetic and of adrenalectomized mice, suggesting that endogenous insulin and glucocorticoids are not essential for the rhythmic expression of the PPARα gene. These results suggested that CLOCK plays an important role in lipid homoeostasis by regulating the transcription of a key protein, PPARα.
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Cardi, P., and F. Nagy. "A rhythmic modulatory gating system in the stomatogastric nervous system of Homarus gammarus. III. Rhythmic control of the pyloric CPG." Journal of Neurophysiology 71, no. 6 (June 1, 1994): 2503–16. http://dx.doi.org/10.1152/jn.1994.71.6.2503.
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1. Two modulatory neurons, P and commissural pyloric (CP), known to be involved in the long-term maintenance of pyloric central pattern generator operation in the rock lobster Homarus gammarus, are members of the commissural pyloric oscillator (CPO), a higher-order oscillator influencing the pyloric network. 2. The CP neuron was endogenously oscillating in approximately 30% of the preparations in which its cell body was impaled. Rhythmic inhibitory feedback from the pyloric pacemaker anterior burster (AB) neuron stabilized the CP neuron's endogenous rhythm. 3. The organization of the CPO is described. Follower commissural neurons, the F cells, and the CP neuron receive a common excitatory postsynaptic potential from another commissural neuron, the large exciter (LE). When in oscillatory state, CP in turn excites the LE neuron. This positive feedback may maintain long episodes of CP oscillations. 4. The pyloric pacemaker neurons follow the CPO rhythm with variable coordination modes (i.e., 1:1, 1:2) and switch among these modes when their membrane potential is modified. The CPO inputs strongly constrain the pyloric period, which as a result may adopt only a few discrete values. This effect is based on mechanisms of entrainment between the CPO and the pyloric oscillator. 5. Pyloric constrictor neurons show differential sensitivity from the pyloric pacemaker neurons with respect to the CPO inputs. Consequently, their bursting period can be a shorter harmonic of the bursting period of the pyloric pacemakers neurons. 6. The CPO neurons seem to be the first example of modulatory gating neurons that also give timing cues to a rhythmic pattern generating network.
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Van Drunen, Rachel, and Kristin Eckel-Mahan. "Circadian Rhythms of the Hypothalamus: From Function to Physiology." Clocks & Sleep 3, no. 1 (February 25, 2021): 189–226. http://dx.doi.org/10.3390/clockssleep3010012.
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The nearly ubiquitous expression of endogenous 24 h oscillations known as circadian rhythms regulate the timing of physiological functions in the body. These intrinsic rhythms are sensitive to external cues, known as zeitgebers, which entrain the internal biological processes to the daily environmental changes in light, temperature, and food availability. Light directly entrains the master clock, the suprachiasmatic nucleus (SCN) which lies in the hypothalamus of the brain and is responsible for synchronizing internal rhythms. However, recent evidence underscores the importance of other hypothalamic nuclei in regulating several essential rhythmic biological functions. These extra-SCN hypothalamic nuclei also express circadian rhythms, suggesting distinct regions that oscillate either semi-autonomously or independent of SCN innervation. Concurrently, the extra-SCN hypothalamic nuclei are also sensitized to fluctuations in nutrient and hormonal signals. Thus, food intake acts as another powerful entrainer for the hypothalamic oscillators’ mediation of energy homeostasis. Ablation studies and genetic mouse models with perturbed extra-SCN hypothalamic nuclei function reveal their critical downstream involvement in an array of functions including metabolism, thermogenesis, food consumption, thirst, mood and sleep. Large epidemiological studies of individuals whose internal circadian cycle is chronically disrupted reveal that disruption of our internal clock is associated with an increased risk of obesity and several neurological diseases and disorders. In this review, we discuss the profound role of the extra-SCN hypothalamic nuclei in rhythmically regulating and coordinating body wide functions.
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Wikelski, Martin, Lynn B. Martin, Alex Scheuerlein, Maisha T. Robinson, Nuriya D. Robinson, Barbara Helm, Michaela Hau, and Eberhard Gwinner. "Avian circannual clocks: adaptive significance and possible involvement of energy turnover in their proximate control." Philosophical Transactions of the Royal Society B: Biological Sciences 363, no. 1490 (July 18, 2007): 411–23. http://dx.doi.org/10.1098/rstb.2007.2147.
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Endogenous circannual clocks are found in many long-lived organisms, but are best studied in mammal and bird species. Circannual clocks are synchronized with the environment by changes in photoperiod, light intensity and possibly temperature and seasonal rainfall patterns. Annual timing mechanisms are presumed to have important ultimate functions in seasonally regulating reproduction, moult, hibernation, migration, body weight and fat deposition/stores. Birds that live in habitats where environmental cues such as photoperiod are poor predictors of seasons (e.g. equatorial residents, migrants to equatorial/tropical latitudes) rely more on their endogenous clocks than birds living in environments that show a tight correlation between photoperiod and seasonal events. Such population-specific/interspecific variation in reliance on endogenous clocks may indicate that annual timing mechanisms are adaptive. However, despite the apparent adaptive importance of circannual clocks, (i) what specific adaptive value they have in the wild and (ii) how they function are still largely untested. Whereas circadian clocks are hypothesized to be generated by molecular feedback loops, it has been suggested that circannual clocks are either based upon (i) a de-multiplication (‘counting’) of circadian days, (ii) a sequence of interdependent physiological states, or (iii) one or more endogenous oscillators, similar to circadian rhythms. We tested the de-multiplication of days (i) versus endogenous regulation hypotheses (ii) and (iii) in captive male and female house sparrows ( Passer domesticus ). We assessed the period of reproductive (testicular and follicular) cycles in four groups of birds kept either under photoperiods of LD 12 L : 12 D (period length: 24 h), 13.5 L : 13.5 D (27 h), 10.5 L : 10.5 D (23 h) or 12 D : 8 L : 3 D : 1 L (24-h skeleton photoperiod), respectively, for 15 months. Contrary to predictions from the de-multiplication hypothesis, individuals experiencing 27-h days did not differ (i.e. did not have longer) annual reproductive rhythms than individuals from the 21- or 24-h day groups. However, in line with predictions from endogenous regulation, birds in the skeleton group had significantly longer circannual period lengths than all other groups. Birds exposed to skeleton photoperiods experienced fewer light hours per year than all other groups (3285 versus 4380) and had a lower daily energy expenditure, as tested during one point of the annual cycle using respirometry. Although our results are tantalizing, they are still preliminary as birds were only studied over a period of 15 months. Nevertheless, the present data fail to support a ‘counting of circadian days’ and instead support hypotheses proposing whole-organism processes as the mechanistic basis for circannual rhythms. We propose a novel energy turnover hypothesis which predicts a dependence of the speed of the circannual clock on the overall energy expenditure of an organism.
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Reisenman, Carolina E., Teresita C. Insausti, and Claudio R. Lazzari. "Light-induced and circadian changes in the compound eye of the haematophagous bug Triatoma infestans (Hemiptera: Reduviidae)." Journal of Experimental Biology 205, no. 2 (January 15, 2002): 201–10. http://dx.doi.org/10.1242/jeb.205.2.201.
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SUMMARY We analysed dynamic changes in the ommatidial structure of the compound eyes of Triatoma infestans. This nocturnal insect possesses open-rhabdom eyes, in which a ring of six rhabdomeres from retinula cells 1–6 (R1–6) surrounds a central pair of rhabdomeres from retinula cells 7 and 8 (R7–8). Screening pigments are located in all the photoreceptors and in the primary (PPC) and secondary (SPC) pigment cells. During the day, pigments within R1–6 and the PPCs form a small ‘pupil’ above the rhabdom and pigments within R7–8 are clustered around the central rhabdomere, allowing light to reach only the central rhabdomere. At night, the ‘pupil’ widens, and pigments inside R7–8 concentrate in the proximal region of the cells, allowing light to reach the peripheral rhabdomeres. In addition, the distance between the cornea and the rhabdom decreases. These rhythmic changes adapt the sensitivity of the eye by controlling the amount of light reaching and travelling within the rhabdom. Furthermore, the rhythm persists under conditions of constant darkness (DD), i.e. it is controlled by an endogenous oscillator. Remarkably, there are differences in pigment movements between the retinula cells of a single ommatidium. The migration of pigments in R1–6 is regulated by a circadian input, while that in R7–8 is regulated by both direct light and circadian inputs. The rhythm vanishes under constant-light conditions (LL). In this species, the circadian rhythm of photonegative behaviour persists in both DD and LL conditions, suggesting that these two rhythms, in retinal morphology and visual behaviour, may be generated by different circadian oscillators.
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Harris, Michael B., Richard J. A. Wilson, Konstantinon Vasilakos, Barbara E. Taylor, and John E. Remmers. "Central respiratory activity of the tadpole in vitro brain stem is modulated diversely by nitric oxide." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 283, no. 2 (August 1, 2002): R417—R428. http://dx.doi.org/10.1152/ajpregu.00513.2001.
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Nitric oxide (NO) is a potent central neuromodulator of respiration, yet its scope and site of action are unclear. We used 7-nitroindazole (7-NI), a selective inhibitor of endogenous neuronal NO synthesis, to investigate the neurogenesis of respiration in larval bullfrog ( Rana catesbeiana) isolated brain stems. 7-NI treatment (0.0625–0.75 mM) increased the specific frequency of buccal ventilation (BV) events, indicating influence on BV central rhythm generators (CRGs). The drug reduced occurrence, altered burst shape, and disrupted clustering of lung ventilation (LV) events, without altering their specific frequency. LV burst occurrence and clustering also differed between pH conditions. We conclude that NO has diverse effects on respiratory rhythmogenesis, being necessary for the expression of respiratory rhythms, inhibiting the frequency of BV CRG, and affecting both shape and clustering of LV bursts through conditional modulation of LV CRG. We confirm central chemosensitivity in these preparations and demonstrate chemomodulation of LV burst clustering and occurrence but not specific frequency. Results support distinct oscillators underlying LV and BV CRGs.
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De Nobrega, Aliza K., and Lisa C. Lyons. "Drosophila: An Emergent Model for Delineating Interactions between the Circadian Clock and Drugs of Abuse." Neural Plasticity 2017 (2017): 1–28. http://dx.doi.org/10.1155/2017/4723836.
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Endogenous circadian oscillators orchestrate rhythms at the cellular, physiological, and behavioral levels across species to coordinate activity, for example, sleep/wake cycles, metabolism, and learning and memory, with predictable environmental cycles. The 21st century has seen a dramatic rise in the incidence of circadian and sleep disorders with globalization, technological advances, and the use of personal electronics. The circadian clock modulates alcohol- and drug-induced behaviors with circadian misalignment contributing to increased substance use and abuse. Invertebrate models, such asDrosophila melanogaster, have proven invaluable for the identification of genetic and molecular mechanisms underlying highly conserved processes including the circadian clock, drug tolerance, and reward systems. In this review, we highlight the contributions ofDrosophilaas a model system for understanding the bidirectional interactions between the circadian system and the drugs of abuse, alcohol and cocaine, and illustrate the highly conserved nature of these interactions betweenDrosophilaand mammalian systems. Research inDrosophilaprovides mechanistic insights into the corresponding behaviors in higher organisms and can be used as a guide for targeted inquiries in mammals.
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Gil-Lozano, Manuel, W. Kelly Wu, Alexandre Martchenko, and Patricia L. Brubaker. "High-Fat Diet and Palmitate Alter the Rhythmic Secretion of Glucagon-Like Peptide-1 by the Rodent L-cell." Endocrinology 157, no. 2 (December 8, 2015): 586–99. http://dx.doi.org/10.1210/en.2015-1732.
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Abstract Secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is rhythmically regulated by an independent molecular clock. However, the impact of factors known to affect the activity of similar cell-autonomous clocks, such as circulating glucocorticoids and high-fat feeding, on GLP-1 secretory patterns remains to be elucidated. Herein the role of the endogenous corticosterone rhythm on the pattern of GLP-1 and insulin nutrient-induced responses was examined in corticosterone pellet-implanted rats. Moreover, the impact of nutrient excess on the time-dependent secretion of both hormones was assessed in rats fed a high-fat, high-sucrose diet. Finally, the effects of the saturated fatty acid, palmitate, on the L-cell molecular clock and GLP-1 secretion were investigated in vitro using murine GLUTag L-cells. Diurnal variations in GLP-1 and insulin nutrient-induced responses were maintained in animals lacking an endogenous corticosterone rhythm, suggesting that glucocorticoids are not the predominant entrainment factor for L-cell rhythmic activity. In addition to hyperglycemia, hyperinsulinemia, insulin resistance, and disorganization of feeding behavior, high-fat high-sucrose-fed rats showed a total abrogation of the diurnal variation in GLP-1 and insulin nutrient-induced responses, with comparable levels of both hormones at the normal peak (5:00 pm) and trough (5:00 am) of their daily pattern. Finally, palmitate incubation induced profound derangements in the rhythmic expression of circadian oscillators in GLUTag L-cells and severely impaired the secretory activity of these cells. Collectively our findings demonstrate that obesogenic diets disrupt the rhythmic activity of the L-cell, partially through a direct effect of specific nutritional components.
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McKenna, Joseph P., Raghuram Dhumpa, Nikita Mukhitov, Michael G. Roper, and Richard Bertram. "Glucose Oscillations Can Activate an Endogenous Oscillator in Pancreatic Islets." PLOS Computational Biology 12, no. 10 (October 27, 2016): e1005143. http://dx.doi.org/10.1371/journal.pcbi.1005143.
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Wolfgang, Werner, Alekos Simoni, Carla Gentile, and Ralf Stanewsky. "The Pyrexia transient receptor potential channel mediates circadian clock synchronization to low temperature cycles in Drosophila melanogaster." Proceedings of the Royal Society B: Biological Sciences 280, no. 1768 (October 7, 2013): 20130959. http://dx.doi.org/10.1098/rspb.2013.0959.
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Circadian clocks are endogenous approximately 24 h oscillators that temporally regulate many physiological and behavioural processes. In order to be beneficial for the organism, these clocks must be synchronized with the environmental cycles on a daily basis. Both light : dark and the concomitant daily temperature cycles (TCs) function as Zeitgeber (‘time giver’) and efficiently entrain circadian clocks. The temperature receptors mediating this synchronization have not been identified. Transient receptor potential (TRP) channels function as thermo-receptors in animals, and here we show that the Pyrexia (Pyx) TRP channel mediates temperature synchronization in Drosophila melanogaster . Pyx is expressed in peripheral sensory organs (chordotonal organs), which previously have been implicated in temperature synchronization. Flies deficient for Pyx function fail to synchronize their behaviour to TCs in the lower range (16–20°C), and this deficit can be partially rescued by introducing a wild-type copy of the pyx gene. Synchronization to higher TCs is not affected, demonstrating a specific role for Pyx at lower temperatures. In addition, pyx mutants speed up their clock after being exposed to TCs. Our results identify the first TRP channel involved in temperature synchronization of circadian clocks.
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GRÈVE, Pierre, Pierre VOISIN, Aline GRECHEZ-CASSIAU, Marianne BERNARD, Jean-Pierre COLLIN, and Jérôme GUERLOTTÉ. "Circadian regulation of hydroxyindole-O-methyltransferase mRNA in the chicken pineal gland in vivo and in vitro." Biochemical Journal 319, no. 3 (November 1, 1996): 761–66. http://dx.doi.org/10.1042/bj3190761.
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The production of the pineal hormone melatonin displays circadian variations with high levels at night. The last enzyme involved in melatonin biosynthesis is hydroxyindole-O-methyltransferase (HIOMT, EC 2.1.1.4). The expression of the mRNA encoding chicken HIOMT was investigated in vivo and in vitro throughout the light/dark cycle, in constant darkness and with light interruption of the dark phase. The stability of HIOMT mRNA was also examined. A day/night rhythm of HIOMT mRNA levels, with a peak at the midlight phase, was observed in vivo as well as in vitro. Constant darkness did not abolish this rhythm in vivo. One cycle of the HIOMT mRNA rhythm could be observed in constant darkness in vitro. In addition, a stimulatory effect of light on HIOMT mRNA levels during the dark phase could be observed in vivo as well as in vitro. HIOMT mRNA stability was not affected by light or dark conditions, as demonstrated by chase experiments with actinomycin D. The results indicate that the daily changes in HIOMT mRNA concentration reflect transcriptional regulation by circadian oscillators and photosensory mechanisms that are endogenous to the pineal gland.
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Puchalski, W., and G. R. Lynch. "Photoperiodic time measurement in Djungarian hamsters evaluated from T-cycle studies." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 267, no. 1 (July 1, 1994): R191—R201. http://dx.doi.org/10.1152/ajpregu.1994.267.1.r191.
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We investigated the photoperiodic response to T-cycles (0.5 h of light at intervals ranging from 23.0 h to 25.3 h) of two phenotypes of Djungarian hamsters that either exhibit or lack physiological short-day adjustments under a photoperiod of 9 h light:15 h darkness. Illumination of the same circadian time caused a similar photoperiodic response in both phenotypes. Thus hamsters found to be insensitive under a full short-day photoperiod can exhibit short-day adjustments after exposure to certain T-cycles. Given these results we conclude that the absence of photoperiodic adjustments normally found in short-day-insensitive hamsters results from their atypical entrainment under a full short-day photoperiod. We further suggest that the photoperiodic phenomena seen in Djungarian hamsters cannot be adequately explained by an external coincidence model of photoperiodic time measurement. As a more suitable model, we propose one form of internal coincidence where duration of daily motor activity reflects the phasing of multiple, endogenous oscillators. This conclusion is supported by the close relationship between duration of activity and the photoperiodic response as well as by the observation that a light pulse modulates duration of activity in a phase-dependent manner.
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Golombek, Diego A., and Ruth E. Rosenstein. "Physiology of Circadian Entrainment." Physiological Reviews 90, no. 3 (July 2010): 1063–102. http://dx.doi.org/10.1152/physrev.00009.2009.
Full textAbstract:
Mammalian circadian rhythms are controlled by endogenous biological oscillators, including a master clock located in the hypothalamic suprachiasmatic nuclei (SCN). Since the period of this oscillation is of ∼24 h, to keep synchrony with the environment, circadian rhythms need to be entrained daily by means of Zeitgeber (“time giver”) signals, such as the light-dark cycle. Recent advances in the neurophysiology and molecular biology of circadian rhythmicity allow a better understanding of synchronization. In this review we cover several aspects of the mechanisms for photic entrainment of mammalian circadian rhythms, including retinal sensitivity to light by means of novel photopigments as well as circadian variations in the retina that contribute to the regulation of retinal physiology. Downstream from the retina, we examine retinohypothalamic communication through neurotransmitter (glutamate, aspartate, pituitary adenylate cyclase-activating polypeptide) interaction with SCN receptors and the resulting signal transduction pathways in suprachiasmatic neurons, as well as putative neuron-glia interactions. Finally, we describe and analyze clock gene expression and its importance in entrainment mechanisms, as well as circadian disorders or retinal diseases related to entrainment deficits, including experimental and clinical treatments.
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Norman, Sharon E., Robert J. Butera, and Carmen C. Canavier. "Stochastic slowly adapting ionic currents may provide a decorrelation mechanism for neural oscillators by causing wander in the intrinsic period." Journal of Neurophysiology 116, no. 3 (September 1, 2016): 1189–98. http://dx.doi.org/10.1152/jn.00193.2016.
Full textAbstract:
Oscillatory neurons integrate their synaptic inputs in fundamentally different ways than normally quiescent neurons. We show that the oscillation period of invertebrate endogenous pacemaker neurons wanders, producing random fluctuations in the interspike intervals (ISI) on a time scale of seconds to minutes, which decorrelates pairs of neurons in hybrid circuits constructed using the dynamic clamp. The autocorrelation of the ISI sequence remained high for many ISIs, but the autocorrelation of the ΔISI series had on average a single nonzero value, which was negative at a lag of one interval. We reproduced these results using a simple integrate and fire (IF) model with a stochastic population of channels carrying an adaptation current with a stochastic component that was integrated with a slow time scale, suggesting that a similar population of channels underlies the observed wander in the period. Using autoregressive integrated moving average (ARIMA) models, we found that a single integrator and a single moving average with a negative coefficient could simulate both the experimental data and the IF model. Feeding white noise into an integrator with a slow time constant is sufficient to produce the autocorrelation structure of the ISI series. Moreover, the moving average clearly accounted for the autocorrelation structure of the ΔISI series and is biophysically implemented in the IF model using slow stochastic adaptation. The observed autocorrelation structure may be a neural signature of slow stochastic adaptation, and wander generated in this manner may be a general mechanism for limiting episodes of synchronized activity in the nervous system.
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Wilde, Christian, Ralf Bruder, Sonja Binder, Lisa Marshall, and Achim Schweikard. "Closed-loop transcranial alternating current stimulation of slow oscillations." Current Directions in Biomedical Engineering 1, no. 1 (September 1, 2015): 85–88. http://dx.doi.org/10.1515/cdbme-2015-0022.
Full textAbstract:
AbstractTranscranial alternating current stimulation (tACS) is an emerging non-invasive tool for modulating brain oscillations. There is evidence that weak oscillatory electrical stimulation during sleep can entrain cortical slow oscillations to improve the memory consolidation in rodents and humans. Using a novel method and a custom built stimulation device, automatic stimulation of slow oscillations in-phase with the endogenous activity in a real-time closed-loop setup is possible. Preliminary data from neuroplasticity experiments show a high detection performance of the proposed method, electrical measurements demonstrate the outstanding quality of the presented stimulation device.
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Sidote, David, John Majercak, Vaishali Parikh, and Isaac Edery. "Differential Effects of Light and Heat on theDrosophila Circadian Clock Proteins PER and TIM." Molecular and Cellular Biology 18, no. 4 (April 1, 1998): 2004–13. http://dx.doi.org/10.1128/mcb.18.4.2004.
Full textAbstract:
ABSTRACT Circadian (≅24-h) rhythms are governed by endogenous biochemical oscillators (clocks) that in a wide variety of organisms can be phase shifted (i.e., delayed or advanced) by brief exposure to light and changes in temperature. However, how changes in temperature reset circadian timekeeping mechanisms is not known. To begin to address this issue, we measured the effects of short-duration heat pulses on the protein and mRNA products from the Drosophila circadian clock genes period (per) andtimeless (tim). Heat pulses at all times in a daily cycle elicited dramatic and rapid decreases in the levels of PER and TIM proteins. PER is sensitive to heat but not light, indicating that individual clock components can markedly differ in sensitivity to environmental stimuli. A similar resetting mechanism involving delays in the per-tim transcriptional-translational feedback loop likely underlies the observation that when heat and light signals are administered in the early night, they both evoke phase delays in behavioral rhythms. However, whereas previous studies showed that the light-induced degradation of TIM in the late night is accompanied by stable phase advances in the temporal regulation of the PER and TIM biochemical rhythms, the heat-induced degradation of PER and TIM at these times in a daily cycle results in little, if any, long-term perturbation in the cycles of these clock proteins. Rather, the initial heat-induced degradation of PER and TIM in the late night is followed by a transient and rapid increase in the speed of the PER-TIM temporal program. The net effect of these heat-induced changes results in an oscillatory mechanism with a steady-state phase similar to that of the unperturbed control situation. These findings can account for the lack of apparent steady-state shifts in Drosophila behavioral rhythms by heat pulses applied in the late night and strongly suggest that stimulus-induced changes in the speed of circadian clocks can contribute to phase-shifting responses.