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1

Neuron, Vol. 45, 293300, January 20, 2005, Copyright 2005 by Elsevier Inc. DOI 10.1016/j.neuron.2004.12.038 Circadian Pacemaker Neurons Transmit  

E-print Network

.neuron.2004.12.038 Circadian Pacemaker Neurons Transmit and Modulate Visual Information to Control a Rapid- clear entry. Conversely, TIM degradation in the secondCircadian pacemaker neurons contain a molecular, controlling entered the nucleus, since CLK/CYC activity is dere-circadian rhythms of behavior. Pacemaker

Desplan, Claude

2

KAYAK-? modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons  

PubMed Central

Circadian rhythms are generated by well-conserved interlocked transcriptional feedback loops in animals. In Drosophila, the dimeric transcription factor CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri) and PAR-domain protein 1 (Pdp1) transcription. PER and TIM negatively feed back on CLK/CYC transcriptional activity, while VRI and PDP1 negatively and positively regulate Clk transcription, respectively. Here, we show that the ? isoform of the Drosophila FOS homolog KAY is required for normal circadian behavior. KAY-? downregulation in circadian pacemaker neurons increases period length by 1.5 hours. This behavioral phenotype is correlated with decreased expression of several circadian proteins. The strongest effects are on CLK and the neuropeptide PIGMENT DISPERSING FACTOR (PDF), which are both under VRI and PDP1 control. Consistently, KAY-? can bind to VRI and inhibit its interaction with the Clk promoter. Interestingly, KAY-? can also repress CLK activity. Hence, in flies with low KAY-? levels, CLK derepression would partially compensate for increased VRI repression, thus attenuating the consequences of KAY-? downregulation on CLK targets. We propose that KAY-?’s double role in the two transcriptional loops controlling Drosophila circadian behavior brings precision and stability to their oscillations. PMID:23175847

Ling, Jinli; Dubruille, Raphaëlle; Emery, Patrick

2012-01-01

3

Electrical Silencing of Drosophila Pacemaker Neurons Stops the Free-Running Circadian Clock  

Microsoft Academic Search

Electrical silencing of Drosophila circadian pacemaker neurons through targeted expression of K+ channels causes severe deficits in free-running circadian locomotor rhythmicity in complete darkness. Pacemaker electrical silencing also stops the free-running oscillation of PERIOD (PER) and TIMELESS (TIM) proteins that constitutes the core of the cell-autonomous molecular clock. In contrast, electrical silencing fails to abolish PER and TIM oscillation in

Michael N. Nitabach; Justin Blau; Todd C. Holmes

2002-01-01

4

Drosophila TRPA1 functions in temperature control of circadian rhythm in pacemaker neurons  

PubMed Central

Most animals from flies to humans count on circadian clocks to synchronize their physiology and behaviors. Daily light cycles are well-known environmental cues for setting circadian rhythms. Warmer and cooler temperatures that mimic day and night are also effective in entraining circadian activity in most animals. Even vertebrate organisms can be induced to show circadian responses through exposure to temperature cycles. In poikilothermic animals such as Drosophila, temperature differences of only 2–3°C are sufficient to synchronize locomotor rhythms. However, the molecular sensors that participate in temperature regulation of circadian activity in fruit flies or other animals are enigmatic. It is also unclear whether such detectors are limited to the periphery or may be in the central brain. Here, we showed that Drosophila TRPA1 (Transient Receptor Potential Cation Channel A1) was necessary for normal activity patterns during temperature cycles. The trpA1 gene was expressed in a subset of pacemaker neurons in the central brain. In response to temperature entrainment, loss of trpA1 impaired activity, and altered expression of the circadian clock protein Period (Per) in a subset of pacemaker neurons. These findings underscore a role for a thermoTRP in temperature regulation that extends beyond avoidance of noxious or suboptimal temperatures. PMID:23595730

Lee, Youngseok; Montell, Craig

2013-01-01

5

Neuromedin s-producing neurons act as essential pacemakers in the suprachiasmatic nucleus to couple clock neurons and dictate circadian rhythms.  

PubMed

Circadian behavior in mammals is orchestrated by neurons within the suprachiasmatic nucleus (SCN), yet the neuronal population necessary for the generation of timekeeping remains unknown. We show that a subset of SCN neurons expressing the neuropeptide neuromedin S (NMS) plays an essential role in the generation of daily rhythms in behavior. We demonstrate that lengthening period within Nms neurons is sufficient to lengthen period of the SCN and behavioral circadian rhythms. Conversely, mice without a functional molecular clock within Nms neurons lack synchronous molecular oscillations and coherent behavioral daily rhythms. Interestingly, we found that mice lacking Nms and its closely related paralog, Nmu, do not lose in vivo circadian rhythms. However, blocking vesicular transmission from Nms neurons with intact cell-autonomous clocks disrupts the timing mechanisms of the SCN, revealing that Nms neurons define a subpopulation of pacemakers that control SCN network synchrony and in vivo circadian rhythms through intercellular synaptic transmission. PMID:25741729

Lee, Ivan T; Chang, Alexander S; Manandhar, Manabu; Shan, Yongli; Fan, Junmei; Izumo, Mariko; Ikeda, Yuichi; Motoike, Toshiyuki; Dixon, Shelley; Seinfeld, Jeffrey E; Takahashi, Joseph S; Yanagisawa, Masashi

2015-03-01

6

Mmp1 Processing of the PDF Neuropeptide Regulates Circadian Structural Plasticity of Pacemaker Neurons  

PubMed Central

In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior. PMID:25356918

Depetris-Chauvin, Ana; Fernández-Gamba, Ágata; Gorostiza, E. Axel; Herrero, Anastasia; Castaño, Eduardo M.; Ceriani, M. Fernanda

2014-01-01

7

A Web of Circadian Pacemakers  

Microsoft Academic Search

The mammalian circadian timing system is composed of almost as many individual clocks as there are cells. These countless oscillators have to be synchronized by a central pacemaker to coordinate temporal physiology and behavior. Recently, there has been some progress in understanding the relationship and communication mechanisms between central and peripheral clocks.

Ueli Schibler; Paolo Sassone-Corsi

2002-01-01

8

The Period Clock Gene is Expressed in Central Nervous System Neurons which Also Produce a Neuropeptide that Reveals the Projections of Circadian Pacemaker Cells Within the Brain of Drosophila melanogaster  

Microsoft Academic Search

The period protein (PER) is an essential component of the circadian clock in Drosophila melanogaster. Although PER-containing pacemaker cells have been previously identified in the brain, the neuronal network that comprises the circadian clock remained unknown. Here it is shown that some PER neurons are also immunostained with an antiserum against the crustacean pigment-dispersing hormone (PDH). This antiserum reveals the

Charlotte Helfrich-Forster

1995-01-01

9

Pacemaking Kisspeptin Neurons  

PubMed Central

Kisspeptin (Kiss1) neurons are vital for reproduction. GnRH neurons express the kisspeptin receptor, GPR 54, and kisspeptins potently stimulate the release of GnRH by depolarising and inducing sustained action potential firing in GnRH neurons. As such Kiss1 neurons may be the pre-synaptic pacemaker neurons in the hypothalamic circuitry that controls reproduction. There are at least two different populations of Kiss1 neurons: one in the rostral periventricular area (RP3V) that is stimulated by oestrogens and the other in the arcuate nucleus that is inhibited by oestrogens. How each of these Kiss1 neuronal populations participate in the regulation of the reproductive cycle is currently under intense investigation. Based on electrophysiological studies in the guinea pig and mouse, Kiss1 neurons in general are capable of generating burst firing behavior. Essentially all Kiss1 neurons, which have been studied thus far in the arcuate nucleus, express the ion channels necessary for burst firing, which include hyperpolarization-activated, cyclic nucleotide gated cation (HCN) channels and the T-type calcium (Cav3.1) channels. Under voltage clamp conditions, these channels produce distinct currents that under current clamp conditions can generate burst firing behavior. The future challenge is to identify other key channels and synaptic inputs involved in the regulation of the firing properties of Kiss1 neurons and the physiological regulation of the expression of these channels and receptors by oestrogens and other hormones. The ultimate goal is to understand how Kiss1 neurons control the different phases of GnRH neurosecretion and hence reproduction. PMID:23884368

Kelly, Martin J.; Zhang, Chunguang; Qiu, Jian; Rønnekleiv, Oline K.

2013-01-01

10

Nonphotic entrainment of the human circadian pacemaker  

NASA Technical Reports Server (NTRS)

In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological clock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals "free run" even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception.

Klerman, E. B.; Rimmer, D. W.; Dijk, D. J.; Kronauer, R. E.; Rizzo, J. F. 3rd; Czeisler, C. A.

1998-01-01

11

Circadian pacemaking in cells and circuits of the suprachiasmatic nucleus.  

PubMed

The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker of the brain. It co-ordinates the daily rhythms of sleep and wakefulness, as well as physiology and behaviour, that set the tempo to our lives. Disturbance of this daily pattern, most acutely with jet-lag but more insidiously with rotational shift-work, can have severely deleterious effects for mental function and long-term health. The present review considers recent developments in our understanding of the properties of the SCN that make it a robust circadian time-keeper. It first focuses on the intracellular transcriptional/ translational feedback loops (TTFL) that constitute the cellular clockwork of the SCN neurone. Daily timing by these loops pivots around the negative regulation of the Period (Per) and Cryptochrome (Cry) genes by their protein products. The period of the circadian cycle is set by the relative stability of Per and Cry proteins, and this can be controlled by both genetic and pharmacological interventions. It then considers the function of these feedback loops in the context of cytosolic signalling by cAMP and intracellular calcium ([Ca(2+) ]i ), which are both outputs from, and inputs to, the TTFL, as well as the critical role of vasoactive intestinal peptide (VIP) signalling in synchronising cellular clocks across the SCN. Synchronisation by VIP in the SCN is paracrine, operating over an unconventionally long time frame (i.e. 24 h) and wide spatial domain, mediated via the cytosolic pathways upstream of the TTFL. Finally, we show how intersectional pharmacogenetics can be used to control G-protein-coupled signalling in individual SCN neurones, and how manipulation of Gq/[Ca(2+) ]i -signalling in VIP neurones can re-programme the circuit-level encoding of circadian time. Circadian pacemaking in the SCN therefore provides an unrivalled context in which to understand how a complex, adaptive behaviour can be organised by the dynamic activity of a relatively few gene products, operating in a clearly defined neuronal circuit, with both cell-autonomous and emergent, circuit-level properties. PMID:24329967

Hastings, M H; Brancaccio, M; Maywood, E S

2014-01-01

12

Differentially Timed Extracellular Signals Synchronize Pacemaker Neuron Clocks  

PubMed Central

Synchronized neuronal activity is vital for complex processes like behavior. Circadian pacemaker neurons offer an unusual opportunity to study synchrony as their molecular clocks oscillate in phase over an extended timeframe (24 h). To identify where, when, and how synchronizing signals are perceived, we first studied the minimal clock neural circuit in Drosophila larvae, manipulating either the four master pacemaker neurons (LNvs) or two dorsal clock neurons (DN1s). Unexpectedly, we found that the PDF Receptor (PdfR) is required in both LNvs and DN1s to maintain synchronized LNv clocks. We also found that glutamate is a second synchronizing signal that is released from DN1s and perceived in LNvs via the metabotropic glutamate receptor (mGluRA). Because simultaneously reducing Pdfr and mGluRA expression in LNvs severely dampened Timeless clock protein oscillations, we conclude that the master pacemaker LNvs require extracellular signals to function normally. These two synchronizing signals are released at opposite times of day and drive cAMP oscillations in LNvs. Finally we found that PdfR and mGluRA also help synchronize Timeless oscillations in adult s-LNvs. We propose that differentially timed signals that drive cAMP oscillations and synchronize pacemaker neurons in circadian neural circuits will be conserved across species. PMID:25268747

Collins, Ben; Kaplan, Harris S.; Cavey, Matthieu; Lelito, Katherine R.; Bahle, Andrew H.; Zhu, Zhonghua; Macara, Ann Marie; Roman, Gregg; Shafer, Orie T.; Blau, Justin

2014-01-01

13

Physiological effects of light on the human circadian pacemaker  

NASA Technical Reports Server (NTRS)

The physiology of the human circadian pacemaker and its influence and on the daily organization of sleep, endocrine and behavioral processes is an emerging interest in science and medicine. Understanding the development, organization and fundamental properties underlying the circadian timing system may provide insight for the application of circadian principles to the practice of clinical medicine, both diagnostically (interpretation of certain clinical tests are dependent on time of day) and therapeutically (certain pharmacological responses vary with the time of day). The light-dark cycle is the most powerful external influence acting upon the human circadian pacemaker. It has been shown that timed exposure to light can both synchronize and reset the phase of the circadian pacemaker in a predictable manner. The emergence of detectable circadian rhythmicity in the neonatal period is under investigation (as described elsewhere in this issue). Therefore, the pattern of light exposure provided in the neonatal intensive care setting has implications. One recent study identified differences in both amount of sleep time and weight gain in infants maintained in a neonatal intensive care environment that controlled the light-dark cycle. Unfortunately, neither circadian phase nor the time of day has been considered in most clinical investigations. Further studies with knowledge of principles characterizing the human circadian timing system, which governs a wide array of physiological processes, are required to integrate these findings with the practice of clinical medicine.

Shanahan, T. L.; Czeisler, C. A.

2000-01-01

14

A functional analysis of circadian pacemakers in nocturnal rodents  

Microsoft Academic Search

Summary 1.The circadian pacemakers controlling activity rhythms in four species of rodents are compared, as freerunning systems in constant darkness. In analyzing their stability the distinction is made between (1) spontaneous day-to-day instability of frequency, and (2) a longer-term lability, some of which is traceable to identified causes.2.Serial correlation analysis indicates that the precision (day-to-day stability) of the pacemaker's period

Colin S. Pittendrigh; Serge Daan

1976-01-01

15

Computational Model of Electrically Coupled, Intrinsically Distinct Pacemaker Neurons  

E-print Network

Computational Model of Electrically Coupled, Intrinsically Distinct Pacemaker Neurons Cristina Soto, and Farzan Nadim. Computational model of electrically coupled, intrinsically distinct pacemaker neurons. J understood. Inspired by the pacemaker group of the crustacean pyloric network, we developed

Nadim, Farzan

16

The neurochemical basis of photic entrainment of the circadian pacemaker  

NASA Technical Reports Server (NTRS)

Circadian rhythmicity in mammals is controlled by the action of a light-entrainable hypothalamus, in association with two cell clusters known as the supra chiasmatic nuclei (SCN). In the absence of temporal environmental clues, this pacemaker continues to measure time by an endogenous mechanism (clock), driving biochemical, physiological, and behavioral rhythms that reflect the natural period of the pacemaker oscillation. This endogenous period usually differs slightly from 24 hours (i.e., circadian). When mammals are maintained under a 24 hour light-dark (LD) cycle, the pacemaker becomes entrained such that the period of the pacemaker oscillation matches that of the LD cycle. Potentially entraining photic information is conveyed to the SCN via a direct retinal projection, the retinohypothalamic tract (RHT). RHT neurotransmission is thought to be mediated by the release of excitatory amino acids (EAA) in the SCN. In support of this hypothesis, recent experiments using nocturnal rodents have shown that EAA antagonists block the effects of light on pacemaker-driven behavioral rhythms, and attenuate light induced gene expression in SCN cells. An understanding of the neurochemical basis of the photic entrainment process would facilitate the development of pharmacological strategies for maintaining synchrony among shift workers in environments, such as the Space Station, which provide unreliable or conflicting temporal photic clues.

Rea, Michael A.; Buckley, Becky; Lutton, Lewis M.

1992-01-01

17

The Drosophila melanogaster circadian pacemaker circuit  

Microsoft Academic Search

As an experimental model system, the fruit fly Drosophila melanogaster has been seminal in shaping our understanding of the circadian clockwork. The wealth of genetic tools at our disposal over\\u000a the past four decades has enabled discovery of the genetic and molecular bases of circadian rhythmicity. More recently, detailed\\u000a investigation leading to the anatomical, neuro-chemical and electrophysiological characterization of the

Vasu Sheeba

2008-01-01

18

Dening the role of Drosophila lateral neurons in the control of circadian activity and eclosion rhythms by  

E-print Network

& Kay, 2000). In both cases, a brain-located circadian pacemaker is responsible for the control that the activity pacemaker stems from a limited number of neurons, in the accessory medulla of the optic lobe and functional organ- ization of the pacemaker that controls activity rhythms. The expression of period (per

Rouyer, Francois

19

Pacemaker neurons within newborn spinal pain circuits  

PubMed Central

Spontaneous activity driven by “pacemakerneurons, defined by their intrinsic ability to generate rhythmic burst-firing, contributes to the development of sensory circuits in many regions of the immature CNS. However, it is unknown if pacemaker-like neurons are present within central pain pathways in the neonate. Here we provide evidence that a subpopulation of glutamatergic interneurons within lamina I of the rat spinal cord exhibits oscillatory burst-firing during early life, which occurs independently of fast synaptic transmission. Pacemaker neurons were distinguished by a higher ratio of persistent, voltage-gated Na+ conductance to leak membrane conductance (gNa,P / gleak) compared to adjacent, non-bursting lamina I neurons. The activation of high-threshold (N-type and L-type) voltage-gated Ca2+ channels also facilitated rhythmic burst-firing by triggering intracellular Ca2+ signaling. Bursting neurons received direct projections from high-threshold sensory afferents, but transmitted nociceptive signals with poor fidelity while in the bursting mode. The observation that pacemaker neurons send axon collaterals throughout the neonatal spinal cord raises the possibility that intrinsic burst-firing could provide an endogenous drive to the developing sensorimotor networks which mediate spinal pain reflexes. PMID:21677184

Li, Jie; Baccei, Mark L.

2011-01-01

20

A pdf Neuropeptide Gene Mutation and Ablation of PDF Neurons Each Cause Severe Abnormalities of Behavioral Circadian Rhythms in Drosophila  

Microsoft Academic Search

The mechanisms by which circadian pacemaker systems transmit timing information to control behavior are largely unknown. Here, we define two critical features of that mechanism in Drosophila. We first describe animals mutant for the pdf neuropeptide gene, which is expressed by most of the candidate pacemakers (LNv neurons). Next, we describe animals in which pdf neurons were selectively ablated. Both

Susan C. P. Renn; Jae H. Park; Michael Rosbash; Jeffrey C. Hall; Paul H. Taghert

1999-01-01

21

Culture and transplantation of the mammalian circadian pacemaker.  

PubMed

In transplantation studies using the tau mutation in the golden hamster, it has been demonstrated that suprachiasmatic nucleus (SCN) pacemaker cells and mechanisms of communication with the host brain are retained even after tissue dissociation and maintenance for many weeks in primary cell culture. Brain grafts of cultured SCN cells are capable of restoring overt rhythms of locomotor activity, and preliminary studies where cells from two tau genotypes are combined in a single graft demonstrate that pacemaker cells may communicate with each other to produce coherent rhythms with intermediate periods. The opportunity is presented, therefore, to study pacemaker-pacemaker communication in circadian chimeras produced by SCN transplantation. Immunocytochemical analysis of graft-host interactions requires the positive identification of host versus donor cells. Although grafted blocks of tissue are easily recognized during immunocytochemical analysis, implants of dissociated and cultured cells may be more diffusely located and are not as readily identified. Unless distinct strain- or species-specific markers are available, it is difficult to identify connections that may carry timing information to the host organism. We have taken an anatomical approach that utilizes cell-labeling techniques for hamster tissue along with foreign protein expression in transgenic mice to identify patterns of communication among graft and host cells, focusing specifically on SCN-SCN communication. The data indicate the usefulness of these transgenes as markers in transplantation studies where communication between graft and host is addressed. PMID:8274766

Ralph, M R; Joyner, A L; Lehman, M N

1993-01-01

22

A forced desynchrony study of circadian pacemaker characteristics in seasonal affective disorder.  

PubMed

The circadian pacemaker is an endogenous clock that regulates oscillations in most physiological and psychological processes with a near 24-h period. In many species, this pacemaker triggers seasonal changes in behavior. The seasonality of symptoms and the efficacy of light therapy suggest involvement of the circadian pacemaker in seasonal affective disorder (SAD), winter type. In this study, circadian pacemaker characteristics of SAD patients were compared with those of controls. Seven SAD patients and matched controls were subjected to a 120-h forced desynchrony protocol, in which core body temperature and melatonin secretion profiles were measured for the characterization of circadian pacemaker parameters. During this protocol, which enables the study of unmasked circadian pacemaker characteristics, subjects were exposed to six 20-h days in time isolation. Patients participated twice in winter (while depressed and while remitted after light therapy) and once in summer. Controls participated once in winter and once in summer. Between the SAD patients and controls, no significant differences were observed in the melatonin-derived period or in the phase of the endogenous circadian temperature rhythm. The amplitude of this rhythm was significantly smaller in depressed and remitted SAD patients than in controls. No abnormalities of the circadian pacemaker were observed in SAD patients. A disturbance in thermoregulatory processes might explain the smaller circadian temperature amplitude in SAD patients during winter. PMID:12375622

Koorengevel, Kathelijne M; Beersma, Domien G M; den Boer, Johan A; van den Hoofdakker, Rutger H

2002-10-01

23

Phase shifting two coupled circadian pacemakers - Implications for jet lag  

NASA Technical Reports Server (NTRS)

Two Van der Pol oscillators with reciprocal linear velocity coupling are utilized to model the response of the human circadian timing system to abrupt displacements of the environmental time cues (zeitgebers). The core temperature rhythm and sleep-wake cycle simulated by the model are examined. The relationship between the masking of circadian rhythms by environmental variables and behavioral and physiological events and the rates of resynchronization is studied. The effects of zeitgeber phase shifts and zeitgeber strength on the resynchronization rates are analyzed. The influence of intrinsic pacemakers periods and coupling strength on resynchronization are investigated. The simulated data reveal that: resynchronization after a time zone shift depends on the magnitude of the shift; the time of day of the shift has little influence on resynchronization; the strength of zeitgebers affects the rate and direction of the resynchronization; the intrinsic pacemaker periods have a significant effect on resynchronization; and increasing the coupling between the oscillators results in an increase in the rate of resynchronization. The model data are compared to transmeridian flight studies data and similar resynchronization patterns are observed.

Gander, P. H.; Kronauer, R. E.; Graeber, R. C.

1985-01-01

24

Dynamic interactions between coupled oscillators within the hamster circadian pacemaker  

PubMed Central

Within the mammalian suprachiasmatic nucleus, multiple oscillators are coupled to form a functional pacemaker coordinating circadian rhythms in behavior and physiology. A clear understanding of circadian coupling has been elusive due to the lack of analytical paradigms well suited for this purpose. We have developed a novel behavioral assay that disassociates central oscillators and allows rigorous study of their formal properties and interactions. Nocturnal rodents held under 24 h light:dark:light:dark (LDLD) cycles display bimodal, or “split,” activity rhythms, which reflect the reorganization of the central pacemaker into two oscillator groups cycling ~ 12 h apart. After transfer from LDLD to constant conditions, the two activity components rapidly rejoin through a series of transients lasting 2–7 days. Here we analyze the dynamics of fusion, characterize the oscillator interactions underlying this process, and assess two factors that influence this dynamic: phase of transfer into constant conditions and lighting conditions upon transfer. Syrian hamsters were split under LDLD with dimly lit nights then transferred to constant dim illumination or complete darkness at the beginning of one of the two daily scotophases. Fusion of the split activity bouts was influenced by the phase of release suggesting that the oscillators split under LDLD exert an asymmetric influence over one another. Constant dim and dark conditions produced similar overall patterns of fusion, but nevertheless differed in the state to which the system rejoined, indicating that dim light likely modulates interactions during this process. The present results are discussed within a model for circadian coupling wherein oscillators are able to influence one another in a phase dependent manner. PMID:20141283

Evans, Jennifer A.; Elliott, Jeffrey A.; Gorman, Michael R.

2010-01-01

25

Circadian Organization of Behavior and Physiology  

E-print Network

Circadian Organization of Behavior and Physiology in Drosophila Ravi Allada and Brian Y. Chung Words peripheral clocks, pacemaker neurons, locomotor activity, feeding, mating Abstract Circadian cellular functions. Here we discuss our current knowledge of circadian clock function in Drosophila

Allada, Ravi

26

Spontaneous Activity in Isolated Somata of Aplysia Pacemaker Neurons  

Microsoft Academic Search

Somata of pacemaker and nonpacemaker neurons were isolated by ligatures tied around the axons between the somata and the synaptic regions, and the transmembrane potentials of the isolated somata were recorded. Iso- lated somata of pacemaker neurons had a spontaneous discharge while isolated somata of nonpacemaker neurons were quiescent. In addition, the time course of accommodation in isolated somata of

BARBARA O. ALVING

1968-01-01

27

Asynchronous response of coupled pacemaker neurons  

E-print Network

We study a network model of two conductance-based pacemaker neurons of differing natural frequency, coupled with either mutual excitation or inhibition, and receiving shared random inhibitory synaptic input. The networks may phase-lock spike-to-spike for strong mutual coupling. But the shared input can desynchronize the locked spike-pairs by selectively eliminating the lagging spike or modulating its timing with respect to the leading spike depending on their separation time window. Such loss of synchrony is also found in a large network of sparsely coupled heterogeneous spiking neurons receiving shared input.

Ramana Dodla; Charles J. Wilson

2009-02-03

28

Putative Pacemakers in the Eyestalk and Brain of the Crayfish Procambarus clarkii Show Circadian Oscillations in Levels of mRNA for Crustacean Hyperglycemic Hormone  

PubMed Central

Crustacean hyperglycemic hormone (CHH) synthesizing cells in the optic lobe, one of the pacemakers of the circadian system, have been shown to be present in crayfish. However, the presence of CHH in the central brain, another putative pacemaker of the multi-oscillatory circadian system, of this decapod and its circadian transcription in the optic lobe and brain have yet to be explored. Therefore, using qualitative and quantitative PCR, we isolated and cloned a CHH mRNA fragment from two putative pacemakers of the multi-oscillatory circadian system of Procambarus clarkii, the optic lobe and the central brain. This CHH transcript synchronized to daily light-dark cycles and oscillated under dark, constant conditions demonstrating statistically significant daily and circadian rhythms in both structures. Furthermore, to investigate the presence of the peptide in the central brain of this decapod, we used immunohistochemical methods. Confocal microscopy revealed the presence of CHH-IR in fibers and cells of the protocerebral and tritocerebal clusters and neuropiles, particularly in some neurons located in clusters 6, 14, 15 and 17. The presence of CHH positive neurons in structures of P. clarkii where clock proteins have been reported suggests a relationship between the circadian clockwork and CHH. This work provides new insights into the circadian regulation of CHH, a pleiotropic hormone that regulates many physiological processes such as glucose metabolism and osmoregulatory responses to stress. PMID:24391849

Nelson-Mora, Janikua; Prieto-Sagredo, Julio; Loredo-Ranjel, Rosaura; Fanjul-Moles, María Luisa

2013-01-01

29

Morphology and pigment-dispersing hormone immunocytochemistry of the accessory medulla, the presumptive circadian pacemaker of the cockroach Leucophaea maderae: a light- and electron-microscopic study  

Microsoft Academic Search

To provide a framework for a cellular analysis of the accessory medulla, which is the presumptive circadian pacemaker of hemimetabolous insects, we have studied this neuropil and its associated neuronal structures by light- and electron-microscopy in the cockroach Leucophaea maderae. The accessory medulla is situated at the ventromedial edge of the medulla and shows no evidence of a retinotopical organization.

Thomas Reischig; Monika Stengl

1996-01-01

30

Circadian pacemaker interferes with sleep onset at specific times each day: role in insomnia  

E-print Network

Circadian pacemaker interferes with sleep onset at specific times each day: role in insomnia STEVEN at specific times each day: role in insomnia. Am. J. Physiol. 253(Regulatory Integrative Comp.Physiol. 22):R of the circadianpacemakermayunderliethe insomniaassociatedwith sleep-schedulingdisorders. insomnia; circadian rhythm; sleep

Schumaker, Mark

31

Behavioral/Systems/Cognitive Sodium and Calcium Current-Mediated Pacemaker Neurons  

E-print Network

Behavioral/Systems/Cognitive Sodium and Calcium Current-Mediated Pacemaker Neurons and RespiratoryICAN enhanceneuronalexcitabilityandpromoterhythmogenesis,eveniftheirmagnitudeisinsufficienttosupport bursting-pacemaker activity in individual neurons excitability, which is inconsistent with a pacemaker-essential mechanism of respiratory rhythmogenesis

Del Negro, Christopher A.

32

Decreased human circadian pacemaker influence after 100 days in space: a case study  

NASA Technical Reports Server (NTRS)

OBJECTIVE: The objectives of this study were (1) to assess the circadian rhythms and sleep of a healthy, 42-year-old male astronaut experiencing microgravity (weightlessness) for nearly 5 months while living aboard Space Station Mir as it orbited Earth and (2) to determine the effects of prolonged space flight on the endogenous circadian pacemaker, as indicated by oral temperature and subjective alertness rhythms, and their ramifications for sleep, alertness, and performance. METHODS: For three 12- to 14-day blocks of time (spread throughout the mission), oral temperatures were taken and subjective alertness was self-rated five times per day. Sleep diaries and performance tests were also completed daily during each block. RESULTS: Examination of the subject's circadian alertness and oral temperature rhythms suggested that the endogenous circadian pacemaker seemed to function quite well up to 90 days in space. Thereafter (on days 110-122), the influence of the endogenous circadian pacemaker on oral temperature and subjective alertness circadian rhythms was considerably weakened, with consequent disruptions in sleep. CONCLUSIONS: Space missions lasting more than 3 months might result in diminished circadian pacemaker influence in astronauts, leading to eventual sleep problems.

Monk, T. H.; Kennedy, K. S.; Rose, L. R.; Linenger, J. M.

2001-01-01

33

Alterations induced by chronic lead exposure on the cells of circadian pacemaker of developing rats  

PubMed Central

Lead (Pb) exposure alters the temporal organization of several physiological and behavioural processes in which the suprachiasmatic nucleus (SCN) of the hypothalamus plays a fundamental role. In this study, we evaluated the effects of chronic early Pb exposure (CePbe) on the morphology, cellular density and relative optical density (OD) in the cells of the SCN of male rats. Female Wistar rats were exposed during gestation and lactation to a Pb solution containing 320 ppm of Pb acetate through drinking water. After weaning, the pups were maintained with the same drinking water until sacrificed at 90 days of age. Pb levels in the blood, hypothalamus, hippocampus and prefrontal cortex were significantly increased in the experimental group. Chronic early Pb exposure induced a significant increase in the minor and major axes and somatic area of vasoactive intestinal polypeptide (VIP)- and vasopressin (VP)-immunoreactive neurons. The density of VIP-, VP- and glial fibrillary acidic protein (GFAP)-immunoreactive cells showed a significant decrease in the experimental group. OD analysis showed a significant increase in VIP neurons of the experimental group. The results showed that CePbe induced alterations in the cells of the SCN, as evidenced by modifications in soma morphology, cellular density and OD in circadian pacemaker cells. These findings provide a morphological and cellular basis for deficits in circadian rhythms documented in Pb-exposed animals. PMID:21324006

Rojas-Castañeda, Julio César; Vigueras-Villaseñor, Rosa María; Rojas, Patricia; Chávez-Saldaña, Margarita; Pérez, Oscar Gutiérrez; Montes, Sergio; Ríos, Camilo

2011-01-01

34

Simulations of light effects on the human circadian pacemaker: implications for assessment of intrinsic period  

NASA Technical Reports Server (NTRS)

The sensitivity of the human circadian system to light has been the subject of considerable debate. Using computer simulations of a recent quantitative model for the effects of light on the human circadian system, we investigated these effects of light during different experimental protocols. The results of the simulations indicate that the nonuniform distribution over the circadian cycle of exposure to ordinary room light seen in classical free-run studies, in which subjects select their exposure to light and darkness, can result in an observed period of approximately 25 h, even when the intrinsic period of the subject's endogenous circadian pacemaker is much closer to 24 h. Other simulation results suggest that accurate assessment of the true intrinsic period of the human circadian pacemaker requires low ambient light intensities (approximately 10-15 lx) during scheduled wake episodes, desynchrony of the imposed light-dark cycle from the endogenous circadian oscillator, and a study length of at least 20 days. Although these simulations await further experimental substantiation, they highlight the sensitivity to light of the human circadian system and the potential confounding influence of light on the assessment of the intrinsic period of the circadian pacemaker.

Klerman, E. B.; Dijk, D. J.; Kronauer, R. E.; Czeisler, C. A.

1996-01-01

35

Neuronal Coding of pacemaker neurons - A random dynamical systems approach  

E-print Network

The behaviour of neurons under the influence of periodic external input has been modelled very successfully by circle maps. The aim of this note is to extend certain aspects of this analysis to a much more general class of forcing processes. We apply results on the fibred rotation number of randomly forced circle maps to show the uniqueness of the asymptotic firing frequency of ergodically forced pacemaker neurons. The details of the analysis are carried out for the forced leaky integrate-and-fire model, but the results should also remain valid for a large class of further models.

Jaeger, T

2009-01-01

36

Contribution of pacemaker neurons to respiratory rhythms generation in vitro.  

PubMed

Neurons with pacemaker properties have been described in several neural networks. Nonlinearity of their bursting activity might enable them to facilitate onset of excitatory states or to synchronize neuronal ensembles. However, whether such neurons are essential for generating a network activity pattern remains mostly unknown. For the mammalian respiratory network, located in the preBötzinger complex (PBC), two types of pacemaker neurons have been described. Bursting properties of one type of pacemakers rely on the riluzole-sensitive persistent sodium current, whereas bursting mechanisms of a second type are sensitive to Cd2+ and flufenamic acid, a calcium-dependent nonspecific cationic current blocker. The role of pacemakers in the generation of respiratory rhythms in vitro is state dependent. Under control conditions, the respiratory network generates fictive eupneic activity; this activity depends on both riluzole-sensitive and flufenamic acid-sensitive pacemakers. During hypoxia, fictive eupneic activity is supplanted by the neural correlate of gasping and only riluzole-sensitive pacemaker neurons appear to be necessary for this rhythm. Thus, at least two types of pacemaker bursting mechanisms are present in the PBC and underlie fictive eupnea, whereas only one burst mechanism seems to be critical for gasping generation in vitro. PMID:18085257

Peña, Fernando

2008-01-01

37

Cyclic AMP signaling control of action potential firing rate and molecular circadian pacemaking in the suprachiasmatic nucleus.  

PubMed

Circadian pacemaking in suprachiasmatic nucleus (SCN) neurons revolves around transcriptional/posttranslational feedback loops, driven by protein products of "clock" genes. These loops are synchronized and sustained by intercellular signaling, involving vasoactive intestinal peptide (VIP) via its VPAC2 receptor, which positively regulates cAMP synthesis. In turn, SCN cells communicate circadian time to the brain via a daily rhythm in electrophysiological activity. To investigate the mechanisms whereby VIP/VPAC2/cAMP signaling controls SCN molecular and electrical pacemaking, we combined bioluminescent imaging of circadian gene expression and whole-cell electrophysiology in organotypic SCN slices. As a potential direct target of cAMP, we focused on hyperpolarization-activated, cyclic nucleotide-gated (HCN) channels. Mutations of VIP-ergic signaling compromised the SCN molecular pacemaker, diminishing the amplitude and intercellular synchrony of circadian gene expression. These deficits were transiently reversed by elevation of cAMP. Similarly, cellular synchrony in electrical firing rates was lost in SCN slices lacking the VPAC2 receptor for VIP. Whole-cell current-clamp recordings in wild-type (WT) slices revealed voltage responses shaped by the conductance I(h), which is mediated by HCN channel activity. The influence of I(h) on voltage responses showed a modest peak in early circadian day, identifying HCN channels as a putative mediator of cAMP-dependent circadian effects on firing rate. I(h), however, was unaffected by loss of VIP-ergic signaling in VPAC2-null slices, and inhibition of cAMP synthesis had no discernible effect on I(h) but did suppress gene expression and SCN firing rates. Moreover, only sustained but not acute, pharmacological blockade of HCN channels reduced action potential (AP) firing. Thus, our evidence suggests that in the SCN, cAMP-mediated signaling is not a principal regulator of HCN channel function and that HCN is not a determinant of AP firing rate. VIP/cAMP-dependent signaling sustains the SCN molecular oscillator and action potential firing via mechanisms yet to be identified. PMID:21628548

Atkinson, Susan E; Maywood, Elizabeth S; Chesham, Johanna E; Wozny, Christian; Colwell, Christopher S; Hastings, Michael H; Williams, Stephen R

2011-06-01

38

Circadian rhythms in healthy aging--effects downstream from the pacemaker  

NASA Technical Reports Server (NTRS)

Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

Monk, T. H.; Kupfer, D. J.

2000-01-01

39

Dynamic resetting of the human circadian pacemaker by intermittent bright light  

NASA Technical Reports Server (NTRS)

In humans, experimental studies of circadian resetting typically have been limited to lengthy episodes of exposure to continuous bright light. To evaluate the time course of the human endogenous circadian pacemaker's resetting response to brief episodes of intermittent bright light, we studied 16 subjects assigned to one of two intermittent lighting conditions in which the subjects were presented with intermittent episodes of bright-light exposure at 25- or 90-min intervals. The effective duration of bright-light exposure was 31% or 63% compared with a continuous 5-h bright-light stimulus. Exposure to intermittent bright light elicited almost as great a resetting response compared with 5 h of continuous bright light. We conclude that exposure to intermittent bright light produces robust phase shifts of the endogenous circadian pacemaker. Furthermore, these results demonstrate that humans, like other species, exhibit an enhanced sensitivity to the initial minutes of bright-light exposure.

Rimmer, D. W.; Boivin, D. B.; Shanahan, T. L.; Kronauer, R. E.; Duffy, J. F.; Czeisler, C. A.

2000-01-01

40

Asynchronous Response of Coupled Pacemaker Neurons Ramana Dodla and Charles J. Wilson  

E-print Network

Asynchronous Response of Coupled Pacemaker Neurons Ramana Dodla and Charles J. Wilson Department; published 10 February 2009) We study a network model of two conductance-based pacemaker neurons of differing. We consider two coupled pacemaking model neurons at dissimilar frequencies (!1;2) and affected

Dodla, Ramana

41

Stability, precision, and near-24-hour period of the human circadian pacemaker  

NASA Technical Reports Server (NTRS)

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

Czeisler, C. A.; Duffy, J. F.; Shanahan, T. L.; Brown, E. N.; Mitchell, J. F.; Rimmer, D. W.; Ronda, J. M.; Silva, E. J.; Allan, J. S.; Emens, J. S.; Dijk, D. J.; Kronauer, R. E.

1999-01-01

42

Manipulating circadian clock neuron firing rate resets molecular circadian rhythms and behavior.  

PubMed

To examine the interaction between molecular, electrical and behavioral circadian rhythms, we combined optogenetic manipulation of suprachiasmatic nucleus (SCN) firing rate with bioluminescence imaging and locomotor activity monitoring. Manipulating firing rate reset circadian rhythms both ex vivo and in vivo, and this resetting required spikes and network communication. This suggests that SCN firing rate is fundamental to circadian pacemaking as both an input to and output of the molecular clockworks. PMID:25643294

Jones, Jeff R; Tackenberg, Michael C; McMahon, Douglas G

2015-03-01

43

Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression  

NASA Technical Reports Server (NTRS)

Ocular exposure to early morning room light can significantly advance the timing of the human circadian pacemaker. The resetting response to such light has a non-linear relationship to illuminance. The dose-response relationship of the human circadian pacemaker to late evening light of dim to moderate intensity has not been well established. Twenty-three healthy young male and female volunteers took part in a 9 day protocol in which a single experimental light exposure6.5 h in duration was given in the early biological night. The effects of the light exposure on the endogenous circadian phase of the melatonin rhythm and the acute effects of the light exposure on plasma melatonin concentration were calculated. We demonstrate that humans are highly responsive to the phase-delaying effects of light during the early biological night and that both the phase resetting response to light and the acute suppressive effects of light on plasma melatonin follow a logistic dose-response curve, as do many circadian responses to light in mammals. Contrary to expectations, we found that half of the maximal phase-delaying response achieved in response to a single episode of evening bright light ( approximately 9000 lux (lx)) can be obtained with just over 1 % of this light (dim room light of approximately 100 lx). The same held true for the acute suppressive effects of light on plasma melatonin concentrations. This indicates that even small changes in ordinary light exposure during the late evening hours can significantly affect both plasma melatonin concentrations and the entrained phase of the human circadian pacemaker.

Zeitzer, J. M.; Dijk, D. J.; Kronauer, R.; Brown, E.; Czeisler, C.

2000-01-01

44

Association of sleep-wake habits in older people with changes in output of circadian pacemaker  

NASA Technical Reports Server (NTRS)

Many elderly people complain of disturbed sleep patterns but there is not evidence that the need to sleep decreases with age; it seems rather that the timing and consolidation of sleep change. We tried to find out whether there is a concurrent change in the output of the circadian pacemaker with age. The phase and amplitude of the pacemaker's output were assessed by continuous measurement of the core body temperature during 40 h of sustained wakefulness under constant behavioural and environmental conditions. 27 young men (18-31 years) were compared with 21 older people (65-85 years; 11 men, 10 women); all were healthy and without sleep complaints. The mean amplitude of the endogenous circadian temperature oscillation (ECA) was 40% greater in young men than in the older group. Older men had a lower mean temperature ECA than older women. The minimum of the endogenous phase of the circadian temperature oscillation (ECP) occurred 1 h 52 min earlier in the older than in the young group. Customary bedtimes and waketimes were also earlier in the older group, as was their daily alertness peak. There was a close correlation between habitual waketime and temperature ECP in young men, which may lose precision with age, especially among women. These findings provide evidence for systematic age-related changes in the output of the human circadian pacemaker. We suggest that these changes may underlie the common complaints of sleep disturbance among elderly people. These changes could reflect the observed age-related deterioration of the hypothalamic nuclei that drive mammalian circadian rhythms.

Czeisler, C. A.; Dumont, M.; Duffy, J. F.; Steinberg, J. D.; Richardson, G. S.; Brown, E. N.; Sanchez, R.; Rios, C. D.; Ronda, J. M.

1992-01-01

45

Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons  

E-print Network

Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons Alexis B August 5, 2009 (received for review March 16, 2009) Circadian rhythms are modeled as reliable and self the hypothesis that circadian cycling is intrinsic to a unique class of SCN neurons by measuring firing rate

Huettner, James E.

46

A functional analysis of circadian pacemakers in nocturnal rodents  

Microsoft Academic Search

Summary 1.This paper is an attempt to integrate in a general model the major findings reported earlier in this series on: lability and history dependence of circadian period, t (Pittendrigh and Daan, 1976 a); dependence of t and a on light intensity as described in Aschoff's Rule (Daan and Pittendrigh, 1976b); the interrelationships between t and phase response curves (Daan

Colin S. Pittendrigh; Serge Daan

1976-01-01

47

Characteristics of a circadian pacemaker in the suprachiasmatic nucleus  

Microsoft Academic Search

The nature of the circadian rhythms of the SCN in a hypothalamic island was examined in male rats by recording multiple unit activity from the SCN for longer durations. Successful continuous recording lasted up to 35 days. Neural activity of the SCN inside the island showed free-running rhythms whose periods were slightly longer than 24 h (Figs. 2, 3, Table

Shin-ichi T. Inouye; Hiroshi Kawamura

1982-01-01

48

Pacemaker Neurons for the Theta Rhythm and Their Synchronization in the Septohippocampal Reciprocal Loop  

E-print Network

Pacemaker Neurons for the Theta Rhythm and Their Synchronization in the Septohippocampal Reciprocal-9110 Received 16 February 2001; accepted in final form 15 October 2001 Wang, Xiao-Jing. Pacemaker neurons. On the other hand, experimental data indicate that GABAergic cells in the medial septum play a pacemaker role

Wang, Xiao-Jing

49

Circadian Rhythms of Neuroendocrine Dopaminergic Neuronal Activity in Ovariectomized Rats  

Microsoft Academic Search

Prolactin (PRL) secretion is inhibited by dopamine (DA) released from hypothalamic neuroendocrine neurons designated tuberoinfundibular (TIDA), tuberohypophyseal (THDA) and periventricular hypophyseal (PHDA) dopaminergic (DAergic) neurons. Since PRL is secreted in many physiological states with a circadian rhythm, the purpose of these experiments was to determine if patterns of neuroendocrine DAergic neuronal activity in rats are also circadian. The activity of

Michael T. Sellix; Marc E. Freeman

2003-01-01

50

Immortalized cell lines for real-time analysis of circadian pacemaker and peripheral oscillator properties.  

PubMed

In the mammalian circadian system, cell-autonomous clocks in the suprachiasmatic nuclei (SCN) are distinguished from those in other brain regions and peripheral tissues by the capacity to generate coordinated rhythms and drive oscillations in other cells. To further establish in vitro models for distinguishing the functional properties of SCN and peripheral oscillators, we developed immortalized cell lines derived from fibroblasts and the SCN anlage of mPer2?(Luc) knockin mice. Circadian rhythms in luminescence driven by the mPER2::LUC fusion protein were observed in cultures of mPer2?(Luc) SCN cells and in serum-shocked or SCN2.2-co-cultured mPer2?(Luc) fibroblasts. SCN mPer2?(Luc) cells generated self-sustained circadian oscillations that persisted for at least four cycles with periodicities of ?24?h. Immortalized fibroblasts only showed circadian rhythms of mPER2::LUC expression in response to serum shock or when co-cultured with SCN2.2 cells. Circadian oscillations of luminescence in mPer2?(Luc) fibroblasts decayed after 3-4 cycles in serum-shocked cultures but robustly persisted for 6-7 cycles in the presence of SCN2.2 cells. In the co-culture model, the circadian behavior of mPer2?(Luc) fibroblasts was dependent on the integrity of the molecular clockworks in co-cultured SCN cells as persistent rhythmicity was not observed in the presence of immortalized SCN cells derived from mice with targeted disruption of Per1 and Per2 (Per1(ldc) /Per2?(ldc) ). Because immortalized mPer2?(Luc) SCN cells and fibroblasts retain their indigenous circadian properties, these in vitro models will be valuable for real-time comparisons of clock gene rhythms in SCN and peripheral oscillators and identifying the diffusible signals that mediate the distinctive pacemaking function of the SCN. PMID:21366728

Farnell, Yuhua F; Shende, Vikram R; Neuendorff, Nichole; Allen, Gregg C; Earnest, David J

2011-04-01

51

Circadian Synchrony in Networks of Protein Rhythm Driven Neurons  

E-print Network

Circadian Synchrony in Networks of Protein Rhythm Driven Neurons WILLIAM S. BUSH AND HAVA T; suprachiasmatic nucleus; protein expression; circadian rhythms INTRODUCTION S yncronicity has been examined M P L E X I T Y 67 DOI 10.1002/cplx.20145 #12;circadian rhythms, such as the sleep­wake cycle

Siegelmann , Hava T

52

Dual PDF Signaling Pathways Reset Clocks Via TIMELESS and Acutely Excite Target Neurons to Control Circadian Behavior  

PubMed Central

Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(?) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(?) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per01 mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per01 flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

2014-01-01

53

Photoperiodic plasticity in circadian clock neurons in insects  

PubMed Central

Since Bünning's observation of circadian rhythms and photoperiodism in the runner bean Phaseolus multiflorus in 1936, many studies have shown that photoperiodism is based on the circadian clock system. In insects, involvement of circadian clock genes or neurons has been recently shown in the photoperiodic control of developmental arrests, diapause. Photoperiod sets peaks of period (per) or timeless (tim) mRNA abundance at lights-off in Sarcophaga crassipalpis, Chymomyza costata and Protophormia terraenovae. Abundance of per and Clock mRNA changes by photoperiod in Pyrrhocoris apterus. Subcellular Per distribution in circadian clock neurons changes with photoperiod in P. terraenovae. Although photoperiodism is not known in Leucophaea maderae, under longer day length, more stomata and longer commissural fibers of circadian clock neurons have been found. These plastic changes in the circadian clock neurons could be an important constituent for photoperiodic clock mechanisms to integrate repetitive photoperiodic information and produce different outputs based on day length. PMID:23986711

Shiga, Sakiko

2013-01-01

54

A peripheral pacemaker drives the circadian rhythm of synaptic boutons in Drosophila independently of synaptic activity  

Microsoft Academic Search

Circadian rhythms in the morphology of neurons have been demonstrated in the fly Drosophila melanogaster. One such rhythm is characterized by changes in the size of synaptic boutons of an identified flight motor neuron, with larger\\u000a boutons during the day compared with those at night. A more detailed temporal resolution of this rhythm shows here that boutons\\u000a grow at a

Kerstin I. Mehnert; Rafael Cantera

2008-01-01

55

A mathematical model of communication between groups of circadian neurons in Drosophila melanogaster.  

PubMed

In the fruit fly, circadian behavior is controlled by a small number of specialized neurons, whose molecular clocks are relatively well known. However, much less is known about how these neurons communicate among themselves. In particular, only 1 circadian neuropeptide, pigment-dispersing factor (PDF), has been identified, and most aspects of its interaction with the molecular clock remain to be elucidated. Furthermore, it is speculated that many other peptides should contribute to circadian communication. We have developed a relatively detailed model of the 2 main groups of circadian pacemaker neurons (sLNvs and LNds) to investigate these issues. We have proposed many possible mechanisms for the interaction between the synchronization factors and the molecular clock, and we have compared the outputs with the experimental results reported in the literature both for the wild-type and PDF-null mutant. We have studied how different the properties of each neuron should be to account for the observations reported for the sLNvs in the mutant. We have found that only a few mechanisms, mostly related to the slowing down of nuclear entry of a circadian protein, can synchronize neurons that present these differences. Detailed immunofluorescent recordings have suggested that, whereas in the mutant, LNd neurons are synchronized, in the wild-type, a subset of the LNds oscillate faster than the rest. With our model, we find that a more likely explanation for the same observations is that this subset is being driven outside its synchronization range and displays therefore a complex pattern of oscillation. PMID:25416595

Risau-Gusman, Sebastián; Gleiser, Pablo M

2014-12-01

56

Cellular Clocks in AVP Neurons of the SCN Are Critical for Interneuronal Coupling Regulating Circadian Behavior Rhythm.  

PubMed

The suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals, is a network structure composed of multiple types of neurons. Here, we report that mice with a Bmal1 deletion specific to arginine vasopressin (AVP)-producing neurons showed marked lengthening in the free-running period and activity time of behavior rhythms. When exposed to an abrupt 8-hr advance of the light/dark cycle, these mice reentrained faster than control mice did. In these mice, the circadian expression of genes involved in intercellular communications, including Avp, Prokineticin 2, and Rgs16, was drastically reduced in the dorsal SCN, where AVP neurons predominate. In slices, dorsal SCN cells showed attenuated PER2::LUC oscillation with highly variable and lengthened periods. Thus, Bmal1-dependent oscillators of AVP neurons may modulate the coupling of the SCN network, eventually coupling morning and evening behavioral rhythms, by regulating expression of multiple factors important for the network property of these neurons. PMID:25741730

Mieda, Michihiro; Ono, Daisuke; Hasegawa, Emi; Okamoto, Hitoshi; Honma, Ken-Ichi; Honma, Sato; Sakurai, Takeshi

2015-03-01

57

Connectivity of pacemaker neurons in the neonatal rat superficial dorsal horn.  

PubMed

Pacemaker neurons with an intrinsic ability to generate rhythmic burst-firing have been characterized in lamina I of the neonatal spinal cord, where they are innervated by high-threshold sensory afferents. However, little is known about the output of these pacemakers, as the neuronal populations that are targeted by pacemaker axons have yet to be identified. The present study combines patch-clamp recordings in the intact neonatal rat spinal cord with tract-tracing to demonstrate that lamina I pacemaker neurons contact multiple spinal motor pathways during early life. Retrograde labeling of premotor interneurons with the trans-synaptic pseudorabies virus PRV-152 revealed the presence of burst-firing in PRV-infected lamina I neurons, thereby confirming that pacemakers are synaptically coupled to motor networks in the spinal ventral horn. Notably, two classes of pacemakers could be distinguished in lamina I based on cell size and the pattern of their axonal projections. Whereas small pacemaker neurons possessed ramified axons that contacted ipsilateral motor circuits, large pacemaker neurons had unbranched axons that crossed the midline and ascended rostrally in the contralateral white matter. Recordings from identified spino-parabrachial and spino-periaqueductal gray neurons indicated the presence of pacemaker activity within neonatal lamina I projection neurons. Overall, these results show that lamina I pacemakers are positioned to regulate both the level of activity in developing motor circuits and the ascending flow of nociceptive information to the brain, thus highlighting a potential role for pacemaker activity in the maturation of pain and sensorimotor networks in the central nervous system. J. Comp. Neurol. 523:1038-1053, 2015. © 2015 Wiley Periodicals, Inc. PMID:25380417

Li, Jie; Kritzer, Elizabeth; Ford, Neil C; Arbabi, Shahriar; Baccei, Mark L

2015-05-01

58

Pacemakers  

NSDL National Science Digital Library

A pacemaker generates electric pulses that regulate heartbeats. This patient education program explains how pacemakers work, and the benefits and risks of having one. It also discusses what to expect after getting a pacemaker. This is a MedlinePlus Interactive Health Tutorial from the National Library of Medicine, designed and developed by the Patient Education Institute. NOTE: The tutorial requires a special Flash plug-in, version 4 or above. If you do not have Flash, you will be prompted to obtain a free download of the software before you start the tutorial. You will also need an Acrobat Reader, available as a free download, in order to view the Reference Summary.

Patient Education Institute

59

Intrinsic near-24-h pacemaker period determines limits of circadian entrainment to a weak synchronizer in humans  

NASA Technical Reports Server (NTRS)

Endogenous circadian clocks are robust regulators of physiology and behavior. Synchronization or entrainment of biological clocks to environmental time is adaptive and important for physiological homeostasis and for the proper timing of species-specific behaviors. We studied subjects in the laboratory for up to 55 days each to determine the ability to entrain the human clock to a weak circadian synchronizing stimulus [scheduled activity-rest cycle in very dim (approximately 1.5 lux in the angle of gaze) light-dark cycle] at three approximately 24-h periods: 23.5, 24.0, and 24.6 h. These studies allowed us to test two competing hypotheses as to whether the period of the human circadian pacemaker is near to or much longer than 24 h. We report here that imposition of a sleep-wake schedule with exposure to the equivalent of candle light during wakefulness and darkness during sleep is usually sufficient to maintain circadian entrainment to the 24-h day but not to a 23.5- or 24.6-h day. Our results demonstrate functionally that, in normally entrained sighted adults, the average intrinsic circadian period of the human biological clock is very close to 24 h. Either exposure to very dim light and/or the scheduled sleep-wake cycle itself can entrain this near-24-h intrinsic period of the human circadian pacemaker to the 24-h day.

Wright, K. P. Jr; Hughes, R. J.; Kronauer, R. E.; Dijk, D. J.; Czeisler, C. A.

2001-01-01

60

Glycinergic pacemaker neurons in preBötzinger complex of neonatal mouse.  

PubMed

The preBötzinger complex (preBötC) is essential for normal respiratory rhythm generation in rodents, for which the underlying mechanisms remain unknown. Excitatory preBötC pacemaker neurons are proposed to be necessary for rhythm generation. Here we report the presence of a population of preBötC glycinergic pacemaker neurons. We used rhythmic in vitro transverse slice preparations from transgenic mice where neurons expressing the glycine transporter 2 (GlyT2) gene coexpress enhanced green fluorescent protein (EGFP). We combined epifluorescence and whole-cell patch-clamp recording to study preBötC EGFP-labeled, i.e., glycinergic, inspiratory-modulated neurons with pacemaker properties. We defined glycinergic pacemaker neurons as those preBötC EGFP neurons that exhibited the following: (1) ectopic bursting in rhythmic slices when depolarized during their normally silent period and (2) bursting when depolarized in nonrhythmic slices (following AMPA receptor blockade). Forty-two percent of EGFP-labeled neurons were inspiratory (n = 48 of 115), of which 23% (n = 11 of 48 inspiratory; 10% of the total recorded) were pacemakers. We conclude that there is a population of preBötC inspiratory-modulated glycinergic, presumably inhibitory, pacemaker neurons that constitute a substantial fraction of all preBötC pacemaker neurons. These findings challenge contemporary models for respiratory rhythmogenesis that assume the excitatory nature of preBötC pacemaker neurons. Testable and nontrivial predictions of the functional role of excitatory and inhibitory pacemaker neurons need to be proposed and the necessary experiments performed. PMID:20219997

Morgado-Valle, Consuelo; Baca, Serapio M; Feldman, Jack L

2010-03-10

61

Circadian pacemakers in lizards: phase-response curves and effects of pinealectomy.  

PubMed

Phase-response curves (PRCs) for 6-h fluorescent light pulses are described for both intact (sham-pinealectomized) and pinealectomized iguanid lizards (Sceloporus occidentalis). Although strongly diurnal in habit the PRC for intact lizards is more typical of those seen in nocturnal rodents. Other "nocturnal" characteristics of this lizard include the fact that the average free-running period (tau) is less than 24 h and the average tau in continuous light is longer than that observed in continuous darkness. The PRC for pinealectomized lizards is greatly distorted relative to that obtained from intact lizards. This "distortion" is discussed in terms of the role of the pineal as a coupling device or as a pacemaker within a multioscillator circadian system. In some individuals pinealectomy was also associated with 1) increased instability in free-running activity rhythms or arrhythmicity and 2) nocturnal entrainment to LD 12:12. PMID:6859292

Underwood, H

1983-06-01

62

Spontaneous Synchronization of Coupled Circadian Oscillators  

Microsoft Academic Search

In mammals, the circadian pacemaker, which controls daily rhythms, is located in the suprachiasmatic nucleus (SCN). Circadian oscillations are generated in individual SCN neurons by a molecular regulatory network. Cells oscillate with periods ranging from 20 to 28h, but at the tissue level, SCN neurons display significant synchrony, suggesting a robust intercellular coupling in which neurotransmitters are assumed to play

Didier Gonze; Samuel Bernard; Christian Waltermann; Achim Kramer; Hanspeter Herzel

2005-01-01

63

Refinement of a limit cycle oscillator model of the effects of light on the human circadian pacemaker  

NASA Technical Reports Server (NTRS)

In 1990, Kronauer proposed a mathematical model of the effects of light on the human circadian pacemaker. Although this model predicted many general features of the response of the human circadian pacemaker to light exposure, additional data now available enable us to refine the original model. We first refined the original model by incorporating the results of a dose response curve to light into the model's predicted relationship between light intensity and the strength of the drive onto the pacemaker. Data from three bright light phase resetting experiments were then used to refine the amplitude recovery characteristics of the model. Finally, the model was tested and further refined using data from an extensive phase resetting experiment in which a 3-cycle bright light stimulus was presented against a background of dim light. In order to describe the results of the four resetting experiments, the following major refinements to the original model were necessary: (i) the relationship between light intensity (I) and drive onto the pacemaker was reduced from I1/3 to I0.23 for light levels between 150 and 10,000 lux; (ii) the van der Pol oscillator from the original model was replaced with a higher-order limit cycle oscillator so that amplitude recovery is slower near the singularity and faster near the limit cycle; (iii) a direct effect of light on circadian period (tau x) was incorporated into the model such that as I increases, tau x decreases, which is in accordance with "Aschoff's rule". This refined model generates the following testable predictions: it should be difficult to enhance normal circadian amplitude via bright light; near the critical point of a type 0 phase response curve (PRC) the slope should be steeper than it is in a type 1 PRC; and circadian period measured during forced desynchrony should be directly affected by ambient light intensity.

Jewett, M. E.; Kronauer, R. E.; Brown, E. N. (Principal Investigator)

1998-01-01

64

Human circadian pacemaker is sensitive to light throughout subjective day without evidence of transients  

NASA Technical Reports Server (NTRS)

Fifty-six resetting trials were conducted across the subjective day in 43 young men using a three-cycle bright-light (approximately 10,000 lx). The phase-response curve (PRC) to these trials was assessed for the presence of a "dead zone" of photic insensitivity and was compared with another three-cycle PRC that had used a background of approximately 150 lx. To assess possible transients after the light stimulus, the trials were divided into 43 steady-state trials, which occurred after several baseline days, and 13 consecutive trials, which occurred immediately after a previous resetting trial. We found that 1) bright light induces phase shifts throughout subjective day with no apparent dead zone; 2) there is no evidence of transients in constant routine assessments of the fitted temperature minimum 1-2 days after completion of the resetting stimulus; and 3) the timing of background room light modulates the resetting response to bright light. These data indicate that the human circadian pacemaker is sensitive to light at virtually all circadian phases, implying that the entire 24-h pattern of light exposure contributes to entrainment.

Jewett, M. E.; Rimmer, D. W.; Duffy, J. F.; Klerman, E. B.; Kronauer, R. E.; Czeisler, C. A.

1997-01-01

65

Two-oscillator structure of the pacemaker controlling the circadian rhythm of N-acetyltransferase in the rat pineal gland  

Microsoft Academic Search

1.The organization of the pacemaker driving the circadian rhythm of N-acetyltransferase activity in the rat pineal gland was studied by observing changes of the rhythm caused by 1 min light pulses applied at night. These pulses proved to be effective phase-shifting signals.2.After 1 min light pulses applied in the first half of the night. N-acetyltransferase activity began to increase anew

Helena Illnerová; Ji?í Van??ek

1982-01-01

66

Does human evolution in different latitudes influence susceptibility to obesity via the circadian pacemaker?: migration and survival of the fittest in the modern age of lifestyle-induced circadian desynchrony.  

PubMed

The variable photoperiods of Northern latitudes challenge the entrainment capacity of the circadian pacemaker, which evolved under constant photoperiods in Equatorial regions. Entrainment to the erratic photoperiods facilitated by artificial light presents an additional challenge. Metabolic dysfunction and obesity are potential consequences of such desynchronization of circadian and environmental rhythms. PMID:22933057

Wyse, Cathy A

2012-11-01

67

Circadian clock proteins regulate neuronal redox homeostasis and neurodegeneration  

PubMed Central

Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator–like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration. PMID:24270424

Musiek, Erik S.; Lim, Miranda M.; Yang, Guangrui; Bauer, Adam Q.; Qi, Laura; Lee, Yool; Roh, Jee Hoon; Ortiz-Gonzalez, Xilma; Dearborn, Joshua T.; Culver, Joseph P.; Herzog, Erik D.; Hogenesch, John B.; Wozniak, David F.; Dikranian, Krikor; Giasson, Benoit I.; Weaver, David R.; Holtzman, David M.; FitzGerald, Garret A.

2013-01-01

68

Drosophila pacemaker neurons require G-protein signaling and GABAergic inputs to generate 24hr behavioral rhythms  

PubMed Central

Summary Intercellular signaling is important for accurate circadian rhythms. In Drosophila, the small ventral lateral neurons (s-LNvs) are the dominant pacemaker neurons and set the pace of most other clock neurons in constant darkness. Here we show that two distinct G-protein signaling pathways are required in LNvs for 24hr rhythms. Reducing signaling in LNvs via the G-alpha subunit Gs, which signals via cAMP, or via the G-alpha subunit Go, which we show signals via Phospholipase 21c, lengthens the period of behavioral rhythms. In contrast, constitutive Gs or Go signaling makes most flies arrhythmic. Using dissociated LNvs in culture, we found that Go and the metabotropic GABAB-R3 receptor are required for the inhibitory effects of GABA on LNvs and that reduced GABAB-R3 expression in vivo lengthens period. Although no clock neurons produce GABA, hyper-exciting GABAergic neurons disrupts behavioral rhythms and s-LNv molecular clocks. Therefore, s-LNvs require GABAergic inputs for 24hr rhythms. PMID:21145008

Dahdal, David; Reeves, David C.; Ruben, Marc; Akabas, Myles H.; Blau, Justin

2010-01-01

69

"Caged Calcium" in Aplysia Pacemaker Neurons Characterization of Calcium-activated Potassium and  

E-print Network

"Caged Calcium" in Aplysia Pacemaker Neurons Characterization of Calcium-activated Potassium-Anatomy, Universityof California, Berkeley, California 94720 ABSTRACT We have studied calcium-activated potassium neurons, using photolysis of a calcium chelator (nitr-5 or nitr-7) to release "caged calcium

Zucker, Robert S.

70

Follower Neurons in Lobster (Panulirus interruptus) Pyloric Network Regulate Pacemaker Period in Complementary Ways  

E-print Network

Follower Neurons in Lobster (Panulirus interruptus) Pyloric Network Regulate Pacemaker Period November 2002 Weaver, Adam L. and Scott L. Hooper. Follower neurons in lobster (Panulirus interruptus this technique to study cycle period control in the rhythmic pyloric network of the lobster, Panulirus

Hooper, Scott

71

Pacemaker rate and depolarization block in nigral dopamine neurons: a somatic sodium channel balancing act  

PubMed Central

Midbrain dopamine (DA) neurons are slow intrinsic pacemakers that undergo depolarization (DP) block upon moderate stimulation. Understanding DP block is important because it has been correlated with the clinical efficacy of chronic antipsychotic drug treatment. Here we describe how voltage-gated sodium (NaV) channels regulate DP block and pacemaker activity in DA neurons of the substantia nigra using rat brain slices. The distribution, density and gating of NaV currents were manipulated by blocking native channels with tetrodotoxin and by creating virtual channels and anti-channels with dynamic clamp. Although action potentials initiate in the axon initial segment (AIS) and NaV channels are distributed in multiple dendrites, selective reduction of NaV channel activity in the soma was sufficient to decrease pacemaker frequency and increase susceptibility to DP block. Conversely, increasing somatic NaV current density raised pacemaker frequency and lowered susceptibility to DP block. Finally, when NaV currents were restricted to the soma, pacemaker activity occurred at abnormally high rates due to excessive local subthreshold NaV current. Together with computational simulations, these data show that both the slow pacemaker rate and the sensitivity to DP block that characterizes DA neurons result from the low density of somatic NaV channels. More generally, we conclude that the somatodendritic distribution of NaV channels is a major determinant of repetitive spiking frequency. PMID:23077037

Tucker, Kristal R.; Huertas, Marco A.; Horn, John P.; Canavier, Carmen C.; Levitan, Edwin S.

2012-01-01

72

Dissecting differential gene expression within the circadian neuronal circuit of Drosophila  

Microsoft Academic Search

Behavioral circadian rhythms are controlled by a neuronal circuit consisting of diverse neuronal subgroups. To understand the molecular mechanisms underlying the roles of neuronal subgroups within the Drosophila circadian circuit, we used cell-type specific gene-expression profiling and identified a large number of genes specifically expressed in all clock neurons or in two important subgroups. Moreover, we identified and characterized two

Emi Nagoshi; Ken Sugino; Ela Kula; Etsuko Okazaki; Taro Tachibana; Sacha Nelson; Michael Rosbash

2009-01-01

73

Synergistic interactions between the molecular and neuronal circadian networks drive robust behavioral circadian rhythms in Drosophila melanogaster.  

PubMed

Most organisms use 24-hr circadian clocks to keep temporal order and anticipate daily environmental changes. In Drosophila melanogaster CLOCK (CLK) and CYCLE (CYC) initiates the circadian system by promoting rhythmic transcription of hundreds of genes. However, it is still not clear whether high amplitude transcriptional oscillations are essential for circadian timekeeping. In order to address this issue, we generated flies in which the amplitude of CLK-driven transcription can be reduced partially (approx. 60%) or strongly (90%) without affecting the average levels of CLK-target genes. The impaired transcriptional oscillations lead to low amplitude protein oscillations that were not sufficient to drive outputs of peripheral oscillators. However, circadian rhythms in locomotor activity were resistant to partial reduction in transcriptional and protein oscillations. We found that the resilience of the brain oscillator is depending on the neuronal communication among circadian neurons in the brain. Indeed, the capacity of the brain oscillator to overcome low amplitude transcriptional oscillations depends on the action of the neuropeptide PDF and on the pdf-expressing cells having equal or higher amplitude of molecular rhythms than the rest of the circadian neuronal groups in the fly brain. Therefore, our work reveals the importance of high amplitude transcriptional oscillations for cell-autonomous circadian timekeeping. Moreover, we demonstrate that the circadian neuronal network is an essential buffering system that protects against changes in circadian transcription in the brain. PMID:24698952

Weiss, Ron; Bartok, Osnat; Mezan, Shaul; Malka, Yuval; Kadener, Sebastian

2014-04-01

74

Synergistic Interactions between the Molecular and Neuronal Circadian Networks Drive Robust Behavioral Circadian Rhythms in Drosophila melanogaster  

PubMed Central

Most organisms use 24-hr circadian clocks to keep temporal order and anticipate daily environmental changes. In Drosophila melanogaster CLOCK (CLK) and CYCLE (CYC) initiates the circadian system by promoting rhythmic transcription of hundreds of genes. However, it is still not clear whether high amplitude transcriptional oscillations are essential for circadian timekeeping. In order to address this issue, we generated flies in which the amplitude of CLK-driven transcription can be reduced partially (approx. 60%) or strongly (90%) without affecting the average levels of CLK-target genes. The impaired transcriptional oscillations lead to low amplitude protein oscillations that were not sufficient to drive outputs of peripheral oscillators. However, circadian rhythms in locomotor activity were resistant to partial reduction in transcriptional and protein oscillations. We found that the resilience of the brain oscillator is depending on the neuronal communication among circadian neurons in the brain. Indeed, the capacity of the brain oscillator to overcome low amplitude transcriptional oscillations depends on the action of the neuropeptide PDF and on the pdf-expressing cells having equal or higher amplitude of molecular rhythms than the rest of the circadian neuronal groups in the fly brain. Therefore, our work reveals the importance of high amplitude transcriptional oscillations for cell-autonomous circadian timekeeping. Moreover, we demonstrate that the circadian neuronal network is an essential buffering system that protects against changes in circadian transcription in the brain. PMID:24698952

Weiss, Ron; Bartok, Osnat; Mezan, Shaul; Malka, Yuval; Kadener, Sebastian

2014-01-01

75

Sodium and calcium current-mediated pacemaker neurons and respiratory rhythm generation.  

PubMed

The breathing motor pattern in mammals originates in brainstem networks. Whether pacemaker neurons play an obligatory role remains a key unanswered question. We performed whole-cell recordings in the preBotzinger Complex in slice preparations from neonatal rodents and tested for pacemaker activity. We observed persistent Na+ current (I(NaP))-mediated bursting in approximately 5% of inspiratory neurons in postnatal day 0 (P0)-P5 and in P8-P10 slices. I(NaP)-mediated bursting was voltage dependent and blocked by 20 mum riluzole (RIL). We found Ca2+ current (I(Ca))-dependent bursting in 7.5% of inspiratory neurons in P8-P10 slices, but in P0-P5 slices these cells were exceedingly rare (0.6%). This bursting was voltage independent and blocked by 100 microm Cd2+ or flufenamic acid (FFA) (10-200 microm), which suggests that a Ca2+-activated inward cationic current (I(CAN)) underlies burst generation. These data substantiate our observation that P0-P5 slices exposed to RIL contain few (if any) pacemaker neurons, yet maintain respiratory rhythm. We also show that 20 nm TTX or coapplication of 20 microm RIL + FFA (100-200 microm) stops the respiratory rhythm, but that adding 2 mum substance P restarts it. We conclude that I(NaP) and I(CAN) enhance neuronal excitability and promote rhythmogenesis, even if their magnitude is insufficient to support bursting-pacemaker activity in individual neurons. When I(NaP) and I(CAN) are removed pharmacologically, the rhythm can be maintained by boosting neural excitability, which is inconsistent with a pacemaker-essential mechanism of respiratory rhythmogenesis by the preBotzinger complex. PMID:15647488

Del Negro, Christopher A; Morgado-Valle, Consuelo; Hayes, John A; Mackay, Devin D; Pace, Ryland W; Crowder, Erin A; Feldman, Jack L

2005-01-12

76

Stochastic resonance on a modular neuronal network of small-world subnetworks with a subthreshold pacemaker  

NASA Astrophysics Data System (ADS)

We study the phenomenon of stochastic resonance on a modular neuronal network consisting of several small-world subnetworks with a subthreshold periodic pacemaker. Numerical results show that the correlation between the pacemaker frequency and the dynamical response of the network is resonantly dependent on the intensity of additive spatiotemporal noise. This effect of pacemaker-driven stochastic resonance of the system depends extensively on the local and the global network structure, such as the intra- and inter-coupling strengths, rewiring probability of individual small-world subnetwork, the number of links between different subnetworks, and the number of subnetworks. All these parameters play a key role in determining the ability of the network to enhance the noise-induced outreach of the localized subthreshold pacemaker, and only they bounded to a rather sharp interval of values warrant the emergence of the pronounced stochastic resonance phenomenon. Considering the rather important role of pacemakers in real-life, the presented results could have important implications for many biological processes that rely on an effective pacemaker for their proper functioning.

Yu, Haitao; Wang, Jiang; Liu, Chen; Deng, Bin; Wei, Xile

2011-12-01

77

Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus.  

PubMed

The hypothalamic arcuate nucleus (ARC) integrates and responds to satiety and hunger signals and forms the origins of the central neural response to perturbations in energy balance. Here we show that rat ARC neurons containing neuropeptide Y (NPY) and agouti-related protein (AgRP), which are conditional pacemakers, are activated by orexigens and inhibited by the anorexigen leptin. We propose a neuron-specific signaling mechanism through which central and peripheral signals engage the central neural anabolic drive. PMID:15097991

van den Top, Marco; Lee, Kevin; Whyment, Andrew D; Blanks, Andrew M; Spanswick, David

2004-05-01

78

Molecular and Neuronal Analysis of Circadian Photoresponses in Drosophila: A Dissertation  

Microsoft Academic Search

Most organisms, from cyanobacteria to humans are equipped with circadian clocks. These endogenous and self-sustained pacemakers allow organisms to adapt their physiology and behavior to daily environmental variations, and to anticipate them. The circadian clock is synchronized by environmental cues (i.e. light and temperature fluctuations).\\u000aThe fruit fly, Drosophila melanogaster, is well established as a model for the study of

Alejandro D. Murad

2007-01-01

79

Pineal and hypothalamic pacemakers: Their role in regulating circadian rhythmicity in Japanese quail  

Microsoft Academic Search

Neither pinealectomy nor administration of melatoninvia silastic capsules had any effect on free-running circadian rhythms of locomotor activity in Japanese quail (Coturnix coturnix japonica). The quail, like the chicken, therefore differs from sparrows and starlings in which pinealectomy dramatically disrupts free-running rhythms. Nevertheless, it seems unlikely that there are fundamental differences in circadian organisation within the Class Aves. The effects

S. M. Simpson; B. K. Follett

1981-01-01

80

Metabolic regulations of the rhythmic activity in pacemaker neurons. II. Metabolically induced conversions of beating to bursting pacemaker activity in isolated Aplysia neurons.  

PubMed

In pacemaker neurons of the sea hare Aplysia californica, isolated from their synaptic, ephaptic and humoral inputs, conversion of the regular beating to a bursting discharge pattern can be induced by certain cell metabolites. Administration of the phosphofructokinase (PFK) activator fructose-6-phosphate (F-6-P), or its nonmetabolizable analogue 1-deoxy-F-6-P, induced bursting discharges in R3, R5, R6 and R11 neurons, with spike doublets and triplets appearing transiently in the time pattern. With another PFK activitor, adenosine-5-monophosphate, only double spikes have been noted in R7, R8 and R14 neurons. Burst activity was induced also in the presence of the fructose-1,6-diphosphatase activators, citrate and 3-phosphoglycerate, in R9, R10 and R12 neurons. Cyclic 3',5'-AMP, which also activates the PFK (beside other effects on cellular metabolism), induced bursting discharges in all R3-R14 neurons. In contrast, the inhibitors of the PFK, citrate and ATP, decreased the spike activity of the bursting L3 and L6 neurons, even changing L3 neurons to the regular beating type. Among a variety of cell metabolites tested only pyruvate was able to induce a burst-like tendency in R9 neurons. The characteristic bursting patterns which appeared in the presence of the described metabolic effectors could not be duplicated by low Ca2+ and/or high K+ media nor by artificial shifts in membrane potential triggered by depolarizing and hyperpolarizing currents. PMID:179661

Chaplain, R A

1976-04-23

81

Influences of the circadian clock on neuronal susceptibility to excitotoxicity  

PubMed Central

Stroke is the third leading cause of death and the primary cause of morbidity in the United States, thus posing an enormous burden on the healthcare system. The factors that determine the risk of an individual toward precipitation of an ischemic event possess a strong circadian component as does the ischemic event itself. This predictability provided a window of opportunity toward the development of chronopharmaceuticals which provided much better clinical outcomes. Experiments from our lab showed for the first time that neuronal susceptibility to ischemic events follows a circadian pattern; hippocampal neurons being most susceptible to an ischemic insult occurring during peak activity in a rodent model of global cerebral ischemia. We also demonstrated that the SCN2.2 cells (like their in vivo counterpart) are resistant to excitotoxicity by glutamate and that this was dependent on activation of ERK signaling. We are currently working on elucidating the complete neuroprotective pathway that provides a barricade against glutamate toxicity in the SCN2.2 cells. Our future experiments will be engaged in hijacking the neuroprotective mechanism in the SCN2.2 cells and applying it to glutamate-susceptible entities in an effort to prevent their death in the presence of excitotoxicity. Despite the advancement in chronopharmaceuticals, optimal clinical outcome with minimal adverse events are difficult to come by at an affordable price. Superior treatment options require a better understanding of molecular mechanisms that define the disease, including the role of the circadian clock. PMID:24204346

Karmarkar, Sumedha W.; Tischkau, Shelley A.

2013-01-01

82

Mop3 Is an Essential Component of the Master Circadian Pacemaker in Mammals  

Microsoft Academic Search

Circadian oscillations in mammalian physiology and behavior are regulated by an endogenous biological clock. Here we show that loss of the PAS protein MOP3 (also known as BMAL1) in mice results in immediate and complete loss of circadian rhythmicity in constant darkness. Additionally, locomotor activity in light–dark (LD) cycles is impaired and activity levels are reduced in Mop3?\\/? mice. Analysis

Maureen K. Bunger; Lisa D. Wilsbacher; Susan M. Moran; Cynthia Clendenin; Laurel A. Radcliffe; John B. Hogenesch; M. Celeste Simon; Joseph S. Takahashi; Christopher A. Bradfield

2000-01-01

83

Calcium-dependent phosphorylation regulates neuronal stability and plasticity in a highly precise pacemaker nucleus  

PubMed Central

Specific types of neurons show stable, predictable excitability properties, while other neurons show transient adaptive plasticity of their excitability. However, little attention has been paid to how the cellular pathways underlying adaptive plasticity interact with those that maintain neuronal stability. We addressed this question in the pacemaker neurons from a weakly electric fish because these neurons show a highly stable spontaneous firing rate as well as an N-methyl-d-aspartate (NMDA) receptor-dependent form of plasticity. We found that basal firing rates were regulated by a serial interaction of conventional and atypical PKC isoforms and that this interaction establishes individual differences within the species. We observed that NMDA receptor-dependent plasticity is achieved by further activation of these kinases. Importantly, the PKC pathway is maintained in an unsaturated baseline state to allow further Ca2+-dependent activation during plasticity. On the other hand, the Ca2+/calmodulin-dependent phosphatase calcineurin does not regulate baseline firing but is recruited to control the duration of the NMDA receptor-dependent plasticity and return the pacemaker firing rate back to baseline. This work illustrates how neuronal plasticity can be realized by biasing ongoing mechanisms of stability (e.g., PKC) and terminated by recruiting alternative mechanisms (e.g., calcineurin) that constrain excitability. We propose this as a general model for regulating activity-dependent change in neuronal excitability. PMID:21525377

Macleod, Gregory T.; Zakon, Harold H.

2011-01-01

84

Individual neurons dissociated from rat suprachiasmatic nucleus express independently phased circadian firing rhythms  

Microsoft Academic Search

Within the mammalian hypothalamus, the suprachiasmatic nucleus (SCN) contains a circadian clock for timing of diverse neuronal, endocrine, and behavioral rhythms. By culturing cells from neonatal rat SCN on fixed microelectrode arrays, we have been able to record spontaneous action potentials from individual SCN neurons for days or weeks, revealing prominent circadian rhythms in firing rate. Despite abundant functional synapses,

David K. Welsh; Diomedes E. Logothetis; Markus Meister; Steven M. Reppert

1995-01-01

85

Contribution of the Circadian Pacemaker and the Sleep Homeostat to Sleep Propensity, Sleep Structure, Electroencephalographic Slow Waves, and Sleep Spindle Activity in Humans  

Microsoft Academic Search

The role of the endogenous circadian pacemaker in the tim- ing of the sleep-wake cycle and the regulation of the in- ternal structure of sleep, including REM sleep, EEG slow- wave (0.7545 Hz) and sleep spindle activity (12.75-15.0 Hz) was investigated. Eight men lived in an environment free of time cues for 33-36 d and were scheduled to a 28

Derk-Jan Dijk; Charles A. Czeisler

1995-01-01

86

Circadian Factor BMAL1 in Histaminergic Neurons Regulates Sleep Architecture  

PubMed Central

Summary Circadian clocks allow anticipation of daily environmental changes [1]. The suprachiasmatic nucleus (SCN) houses the master clock, but clocks are also widely expressed elsewhere in the body [1]. Although some peripheral clocks have established roles [1], it is unclear what local brain clocks do [2, 3]. We tested the contribution of one putative local clock in mouse histaminergic neurons in the tuberomamillary nucleus to the regulation of the sleep-wake cycle. Histaminergic neurons are silent during sleep, and start firing after wake onset [4–6]; the released histamine, made by the enzyme histidine decarboxylase (HDC), enhances wakefulness [7–11]. We found that hdc gene expression varies with time of day. Selectively deleting the Bmal1 (also known as Arntl or Mop3 [12]) clock gene from histaminergic cells removes this variation, producing higher HDC expression and brain histamine levels during the day. The consequences include more fragmented sleep, prolonged wake at night, shallower sleep depth (lower nonrapid eye movement [NREM] ? power), increased NREM-to-REM transitions, hindered recovery sleep after sleep deprivation, and impaired memory. Removing BMAL1 from histaminergic neurons does not, however, affect circadian rhythms. We propose that for mammals with polyphasic/nonwake consolidating sleep, the local BMAL1-dependent clock directs appropriately timed declines and increases in histamine biosynthesis to produce an appropriate balance of wake and sleep within the overall daily cycle of rest and activity specified by the SCN. PMID:25454592

Yu, Xiao; Zecharia, Anna; Zhang, Zhe; Yang, Qianzi; Yustos, Raquel; Jager, Polona; Vyssotski, Alexei L.; Maywood, Elizabeth S.; Chesham, Johanna E.; Ma, Ying; Brickley, Stephen G.; Hastings, Michael H.; Franks, Nicholas P.; Wisden, William

2014-01-01

87

Circadian modulation of osmoregulated firing in rat supraoptic nucleus neurones.  

PubMed

The antidiuretic hormone vasopressin (VP) promotes water reabsorption from the kidney and levels of circulating VP are normally related linearly to plasma osmolality, aiming to maintain the latter close to a predetermined set point. Interestingly, VP levels rise also in the absence of an increase in osmolality during late sleep in various mammals, including rats and humans. This circadian rhythm is functionally important because the absence of a late night VP surge results in polyuria and disrupts sleep in humans. Previous work has indicated that the VP surge may be caused by facilitation of the central processes mediating the osmotic control of VP release, and the mechanism by which this occurs was recently studied in angled slices of rat hypothalamus that preserve intact network interactions between the suprachiasmatic nucleus (SCN; the biological clock), the organum vasculosum lamina terminalis (OVLT; the central osmosensory nucleus) and the supraoptic nucleus (SON; which contains VP-releasing neurohypophysial neurones). These studies confirmed that the electrical activity of SCN clock neurones is higher during the middle sleep period (MSP) than during the late sleep period (LSP). Moreover, they revealed that the excitation of SON neurones caused by hyperosmotic stimulation of the OVLT was greater during the LSP than during the MSP. Activation of clock neurones by repetitive electrical stimulation, or by injection of glutamate into the SCN, caused a presynaptic inhibition of glutamatergic synapses made between the axon terminals of OVLT neurones and SON neurones. Consistent with this effect, activation of clock neurones with glutamate also reduced the excitation of SON neurones caused by hyperosmotic stimulation of the OVLT. These results suggest that clock neurones in the SCN can mediate an increase in VP release through a disinhibition of excitatory synapses between the OVLT and the SON during the LSP. PMID:22330181

Trudel, E; Bourque, C W

2012-04-01

88

Alterations of Estrous Activity in the Ewe by Circadian-Based Manipulation of the Endogenous Pacemaker  

Microsoft Academic Search

The timing of reproductive activity in the seasonal breeding Romney Marsh ewe depends on the measurement of photoperiodic time. In this experiment, artificial light and dark signals are provided in a measured sequence at an inappropriate time of year to induce breeding out of phase with environmental photoperiod. The endogenous circadian responses and reproductive effects are documented. One group (Group

Michael V. Guerin; Colin D. Matthews

1998-01-01

89

PDF neuron firing phase-shifts key circadian activity neurons in Drosophila  

PubMed Central

Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY. DOI: http://dx.doi.org/10.7554/eLife.02780.001 PMID:24939987

Guo, Fang; Cerullo, Isadora; Chen, Xiao; Rosbash, Michael

2014-01-01

90

Dual regulation of clock gene Per2 expression in discrete brain areas by the circadian pacemaker and methamphetamine-induced oscillator in rats.  

PubMed

Behavioral rhythms induced by methamphetamine (MAP) treatment in rats are independent of the circadian pacemaker in the suprachiasmatic nucleus (SCN). To know the site and mechanism of an underlying oscillation (MAP-induced oscillator; MAO), extra-SCN circadian rhythms in the discrete brain areas were examined in rats with and without the SCN. To fix the phase of MAO, MAP was supplied in drinking water at a restricted time of day for 14 days (R-MAP) and subsequently given ad libitum (ad-MAP). Plain water was given to the controls at the same restricted time (R-Water). Clock gene Per2 expression was measured by a bioluminescence reporter in cultured brain tissues. In SCN-intact rats, MAO was induced by R-MAP and behavioral rhythms were phase-delayed from the restricted time under ad-MAP with relative coordination. Circadian Per2 rhythms in R-MAP rats were not affected in the SCN but were slightly phase-advanced in the olfactory bulb (OB), caudate-putamen (CPU) and substantia nigra (SN) as compared with R-Water rats. Following SCN lesion, R-MAP-induced MAO phase-shifted more slowly and did not show a sign of relative coordination. In these rats, circadian Per2 rhythms were significantly phase-shifted in the OB and SN as compared with SCN-intact rats. These findings indicate that MAO was induced by MAP given at a restricted time of day in association with phase-shifts of the extra-SCN circadian oscillators in the brain dopaminergic areas. The findings also suggest that these extra-SCN oscillators are the components of MAO and receive dual regulation by MAO and the SCN circadian pacemaker. PMID:24438490

Natsubori, Akiyo; Honma, Ken-ichi; Honma, Sato

2014-01-01

91

Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock  

Microsoft Academic Search

The Drosophila period protein (PER) is a predominantly nuclear protein and a likely component of a circadian clock. PER is required for daily oscillations in the transcription of its own gene and thus participates in a circadian feedback loop. In this study, key pacemaker neurons of the Drosophila brain were examined to determine whether the subcellular distribution of PER changes

Kathryn D Curtin; Zuoshi J Huang; Michael Rosbash

1995-01-01

92

Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component.  

PubMed

Many organisms use circadian clocks to keep temporal order and anticipate daily environmental changes. In Drosophila, the master clock gene Clock promotes the transcription of several key target genes. Two of these gene products, PER and TIM, repress CLK-CYC-mediated transcription. To recognize additional direct CLK target genes, we designed a genome-wide approach and identified clockwork orange (cwo) as a new core clock component. cwo encodes a transcriptional repressor that synergizes with PER and inhibits CLK-mediated activation. Consistent with this function, the mRNA profiles of CLK direct target genes in cwo mutant flies manifest high trough values and low amplitude oscillations. Because behavioral rhythmicity fails to persist in constant darkness (DD) with little or no effect on average mRNA levels in flies lacking cwo, transcriptional oscillation amplitude appears to be linked to rhythmicity. Moreover, the mutant flies are long period, consistent with the late repression indicated by the RNA profiles. These findings suggest that CWO acts preferentially in the late night to help terminate CLK-CYC-mediated transcription of direct target genes including cwo itself. The presence of mammalian homologs with circadian expression features (Dec1 and Dec2) suggests that a similar feedback mechanism exists in mammalian clocks. PMID:17578907

Kadener, Sebastian; Stoleru, Dan; McDonald, Michael; Nawathean, Pipat; Rosbash, Michael

2007-07-01

93

Sequential Nuclear Accumulation of the Clock Proteins Period and Timeless in the Pacemaker Neurons of Drosophila melanogaster  

Microsoft Academic Search

Antisera against the circadian clock proteins Period (PER) and Timeless (TIM) were used to construct a detailed time course of PER and TIM expression and subcellular localization in a subset of the ventrolateral neurons (vLNs) in the Drosophila accessory medulla (AMe). These neurons, which express pigment- dispersing factor, play a central role in the control of behavioral rhythms. The data

Orie T. Shafer; Michael Rosbash; James W. Truman

2002-01-01

94

Contribution of Drosophila TRPA1-Expressing Neurons to Circadian Locomotor Activity Patterns  

PubMed Central

In both vertebrates and invertebrates, Transient Receptor Potential (TRP) channels are expressed in sensory neurons and mediate environmental stimuli such as light, sound, temperature, and taste. Some of these channels, however, are expressed only in the brain and their functions remain incompletely understood. Using the GAL4/UAS binary system with a line in which the GAL4 had been knocked into the trpA1 locus in Drosophila, we recently reported new insights into TRPA1 localization and function, including its expression in approximately 15% of all circadian neurons. TRPA1 is expressed in lateral posterior neurons (LPNs), which are known to be highly sensitive to entrainment by temperature cycles. Here, I used the bacterial sodium channel, NaChBac, to examine the effects of altering the electrical properties of trpA1 neurons on circadian rhythms. My results indicate that circadian activity of the flies in the morning, daytime, and evening was affected in a temperature-dependent manner following TRPA1 neuronal activation. Remarkably, TRPA1 neuron activation in flies kept at 18°C impacted the morning peak of circadian activity even though TRPA1 is not expressed in morning cells. Taken together, these results suggest that the activation of TRPA1-expressing neurons may differentially coordinate light/dark circadian entrainment, depending on the temperature. PMID:24367706

Lee, Youngseok

2013-01-01

95

Persistent Sodium Current Drives Conditional Pacemaking in CA1 Pyramidal Neurons under Muscarinic Stimulation  

PubMed Central

Hippocampal CA1 pyramidal neurons are normally quiescent but can fire spontaneously when stimulated by muscarinic agonists. In brain slice recordings from mouse CA1 pyramidal neurons, we examined the ionic basis of this activity using interleaved current-clamp and voltage-clamp experiments. Both in control and after muscarinic stimulation, the steady-state current–voltage curve was dominated by inward TTX-sensitive persistent sodium current (INaP) that activated near ?75 mV and increased steeply with depolarization. In control, total membrane current was net outward (hyperpolarizing) near ?70 mV so that cells had a stable resting potential. Muscarinic stimulation activated a small nonselective cation current so that total membrane current near ?70 mV shifted to become barely net inward (depolarizing). The small depolarization triggers regenerative activation of INaP, which then depolarizes the cell from ?70 mV to spike threshold. We quantified the relative contributions of INaP, hyperpolarization-activated cation current (Ih), and calcium current to pacemaking by using the cell's own firing as a voltage command along with specific blockers. TTX-sensitive sodium current was substantial throughout the entire interspike interval, increasing as the membrane potential approached threshold, while both Ih and calcium current were minimal. Thus, spontaneous activity is driven primarily by activation of INaP in a positive feedback loop starting near ?70 mV and providing increasing inward current to threshold. These results show that the pacemaking “engine” from INaP is an inherent property of CA1 pyramidal neurons that can be engaged or disengaged by small shifts in net membrane current near ?70 mV, as by muscarinic stimulation. PMID:24048831

Yamada-Hanff, Jason

2013-01-01

96

Circadian regulation of cellular physiology.  

PubMed

The circadian clock synchronizes behavioral and physiological processes on a daily basis in anticipation of the light-dark cycle. In mammals, molecular clocks are present in both the central pacemaker neurons and in nearly all peripheral tissues. Clock transcription factors in metabolic tissues coordinate metabolic fuel utilization and storage with alternating periods of feeding and fasting corresponding to the rest-activity cycle. In vitro and in vivo biochemical approaches have led to the discovery of mechanisms underlying the interplay between the molecular clock and the metabolic networks. For example, recent studies have demonstrated that the circadian clock controls rhythmic synthesis of the cofactor nicotinamide adenine dinucleotide (NAD(+)) and activity of NAD(+)-dependent sirtuin deacetylase enzymes to regulate mitochondrial function across the circadian cycle. In this chapter, we review current state-of-the-art methods to analyze circadian cycles in mitochondrial bioenergetics, glycolysis, and nucleotide metabolism in both cell-based and animal models. PMID:25707277

Peek, C B; Ramsey, K M; Levine, D C; Marcheva, B; Perelis, M; Bass, J

2015-01-01

97

Millimeter waves thermally alter the firing rate of the Lymnaea pacemaker neuron  

SciTech Connect

The effects of millimeter waves (mm-waves, 75 GHz) and temperature elevation on the firing rate of the BP-4 pacemaker neuron of the pond snail Lymnaea stagnalis were studied by using microelectrode techniques. The open end of a rectangular waveguide covered with a thin Teflon film served as a radiator. Specific absorption rates (SARs), measured in physiological solution at the radiator outlet, ranged from 600 to 4,200 W/kg, causing temperature rises from 0.3 to 2.2 C, respectively. Irradiation at an SAR of 4,200 W/kg caused a biphasic change in the firing rate, i.e., a transient decrease in the firing rate followed by a gradual increase to a new level that was 68 {+-} 21% above control. The biphasic changes in the firing rate were reproduced by heating under the condition that the magnitude (2 C) and the rate of temperature rise were equal to those produced by the irradiation. The addition of 0.05 mM of ouabain caused the disappearance of transient responses of the neuron to the irradiation. It was shown that the rate of temperature rise played an important role in the development of a transient neuronal response. The threshold stimulus for a transient response of the BP-4 neutron found in warming experiments was a temperature rise of 0.0025 C/s.

Alekseev, S.I.; Kochetkova, N.V. [Russian Academy of Sciences, Puschino (Russian Federation). Inst. of Cell Biophysics] [Russian Academy of Sciences, Puschino (Russian Federation). Inst. of Cell Biophysics; Ziskin, M.C.; Bolshakov, M.A. [Temple Univ. Medical School, Philadelphia, PA (United States). Center for Biomedical Physics] [Temple Univ. Medical School, Philadelphia, PA (United States). Center for Biomedical Physics

1997-05-01

98

Circadian gating of neuronal functionality: a basis for iterative metaplasticity1  

PubMed Central

Brain plasticity, the ability of the nervous system to encode experience, is a modulatory process leading to long-lasting structural and functional changes. Salient experiences induce plastic changes in neurons of the hippocampus, the basis of memory formation and recall. In the suprachiasmatic nucleus (SCN), the central circadian (~24-h) clock, experience with light at night induces changes in neuronal state, leading to circadian plasticity. The SCN's endogenous ~24-h time-generator comprises a dynamic series of functional states, which gate plastic responses. This restricts light-induced alteration in SCN state-dynamics and outputs to the nighttime. Endogenously generated circadian oscillators coordinate the cyclic states of excitability and intracellular signaling molecules that prime SCN receptivity to plasticity signals, generating nightly windows of susceptibility. We propose that this constitutes a paradigm of ~24-h iterative metaplasticity, the repeated, patterned occurrence of susceptibility to induction of neuronal plasticity. We detail effectors permissive for the cyclic susceptibility to plasticity. We consider similarities of intracellular and membrane mechanisms underlying plasticity in SCN circadian plasticity and in hippocampal long-term potentiation (LTP). The emerging prominence of the hippocampal circadian clock points to iterative metaplasticity in that tissue as well. Exploring these links holds great promise for understanding circadian shaping of synaptic plasticity, learning, and memory. PMID:25285070

Iyer, Rajashekar; Wang, Tongfei A.; Gillette, Martha U.

2014-01-01

99

Heterogeneous Expression of the Core Circadian Clock Proteins among Neuronal Cell Types in Mouse Retina  

PubMed Central

Circadian rhythms in metabolism, physiology, and behavior originate from cell-autonomous circadian clocks located in many organs and structures throughout the body and that share a common molecular mechanism based on the clock genes and their protein products. In the mammalian neural retina, despite evidence supporting the presence of several circadian clocks regulating many facets of retinal physiology and function, the exact cellular location and genetic signature of the retinal clock cells remain largely unknown. Here we examined the expression of the core circadian clock proteins CLOCK, BMAL1, NPAS2, PERIOD 1(PER1), PERIOD 2 (PER2), and CRYPTOCHROME2 (CRY2) in identified neurons of the mouse retina during daily and circadian cycles. We found concurrent clock protein expression in most retinal neurons, including cone photoreceptors, dopaminergic amacrine cells, and melanopsin-expressing intrinsically photosensitive ganglion cells. Remarkably, diurnal and circadian rhythms of expression of all clock proteins were observed in the cones whereas only CRY2 expression was found to be rhythmic in the dopaminergic amacrine cells. Only a low level of expression of the clock proteins was detected in the rods at any time of the daily or circadian cycle. Our observations provide evidence that cones and not rods are cell-autonomous circadian clocks and reveal an important disparity in the expression of the core clock components among neuronal cell types. We propose that the overall temporal architecture of the mammalian retina does not result from the synchronous activity of pervasive identical clocks but rather reflects the cellular and regional heterogeneity in clock function within retinal tissue. PMID:23189207

Liu, Xiaoqin; Zhang, Zhijing; Ribelayga, Christophe P.

2012-01-01

100

Role of a novel maintained low-voltage-activated inward current permeable to sodium and calcium in pacemaking of insect neurosecretory neurons  

Microsoft Academic Search

Among ionic currents underlying neuronal pacemaker activity, low-threshold-activated calcium currents contribute to setting the threshold for spike firing. In the insect central nervous system, dorsal unpaired median (DUM) neurons are capable of generating spontaneous electrical activity. It has previously been shown that two distinct (transient and maintained) low-voltage-activated (LVA) calcium currents are responsible for the generation of the pacemaker potential.

Antoine Defaix; Bruno Lapied

2005-01-01

101

Electrical Properties of the Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla oratoria  

PubMed Central

In the Squilla heart ganglion, the pacemaker is located in the rostral group of cells. After spontaneous firing ceased, the electrophysiological properties of these cells were examined with intracellular electrodes. Cells respond to electrical stimuli with all-or-none action potentials. Direct stimulation by strong currents decreases the size of action potentials. Comparison with action potentials caused by axonal stimulation and analysis of time relations indicate that with stronger currents the soma membrane is directly stimulated whereas with weaker currents the impulse first arises in the axon and then invades the soma. Spikes evoked in a neuron spread into all other neurons. Adjacent cells are interconnected by electrotonic connections. Histologically axons are tied with the side-junction. B spikes of adjacent cells are blocked simultaneously by hyperpolarization or by repetitive stimulation. Experiments show that under such circumstances the B spike is not directly elicited from the A spike but is evoked by invasion of an impulse or electrotonic potential from adjacent cells. On rostral stimulation a small prepotential precedes the main spike. It is interpreted as an action potential from dendrites. PMID:6034505

Watanabe, Akira; Obara, Shosaku; Akiyama, Toyohiro; Yumoto, Katsuto

1967-01-01

102

Development of Circadian Oscillators in Neurosphere Cultures during Adult Neurogenesis  

PubMed Central

Circadian rhythms are common in many cell types but are reported to be lacking in embryonic stem cells. Recent studies have described possible interactions between the molecular mechanism of circadian clocks and the signaling pathways that regulate stem cell differentiation. Circadian rhythms have not been examined well in neural stem cells and progenitor cells that produce new neurons and glial cells during adult neurogenesis. To evaluate circadian timing abilities of cells undergoing neural differentiation, neurospheres were prepared from the mouse subventricular zone (SVZ), a rich source of adult neural stem cells. Circadian rhythms in mPer1 gene expression were recorded in individual spheres, and cell types were characterized by confocal immunofluorescence microscopy at early and late developmental stages in vitro. Circadian rhythms were observed in neurospheres induced to differentiate into neurons or glia, and rhythms emerged within 3–4 days as differentiation proceeded, suggesting that the neural stem cell state suppresses the functioning of the circadian clock. Evidence was also provided that neural stem progenitor cells derived from the SVZ of adult mice are self-sufficient clock cells capable of producing a circadian rhythm without input from known circadian pacemakers of the organism. Expression of mPer1 occurred in high frequency oscillations before circadian rhythms were detected, which may represent a role for this circadian clock gene in the fast cycling of gene expression responsible for early cell differentiation. PMID:25826427

Jamasbi, Roudabeh J.; Kondratov, Roman V.

2015-01-01

103

Fetal alcohol exposure disrupts metabolic signaling in hypothalamic proopiomelanocortin neurons via a circadian mechanism in male mice.  

PubMed

Early-life ethanol feeding (ELAF) alters the metabolic function of proopiomelanocortin (POMC)-producing neurons and the circadian expression of clock regulatory genes in the hypothalamus. We investigated whether the circadian mechanisms control the action of ELAF on metabolic signaling genes in POMC neurons. Gene expression measurements of Pomc and a selected group of metabolic signaling genes, Stat3, Sirt1, Pgc1-?, and Asb4 in laser-captured microdissected POMC neurons in the hypothalamus of POMC-enhanced green fluorescent protein mice showed circadian oscillations under light/dark and constant darkness conditions. Ethanol programmed these neurons such that the adult expression of Pomc, Stat3, Sirt, and Asb4 gene transcripts became arrhythmic. In addition, ELAF dampened the circadian peak of gene expression of Bmal1, Per1, and Per2 in POMC neurons. We crossed Per2 mutant mice with transgenic POMC-enhanced green fluorescent protein mice to determine the role of circadian mechanism in ELAF-altered metabolic signaling in POMC neurons. We found that ELAF failed to alter arrhythmic expression of most circadian genes, with the exception of the Bmal1 gene and metabolic signaling regulating genes in Per2 mutant mice. Comparison of the ELAF effects on the circadian blood glucose in wild-type and Per2 mutant mice revealed that ELAF dampened the circadian peak of glucose, whereas the Per2 mutation shifted the circadian cycle and prevented the ELAF dampening of the glucose peak. These data suggest the possibility that the Per2 gene mutation may regulate the ethanol actions on Pomc and the metabolic signaling genes in POMC neurons in the hypothalamus by blocking circadian mechanisms. PMID:24797626

Agapito, Maria A; Zhang, Changqing; Murugan, Sengottuvelan; Sarkar, Dipak K

2014-07-01

104

The role of spiking and bursting pacemakers in the neuronal control of breathing.  

PubMed

Breathing is controlled by a distributed network involving areas in the neocortex, cerebellum, pons, medulla, spinal cord, and various other subcortical regions. However, only one area seems to be essential and sufficient for generating the respiratory rhythm: the preBötzinger complex (preBötC). Lesioning this area abolishes breathing and following isolation in a brain slice the preBötC continues to generate different forms of respiratory activities. The use of slice preparations led to a thorough understanding of the cellular mechanisms that underlie the generation of inspiratory activity within this network. Two types of inward currents, the persistent sodium current (I(NaP)) and the calcium-activated non-specific cation current (I(CAN)), play important roles in respiratory rhythm generation. These currents give rise to autonomous pacemaker activity within respiratory neurons, leading to the generation of intrinsic spiking and bursting activity. These membrane properties amplify as well as activate synaptic mechanisms that are critical for the initiation and maintenance of inspiratory activity. In this review, we describe the dynamic interplay between synaptic and intrinsic membrane properties in the generation of the respiratory rhythm and we relate these mechanisms to rhythm generating networks involved in other behaviors. PMID:22654176

Ramirez, Jan-Marino; Koch, Henner; Garcia, Alfredo J; Doi, Atsushi; Zanella, Sebastien

2011-06-01

105

Circadian modulation of dopamine levels and dopaminergic neuron development contributes to attention deficiency and hyperactive behavior.  

PubMed

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children and adults. While ADHD patients often display circadian abnormalities, the underlying mechanisms are unclear. Here we found that the zebrafish mutant for the circadian gene period1b (per1b) displays hyperactive, impulsive-like, and attention deficit-like behaviors and low levels of dopamine, reminiscent of human ADHD patients. We found that the circadian clock directly regulates dopamine-related genes monoamine oxidase and dopamine ? hydroxylase, and acts via genes important for the development or maintenance of dopaminergic neurons to regulate their number and organization in the ventral diencephalic posterior tuberculum. We then found that Per1 knock-out mice also display ADHD-like symptoms and reduced levels of dopamine, thereby showing highly conserved roles of the circadian clock in ADHD. Our studies demonstrate that disruption of a circadian clock gene elicits ADHD-like syndrome. The circadian model for attention deficiency and hyperactive behavior sheds light on ADHD pathogenesis and opens avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder. PMID:25673850

Huang, Jian; Zhong, Zhaomin; Wang, Mingyong; Chen, Xifeng; Tan, Yicheng; Zhang, Shuqing; He, Wei; He, Xiong; Huang, Guodong; Lu, Haiping; Wu, Ping; Che, Yi; Yan, Yi-Lin; Postlethwait, John H; Chen, Wenbiao; Wang, Han

2015-02-11

106

Survival of adult generated hippocampal neurons is altered in circadian arrhythmic mice.  

PubMed

The subgranular zone of the hippocampal formation gives rise to new neurons that populate the dentate gyrus throughout life. Cells in the hippocampus exhibit rhythmic clock gene expression and the circadian clock is known to regulate the cycle of cell division in other areas of the body. These facts suggest that the circadian clock may regulate adult neurogenesis in the hippocampus as well. In the present study, neurogenesis in the hippocampal subgranular zone was examined in arrhythmic Bmal1 knockout (-KO) mice and their rhythmic heterozygous and wildtype littermates. Proliferation and survival of newly generated subgranular zone cells were examined using bromodeoxyuridine labelling, while pyknosis (a measure of cell death) and hippocampal volume were examined in cresyl violet stained sections. There was no significant difference in cellular proliferation between any of the groups, yet survival of proliferating cells, 6 weeks after the bromodeoxyuridine injection, was significantly greater in the BMAL1-KO animals. The number of pyknotic cells was significantly decreased in Bmal1-KO animals, yet hippocampal volume remained the same across genotypes. These findings suggest that while a functional circadian clock is not necessary for normal proliferation of neuronal precursor cells, the normal pruning of newly generated neurons in the hippocampus may require a functional circadian clock. PMID:24941219

Rakai, Brooke D; Chrusch, Michael J; Spanswick, Simon C; Dyck, Richard H; Antle, Michael C

2014-01-01

107

Survival of Adult Generated Hippocampal Neurons Is Altered in Circadian Arrhythmic Mice  

PubMed Central

The subgranular zone of the hippocampal formation gives rise to new neurons that populate the dentate gyrus throughout life. Cells in the hippocampus exhibit rhythmic clock gene expression and the circadian clock is known to regulate the cycle of cell division in other areas of the body. These facts suggest that the circadian clock may regulate adult neurogenesis in the hippocampus as well. In the present study, neurogenesis in the hippocampal subgranular zone was examined in arrhythmic Bmal1 knockout (-KO) mice and their rhythmic heterozygous and wildtype littermates. Proliferation and survival of newly generated subgranular zone cells were examined using bromodeoxyuridine labelling, while pyknosis (a measure of cell death) and hippocampal volume were examined in cresyl violet stained sections. There was no significant difference in cellular proliferation between any of the groups, yet survival of proliferating cells, 6 weeks after the bromodeoxyuridine injection, was significantly greater in the BMAL1-KO animals. The number of pyknotic cells was significantly decreased in Bmal1-KO animals, yet hippocampal volume remained the same across genotypes. These findings suggest that while a functional circadian clock is not necessary for normal proliferation of neuronal precursor cells, the normal pruning of newly generated neurons in the hippocampus may require a functional circadian clock. PMID:24941219

Rakai, Brooke D.; Chrusch, Michael J.; Spanswick, Simon C.; Dyck, Richard H.; Antle, Michael C.

2014-01-01

108

The membrane potential waveform of bursting pacemaker neurons is a predictor of their preferred frequency and the network cycle frequency  

PubMed Central

Many oscillatory networks involve neurons that exhibit intrinsic rhythmicity, but possess a large variety of voltage-gated currents which interact in a complex fashion making it difficult to determine which factors control frequency. Yet, these neurons often have preferred (resonance) frequencies that can be close to the network frequency. Because the preferred frequency results from the dynamics of ionic currents, it can be assumed to depend on parameters that determine the neuron’s oscillatory waveform shape. The pyloric network frequency in the crab Cancer borealis is correlated with the preferred frequency of its bursting pacemaker neurons AB and PD. We measure the preferred frequency of the PD neuron in voltage-clamp, which allows control of the oscillation voltage range and waveforms (sine waves and realistic oscillation waveforms), and showthat1) the preferred frequency depends on the voltage range of the oscillating voltage waveform; 2) the slope of the waveform near its peak has a strongly negative correlation with the preferred frequency; and 3) correlations between parameters of the PD neuron oscillation waveform and its preferred frequency can be used to predict shifts in the network frequency. As predicted by these results, dynamic clamp shifts of the upper or lower voltage limits of the PD neuron waveform during ongoing oscillations changed the network frequency, consistent with the predictions from the preferred frequency. These results show that the voltage waveform of oscillatory neurons can be predictive of their preferred frequency and thus the network oscillation frequency. PMID:20702710

Tseng, Hua-an; Nadim, Farzan

2010-01-01

109

Ultrastructure of pigment-dispersing hormone-immunoreactive neurons in a three-dimensional model of the accessory medulla of the cockroach Leucophaea maderae  

Microsoft Academic Search

Locomotor activity rhythms of the cockroach Leucophaea maderae are orchestrated by two bilaterally symmetric, mutually coupled, circadian pacemakers. They lie in the optic lobes of the brain and are confined to the accessory medulla (AMe), ventro-medially to the medulla. The AMe is innervated by approximately 12 pigment-dispersing hormone (PDH)-immunoreactive anterior medulla neurons (PDHMe), which are circadian pacemaker candidates in the

Thomas Reischig; Monika Stengl

2003-01-01

110

Fractal-like correlations of the fluctuating inter-spike membrane potential of a Helix aspersa pacemaker neuron.  

PubMed

We analyzed the voltage fluctuations of the membrane potential manifested along the inter-spike segment of a pacemaker neuron. Time series of intracellular inter-spike voltage fluctuations were obtained in the current-clamp configuration from the F1 neuron of 12 Helix aspersa specimens. To assess the dynamic or stochastic nature of the voltage fluctuations these series were analyzed by Detrended Fluctuation Analysis (DFA), providing the scaling exponent ?. The median ? result obtained for the inter-spike segments was 0.971 ([0.963, 0.995] lower and upper quartiles). Our results indicate a critical-like dynamic behavior in the inter-spike membrane potential that, far from being random, shows long-term correlations probably linked to the dynamics of the mechanisms involved in the regulation of the membrane potential, thereby endorsing the occurrence of critical-like phenomena at a single-neuron level. PMID:25189698

Seseña-Rubfiaro, Alberto; Echeverría, Juan Carlos; Godínez-Fernández, Jose Rafael

2014-10-01

111

In vitro entrainment of the circadian rhythm of vasopressin-releasing cells in suprachiasmatic nucleus by vasoactive intestinal polypeptide  

Microsoft Academic Search

Mammalian circadian pacemaker is located in suprachiasmatic nuclei (SCN) of the hypothalamus. The pacemaker is entrained by light–dark cycle; the photic information is transmitted primarily via the retino–hypothalamic tract (RHT). The main neurotransmitter of the tract is glutamate. RHT fibers end on the ventrolateral part of the nucleus, where vasoactive intestinal peptide (VIP)–immunopositive neurons are localized. They send their axons

Kazuto Watanabe; Jiri Vanecek; Sadao Yamaoka

2000-01-01

112

Molecular Mechanisms of Circadian Regulation During Spaceflight  

NASA Technical Reports Server (NTRS)

The physiology of both vertebrates and invertebrates follows internal rhythms coordinated in phase with the 24-hour daily light cycle. This circadian clock is governed by a central pacemaker, the suprachiasmatic nucleus (SCN) in the brain. However, peripheral circadian clocks or oscillators have been identified in most tissues. How the central and peripheral oscillators are synchronized is still being elucidated. Light is the main environmental cue that entrains the circadian clock. Under the absence of a light stimulus, the clock continues its oscillation in a free-running condition. In general, three functional compartments of the circadian clock are defined. The vertebrate retina contains endogenous clocks that control many aspects of retinal physiology, including retinal sensitivity to light, neurohormone synthesis (melatonin and dopamine), rod disk shedding, signalling pathways and gene expression. Neurons with putative local circadian rhythm generation are found among all the major neuron populations in the mammalian retina. In the mouse, clock genes and function are more localized to the inner retinal and ganglion cell layers. The photoreceptor, however, secrete melatonin which may still serve a an important circadian signal. The reception and transmission of the non-visual photic stimulus resides in a small subpopulation (1-3%) or retinal ganglion cells (RGC) that express the pigment melanopsin (Opn4) and are called intrisically photoreceptive RGC (ipRGC). Melanopsin peak absorption is at 420 nm and all the axons of the ipRGC reach the SCN. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate the risk of fatigue and health and performance decrement due to circadian rhythm disruption. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. We hypothesize that spaceflight may affect ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight.

Zanello, S. B.; Boyle, R.

2012-01-01

113

Lhx1 maintains synchrony among circadian oscillator neurons of the SCN.  

PubMed

The robustness and limited plasticity of the master circadian clock in the suprachiasmatic nucleus (SCN) is attributed to strong intercellular communication among its constituent neurons. However, factors that specify this characteristic feature of the SCN are unknown. Here, we identified Lhx1 as a regulator of SCN coupling. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. Consequently, the mice rapidly phase shift under a jet lag paradigm and their behavior rhythms gradually deteriorate under constant condition. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Therefore, by regulating expression of genes mediating intercellular communication, Lhx1 imparts synchrony among SCN neurons and ensures consolidated rhythms of activity and rest that is resistant to photic noise. PMID:25035422

Hatori, Megumi; Gill, Shubhroz; Mure, Ludovic S; Goulding, Martyn; O'Leary, Dennis D M; Panda, Satchidananda

2014-01-01

114

The circadian system: plasticity at many levels.  

PubMed

Over the years it has become crystal clear that a variety of processes encode time-of-day information, ranging from gene expression, protein stability, or subcellular localization of key proteins, to the fine tuning of network properties and modulation of input signals, ultimately ensuring that physiology and behavior are properly synchronized to a changing environment. The purpose of this review is to put forward examples (as opposed to generate a comprehensive revision of all the available literature) in which the circadian system displays a remarkable degree of plasticity, from cell autonomous to circuit-based levels. In the literature, the term circadian plasticity has been used to refer to different concepts. The obvious one, more literally, refers to any change that follows a circadian (circa=around, diem=day) pattern, i.e. a daily change of a given parameter. The discovery of daily remodeling of neuronal structures will be referred herein as structural circadian plasticity, and represents an additional and novel phenomenon modified daily. Finally, any plasticity that has to do with a circadian parameter would represent a type of circadian plasticity; as an example, adjustments that allow organisms to adapt their daily behavior to the annual changes in photoperiod is a form of circadian plasticity at a higher organizational level, which is an emergent property of the whole circadian system. Throughout this work we will revisit these types of changes by reviewing recent literature delving around circadian control of clock outputs, from the most immediate ones within pacemaker neurons to the circadian modulation of rest-activity cycles. PMID:23727010

Muraro, N I; Pírez, N; Ceriani, M F

2013-09-01

115

Metabolic regulations of the rhythmic activity in pacemaker neurons. III. Neutralization of the pentylenetetrazol effect in regularly beating Aplysia neurons by metabolic modifiers.  

PubMed

In regular beating pacemaker neurons isolated from the sea hare Aplysia californica, 30-50 mM pentylenetetrazol (PTZ) induces spike doublets and triplets, multi-spike bursts, and paroxysmal depolarizing shifts. The development of the characteristic PTZ-induced changes in impluse pattern is preceded by a transient increase in discharge frequency and a reduction in after-hyperpolarization. According to earlier findings, the rhythmic spike activity of pacemaker neurons is governed by a phosphofructokinase-fructose-1,6-diphosphatase-mediated substrate cycle, the activation of which leads to the appearance of spike bursts. Inhibitory modifiers of this neuronal substrate cycle, such as citrate, ATP, and 3-phosphoglycerate, are able to neutralize the changes in the impluse characteristics occurring as the result of PTZ action. Since the reinitiated single-spike trains reverted again to the PTZ pattern following the further addition of activating modifiers, such as fructose-1,6-diphosphate or fructose-6-phosphate, it appears likely that PTZ exerts an influence on the metabolic reactions driving the rhythmic spike activity. In contrast to the reversible effects of the metabolic modifiers the conventional anti-convulsants, phenobarbital and pentobarbital, merely block all spike activity. PMID:1276874

Krämer, G; Chaplain, R A

1976-04-23

116

Endogenous circadian rhythm in human motor activity uncoupled from circadian influences  

E-print Network

Endogenous circadian rhythm in human motor activity uncoupled from circadian influences on cardiac. Eugene Stanley, October 31, 2007 (sent for review September 27, 2007) The endogenous circadian pacemaker found that a scaling index of cardiac vulnerability has an endogenous circadian peak at the circadian

Stanley, H. Eugene

117

Experimental assessment of the network properties of the Drosophila circadian clock.  

PubMed

Circadian rhythms are conserved across kingdoms and coordinate physiology and behavior for appropriate time-keeping. The neuronal populations that govern circadian rhythms are described in many animal models, and the current challenge is to understand how they interact to control overt rhythms, remaining plastic enough to respond and adapt to a changing environment. In Drosophila melanogaster, the circadian network comprises about 150 neurons, and the main synchronizer is the neuropeptide pigment-dispersing factor (PDF), released by the well-characterized central pacemaker neurons, the small ventral lateral neurons (sLNvs). However, the rules and properties governing the communication and coupling between this central pacemaker and downstream clusters are not fully elucidated. Here we genetically manipulate the speed of the molecular clock specifically in the central pacemaker neurons of Drosophila and provide experimental evidence of their restricted ability to synchronize downstream clusters. We also demonstrate that the sLNv-controlled clusters have an asymmetric entrainment range and were able to experimentally assess it. Our data imply that different clusters are subjected to different coupling strengths, and display independent endogenous periods. Finally, the manipulation employed here establishes a suitable paradigm to test other network properties as well as the cell-autonomous mechanisms running in different circadian-relevant clusters. PMID:25504089

Beckwith, Esteban J; Ceriani, M Fernanda

2015-04-15

118

The Role of Kisspeptin and RFRP-3 Neurons in the Circadian-Timed Preovulatory Luteinizing Hormone Surge  

PubMed Central

Many aspects of female reproduction often require intricate timing, ranging from temporal regulation of reproductive hormone secretion to the precise timing of sexual behavior. In particular, in rodents and other species, ovulation is triggered by a surge in pituitary luteinizing hormone (LH) secretion that is governed by a complex interaction between circadian signals arising in the hypothalamus and ovarian-derived estradiol signals acting on multiple brain circuitries. These circadian and hormonal pathways converge to stimulate a precisely-timed surge in gonadotropin-releasing hormone (GnRH) release (i.e., positive feedback), thereby triggering the preovulatory LH surge. Reflecting its control by afferent circadian signals, the preovulatory LH surge occurs at a specific time of day, typically late afternoon in nocturnal rodents. Although the specific mechanisms mediating the hormonal and circadian regulation of GnRH/LH release have remained poorly understood, recent findings now suggest that estradiol and circadian signals govern specific reproductive neuropeptide circuits in the hypothalamus, including the newly-identified kisspeptin and RFamide-related peptide-3 (RFRP-3) neuronal populations. Neurons producing kisspeptin, the protein product of the Kiss1 gene, and RFRP-3 have been shown to provide excitatory and inhibitory input to GnRH neurons, respectively, and are also influenced by sex steroid and circadian signals. Here, we integrate classic and recent findings to form a new working model for the neuroendocrine regulation of the circadian-timed preovulatory LH surge in rodents. This model proposes kisspeptin and RFRP-3 neuronal populations as key nodal points for integrating and transducing circadian and hormonal signals to the reproductive axis, thereby governing the precisely-timed LH surge. PMID:21592236

Khan, Azim R.; Kauffman, Alexander S.

2011-01-01

119

Circadian control of membrane excitability in Drosophila melanogaster lateral ventral clock neurons.  

PubMed

Drosophila circadian rhythms are controlled by a neural circuit containing approximately 150 clock neurons. Although much is known about mechanisms of autonomous cellular oscillation, the connection between cellular oscillation and functional outputs that control physiological and behavioral rhythms is poorly understood. To address this issue, we performed whole-cell patch-clamp recordings on lateral ventral clock neurons (LN(v)s), including large (lLN(v)s) and small LN(v)s (sLN(v)s), in situ in adult fly whole-brain explants. We found two distinct sizes of action potentials (APs) in >50% of lLN(v)s that fire APs spontaneously, and determined that large APs originate in the ipsilateral optic lobe and small APs in the contralateral. lLN(v) resting membrane potential (RMP), spontaneous AP firing rate, and membrane resistance are cyclically regulated as a function of time of day in 12 h light/dark conditions (LD). lLN(v) RMP becomes more hyperpolarized as time progresses from dawn to dusk with a concomitant decrease in spontaneous AP firing rate and membrane resistance. From dusk to dawn, lLN(v) RMP becomes more depolarized, with spontaneous AP firing rate and membrane resistance remaining stable. In contrast, circadian defective per(0) null mutant lLN(v) membrane excitability is nearly constant in LD. Over 24 h in constant darkness (DD), wild-type lLN(v) membrane excitability is not cyclically regulated, although RMP gradually becomes slightly more depolarized. sLN(v) RMP is most depolarized around lights-on, with substantial variability centered around lights-off in LD. Our results indicate that LN(v) membrane excitability encodes time of day via a circadian clock-dependent mechanism, and likely plays a critical role in regulating Drosophila circadian behavior. PMID:18562620

Cao, Guan; Nitabach, Michael N

2008-06-18

120

Circadian Rhythmicity and Light Sensitivity of the Zebrafish Brain  

PubMed Central

Traditionally, circadian clocks have been thought of as a neurobiological phenomenon. This view changed somewhat over recent years with the discovery of peripheral tissue circadian oscillators. In mammals, however, the suprachiasmatic nucleus (SCN) in the hypothalamus still retains the critical role of a central synchronizer of biological timing. Zebrafish, in contrast, have always reflected a more highly decentralized level of clock organization, as individual cells and tissues contain directly light responsive circadian pacemakers. As a consequence, clock function in the zebrafish brain has remained largely unexplored, and the precise organization of rhythmic and light-sensitive neurons within the brain is unknown. To address this issue, we used the period3 (per3)-luciferase transgenic zebrafish to confirm that multiple brain regions contain endogenous circadian oscillators that are directly light responsive. In addition, in situ hybridization revealed localised neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as numerous hypothalamic nuclei, the periventricular grey zone (PGZ) of the optic tectum, and granular cells of the rhombencephalon. To further investigate the light sensitive properties of neurons, expression of c-fos, a marker for neuronal activity, was examined. c-fos mRNA was upregulated in response to changing light conditions in different nuclei within the zebrafish brain. Furthermore, under constant dark (DD) conditions, c-fos shows a significant circadian oscillation. Taken together, these results show that there are numerous areas of the zebrafish central nervous system, which contain deep brain photoreceptors and directly light-entrainable circadian pacemakers. However, there are also multiple brain nuclei, which possess neither, demonstrating a degree of pacemaker complexity that was not previously appreciated. PMID:24465943

Moore, Helen A.; Whitmore, David

2014-01-01

121

Oscillatory Mechanisms Underlying the Drosophila Circadian Clock  

NSDL National Science Digital Library

This animation depicts a schematic of the Drosophila circadian clock mechanism in a single, pacemaking lateral brain neuron. Circadian clocks allow organisms to exhibit rhythmic behaviors and processes based on a nearly 24-hour cycle in the absence of any light stimulation. In the fruit fly, the basic molecular mechanism consists of two intertwined transcription-translation negative feedback loops. One loop--the "positive loop"--controls the rhythmic expression of a positive transcription factor gene, Clock. The second loop--the "negative loop"--controls the transcription of period and timeless, two genes that encode repressor proteins. The loops are intertwined because Period and Timeless repress transcription mediated by the transcription factors Clock and Cycle, whereas the Clock:Cycle heterodimer drives transcription of period and timeless, as well as that of vrille, a repressor of Clock expression. Light cycles can synchronize the Drosophila circadian pathway by directly stimulating cryptochrome-dependent degradation of Timeless.

Russell N. Van Gelder (Washington University Medical School; Department of Ophthalmology and Visual Sciences, Department of Molecular Biology and Pharmacology REV)

2003-11-18

122

Dynamic interactions mediated by non-redundant signaling mechanisms couple circadian clock neurons  

PubMed Central

Summary Interactions among suprachiasmatic nucleus (SCN) neurons are required for robust circadian rhythms entrained to local time. To investigate these coupling mechanisms, we developed a novel functional coupling assay that uniquely captures the dynamic process by which SCN neurons interact. As a population, SCN neurons typically display synchronized rhythms with similar peak times, but will peak 6–12h apart after in vivo exposure to long days. Once removed from these conditions, SCN neurons resynchronize through a phase-dependent coupling process mediated by both vasoactive intestinal polypeptide (VIP) and GABAA signaling. Notably, GABAA signaling contributes to coupling when the SCN network in an anti-phase configuration, but opposes synchrony under steady-state conditions. Further, VIP acts together with GABAA signaling to couple the network in an anti-phase configuration, but promotes synchrony under steady-state conditions by counteracting the actions of GABAA signaling. Thus, SCN neurons interact through non-redundant coupling mechanisms influenced by the state of the network. PMID:24267653

Evans, Jennifer A.; Leise, Tanya L.; Castanon-Cervantes, Oscar; Davidson, Alec J.

2013-01-01

123

Lhx1 maintains synchrony among circadian oscillator neurons of the SCN  

PubMed Central

The robustness and limited plasticity of the master circadian clock in the suprachiasmatic nucleus (SCN) is attributed to strong intercellular communication among its constituent neurons. However, factors that specify this characteristic feature of the SCN are unknown. Here, we identified Lhx1 as a regulator of SCN coupling. A phase-shifting light pulse causes acute reduction in Lhx1 expression and of its target genes that participate in SCN coupling. Mice lacking Lhx1 in the SCN have intact circadian oscillators, but reduced levels of coupling factors. Consequently, the mice rapidly phase shift under a jet lag paradigm and their behavior rhythms gradually deteriorate under constant condition. Ex vivo recordings of the SCN from these mice showed rapid desynchronization of unit oscillators. Therefore, by regulating expression of genes mediating intercellular communication, Lhx1 imparts synchrony among SCN neurons and ensures consolidated rhythms of activity and rest that is resistant to photic noise. DOI: http://dx.doi.org/10.7554/eLife.03357.001 PMID:25035422

Hatori, Megumi; Gill, Shubhroz; Mure, Ludovic S; Goulding, Martyn; O'Leary, Dennis D M; Panda, Satchidananda

2014-01-01

124

Network bursts in cortical neuronal cultures ‘Noise versus pacemaker’- driven neural network simulations  

Microsoft Academic Search

Dissociated neuronal cultures provide a useful platform to study behavior and development of biological neural networks. Isolated from external inputs neural cultures generate electrical activity of their own, showing several features. The most striking feature is the phenomenon of, more or less regular, network bursts, i.e. simultaneous firing of many neurons in a relatively short time window. In this paper

T. Gritsun; J. Stegenga; J. le Feber; W. L. C. Rutten

2009-01-01

125

348 Brain Research, 474(1988)348-352 Circadian rhythm of the rat suprachiasmatic brain slice is  

E-print Network

: Brainslice;cAMP;Circadianrhythm;Hypothalamus;Oscillator;Pacemaker;Phase-shift;Suprachiasmaticnuclei Cellular phaseofthe pacemaker.Thisrhythmwasrapidlyreset bybath applicationofc. The oscillations of this endogenous pacemaker time the circadian rhythms of the organism's behavior and physiology

Gillette, Martha U.

126

Pacemaker (image)  

MedlinePLUS

A pacemaker is a small, battery-operated electronic device which is inserted under the skin to help the heart beat regularly and at an appropriate rate. The pacemaker has leads that travel through a large vein ...

127

Electronic pacemakers.  

PubMed

The number of patients who have cardiac pacemakers has increased markedly over the past few decades since the technology was first introduced in the 1950s. Advances in technology, expanding indications, and the aging of the population ensure that clinicians will encounter patients with cardiac pacemakers on a regular basis. This article summarizes the electrocardiographic manifestations of the normally functioning permanent cardiac pacemaker and abnormalities associated with pacemaker malfunction. PMID:16308119

Chan, Theodore C; Cardall, Taylor Y

2006-02-01

128

The Journal of Neuroscience, March 1989, g(3): 1073-l 081 The Mammalian Circadian Clock in the Suprachiasmatic Nuclei Is  

E-print Network

of the circadian clock of the rat. We mon- itored a primary expression of the clock or pacemaker, the circadian de- pended on the phase of the pacemaker at the time of treat- ment: the peak was maximally advanced- sustaining pacemaker that survives removal from the animal and can be reset in vitro, and (2) this pacemaker

Gillette, Martha U.

129

RNA-Interference Knockdown of Drosophila Pigment Dispersing Factor in Neuronal Subsets: The Anatomical Basis of a Neuropeptide's Circadian Functions  

PubMed Central

Background In animals, neuropeptide signaling is an important component of circadian timekeeping. The neuropeptide pigment dispersing factor (PDF) is required for several aspects of circadian activity rhythms in Drosophila. Methodology/Principal Findings Here we investigate the anatomical basis for PDF's various circadian functions by targeted PDF RNA-interference in specific classes of Drosophila neuron. We demonstrate that PDF is required in the ventro-lateral neurons (vLNs) of the central brain and not in the abdominal ganglion for normal activity rhythms. Differential knockdown of PDF in the large or small vLNs indicates that PDF from the small vLNs is likely responsible for the maintenance of free-running activity rhythms and that PDF is not required in the large vLNs for normal behavior. PDF's role in setting the period of free-running activity rhythms and the proper timing of evening activity under light:dark cycles emanates from both subtypes of vLN, since PDF in either class of vLN was sufficient for these aspects of behavior. Conclusions/Significance These results reveal the neuroanatomical basis PDF's various circadian functions and refine our understanding of the clock neuron circuitry of Drosophila. PMID:20011537

Shafer, Orie T.; Taghert, Paul H.

2009-01-01

130

PREBOTZINGER COMPLEX AND PACEMAKER NEURONS: Hypothesized Site and Kernel for Respiratory Rhythm Generation  

Microsoft Academic Search

Identification of the sites and mechanisms underlying the generation of respiratory rhythm is of longstanding interest to physiologists and neurobiologists. Recently, with the development of novel experimental preparations, especially in vitro en bloc and slice preparations of rodent brainstem, progress has been made. In particular, a site in the ventrolateral medulla, the preBotzinger Complex, is hypothesized to contain neuronal circuits

Jens C. Rekling; Jack L. Feldman

1998-01-01

131

CHAOS AND STABILITY IN A MODEL OF INHIBITORY NEURONAL NETWORK.  

E-print Network

neuronal networks, without delays, composed by equally or different 2 n pacemaker neurons, evolving pacemaker neurons, with strictly increasing potentials in dissipative regime, providing negative concavity

132

Circadian dysfunction in a mouse model of Parkinson's disease.  

PubMed

Many Parkinson's disease (PD) patients exhibit sleep disorders as part of their symptoms with evidence suggesting that REM sleep disorders may be intimately associated with this disease. Possible dysfunction in the circadian system in PD has received less attention, yet problems in circadian timing are common in neurodegenerative diseases. In the present study, we examined the expression of daily and circadian rhythms in the alpha-synuclein overexpressing (ASO) transgenic line. We found selective deficits in the expression of circadian rhythms of locomotor activity, including lower night-time activity and greater fragmentation in the wheel-running activity in this PD model. These alterations were prominent in young adult (3-4 mo) ASO mice and worsened progressively with age, consistent with prior reports of age-related loss of motor skills. The temporal distribution of sleep was also altered in the ASO mice compared to littermate controls. In the ASO mice, the peak/trough expression of the clock gene PERIOD2 was normal in the master pacemaker of the circadian system: the suprachiasmatic nucleus (SCN); however, the daytime firing rate of SCN neurons was reduced in the mutant mice. Together, this data raises the possibility that a weakening of circadian output is a core feature of PD. The reduction in magnitude of circadian output would be expected to have functional consequences throughout the body. PMID:21864527

Kudo, Takashi; Loh, Dawn H; Truong, Danny; Wu, Yingfei; Colwell, Christopher S

2011-11-01

133

NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator  

PubMed Central

Circadian rhythms are driven by gene expression feedback loops in metazoans. Based on the success of genetic screens for circadian mutants in Drosophila melanogaster, we undertook a targeted RNAi screen to study the impact of translation control genes on circadian locomotor activity rhythms in flies. Knockdown of vital translation factors in timeless protein-positive circadian neurons caused a range of effects including lethality. Knockdown of the atypical translation factor NAT1 had the strongest effect and lengthened circadian period. It also dramatically reduced PER protein levels in pigment dispersing factor (PDF) neurons. BELLE (BEL) protein was also reduced by the NAT1 knockdown, presumably reflecting a role of NAT1 in belle mRNA translation. belle and NAT1 are also targets of the key circadian transcription factor Clock (CLK). Further evidence for a role of NAT1 is that inhibition of the target of rapamycin (TOR) kinase increased oscillator activity in cultured wings, which is absent under conditions of NAT1 knockdown. Moreover, the per 5?- and 3?-UTRs may function together to facilitate cap-independent translation under conditions of TOR inhibition. We suggest that NAT1 and cap-independent translation are important for per mRNA translation, which is also important for the circadian oscillator. A circadian translation program may be especially important in fly pacemaker cells. PMID:22904033

Bradley, Sean; Narayanan, Siddhartha; Rosbash, Michael

2012-01-01

134

Oscillatory Mechanisms Underlying the Murine Circadian Clock  

NSDL National Science Digital Library

This animation depicts a schematic of the murine circadian clock mechanism in a single, pacemaking neuron in the suprachiasmatic nucleus (SCN) of the hypothalamus, where the master pacemaker is located. Circadian clocks allow organisms to display behaviors and processes with a 24-hour rhythm even in the absence of light input. The basic molecular mechanism consists of two intertwined transcription-translation negative feedback loops. One loop--the "positive loop"--controls the rhythmic expression of a positive transcription factor gene, Bmal1 (also called Mop3). The second loop--the "negative loop"--controls the transcription of genes in the Period and Cryptochrome families, which encode repressor proteins. The loops are intertwined because the proteins PERIOD and CRYPTOCHROME directly repress transcription mediated by the transcription factors CLOCK and BMAL1, whereas the CLOCK:BMAL1 heterodimer drives transcription of the Period and Cryptochrome genes, as well as that of Rev-erb-alpha, which represses Bmal1 expression. Other proteins, such as casein kinase I ε (CKIε) play essential modulatory roles in mammalian circadian timekeeping.

Russell N. Van Gelder (Washington University Medical School; Department of Ophthalmology and Visual Sciences, Department of Molecular Biology and Pharmacology REV)

2003-11-18

135

A defined heteromeric KV1 channel stabilizes the intrinsic pacemaking and regulates the output of deep cerebellar nuclear neurons to thalamic targets  

PubMed Central

The output of the cerebellum to the motor axis of the central nervous system is orchestrated mainly by synaptic inputs and intrinsic pacemaker activity of deep cerebellar nuclear (DCN) projection neurons. Herein, we demonstrate that the soma of these cells is enriched with KV1 channels produced by mandatory multi-merization of KV1.1, 1.2 ? and KV?2 subunits. Being constitutively active, the K+ current (IKV1) mediated by these channels stabilizes the rate and regulates the temporal precision of self-sustained firing of these neurons. Placed strategically, IKV1 provides a powerful counter-balance to prolonged depolarizing inputs, attenuates the rebound excitation, and dampens the membrane potential bi-stability. Somatic location with low activation threshold render IKV1 instrumental in voltage-dependent de-coupling of the axon initial segment from the cell body of projection neurons, impeding invasion of back-propagating action potentials into the somato-dendritic compartment. The latter is also demonstrated to secure the dominance of clock-like somatic pacemaking in driving the regenerative firing activity of these neurons, to encode time variant inputs with high fidelity. Through the use of multi-compartmental modelling and retro-axonal labelling, the physiological significance of the described functions for processing and communication of information from the lateral DCN to thalamic relay nuclei is established. PMID:23318870

Ovsepian, Saak V; Steuber, Volker; Le Berre, Marie; O’Hara, Liam; O’Leary, Valerie B; Dolly, J Oliver

2013-01-01

136

How coupling determines the entrainment of circadian clocks  

NASA Astrophysics Data System (ADS)

Autonomous circadian clocks drive daily rhythms in physiology and behaviour. A network of coupled neurons, the suprachiasmatic nucleus (SCN), serves as a robust self-sustained circadian pacemaker. Synchronization of this timer to the environmental light-dark cycle is crucial for an organism's fitness. In a recent theoretical and experimental study it was shown that coupling governs the entrainment range of circadian clocks. We apply the theory of coupled oscillators to analyse how diffusive and mean-field coupling affects the entrainment range of interacting cells. Mean-field coupling leads to amplitude expansion of weak oscillators and, as a result, reduces the entrainment range. We also show that coupling determines the rigidity of the synchronized SCN network, i.e. the relaxation rates upon perturbation. Our simulations and analytical calculations using generic oscillator models help to elucidate how coupling determines the entrainment of the SCN. Our theoretical framework helps to interpret experimental data.

Bordyugov, G.; Granada, A. E.; Herzel, H.

2011-08-01

137

Pharmacological characterization of postsynaptic potentials evoked in the bimodal pacemaker neuron of Helix pomatia L.  

PubMed

Stimulation of various peripheral nerve trunks evokes very similar compound postsynaptic potentials (PSP) composed of one or more excitatory postsynaptic potentials (EPSP) followed by fast and slow inhibitory postsynaptic potentials (IPSP) on the identified RPal neuron of Helix pomatia L. Evoked EPSPs were reduced or blocked by nicotine, atropine and d-tubocurarine. The two components of IPSP were different in their pharmacological sensitivity. Slow IPSP was partly or totally eliminated by ergometrine and chlorpromazine and was reduced by atropine, nicotine as well as by propranolol. Fast IPSP was reduced only in the presence of ergometrine and could not be blocked by either of the applied drugs. Participation of cholinergic transmission seems to be essential in the evoked EPSP but its partial involvement in the slow IPSP can also be supposed. A dopaminergic mechanism may take part in the generation of both components of IPSP but the receptors responsible for the slow IPSP were sensitive to other catecholamine antagonists as well, referring to a more complex origin, or to the involvement of an unknown transmitter. Comparison of PSPs evoked by stimulation of different nerves shows that presynaptic areas belonging to various peripheral sources are overlapped on the RPal neuron, and they probably act by similar transmitter substances. PMID:6650194

Vehovszky, A; Salánki, J

1983-01-01

138

Programmable Pacemaker  

NASA Technical Reports Server (NTRS)

St. Jude Medical's Cardiac Rhythm Management Division, formerly known as Pacesetter Systems, Inc., incorporated Apollo technology into the development of the programmable pacemaker system. This consists of the implantable pacemaker together with a physician's console containing the programmer and a data printer. Physician can communicate with patient's pacemaker by means of wireless telemetry signals transmitted through the communicating head held over the patient's chest. Where earlier pacemakers deliver a fixed type of stimulus once implanted, Programalith enables surgery free "fine tuning" of device to best suit the patient's changing needs.

1980-01-01

139

Circadian integration of sleep-wake and feeding requires NPY receptor-expressing neurons in the mediobasal hypothalamus  

PubMed Central

Sleep and feeding rhythms are highly coordinated across the circadian cycle, but the brain sites responsible for this coordination are unknown. We examined the role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially hyperphagic, became obese, exhibited sustained disruption of circadian feeding patterns, and had abnormal circadian distribution of sleep-wake patterns. Total amounts of rapid eye movement sleep (REMS) and non-REMS (NREMS) were not altered by NPY-SAP lesions, but a peak amount of REMS was permanently displaced to the dark period, and circadian variation in NREMS was eliminated. The phase reversal of REMS to the dark period by the lesion suggests that REMS timing is independently linked to the function of MBH NPY receptor-expressing neurons and is not dependent on NREMS pattern, which was altered but not phase reversed by the lesion. Sleep-wake patterns were altered in controls by restricting feeding to the light period, but were not altered in NPY-SAP rats by restricting feeding to either the light or dark period, indicating that disturbed sleep-wake patterns in lesioned rats were not secondary to changes in food intake. Sleep abnormalities persisted even after hyperphagia abated during the static phase of the lesion. Results suggest that the MBH is required for the essential task of integrating sleep-wake and feeding rhythms, a function that allows animals to accommodate changeable patterns of food availability. NPY receptor-expressing neurons are key components of this integrative function. PMID:21880863

Mukherjee, S.; Li, A.-J.; Dinh, T. T.; Rooney, E. M.; Simasko, S. M.; Ritter, S.

2011-01-01

140

Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice  

PubMed Central

Daily rhythms of food anticipatory activity (FAA) are regulated independently of the suprachiasmatic nucleus, which mediates entrainment of rhythms to light, but the neural circuits that establish FAA remain elusive. In this study, we show that mice lacking the dopamine D1 receptor (D1R KO mice) manifest greatly reduced FAA, whereas mice lacking the dopamine D2 receptor have normal FAA. To determine where dopamine exerts its effect, we limited expression of dopamine signaling to the dorsal striatum of dopamine-deficient mice; these mice developed FAA. Within the dorsal striatum, the daily rhythm of clock gene period2 expression was markedly suppressed in D1R KO mice. Pharmacological activation of D1R at the same time daily was sufficient to establish anticipatory activity in wild-type mice. These results demonstrate that dopamine signaling to D1R-expressing neurons in the dorsal striatum plays an important role in manifestation of FAA, possibly by synchronizing circadian oscillators that modulate motivational processes and behavioral output. DOI: http://dx.doi.org/10.7554/eLife.03781.001 PMID:25217530

Gallardo, Christian M; Darvas, Martin; Oviatt, Mia; Chang, Chris H; Michalik, Mateusz; Huddy, Timothy F; Meyer, Emily E; Shuster, Scott A; Aguayo, Antonio; Hill, Elizabeth M; Kiani, Karun; Ikpeazu, Jonathan; Martinez, Johan S; Purpura, Mari; Smit, Andrea N; Patton, Danica F; Mistlberger, Ralph E; Palmiter, Richard D; Steele, Andrew D

2014-01-01

141

The Tau Mutation of Casein Kinase 1? Sets the Period of the Mammalian Pacemaker via Regulation of Period1 or Period2 Clock Proteins  

PubMed Central

The suprachiasmatic nucleus (SCN) of the hypothalamus is the principal circadian pacemaker in mammals, coordinating daily metabolic and physiological rhythms with the cycle of sleep and wakefulness. SCN neurons define circadian time via an auto-regulatory feedback loop in which the activation of Period (Per) and Cryptochrome genes is periodically suppressed by their own protein products. Casein kinase 1 (CK1) enzymes have a critical role in circadian pacemaking because they phosphorylate PER proteins and thereby direct their proteasomal degradation. In human pedigrees, individual mutations in either hCK1 or hPER2 lead to advanced sleep phase disorders, whereas in rodents, the Tau mutation of CK1 epsilon (CK1?Tau) accelerates rest-activity cycles and shortens the period of the SCN molecular pacemaker. Biochemical analyses of recombinant PER proteins in cultured cells and endogenous proteins in peripheral tissues have identified PER1 and PER2, but not PER3, as direct substrates of CK1?. The purpose of this study, therefore, was to determine the relative contributions of endogenous PER proteins to the period-accelerating effects of CK1?Tau, both in vivo and in vitro. CK1?Tau mice were mated onto Per1-, Per2-, and Per1-Per2 (Per1/2) double-null backgrounds, in all cases carrying the Per1-luciferase bioluminescent circadian reporter gene. Mice lacking both PER1 and PER2 were behaviorally arrhythmic, confirming the inadequacy of PER3 as a circadian factor. Individual loss of either PER1 or PER2 had no significant effect on the circadian period or quality of wheel-running behavior, and CK1?Tau accelerated behavioral rhythms in both Per1- and Per2-null mice. CK1?Tau also accelerated in vitro molecular pacemaking in SCN lacking either PER1 or PER2, with a greater effect in PER2-dependent (i.e., Per1-null) SCN than in PER1-dependent slices. In double-null slices, some SCN were arrhythmic, whereas others exhibited transient rhythms, which trended nonsignificantly toward a shorter period. Both short-period and long-period rhythms could be identified in individual SCN neurons imaged by charge-coupled device camera. CK1?Tau had no effect, however, on SCN-level or individual neuronal rhythms in the absence of PER1 and PER2. Thus, the CK1?Tau allele has divergent actions, acting via both endogenous PER1 and PER2, but not PER3 protein, to mediate its circadian actions in vivo. Moreover, PER-independent cellular oscillations may contribute to pacemaking, but they are unstable and imprecise, and are not affected by the Tau mutation. PMID:24682205

Maywood, E.S.; Chesham, J.E.; Smyllie, N.J.; Hastings, M.H.

2014-01-01

142

Phase Angle Difference Alters Coupling Relations of Functionally Distinct Circadian Oscillators Revealed by Rhythm Splitting  

Microsoft Academic Search

The interactions (i.e., coupling) between multiple oscillators of a circadian system determine basic properties of the integrated pacemaker. Unfortunately, there are few experimental models to investigate the putative interactions of functionally defined oscillators comprising the mammalian circadian pacemaker. Here the authors induce in hamsters a novel circadian entrainment pattern that is characterized by the daily expression of robust wheel-running activity

Michael R. Gorman; Nicholas A. Steele

2006-01-01

143

Embryonic development of circadian clocks in the mammalian suprachiasmatic nuclei  

PubMed Central

In most species, self-sustained molecular clocks regulate 24-h rhythms of behavior and physiology. In mammals, a circadian pacemaker residing in the hypothalamic suprachiasmatic nucleus (SCN) receives photic signals from the retina and synchronizes subordinate clocks in non-SCN tissues. The emergence of circadian rhythmicity during development has been extensively studied for many years. In mice, neuronal development in the presumptive SCN region of the embryonic hypothalamus occurs on days 12–15 of gestation. Intra-SCN circuits differentiate during the following days and retinal projections reach the SCN, and thus mediate photic entrainment, only after birth. In contrast the genetic components of the clock gene machinery are expressed much earlier and during midgestation SCN explants and isolated neurons are capable of generating molecular oscillations in culture. In vivo metabolic rhythms in the SCN, however, are observed not earlier than the 19th day of rat gestation, and rhythmic expression of clock genes is hardly detectable until after birth. Together these data indicate that cellular coupling and, thus, tissue-wide synchronization of single-cell rhythms, may only develop very late during embryogenesis. In this mini-review we describe the developmental origin of the SCN structure and summarize our current knowledge about the functional initiation and entrainment of the circadian pacemaker during embryonic development. PMID:25520627

Landgraf, Dominic; Koch, Christiane E.; Oster, Henrik

2014-01-01

144

Circadian Effects of Light No Brighter Than Moonlight  

Microsoft Academic Search

In mammals, light entrains endogenous circadian pacemakers by inducing daily phase shifts via a photoreceptor mechanism recently discovered in retinal ganglion cells. Light that is comparable in intensity to moonlight is generally ineffective at inducing phase shifts or suppressing melatonin secretion, which has prompted the view that circadian photic sensitivity has been titrated so that the central pacemaker is unaffected

Jennifer A. Evans; Jeffrey A. Elliott; Michael R. Gorman

2007-01-01

145

Advanced Pacemaker  

NASA Technical Reports Server (NTRS)

Synchrony, developed by St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.) is an advanced state-of-the-art implantable pacemaker that closely matches the natural rhythm of the heart. The companion element of the Synchrony Pacemaker System is the Programmer Analyzer APS-II which allows a doctor to reprogram and fine tune the pacemaker to each user's special requirements without surgery. The two-way communications capability that allows the physician to instruct and query the pacemaker is accomplished by bidirectional telemetry. APS-II features 28 pacing functions and thousands of programming combinations to accommodate diverse lifestyles. Microprocessor unit also records and stores pertinent patient data up to a year.

1990-01-01

146

Differential effects of omega-3 fatty acid docosahexaenoic acid and palmitate on the circadian transcriptional profile of clock genes in immortalized hypothalamic neurons.  

PubMed

Diets high in saturated fatty acids (SFAs) are associated with the development of circadian dysregulation, obesity, and Type 2 diabetes mellitus. Conversely, polyunsaturated fatty acids (PUFAs) have recently been identified to improve insulin sensitivity, reduce weight gain, and relieve obesity-induced inflammation. While saturated fatty acids, such as the prevalent dietary fatty acid palmitate, have been implicated in circadian disruption, there is a paucity of studies regarding the effects of PUFAs on circadian parameters. Therefore, the immortalized murine neuronal model, mHypoE-37, was utilized to examine the effects of the SFA palmitate and omega-3 PUFA docosahexaenoic acid (DHA) on circadian rhythms. The mHypoE-37 neurons express the core clock genes, Bmal1, Per2, and Rev-erb?, in a circadian manner. 25 ?M of palmitate significantly increased the transcriptional expression of Bmal1, without altering the expression of inflammatory markers TLR4, I?B?, and IL-6, nor the orexigenic neuropeptide AgRP, suggesting that the observed disruption of the molecular clock is the result of a mechanism distinct from that of hypothalamic cellular inflammation. Furthermore, treatment with the PUFA DHA resulted in alterations in the circadian expression profile of Bmal1, although differentially from the effects of palmitate. In the presence of DHA, the disruptive effects of palmitate on Bmal1 were less pronounced, suggesting a protective effect of DHA. These studies are the first to identify the potential for omega-3 PUFAs to protect against palmitate-mediated dysregulation of circadian parameters and will ultimately improve the understanding of circadian control mechanisms. PMID:25144192

Greco, James A; Oosterman, Johanneke E; Belsham, Denise D

2014-10-15

147

Programmable Pacemaker  

NASA Technical Reports Server (NTRS)

Released in 1995, the Trilogy cardiac pacemaker is the fourth generation of a unit developed in the 1970s by NASA, Johns Hopkins Applied Physics Laboratory and St. Jude Medical's Cardiac Rhythm Management Division (formerly known as Pacesetter Systems, Inc.). The new system incorporates the company's PDx diagnostic and programming software and a powerful microprocessor that allows more functions to be fully automatic and gives more detailed information on the patient's health and the performance of the pacing systems. The pacemaker incorporates bidirectional telemetry used for space communications for noninvasive communication with the implanted pacemaker, smaller implantable pulse generators from space microminiaturization, and longer-life batteries from technology for spacecraft electrical power systems.

1996-01-01

148

Epigenetic control and the circadian clock: linking metabolism to neuronal responses.  

PubMed

Experimental and epidemiological evidence reveal the profound influence that industrialized modern society has imposed on human social habits and physiology during the past 50 years. This drastic change in life-style is thought to be one of the main causes of modern diseases including obesity, type 2 diabetes, mental illness such as depression, sleep disorders, and certain types of cancer. These disorders have been associated to disruption of the circadian clock, an intrinsic time-keeper molecular system present in virtually all cells and tissues. The circadian clock is a key element in homeostatic regulation by controlling a large array of genes implicated in cellular metabolism. Importantly, intimate links between epigenetic regulation and the circadian clock exist and are likely to prominently contribute to the plasticity of the response to the environment. In this review, we summarize some experimental and epidemiological evidence showing how environmental factors such as stress, drugs of abuse and changes in circadian habits, interact through different brain areas to modulate the endogenous clock. Furthermore we point out the pivotal role of the deacetylase silent mating-type information regulation 2 homolog 1 (SIRT1) as a molecular effector of the environment in shaping the circadian epigenetic landscape. PMID:24486964

Orozco-Solis, R; Sassone-Corsi, P

2014-04-01

149

Resetting of Circadian Time in Peripheral Tissues by Glucocorticoid Signaling  

Microsoft Academic Search

In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not

Aurélio Balsalobre; Steven A. Brown; Lysiane Marcacci; François Tronche; Christoph Kellendonk; Holger M. Reichardt; Günther Schütz; Ueli Schibler

2000-01-01

150

Implantable pacemakers  

Microsoft Academic Search

Advances in cardiac pacing have greatly reduced the size of pacemakers, while improving their longevity and reliability, expanding their clinical applications and increasing their sophistication in terms of programming and automatic features. Significant reductions in the size of pacing systems have been mainly due to improvements in power sources, increased circuit integration, hybrid packaging, and the development of smaller leads

RICHARD S. SANDERS; MICHAEL T. LEE

1996-01-01

151

UNC79 and UNC80, Putative Auxiliary Subunits of the NARROW ABDOMEN Ion Channel, Are Indispensable for Robust Circadian Locomotor Rhythms in Drosophila  

PubMed Central

In the fruit fly Drosophila melanogaster, a network of circadian pacemaker neurons drives daily rhythms in rest and activity. The ion channel NARROW ABDOMEN (NA), orthologous to the mammalian sodium leak channel NALCN, functions downstream of the molecular circadian clock in pacemaker neurons to promote behavioral rhythmicity. To better understand the function and regulation of the NA channel, we have characterized two putative auxiliary channel subunits in Drosophila, unc79 (aka dunc79) and unc80 (aka CG18437). We have generated novel unc79 and unc80 mutations that represent strong or complete loss-of-function alleles. These mutants display severe defects in circadian locomotor rhythmicity that are indistinguishable from na mutant phenotypes. Tissue-specific RNA interference and rescue analyses indicate that UNC79 and UNC80 likely function within pacemaker neurons, with similar anatomical requirements to NA. We observe an interdependent, post-transcriptional regulatory relationship among the three gene products, as loss of na, unc79, or unc80 gene function leads to decreased expression of all three proteins, with minimal effect on transcript levels. Yet despite this relationship, we find that the requirement for unc79 and unc80 in circadian rhythmicity cannot be bypassed by increasing NA protein expression, nor can these putative auxiliary subunits substitute for each other. These data indicate functional requirements for UNC79 and UNC80 beyond promoting channel subunit expression. Immunoprecipitation experiments also confirm that UNC79 and UNC80 form a complex with NA in the Drosophila brain. Taken together, these data suggest that Drosophila NA, UNC79, and UNC80 function together in circadian clock neurons to promote rhythmic behavior. PMID:24223770

Lear, Bridget C.; Darrah, Eric J.; Aldrich, Benjamin T.; Gebre, Senetibeb; Scott, Robert L.; Allada, Ravi

2013-01-01

152

Circadian Rhythms and Cancer Chronotherapeutics  

Microsoft Academic Search

\\u000a The Circadian Timing System (CTS) controls cellular proliferation and drug metabolism over a 24-h period through molecular\\u000a clocks in each cell. These cellular clocks are coordinated by a hypothalamic pacemaker, the suprachiasmatic nuclei, which\\u000a generate or control circadian physiology. The CTS down-regulates malignant growth in experimental models and in cancer patients.\\u000a It also generates large and predictable 24-h changes in

Francis Lévi; Atilla Altinok; Albert Goldbeter

153

Aging Decreases L-Type Calcium Channel Currents and Pacemaker Firing Fidelity in Substantia Nigra Dopamine Neurons  

PubMed Central

Substantia nigra dopamine neurons are involved in behavioral processes that include cognition, reward learning, and voluntary movement. Selective deterioration of these neurons is responsible for the motor deficits associated with Parkinson's disease (PD). Aging is the leading risk factor for PD, suggesting that adaptations occurring in dopamine neurons during normal aging may predispose individuals to the development of PD. Previous studies suggest that the unique set of ion conductances that drive spontaneous, rhythmic firing of action potentials could predispose substantia nigra dopamine neurons to selective neurodegeneration. Here we show, using patch-clamp electrophysiological recordings in brain slices, that substantia nigra dopamine neurons from mice 25–30 months of age (old) have comparable membrane capacitance and input resistance to neurons from mice 2–7 months of age (young). However, neurons from old mice exhibit slower firing rates, narrower spike widths, and more variable interspike intervals compared with neurons from young mice. Dopamine neurons from old mice also exhibit smaller L-type calcium channel currents, providing a plausible mechanism that likely contributes to the changes in impulse activity. Age-related decrements in the physiological function of dopamine neurons could contribute to the decrease in voluntary movement and other dopamine-mediated behaviors observed in aging populations. Furthermore, as pharmacological antagonism of L-type calcium channels has been proposed as a potential treatment for the early stages of PD, our results could point to a limited temporal window of opportunity for this therapeutic intervention. PMID:25009264

Branch, Sarah Y.; Sharma, Ramaswamy

2014-01-01

154

Association of intrinsic circadian period with morningness-eveningness, usual wake time, and circadian phase  

NASA Technical Reports Server (NTRS)

The biological basis of preferences for morning or evening activity patterns ("early birds" and "night owls") has been hypothesized but has remained elusive. The authors reported that, compared with evening types, the circadian pacemaker of morning types was entrained to an earlier hour with respect to both clock time and wake time. The present study explores a chronobiological mechanism by which the biological clock of morning types may be set to an earlier hour. Intrinsic period, a fundamental property of the circadian system, was measured in a month-long inpatient study. A subset of participants also had their circadian phase assessed. Participants completed a morningness-eveningness questionnaire before study. Circadian period was correlated with morningness-eveningness, circadian phase, and wake time, demonstrating that a fundamental property of the circadian pacemaker is correlated with the behavioral trait of morningness-eveningness.

Duffy, J. F.; Rimmer, D. W.; Czeisler, C. A.

2001-01-01

155

Perturbing Dynamin Reveals Potent Effects on the Drosophila Circadian Clock  

E-print Network

in the pacemaker lateral ventral neurons (LNv) was necessary and sufficient for this effect. Manipulation of other pathways. Levels of the clock component PERIOD were reduced in the shits1 -expressing pacemaker small LNv of sleep and wake are driven by transcriptional feedback loops in pacemaker neurons. In Drosophila

Allada, Ravi

156

Let there be ``more'' light: enhancement of light actions on the circadian system through  

E-print Network

are internally generated circa 24 h rhythms. The phase of the circadian pacemaker in mammals can be adjusted the master pacemaker oscillation when applied during the subjective day, as do several behavioral, suggesting a dynamic interaction between photic and non-photic stimuli in the fine-tuning of the pacemaker

Harrington, Mary

157

Suprachiasmatic nuclei and Circadian rhythms. The role of suprachiasmatic nuclei on rhythmic activity of neurons in the lateral hypothalamic area, ventromedian nuclei and pineal gland  

NASA Technical Reports Server (NTRS)

Unit activity of lateral hypothalamic area (LHA) and Ventromedian nuclei (VMN) was recorded in urethane anesthetized male rats. A 5 to 10 sec. a 3-5 min and a circadian rhythmicity were observed. In about 15% of all neurons, spontaneous activity of LHA and VMN showed reciprocal relationships. Subthreshold stimuli applied at a slow rate in the septum and the suprachiasmatic nuclei (SCN) suppressed the rhythms without changing firing rates. On the other hand, stimulation of the optic nerve at a rate of 5 to 10/sec increased firing rates in 1/3 of neurons of SCN. Iontophoretically applied acetylcholine increased 80% of tested neurons of SCN, whereas norepinephrine, dopamine and 5 HT inhibited 64, 60 and 75% of SCN neurons respectively. These inhibitions were much stronger in neurons, the activity of which was increased by optic nerve stimulation. Stimulation of the SCN inhibited the tonic activity in cervical sympathetic nerves.

Nishino, H.

1977-01-01

158

Interactions between bilaterally paired components of the cockroach circadian system  

Microsoft Academic Search

The hypothesis that bilaterally redundant, and mutually coupled circadian pacemakers are located near the lobula of the optic lobes of the cockroach,Leucophaea maderae, was investigated in a series of lesion experiments.

Terry L. Page

1978-01-01

159

Circadian control of neuroendocrine circuits regulating female reproductive function.  

PubMed

Female reproduction requires the precise temporal organization of interacting, estradiol-sensitive neural circuits that converge to optimally drive hypothalamo-pituitary-gonadal (HPG) axis functioning. In mammals, the master circadian pacemaker in the suprachiasmatic nucleus (SCN) of the anterior hypothalamus coordinates reproductively relevant neuroendocrine events necessary to maximize reproductive success. Likewise, in species where periods of fertility are brief, circadian oversight of reproductive function ensures that estradiol-dependent increases in sexual motivation coincide with ovulation. Across species, including humans, disruptions to circadian timing (e.g., through rotating shift work, night shift work, poor sleep hygiene) lead to pronounced deficits in ovulation and fecundity. Despite the well-established roles for the circadian system in female reproductive functioning, the specific neural circuits and neurochemical mediators underlying these interactions are not fully understood. Most work to date has focused on the direct and indirect communication from the SCN to the gonadotropin-releasing hormone (GnRH) system in control of the preovulatory luteinizing hormone (LH) surge. However, the same clock genes underlying circadian rhythms at the cellular level in SCN cells are also common to target cell populations of the SCN, including the GnRH neuronal network. Exploring the means by which the master clock synergizes with subordinate clocks in GnRH cells and its upstream modulatory systems represents an exciting opportunity to further understand the role of endogenous timing systems in female reproduction. Herein we provide an overview of the state of knowledge regarding interactions between the circadian timing system and estradiol-sensitive neural circuits driving GnRH secretion and the preovulatory LH surge. PMID:22661968

Williams, Wilbur P; Kriegsfeld, Lance J

2012-01-01

160

A Plastic Clock: How Circadian Rhythms Respond to Environmental Cues in Drosophila  

Microsoft Academic Search

Circadian clocks synchronize the physiology and behavior of most animals with the day to night cycle. A fundamental property\\u000a of the molecular pacemakers generating circadian rhythms is their self-sustained nature: they keep oscillating even under\\u000a constant conditions, with a period close to, but not exactly, 24 h. However, circadian pacemakers have to be sensitive to\\u000a environmental cues to be beneficial. They

Raphaelle Dubruille; Patrick Emery

2008-01-01

161

[Intercellular communication-based robust circadian oscillation of the suprachiasmatic nucleus in the brain: mechanisms beyond intracellular clock machinery].  

PubMed

Recent advances in circadian biology strongly suggest that there are still genes involved in the generation and maintenance of biological rhythms that remain to be identified. It has been generally appreciated that circadian rhythms are generated intracellularly through transcription/translation-based autoregulatory feedback circuits of the clock genes. However, the existence of new intracellular clock machinery that cannot be explained by existing clock genes has recently been reported. This clock manifests as oxidation-reduction cycles of peroxiredoxin proteins, implying that as-yet-undiscovered clock genes may exist within cells to regulate redox cycling. Moreover, great strides have also been made in understanding the cell-cell communication-based robust circadian oscillations of the suprachiasmatic nucleus (SCN), the central pacemaker in the brain. Thousands of neurons that constitute the SCN maintain a high degree of synchrony in a way that allows the SCN neurons to create coherent signals as a whole. Inactivation of the genes involved in the cell-cell synchronization of the SCN, which include the genes encoding VIP, VPAC2, and RGS16, leads to altered circadian rhythms in behavior and physiologies. The purpose of this review is to provide an overview of recent advances in the circadian biology, with a special emphasis on the importance of cell-cell interactions within the SCN. PMID:24437257

Doi, Masao

2013-12-01

162

Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior  

E-print Network

Endogenous circadian rhythm in an index of cardiac vulnerability independent of changes in behavior, influences from the endogenous circadian pacemaker independent from behaviors may also affect cardiac control features of the healthy human heartbeat have an endogenous circadian rhythm that brings the features closer

Stanley, H. Eugene

163

Calcium-activated potassium channels in insect pacemaker neurons as unexpected target site for the novel fumigant dimethyl disulfide.  

PubMed

Dimethyl disulfide (DMDS), a plant-derived insecticide, is a promising fumigant as a substitute for methyl bromide. To further understand the mode of action of DMDS, we examined its effect on cockroach octopaminergic neurosecretory cells, called dorsal unpaired median (DUM) neurons, using whole-cell patch-clamp technique, calcium imaging and antisense oligonucleotide strategy. At low concentration (1 microM), DMDS modified spontaneous regular spike discharge into clear bursting activity associated with a decrease of the amplitude of the afterhyperpolarization. This effect led us to suspect alterations of calcium-activated potassium currents (IKCa) and [Ca(2+)](i) changes. We showed that DMDS reduced amplitudes of both peak transient and sustained components of the total potassium current. IKCa was confirmed as a target of DMDS by using iberiotoxin, cadmium chloride, and pSlo antisense oligonucleotide. In addition, we showed that DMDS induced [Ca(2+)](i) rise in Fura-2-loaded DUM neurons. Using calcium-free solution, and (R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2-(2,3,4-trimethoxy-phenyl)ethyl]-acetamide (LOE 908) [an inhibitor of transient receptor potential (TRP)gamma], we demonstrated that TRPgamma initiated calcium influx. By contrast, omega-conotoxin GVIA (an inhibitor of N-type high-voltage-activated calcium channels), did not affect the DMDS-induced [Ca(2+)](i) rise. Finally, the participation of the calcium-induced calcium release mechanism was investigated using thapsigargin, caffeine, and ryanodine. Our study revealed that DMDS-induced elevation in [Ca(2+)](i) modulated IKCa in an unexpected bell-shaped manner via intracellular calcium. In conclusion, DMDS affects multiple targets, which could be an effective way to improve pest control efficacy of fumigation. PMID:17942746

Gautier, Hélène; Auger, Jacques; Legros, Christian; Lapied, Bruno

2008-01-01

164

[Circadian rhythm sleep disorder].  

PubMed

Primary pathophysiology of circadian rhythm sleep disorders(CRSDs) is a misalignment between the endogenous circadian rhythm phase and the desired or socially required sleep-wake schedule, or dysfunction of the circadian pacemaker and its afferent/efferent pathways. CRSDs consist of delayed sleep phase type, advanced sleep phase type, free-running type, irregular sleep-wake type, shift work type and jet lag type. Chronotherapy using strong zeitgebers (time cues), such as bright light and melatonin/ melatonin type 2 receptor agonist, is effective when administered with proper timing. Bright light is the strongest entraining agent of circadian rhythms. Bright light therapy (appropriately-timed exposure to bright light) for CRSDs is an effective treatment option, and can shift the sleep-wake cycle to earlier or later times, in order to correct for misalignment between the circadian system and the desired sleep-wake schedule. Timed administration of melatonin, either alone or in combination with light therapy has also been shown to be useful in the treatment of CRSDs. PMID:24437262

Mishima, Kazuo

2013-12-01

165

Pacemaker insertion.  

PubMed

A pacemaker (PM) (or artificial PM, so as not to be confused with the heart's natural PM) is a medical device that uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate the beating of the heart. The primary purpose of this device is to maintain an adequate heart rate, either because the heart's natural PM is not fast enough, or there is a block in the heart's electrical conduction system. Modern PMs are externally programmable and allow the cardiologist to select the optimum pacing modes for individual patients. Some combine a PM and defibrillator in a single implantable device. PMs can be temporary or permanent. Temporary PMs are used to treat short-term heart problems, such as a slow heartbeat that's caused by a heart attack, heart surgery, or an overdose of medicine. Permanent PMs are used to control long-term heart rhythm problems. A PM can relieve some arrhythmia symptoms, such as fatigue and fainting. A PM also can help a person who has abnormal HRs resume a more active lifestyle. In the current mini review we will focus on the insertion of a PM and the possible pneumothorax that can be caused. PMID:25815303

Kotsakou, Maria; Kioumis, Ioannis; Lazaridis, George; Pitsiou, Georgia; Lampaki, Sofia; Papaiwannou, Antonis; Karavergou, Anastasia; Tsakiridis, Kosmas; Katsikogiannis, Nikolaos; Karapantzos, Ilias; Karapantzou, Chrysanthi; Baka, Sofia; Mpoukovinas, Ioannis; Karavasilis, Vasilis; Rapti, Aggeliki; Trakada, Georgia; Zissimopoulos, Athanasios; Zarogoulidis, Konstantinos; Zarogoulidis, Paul

2015-03-01

166

Pacemaker insertion  

PubMed Central

A pacemaker (PM) (or artificial PM, so as not to be confused with the heart’s natural PM) is a medical device that uses electrical impulses, delivered by electrodes contracting the heart muscles, to regulate the beating of the heart. The primary purpose of this device is to maintain an adequate heart rate, either because the heart’s natural PM is not fast enough, or there is a block in the heart’s electrical conduction system. Modern PMs are externally programmable and allow the cardiologist to select the optimum pacing modes for individual patients. Some combine a PM and defibrillator in a single implantable device. PMs can be temporary or permanent. Temporary PMs are used to treat short-term heart problems, such as a slow heartbeat that’s caused by a heart attack, heart surgery, or an overdose of medicine. Permanent PMs are used to control long-term heart rhythm problems. A PM can relieve some arrhythmia symptoms, such as fatigue and fainting. A PM also can help a person who has abnormal HRs resume a more active lifestyle. In the current mini review we will focus on the insertion of a PM and the possible pneumothorax that can be caused.

Kotsakou, Maria; Kioumis, Ioannis; Lazaridis, George; Pitsiou, Georgia; Lampaki, Sofia; Papaiwannou, Antonis; Karavergou, Anastasia; Tsakiridis, Kosmas; Katsikogiannis, Nikolaos; Karapantzos, Ilias; Karapantzou, Chrysanthi; Baka, Sofia; Mpoukovinas, Ioannis; Karavasilis, Vasilis; Rapti, Aggeliki; Trakada, Georgia; Zissimopoulos, Athanasios; Zarogoulidis, Konstantinos

2015-01-01

167

Photopic transduction implicated in human circadian entrainment  

NASA Technical Reports Server (NTRS)

Despite the preeminence of light as the synchronizer of the circadian timing system, the phototransductive machinery in mammals which transmits photic information from the retina to the hypothalamic circadian pacemaker remains largely undefined. To determine the class of photopigments which this phototransductive system uses, we exposed a group (n = 7) of human subjects to red light below the sensitivity threshold of a scotopic (i.e. rhodopsin/rod-based) system, yet of sufficient strength to activate a photopic (i.e. cone-based) system. Exposure to this light stimulus was sufficient to reset significantly the human circadian pacemaker, indicating that the cone pigments which mediate color vision can also mediate circadian vision.

Zeitzer, J. M.; Kronauer, R. E.; Czeisler, C. A.

1997-01-01

168

CIRCADIAN RHYTHMS Circadian Photoreception  

NSDL National Science Digital Library

The circadian rhythms of physiology and behavior are driven by autonomous cellular clocks. To be useful, these clocks must be synchronized to the day-night cycles of the real world. This article provides a review of research on circadian photoreceptors in mammals.

Michael Menaker (University of Virginia; Department of Biology)

2003-01-10

169

Pacemakers and Implantable Defibrillators  

MedlinePLUS

... arrhythmia is serious, you may need a cardiac pacemaker or an implantable cardioverter defibrillator (ICD). They are ... are implanted in your chest or abdomen. A pacemaker helps control abnormal heart rhythms. It uses electrical ...

170

Choosing pacemakers appropriately  

Microsoft Academic Search

The range of implantable cardiac pacing devices has expanded, with the advances in available technology. Indications for cardiac pacing devices, that is pacemakers, implantable cardioverter defibrillators (ICDs) and cardiac resynchronisation therapy devices (CRTs), have expanded for the treatment, diagnosis and monitoring of bradycardia, tachycardia and heart failure. While the need for pacemakers is increasing, not all patients who require pacemakers

G K Panicker; B Desai; Y Lokhandwala

2009-01-01

171

Circadian rhythm and its role in malignancy  

PubMed Central

Circadian rhythms are daily oscillations of multiple biological processes directed by endogenous clocks. The circadian timing system comprises peripheral oscillators located in most tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs) including various cell cycle genes. Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. This may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. Different lines of evidence in mice and humans suggest that cancer may be a circadian-related disorder. The genetic or functional disruption of the molecular circadian clock has been found in various cancers including breast, ovarian, endometrial, prostate and hematological cancers. The acquisition of current data in circadian clock mechanism may help chronotherapy, which takes into consideration the biological time to improve treatments by devising new therapeutic approaches for treating circadian-related disorders, especially cancer. PMID:20353609

2010-01-01

172

Synchronization and entrainment of coupled circadian oscillators  

E-print Network

Synchronization and entrainment of coupled circadian oscillators N. Komin, A. C. Murza, E. Herna, 07122 Palma de Mallorca, Spain Circadian rhythms in mammals are controlled by the neurons located periods. Keywords: circadian oscillations; quenched noise; noise-induced oscillator death; modified

Toral, Raúl

173

Permanent pacemakers in pregnancy.  

PubMed

Advances in cardiology and cardiovascular surgery have increased the use of permanent pacemakers in young adults such that there are more women with pacemakers becoming pregnant. This case report describes the pregnancy and delivery of a young woman with a demand pacemaker and reviews the principles of management of cardiac pacemakers in pregnancy. As part of the multidisciplinary team including cardiology, anesthesia, nursing and caring for these patients, it is important that obstetricians be informed and follow the principles of management of cardiac pacemakers in pregnancy to continue to achieve successful pregnancy outcomes. PMID:21995172

Coolen, J; Turnelp, R; Vonder Muhll, I; Chandra, S

2011-01-01

174

Circadian periods of sensitivity for ramelteon on the onset of running-wheel activity and the peak of suprachiasmatic nucleus neuronal firing rhythms in C3H/HeN mice.  

PubMed

Ramelteon, an MT(1)/MT(2) melatonin receptor agonist, is used for the treatment of sleep-onset insomnia and circadian sleep disorders. Ramelteon phase shifts circadian rhythms in rodents and humans when given at the end of the subjective day; however, its efficacy at other circadian times is not known. Here, the authors determined in C3H/HeN mice the maximal circadian sensitivity for ramelteon in vivo on the onset of circadian running-wheel activity rhythms, and in vitro on the peak of circadian rhythm of neuronal firing in suprachiasmatic nucleus (SCN) brain slices. The phase response curve (PRC) for ramelteon (90?µg/mouse, subcutaneous [sc]) on circadian wheel-activity rhythms shows maximal sensitivity during the late mid to end of the subjective day, between CT8 and CT12 (phase advance), and late subjective night and early subjective day, between CT20 and CT2 (phase delay), using a 3-day-pulse treatment regimen in C3H/HeN mice. The PRC for ramelteon resembles that for melatonin in C3H/HeN mice, showing the same magnitude of maximal shifts at CT10 and CT2, except that the range of sensitivity for ramelteon (CT8-CT12) during the subjective day is broader. Furthermore, in SCN brain slices in vitro, ramelteon (10 pM) administered at CT10 phase advances (5.6?±?0.29?h, n?=?3) and at CT2 phase delays (-3.2?±?0.12?h, n?=?6) the peak of circadian rhythm of neuronal firing, with the shifts being significantly larger than those induced by melatonin (10 pM) at the same circadian times (CT10: 2.7?±?0.15?h, n?=?4, p?circadian sensitivity at CT10 (advance) and CT2 (delay) to shift the onset of circadian activity rhythms in vivo and the peak of SCN neuronal firing rhythms in vitro. PMID:21182402

Rawashdeh, Oliver; Hudson, Randall L; Stepien, Iwona; Dubocovich, Margarita L

2011-02-01

175

Cellular/Molecular D2 Autoreceptors Chronically Enhance Dopamine Neuron  

E-print Network

Cellular/Molecular D2 Autoreceptors Chronically Enhance Dopamine Neuron Pacemaker Activity Junghyun and fidelity of dopamine neuron pacemaker activity. Key words: dopamine neuron; K channel; D2 receptor; channel noise; pacemaker; antipsychotic drug Introduction Midbrain dopamine (DA) neurons are important in normal

Horn, John P.

176

Circadian Rhythms  

MedlinePLUS

... get drowsy. How are circadian rhythms related to jet lag? Jet lag occurs when travelers suffer from disrupted circadian rhythms. ... may lead researchers to treatments for sleep disorders, jet lag and other health problems. Learning more about the ...

177

Circadian entrainment and phase resetting differ markedly under dimly illuminated versus completely dark nights  

Microsoft Academic Search

An endogenous circadian pacemaker uses photic input to synchronize mammalian physiological and behavioral rhythms to the 24h day. Sunlight during dusk and dawn is thought to entrain the pacemaker of nocturnal rodents, whereas moonlight and starlight are presumed to exert little influence. We show that, to the contrary, dim illumination (<0.005lux), similar in intensity to starlight and dim moonlight, markedly

Jennifer A. Evans; Jeffrey A. Elliott; Michael R. Gorman

2005-01-01

178

Pacemaker-mediated angina.  

PubMed

Angina is a clinical syndrome characterized by discomfort in the chest, jaw, shoulder, back or arm. It is typically aggravated by exertion or emotional stress and relieved by nitroglycerin. Atherosclerotic coronary artery disease is the most common cause of angina. Dual-chamber pacemakers track the atrial electrical activity by pacing the ventricle. The present article reports the first case in the literature involving pacemaker-mediated angina. A 78-year-old man complained of chest pain shortly after the placement of a permanent dual-chamber pacemaker and experienced immediate relief of his pain after the pacemaker mode was switched from tracking the atrium and pacing the ventricle to sensing and pacing the ventricle. The pain was identified as angina pectoris. The comprehensive history-taking performed before pacemaker placement helped to quickly identify the cause of the patient's pain. PMID:24294035

Ibrahim, Morhaf; Hasan, Reham

2013-01-01

179

Getting through to circadian oscillators: why use constant routines?  

NASA Technical Reports Server (NTRS)

Overt 24-h rhythmicity is composed of both exogenous and endogenous components, reflecting the product of multiple (periodic) feedback loops with a core pacemaker at their center. Researchers attempting to reveal the endogenous circadian (near 24-h) component of rhythms commonly conduct their experiments under constant environmental conditions. However, even under constant environmental conditions, rhythmic changes in behavior, such as food intake or the sleep-wake cycle, can contribute to observed rhythmicity in many physiological and endocrine variables. Assessment of characteristics of the core circadian pacemaker and its direct contribution to rhythmicity in different variables, including rhythmicity in gene expression, may be more reliable when such periodic behaviors are eliminated or kept constant across all circadian phases. This is relevant for the assessment of the status of the circadian pacemaker in situations in which the sleep-wake cycle or food intake regimes are altered because of external conditions, such as in shift work or jet lag. It is also relevant for situations in which differences in overt rhythmicity could be due to changes in either sleep oscillatory processes or circadian rhythmicity, such as advanced or delayed sleep phase syndromes, in aging, or in particular clinical conditions. Researchers studying human circadian rhythms have developed constant routine protocols to assess the status of the circadian pacemaker in constant behavioral and environmental conditions, whereas this technique is often thought to be unnecessary in the study of animal rhythms. In this short review, the authors summarize constant routine methodology and what has been learned from constant routines and argue that animal and human circadian rhythm researchers should (continue to) use constant routines as a step on the road to getting through to central and peripheral circadian oscillators in the intact organism.

Duffy, Jeanne F.; Dijk, Derk-Jan

2002-01-01

180

Circadian rhythms of women with fibromyalgia  

NASA Technical Reports Server (NTRS)

Fibromyalgia syndrome is a chronic and debilitating disorder characterized by widespread nonarticular musculoskeletal pain whose etiology is unknown. Many of the symptoms of this syndrome, including difficulty sleeping, fatigue, malaise, myalgias, gastrointestinal complaints, and decreased cognitive function, are similar to those observed in individuals whose circadian pacemaker is abnormally aligned with their sleep-wake schedule or with local environmental time. Abnormalities in melatonin and cortisol, two hormones whose secretion is strongly influenced by the circadian pacemaker, have been reported in women with fibromyalgia. We studied the circadian rhythms of 10 women with fibromyalgia and 12 control healthy women. The protocol controlled factors known to affect markers of the circadian system, including light levels, posture, sleep-wake state, meals, and activity. The timing of the events in the protocol were calculated relative to the habitual sleep-wake schedule of each individual subject. Under these conditions, we found no significant difference between the women with fibromyalgia and control women in the circadian amplitude or phase of rhythms of melatonin, cortisol, and core body temperature. The average circadian phases expressed in hours posthabitual bedtime for women with and without fibromyalgia were 3:43 +/- 0:19 and 3:46 +/- 0:13, respectively, for melatonin; 10:13 +/- 0:23 and 10:32 +/- 0:20, respectively for cortisol; and 5:19 +/- 0:19 and 4:57 +/- 0:33, respectively, for core body temperature phases. Both groups of women had similar circadian rhythms in self-reported alertness. Although pain and stiffness were significantly increased in women with fibromyalgia compared with healthy women, there were no circadian rhythms in either parameter. We suggest that abnormalities in circadian rhythmicity are not a primary cause of fibromyalgia or its symptoms.

Klerman, E. B.; Goldenberg, D. L.; Brown, E. N.; Maliszewski, A. M.; Adler, G. K.

2001-01-01

181

Electromagnetic Interference on Pacemakers  

PubMed Central

External sources, either within or outside the hospital environment, may interfere with the appropriate function of pacemakers which are being implanted all around the world in current medical practice. The patient and the physician who is responsible for follow-up of the pacing systems may be confronted with some specific problems regarding the various types of electromagnetic interference (EMI). To avoid these unwanted EMI effects one must be aware of this potential problem and need to take some precautions. The effects of EMI on pacemaker function and precautions to overcome some specific problems were discussed in this review article. There are many sources of EMI interacting with pacemakers. Magnetic resonance imaging creates real problem and should be avoided in pacemaker patients. Cellular phones might be responsible for EMI when they were held on the same side with the pacemaker. Otherwise they don't cause any specific type of interaction with pacemakers. Sale security systems are not a problem if one walks through it without lingering in or near it. Patients having unipolar pacemaker systems are prone to develop EMI because of pectoral muscle artifacts during vigorous active physical exercise. PMID:17006562

Erdogan, Okan

2002-01-01

182

Phase relationships between core body temperature, melatonin, and sleep are associated with depression severity: further evidence for circadian misalignment in non-seasonal depression.  

PubMed

Misalignment between the timing of sleep and the circadian pacemaker has been linked to depression symptoms. This study sought to extend earlier findings by comparing sleep and circadian markers in healthy controls and individuals with major depression. Two markers of circadian misalignment correlated with depression severity in the depressed group. PMID:20471106

Hasler, Brant P; Buysse, Daniel J; Kupfer, David J; Germain, Anne

2010-06-30

183

Neonatal monosodium glutamate treatment prevents effects of constant light on circadian temperature rhythms of adult rats  

Microsoft Academic Search

Housing rats under continuous illumination (LL) disrupts circadian rhythms controlled by a pacemaker located in the hypothalamic suprachiasmatic nucleus (SCN). The neural mechanisms underlying this effect are not well understood. The present study examined the effects of LL on circadian rhythms and on light-induced expression of Fos protein in the SCN, intergeniculate leaflet (IGL), and ventrolateral geniculate nucleus (vLGN) in

K. Edelstein; J. G. Pfaus; B. Rusak; S. Amir

1995-01-01

184

Cardiac pacemakers: an update.  

PubMed

In this update of cardiac pacing we review the new revised ACC/AHA/NASPE Guidelines for implantation of cardiac pacemakers, including selection of pacing mode, possible new indications, and other more recent advances in cardiac pacing. PMID:15008358

Johnson, Charles D; Arzola-Castañer, Daniel

2003-01-01

185

Heart pacemaker - discharge  

MedlinePLUS

... interfere with your pacemaker. But some with strong magnetic fields may. Always ask your health care provider ... and high-voltage power lines Products that use magnetic therapy, such as some mattresses, pillows, and massagers ...

186

JOURNAL OF BIOLOGICAL RHYTHMS / December 2001Gorman et al. / SPLIT CIRCADIAN RHYTHMS IN HAMSTERS Temporal Reorganization of the Suprachiasmatic  

E-print Network

and by the photoperiodic control of pineal melatonin secretion and phase-resetting effects of light. Because splitting to the principal circadian pacemaker (Mason, 1991). Studies of pineal melatonin synthesis and photo- periodic

Lee, Theresa

187

Simulated body temperature rhythms reveal the phase-shifting behavior and plasticity of mammalian circadian oscillators  

PubMed Central

The circadian pacemaker in the suprachiasmatic nuclei (SCN) of the hypothalamus maintains phase coherence in peripheral cells through metabolic, neuronal, and humoral signaling pathways. Here, we investigated the role of daily body temperature fluctuations as possible systemic cues in the resetting of peripheral oscillators. Using precise temperature devices in conjunction with real-time monitoring of the bioluminescence produced by circadian luciferase reporter genes, we showed that simulated body temperature cycles of mice and even humans, with daily temperature differences of only 3°C and 1°C, respectively, could gradually synchronize circadian gene expression in cultured fibroblasts. The time required for establishing the new steady-state phase depended on the reporter gene, but after a few days, the expression of each gene oscillated with a precise phase relative to that of the temperature cycles. Smooth temperature oscillations with a very small amplitude could synchronize fibroblast clocks over a wide temperature range, and such temperature rhythms were also capable of entraining gene expression cycles to periods significantly longer or shorter than 24 h. As revealed by genetic loss-of-function experiments, heat-shock factor 1 (HSF1), but not HSF2, was required for the efficient synchronization of fibroblast oscillators to simulated body temperature cycles. PMID:22379191

Saini, Camille; Morf, Jörg; Stratmann, Markus; Gos, Pascal; Schibler, Ueli

2012-01-01

188

A neural theory of circadian rhythms: Aschoff s rule in diurnal and nocturnal mammals  

E-print Network

"" , - , ,\\i', (-\\' A neural theory of circadian rhythms: Aschoff s rule in diurnal and nocturnal- theory of circadian rhythms: A~choff's rule in diurnal and nr:c- mals, including the "dead zone" of phase.lcnuclelsuggest~h°v.:beha":lor~lac~lvIty,rest, of the pacemaker by high light intensities (3,11). Due to and circadian period depend on light intensity In diurnal

Grossberg, Stephen

189

Integration of human sleep-wake regulation and circadian rhythmicity  

NASA Technical Reports Server (NTRS)

The human sleep-wake cycle is generated by a circadian process, originating from the suprachiasmatic nuclei, in interaction with a separate oscillatory process: the sleep homeostat. The sleep-wake cycle is normally timed to occur at a specific phase relative to the external cycle of light-dark exposure. It is also timed at a specific phase relative to internal circadian rhythms, such as the pineal melatonin rhythm, the circadian sleep-wake propensity rhythm, and the rhythm of responsiveness of the circadian pacemaker to light. Variations in these internal and external phase relationships, such as those that occur in blindness, aging, morning and evening, and advanced and delayed sleep-phase syndrome, lead to sleep disruptions and complaints. Changes in ocular circadian photoreception, interindividual variation in the near-24-h intrinsic period of the circadian pacemaker, and sleep homeostasis can contribute to variations in external and internal phase. Recent findings on the physiological and molecular-genetic correlates of circadian sleep disorders suggest that the timing of the sleep-wake cycle and circadian rhythms is closely integrated but is, in part, regulated differentially.

Dijk, Derk-Jan; Lockley, Steven W.

2002-01-01

190

Acute exposure to 2G phase shifts the rat circadian timing system  

NASA Technical Reports Server (NTRS)

The circadian timing system (CTS) provides internal and external temporal coordination of an animal's physiology and behavior. In mammals, the generation and coordination of these circadian rhythms is controlled by a neural pacemaker, the suprachiasmatic nucleus (SCN), located within the hypothalamus. The pacemaker is synchronized to the 24 hour day by time cures (zeitgebers) such as the light/dark cycle. When an animal is exposed to an environment without time cues, the circadian rhythms maintain internal temporal coordination, but exhibit a 'free-running' condition in which the period length is determined by the internal pacemaker. Maintenance of internal and external temporal coordination are critical for normal physiological and psychological function in human and non-human primates. Exposure to altered gravitational environments has been shown to affect the amplitude, mean, and timing of circadian rhythms in species ranging from unicellular organisms to man. However, it has not been determined whether altered gravitational fields have a direct effect on the neural pacemaker, or affect peripheral parameters. In previous studies, the ability of a stimulus to phase shift circadian rhythms was used to determine whether a stimulus has a direct effect on the neural pacemaker. The present experiment was performed in order to determine whether acute exposure to a hyperdynamic field could phase shift circadian rhythms.

Hoban-Higgins, T. M.; Murakami, D. M.; Tandon, T.; Fuller, C. A.

1995-01-01

191

Wavelet Measurement Suggests Cause of Period Instability in Mammalian Circadian  

E-print Network

Wavelet Measurement Suggests Cause of Period Instability in Mammalian Circadian Neurons Kirsten cells as either arrhythmic or circadian, our wavelet analysis reveals that individual cells, when removed from network interac- tions, intermittently express circadian and/or longer infradian periods. We

Petzold, Linda R.

192

Circadian chronotherapy for human cancers.  

PubMed

Cell physiology is regulated by a 24-hour clock, consisting of interconnected molecular loops, involving at least nine genes. The cellular clock is coordinated by the suprachiasmatic nucleus, a hypothalamic pacemaker which also helps the organism to adjust to environmental cycles. This circadian organisation brings about predictable changes in the body's tolerance and tumour responsiveness to anticancer agents, and possibly also for cancer promotion or growth. The clinical relevance of the chronotherapy principle, ie treatment regimens based upon circadian rhythms, has been demonstrated in randomised, multicentre trials. Chronotherapeutic schedules have been used to document the safety and activity of oxaliplatin against metastatic colorectal cancer and have formed the basis for a new approach to the medicosurgical management of this disease, which achieved unprecedented long-term survival. The chronotherapy concept offers further promise for improving current cancer-treatment options, as well as for optimising the development of new anticancer or supportive agents. PMID:11905786

Lévi, F

2001-05-01

193

Neurons and networks in daily rhythms  

Microsoft Academic Search

Biological pacemakers dictate our daily schedules in physiology and behaviour. The molecules, cells and networks that underlie these circadian rhythms can now be monitored using long-term cellular imaging and electrophysiological tools, and initial studies have already suggested a theme — circadian clocks may be crucial for widespread changes in brain activity and plasticity. These daily changes can modify the amount

Erik D. Herzog

2007-01-01

194

Connecting the Circadian Clock with Chemosensation  

E-print Network

responses are under control of the circadian clock. I found that local oscillators in afferent (primary) chemosensory neurons drive rhythms in physiological and behavioral responses to attractive and aversive chemical signals. During the middle of the night...

Chatterjee, Abhishek

2012-07-16

195

Radiation effect on implanted pacemakers  

SciTech Connect

It was previously thought that diagnostic or therapeutic ionizing radiation did not have an adverse effect on the function of cardiac pacemakers. Recently, however, some authors have reported damaging effect of therapeutic radiation on cardiac pulse generators. An analysis of a recently-extracted pacemaker documented the effect of radiation on the pacemaker pulse generator.

Pourhamidi, A.H.

1983-10-01

196

Circadian oscillators in the epithalamus  

PubMed Central

The habenula complex is implicated in a range of cognitive, emotional and reproductive behaviors, and recently this epithalamic structure was suggested to be a component of the brain's circadian system. Circadian timekeeping is driven in cells by the cyclical activity of core clock genes and proteins such as per2/PER2. There are currently no reports of rhythmic clock gene/protein expression in the habenula and therefore the question of whether this structure has an intrinsic molecular clock remains unresolved. Here, using videomicroscopy imaging and photon-counting of a PER2::luciferase (LUC) fusion protein together with multiunit electrophysiological recordings, we tested the endogenous circadian properties of the mouse habenula in vitro. We show that a circadian oscillator is localized primarily to the medial portion of the lateral habenula. Rhythms in PER2:: LUC bioluminescence here are visualized in single cells and oscillations continue in the presence of the sodium channel blocker, tetrodotoxin, indicating that individual cells have intrinsic timekeeping properties. Ependymal cells lining the dorsal third ventricle also express circadian oscillations of PER2. These findings establish that neurons and non-neuronal cells in the epithalamus express rhythms in cellular and molecular activities, indicating a role for circadian oscillators in the temporal regulation of habenula controlled processes and behavior. PMID:20547209

Guilding, C.; Hughes, A.T.L.; Piggins, H.D.

2010-01-01

197

Potent Circadian Effects of Dim Illumination at Night in Hamsters  

Microsoft Academic Search

Conventional wisdom holds that the circadian pacemaker of rodents and humans is minimally responsive to light of the intensity provided by dim moonlight and starlight. However, dim illumination (,0.005 lux) provided during the daily dark periods markedly alters entrainment in hamsters. Under dimly lit scotophases, compared to completely dark ones phases, the upper range of entrainment is increased by 4h

Michael R. Gorman; Jennifer A. Evans; Jeffrey A. Elliott

2006-01-01

198

Local photic entrainment of the retinal circadian oscillator in the absence of rods, cones, and melanopsin  

PubMed Central

Synchronization of the mammalian master circadian pacemaker to the daily light/dark cycle is mediated exclusively through retinal photoreceptors. The mammalian retina itself is also a self-sustained circadian oscillator. Here we report that the retinal molecular circadian clock can be entrained by lighting cycles in vitro, but that rods, cones, and melanopsin (Opn4) are not required for this entrainment. In vivo, retinas of Opn4?/?;rd1/rd1 mice synchronize to light/dark cycles regardless of the phase of the master circadian pacemakers of the suprachiasmatic nuclei or the behavior of the animal. These data demonstrate that the retina uses a separate mechanism for local entrainment of its circadian clock than for entrainment of organism-level rhythmicity. PMID:24843129

Buhr, Ethan D.; Van Gelder, Russell N.

2014-01-01

199

How Modeling Can Reconcile Apparently Discrepant Experimental Results: The Case of Pacemaking in  

E-print Network

this case, the SK conductance) can have a different effect on these two oscillatory behaviors (pacemaking, schizophrenia, and drug abuse [3]. Under physiological conditions, DA neurons can switch between three distinct

Vetter, Frederick J.

200

A circadian clock nanomachine that runs without transcription or translation  

PubMed Central

The biochemical basis of circadian timekeeping is best characterized in cyanobacteria. The structures of its key molecular players, KaiA, KaiB, and KaiC are known and these proteins can reconstitute a remarkable circadian oscillation in a test tube. KaiC is rhythmically phosphorylated and its phospho-status is a marker of circadian phase that regulates ATPase activity and the oscillating assembly of a nanomachine. Analyses of the nanomachines have revealed how their timing circuit is ratcheted to be unidirectional and how they stay in synch to ensure a robust oscillator. These insights are likely to elucidate circadian timekeeping in higher organisms, including how transcription and translation could appear to be a core circadian timer when the true pacemaker is an embedded biochemical oscillator. PMID:23571120

Egli, Martin; Johnson, Carl Hirschie

2013-01-01

201

Melatonin modulates the ERG circadian rhythm in crayfish.  

PubMed

One of the most important functions modulated by melatonin is the synchronization of circadian rhythms. In crayfish (Procambarus clarkii), we have obtained evidence that the amplitude of the electrical response to light of the retinal photoreceptors the receptor potential, is modified by the action of melatonin and that the magnitude of this action depends on the circadian time of melatonin application. In contrast, the electroretinogram (ERG) circadian rhythm can be synchronized by either single or periodic melatonin application. In this work we hypothesized that, in crayfish, melatonin acts on effectors and on pacemaker of ERG circadian rhythm as a non-photic synchronizer. Melatonin could be a hormone that sends a signal of darkness to the ERG circadian system. PMID:18313959

Solís-Chagoyán, Héctor; Mendoza-Vargas, Leonor; Fuentes-Pardo, Beatriz

2008-04-01

202

The Circadian Clock System in the Mammalian Retina  

PubMed Central

Daily rhythms are a ubiquitous feature of living systems. Generally, these rhythms are not just passive consequences of cyclic fluctuations in the environment, but instead originate within the organism. In mammals, including humans, the master pacemaker controlling 24-hour rhythms is localized in the suprachiasmatic nuclei of the hypothalamus. This circadian clock is responsible for the temporal organization of a wide variety of functions, ranging from sleep and food intake, to physiological measures such as body temperature, heart rate and hormone release. The retinal circadian clock was the first extra-SCN circadian oscillator to be discovered in mammals and several studies have now demonstrated that many of the physiological, cellular, and molecular rhythms that are present within the retina are under the control of a retinal circadian clock, or more likely a network of hierarchically organized circadian clocks that are present within this tissue. PMID:18536031

Tosini, Gianluca; Pozdeyev, Nikita; Sakamoto, Katsuhiko; Iuvone, P. Michael

2008-01-01

203

Pacemaker infective endocarditis  

Microsoft Academic Search

We identified 33 patients with definite pacemaker endocarditis—that is, with direct evidence of infective endocarditis, based on surgery or autopsy histologic findings of or bacteriologic findings (Gram stain or culture) of valvular vegetation or electrode-tip wire vegetation. Most of the patients (75%) were ?60 years of age (mean 66 ± 3; range 21 to 86). Pouch hematoma or inflammation was

Patrice Cacoub; Pascal Leprince; Patrick Nataf; Pierre Hausfater; Richard Dorent; Bertrand Wechsler; Valéria Bors; Alain Pavie; Jean Charles Piette; Iradj Gandjbakhch

1998-01-01

204

Light-induced suppression of endogenous circadian amplitude in humans  

NASA Technical Reports Server (NTRS)

A recent demonstration that the phase of the human circadian pacemaker could be inverted using an unconventional three-cycle stimulus has led to an investigation of whether critically timed exposure to a more moderate stimulus could drive that oscillator toward its singularity, a phaseless position at which the amplitude of circadian oscillation is zero. It is reported here that exposure of humans to fewer cycles of bright light, centered around the time at which the human circadian pacemaker is most sensitive to light-induced phase shifts, can markedly attenuate endogenous cicadian amplitude. In some cases this results in an apparent loss of rhythmicity, as expected to occur in the region of singularity.

Jewett, Megan; Czeisler, Charles A.; Kronauer, Richard E.

1991-01-01

205

Differential effects of ionizing radiation on the circadian oscillator and other functions in the eye of Aplysia. [X-rays  

SciTech Connect

Ionizing radiation has been used to selectively separate the circadian oscillator function of the eye of Aplysia from some of its other functions-synchronous compound action potential (CAP) generation, the light response, synaptic transmission between photoreceptors and output neurons, and the bursting pacemaker mechanism. Doses of 4-krad (50 kV peak) x-rays have a minimal effect on the circadian rhythm of CAP frequency, measured from the optic nerve, whereas irradiation with a 40-krad dose abolishes the rhythm without affecting any of the four other functions of this eye. We estimate a 50% survival of the oscillator function at doses of about 6 krad. The results, including those from selective irradiation of the anterior or posterior poles of the eye, suggest that there are a number of circadian oscillators in the eye-most of them in the posterior portion near the optic nerve. An approximate target size has been obtained from target theory, approx. =10/sup 8/ A/sup 3/, which is somewhat larger than the target size for viral infectivity function, as one example. However, this approximate target size and the fact that recovery or repair can occur in vivo suggest that the oscillator may involve nucleic acid molecules.

Woolum, J.C.; Strumwasser, F.

1980-09-01

206

Biventricular pacemakers in patients with heart failure.  

PubMed

Patients with heart failure may benefit from implantation of a biventricular pacemaker. This article discusses the indications for biventricular pacemaker implantation and the assessment of patients with biventricular pacemakers. Biventricular pacemakers require more assessments than do traditional single- or dual-chamber pacemakers. PMID:25834005

Cooper, Karen Leslie

2015-04-01

207

Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals  

Microsoft Academic Search

The circadian pacemaker in the suprachiasmatic nuclei is primarily synchronized to the daily light–dark cycle. The phase-shifting and synchronizing effects of light can be modulated by non-photic factors, such as behavioral, metabolic or serotonergic cues. The present experiments examine the effects of sleep deprivation on the response of the circadian pacemaker to light and test the possible involvement of serotonergic

Etienne Challet; Fred W. Turek; Marie-Aline Laute; Olivier Van Reeth

2001-01-01

208

The Logic of Circadian Organization in Drosophila  

PubMed Central

Summary Background In the fruit fly Drosophila melanogaster, interlocked negative transcription/translation feedback loops provide the core of the circadian clock that generates rhythmic phenotypes. Although the current molecular model portrays the oscillator as cell autonomous, cross-talk among clock neurons is essential for robust cycling behavior. Nevertheless, the functional organization of the neuronal network remains obscure. Results Here we show that shortening or lengthening of the circadian period of locomotor activity can be obtained either by targeting different groups of clock cells with the same genetic manipulation or by challenging the same group of cells with activators and repressors of neuronal excitability. Conclusions Based on these observations we interpret circadian rhythmicity as an emerging property of the circadian network and we propose an initial model for its architectural design. PMID:25220056

Dissel, Stephane; Hansen, Celia N.; Özkaya, Özge; Hemsley, Matthew; Kyriacou, Charalambos P.; Rosato, Ezio

2014-01-01

209

Synchronization of the circadian rhythm generator and the effects of glucagon on hypothalamic mouse neurons detected by acoustic wave propagation.  

PubMed

A thickness shear mode acoustic wave sensor has been used to study the reaction of clonal, immortalized hypothalamic murine neurons in response to glucagon and serum shock in a label free, continuous and real time manner under physiological conditions. Two cell lines were examined; these were the mHypoE-38s and the mHypoE-46s. The technique possesses sufficient sensitivity to detect minor neuronal changes and is capable of discerning subtle differences in cellular behaviors under both stimuli. The kinetics and magnitude of the changes observed here are significantly different compared to those instigated upon causing depolarization, cytoskeletal modifications and surface-adhesion specific interaction alterations with the same cells. Interestingly, this technique has the sensitivity and capability of observing all such changes at the neuronal level without the necessity for invasive interrogation. Under the influence of glucagon, the neurons display both short- and long-term changes, in particular the resonant frequency shifts by -23 ± 8 Hz (n = 13, std. dev.) and the motional resistance decays at a rate of approximately 10 ? h(-1) over a 2 hour interval. The effect of synchronizing the neurons prior to glucagon stimulation did not influence the cellular changes observed. The process of partial and full synchronization of the cells resulted in different responses. For full synchronization, the addition of the serum bolus triggered resonant frequency and motional resistance shifts of +75 Hz and +18.5 ? respectively, which decayed back to baseline levels after 30 minutes. The duration of this decay closely matched the time required for full synchronization in a separate study. The changes observed for partial synchronization were significantly different from full synchronization as the baseline levels in both resonant frequency and motional resistance were not re-achieved indicative of the cell-sensor system detecting the difference between full and partial synchronization. Preliminary qualitative immunocytochemistry and RT-PCR studies on these cells support the results obtained with the TSM sensor for the glucagon receptor study. PMID:21594261

Cheung, Shilin; Fick, Laura J; Belsham, Denise D; Thompson, Michael

2011-07-01

210

Fibroblast PER2 Circadian Rhythmicity Depends on Cell Density  

PubMed Central

Like neurons in the suprachiasmatic nucleus (SCN), the master circadian pacemaker in the brain, single fibroblasts can function as independent oscillators. In the SCN, synaptic and paracrine signaling among cells creates a robust, synchronized circadian oscillation, whereas there is no evidence for such integration in fibroblast cultures. However, interactions among single-cell fibroblast oscillators cannot be completely excluded, because fibroblasts were not isolated in previous work. In this study, we tested the autonomy of fibroblasts as single-cell circadian oscillators in high and low density culture, by single-cell imaging of cells from PER2::LUC circadian reporter mice. We found greatly reduced PER2::LUC rhythmicity in low density cultures, which could result from lack of either constitutive or rhythmic paracrine signals from neighboring fibroblasts. To discriminate between these two possibilities, we mixed PER2::LUC wild type (WT) cells with non-luminescent, non-rhythmic Bmal1?/? cells, so that density of rhythmic cells was low but overall cell density remained high. In this condition, WT cells showed clear rhythmicity similar to high density cultures. We also mixed PER2::LUC WT cells with non-luminescent, long period Cry2?/? cells. In this condition, WT cells showed a period no different from cells cultured with rhythmic WT cells or non-rhythmic Bmal1?/? cells. In previous work, we found that low K+ suppresses fibroblast rhythmicity, and we and others have found that either low K+ or low Ca2+ suppresses SCN rhythmicity. Therefore, we attempted to rescue rhythmicity of low density fibroblasts with high K+ (21 mM), high Ca2+ (3.6 mM), or conditioned medium. Conditioned medium from high density fibroblast cultures rescued rhythmicity of low density cultures, whereas high K+ or Ca2+ medium did not consistently rescue rhythmicity. These data suggest that fibroblasts require paracrine signals from adjacent cells for normal expression of rhythmicity, but that these signals do not have to be rhythmic, and that rhythmic signals from other cells do not affect the intrinsic periods of fibroblasts. PMID:23735497

Noguchi, Takako; Wang, Lexie L.; Welsh, David K.

2013-01-01

211

The Effects of Spaceflight on the Rat Circadian Timing System  

NASA Technical Reports Server (NTRS)

Two fundamental environmental influences that have shaped the evolution of life on Earth are gravity and the cyclic changes occurring over the 24-hour day. Light levels, temperature, and humidity fluctuate over the course of a day, and organisms have adapted to cope with these variations. The primary adaptation has been the evolution of a biological timing system. Previous studies have suggested that this system, named the circadian (circa - about; dies - a day) timing system (CTS), may be sensitive to changes in gravity. The NASA Neurolab spaceflight provided a unique opportunity to evaluate the effects of microgravity on the mammalian CTS. Our experiment tested the hypotheses that microgravity would affect the period, phasing, and light sensitivity of the CTS. Twenty-four Fisher 344 rats were exposed to 16 days of microgravity on the Neurolab STS-90 mission, and 24 Fisher 344 rats were also studied on Earth as one-G controls. Rats were equipped with biotelemetry transmitters to record body temperature (T(sub b)) and heart rate (HR) continuously while the rats moved freely. In each group, 18 rats were exposed to a 24-hour light-dark (LD 12:12) cycle, and six rats were exposed to constant dim red-light (LL). The ability of light to induce a neuronal activity marker (c-fos) in the circadian pacemaker of the brain, the suprachiasmatic nucleus (SCN), was examined in rats studied on flight days two (FD2) and 14 (FD14), and postflight days two (R+1) and 14 (R+13). The flight rats in LD remained synchronized with the LD cycle. However, their T(sub b), rhythm was markedly phase-delayed relative to the LD cycle. The LD flight rats also had a decreased T(sub b) and a change in the waveform of the T(sub b) rhythm compared to controls. Rats in LL exhibited free-running rhythms of T(sub b), and HR; however, the periods were longer in microgravity. Circadian period returned to preflight values after landing. The internal phase angle between rhythms was different in flight than in one-G. Compared with control rats, the flight rats exhibited no change in HR. Finally, the LD FD2 flight rats demonstrated a reduced sensitivity to light as shown by significantly reduced c-fos expression in the SCN in comparison with controls. These findings constitute the first demonstration that microgravity affects the fundamental properties of the mammalian circadian timing system, specifically by influencing the clock's period, and its ability to maintain temporal organization and phase angle of synchronization to an external LD cycle.

Fuller, Charles A.; Murakami, Dean M.; Hoban-Higgins, Tana M.; Fuller, Patrick M.; Robinson, Edward L.; Tang, I.-Hsiung

2003-01-01

212

Nuclear Receptor-mediated Cell-autonomous Oscillatory Expression of the Circadian Transcription Factor, Neuronal PAS Domain Protein 2 (NPAS2)*  

PubMed Central

NPAS2 (MOP4) is a heme-containing sensor transcription factor responsive to a wide range of intra- and extracellular stimuli, which also functions as a circadian transcription factor. This molecule forms a heterodimer with another circadian transcription factor, BMAL1, and activates transcription via E-box elements, indicating that circadian phase synchronization between NPAS2 and BMAL1 expression is important for the efficient transcriptional activation of target genes. However, details of the mechanism of cell-autonomous circadian transcription of Npas2 remain unclear. Here, we show that one of the ROREs (retinoid-related orphan receptor response elements) in the upstream region of the transcription start site is essential for circadian transcription of the Npas2 gene. Furthermore, we also show that endogenous ROR? indeed plays an essential role in cell-autonomous circadian transcription of Npas2, because a damped transcriptional oscillation was observed not only by introduction of a dominant negative form or small interfering RNA but also in embryonic fibroblasts obtained from ROR?-mutant (sg/sg) mice. These results indicate that circadian transcription of Npas2 is synchronized with that of Bmal1 in a cell-autonomous nuclear receptor-mediated fashion. PMID:24196956

Matsumura, Ritsuko; Matsubara, Chiaki; Node, Koichi; Takumi, Toru; Akashi, Makoto

2013-01-01

213

21 CFR 870.3670 - Pacemaker charger.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Pacemaker charger. 870.3670 Section 870.3670...Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used...

2014-04-01

214

21 CFR 870.3670 - Pacemaker charger.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Pacemaker charger. 870.3670 Section 870.3670...Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used...

2011-04-01

215

21 CFR 870.3670 - Pacemaker charger.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Pacemaker charger. 870.3670 Section 870.3670...Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used...

2013-04-01

216

21 CFR 870.3670 - Pacemaker charger.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Pacemaker charger. 870.3670 Section 870.3670...Cardiovascular Prosthetic Devices § 870.3670 Pacemaker charger. (a) Identification. A pacemaker charger is a device used...

2012-04-01

217

21 CFR 870.3700 - Pacemaker programmers.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Pacemaker programmers. 870.3700 Section 870...Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used to...

2011-04-01

218

Experimental evidence of a chaotic region in a neural pacemaker  

NASA Astrophysics Data System (ADS)

In this Letter, we report the finding of period-adding scenarios with chaos in firing patterns, observed in biological experiments on a neural pacemaker, with fixed extra-cellular potassium concentration at different levels and taken extra-cellular calcium concentration as the bifurcation parameter. The experimental bifurcations in the two-dimensional parameter space demonstrate the existence of a chaotic region interwoven with the periodic region thereby forming a period-adding sequence with chaos. The behavior of the pacemaker in this region is qualitatively similar to that of the Hindmarsh-Rose neuron model in a well-known comb-shaped chaotic region in two-dimensional parameter spaces.

Gu, Hua-Guang; Jia, Bing; Chen, Guan-Rong

2013-03-01

219

Dkhissi-Benyahya et al. : role of cones in circadian responses 1 Modelling the role of mid-wavelength cones in circadian responses to light  

E-print Network

Dkhissi-Benyahya et al. : role of cones in circadian responses 1 Modelling the role of mid-wavelength cones in circadian responses to light Dkhissi-Benyahya O.1, 2 , Gronfier C. 1, 2 , De Vanssay W.1, 2 manuscript Neuron 01/03/2007; 53(5): 677-87 #12;Dkhissi-Benyahya et al. : role of cones in circadian

Paris-Sud XI, Université de

220

A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract  

Microsoft Academic Search

Electrical rhythmicity in gastrointestinal muscles has been studied for a century, but the pacemakers driving this phenomenon have been elusive. Anatomic studies suggest that interstitial cells of Cajal (ICC) may be pacemakers and conductors of electrical activity. ICC may also mediate neurotransmission from enteric neurons. Functional evaluations of ICC include the following. (1) Electrophysiology experiments on dissected muscle strips show

KM Sanders

1996-01-01

221

When Weak Inhibition Synchronizes Strongly Desynchronizing Networks of Bursting Neurons Igor Belykh and Andrey Shilnikov  

E-print Network

synchronizing inhibition from the same pacemaker neuron can win out over much stronger desynchro- nizing received from one or several pacemaker neurons was shown to favor synchronization [11]. It was also shown of mutually inhibiting cells, driven by a common bursting pacemaker [13,14]. Understanding the emergence

Belykh, Igor

222

Trends in cardiac pacemaker batteries.  

PubMed

Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future. PMID:16943934

Mallela, Venkateswara Sarma; Ilankumaran, V; Rao, N Srinivasa

2004-01-01

223

The statistical analysis of circadian phase and amplitude in constant-routine core-temperature data  

NASA Technical Reports Server (NTRS)

Accurate estimation of the phases and amplitude of the endogenous circadian pacemaker from constant-routine core-temperature series is crucial for making inferences about the properties of the human biological clock from data collected under this protocol. This paper presents a set of statistical methods based on a harmonic-regression-plus-correlated-noise model for estimating the phases and the amplitude of the endogenous circadian pacemaker from constant-routine core-temperature data. The methods include a Bayesian Monte Carlo procedure for computing the uncertainty in these circadian functions. We illustrate the techniques with a detailed study of a single subject's core-temperature series and describe their relationship to other statistical methods for circadian data analysis. In our laboratory, these methods have been successfully used to analyze more than 300 constant routines and provide a highly reliable means of extracting phase and amplitude information from core-temperature data.

Brown, E. N.; Czeisler, C. A.

1992-01-01

224

Introduction: circadian rhythm and its disruption: impact on reproductive function.  

PubMed

Almost all forms of life have predictable daily or circadian rhythms in molecular, endocrine, and behavioral functions. In mammals, a central pacemaker located in the suprachiasmatic nuclei coordinates the timing of these rhythms. Daily light exposure that affects the retina of the eye directly influences this area, which is required to align endogenous processes to the appropriate time of day. The present "Views and Reviews" articles discuss the influence of circadian rhythms, especially nightly secretion of melatonin, on reproductive function and parturition. In addition, an examination is made of problems that arise from recurrent circadian rhythm disruption associated with changes in light exposure patterns common to modern day society. Finally, a possible solution to prevent disruptions in circadian phase markers by filtering out short wavelengths from nocturnal light is reviewed. PMID:24954773

Casper, Robert F; Gladanac, Bojana

2014-08-01

225

Metabolic Compensation and Circadian Resilience in Prokaryotic Cyanobacteria  

PubMed Central

For a biological oscillator to function as a circadian pacemaker that confers a fitness advantage, its timing functions must be stable in response to environmental and metabolic fluctuations. One such stability enhancer, temperature compensation, has long been a defining characteristic of these timekeepers. However, an accurate biological timekeeper must also resist changes in metabolism, and this review suggests that temperature compensation is actually a subset of a larger phenomenon, namely metabolic compensation, which maintains the frequency of circadian oscillators in response to a host of factors that impinge on metabolism and would otherwise destabilize these clocks. The circadian system of prokaryotic cyanobacteria is an illustrative model because it is composed of transcriptional and nontranscriptional oscillators that are coupled to promote resilience. Moreover, the cyanobacterial circadian program regulates gene activity and metabolic pathways, and it can be manipulated to improve the expression of bioproducts that have practical value. PMID:24905782

Johnson, Carl Hirschie; Egli, Martin

2014-01-01

226

Inward-rectifying potassium (Kir) channels regulate pacemaker activity in spinal nociceptive circuits during early life  

PubMed Central

Pacemaker neurons in neonatal spinal nociceptive circuits generate intrinsic burst-firing and are distinguished by a lower “leak” membrane conductance compared to adjacent, non-bursting neurons. However, little is known about which subtypes of leak channels regulate the level of pacemaker activity within the developing rat superficial dorsal horn (SDH). Here we demonstrate that a hallmark feature of lamina I pacemaker neurons is a reduced conductance through inward-rectifying potassium (Kir) channels at physiological membrane potentials. Differences in the strength of inward rectification between pacemakers and non-pacemakers indicate the presence of functionally distinct Kir currents in these two populations at room temperature. However, Kir currents in both groups showed high sensitivity to block by extracellular Ba2+ (IC50 ~ 10 µM), which suggests the presence of ‘classical’ Kir (Kir2.x) channels in the neonatal SDH. The reduced Kir conductance within pacemakers is unlikely to be explained by an absence of particular Kir2.x isoforms, as immunohistochemical analysis revealed the expression of Kir2.1, Kir2.2 and Kir2.3 within spontaneously bursting neurons. Importantly, Ba2+ application unmasked rhythmic burst-firing in ~42% of non-bursting lamina I neurons, suggesting that pacemaker activity is a latent property of a sizeable population of SDH cells during early life. In addition, the prevalence of spontaneous burst-firing within lamina I was enhanced in the presence of high internal concentrations of free Mg2+, consistent with its documented ability to block Kir channels from the intracellular side. Collectively, the results indicate that Kir channels are key modulators of pacemaker activity in newborn central pain networks. PMID:23426663

Li, Jie; Blankenship, Meredith L.; Baccei, Mark L.

2013-01-01

227

Circadian Performance of Suprachiasmatic Nuclei (SCN)-Lesioned Antelope Ground Squirrels in a Desert Enclosure  

Microsoft Academic Search

Circadian activity parameters of 53 white-tailed antelope ground squirrels, Ammospermophilus leucurus, were measured to determine the role of the suprachiasmatic nuclei (SCN) pacemaker in their health and survival. Wheel-running activity was monitored in the laboratory with 44 individuals to document the presence of free-running circadian rhythms and ability to entrain to light-dark cycles. Twenty-two individuals were returned to the desert

Patricia J DeCoursey; Jill R Krulas; Gary Mele; Daniel C Holley

1997-01-01

228

Pigment dispersing hormone generates a circadian response to light in the crayfish, Procambarus clarkii.  

PubMed

Photoreceptor cells have been identified as important structures in the organization of the circadian system responsible for the generation and expression of the electroretinogram (ERG) circadian rhythm. They are the structures where the circadian periodicity is expressed (effectors) and which transform information from external light signals to be conducted to the pacemaker in order to induce adjustments of the rhythm (synchronizers). After isolation, eyestalks perfused in a pigment dispersing hormone (PDH) solution, show significant changes in receptor potential (RP) amplitude and duration. Exogenous PDH injected into intact crayfish induces a migration of retinal shielding pigments to a light-adapted state. A single dose of PDH produces advances or delays in the circadian rhythm of response to light of visual photoreceptors. All these effects depend on the circadian phase of PDH application. Consequently, the determination of the action of exogenous PDH on photoreceptor cells proved to be very helpful in understanding some mechanisms underlying the circadian organization of crayfish. PMID:17428715

Verde, M A; Barriga-Montoya, C; Fuentes-Pardo, B

2007-08-01

229

Time-of-Day- and Light-Dependent Expression of Ubiquitin Protein Ligase E3 Component N-Recognin 4 (UBR4) in the Suprachiasmatic Nucleus Circadian Clock  

PubMed Central

Circadian rhythms of behavior and physiology are driven by the biological clock that operates endogenously but can also be entrained to the light-dark cycle of the environment. In mammals, the master circadian pacemaker is located in the suprachiasmatic nucleus (SCN), which is composed of individual cellular oscillators that are driven by a set of core clock genes interacting in transcriptional/translational feedback loops. Light signals can trigger molecular events in the SCN that ultimately impact on the phase of expression of core clock genes to reset the master pacemaker. While transcriptional regulation has received much attention in the field of circadian biology in the past, other mechanisms including targeted protein degradation likely contribute to the clock timing and entrainment process. In the present study, proteome-wide screens of the murine SCN led to the identification of ubiquitin protein ligase E3 component N-recognin 4 (UBR4), a novel E3 ubiquitin ligase component of the N-end rule pathway, as a time-of-day-dependent and light-inducible protein. The spatial and temporal expression pattern of UBR4 in the SCN was subsequently characterized by immunofluorescence microscopy. UBR4 is expressed across the entire rostrocaudal extent of the SCN in a time-of-day-dependent fashion. UBR4 is localized exclusively to arginine vasopressin (AVP)-expressing neurons of the SCN shell. Upon photic stimulation in the early subjective night, the number of UBR4-expressing cells within the SCN increases. This study is the first to identify a novel E3 ubiquitin ligase component, UBR4, in the murine SCN and to implicate the N-end rule degradation pathway as a potential player in regulating core clock mechanisms and photic entrainment. PMID:25084275

Ling, Harrod H.; Beaulé, Christian; Chiang, Cheng-Kang; Tian, Ruijun; Figeys, Daniel; Cheng, Hai-Ying M.

2014-01-01

230

Electromagnetic and radiation environment effects on pacemakers  

Microsoft Academic Search

The increase, on one hand, of patients bearing pacemakers for cardiac deficiencies and on the other hand, of the number of cancer patients, increases the probability of several simultaneous therapy needs. Cancer radiation therapy involves specific damages to sensitive electronic devices such as pacemakers. Oncologists demand risk evaluation and rules for applying radiation therapy to cancer patients bearing pacemakers. Pacemaker

J. Mouton; R. Trochet; J. Vicrey; M. Sauvage; B. Chauvenet; A. Ostrovski; E. Leroy; R. Haug; B. Dodinot; F. Joffre

1999-01-01

231

A statistical model of the human core-temperature circadian rhythm  

NASA Technical Reports Server (NTRS)

We formulate a statistical model of the human core-temperature circadian rhythm in which the circadian signal is modeled as a van der Pol oscillator, the thermoregulatory response is represented as a first-order autoregressive process, and the evoked effect of activity is modeled with a function specific for each circadian protocol. The new model directly links differential equation-based simulation models and harmonic regression analysis methods and permits statistical analysis of both static and dynamical properties of the circadian pacemaker from experimental data. We estimate the model parameters by using numerically efficient maximum likelihood algorithms and analyze human core-temperature data from forced desynchrony, free-run, and constant-routine protocols. By representing explicitly the dynamical effects of ambient light input to the human circadian pacemaker, the new model can estimate with high precision the correct intrinsic period of this oscillator ( approximately 24 h) from both free-run and forced desynchrony studies. Although the van der Pol model approximates well the dynamical features of the circadian pacemaker, the optimal dynamical model of the human biological clock may have a harmonic structure different from that of the van der Pol oscillator.

Brown, E. N.; Choe, Y.; Luithardt, H.; Czeisler, C. A.

2000-01-01

232

A Molecular Model for Intercellular Synchronization in the Mammalian Circadian Clock  

E-print Network

A Molecular Model for Intercellular Synchronization in the Mammalian Circadian Clock Tsz-Leung To understood in biological systems. We present a multicellular, molecular model of the mammalian circadian (VIP) as the key synchronizing agent. The model postulates that synchronyarises among circadian neurons

Mountziaris, T. J.

233

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).  

Code of Federal Regulations, 2011 CFR

...false External transcutaneous cardiac pacemaker (noninvasive). 870.5550 Section...5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device...

2011-04-01

234

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).  

Code of Federal Regulations, 2013 CFR

...false External transcutaneous cardiac pacemaker (noninvasive). 870.5550 Section...5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac pacemaker (noninvasive) is a device...

2013-04-01

235

1978 Pacemaker Newspaper Awards: What Makes a Pacemaker?  

ERIC Educational Resources Information Center

Lists the nine high school and college newspapers, and the one newsmagazine, that won Pacemaker Awards in 1978; discusses characteristics that make each of them outstanding, and provides reproductions of a front page from each publication. (GT)

Brasler, Wayne

1979-01-01

236

Differential contributions of intra-cellular and inter-cellular mechanisms to the spatial and temporal architecture of the suprachiasmatic nucleus circadian circuitry in wild-type, cryptochrome-null and vasoactive intestinal peptide receptor 2-null mutant mice.  

PubMed

To serve as a robust internal circadian clock, the cell-autonomous molecular and electrophysiological activities of the individual neurons of the mammalian suprachiasmatic nucleus (SCN) are coordinated in time and neuroanatomical space. Although the contributions of the chemical and electrical interconnections between neurons are essential to this circuit-level orchestration, the features upon which they operate to confer robustness to the ensemble signal are not known. To address this, we applied several methods to deconstruct the interactions between the spatial and temporal organisation of circadian oscillations in organotypic slices from mice with circadian abnormalities. We studied the SCN of mice lacking Cryptochrome genes (Cry1 and Cry2), which are essential for cell-autonomous oscillation, and the SCN of mice lacking the vasoactive intestinal peptide receptor 2 (VPAC2-null), which is necessary for circuit-level integration, in order to map biological mechanisms to the revealed oscillatory features. The SCN of wild-type mice showed a strong link between the temporal rhythm of the bioluminescence profiles of PER2::LUC and regularly repeated spatially organised oscillation. The Cry-null SCN had stable spatial organisation but lacked temporal organisation, whereas in VPAC2-null SCN some specimens exhibited temporal organisation in the absence of spatial organisation. The results indicated that spatial and temporal organisation were separable, that they may have different mechanistic origins (cell-autonomous vs. interneuronal signaling) and that both were necessary to maintain robust and organised circadian rhythms throughout the SCN. This study therefore provided evidence that the coherent emergent properties of the neuronal circuitry, revealed in the spatially organised clusters, were essential to the pacemaking function of the SCN. PMID:24891292

Pauls, S; Foley, N C; Foley, D K; LeSauter, J; Hastings, M H; Maywood, E S; Silver, R

2014-08-01

237

Avian Circadian Organization: A Chorus of Clocks  

PubMed Central

In birds, biological clock function pervades all aspects of biology, controlling daily changes in sleep: wake, visual function, song, migratory patterns and orientation, as well as seasonal patterns of reproduction, song and migration. The molecular bases for circadian clocks are highly conserved, and it is likely the avian molecular mechanisms are similar to those expressed in mammals, including humans. The central pacemakers in the avian pineal gland, retinae and SCN dynamically interact to maintain stable phase relationships and then influence downstream rhythms through entrainment of peripheral oscillators in the brain controlling behavior and peripheral tissues. Birds represent an excellent model for the role played by biological clocks in human neurobiology; unlike most rodent models, they are diurnal, they exhibit cognitively complex social interactions, and their circadian clocks are more sensitive to the hormone melatonin than are those of nocturnal rodents. PMID:24157655

Cassone, Vincent M

2013-01-01

238

Effects of circadian disruption on the cardiometabolic system  

Microsoft Academic Search

The presence of day–night variations in cardiovascular and metabolic functioning is well known. However, only recently it\\u000a has been shown that cardiovascular and metabolic processes are not only affected by the behavioral sleep\\/wake cycle but are\\u000a partly under direct control of the master circadian pacemaker located in the suprachiasmatic nucleus (SCN). Heart rate, cardiac\\u000a autonomic activity, glucose metabolism and leptin—involved

Melanie Rüger; Frank A. J. L. Scheer

2009-01-01

239

VideoLab: Optogenetic Pacemaker  

NSDL National Science Digital Library

In mammals, the heart's primary pacemaker lies in a specialized group of cells -- but do non-mammalian vertebrates have a similar control system? To find out, Arrenberg et al. genetically engineered zebrafish to express light-sensitive proteins, and then used light beams generated with a digital micromirror device to locate and manipulate the function of the pacemaker cells in the hearts of zebrafish embryos -- capturing the action on high-speed video.

Aristides B. Arrenberg (University of California; University of Freiburg; Department of Physiology; Institute of Biology)

2010-11-12

240

In vivo monitoring of multi-unit neural activity in the suprachiasmatic nucleus reveals robust circadian rhythms in Period1?/? mice.  

PubMed

The master pacemaker in the suprachiasmatic nucleus (SCN) controls daily rhythms of behavior in mammals. C57BL/6J mice lacking Period1 (Per1?/?) are an anomaly because their SCN molecular rhythm is weak or absent in vitro even though their locomotor activity rhythm is robust. To resolve the contradiction between the in vitro and in vivo circadian phenotypes of Per1?/? mice, we measured the multi-unit activity (MUA) rhythm of the SCN neuronal population in freely-behaving mice. We found that in vivo Per1?/? SCN have high-amplitude MUA rhythms, demonstrating that the ensemble of neurons is driving robust locomotor activity in Per1?/? mice. Since the Per1?/? SCN electrical activity rhythm is indistinguishable from wild-types, in vivo physiological factors or coupling of the SCN to a known or unidentified circadian clock(s) may compensate for weak endogenous molecular rhythms in Per1?/? SCN. Consistent with the behavioral light responsiveness of Per1?/? mice, in vivo MUA rhythms in Per1?/? SCN exhibited large phase shifts in response to light. Since the acute response of the MUA rhythm to light in Per1?/? SCN is equivalent to wild-types, an unknown mechanism mediates enhanced light responsiveness of Per1?/? mice. Thus, Per1?/? mice are a unique model for investigating the component(s) of the in vivo environment that confers robust rhythmicity to the SCN as well as a novel mechanism of enhanced light responsiveness. PMID:23717599

Takasu, Nana N; Pendergast, Julie S; Olivas, Cathya S; Yamazaki, Shin; Nakamura, Wataru

2013-01-01

241

Circadian Rhythm Disruption in Cancer Biology  

PubMed Central

Circadian rhythms show universally a 24-h oscillation pattern in metabolic, physiological and behavioral functions of almost all species. This pattern is due to a fundamental adaptation to the rotation of Earth around its own axis. Molecular mechanisms of generation of circadian rhythms organize a biochemical network in suprachiasmatic nucleus and peripheral tissues, building cell autonomous clock pacemakers. Rhythmicity is observed in transcriptional expression of a wide range of clock-controlled genes that regulate a variety of normal cell functions, such as cell division and proliferation. Desynchrony of this rhythmicity seems to be implicated in several pathologic conditions, including tumorigenesis and progression of cancer. In 2007, the International Agency for Research on Cancer (IARC) categorized “shiftwork that involves circadian disruption [as] probably carcinogenic to humans” (Group 2A in the IARC classification system of carcinogenic potency of an agentagent) (Painting, Firefighting, and Shiftwork; IARC; 2007). This review discusses the potential relation between disruptions of normal circadian rhythms with genetic driving machinery of cancer. Elucidation of the role of clockwork disruption, such as exposure to light at night and sleep disruption, in cancer biology could be important in developing new targeted anticancer therapies, optimizing individualized chronotherapy and modifying lighting environment in workplaces or homes. PMID:22811066

Savvidis, Christos; Koutsilieris, Michael

2012-01-01

242

Time’s arrow flies like a bird: Two paradoxes for avian circadian biology  

Microsoft Academic Search

Biological timekeeping in birds is a fundamental feature of avian physiology, behavior and ecology. The physiological basis for avian circadian rhythmicity has pointed to a multi-oscillator system of mutually coupled pacemakers in the pineal gland, eyes and hypothalamic suprachiasmatic nuclei (SCN). In passerines, the role of the pineal gland and its hormone melatonin is particularly important. More recent molecular biological

Vincent M. Cassone; Jiffin K. Paulose; Melissa G. Whitfield-Rucker; Jennifer L. Peters

2009-01-01

243

Coordinated Transcription of Key Pathways in the Mouse by the Circadian Clock  

Microsoft Academic Search

In mammals, circadian control of physiology and behavior is driven by a master pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. We have used gene expression profiling to identify cycling transcripts in the SCN and in the liver. Our analysis revealed ?650 cycling transcripts and showed that the majority of these were specific to either the SCN or

Satchidananda Panda; Marina P. Antoch; Brooke H. Miller; Andrew I. Su; Andrew B. Schook; Marty Straume; Peter G. Schultz; Steve A. Kay; Joseph S. Takahashi; John B. Hogenesch

2002-01-01

244

Circadian regulation of bird song, call, and locomotor behavior by pineal melatonin in the zebra finch.  

PubMed

As both a photoreceptor and pacemaker in the avian circadian clock system, the pineal gland is crucial for maintaining and synchronizing overt circadian rhythms in processes such as locomotor activity and body temperature through its circadian secretion of the pineal hormone melatonin. In addition to receptor presence in circadian and visual system structures, high-affinity melatonin binding and receptor mRNA are present in the song control system of male oscine passeriform birds. The present study explores the role of pineal melatonin in circadian organization of singing and calling behavior in comparison to locomotor activity under different lighting conditions. Similar to locomotor activity, both singing and calling behavior were regulated on a circadian basis by the central clock system through pineal melatonin, since these behaviors free-ran with a circadian period and since pinealectomy abolished them in constant environmental conditions. Further, rhythmic melatonin administration restored their rhythmicity. However, the rates by which these behaviors became arrhythmic and the rates of their entrainment to rhythmic melatonin administration differed among locomotor activity, singing and calling under constant dim light and constant bright light. Overall, the study demonstrates a role for pineal melatonin in regulating circadian oscillations of avian vocalizations in addition to locomotor activity. It is suggested that these behaviors might be controlled by separable circadian clockworks and that pineal melatonin entrains them all through a circadian clock. PMID:22476775

Wang, Gang; Harpole, Clifford E; Trivedi, Amit K; Cassone, Vincent M

2012-04-01

245

Circadian influences on myocardial infarction  

PubMed Central

Components of circadian rhythm maintenance, or “clock genes,” are endogenous entrainable oscillations of about 24 h that regulate biological processes and are found in the suprachaismatic nucleus (SCN) and many peripheral tissues, including the heart. They are influenced by external cues, or Zeitgebers, such as light and heat, and can influence such diverse phenomena as cytokine expression immune cells, metabolic activity of cardiac myocytes, and vasodilator regulation by vascular endothelial cells. While it is known that the central master clock in the SCN synchronizes peripheral physiologic rhythms, the mechanisms by which the information is transmitted are complex and may include hormonal, metabolic, and neuronal inputs. Whether circadian patterns are causally related to the observed periodicity of events, or whether they are simply epi-phenomena is not well established, but a few studies suggest that the circadian effects likely are real in their impact on myocardial infarct incidence. Cycle disturbances may be harbingers of predisposition and subsequent response to acute and chronic cardiac injury, and identifying the complex interactions of circadian rhythms and myocardial infarction may provide insights into possible preventative and therapeutic strategies for susceptible populations. PMID:25400588

Virag, Jitka A. I.; Lust, Robert M.

2014-01-01

246

Circadian Organization of Behavior and Physiology in Drosophila  

PubMed Central

Circadian clocks organize behavior and physiology to adapt to daily environmental cycles. Genetic approaches in the fruit fly, Drosophila melanogaster, have revealed widely conserved molecular gears of these 24-h timers. Yet much less is known about how these cell-autonomous clocks confer temporal information to modulate cellular functions. Here we discuss our current knowledge of circadian clock function in Drosophila, providing an overview of the molecular underpinnings of circadian clocks. We then describe the neural network important for circadian rhythms of locomotor activity, including how these molecular clocks might influence neuronal function. Finally, we address a range of behaviors and physiological systems regulated by circadian clocks, including discussion of specific peripheral oscillators and key molecular effectors where they have been described. These studies reveal a remarkable complexity to circadian pathways in this “simple” model organism. PMID:20148690

Allada, Ravi; Chung, Brian Y.

2010-01-01

247

Dose-response relationships for resetting of human circadian clock by light  

NASA Technical Reports Server (NTRS)

Since the first report in unicells, studies across diverse species have demonstrated that light is a powerful synchronizer which resets, in an intensity-dependent manner, endogenous circadian pacemakers. Although it is recognized that bright light (approximately 7,000 to 13,000 lux) is an effective circadian synchronizer in humans, it is widely believed that the human circadian pacemaker is insensitive to ordinary indoor illumination (approximately 50-300 lux). It has been proposed that the relationship between the resetting effect of light and its intensity follows a compressive nonlinear function, such that exposure to lower illuminances still exerts a robust effect. We therefore undertook a series of experiments which support this hypothesis and report here that light of even relatively low intensity (approximately 180 lux) significantly phase-shifts the human circadian pacemaker. Our results clearly demonstrate that humans are much more sensitive to light than initially suspected and support the conclusion that they are not qualitatively different from other mammals in their mechanism of circadian entrainment.

Boivin, D. B.; Duffy, J. F.; Kronauer, R. E.; Czeisler, C. A.

1996-01-01

248

Circadian clock function in the mammalian ovary.  

PubMed

Rhythmic events in the female reproductive system depend on the coordinated and synchronized activity of multiple neuroendocrine and endocrine tissues. This coordination is facilitated by the timing of gene expression and cellular physiology at each level of the hypothalamo-pituitary-ovarian (HPO) axis, including the basal hypothalamus and forebrain, the pituitary gland, and the ovary. Central to this pathway is the primary circadian pacemaker in the suprachiasmatic nucleus (SCN) that, through its myriad outputs, provides a temporal framework for gonadotropin release and ovulation. The heart of the timing system, a transcription-based oscillator, imparts SCN pacemaker cells and a company of peripheral tissues with the capacity for daily oscillations of gene expression and cellular physiology. Although the SCN sits comfortably at the helm, peripheral oscillators (such as the ovary) have undefined but potentially critical roles. Each cell type of the ovary, including theca cells, granulosa cells, and oocytes, harbor a molecular clock implicated in the processes of follicular growth, steroid hormone synthesis, and ovulation. The ovarian clock is influenced by the reproductive cycle and diseases that perturb the cycle and/or follicular growth can disrupt the timing of clock gene expression in the ovary. Chronodisruption is known to negatively affect reproductive function and fertility in both rodent models and women exposed to shiftwork schedules. Thus, influencing clock function in the HPO axis with chronobiotics may represent a novel avenue for the treatment of common fertility disorders, particularly those resulting from chronic circadian disruption. PMID:25367899

Sellix, Michael T

2015-02-01

249

Defibrillator/monitor/pacemakers.  

PubMed

Defibrillator/monitors allow operators to assess and monitor a patient's ECG and, when necessary, deliver a defibrillating shock to the heart. When integral noninvasive pacing capability is added, the resulting device is referred to as a defibrillator/monitor/pacemaker. In this Update Evaluation, we present our findings for nine such units, including complete Product Profiles for two newly evaluated models and update information for seven other models evaluated in our May-June 1993 and February 1998 studies. We tested the two newly evaluated models using the same basic protocol as in our previous studies. However, we did add some new tests--and revise some old ones--to account for advances in the technology. These advancements include the increasing use of advisory modes and the increasing availability of expanded monitoring capabilities (which allow units to function, at least to some degree, like a physiologic monitor). As in our previous studies, we rated each model separately for three common defibrillation applications: (1) general crashcart use, (2) in-hospital transport use, and (3) prehospital use by emergency medical services (EMS) personnel. Because each application requires its own set of capabilities, it's not surprising that few models are appropriate for all applications. However, we did identify three models that perform well--earning a rating of either Acceptable or Preferred--in all three areas. PMID:11022316

2000-09-01

250

The bird circadian clock: insights from a computational model.  

PubMed

The circadian timekeeping system appears more complex in birds than in mammals. In mammals, the main pacemaker is centralized in the suprachiasmatic nuclei, whereas in birds, the pacemaker involves the interplay between the pineal and hypothalamic oscillators. In order to investigate the consequence of this complex mechanism, we propose here a mathematical model for the bird circadian clock. The model is based on the internal resonance between the pineal and hypothalamic oscillators, each described by Goodwin-like equations. We show that, consistently with experimental observations, self-sustained oscillations can be generated by mutual inhibitory coupling of the 2 clocks, even if individual oscillators present damped oscillations. We study the effect of constant and periodic administrations of melatonin, which, in intact birds, acts as the coupling variable between the pineal and the hypothalamus, and compare the prediction of the model with the experiments performed in pinealectomized birds. We also assess the entrainment properties when the system is subject to light-dark cycles. Analyses of the entrainment range, resynchronization time after jet lag, and entrainment phase with respect to the photoperiod lead us to formulate hypotheses about the physiological advantage of the particular architecture of the avian circadian clock. Although minimal, our model opens promising perspectives in modeling and understanding the bird circadian clock. PMID:24336417

Woller, Aurore; Gonze, Didier

2013-12-01

251

Impaired Leukocyte Trafficking and Skin Inflammatory Responses in Hamsters Lacking a Functional Circadian System  

PubMed Central

The immune system is under strong circadian control, and circadian desynchrony is a risk factor for metabolic disorders, inflammatory responses and cancer. Signaling pathways that maintain circadian rhythms (CRs) in immune function in vivo, and the mechanisms by which circadian desynchrony impairs immune function, remain to be fully-identified. These experiments tested the hypothesis that the hypothalamic circadian pacemaker in the suprachiasmatic nucleus (SCN) drives CRs in the immune system, using a non-invasive model of SCN circadian arrhythmia. Robust CRs in blood leukocyte trafficking, with a peak during the early light phase (ZT4) and nadir in the early dark phase (ZT18), were absent in arrhythmic hamsters, as were CRs in spleen clock gene (per1, bmal1) expression, indicating that a functional pacemaker in the SCN is required for the generation of CRs in leukocyte trafficking and for driving peripheral clocks in secondary lymphoid organs. Pinealectomy was without effect on CRs in leukocyte trafficking, but abolished CRs in spleen clock gene expression, indicating that nocturnal melatonin secretion is necessary for communicating circadian time information to the spleen. CRs in trafficking of antigen presenting cells (CD11c+ dendritic cells) in the skin were abolished, and antigen-specific delayed-type hypersensitivity skin inflammatory responses were markedly impaired in arrhythmic hamsters. The SCN drives robust CRs in leukocyte trafficking and lymphoid clock gene expression; the latter of which is not expressed in the absence of melatonin. Robust entrainment of the circadian pacemaker provides a signal critical to diurnal rhythms in immunosurveilliance and optimal memory T-cell dependent immune responses. PMID:23474187

Prendergast, Brian J.; Cable, Erin J.; Patel, Priyesh N.; Pyter, Leah M.; Onishi, Kenneth G.; Stevenson, Tyler J.; Ruby, Norman F.; Bradley, Sean P.

2013-01-01

252

Mechanical, but not infective, pacemaker erosion may be successfully managed by re-implantation of pacemakers  

Microsoft Academic Search

OBJECTIVE--When a pacemaker box causes erosion it is usually removed and a new pacemaker implanted at a contralateral site. In this study when there was no evidence of systemic infection an attempt was made to clean and reimplant the same pacemaker in the same site. RESULTS--Over 10 years 62 patients had pacemaker reimplantation. In 18 patients the procedure was repeated

M. J. Griffith; J. P. Mounsey; R. S. Bexton; M. P. Holden

1994-01-01

253

Sensitivity and integration in a visual pathway for circadian entrainment in the hamster (Mesocricetus auratus).  

PubMed Central

1. Light-induced phase shifts of the circadian rhythm of wheel-running activity were used to measure the photic sensitivity of a circadian pacemaker and the visual pathway that conveys light information to it in the golden hamster (Mesocricetus auratus). The sensitivity to stimulus irradiance and duration was assessed by measuring the magnitude of phase-shift responses to photic stimuli of different irradiance and duration. The visual sensitivity was also measured at three different phases of the circadian rhythm. 2. The stimulus-response curves measured at different circadian phases suggest that the maximum phase-shift is the only aspect of visual responsivity to change as a function of the circadian day. The half-saturation constants (sigma) for the stimulus-response curves are not significantly different over the three circadian phases tested. The photic sensitivity to irradiance (1/sigma) appears to remain constant over the circadian day. 3. The hamster circadian pacemaker and the photoreceptive system that subserves it are more sensitive to the irradiance of longer-duration stimuli than to irradiance of briefer stimuli. The system is maximally sensitive to the irradiance of stimuli of 300 s and longer in duration. A quantitative model is presented to explain the changes that occur in the stimulus-response curves as a function of photic stimulus duration. 4. The threshold for photic stimulation of the hamster circadian pacemaker is also quite high. The threshold irradiance (the minimum irradiance necessary to induce statistically significant responses) is approximately 10(11) photons cm-2 s-1 for optimal stimulus durations. This threshold is equivalent to a luminance at the cornea of 0.1 cd m-2. 5. We also measured the sensitivity of this visual pathway to the total number of photons in a stimulus. This system is maximally sensitive to photons in stimuli between 30 and 3600 s in duration. The maximum quantum efficiency of photic integration occurs in 300 s stimuli. 6. These results suggest that the visual pathways that convey light information to the mammalian circadian pacemaker possess several unique characteristics. These pathways are relatively insensitive to light irradiance and also integrate light inputs over relatively long durations. This visual system, therefore, possesses an optimal sensitivity of 'tuning' to total photons delivered in stimuli of several minutes in duration. Together these characteristics may make this visual system unresponsive to environmental 'noise' that would interfere with the entrainment of circadian rhythms to light-dark cycles. PMID:1895235

Nelson, D E; Takahashi, J S

1991-01-01

254

Circadian Role in Daily Pattern of Cardiovascular Risk  

NASA Astrophysics Data System (ADS)

Numerous epidemiological studies demonstrate that sudden cardiac death, pulmonary embolism, myocardial infarction, and stroke have a 24-hour daily pattern with a broad peak between 9-11am. Such a daily pattern in cardiovascular risk could be attributable to external factors, such as the daily behavior patterns, including sleep-wake cycles and activity levels, or internal factors, such as the endogenous circadian pacemaker. Findings of significant alternations in the temporal organization and nonlinear properties of heartbeat fluctuations with disease and with sleep-wake transitions raise the intriguing possibility that changes in the mechanism of control associated with behavioral sleep-wake transition may be responsible for the increased cardiac instability observed in particular circadian phases. Alternatively, we hypothesize that there is a circadian clock, independent of the sleep-wake cycle, which affects the cardiac dynamics leading to increased cardiovascular risk. We analyzed continuous recordings from healthy subjects during 7 cycles of forced desynchrony routine wherein subjects' sleep-wake cycles are adjusted to 28 hours so that their behaviors occur across all circadian phases. Heartbeat data were divided into one-hour segments. For each segment, we estimated the correlations and the nonlinear properties of the heartbeat fluctuations at the corresponding circadian phase. Since the sleep and wake contributions are equally weighted in our experiment, a change of the properties of the heartbeat dynamics with circadian phase suggest a circadian rhythm. We show significant circadian-mediated alterations in the correlation and nonlinear properties of the heartbeat resembling those observed in patients with heart failure. Remarkably, these dynamical alterations are centered at 60 degrees circadian phase, coinciding with the 9-11am window of cardiac risk.

Ivanov, Plamen Ch.; Hu, Kun; Chen, Zhi; Hilton, Michael F.; Stanley, H. Eugene; Shea, Steven A.

2004-03-01

255

What Are the Risks of Pacemaker Surgery?  

MedlinePLUS

... or nerve damage A collapsed lung A bad reaction to the medicine used during the procedure Talk with your doctor about the benefits and risks of pacemaker surgery. Rate This Content: Next >> February 28, 2012 Pacemakers Clinical ...

256

Devices That May Interfere with Pacemakers  

MedlinePLUS

... that uses high-frequency, high-intensity signals for physical therapy. These may bypass your pacemaker's noise protection and ... that uses high-frequency, high-intensity signals for physical therapy. These may bypass your pacemaker's noise protection and ...

257

21 CFR 870.3700 - Pacemaker programmers.  

Code of Federal Regulations, 2012 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3700 Pacemaker programmers. (a) Identification. A pacemaker programmer is a device used...

2012-04-01

258

Biological pacemaker created by fetal cardiomyocyte transplantation  

Microsoft Academic Search

Summary Background—The aim of this study was to investigate the feasibility of an alternative approach to electronic pacemaker by using spontaneously excitable cell grafts as a biological pacemaker in a large animal model of complete atrioventricular block.

Guosheng Lin; Jun Cai; Hong Jiang; Hui Shen; Xuejun Jiang; Qijing Yu; Jian Song

2005-01-01

259

Robust circadian oscillations in growing cyanobacteria require transcriptional feedback  

PubMed Central

The remarkably stable circadian oscillations of single cyanobacteria enable a population of growing cells to maintain synchrony for weeks. The cyanobacterial pacemaker is a post-translational regulation (PTR) circuit that generates circadian oscillations in the phosphorylation state of the clock protein, KaiC. Layered on top of the PTR is transcriptional-translational feedback regulation (TTR), common to all circadian systems, consisting of a negative feedback loop in which KaiC regulates its own production. We demonstrate that the PTR circuit is sufficient to generate oscillations in growing cyanobacteria. However, in the absence of TTR individual oscillators were less stable and synchrony was not maintained in a population of cells. Experimentally-constrained, mathematical modeling reproduced sustained oscillations in the PTR circuit alone and the importance of TTR for oscillator synchrony. PMID:23661759

Teng, Shu-Wen; Mukherji, Shankar; Moffitt, Jeffrey R.; de Buyl, Sophie; O’Shea, Erin K.

2013-01-01

260

Circadian timing of metabolism in animal models and humans.  

PubMed

Most living beings, including humans, must adapt to rhythmically occurring daily changes in their environment that are generated by the Earth's rotation. In the course of evolution, these organisms have acquired an internal circadian timing system that can anticipate environmental oscillations and thereby govern their rhythmic physiology in a proactive manner. In mammals, the circadian timing system coordinates virtually all physiological processes encompassing vigilance states, metabolism, endocrine functions and cardiovascular activity. Research performed during the past two decades has established that almost every cell in the body possesses its own circadian timekeeper. The resulting clock network is organized in a hierarchical manner. A master pacemaker, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, is synchronized every day to the photoperiod. In turn, the SCN determines the phase of the cellular clocks in peripheral organs through a wide variety of signalling pathways dependent on feeding cycles, body temperature rhythms, oscillating bloodborne signals and, in some organs, inputs of the peripheral nervous system. A major purpose of circadian clocks in peripheral tissues is the temporal orchestration of key metabolic processes, including food processing (metabolism and xenobiotic detoxification). Here, we review some recent findings regarding the molecular and cellular composition of the circadian timing system and discuss its implications for the temporal coordination of metabolism in health and disease. We focus primarily on metabolic disorders such as obesity and type 2 diabetes, although circadian misalignments (shiftwork or 'social jet lag') have also been associated with the aetiology of human malignancies. PMID:25599827

Dibner, C; Schibler, U

2015-05-01

261

Circadian Rhythm Sleep Disorders  

PubMed Central

There have been remarkable advances in our understanding of the molecular, cellular and physiological mechanisms underlying the regulation of circadian rhythms, as well as the impact of circadian dysfunction on health and disease. This information has transformed our understanding of the effect of circadian rhythm sleep disorders (CRSD) on health, performance and safety. CRSDs are caused by alterations of the central circadian time-keeping system, or a misalignment of the endogenous circadian rhythm and the external environment. In this section, we provide a review of circadian biology and discuss the pathophysiology, clinical features, diagnosis, and treatment of the most commonly encountered CRSDs in clinical practice. PMID:23099133

Zhu, Lirong; Zee, Phyllis C.

2012-01-01

262

An Intelligent System for Pacemaker Reprogramming  

E-print Network

a cardiac pacemaker can be described in terms similar to those used for describing diagnostic problem required. One of the possible treatments for these patients is assistance by a cardiac pacemaker. Modern of intelligent decision support is needed in order to let patients benefit from further advances in pacemaker

Lucas, Peter

263

An Intelligent System for Pacemaker Reprogramming  

E-print Network

a cardiac pacemaker can be described in terms similar to those used for describing diagnostic problem is nevertheless required. One of the possible treatments for these patients is assistance by a cardiac pacemaker in order to let patients benefit from further advances in pacemaker technology. The process

Utrecht, Universiteit

264

Circadian adaptations to meal timing: neuroendocrine mechanisms  

PubMed Central

Circadian rhythms of behavior and physiology are generated by central and peripheral circadian oscillators entrained by periodic environmental or physiological stimuli. A master circadian pacemaker in the hypothalamic suprachiasmatic nucleus (SCN) is directly entrained by daily light-dark (LD) cycles, and coordinates the timing of other oscillators by direct and indirect neural, hormonal and behavioral outputs. The daily rhythm of food intake provides stimuli that entrain most peripheral and central oscillators, some of which can drive a daily rhythm of food anticipatory activity if food is restricted to one daily mealtime. The location of food-entrainable oscillators (FEOs) that drive food anticipatory rhythms, and the food-related stimuli that entrain these oscillators, remain to be clarified. Here, we critically examine the role of peripheral metabolic hormones as potential internal entrainment stimuli or outputs for FEOs controlling food anticipatory rhythms in rats and mice. Hormones for which data are available include corticosterone, ghrelin, leptin, insulin, glucagon, and glucagon-like peptide 1. All of these hormones exhibit daily rhythms of synthesis and secretion that are synchronized by meal timing. There is some evidence that ghrelin and leptin modulate the expression of food anticipatory rhythms, but none of the hormones examined so far are necessary for entrainment. Ghrelin and leptin likely modulate food-entrained rhythms by actions in hypothalamic circuits utilizing melanocortin and orexin signaling, although again food-entrained behavioral rhythms can persist in lesion and gene knockout models in which these systems are disabled. Actions of these hormones on circadian oscillators in central reward circuits remain to be evaluated. Food-entrained activity rhythms are likely mediated by a distributed system of circadian oscillators sensitive to multiple feeding related inputs. Metabolic hormones appear to play a modulatory role within this system. PMID:24133410

Patton, Danica F.; Mistlberger, Ralph E.

2013-01-01

265

Lithium pacemaker batteries - an overview  

SciTech Connect

Batteries used as power sources in cardiac pacemakers are expected to have high energy density, long storage and operating life and high reliability. They must be nonhazardous under normal operating as well as abusive conditions. Intensive research activities on the past 10-15 years have resulted in the development of a variety of high energy density batteries using Li as the anode material (Li-batteries). At least six different chemical systems with Li anodes are in use as power sources for cardiac pacemakers. Some basic characteristics of these systems are discussed. 11 refs.

Liang, C.C.; Holmes, C.F.

1980-01-01

266

The suprachiasmatic nucleus and the circadian time-keeping system revisited.  

PubMed

Many physiological and behavioral processes show circadian rhythms which are generated by an internal time-keeping system, the biological clock. In rodents, evidence from a variety of studies has shown the suprachiasmatic nucleus (SCN) to be the site of the master pacemaker controlling circadian rhythms. The clock of the SCN oscillates with a near 24-h period but is entrained to solar day/night rhythm by light. Much progress has been made recently in understanding the mechanisms of the circadian system of the SCN, its inputs for entrainment and its outputs for transfer of the rhythm to the rest of the brain. The present review summarizes these new developments concerning the properties of the SCN and the mechanisms of circadian time-keeping. First, we will summarize data concerning the anatomical and physiological organization of the SCN, including the roles of SCN neuropeptide/neurotransmitter systems, and our current knowledge of SCN input and output pathways. Second, we will discuss SCN transplantation studies and how they have contributed to knowledge of the intrinsic properties of the SCN, communication between the SCN and its targets, and age-related changes in the circadian system. Third, recent findings concerning the genes and molecules involved in the intrinsic pacemaker mechanisms of insect and mammalian clocks will be reviewed. Finally, we will discuss exciting new possibilities concerning the use of viral vector-mediated gene transfer as an approach to investigate mechanisms of circadian time-keeping. PMID:10967353

van Esseveldt, K E; Lehman, M N; Boer, G J

2000-08-01

267

Circadian clocks in symbiotic corals: the duet between Symbiodinium algae and their coral host.  

PubMed

To date, the association and synchronization between two organismal circadian clocks ticking in parallel as part of a meta-organism (termed a symbiotic association), have rarely been investigated. Reef-building corals exhibit complex rhythmic responses to diurnal, lunar, and annual changes. Understanding circadian, circatidal, and annual regulation in reef-building corals is complicated by the presence of photosynthetic endosymbionts, which have a profound physiochemical influence on the intracellular environment. How corals tune their animal-based clock machinery to respond to external cues while simultaneously responding to internal physiological changes imposed by the symbiont, is not clear. There is insufficient molecular or physiological evidence of the existence of a circadian pacemaker that controls the metabolism, photosynthesis, synchronized mass spawning, and calcification processes in symbiotic corals. In this review, we present current knowledge regarding the animal pacemaker and the symbiotic-algal pacemaker. We examine the evidence from behavioral, physiological, molecular, and evolutionary perspectives. We explain why symbiotic corals are an interesting model with which to study the complexities and evolution of the metazoan circadian clock. We also provide evidence of why the chronobiology of corals is fundamental and extremely important for explaining the biology, physiology, and metabolism of coral reefs. A deeper understanding of these complex issues can help explain coral mass spawning, one of the earth's greatest and most mysterious behavioral phenomena. PMID:24508015

Sorek, Michal; Díaz-Almeyda, Erika M; Medina, Mónica; Levy, Oren

2014-04-01

268

Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics  

NASA Technical Reports Server (NTRS)

The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

Dijk, D. J.; Duffy, J. F.

1999-01-01

269

The circadian timing system: a recent addition in the physiological mechanisms underlying pathological and aging processes.  

PubMed

Experimental findings and clinical observations have strengthened the association between physio-pathologic aspects of several diseases, as well as aging process, with the occurrence and control of circadian rhythms. The circadian system is composed by a principal pacemaker in the suprachiasmatic nucleus (SNC) which is in coordination with a number of peripheral circadian oscillators. Many pathological entities such as metabolic syndrome, cancer and cardiovascular events are strongly connected with a disruptive condition of the circadian cycle. Inadequate circadian physiology can be elicited by genetic defects (mutations in clock genes or circadian control genes) or physiological deficiencies (desynchronization between SCN and peripheral oscillators). In this review, we focus on the most recent experimental findings regarding molecular defects in the molecular circadian clock and the altered coordination in the circadian system that are related with clinical conditions such as metabolic diseases, cancer predisposition and physiological deficiencies associated to jet-lag and shiftwork schedules. Implications in the aging process will be also reviewed. PMID:25489492

Arellanes-Licea, Elvira; Caldelas, Ivette; De Ita-Pérez, Dalia; Díaz-Muñoz, Mauricio

2014-12-01

270

Dual KaiC-based oscillations constitute the circadian system of cyanobacteria  

PubMed Central

In the cyanobacterium Synechococcus elongatus PCC 7942, the KaiA, KaiB, and KaiC proteins are essential for the generation of circadian rhythms. Both in vivo and in vitro, phosphorylation of KaiC is regulated positively by KaiA and negatively by KaiB and shows circadian rhythmicity. The autonomous circadian cycling of KaiC phosphorylation is thought to be the basic pacemaker of the circadian clock and to control genome-wide gene expression in cyanobacteria. In this study, we found that temperature-compensated circadian oscillations of gene expression persisted even when KaiC was arrested in the phosphorylated state due to kaiA overexpression. Moreover, two phosphorylation mutants showed transcriptional oscillation with a long period. In kaiA-overexpressing and phosphorylation-deficient strains, KaiC oscillated and transient overexpression of phosphorylation-deficient kaiC reset the phase of the rhythm. These results suggest that transcription- and translation-based oscillations in KaiC abundance are also important for circadian rhythm generation in cyanobacteria. Furthermore, at low temperature, cyanobacteria can show circadian rhythms only when both the KaiC phosphorylation cycle and the transcription and translation cycle are intact. Our findings indicate that multiple coupled oscillatory systems based on the biochemical properties of KaiC are important to maintain robust and precise circadian rhythms in cyanobacteria. PMID:18477603

Kitayama, Yohko; Nishiwaki, Taeko; Terauchi, Kazuki; Kondo, Takao

2008-01-01

271

The Circadian Timing System: A Recent Addition in the Physiological Mechanisms Underlying Pathological and Aging Processes  

PubMed Central

Experimental findings and clinical observations have strengthened the association between physio-pathologic aspects of several diseases, as well as aging process, with the occurrence and control of circadian rhythms. The circadian system is composed by a principal pacemaker in the suprachiasmatic nucleus (SNC) which is in coordination with a number of peripheral circadian oscillators. Many pathological entities such as metabolic syndrome, cancer and cardiovascular events are strongly connected with a disruptive condition of the circadian cycle. Inadequate circadian physiology can be elicited by genetic defects (mutations in clock genes or circadian control genes) or physiological deficiencies (desynchronization between SCN and peripheral oscillators). In this review, we focus on the most recent experimental findings regarding molecular defects in the molecular circadian clock and the altered coordination in the circadian system that are related with clinical conditions such as metabolic diseases, cancer predisposition and physiological deficiencies associated to jet-lag and shiftwork schedules. Implications in the aging process will be also reviewed. PMID:25489492

Arellanes-Licea, Elvira; Caldelas, Ivette; De Ita-Pérez, Dalia; Díaz-Muñoz, Mauricio

2014-01-01

272

Circadian rhythms of temperature and activity in obese and lean Zucker rats  

NASA Technical Reports Server (NTRS)

The circadian timing system is important in the regulation of feeding and metabolism, both of which are aberrant in the obese Zucker rat. This study tested the hypothesis that these abnormalities involve a deficit in circadian regulation by examining the circadian rhythms of body temperature and activity in lean and obese Zucker rats exposed to normal light-dark cycles, constant light, and constant dark. Significant deficits in both daily mean and circadian amplitude of temperature and activity were found in obese Zucker female rats relative to lean controls in all lighting conditions. However, the circadian period of obese Zucker rats did not exhibit differences relative to lean controls in either of the constant lighting conditions. These results indicate that although the circadian regulation of temperature and activity in obese Zucker female rats is in fact depressed, obese rats do exhibit normal entrainment and pacemaker functions in the circadian timing system. The results suggest a deficit in the process that generates the amplitude of the circadian rhythm.

Murakami, D. M.; Horwitz, B. A.; Fuller, C. A.

1995-01-01

273

Synchronization and entrainment of coupled circadian oscillators  

E-print Network

Circadian rhythms in mammals are controlled by the neurons located in the suprachiasmatic nucleus of the hypothalamus. In physiological conditions, the system of neurons is very efficiently entrained by the 24-hour light-dark cycle. Most of the studies carried out so far emphasize the crucial role of the periodicity imposed by the light dark cycle in neuronal synchronization. Nevertheless, heterogeneity as a natural and permanent ingredient of these cellular interactions is seemingly to play a major role in these biochemical processes. In this paper we use a model that considers the neurons of the suprachiasmatic nucleus as chemically-coupled modified Goodwin oscillators, and introduce non-negligible heterogeneity in the periods of all neurons in the form of quenched noise. The system response to the light-dark cycle periodicity is studied as a function of the interneuronal coupling strength, external forcing amplitude and neuronal heterogeneity. Our results indicate that the right amount of heterogeneity hel...

Komin, Niko; Hernandez-Garcia, Emilio; Toral, Raul

2010-01-01

274

A short history on pacemakers.  

PubMed

Artificial pacemakers have taken part or possibly driven many developments in cardiac science and medicine and are therefore a very important story to remember. This 300-year journey of discovery has been contributed to by experts from across the Globe. The essential foundation of knowledge such as basic electrophysiology and applied electrotherapy was built in the 18th century and is now academically and socially accepted. This line of inventions and research has seen: early use of meta-analyses, the initial coming together of medical or bioengineering and the concept of cardiac monitoring--now a mainstay in the hospital care of a patient. In the 21st century pacemaker developments are no longer solely about reducing mortality but improving morbidity. Design developments reduce: discomfort, additional surgeries and invasive procedures. New energy sources have become lighter, smaller and with a longer life span. PMID:24083883

Ward, Catherine; Henderson, Susannah; Metcalfe, Neil H

2013-11-15

275

p38 MAP kinase regulates circadian rhythms in Drosophila.  

PubMed

The large repertoire of circadian rhythms in diverse organisms depends on oscillating central clock genes, input pathways for entrainment, and output pathways for controlling rhythmic behaviors. Stress-activated p38 MAP Kinases (p38K), although sparsely investigated in this context, show circadian rhythmicity in mammalian brains and are considered part of the circadian output machinery in Neurospora. We find that Drosophila p38Kb is expressed in clock neurons, and mutants in p38Kb either are arrhythmic or have a longer free-running periodicity, especially as they age. Paradoxically, similar phenotypes are observed through either transgenic inhibition or activation of p38Kb in clock neurons, suggesting a requirement for optimal p38Kb function for normal free-running circadian rhythms. We also find that p38Kb genetically interacts with multiple downstream targets to regulate circadian locomotor rhythms. More specifically, p38Kb interacts with the period gene to regulate period length and the strength of rhythmicity. In addition, we show that p38Kb suppresses the arrhythmic behavior associated with inhibition of a second p38Kb target, the transcription factor Mef2. Finally, we find that manipulating p38K signaling in free-running conditions alters the expression of another downstream target, MNK/Lk6, which has been shown to cycle with the clock and to play a role in regulating circadian rhythms. These data suggest that p38Kb may affect circadian locomotor rhythms through the regulation of multiple downstream pathways. PMID:25403440

Vrailas-Mortimer, Alysia D; Ryan, Sarah M; Avey, Matthew J; Mortimer, Nathan T; Dowse, Harold; Sanyal, Subhabrata

2014-12-01

276

21 CFR 870.3710 - Pacemaker repair or replacement material.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 2014-04-01 false Pacemaker repair or replacement material. ...Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material...

2014-04-01

277

21 CFR 870.3730 - Pacemaker service tools.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Pacemaker service tools. 870.3730 Section...Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as...

2010-04-01

278

21 CFR 870.3620 - Pacemaker lead adaptor.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Pacemaker lead adaptor. 870.3620 Section 870...Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to...

2012-04-01

279

21 CFR 870.3730 - Pacemaker service tools.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Pacemaker service tools. 870.3730 Section...Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices such as...

2012-04-01

280

21 CFR 870.3690 - Pacemaker test magnet.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Pacemaker test magnet. 870.3690 Section 870...Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used to test...

2013-04-01

281

21 CFR 870.3690 - Pacemaker test magnet.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Pacemaker test magnet. 870.3690 Section 870...Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used to test...

2012-04-01

282

21 CFR 870.3710 - Pacemaker repair or replacement material.  

Code of Federal Regulations, 2012 CFR

...2012-04-01 2012-04-01 false Pacemaker repair or replacement material. ...Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair or replacement material...

2012-04-01

283

21 CFR 870.3630 - Pacemaker generator function analyzer.  

Code of Federal Regulations, 2010 CFR

... 2010-04-01 false Pacemaker generator function analyzer. 870.3630 ...Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device...

2010-04-01

284

21 CFR 870.1750 - External programmable pacemaker pulse generator.  

Code of Federal Regulations, 2013 CFR

...External programmable pacemaker pulse generator. 870.1750 Section 870.1750...External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker pulse generators is a device that can be...

2013-04-01

285

21 CFR 870.3630 - Pacemaker generator function analyzer.  

Code of Federal Regulations, 2011 CFR

... 2011-04-01 false Pacemaker generator function analyzer. 870.3630 ...Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device...

2011-04-01

286

21 CFR 870.1750 - External programmable pacemaker pulse generator.  

Code of Federal Regulations, 2012 CFR

...External programmable pacemaker pulse generator. 870.1750 Section 870.1750...External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker pulse generators is a device that can be...

2012-04-01

287

21 CFR 870.3630 - Pacemaker generator function analyzer.  

Code of Federal Regulations, 2012 CFR

... 2012-04-01 false Pacemaker generator function analyzer. 870.3630 ...Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator function analyzer is a device...

2012-04-01

288

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.  

Code of Federal Regulations, 2014 CFR

...2014-04-01 false Indirect pacemaker generator function analyzer. 870.3640...870.3640 Indirect pacemaker generator function analyzer. (a) Identification. An indirect pacemaker generator function analyzer is an...

2014-04-01

289

21 CFR 870.1750 - External programmable pacemaker pulse generator.  

Code of Federal Regulations, 2014 CFR

...External programmable pacemaker pulse generator. 870.1750 Section 870.1750...External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker pulse generators is a device that can be...

2014-04-01

290

21 CFR 870.1750 - External programmable pacemaker pulse generator.  

Code of Federal Regulations, 2011 CFR

...External programmable pacemaker pulse generator. 870.1750 Section 870.1750...External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker pulse generators is a device that can be...

2011-04-01

291

21 CFR 870.1750 - External programmable pacemaker pulse generator.  

Code of Federal Regulations, 2010 CFR

...External programmable pacemaker pulse generator. 870.1750 Section 870.1750...External programmable pacemaker pulse generator. (a) Identification. An external programmable pacemaker pulse generators is a device that can be...

2010-04-01

292

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2013 CFR

...false External pacemaker pulse generator. 870.3600 Section 870...3600 External pacemaker pulse generator. (a) Identification. An external pacemaker pulse generator is a device that has a power supply and...

2013-04-01

293

21 CFR 870.3610 - Implantable pacemaker pulse generator.  

Code of Federal Regulations, 2010 CFR

...Implantable pacemaker pulse generator. 870.3610 Section 870...Implantable pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has a power supply and...

2010-04-01

294

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2011 CFR

...false External pacemaker pulse generator. 870.3600 Section 870...3600 External pacemaker pulse generator. (a) Identification. An external pacemaker pulse generator is a device that has a power supply and...

2011-04-01

295

21 CFR 870.3610 - Implantable pacemaker pulse generator.  

Code of Federal Regulations, 2012 CFR

...Implantable pacemaker pulse generator. 870.3610 Section 870...Implantable pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has a power supply and...

2012-04-01

296

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2012 CFR

...false External pacemaker pulse generator. 870.3600 Section 870...3600 External pacemaker pulse generator. (a) Identification. An external pacemaker pulse generator is a device that has a power supply and...

2012-04-01

297

21 CFR 870.3610 - Implantable pacemaker pulse generator.  

Code of Federal Regulations, 2014 CFR

...Implantable pacemaker pulse generator. 870.3610 Section 870...Implantable pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has a power supply and...

2014-04-01

298

21 CFR 870.3610 - Implantable pacemaker pulse generator.  

Code of Federal Regulations, 2013 CFR

...Implantable pacemaker pulse generator. 870.3610 Section 870...Implantable pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has a power supply and...

2013-04-01

299

21 CFR 870.3610 - Implantable pacemaker pulse generator.  

Code of Federal Regulations, 2011 CFR

...Implantable pacemaker pulse generator. 870.3610 Section 870...Implantable pacemaker pulse generator. (a) Identification. An implantable pacemaker pulse generator is a device that has a power supply and...

2011-04-01

300

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2014 CFR

...false External pacemaker pulse generator. 870.3600 Section 870...3600 External pacemaker pulse generator. (a) Identification. An external pacemaker pulse generator is a device that has a power supply and...

2014-04-01

301

Lithium-iodine pacemaker cell  

SciTech Connect

The lithium-iodine pacemaker cell is described as supplied by several manufacturers. The features of each design are discussed along with their effect on energy density, self-discharge and shape of the discharge curve. Differences in performance characteristics are related to morphology of the lithium iodine electrolyte and to the form of the cathode. A new, high-drain cell is mentioned which can supply 60 /mu/a/cm/sup 2/. 10 refs.

Schneider, A.A.; Snyder, S.E.; DeVan, T.; Harney, M.J.; Harney, D.E.

1980-01-01

302

Pacemakers—A journey through the years  

Microsoft Academic Search

This is an article on the history of artificial cardiac pacemakers. Before the advent of pacemakers, not much could be done\\u000a for patients who suffered from cardiac asystole and other cardiac rhythm disturbances. Although the concept that an artificial\\u000a pacemaker could be used to stimulate the heart in standstill evolved much earlier, it was not until 1952 that the first

Tarun Mittal

2005-01-01

303

Gene therapy to create biological pacemakers  

Microsoft Academic Search

Old age and a variety of cardiovascular disorders may disrupt normal sinus node function. Currently, this is successfully\\u000a treated with electronic pacemakers, which, however, leave room for improvement. During the past decade, different strategies\\u000a to initiate pacemaker function by gene therapy were developed. In the search for a biological pacemaker, various approaches\\u000a were explored, including ?2-adrenergic receptor overexpression, down regulation

Gerard J. J. Boink; Jurgen Seppen; Jacques M. T. de Bakker; Hanno L. Tan

2007-01-01

304

Gene Therapy to Create Biological Pacemakers  

Microsoft Academic Search

Old age and a variety of cardiovascular disorders may disrupt normal sinus node function. Currently, this is successfully\\u000a treated with electronic pacemakers, which, however, leave room for improvement. During the past decade, different strategies\\u000a to initiate pacemaker function by gene therapy were developed. In the search for a biological pacemaker, various approaches\\u000a were explored, including ?\\u000a 2-adrenergic receptor overexpression, down

Gerard J. J. Boink; Jurgen Seppen; Jacques M. T. Bakker; Hanno L. Tan

305

Identification of the molecular components of a Tigriopus californicus (Crustacea, Copepoda) circadian clock.  

PubMed

Copepods of the genus Tigriopus have been proposed as marine models for investigations of environmental perturbation. One rapidly increasing anthropogenic stressor for intertidal organisms is light pollution. Given the sensitivity of circadian rhythms to exogenous light, the genes/proteins of a Tigriopus circadian pacemaker represent a potential system for investigating the influences of artificial light sources on circadian behavior in an intertidal species. Here, the molecular components of a putative Tigriopus californicus circadian clock were identified using publicly accessible transcriptome data; the recently deduced circadian proteins of the copepod Calanus finmarchicus were used as a reference. Transcripts encoding homologs of all commonly recognized ancestral arthropod core clock proteins were identified (i.e. CLOCK, CRYPTOCHROME 2, CYCLE, PERIOD and TIMELESS), as were ones encoding proteins likely to modulate the core clock (i.e. CASEIN KINASE II, CLOCKWORK ORANGE, DOUBLETIME, PROTEIN PHOSPHATASE 1, PROTEIN PHOSPHATASE 2A, SHAGGY, SUPERNUMERARY LIMBS and VRILLE) or to act as inputs to it (i.e. CRYPTOCHROME 1). PAR DOMAIN PROTEIN 1 was the only circadian-associated protein not identified in Tigriopus; it appears absent in Calanus too. These data represent just the third full set of molecular components for a crustacean circadian pacemaker (Daphnia pulex and C. finmarchicus previously), and only the second obtained from transcribed sequences (C. finmarchicus previously). Given Tigriopus' proposed status as a model for investigating the influences of anthropogenic stressors in the marine environment, these data provide the first suite of gene/protein targets for understanding how light pollution may influence circadian physiology and behavior in an intertidal organism. PMID:25310881

Nesbit, Katherine T; Christie, Andrew E

2014-12-01

306

Effects of gravity on the circadian period in rats  

NASA Technical Reports Server (NTRS)

The effect of increased gravity force on the circadian period of body temperature and activity of rats was investigated using rats implanted with a small radio telemetry device and, after a 2-week recovery and a 3-week control period at 1G, rotated at for 4 weeks at a constant 2G field in a 18-ft-diam centrifuge. Measurements of the mean freerunning period of the temperature and activity rhythms after 10 days showed that the exposure to 2G led to a functional separation of the pacemakers that regulate the activity and the temperature in the animals. Each pacemaker reacted differently: the activity period increased and the temperature period decreased. By the third or the fourth week, the activity and the temperature periods have returned to 1G control levels.

Murakami, Dean M.; Demaria, Victor H.; Fuller, Charles A.

1991-01-01

307

The nuclear pacemaker: Is renewed interest warranted  

SciTech Connect

From 1973 through 1987, 155 radioisotope-powered nuclear pacemakers were implanted in 132 patients at the Newark Beth Israel Medical Center. The longevity of the first 15 devices, all of which were fixed-rate (VOO) pacemakers, was significantly better than that of 15 lithium-chemistry demand (VVI) pacemakers used as control devices (p = 0.0002). Of the entire cohort of 155 nuclear pacemakers, 136 were VVI devices and 19 were VOO units. The patients with VOO pacemakers needed reoperations more often than did those with VVI pacemakers, chiefly for mode change (p less than 0.001). Power-source failure was observed in only 1 case, but 47 nuclear pacemakers were removed for other reasons, including component malfunction (15 units), mode change (12 units), high pacing thresholds (8 units) and lead or connector problems (5 units). The actuarial survival at 15 years was 99% for power sources and 82% for the entire pacing systems (pulse generators plus leads). The frequency of malignancy was similar to that of the population at large and primary tumor sites were randomly distributed. Deaths most commonly were due to cardiac causes (68%). Thus, nuclear pacemakers are safe and reliable and their greater initial cost appears to be offset by their longevity and the resulting decrease in the frequency of reoperations. It is reasonable to suggest that further use be made of long-lasting nuclear power sources for modern pacemakers and other implantable rhythm-management devices.

Parsonnet, V.; Berstein, A.D.; Perry, G.Y. (Newark Beth Israel Medical Center, NJ (USA))

1990-10-01

308

Space Derived Health Aids (Cardiac Pacemaker)  

NASA Technical Reports Server (NTRS)

St. Jude Medical's Cardiac Rhythm Management Division's (formerly known as Pacesetter Systems, Inc.) pacer is a rechargeable cardiac pacemaker that eliminates the recurring need for surgery to implant a new battery. The Programalith is an advanced cardiac pacing system which permits a physician to reprogram a patient's implanted pacemaker without surgery. System consists of a pacemaker, together with a physician's console containing the programmer and a data printer. Signals are transmitted by wireless telemetry. Two-way communications, originating from spacecraft electrical power systems technology, allows physician to interrogate the pacemaker as to the status of the heart, then to fine tune the device to best suit the patient's needs.

1981-01-01

309

Gene therapy to create biological pacemakers.  

PubMed

Old age and a variety of cardiovascular disorders may disrupt normal sinus node function. Currently, this is successfully treated with electronic pacemakers, which, however, leave room for improvement. During the past decade, different strategies to initiate pacemaker function by gene therapy were developed. In the search for a biological pacemaker, various approaches were explored, including beta(2)-adrenergic receptor overexpression, down regulation of the inward rectifier current, and overexpression of the pacemaker current. The most recent advances include overexpression of bioengineered ion channels and genetically modified stem cells. This review considers the strengths and the weaknesses of the different approaches and discusses some of the different viral vectors currently used. PMID:17048028

Boink, Gerard J J; Seppen, Jurgen; de Bakker, Jacques M T; Tan, Hanno L

2007-02-01

310

Electrocautery-induced pacemaker malfunction during surgery.  

PubMed

We report a case of electrocautery-induced pacemaker failure that resulted in asystole in a 15-year-old girl scheduled for cardiac surgery. Her pacemaker was converted to the asynchronous mode the night before surgery. Electromagnetic interference from the unipolar electrocautery caused a reduction in the battery voltage, which allowed the digital circuitry, but not the voltage control oscillator (VCO), to work properly. Eventually the battery current drain caused VCO "lock-out," and pacemaker and battery failure. This report demonstrates that electrocautery-induced pacemaker failure can occur, even after conversion to asynchronous mode. PMID:1934215

Mangar, D; Atlas, G M; Kane, P B

1991-07-01

311

Epithermal neutron beam interference with cardiac pacemakers.  

PubMed

In this paper, a phantom study was performed to evaluate the effect of an epithermal neutron beam irradiation on the cardiac pacemaker function. Severe malfunction occurred in the pacemakers after substantially lower dose from epithermal neutron irradiation than reported in the fast neutron or photon beams at the same dose rate level. In addition the pacemakers got activated, resulting in nuclides with half-lives from 25 min to 115 d. We suggest that BNCT should be administrated only after removal of the pacemaker from the vicinity of the tumor. PMID:21478029

Koivunoro, H; Serén, T; Hyvönen, H; Kotiluoto, P; Iivonen, P; Auterinen, I; Seppälä, T; Kankaanranta, L; Pakarinen, S; Tenhunen, M; Savolainen, S

2011-12-01

312

Inference on periodicity of circadian time series.  

PubMed

Estimation of the period length of time-course data from cyclical biological processes, such as those driven by the circadian pacemaker, is crucial for inferring the properties of the biological clock found in many living organisms. We propose a methodology for period estimation based on spectrum resampling (SR) techniques. Simulation studies show that SR is superior and more robust to non-sinusoidal and noisy cycles than a currently used routine based on Fourier approximations. In addition, a simple fit to the oscillations using linear least squares is available, together with a non-parametric test for detecting changes in period length which allows for period estimates with different variances, as frequently encountered in practice. The proposed methods are motivated by and applied to various data examples from chronobiology. PMID:23743206

Costa, Maria J; Finkenstädt, Bärbel; Roche, Véronique; Lévi, Francis; Gould, Peter D; Foreman, Julia; Halliday, Karen; Hall, Anthony; Rand, David A

2013-09-01

313

Inference on periodicity of circadian time series  

PubMed Central

Estimation of the period length of time-course data from cyclical biological processes, such as those driven by the circadian pacemaker, is crucial for inferring the properties of the biological clock found in many living organisms. We propose a methodology for period estimation based on spectrum resampling (SR) techniques. Simulation studies show that SR is superior and more robust to non-sinusoidal and noisy cycles than a currently used routine based on Fourier approximations. In addition, a simple fit to the oscillations using linear least squares is available, together with a non-parametric test for detecting changes in period length which allows for period estimates with different variances, as frequently encountered in practice. The proposed methods are motivated by and applied to various data examples from chronobiology. PMID:23743206

Costa, Maria J.; Finkenstädt, Bärbel; Roche, Véronique; Lévi, Francis; Gould, Peter D.; Foreman, Julia; Halliday, Karen; Hall, Anthony; Rand, David A.

2013-01-01

314

21 CFR 870.3630 - Pacemaker generator function analyzer.  

Code of Federal Regulations, 2014 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator...

2014-04-01

315

21 CFR 870.3720 - Pacemaker electrode function tester.  

Code of Federal Regulations, 2011 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3720 Pacemaker electrode function tester. (a) Identification. A pacemaker electrode...

2011-04-01

316

21 CFR 870.3720 - Pacemaker electrode function tester.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3720 Pacemaker electrode function tester. (a) Identification. A pacemaker electrode...

2010-04-01

317

21 CFR 870.3710 - Pacemaker repair or replacement material.  

Code of Federal Regulations, 2011 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3710 Pacemaker repair or replacement material. (a) Identification. A pacemaker repair...

2011-04-01

318

21 CFR 870.3630 - Pacemaker generator function analyzer.  

Code of Federal Regulations, 2013 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3630 Pacemaker generator function analyzer. (a) Identification. A pacemaker generator...

2013-04-01

319

21 CFR 870.3730 - Pacemaker service tools.  

Code of Federal Regulations, 2014 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3730 Pacemaker service tools. (a) Identification. Pacemaker service tools are devices...

2014-04-01

320

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3600 External pacemaker pulse generator. (a) Identification. An external pacemaker...

2010-04-01

321

Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators.  

PubMed

Aging produces a decline in the amplitude and precision of 24 h behavioral, endocrine, and metabolic rhythms, which are regulated in mammals by a central circadian pacemaker within the suprachiasmatic nucleus (SCN) and local oscillators in peripheral tissues. Disruption of the circadian system, as experienced during transmeridian travel, can lead to adverse health consequences, particularly in the elderly. To test the hypothesis that age-related changes in the response to simulated jet lag will reflect altered circadian function, we examined re-entrainment of central and peripheral oscillators from young and old PER2::luciferase mice. As in previous studies, locomotor activity rhythms in older mice required more days to re-entrain following a shift than younger mice. At the tissue level, effects of age on baseline entrainment were evident, with older mice displaying earlier phases for the majority of peripheral oscillators studied and later phases for cells within most SCN subregions. Following a 6 h advance of the light:dark cycle, old mice displayed slower rates of re-entrainment for peripheral tissues but a larger, more rapid SCN response compared to younger mice. Thus, aging alters the circadian timing system in a manner that differentially affects the re-entrainment responses of central and peripheral circadian clocks. This pattern of results suggests that a major consequence of aging is a decrease in pacemaker amplitude, which would slow re-entrainment of peripheral oscillators and reduce SCN resistance to external perturbation. PMID:23152603

Sellix, Michael T; Evans, Jennifer A; Leise, Tanya L; Castanon-Cervantes, Oscar; Hill, DiJon D; DeLisser, Patrick; Block, Gene D; Menaker, Michael; Davidson, Alec J

2012-11-14

322

Combined effects on the circadian clock of agents with different phase response curves: phase-shifting effects of triazolam and light.  

PubMed

Although light provides the primary signal for the entrainment of circadian pacemakers, a number of endogenous substances and pharmacological agents are also capable of resetting circadian pacemakers. Very little is known about the combined effects of photic and nonphotic agents on clock functions. We conducted a "double-pulse" experiment, in which two discrete stimuli are presented at different times within a single circadian cycle, to determine the combined effects of a 1-hr light pulse and injections of a benzodiazepine, triazolam, on the circadian rhythm of activity in the golden hamster. Our results suggest that, first, when given together as done in these experiments, the effects of triazolam and light are partially but not completely additive. Triazolam-induced phase advances appeared to make the effects of subsequent 1-hr light pulses more negative; phase delays were increased, and phase advances were decreased. Second, it appears that triazolam and light may alter the circadian pacemaker in very different ways, beyond the obvious difference in the shape of their phase response curves. The phase-shifting mechanics of the circadian system of the golden hamster appear to involve a longer response time to triazolam than to light pulses. Alternative possibilities to account for this difference are discussed. PMID:1571593

Joy, J E; Turek, F W

1992-01-01

323

Circadian clocks and metabolism.  

PubMed

Circadian clocks maintain periodicity in internal cycles of behavior, physiology, and metabolism, enabling organisms to anticipate the 24-h rotation of the Earth. In mammals, circadian integration of metabolic systems optimizes energy harvesting and utilization across the light/dark cycle. Disruption of clock genes has recently been linked to sleep disorders and to the development of cardiometabolic disease. Conversely, aberrant nutrient signaling affects circadian rhythms of behavior. This chapter reviews the emerging relationship between the molecular clock and metabolic systems and examines evidence that circadian disruption exerts deleterious consequences on human health. PMID:23604478

Marcheva, Biliana; Ramsey, Kathryn M; Peek, Clara B; Affinati, Alison; Maury, Eleonore; Bass, Joseph

2013-01-01

324

Pacemaker interactions induce reentrant wave dynamics in engineered cardiac culture  

NASA Astrophysics Data System (ADS)

Pacemaker interactions can lead to complex wave dynamics seen in certain types of cardiac arrhythmias. We use experimental and mathematical models of pacemakers in heterogeneous excitable media to investigate how pacemaker interactions can be a mechanism for wave break and reentrant wave dynamics. Embryonic chick ventricular cells are cultured invitro so as to create a dominant central pacemaker site that entrains other pacemakers in the medium. Exposure of those cultures to a potassium channel blocker, E-4031, leads to emergence of peripheral pacemakers that compete with each other and with the central pacemaker. Waves emitted by faster pacemakers break up over the slower pacemaker to form reentrant waves. Similar dynamics are observed in a modified FitzHugh-Nagumo model of heterogeneous excitable media with two distinct sites of pacemaking. These findings elucidate a mechanism of pacemaker-induced reentry in excitable media.

Borek, Bart?omiej; Shajahan, T. K.; Gabriels, James; Hodge, Alex; Glass, Leon; Shrier, Alvin

2012-09-01

325

Recent advances of sensors for pacemakers  

Microsoft Academic Search

In this paper, the recent advances of sensors incorporated in pacemakers are presented. Based on the functions and operations of modern pacemakers, a variety of sensors are described with their rationales, features and applications. Further improvements and future trend of body sensors are pointed out. The comparison of the sensors' features is performed.

Wei Vivien Shi; MengChu Zhou

2011-01-01

326

Research on sleep, circadian rhythms and aging - Applications to manned spaceflight  

NASA Technical Reports Server (NTRS)

Disorders of sleep and circadian rhythmicity are characteristic of both advancing age and manned spaceflight. Sleep fragmentation, reduced nocturnal sleep tendency and sleep efficiency, reduced daytime alertness, and increased daytime napping are common to both of these conditions. Recent research on the pathophysiology and treatment of disrupted sleep in older people has led to a better understanding of how the human circadian pacemaker regulates the timing of the daily sleep-wake cycle and how it responds to the periodic changes in the light-dark cycle to which we are ordinarily exposed. These findings have led to new treatments for some of the sleep disorders common to older individuals, using carefully timed exposure to bright light and darkness to manipulate the phase and/or amplitude of the circadian timing system. These insights and treatment approaches have direct applications in the design of countermeasures allowing astronauts to overcome some of the challenges which manned spaceflight poses for the human circadian timing system. We have conducted an operational feasibility study on the use of scheduled exposure to bright light and darkness prior to launch in order to facilitate adaptation of the circadian system of a NASA Space Shuttle crew to the altered sleep-wake schedule required for their mission. The results of this study illustrate how an understanding of the properties of the human circadian timing system and the consequences of circadian disruption can be applied to manned spaceflight.

Czeisler, Charles A.; Chiasera, August J.; Duffy, Jeanne F.

1991-01-01

327

Individual differences in circadian waveform of Siberian hamsters under multiple lighting conditions  

PubMed Central

Because the circadian clock in the mammalian brain derives from a network of interacting cellular oscillators, characterizing the nature and bases of circadian coupling is fundamental to understanding how the pacemaker operates. Various phenomena involving plasticity in circadian waveform have been theorized to reflect changes in oscillator coupling; however, it remains unclear whether these different behavioral paradigms reference a unitary underlying process. To test if disparate coupling assays index a common mechanism, we examined whether there is co-variation among behavioral responses to various lighting conditions that produce changes in circadian waveform. Siberian hamsters, Phodopus sungorus, were transferred from long to short photoperiods to distinguish short photoperiod responders (SP-R) from non-responders (SP-NR). Short photoperiod chronotyped hamsters were subsequently transferred, along with unselected controls, to 24 h light:dark:light:dark cycles (LDLD) with dim nighttime illumination, a procedure that induces bifurcated entrainment. Under LDLD, SP-R hamsters were more likely to bifurcate their rhythms than SP-NR hamsters or unselected controls. After transfer from LDLD to constant dim light, SP-R hamsters were also more likely to become arrhythmic compared to SP-NR hamsters and unselected controls. In contrast, short photoperiod chronotype did not influence more transient changes in circadian waveform. The present data reveal a clear relationship in the plasticity of circadian waveform across three distinct lighting conditions, suggesting a common mechanism wherein individual differences reflect variation in circadian coupling. PMID:23010663

Evans, Jennifer A.; Elliott, Jeffrey A.; Gorman, Michael R.

2013-01-01

328

Circadian rhythms of gastrointestinal function are regulated by both central and peripheral oscillators  

PubMed Central

Circadian clocks are responsible for daily rhythms in a wide array of processes, including gastrointestinal (GI) function. These are vital for normal digestive rhythms and overall health. Previous studies demonstrated circadian clocks within the cells of GI tissue. The present study examines the roles played by the suprachiasmatic nuclei (SCN), master circadian pacemaker for overt circadian rhythms, and the sympathetic nervous system in regulation of circadian GI rhythms in the mouse Mus musculus. Surgical ablation of the SCN abolishes circadian locomotor, feeding, and stool output rhythms when animals are presented with food ad libitum, while restricted feeding reestablishes these rhythms temporarily. In intact mice, chemical sympathectomy with 6-hydroxydopamine has no effect on feeding and locomotor rhythmicity in light-dark cycles or constant darkness but attenuates stool weight and stool number rhythms. Again, however, restricted feeding reestablishes rhythms in locomotor activity, feeding, and stool output rhythms. Ex vivo, intestinal tissue from PER2::LUC transgenic mice expresses circadian rhythms of luciferase bioluminescence. Chemical sympathectomy has little effect on these rhythms, but timed administration of the ?-adrenergic agonist isoproterenol causes a phase-dependent shift in PERIOD2 expression rhythms. Collectively, the data suggest that the SCN are required to maintain feeding, locomotor, and stool output rhythms during ad libitum conditions, acting at least in part through daily activation of sympathetic activity. Even so, this input is not necessary for entrainment to timed feeding, which may be the province of oscillators within the intestines themselves or other components of the GI system. PMID:22723262

Malloy, Jaclyn N.; Paulose, Jiffin K.; Li, Ye

2012-01-01

329

In: Graybiel, A.M. et al., (Eds.) The Basal Ganglia VI, Kluwer Academic Publishers, Norwell, 2002 pp 641-651 Afferent Control of Nigral Dopaminergic Neurons  

E-print Network

of firing. The first is that of pacemaker-like firing, characterized by very regular interspike intervals different firing modes, and the three firing patterns are best thought of as a continuum, with the pacemaker and the random pattern are not seen. Instead, virtually all dopaminergic neurons fire in the pacemaker mode

Tepper, James M.

330

Regulation of jun-B messenger RNA and AP-1 activity by light and a circadian clock.  

PubMed

The suprachiasmatic nuclei (SCN) of the hypothalamus comprise the primary pacemaker responsible for generation of circadian rhythms in mammals. Light stimuli that synchronize this circadian clock induce expression of the c-fos gene in rodent SCN, which suggests a possible role for Fos in circadian entrainment. Appropriate light stimuli also induce the expression of jun-B messenger RNA in the SCN of golden hamsters but only slightly elevate c-jun messenger RNA levels. In addition, light increases the amount of a protein complex in the SCN that binds specifically to sites on DNA known to mediate regulation by the AP-1 transcription factor. The photic regulation of both jun-B messenger RNA expression and AP-1 binding activity is dependent on circadian phase: only light stimuli that shift behavioral rhythms induce jun-B and AP-1 expression. Thus, light and the circadian pacemaker interact to regulate a specific set of immediate-early genes in the SCN that may participate in entrainment of the circadian clock. PMID:1549784

Kornhauser, J M; Nelson, D E; Mayo, K E; Takahashi, J S

1992-03-20

331

Creating a cardiac pacemaker by gene therapy.  

PubMed

While electronic cardiac pacing in its various modalities represents standard of care for treatment of symptomatic bradyarrhythmias and heart failure, it has limitations ranging from absent or rudimentary autonomic modulation to severe complications. This has prompted experimental studies to design and validate a biological pacemaker that could supplement or replace electronic pacemakers. Advances in cardiac gene therapy have resulted in a number of strategies focused on beta-adrenergic receptors as well as specific ion currents that contribute to pacemaker function. This article reviews basic pacemaker physiology, as well as studies in which gene transfer approaches to develop a biological pacemaker have been designed and validated in vivo. Additional requirements and refinements necessary for successful biopacemaker function by gene transfer are discussed. PMID:17139515

Anghel, Traian M; Pogwizd, Steven M

2007-02-01

332

Biological Clocks & Circadian Rhythms  

ERIC Educational Resources Information Center

The study of biological clocks and circadian rhythms is an excellent way to address the inquiry strand in the National Science Education Standards (NSES) (NRC 1996). Students can study these everyday phenomena by designing experiments, gathering and analyzing data, and generating new experiments. As students explore biological clocks and circadian

Robertson, Laura; Jones, M. Gail

2009-01-01

333

Later endogenous circadian temperature nadir relative to an earlier wake time in older people  

NASA Technical Reports Server (NTRS)

The contribution of the circadian timing system to the age-related advance of sleep-wake timing was investigated in two experiments. In a constant routine protocol, we found that the average wake time and endogenous circadian phase of 44 older subjects were earlier than that of 101 young men. However, the earlier circadian phase of the older subjects actually occurred later relative to their habitual wake time than it did in young men. These results indicate that an age-related advance of circadian phase cannot fully account for the high prevalence of early morning awakening in healthy older people. In a second study, 13 older subjects and 10 young men were scheduled to a 28-h day, such that they were scheduled to sleep at many circadian phases. Self-reported awakening from scheduled sleep episodes and cognitive throughput during the second half of the wake episode varied markedly as a function of circadian phase in both groups. The rising phase of both rhythms was advanced in the older subjects, suggesting an age-related change in the circadian regulation of sleep-wake propensity. We hypothesize that under entrained conditions, these age-related changes in the relationship between circadian phase and wake time are likely associated with self-selected light exposure at an earlier circadian phase. This earlier exposure to light could account for the earlier clock hour to which the endogenous circadian pacemaker is entrained in older people and thereby further increase their propensity to awaken at an even earlier time.

Duffy, J. F.; Dijk, D. J.; Klerman, E. B.; Czeisler, C. A.

1998-01-01

334

DsRNA as a stimulator of cell pacemaker activity  

SciTech Connect

The authors study the action of double-stranded RNAs (dsRNA) on the characteristics of neuron pacemaker activity which permits prediction of the character of action of dsRNA on the pacemaker activity of cells and organs, and takes the investigators closer to an understanding of the membrane mechanisms underlying the action of dsRNA on the cell. The methods for isolating and fractionating dsRNA from yeasts and the intracellular recording of the electrical activity of the snail giant neuron have been described by the authors earlier. The authors determined the dependence of Ca/sup 2 +/ entry upon dsRNA concentration using the isotope /sup 45/Ca. Preweighed ganglia were incubated five each for an hour in 2 ml Ringer's solution containing dsRNA and 5 microliters /sup 45/CaCl/sub 2/ of 12.5 mCi activity. After incubation, the ganglia were rinsed three times for 8 min each time in normal Ringers solution. The washed ganglia were dissolved for one day in KOH. The amount of isotope entering was counted using Brav's scintillator and an RGT counter tuned to the /sup 45/Ca isotope. The physiological saline used for the isolated ganglion contained 85 mmole NaCl, 4 mmole KCl, 8 mmole CaCl/sub 2/, 10 mmole MgCl/sub 2/, 10 mmole Tris-HCl, and 5 mmole glucose.

Airapetyan, S.N.; Zakharyan, R.A.; Rychkov, G.E.; Dadalyan, S.S.; Bakunts, I.S.; Agabalyan, A.S.

1986-03-01

335

Serotonin-2C receptor involved serotonin-induced Ca2+ mobilisations in neuronal progenitors and neurons in rat suprachiasmatic nucleus  

PubMed Central

The hypothalamic suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals, undergoes serotonergic regulation, but the underlying mechanisms remain obscure. Here, we generated a subclone of an SCN progenitor cell line expressing Ca2+ sensors (SCN2.2YC) and compared its 5-HT receptor signalling with that of rat SCN neurons in brain slices. SCN2.2YC cells expressed 5-HT1A/2A/2B/2C, but not 5A/7, while all six subtypes were expressed in SCN tissues. High K+ or 5-HT increased cytosolic Ca2+ in SCN2.2YC cells. The 5-HT responses were inhibited by ritanserin and SB-221284, but resistant to WAY-100635 and RS-127445, suggesting predominant involvement of 5-HT2C for Ca2+ mobilisations. Consistently, Ca2+ imaging and voltage-clamp electrophysiology using rat SCN slices demonstrated post-synaptic 5-HT2C expression. Because 5-HT2C expression was postnatally increased in the SCN and 5-HT-induced Ca2+ mobilisations were amplified in differentiated SCN2.2YC cells and developed SCN neurons, we suggest that this signalling development occurs in accordance with central clock maturations. PMID:24531181

Takeuchi, Kouhei; Mohammad, Shahid; Ozaki, Tomoya; Morioka, Eri; Kawaguchi, Kaori; Kim, Juhyon; Jeong, Byeongha; Hong, Jin Hee; Lee, Kyoung J.; Ikeda, Masayuki

2014-01-01

336

Regulation and Synchronization of the Master Circadian Clock by Purinergic Signaling from Suprachiasmatic Nucleus Astrocytes  

E-print Network

in coordinating system-level physiological rhythms that are entrained to environmental light cues. Many of these neurons and glia are individual circadian oscillators, and the cellular mechanisms that couple them into ensemble oscillations are emerging. Adenosine...

Womac, Alisa Diane

2012-10-19

337

Circadian Rhythm Abnormalities  

PubMed Central

Purpose: This article reviews the recent advances in understanding of the fundamental properties of circadian rhythms and discusses the clinical features, diagnosis, and treatment of circadian rhythm sleep disorders (CRSDs). Recent Findings: Recent evidence strongly points to the ubiquitous influence of circadian timing in nearly all physiologic functions. Thus, in addition to the prominent sleep and wake disturbances, circadian rhythm disorders are associated with cognitive impairment, mood disturbances, and increased risk of cardiometabolic disorders. The recent availability of biomarkers of circadian timing in clinical practice has improved our ability to identify and treat these CRSDs. Summary: Circadian rhythms are endogenous rhythms with a periodicity of approximately 24 hours. These rhythms are synchronized to the physical environment by social and work schedules by various photic and nonphotic stimuli. CRSDs result from a misalignment between the timing of the circadian rhythm and the external environment (eg, jet lag and shift work) or a dysfunction of the circadian clock or its afferent and efferent pathways (eg, delayed sleep-phase, advanced sleep-phase, non–24-hour, and irregular sleep-wake rhythm disorders). The most common symptoms of these disorders are difficulties with sleep onset and/or sleep maintenance and excessive sleepiness that are associated with impaired social and occupational functioning. Effective treatment for most of the CRSDs requires a multimodal approach to accelerate circadian realignment with timed exposure to light, avoidance of bright light at inappropriate times, and adherence to scheduled sleep and wake times. In addition, pharmacologic agents are recommended for some of the CRSDs. For delayed sleep-phase, non–24-hour, and shift work disorders, timed low-dose melatonin can help advance or entrain circadian rhythms; and for shift work disorder, wake-enhancing agents such as caffeine, modafinil, and armodafinil are options for the management of excessive sleepiness. PMID:23385698

Zee, Phyllis C.; Attarian, Hrayr; Videnovic, Aleksandar

2013-01-01

338

Pacemakers charging using body energy.  

PubMed

Life-saving medical implants like pacemakers and defibrillators face a big drawback that their batteries eventually run out and patients require frequent surgery to have these batteries replaced. With the advent of technology, alternatives can be provided for such surgeries. To power these devices, body energy harvesting techniques may be employed. Some of the power sources are patient's heartbeat, blood flow inside the vessels, movement of the body parts, and the body temperature (heat). Different types of sensors are employed, such as for sensing the energy from the heartbeat the piezoelectric and semiconducting coupled nanowires are used that convert the mechanical energy into electricity. Similarly, for sensing the blood flow energy, nanogenerators driven by ultrasonic waves are used that have the ability to directly convert the hydraulic energy in human body to electrical energy. Another consideration is to use body heat employing biothermal battery to generate electricity using multiple arrays of thermoelectric generators built into an implantable chip. These generators exploit the well-known thermocouple effect. For the biothermal device to work, it needs a 2°C temperature difference across it. But there are many parts of the body where a temperature difference of 5°C exists - typically in the few millimeters just below the skin, where it is planned to place this device. This study focuses on using body heat as an alternative energy source to recharge pacemaker batteries and other medical devices and prevent the possibility of life-risk during repeated surgery. PMID:21814432

Bhatia, Dinesh; Bairagi, Sweeti; Goel, Sanat; Jangra, Manoj

2010-01-01

339

Persistent Sodium Current, Membrane Properties and Bursting Behavior of Pre-Botzinger Complex Inspiratory Neurons In Vitro  

E-print Network

­2250, 2002; 10.1152/jn.00081.2002. We measured persistent Na current and membrane properties of bursting-pacemaker-generation mechanism in pacemaker neurons of the pre-Bo¨tC, suggest that INaP predominantly influences bursting dynamics of pre-Bo¨tC inspiratory pacemaker neurons in vitro. We also found that the ratio of persistent Na

Del Negro, Christopher A.

340

Pacemaker failure associated with therapeutic radiation  

SciTech Connect

A 48-year-old white man with a multiprogrammable Intramedics 259-01 pacemaker was treated for inoperable lung cancer with a course of cobalt-60 radiotherapy (total 3500 rad). Several weeks subsequent to his last radiation treatment, the patient presented to the emergency department with chest and abdominal pain, shortness of breath, hypotension, and tachycardia. A paced tachycardia was noted, and application of a magnet over the pacemaker completely inhibited its function, allowing a normal sinus rhythm to ensue and the patient's symptoms to be relieved. Pacemaker failure probably was a complication of radiotherapy.

Brooks, C.; Mutter, M.

1988-11-01

341

Pacemaker  

MedlinePLUS

... the signal travels, it causes the heart to contract and pump blood. Each electrical signal normally begins ... two upper chambers, the atria (AY-tree-uh), contract. This contraction pumps blood into the heart's two ...

342

Pacemakers.  

PubMed

Rapid advances in pacing technology will continue to affect the quality of life of many patients with cardiovascular disease. A truly "smart" device that seemed fanciful 30 years ago now seems to be a virtual certainty by early in the next century. The surgical contributions and expertise of individuals trained in cardiothoracic surgery in these bradypacing developments is highly desirable to minimize morbidity to the greatest possible degree, to optimize the outcome of the procedure for the individual patient, and to conserve health care costs as much as possible. To maintain this cardiothoracic presence in cardiac pacing, acquisition of knowledge and expertise in the basic electrophysiology and technology of cardiac pacing, to go along with surgical expertise, is necessary on the part of individuals with the interest and opportunity to do so. PMID:9001543

Ferguson, T B

1997-01-01

343

Regulation of Drosophila circadian rhythms by miRNA let-7 is mediated by a regulatory cycle.  

PubMed

MicroRNA-mediated post-transcriptional regulations are increasingly recognized as important components of the circadian rhythm. Here we identify microRNA let-7, part of the Drosophila let-7-Complex, as a regulator of circadian rhythms mediated by a circadian regulatory cycle. Overexpression of let-7 in clock neurons lengthens circadian period and its deletion attenuates the morning activity peak as well as molecular oscillation. Let-7 regulates the circadian rhythm via repression of CLOCKWORK ORANGE (CWO). Conversely, upregulated cwo in cwo-expressing cells can rescue the phenotype of let-7-Complex overexpression. Moreover, circadian prothoracicotropic hormone (PTTH) and CLOCK-regulated 20-OH ecdysteroid signalling contribute to the circadian expression of let-7 through the 20-OH ecdysteroid receptor. Thus, we find a regulatory cycle involving PTTH, a direct target of CLOCK, and PTTH-driven miRNA let-7. PMID:25417916

Chen, Wenfeng; Liu, Zhenxing; Li, Tianjiao; Zhang, Ruifeng; Xue, Yongbo; Zhong, Yang; Bai, Weiwei; Zhou, Dasen; Zhao, Zhangwu

2014-01-01

344

Persistence of circadian rhythmicity in a mammalian hypothalamic "island" containing the suprachiasmatic nucleus.  

PubMed Central

The experimental work described tested the prosposition that the suprachiasmatic nucleus of the hypothalamus is an autonomous circadian pacemaker. Simultaneous recording from two extracellular electrodes indicated neural (multiple unit) activity at two sites in the brain, one of which is in or near the suprachiasmatic nucleus and the other in one of many other brain locations. Both sites in intact rats displayed clear circadian rhythmicity of spontaneous neural activity. In experimental animals, a Halasz knife was used to create an island of hypothalamic tissue that contained the suprachiasmatic nuclei. In such animals that were also blinded by bilateral ocular enucleation, circadian rhythmicity was lost at all brain locations recorded outside the island, but it persisted within the island that contained the suprachiasmatic nuclei. The rhythmicity of the island is thus not dependent on afferent inputs from elsewhere in the brain. Images PMID:293695

Inouye, S T; Kawamura, H

1979-01-01

345

Resetting of circadian melatonin and cortisol rhythms in humans by ordinary room light  

NASA Technical Reports Server (NTRS)

The present study was designed to investigate whether a weak photic stimulus can reset the endogenous circadian rhythms of plasma melatonin and plasma cortisol in human subjects. A stimulus consisting of three cycles of 5 h exposures to ordinary room light (approximately 180 lux), centered 1.5 h after the endogenous temperature nadir, significantly phase-advanced the plasma melatonin rhythm in eight healthy young men compared with the phase delays observed in eight control subjects who underwent the same protocol but were exposed to darkness (p < or = 0.003). After light-induced phase advances, the circadian rhythms of plasma melatonin and plasma cortisol maintained stable temporal relationships with the endogenous core body temperature cycle, consistent with the conclusion that exposure to ordinary indoor room light had shifted a master circadian pacemaker.

Boivin, D. B.; Czeisler, C. A.

1998-01-01

346

SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging.  

PubMed

SIRT1 is a NAD(+)-dependent protein deacetylase that governs many physiological pathways, including circadian rhythm in peripheral tissues. Here, we show that SIRT1 in the brain governs central circadian control by activating the transcription of the two major circadian regulators, BMAL1 and CLOCK. This activation comprises an amplifying circadian loop involving SIRT1, PGC-1?, and Nampt. In aged wild-type mice, SIRT1 levels in the suprachiasmatic nucleus are decreased, as are those of BMAL1 and PER2, giving rise to a longer intrinsic period, a more disrupted activity pattern, and an inability to adapt to changes in the light entrainment schedule. Young mice lacking brain SIRT1 phenocopy these aging-dependent circadian changes, whereas mice that overexpress SIRT1 in the brain are protected from the effects of aging. Our findings indicate that SIRT1 activates the central pacemaker to maintain robust circadian control in young animals, and a decay in this activity may play an important role in aging. PMID:23791176

Chang, Hung-Chun; Guarente, Leonard

2013-06-20

347

Mangalith: a new lithium pacemaker battery  

SciTech Connect

An original lithium battery system is being developed for pacemaker application. The material used, lithium-manganese dioxide, industrially available at the present time for a variety of electronic applications, has been modified and adapted for pacemaker power requirements. The utilization of a different modification of manganese dioxide offers performance advantages. The cell technology is described and performance comparisons between this new cathode material and the industrial counterpart are reported. 7 refs.

Gerbier, G.; Lehmann, G.

1980-01-01

348

The Evolution of Pacemakers: An Electronics Perspective  

Microsoft Academic Search

A brief overview of the history and development of circuit designs applied in cardiac pacemakers is presented in Chapter 2.\\u000a The advances in integrated circuit designs have resulted in, for instance, diagnostic analysis, adaptive rate response and\\u000a programmability. Also, based on future trends for pacemakers, some features and improvements for modern cardiac sensing systems\\u000a are described and we point out

Sandro A. P. Haddad; Wouter A. Serdijn

349

Creating a Cardiac Pacemaker by Gene Therapy  

Microsoft Academic Search

While electronic cardiac pacing in its various modalities represents standard of care for treatment of symptomatic bradyarrhythmias\\u000a and heart failure, it has limitations ranging from absent or rudimentary autonomic modulation to severe complications. This\\u000a has prompted experimental studies to design and validate a biological pacemaker that could supplement or replace electronic\\u000a pacemakers. Advances in cardiac gene therapy have resulted in

Traian M. Anghel; Steven M. Pogwizd

350

Creating a cardiac pacemaker by gene therapy  

Microsoft Academic Search

While electronic cardiac pacing in its various modalities represents standard of care for treatment of symptomatic bradyarrhythmias\\u000a and heart failure, it has limitations ranging from absent or rudimentary autonomic modulation to severe complications. This\\u000a has prompted experimental studies to design and validate a biological pacemaker that could supplement or replace electronic\\u000a pacemakers. Advances in cardiac gene therapy have resulted in

Traian M. Anghel; Steven M. Pogwizd

2007-01-01

351

Mathematical Models of Cardiac Pacemaking Function  

NASA Astrophysics Data System (ADS)

Over the past half century, there has been intense and fruitful interaction between experimental and computational investigations of cardiac function. This interaction has, for example, led to deep understanding of cardiac excitation-contraction coupling; how it works, as well as how it fails. However, many lines of inquiry remain unresolved, among them the initiation of each heartbeat. The sinoatrial node, a cluster of specialized pacemaking cells in the right atrium of the heart, spontaneously generates an electro-chemical wave that spreads through the atria and through the cardiac conduction system to the ventricles, initiating the contraction of cardiac muscle essential for pumping blood to the body. Despite the fundamental importance of this primary pacemaker, this process is still not fully understood, and ionic mechanisms underlying cardiac pacemaking function are currently under heated debate. Several mathematical models of sinoatrial node cell membrane electrophysiology have been constructed as based on different experimental data sets and hypotheses. As could be expected, these differing models offer diverse predictions about cardiac pacemaking activities. This paper aims to present the current state of debate over the origins of the pacemaking function of the sinoatrial node. Here, we will specifically review the state-of-the-art of cardiac pacemaker modeling, with a special emphasis on current discrepancies, limitations, and future challenges.

Li, Pan; Lines, Glenn T.; Maleckar, Mary M.; Tveito, Aslak

2013-10-01

352

Pigment dispersing hormone modulates spontaneous electrical activity of the cerebroid ganglion and synchronizes electroretinogram circadian rhythm in crayfish Procambarus clarkii.  

PubMed

In crayfish, one very well-studied circadian rhythm is that of electroretinogram (ERG) amplitude. The cerebroid ganglion has been considered a plausible site for the circadian pacemaker of this rhythm and for the retinular photoreceptors, as the corresponding effectors. The pigment dispersing hormone (PDH) appears to synchronize ERG rhythm, but its characterization as a synchronizer cue remains incomplete. The main purposes of this work were a) to determine whether PDH acts on the cerebroid ganglion, and b) to complete its characterization as a non-photic synchronizer. Here we show that PDH increases the number of the spontaneous potentials of the cerebroid ganglion, reaching 149.92±6.42% of the activity recorded in the controls, and that daily application of PDH for 15 consecutive days adjusts the ERG circadian rhythm period to 24.0±0.2h and the end of the activity period of the rhythm coincides with the injection of the hormone. In this work, we hypothesized that in crayfish, PDH transmits the "day" signal to the ERG circadian system and acts upon both the presumptive circadian pacemaker and the corresponding effectors to reinforce the synchronization of the system. PMID:22252127

Solís-Chagoyán, Héctor; Alvarado, Ramón; Figueroa, Alejandra; Mendoza-Vargas, Leonor; Fuentes-Pardo, Beatriz

2012-04-01

353

Circadian Rhythms in the Mouse: A Connections Map  

NSDL National Science Digital Library

Genetic and biochemical experiments over the past decade have facilitated the construction of a viable working model for the molecular mechanisms that generate the circadian rhythm in Mus musculus. The basic mechanism consists of two intertwined transcription-translation negative feedback loops. One, the "positive loop," controls the rhythmic expression of a Per-Arnt-Sim (PAS)-domain-containing positive transcription factor, BMAL1 (also called MOP3). The other, the "negative loop," controls the transcription of mPeriod 1 and 2 and mCryptochrome 1 and 2, two families of genes that encode repressor proteins. The loops are intertwined because the proteins mPeriod and mCryptochrome directly repress transcription mediated by the CLOCK:BMAL1 heterodimer, whereas CLOCK:BMAL1 drives transcription of the mPeriod and mCryptochrome genes, as well as that of Rev-erb-alpha, a repressor of Bmal1 expression. Mutations, including the tau mutation in hamsters [encoding Casein kinase I ε (CkIε)], have identified essential functions for other proteins in the timekeeping mechanism. The master pacemaker for circadian rhythms in mice is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. Light cycles can synchronize molecular rhythms in the SCN by stimulating the release of glutamate and the neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) from melanopsin-containing retinal ganglion cells. This results in increased transcription of mPeriod genes and a shift in the phase of the clock. This Pathway Map of the murine circadian mechanism describes the individual known components of the mouse circadian clock and their mutual interactions. Science Viewpoint R. N. Van Gelder, E. D. Herzog, W. J. Schwartz, P. H. Taghert, Circadian rhythms: In the loop at last. Science 300, 1534-1535 (2003). [Abstract] [Full Text

Russell N. Van Gelder (Washington University Medical School; Department of Molecular Biology and Pharmacology REV)

2003-08-05

354

Modeling circadian and sleep-homeostatic effects on short-term interval timing  

PubMed Central

Short-term interval timing i.e., perception and action relating to durations in the seconds range, has been suggested to display time-of-day as well as wake dependent fluctuations due to circadian and sleep-homeostatic changes to the rate at which an underlying pacemaker emits pulses; pertinent human data being relatively sparse and lacking in consistency however, the phenomenon remains elusive and its mechanism poorly understood. To better characterize the putative circadian and sleep-homeostatic effects on interval timing and to assess the ability of a pacemaker-based mechanism to account for the data, we measured timing performance in eighteen young healthy male subjects across two epochs of sustained wakefulness of 38.67 h each, conducted prior to (under entrained conditions) and following (under free-running conditions) a 28 h sleep-wake schedule, using the methods of duration estimation and duration production on target intervals of 10 and 40 s. Our findings of opposing oscillatory time courses across both epochs of sustained wakefulness that combine with increasing and, respectively, decreasing, saturating exponential change for the tasks of estimation and production are consistent with the hypothesis that a pacemaker emitting pulses at a rate controlled by the circadian oscillator and increasing with time awake determines human short-term interval timing; the duration-specificity of this pattern is interpreted as reflecting challenges to maintaining stable attention to the task that progressively increase with stimulus magnitude and thereby moderate the effects of pacemaker-rate changes on overt behavior. PMID:25741253

Späti, Jakub; Aritake, Sayaka; Meyer, Andrea H.; Kitamura, Shingo; Hida, Akiko; Higuchi, Shigekazu; Moriguchi, Yoshiya; Mishima, Kazuo

2015-01-01

355

CHAPTER SEVEN Circadian Rhythms, Sleep  

E-print Network

CHAPTER SEVEN Circadian Rhythms, Sleep Deprivation, and Human Performance Namni Goel*, Mathias, Philadelphia, Pennsylvania, USA Contents 1. Introduction 156 2. Sleep­Wake and Circadian Regulation: Two-Process Model 157 3. Circadian Rhythms of Performance 162 3.1 Subjective measures of sleepiness and alertness

Pennsylvania, University of

356

Circadian Timing in Cancer Treatments  

E-print Network

Circadian Timing in Cancer Treatments Francis L´evi,1,2,3 Alper Okyar,1,4 Sandrine Dulong,1, systems biology, personalized medicine Abstract The circadian timing system is composed of molecular repair, apoptosis, and angiogenesis. The cellular circadian clocks are coordinated by endogenous

Clairambault, Jean

357

Dim light melatonin onset (DLMO): A tool for the analysis of circadian phase in human sleep and chronobiological disorders  

Microsoft Academic Search

The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6-sulphatoxymelatonin (aMT6S) in urine, is a defining feature of suprachiasmatic nucleus (SCN) function, the endogenous oscillatory pacemaker. A substantial number of studies have shown that, within this rhythmic profile, the onset of melatonin secretion under dim light conditions (the dim light melatonin onset or DLMO) is

Seithikurippu R. Pandi-Perumal; Marcel Smits; Warren Spence; Venkataramanujan Srinivasan; Daniel P. Cardinali; Alan D. Lowe; Leonid Kayumov

2007-01-01

358

Role of membrane conductances and protein synthesis in subjective day phase advances of the hamster circadian clock by neuropeptide Y.  

PubMed

Neurons of the mammalian circadian pacemaker in the hypothalamic suprachiasmatic nuclei exhibit a rhythm in firing rate that can be reset by neuropeptide Y. We recorded the effects of neuropeptide Y on Na+ and K+ conductances of hamster suprachiasmatic nuclei neurons using whole-cell, perforated-patch and cell-attached patch-clamp recordings, both in dissociated and brain slice preparations. While neuropeptide Y had no effect on voltage-gated Na+ currents, neuropeptide Y activated a leak K+ current. Neuropeptide Y phase advances in the suprachiasmatic nuclei brain slice preparation were blocked by a number of K+ channel blockers (tetraethylammonium chloride, dendrotoxin-I, glybenclamide). However, a K+ ionophore, valinomycin, did not shift the rhythm. The inhibition by tetraethylammonium chloride did not persist in the presence of glutamatergic receptor blockers. We have previously shown that glutamate can oppose neuropeptide Y phase-shifting actions, suggesting that K+ channel inhibition acts by inducing glutamate release. Protein synthesis inhibitors had no effect on clock phase when applied during the subjective day, and had no influence on neuropeptide Y-induced phase shifts. On the other hand, glutamate's ability to inhibit neuropeptide Y shifts was abolished by protein synthesis inhibition. Thus, while neuropeptide Y phase shifts do not require protein synthesis, glutamate blocks neuropeptide Y shifts via increased gene expression during the subjective day, at a time when it does not reset the clock. These results indicate that neuropeptide Y phase shifts via a mechanism that does not involve changes in membrane conductance or protein synthesis. PMID:10564350

Hall, A C; Earle-Cruikshanks, G; Harrington, M E

1999-10-01

359

Influence of gravity on the circadian timing system  

NASA Technical Reports Server (NTRS)

The circadian timing system (CTS) is responsible for daily temporal coordination of physiological and behavioral functions both internally and with the external environment. Experiments in altered gravitational environments have revealed changes in circadian rhythms of species ranging from fungi to primates. The altered gravitational environments examined included both the microgravity environment of spaceflight and hyperdynamic environments produced by centrifugation. Acute exposure to altered gravitational environments changed homeostatic parameters such as body temperature. These changes were time of day dependent. Exposure to gravitational alterations of relatively short duration produced changes in both the homeostatic level and the amplitude of circadian rhythms. Chronic exposure to a non-earth level of gravity resulted in changes in the period of the expressed rhythms as well as in the phase relationships between the rhythms and between the rhythms and the external environment. In addition, alterations in gravity appeared to act as a time cue for the CTS. Altered gravity also affected the sensitivity of the pacemaker to other aspects of the environment (i.e., light) and to shifts of time cues. Taken together, these studies lead to the conclusion that the CTS is indeed sensitive to gravity and its alterations. This finding has implications for both basic biology and space medicine.

Fuller, C. A.; Hoban-Higgins, T. M.; Griffin, D. W.; Murakami, D. M.

1994-01-01

360

Separation of circadian and wake duration-dependent modulation of EEG activation during wakefulness  

NASA Technical Reports Server (NTRS)

The separate contribution of circadian rhythmicity and elapsed time awake on electroencephalographic (EEG) activity during wakefulness was assessed. Seven men lived in an environmental scheduling facility for 4 weeks and completed fourteen 42.85-h 'days', each consisting of an extended (28.57-h) wake episode and a 14.28-h sleep opportunity. The circadian rhythm of plasma melatonin desynchronized from the 42.85-h day. This allowed quantification of the separate contribution of circadian phase and elapsed time awake to variation in EEG power spectra (1-32 Hz). EEG activity during standardized behavioral conditions was markedly affected by both circadian phase and elapsed time awake in an EEG frequency- and derivation-specific manner. The nadir of the circadian rhythm in alpha (8-12 Hz) activity in both fronto-central and occipito-parietal derivations occurred during the biological night, close to the crest of the melatonin rhythm. The nadir of the circadian rhythm of theta (4.5-8 Hz) and beta (20-32 Hz) activity in the fronto-central derivation was located close to the onset of melatonin secretion, i.e. during the wake maintenance zone. As time awake progressed, delta frequency (1-4.5 Hz) and beta (20-32 Hz) activity rose monotonically in frontal derivations. The interaction between the circadian and wake-dependent increase in frontal delta was such that the intrusion of delta was minimal when sustained wakefulness coincided with the biological day, but pronounced during the biological night. Our data imply that the circadian pacemaker facilitates frontal EEG activation during the wake maintenance zone, by generating an arousal signal that prevents the intrusion of low-frequency EEG components, the propensity for which increases progressively during wakefulness.

Cajochen, C.; Wyatt, J. K.; Czeisler, C. A.; Dijk, D. J.

2002-01-01

361

An Autonomous Circadian Clock in the Inner Mouse Retina Regulated by Dopamine and GABA  

PubMed Central

The influence of the mammalian retinal circadian clock on retinal physiology and function is widely recognized, yet the cellular elements and neural regulation of retinal circadian pacemaking remain unclear due to the challenge of long-term culture of adult mammalian retina and the lack of an ideal experimental measure of the retinal circadian clock. In the current study, we developed a protocol for long-term culture of intact mouse retinas, which allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC) clock gene reporter. With this in vitro assay, we studied the characteristics and location within the retina of circadian PER2::LUC rhythms, the influence of major retinal neurotransmitters, and the resetting of the retinal circadian clock by light. Retinal PER2::LUC rhythms were routinely measured from whole-mount retinal explants for 10 d and for up to 30 d. Imaging of vertical retinal slices demonstrated that the rhythmic luminescence signals were concentrated in the inner nuclear layer. Interruption of cell communication via the major neurotransmitter systems of photoreceptors and ganglion cells (melatonin and glutamate) and the inner nuclear layer (dopamine, acetylcholine, GABA, glycine, and glutamate) did not disrupt generation of retinal circadian PER2::LUC rhythms, nor did interruption of intercellular communication through sodium-dependent action potentials or connexin 36 (cx36)-containing gap junctions, indicating that PER2::LUC rhythms generation in the inner nuclear layer is likely cell autonomous. However, dopamine, acting through D1 receptors, and GABA, acting through membrane hyperpolarization and casein kinase, set the phase and amplitude of retinal PER2::LUC rhythms, respectively. Light pulses reset the phase of the in vitro retinal oscillator and dopamine D1 receptor antagonists attenuated these phase shifts. Thus, dopamine and GABA act at the molecular level of PER proteins to play key roles in the organization of the retinal circadian clock. PMID:18959477

Ruan, Guo-Xiang; Allen, Gregg C; Yamazaki, Shin; McMahon, Douglas G

2008-01-01

362

The human circadian metabolome  

PubMed Central

The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest–activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that ?15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure. PMID:22308371

Dallmann, Robert; Viola, Antoine U.; Tarokh, Leila; Cajochen, Christian; Brown, Steven A.

2012-01-01

363

Socially synchronized circadian oscillators  

PubMed Central

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. PMID:23825203

Bloch, Guy; Herzog, Erik D.; Levine, Joel D.; Schwartz, William J.

2013-01-01

364

Light evokes rapid circadian network oscillator desynchrony followed by gradual phase retuning of synchrony.  

PubMed

Circadian neural circuits generate near 24-hr physiological rhythms that can be entrained by light to coordinate animal physiology with daily solar cycles. To examine how a circadian circuit reorganizes its activity in response to light, we imaged period (per) clock gene cycling for up to 6 days at single-neuron resolution in whole-brain explant cultures prepared from per-luciferase transgenic flies. We compared cultures subjected to a phase-advancing light pulse (LP) to cultures maintained in darkness (DD). In DD, individual neuronal oscillators in all circadian subgroups are initially well synchronized but then show monotonic decrease in oscillator rhythm amplitude and synchrony with time. The small ventral lateral neurons (s-LNvs) and dorsal lateral neurons (LNds) exhibit this decrease at a slower relative rate. In contrast, the LP evokes a rapid loss of oscillator synchrony between and within most circadian neuronal subgroups, followed by gradual phase retuning of whole-circuit oscillator synchrony. The LNds maintain high rhythmic amplitude and synchrony following the LP along with the most rapid coherent phase advance. Immunocytochemical analysis of PER shows that these dynamics in DD and LP are recapitulated in vivo. Anatomically distinct circadian neuronal subgroups vary in their response to the LP, showing differences in the degree and kinetics of their loss, recovery and/or strengthening of synchrony, and rhythmicity. Transient desynchrony appears to be an integral feature of light response of the Drosophila multicellular circadian clock. Individual oscillators in different neuronal subgroups of the circadian circuit show distinct kinetic signatures of light response and phase retuning. PMID:25754644

Roberts, Logan; Leise, Tanya L; Noguchi, Takako; Galschiodt, Alexis M; Houl, Jerry H; Welsh, David K; Holmes, Todd C

2015-03-30

365

21 CFR 870.3650 - Pacemaker polymeric mesh bag.  

Code of Federal Regulations, 2013 CFR

... MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. ...pacemaker pulse generator. The bag is designed to create a stable implant environment for the pulse generator. (b)...

2013-04-01

366

21 CFR 870.3650 - Pacemaker polymeric mesh bag.  

Code of Federal Regulations, 2011 CFR

... MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. ...pacemaker pulse generator. The bag is designed to create a stable implant environment for the pulse generator. (b)...

2011-04-01

367

21 CFR 870.3650 - Pacemaker polymeric mesh bag.  

Code of Federal Regulations, 2012 CFR

... MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. ...pacemaker pulse generator. The bag is designed to create a stable implant environment for the pulse generator. (b)...

2012-04-01

368

21 CFR 870.5550 - External transcutaneous cardiac pacemaker (noninvasive).  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false External transcutaneous cardiac pacemaker (noninvasive...Therapeutic Devices § 870.5550 External transcutaneous cardiac pacemaker (noninvasive). (a) Identification. An external transcutaneous cardiac...

2010-04-01

369

21 CFR 870.3690 - Pacemaker test magnet.  

Code of Federal Regulations, 2014 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used...

2014-04-01

370

21 CFR 870.3620 - Pacemaker lead adaptor.  

Code of Federal Regulations, 2014 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device...

2014-04-01

371

21 CFR 870.3620 - Pacemaker lead adaptor.  

Code of Federal Regulations, 2013 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device...

2013-04-01

372

21 CFR 870.3650 - Pacemaker polymeric mesh bag.  

Code of Federal Regulations, 2014 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. (a) Identification. A pacemaker polymeric mesh bag is...

2014-04-01

373

21 CFR 870.3650 - Pacemaker polymeric mesh bag.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3650 Pacemaker polymeric mesh bag. (a) Identification. A pacemaker polymeric mesh bag is...

2010-04-01

374

21 CFR 870.3690 - Pacemaker test magnet.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3690 Pacemaker test magnet. (a) Identification. A pacemaker test magnet is a device used...

2010-04-01

375

Interactions Between Cognition and Circadian Rhythms: Attentional Demands Modify Circadian Entrainment  

E-print Network

Interactions Between Cognition and Circadian Rhythms: Attentional Demands Modify Circadian to changes in activity patterns during the rest of the circadian cycle. Here the authors demonstrate modification in the animals' activity throughout the entire circadian cycle. In particular, normally nocturnal

Lee, Theresa

376

Selective interference with pacemaker activity by electrical dental devices  

Microsoft Academic Search

Objective. We sought to determine whether electromagnetic interference with cardiac pacemakers occurs during the operation of contemporary electrical dental equipment.Study Design. Fourteen electrical dental devices were tested in vitro for their ability to interfere with the function of two Medtronics cardiac pacemakers (one a dual-chamber, bipolar Thera 7942 pacemaker, the other a single-chamber, unipolar Minix 8340 pacemaker). Atrial and ventricular

Craig S Miller; Fabio M Leonelli; Emma Latham

1998-01-01

377

Acute Suppressive and Long-Term Phase Modulation Actions of Orexin on the Mammalian Circadian Clock  

PubMed Central

Circadian and homeostatic neural circuits organize the temporal architecture of physiology and behavior, but knowledge of their interactions is imperfect. For example, neurons containing the neuropeptide orexin homeostatically control arousal and appetitive states, while neurons in the suprachiasmatic nuclei (SCN) function as the brain's master circadian clock. The SCN regulates orexin neurons so that they are much more active during the circadian night than the circadian day, but it is unclear whether the orexin neurons reciprocally regulate the SCN clock. Here we show both orexinergic innervation and expression of genes encoding orexin receptors (OX1 and OX2) in the mouse SCN, with OX1 being upregulated at dusk. Remarkably, we find through in vitro physiological recordings that orexin predominantly suppresses mouse SCN Period1 (Per1)-EGFP-expressing clock cells. The mechanisms underpinning these suppressions vary across the circadian cycle, from presynaptic modulation of inhibitory GABAergic signaling during the day to directly activating leak K+ currents at night. Orexin also augments the SCN clock-resetting effects of neuropeptide Y (NPY), another neurochemical correlate of arousal, and potentiates NPY's inhibition of SCN Per1-EGFP cells. These results build on emerging literature that challenge the widely held view that orexin signaling is exclusively excitatory and suggest new mechanisms for avoiding conflicts between circadian clock signals and homeostatic cues in the brain. PMID:24599460

Belle, Mino D.C.; Hughes, Alun T.L.; Bechtold, David A.; Cunningham, Peter; Pierucci, Massimo; Burdakov, Denis

2014-01-01

378

Measuring stem cell circadian rhythm.  

PubMed

Circadian rhythms are biological rhythms that occur within a 24-h time cycle. Sleep is a prime example of a circadian rhythm and with it melatonin production. Stem cell systems also demonstrate circadian rhythms. This is particularly the case for the proliferating cells within the system. In fact, all proliferating cell populations exhibit their own circadian rhythm, which has important implications for disease and the treatment of disease. Stem cell chronobiology is particularly important because the treatment of cancer can be significantly affected by the time of day a drug is administered. This protocol provides a basis for measuring hematopoietic stem cell circadian rhythm for future stem cell chronotherapeutic applications. PMID:25388388

Hrushesky, William; Rich, Ivan N

2015-01-01

379

Circadian Rhythm Sleep Disorders  

PubMed Central

Objective To review circadian rhythm sleep disorders, including underlying causes, diagnostic considerations, and typical treatments. Methods Literature review and discussion of specific cases. Results Survey studies 1,2 suggest that up to 3% of the adult population suffers from a circadian rhythm sleep disorder (CRSD). However, these sleep disorders are often confused with insomnia, and an estimated 10% of adult and 16% of adolescent sleep disorders patients may have a CRSD 3-6. While some CRSD (such as jet lag) can be self-limiting, others when untreated can lead to adverse medical, psychological, and social consequences. The International Classification of Sleep Disorders classifies CRSD as dyssomnias, with six subtypes: Advanced Sleep Phase Type, Delayed Sleep Phase Type, Irregular Sleep Wake Type, Free Running Type, Jet Lag Type, and Shift Work Type. The primary clinical characteristic of all CRSD is an inability to fall asleep and wake at the desired time. It is believed that CRSD arise from a problem with the internal biological clock (circadian timing system) and/or misalignment between the circadian timing system and the external 24-hour environment. This misalignment can be the result of biological and/or behavioral factors. CRSD can be confused with other sleep or medical disorders. Conclusions Circadian rhythm sleep disorders are a distinct class of sleep disorders characterized by a mismatch between the desired timing of sleep and the ability to fall asleep and remain asleep. If untreated, CRSD can lead to insomnia and excessive daytime sleepiness, with negative medical, psychological, and social consequences. It is important for physicians to recognize potential circadian rhythm sleep disorders so that appropriate diagnosis, treatment, and referral can be made. PMID:25368503

Kim, Min Ju; Lee, Jung Hie; Duffy, Jeanne F.

2014-01-01

380

Resonance Pacemakers in Excitable Media Tabitha Ruvarashe Chigwada,1  

E-print Network

Resonance Pacemakers in Excitable Media Tabitha Ruvarashe Chigwada,1 P. Parmananda,2,3 and Kenneth oscillatory region that serves as a pacemaker, emitting successive waves into the medium. In the Belousov adsorption of bromide (or bromine) is responsible for the spontaneous pacemakers at hetero- geneities

Showalter, Kenneth

381

background Na+ conductance in pacemaking activity is unproven,  

E-print Network

background Na+ conductance in pacemaking activity is unproven, only the hasty would suggest that it is unlikely. Arrested pacemaker cells have membrane potentials of -35mY: some outward current must flow the membranes of arrested pacemaker cells whereas vagal stimulation does7. In beat- ing hearts vagal stimulation

Apkarian, A. Vania

382

Autonomic control and innervation of the atrioventricular junctional pacemaker  

E-print Network

Autonomic control and innervation of the atrioventricular junctional pacemaker William J. Hucker junction may be- come the pacemaker of the heart. Unlike the well-characterized sinoatrial node (SAN), autonomic control of the AV junctional pacemaker has not been studied. OBJECTIVE The purpose of this study

383

How Genetic Algorithms Can Improve a Pacemaker Effciency  

E-print Network

How Genetic Algorithms Can Improve a Pacemaker Effciency Laurent Dumas Laboratoire Jacques In this paper, we propose the use of Genetic Algorithms as a tool for improving a pacemaker efficiency induced in the sinus node, the natural pacemaker, then propagates through the atria and reaches

Dumas, Laurent

384

Functional Imaging of the Embryonic Pacemaking and Cardiac Conduction  

E-print Network

Functional Imaging of the Embryonic Pacemaking and Cardiac Conduction System Over the Past 150 ABSTRACT Early analyses of cardiac pacemaking and conduction system (CPCS) development relied on classic Ebbe et al., 1939). The events guiding the formation of a normal cardiac pacemaking and conduction

385

Automated Verification of Quantitative Properties of Cardiac Pacemaker Software  

E-print Network

Automated Verification of Quantitative Properties of Cardiac Pacemaker Software Marta Kwiatkowska that is suitable for quantitative verification of pacemakers. The heart model is formulated at the level of cardiac, such as cardiac pacemakers [6], GPCA infusion pumps [8] and continuous glucose monitors [11], are stochastic

Oxford, University of

386

Complications of Dual Chamber Pacemaker Implantation in the Elderly  

Microsoft Academic Search

Pacemakers are frequently implanted, yet accurate prospective data on implant complications are limited. Elderly patients may be at increased risk of implant complications and are increasingly being referred for pacemaker implantation. The purpose of the present analysis was to define the incidence and possible predictors of serious complications of dual chamber permanent pacemaker implantation in the elderly. Therefore, we sought

Mark S. Link; N. A. Mark Estes III; John J. Griffin; Paul J. Wang; James D. Maloney; James B. Kirchhoffer; Gary F. Mitchell; John Orav; Lee Goldman; Gervasio A. Lamas

1998-01-01

387

On Quantitative Software Quality Assurance Methodologies for Cardiac Pacemakers  

E-print Network

On Quantitative Software Quality Assurance Methodologies for Cardiac Pacemakers Marta Kwiatkowska. Embedded software is at the heart of implantable medical de- vices such as cardiac pacemakers, and rigorous-based design; quantitative verification; hybrid au- tomata; heart modelling; cardiac pacemakers. 1 Introduction

Oxford, University of

388

Myopotential inhibition of unipolar lithium pacemakers.  

PubMed

The effect of isometric upper extremity exercise on pacemaker function was evaluated in 27 patients who remained pacemaker-dependent during testing. Inhibition was demonstrated in eight (31 percent) of which five were symptomatic. Based on design of the sensing amplifier and return to an all-metal housing in the unipolar lithium pulse generators, myopotential inhibition is being recognized as one cause of symptomatic pacemaker inhibition that is more common than generally appreciated. A method of evaluation and management options for symptomatic patients are discussed. Routine testing of all patients should be performed at the time of a regular office evaluation. If one model pulse generator appears to be particularly prone to myopotential inhibition, this knowledge should be considered in the choice of future pacing systems. PMID:7116965

Levine, P A; Caplan, C H; Klein, M D; Brodsky, S J; Ryan, T J

1982-10-01

389

How does calcium-dependent intracellular regulation of voltage-dependent sodium current increase the sensitivity to the oxadiazine insecticide indoxacarb metabolite decarbomethoxylated JW062 (DCJW) in insect pacemaker neurons?  

PubMed

Decarbomethoxylated JW062 (DCJW), the active component of the oxadiazine insecticide (S)-methyl 7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-(trifluoromethoxy)phenyl] amino]carbonyl] indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate (DPX-JW062) (indoxacarb), was tested on 2 inward voltage-dependent sodium currents (named INa1 and INa2) expressed in short-term cultured dorsal unpaired median neurons of the cockroach Periplaneta americana. Under whole-cell voltage-clamp conditions, application of DCJW resulted in a biphasic dose-dependent inhibition of the global sodium current amplitude illustrating the differing sensitivity of sodium channels to DCJW. INa2 was less sensitive to DCJW [half-maximal inhibitory concentration (IC(50)) = 1.6 microM] compared with INa1 (IC(50) = 1.7 nM). Although a previous study demonstrated that INa1 was regulated by the cAMP/protein kinase A cascade, we showed that INa2 was mainly regulated in an opposite way by the activation of calcium-calmodulin-dependent protein phosphatase 2B (PP2B) and calcium-calmodulin-dependent protein kinase II (CaM-kinase II). Furthermore, we demonstrated that activation of CaM-kinase II by intracellular calcium via the calcium-calmodulin complex affected the sensitivity of INa2 channels to DCJW. By increasing the intracellular calcium concentration and/or using 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) (a calcium chelator), N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7) (a calmodulin inhibitor), cyclosporine A (a PP2B inhibitor), and 1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine (KN-62) (a CaM-kinase II inhibitor), we revealed that activation of CaM-kinase II was involved in the modulation of the voltage dependence of steady-state inactivation and that the CaM-kinase II pathway activated by elevation of the intracellular calcium concentration might render INa2 channels approximately 3000-fold more sensitive to DCJW. These results indicated that manipulating specific intracellular signaling pathways involved in the regulation of sodium channels might have fundamental consequences for the sensitivity of insects to insecticides. This finding reveals an exciting research area that could lead to improvement in the efficiency of insecticides. PMID:20056780

Lavialle-Defaix, Céline; Moignot, Bénédicte; Legros, Christian; Lapied, Bruno

2010-04-01

390

Cellular and molecular mechanisms that regulate olfactory rhythms in drosophila melanogaster  

E-print Network

techniques, were used to investigate the extent of autonomy of peripheral oscillators from central pacemaker cells, the molecular targets of the circadian oscillator in antennal neurons, and the nature of circadian influence on single unit responses recorded...

Krishnan, Parthasarathy

2009-05-15

391

Circadian Rhythms of PER2::LUC in Individual Primary Mouse Hepatocytes and Cultures  

PubMed Central

Background Hepatocytes, the parenchymal cells of the liver, express core clock genes, such as Period2 and Cryptochrome2, which are involved in the transcriptional/translational feedback loop of the circadian clock. Whether or not the liver is capable of sustaining rhythms independent of a central pacemaker is controversial. Whether and how circadian information may be shared among cells in the liver in order to sustain oscillations is currently unknown. Results In this study we isolated primary hepatocytes from transgenic Per2Luc mice and used bioluminescence as a read-out of the state of the circadian clock. Hepatocytes cultured in a collagen gel sandwich configuration exhibited persistent circadian rhythms for several weeks. The amplitude of the rhythms damped, but medium changes consistently reset the phase and amplitude of the cultures. Cry2?/? Per2Luc cells oscillated robustly and expressed a longer period. Co-culturing with wildtype cells did not significantly shorten the period, indicating that coupling among hepatocytes is insufficient to synchronize cells with significantly differing periods. However, spatial patterns revealed by cellular imaging of wildtype cultures provided evidence of weak local coupling among the hepatocytes. Conclusions Our results with primary hepatocyte cultures demonstrate that cultured hepatocytes are weakly coupled. While this coupling is not sufficient to sustain global synchrony, it does increase local synchrony, which may stabilize the circadian rhythms of peripheral oscillators, such as the liver, against noise in the entraining signals. PMID:24498336

Molyneux, Penny C.; Yu, Jimmy K.; Li, Alexander S.; Leise, Tanya L.; Harrington, Mary E.

2014-01-01

392

Circadian Rhythms of Glucocorticoid Hormone Actions in Target Tissues: Potential Clinical Implications  

NSDL National Science Digital Library

Organisms face unforeseen short- and long-term changes in the environment (stressors). To defend against these changes, organisms have developed a stress system that includes the hypothalamic-pituitary-adrenal (HPA) axis, which employs glucocorticoids and the glucocorticoid receptor (GR) for signal transduction. In addition, organisms live under the strong influence of day-night cycles and, hence, have also developed a highly conserved circadian clock system for adjusting their activities to recurring environmental changes. This regulatory system creates and maintains internal circadian rhythmicity by employing a self-oscillating molecular pacemaker composed of the Clock-Bmal1 heterodimer and other transcription factors. The circadian clock consists of a central master clock in the suprachiasmatic nucleus of the brain hypothalamus and peripheral slave clocks in virtually all organs and tissues. The HPA axis and the circadian clock system communicate with each other at multiple levels. The central clock controls the HPA axis, creating the diurnal oscillation of circulating adrenocorticotropic hormone and cortisol, and the HPA axis adjusts the circadian rhythmicity of the peripheral clocks in response to various stressors through the GR. Further, Clock-Bmal1 regulates the response to glucocorticoids in peripheral tissues through acetylation of the GR, possibly antagonizing the biologic actions of diurnally fluctuating circulating cortisol. Importantly, dysregulation in the clock system and the HPA axis may cause similar pathologic manifestations—including obesity, metabolic syndrome, and cardiovascular disease—by uncoupling circulating cortisol concentrations from tissue sensitivity to glucocorticoids.

Tomoshige Kino (NIH; Eunice Kennedy Shriver National Institute of Child Health and Human Development REV)

2012-10-02

393

Adrenal clocks and the role of adrenal hormones in the regulation of circadian physiology.  

PubMed

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) and subordinate clocks that disseminate time information to various central and peripheral tissues. While the function of the SCN in circadian rhythm regulation has been extensively studied, we still have limited understanding of how peripheral tissue clock function contributes to the regulation of physiological processes. The adrenal gland plays a special role in this context as adrenal hormones show strong circadian secretion rhythms affecting downstream physiological processes. At the same time, they have been shown to affect clock gene expression in various other tissues, thus mediating systemic entrainment to external zeitgebers and promoting internal circadian alignment. In this review, we discuss the function of circadian clocks in the adrenal gland, how they are reset by the SCN and may further relay time-of-day information to other tissues. Focusing on glucocorticoids, we conclude by outlining the impact of adrenal rhythm disruption on neuropsychiatric, metabolic, immune, and malignant disorders. PMID:25367898

Leliavski, Alexei; Dumbell, Rebecca; Ott, Volker; Oster, Henrik

2015-02-01

394

Is metabolic rate a universal 'pacemaker' for biological processes?  

PubMed

A common, long-held belief is that metabolic rate drives the rates of various biological, ecological and evolutionary processes. Although this metabolic pacemaker view (as assumed by the recent, influential 'metabolic theory of ecology') may be true in at least some situations (e.g. those involving moderate temperature effects or physiological processes closely linked to metabolism, such as heartbeat and breathing rate), it suffers from several major limitations, including: (i) it is supported chiefly by indirect, correlational evidence (e.g. similarities between the body-size and temperature scaling of metabolic rate and that of other biological processes, which are not always observed) - direct, mechanistic or experimental support is scarce and much needed; (ii) it is contradicted by abundant evidence showing that various intrinsic and extrinsic factors (e.g. hormonal action and temperature changes) can dissociate the rates of metabolism, growth, development and other biological processes; (iii) there are many examples where metabolic rate appears to respond to, rather than drive the rates of various other biological processes (e.g. ontogenetic growth, food intake and locomotor activity); (iv) there are additional examples where metabolic rate appears to be unrelated to the rate of a biological process (e.g. ageing, circadian rhythms, and molecular evolution); and (v) the theoretical foundation for the metabolic pacemaker view focuses only on the energetic control of biological processes, while ignoring the importance of informational control, as mediated by various genetic, cellular, and neuroendocrine regulatory systems. I argue that a comprehensive understanding of the pace of life must include how biological activities depend on both energy and information and their environmentally sensitive interaction. This conclusion is supported by extensive evidence showing that hormones and other regulatory factors and signalling systems coordinate the processes of growth, metabolism and food intake in adaptive ways that are responsive to an organism's internal and external conditions. Metabolic rate does not merely dictate growth rate, but is coadjusted with it. Energy and information use are intimately intertwined in living systems: biological signalling pathways both control and respond to the energetic state of an organism. This review also reveals that we have much to learn about the temporal structure of the pace of life. Are its component processes highly integrated and synchronized, or are they loosely connected and often discordant? And what causes the level of coordination that we see? These questions are of great theoretical and practical importance. PMID:24863680

Glazier, Douglas S

2014-05-23

395

Light Preference Assay to Study Innate and Circadian Regulated Photobehavior in Drosophila Larvae  

PubMed Central

Light acts as environmental signal to control animal behavior at various levels. The Drosophila larval nervous system is used as a unique model to answer basic questions on how light information is processed and shared between rapid and circadian behaviors. Drosophila larvae display a stereotypical avoidance behavior when exposed to light. To investigate light dependent behaviors comparably simple light-dark preference tests can be applied. In vertebrates and arthropods the neural pathways involved in sensing and processing visual inputs partially overlap with those processing photic circadian information. The fascinating question of how the light sensing system and the circadian system interact to keep behavioral outputs coordinated remains largely unexplored. Drosophila is an impacting biological model to approach these questions, due to a small number of neurons in the brain and the availability of genetic tools for neuronal manipulation. The presented light-dark preference assay allows the investigation of a range of visual behaviors including circadian control of phototaxis. PMID:23629021

Farca Luna, Abud J.; von Essen, Alina M. H. J.; Widmer, Yves F.; Sprecher, Simon G.

2013-01-01

396

Melatonin Signaling Controls Circadian Swimming Behavior in Marine Zooplankton  

PubMed Central

Summary Melatonin, the “hormone of darkness,” is a key regulator of vertebrate circadian physiology and behavior. Despite its ubiquitous presence in Metazoa, the function of melatonin signaling outside vertebrates is poorly understood. Here, we investigate the effect of melatonin signaling on circadian swimming behavior in a zooplankton model, the marine annelid Platynereis dumerilii. We find that melatonin is produced in brain photoreceptors with a vertebrate-type opsin-based phototransduction cascade and a light-entrained clock. Melatonin released at night induces rhythmic burst firing of cholinergic neurons that innervate locomotor-ciliated cells. This establishes a nocturnal behavioral state by modulating the length and the frequency of ciliary arrests. Based on our findings, we propose that melatonin signaling plays a role in the circadian control of ciliary swimming to adjust the vertical position of zooplankton in response to ambient light. PMID:25259919

Tosches, Maria Antonietta; Bucher, Daniel; Vopalensky, Pavel; Arendt, Detlev

2014-01-01

397

SLEEP&CIRCADIAN NEUROBIOLOGY  

E-print Network

CENTER FOR SLEEP&CIRCADIAN NEUROBIOLOGY ANNUAL REPORT 2013 #12;#12;Annual Report 2013 TABLE Programs in Sleep 6 Medicine Pediatrics Psychiatry Basic Science Programs 19 Clinical Program 24 Fellowship Program 25 Sleep Research Program at the Children's Hospital of Philadelphia 26 Sleep Research in Nursing

Bushman, Frederic

398

Protein localization during the cyanobacterial circadian cycle  

E-print Network

Circadian clocks are ubiquitous throughout the living world. Of these circadian clocks, the simplest one is found in cyanobacteria - unicellular, photosynthetic marine organisms. Studies of the circadian clock of Synechococcus ...

Luitel, Prashant

2008-01-01

399

Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila  

PubMed Central

Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (?24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal's endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties. PMID:20972399

Chiu, Joanna C.; Low, Kwang Huei; Pike, Douglas H.; Yildirim, Evrim; Edery, Isaac

2010-01-01

400

Clinical assessment of pacemaker power sources  

SciTech Connect

The development of power sources for cardiac pacemakers has progressed from a 15-year usage of mercury-zinc batteries to widely used and accepted lithium cells. At present, there are about 6 different types of lithium cells incorporated into commercially distributed pacemakers. The authors reviewed experience over a 5-year period with 1711 mercury-zinc, 130 nuclear (P238) and 1912 lithium powered pacemakers. The lithium units have included 698 lithium-iodide, 270 lithium-silver chromate, 135 lithium-thionyl chloride, 31 lithium-lead and 353 lithium-cupric sulfide batteries. 57 of the lithium units have failed (91.2% component failure and 5.3% battery failure). 459 mercury-zinc units failed (25% component failure and 68% battery depletion). The data show that lithium powered pacemaker failures are primarily component, while mercury-zinc failures are primarily battery related. It is concluded that mercury-zinc powered pulse generators are obsolete and that lithium and nuclear (P238) power sources are highly reliable over the 5 years for which data are available. 3 refs.

Bilitch, M.; Parsonnet, V.; Furman, S.

1980-01-01

401

Technical Series Trends in Cardiac Pacemaker Batteries  

Microsoft Academic Search

Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads\\/electrodes have reduced energy requirements by two orders of magnitude. Micro- electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality,

Venkateswara Sarma Mallela; V. Ilankumaran; N. Srinivasa Rao

402

Recent Advances in Pacemaker Lead Technology  

Microsoft Academic Search

The cardiac pacemaker lead is a relatively fragile cable of insulated conductor wire implanted into the hostile environment of the human body. In comparison with the marked advances in pulse generator and sensor technology, concomitant advances in pacing leads have occurred slowly. This chapter will address recent engineering advances and clinical application of modern lead design.

Harry G. Mond

1999-01-01

403

MRI-conditional pacemakers: current perspectives  

PubMed Central

Use of both magnetic resonance imaging (MRI) and pacing devices has undergone remarkable growth in recent years, and it is estimated that the majority of patients with pacemakers will need an MRI during their lifetime. These investigations will generally be denied due to the potentially dangerous interactions between cardiac devices and the magnetic fields and radio frequency energy used in MRI. Despite the increasing reports of uneventful scanning in selected patients with conventional pacemakers under close surveillance, MRI is still contraindicated in those circumstances and cannot be considered a routine procedure. These limitations prompted a series of modifications in generator and lead engineering, designed to minimize interactions that could compromise device function and patient safety. The resulting MRI-conditional pacemakers were first introduced in 2008 and the clinical experience gathered so far supports their safety in the MRI environment if certain conditions are fulfilled. With this technology, new questions and controversies arise regarding patient selection, clinical impact, and cost-effectiveness. In this review, we discuss the potential risks of MRI in patients with electronic cardiac devices and present updated information regarding the features of MRI-conditional pacemakers and the clinical experience with currently available models. Finally, we provide some guidance on how to scan patients who have these devices and discuss future directions in the field. PMID:24851058

Ferreira, António M; Costa, Francisco; Tralhão, António; Marques, Hugo; Cardim, Nuno; Adragão, Pedro

2014-01-01

404

N-nitrosomelatonin enhances photic synchronization of mammalian circadian rhythms.  

PubMed

Most physiological processes in mammals are synchronized to the daily light:dark cycle by a circadian clock located in the hypothalamic suprachiasmatic nucleus. Signal transduction of light-induced phase advances of the clock is mediated through a neuronal nitric oxide synthase-guanilyl cyclase pathway. We have employed a novel nitric oxide-donor, N-nitrosomelatonin, to enhance the photic synchronization of circadian rhythms in hamsters. The intraperitoneal administration of this drug before a sub-saturating light pulse at circadian time 18 generated a twofold increase of locomotor rhythm phase-advances, having no effect over saturating light pulses. This potentiation was also obtained even when inhibiting suprachiasmatic nitric oxide synthase activity. However, N-nitrosomelatonin had no effect on light-induced phase delays at circadian time 14. The photic-enhancing effects were correlated with an increased suprachiasmatic immunoreactivity of FBJ murine osteosarcoma viral oncogene and period1. Moreover, in vivo nitric oxide release by N-nitrosomelatonin was verified by measuring nitrate and nitrite levels in suprachiasmatic nuclei homogenates. The compound also accelerated resynchronization to an abrupt 6-h advance in the light:dark cycle (but not resynchronization to a 6-h delay). Here, we demonstrate the chronobiotic properties of N-nitrosomelatonin, emphasizing the importance of nitric oxide-mediated transduction for circadian phase advances. PMID:24261470

Baidanoff, Fernando M; Plano, Santiago A; Doctorovich, Fabio; Suárez, Sebastián A; Golombek, Diego A; Chiesa, Juan J

2014-04-01

405

Circadian Rhythms and Psychiatric Illness  

PubMed Central

Purpose of review The present review provides a conceptual introduction to sleep and circadian research in psychiatric illness, and discusses recent experimental and intervention findings in this area. Recent Findings In this review, studies published since January 2011 on circadian disturbance and psychiatric illness have been summarized. Summary Exciting new results have increasingly utilized objective and validated instruments to measure the circadian system in experimental studies. Since 2011, treatment research has still predominantly utilized self-report measures as outcome variables. However, research in the treatment domain for sleep/circadian disturbances comorbid with psychiatric illness has advanced the field in its work to broaden the validation of existing sleep treatments to additional patient populations with comorbid sleep/circadian disruptions, address how to increase access to and affordability of treatment for sleep and circadian dysfunction for patients with psychiatric disorders, and how to combine psychosocial treatments with psychopharmacology to optimize treatment outcomes. PMID:24060916

Asarnow, Lauren D.; Soehner, Adriane M.; Harvey, Allison G.

2014-01-01

406

Measuring pacemaker dose: A clinical perspective  

SciTech Connect

Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired.

Studenski, Matthew T., E-mail: matthew.studenski@jeffersonhospital.org [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Xiao Ying; Harrison, Amy S. [Department of Radiation Oncology at the Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

2012-07-01

407

Measuring pacemaker dose: a clinical perspective.  

PubMed

Recently in our clinic, we have seen an increased number of patients presenting with pacemakers and defibrillators. Precautions are taken to develop a treatment plan that minimizes the dose to the pacemaker because of the adverse effects of radiation on the electronics. Here we analyze different dosimeters to determine which is the most accurate in measuring pacemaker or defibrillator dose while at the same time not requiring a significant investment in time to maintain an efficient workflow in the clinic. The dosimeters analyzed here were ion chambers, diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to quantify the angular and energy dependence of each dosimeter. Next, 8 patients plans were delivered to a Rando phantom with all the dosimeters located where the pacemaker would be, and the measurements were compared with the predicted dose. A cone beam computed tomography (CBCT) image was obtained to determine the dosimeter response in the kilovoltage energy range. In terms of the angular and energy dependence of the dosimeters, the ion chamber and diode were the most stable. For the clinical cases, all the dosimeters match relatively well with the predicted dose, although the ideal dosimeter to use is case dependent. The dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with many lateral beams. Because of their efficiency, we recommend using a MOSFET or a diode to measure the dose. If a discrepancy is observed between the measured and expected dose (especially when the pacemaker to field edge is <10 cm), we recommend analyzing the treatment plan to see whether there are many lateral beams. Follow-up with another dosimeter rather than repeating multiple times with the same type of dosimeter. All dosimeters should be placed after the CBCT has been acquired. PMID:21875785

Studenski, Matthew T; Xiao, Ying; Harrison, Amy S

2012-01-01

408

Circadian rhythms. Decoupling circadian clock protein turnover from circadian period determination.  

PubMed

The mechanistic basis of eukaryotic circadian oscillators in model systems as diverse as Neurospora, Drosophila, and mammalian cells is thought to be a transcription-and-translation-based negative feedback loop, wherein progressive and controlled phosphorylation of one or more negative elements ultimately elicits their own proteasome-mediated degradation, thereby releasing negative feedback and determining circadian period length. The Neurospora crassa circadian negative element FREQUENCY (FRQ) exemplifies such proteins; it is progressively phosphorylated at more than 100 sites, and strains bearing alleles of frq with anomalous phosphorylation display abnormal stability of FRQ that is well correlated with altered periods or apparent arrhythmicity. Unexpectedly, we unveiled normal circadian oscillations that reflect the allelic state of frq but that persist in the absence of typical degradation of FRQ. This manifest uncoupling of negative element turnover from circadian period length determination is not consistent with the consensus eukaryotic circadian model. PMID:25635104

Larrondo, Luis F; Olivares-Yañez, Consuelo; Baker, Christopher L; Loros, Jennifer J; Dunlap, Jay C

2015-01-30

409

Circadian regulation of metabolism.  

PubMed

In association with sleep-wake and fasting-feeding cycles, organisms experience dramatic oscillations in energetic demands and nutrient supply. It is therefore not surprising that various metabolic parameters, ranging from the activity status of molecular energy sensors to circulating nutrient levels, oscillate in time-of-day-dependent manners. It has become increasingly clear that rhythms in metabolic processes are not simply in response to daily environmental/behavioral influences, but are driven in part by cell autonomous circadian clocks. By synchronizing the cell with its environment, clocks modulate a host of metabolic processes in a temporally appropriate manner. The purpose of this article is to review current understanding of the interplay between circadian clocks and metabolism, in addition to the pathophysiologic consequences of disruption of this molecular mechanism, in terms of cardiometabolic disease development. PMID:24928941

Bailey, Shannon M; Udoh, Uduak S; Young, Martin E

2014-08-01

410

Sleep and circadian rhythms  

NASA Technical Reports Server (NTRS)

Three interacting processes are involved in the preservation of circadian rhythms: (1) endogenous rhythm generation mechanisms, (2) entrainment mechanisms to keep these rhythms 'on track', and (3) exogenous masking processes stemming from changes in environment and bahavior. These processes, particularly the latter two, can be dramatically affected in individuals of advanced age and in space travelers, with a consequent disruption in sleep and daytime functioning. This paper presents results of a phase-shift experiment investigating the age-related effects of the exogeneous component of circadian rhythms in various physiological and psychological functions by comparing these functions in middle aged and old subjects. Dramatic differences were found between the two age groups in measures of sleep, mood, activation, and performance efficiency.

Monk, Timothy H.

1991-01-01

411

Pacemaker deactivation: withdrawal of support or active ending of life?  

PubMed

In spite of ethical analyses assimilating the palliative deactivation of pacemakers to commonly accepted withdrawings of life-sustaining therapy, many clinicians remain ethically uncomfortable with pacemaker deactivation at the end of life. Various reasons have been posited for this discomfort. Some cardiologists have suggested that reluctance to deactivate pacemakers may stem from a sense that the pacemaker has become part of the patient's "self." The authors suggest that Daniel Sulmasy is correct to contend that any such identification of the pacemaker is misguided. The authors argue that clinicians uncomfortable with pacemaker deactivation are nevertheless correct to see it as incompatible with the traditional medical ethics of withdrawal of support. Traditional medical ethics is presently taken by many to sanction pacemaker deactivation when such deactivation honors the patient's right to refuse treatment. The authors suggest that the right to refuse treatment applies to treatments involving ongoing physician agency. This right cannot underwrite patient demands that physicians reverse the effects of treatments previously administered, in which ongoing physician agency is no longer implicated. The permanently indwelling pacemaker is best seen as such a treatment. As such, its deactivation in the pacemaker-dependent patient is best seen not as withdrawal of support but as active ending of life. That being the case, clinicians adhering to the usual ethical analysis of withdrawal of support are correct to be uncomfortable with pacemaker deactivation at the end of life. PMID:22351107

Huddle, Thomas S; Amos Bailey, F

2012-12-01

412

Effects of partial destruction of the suprachiasmatic nuclei on two circadian parameters: wheel-running activity and short-day induced testicular regression  

Microsoft Academic Search

Many circadian rhythms in mammals are regulated by the suprachiasmatic nuclei located in the anterior hypothalamus. The suprachiasmatic nuclei are a heterogeneous population of neurons loosely segregated into regions. In an effort to determine if a regional specificity of control of different circadian rhythms exists within the SCN, the effect of small electrolytic lesions of the suprachiasmatic nuclei was examined

Gary E. Pickard; Fred W. Turek

1985-01-01

413

Circadian and sleep-dependent regulation of hormone release in humans  

NASA Technical Reports Server (NTRS)

Daily oscillations characterize the release of nearly every hormone. The circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, generates circadian, approximately 24-hour rhythms in many physiologic functions. However, the observed hormonal oscillations do not simply reflect the output of this internal clock. Instead, daily hormonal profiles are the product of a complex interaction between the output of the circadian pacemaker, periodic changes in behavior, light exposure, neuroendocrine feedback mechanisms, gender, age, and the timing of sleep and wakefulness. The interaction of these factors can affect hormonal secretory pulse frequency and amplitude, with each endocrine system differentially affected by these factors. This chapter examines recent advances in understanding the effects on endocrine rhythms of a number of these factors. Sleep exerts a profound effect on endocrine secretion. Sleep is a dynamic process that is characterized by periodic changes in electrophysiologic activity. These electrophysiologic changes, which are used to mark the state and depth of sleep, are associated with periodic, short-term variations in hormonal levels. The secretion of hormones such as renin and human growth hormone are strongly influenced by sleep or wake state, while melatonin and cortisol levels are relatively unaffected by sleep or wake state. In addition, sleep is associated with changes in posture, behavior, and light exposure, each of which is known to affect endocrine secretion. Furthermore, the tight concordance of habitual sleep and wake times with certain circadian phases has made it difficult to distinguish sleep and circadian effects on these hormones. Specific protocols, designed to extract circadian and sleep information semi-independently, have been developed and have yielded important insights into the effects of these regulatory processes. These results may help to account for changes in endocrine rhythms observed in circadian rhythm sleep disorders, including the dyssomnia of shift work and visual impairment. Yet to be fully investigated are the interactions of these factors with age and gender. Characterization of the factors governing hormone secretion is critical to understanding the temporal regulation of endocrine systems and presents many exciting areas for future research.

Czeisler, C. A.; Klerman, E. B.

1999-01-01

414

The circadian clock controls the expression pattern of the circadian input photoreceptor, phytochrome B  

E-print Network

The circadian clock controls the expression pattern of the circadian input photoreceptor responses, including most light responses, also are mod- ulated by circadian rhythms that are generated by an endogenous oscillator, the circadian clock. To provide information on local time, circadian clocks

Millar, Andrew J.

415

Shockwave lithotripsy and pacemakers: experience with 20 cases.  

PubMed

Lithotripsy treatment of urinary tract calculi initially excluded patients with cardiac pacemakers. Continued research and clinical study of patient outcomes has promoted a change in that initial concept. The Oklahoma Lithotripsy Center has successfully treated 20 patients with various types of pacemakers. No significant cardiovascular events occurred during treatment. Patients should be evaluated before the procedure by a cardiologist, and dual-chamber pacemakers should be reprogrammed to the single-chamber mode. Patients who cannot tolerate this should not undergo SWL. Rate-responsive pacemakers should be programmed to the non-rate-responsive (VVI) mode. The pacemaker should be at least 5 cm from the blast path. With these precautions and careful monitoring, SWL can be performed safely in most patients with pacemakers. PMID:8535456

Albers, D D; Lybrand, F E; Axton, J C; Wendelken, J R

1995-08-01

416

Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders  

PubMed Central

Recent evidence shows that the temporal alignment between the sleep-wake cycle and the circadian pacemaker affects self-assessment of mood in healthy subjects. Despite the differences in affective state between healthy subjects and patients with psychiatric disorders, these results have implications for analyzing diurnal variation of mood in unipolar and bipolar affective disorders and sleep disturbances in other major psychiatric conditions such as chronic schizophrenia. In a good proportion of patients with depression, mood often improves over the course of the day; an extension of waking often has an antidepressant effect. Sleep deprivation has been described as a treatment for depression for more than 30 years, and approximately 50% to 60% of patients with depression respond to this approach, especially those patients who report that their mood improves over the course of the day. The mechanisms by which sleep deprivation exerts its antidepressant effects are still controversial, but a reduction in rapid eye movement sleep (REM sleep), sleep pressure and slow-wave sleep (SWS), or a circadian phase disturbance, have been proposed. Although several studies support each of these hypotheses, none is sufficient to explain all observations reported to date. Unfortunately, the disturbed sleep-wake cycle or behavioural activities of depressed patients often explain several of the abnormalities reported in the diurnal rhythms of these patients. Thus, protocols that specifically manipulate the sleep-wake cycle to unmask the expression of the endogenous circadian pacemaker are greatly needed. In chronic schizophrenia, significant disturbances in sleep continuity, REM sleep, and SWS have been consistently reported. These disturbances are different from those observed in depression, especially with regard to REM sleep. Circadian phase abnormalities in schizophrenic patients have also been reported. Future research is expected to clarify the nature of these abnormalities. Images Fig. 1 PMID:11109296

Boivin, DB

2000-01-01

417

Circadian disorganization alters intestinal microbiota.  

PubMed

Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases. PMID:24848969

Voigt, Robin M; Forsyth, Christopher B; Green, Stefan J; Mutlu, Ece; Engen, Phillip; Vitaterna, Martha H; Turek, Fred W; Keshavarzian, Ali

2014-01-01

418

Circadian gene variants in cancer  

Technology Transfer Automated Retrieval System (TEKTRAN)

Humans as diurnal beings are active during the day and rest at night. This daily oscillation of behavior and physiology is driven by an endogenous circadian clock not environmental cues. In modern societies, changes in lifestyle have led to a frequent disruption of the endogenous circadian homeostas...

419

Circadian Disorganization Alters Intestinal Microbiota  

PubMed Central

Intestinal dysbiosis and circadian rhythm disruption are associated with similar diseases including obesity, metabolic syndrome, and inflammatory bowel disease. Despite the overlap, the potential relationship between circadian disorganization and dysbiosis is unknown; thus, in the present study, a model of chronic circadian disruption was used to determine the impact on the intestinal microbiome. Male C57BL/6J mice underwent once weekly phase reversals of the light:dark cycle (i.e., circadian rhythm disrupted mice) to determine the impact of circadian rhythm disruption on the intestinal microbiome and were fed either standard chow or a high-fat, high-sugar diet to determine how diet influences circadian disruption-induced effects on the microbiome. Weekly phase reversals of the light:dark (LD) cycle did not alter the microbiome in mice fed standard chow; however, mice fed a high-fat, high-sugar diet in conjunction with phase shifts in the light:dark cycle had significantly altered microbiota. While it is yet to be established if some of the adverse effects associated with circadian disorganization in humans (e.g., shift workers, travelers moving across time zones, and in individuals with social jet lag) are mediated by dysbiosis, the current study demonstrates that circadian disorganization can impact the intestinal microbiota which may have implications for inflammatory diseases. PMID:24848969

Voigt, Robin M.; Forsyth, Christopher B.; Green, Stefan J.; Mutlu, Ece; Engen, Phillip; Vitaterna, Martha H.; Turek, Fred W.; Keshavarzian, Ali

2014-01-01

420

Model-Based Conformance Testing for Implantable Pacemakers George Chen, Zhihao Jiang, Rahul Mangharam  

E-print Network

Model-Based Conformance Testing for Implantable Pacemakers George Chen, Zhihao Jiang, Rahul References Methods Testing Framework -The increasing complexity of pacemaker software has resulted the safety of pacemaker software. -Develop tools and methodologies to test and formally verify whether

Plotkin, Joshua B.

421

Limit Cycle Oscillations in Pacemaker Cells  

E-print Network

In recent decades, several mathematical models describing the pacemaker activity of the rabbit sinoatrial node have been developed. We demonstrate that it is not possible to establish the existence, uniqueness, and stability of a limit cycle oscillation in those models. Instead we observe an infinite number of limit cycles. We then display numerical results from a new model, with a limit cycle that can be reached from many different initial conditions.

Endresen, L P; Endresen, Lars Petter; Skarland, Nils

1999-01-01

422

Pacemaker failure associated with therapeutic radiation  

Microsoft Academic Search

A 48-year-old white man with a multiprogrammable Intramedics 259-01 pacemaker was treated for inoperable lung cancer with a course of cobalt-60 radiotherapy (total 3500 rad). Several weeks subsequent to his last radiation treatment, the patient presented to the emergency department with chest and abdominal pain, shortness of breath, hypotension, and tachycardia. A paced tachycardia was noted, and application of a

Christopher Brooks; Mitchell Mutter

1988-01-01

423

Pacemaker Endocarditis Due to Propionibacterium acnes  

Microsoft Academic Search

.  \\u000a \\u000a Propionibacterium acnes belongs to the cutaneous flora of humans; it is often considered to be contaminant but has also been found to be a pathogen\\u000a in human diseases. It is an uncommon causal agent in infective endocarditis and appears to have a predilection for prosthetic\\u000a valves and foreign bodies. We describe a case of pacemaker endocarditis which shows that

K. Zedtwitz-Liebenstein; H. Gabriel; W. Graninger

2003-01-01

424

Should surgeons still be implanting pacemakers?  

PubMed

Cardiac pacing has undergone major changes in the areas of manpower, technology, and cost over the past 10 years. Arguments have been made to eliminate cardiac surgical involvement in pacing on the basis of these three areas of change: implantations are increasingly performed by nonsurgeons, surgeons have not kept up with the technologic advances in pacing, and consolidation of bradypacing resources is necessary during a time when reimbursement has declined significantly. This study examined two eras of pacing therapy at an institution where pacemaker implantation has always been performed by cardiothoracic surgeons. The purpose of the study was to critically analyze (1) the current role (if any) of cardiothoracic surgeons in delivery of pacemaker therapy and (2) the current results of cardiothoracic surgical involvement in pacemaker implantation. In 1,562 procedures performed between 1986 and 1992, the infection rate was 0.51% and the overall complication rate (both short-term and long-term) was 5.2%. During era 1 (1/1/86 to 6/30/89), 80% of implants were single-chamber and follow-up was incomplete and dependent in many instances on the referring cardiologist/internist. For the implantations performed in the second era (7/1/89 to 12/31/92) as part of an established Pacemaker Service, complete clinical and transtelephonic follow-up services were provided by this coordinated medical-surgical approach. During era 2, 53.9% of implants were dual-chamber (79% during 1992). Total and infectious complication rates remained low in era 2 despite this change in technology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8147626

Ferguson, T B; Lindsay, B D; Boineau, J P

1994-03-01

425

Activity-Dependent Changes in Extracellular Ca2+ and K+ Reveal Pacemakers in the Spinal Locomotor-Related Network  

PubMed Central

SUMMARY Changes in the extracellular ionic concentrations occur as a natural consequence of firing activity in large populations of neurons. The extent to which these changes alter the properties of individual neurons and the operation of neuronal networks remains unknown. Here, we show that the locomotor-like activity in the isolated neonatal rodent spinal cord reduces the extracellular calcium ([Ca2+]o) to 0.9 mM and increases the extracellular potassium ([K+]o) to 6 mM. Such changes in [Ca2+]o and [K+]o trigger pacemaker activities in interneurons considered to be part of the locomotor network. Experimental data and a modeling study show that the emergence of pacemaker properties critically involves a [Ca2+]o-dependent activation of the persistent sodium current (INaP). These results support a concept for locomotor rhythm generation in which INaP-dependent pacemaker properties in spinal interneurons are switched on and tuned by activity-dependent changes in [Ca2+]o and [K+]o. PMID:23522041

Brocard, Frédéric; Shevtsova, Natalia A.; Bouhadfane, Mouloud; Tazerart, Sabrina; Heinemann, Uwe; Rybak, Ilya A.; Vinay, Laurent

2013-01-01

426

Systems Biology of the Mammalian Circadian Clock  

E-print Network

Systems Biology of the Mammalian Circadian Clock Hanspeter Herzel Institute for Theoretical Biology Molecular Chronobiology #12;The circadian oscillator Circadian rhythm Oster et al., 2002 Feedback loopsOscillations Reppert and Weaver, 2001 #12;Simplified model of the circadian core oscillator S. Becker-Weimann, J. Wolf

Spang, Rainer

427

METABOLISM AND THE CONTROL OF CIRCADIAN RHYTHMS  

E-print Network

METABOLISM AND THE CONTROL OF CIRCADIAN RHYTHMS Jared Rutter, Martin Reick, and Steven L. Mc@biochem.swmed.edu Key Words entrainment, suprachiasmatic nucleus, circadian rhythm, neural activity, restricted feeding, central circadian oscillator f Abstract The core apparatus that regulates circadian rhythm has been exten

Rutter, Jared

428

Effects of magnetic resonance imaging on cardiac pacemakers and electrodes  

Microsoft Academic Search

In phantom studies we investigated the effects of magnetic resonance imaging (MRI) on pacemakers and electrodes. Twenty-five electrodes were exposed to MRI in a 1.5T scanner with continuous registration of the temperature at the electrode tip. Eleven pacemakers (five single chamber and six dual chamber) were exposed to MRI. Pacemaker output was monitored to detect malfunction in VOO\\/DOO and VVI\\/DDD

Stephan Achenbach; Werner Moshage; Björn Diem; Tobias Bieberle; Volker Schibgilla; Kurt Bachmann

1997-01-01

429

Pacemaker lead erosion simulating "Loch Ness Monster": conservative management.  

PubMed

The majority of pacemaker pocket or lead erosions are due to either mechanical erosion by the bulky pulse generator or secondary to pacemaker pocket infection. We describe an unusual case of delayed pacemaker lead erosion causing extrusion of a portion of the pacing lead, with separate entry and exit points, with the gap filled with new skin formation, simulating the "Loch Ness Monster", which was successfully managed conservatively by surgical reinsertion. PMID:23284119

Garg, Naveen; Moorthy, Nagaraja

2012-12-01

430

Circadian entrainment and its role in depression: a mechanistic review.  

PubMed

The natural rotation of the earth generates an environmental day-night cycle that repeats every 24 h. This daily transition from dawn to dusk provides one of the most important time cues to which the majority of organisms synchronise their activity. Under these conditions, natural light, a photic stimulus, provides the principal entraining cue. In mammals, an endogenous circadian pacemaker located within the suprachiasmatic nucleus (SCN) of the hypothalamus acts as a coordinating centre to align physiological activity with the environmental light-dark cycle. However, the SCN also receives regulatory input from a number of behavioural, non-photic, cues such as physical activity, social interactions and feeding routines. The unique ability of the SCN to integrate both photic and non-photic cues allows it to generate a rhythm that is tailored to the individual and entrained to the environment. Here, we review the key neurotransmitter systems involved in both photic and non-photic transmission to the SCN and their interactions that assist in generating an entrained output rhythm. We also consider the impact on health of a desynchronised circadian system with a focus on depressive affective disorders and current therapies aimed at manipulating the relationship between photic and non-photic SCN regulators. PMID:22798027

Lall, G S; Atkinson, L A; Corlett, S A; Broadbridge, P J; Bonsall, D R

2012-10-01

431

Acute melatonin treatment alters dendritic morphology and circadian clock gene expression in the hippocampus of Siberian Hamsters.  

PubMed

In the hippocampus of Siberian hamsters, dendritic length and dendritic complexity increase in the CA1 region whereas dendritic spine density decreases in the dentate gyrus region at night. However, the underlying mechanism of the diurnal rhythmicity in hippocampal neuronal remodeling is unknown. In mammals, most daily rhythms in physiology and behaviors are regulated by a network of circadian clocks. The central clock, located in the hypothalamus, controls melatonin secretion at night and melatonin modifies peripheral clocks by altering expression of circadian clock genes. In this study, we examined the effects of acute melatonin treatment on the circadian clock system as well as on morphological changes of hippocampal neurons. Male Siberian hamsters were injected with melatonin in the afternoon; 4 h later, mRNA levels of hypothalamic and hippocampal circadian clock genes and hippocampal neuron dendritic morphology were assessed. In the hypothalamus, melatonin treatment did not alter Period1 and Bmal1 expression. However, melatonin treatment increased both Period1 and Bmal1 expression in the hippocampus, suggesting that melatonin affected molecular oscillations in the hippocampus. Melatonin treatment also induced rapid remodeling of hippocampal neurons; melatonin increased apical dendritic length and dendritic complexity in the CA1 region and reduced the dendritic spine density in the dentate gyrus region. These data suggest that structural changes in hippocampal neurons are regulated by a circadian clock and that melatonin functions as a nighttime signal to coordinate the diurnal rhythm in neuronal remodeling. PMID:25160468

Ikeno, Tomoko; Nelson, Randy J

2015-02-01

432

Pacemaker implantation after transcatheter aortic valve implantation.  

PubMed

Thirty- to 35% of patients after transcatheter aortic valve implantation undergo implantation of a permanent pacemaker (PPM) because of development of atrioventricular block (AVB) or development of a condition with high risk of progression to AVB. There are insufficient data regarding long-term follow-up on pacing dependency. From February 2009 to July 2011, 191 transcatheter aortic valve implantation procedures were performed at the Rabin Medical Center (125 CoreValve and 66 Edwards SAPIEN). Thirty-two patients (16.7%) received a PPM (30 with CoreValve and 2 with Edwards SAPIEN). Data from the pacemaker clinic follow-up was available in 27 patients. After a mean follow-up of 52 weeks (range, 22 to 103), only 8 (29%) of 27 patients were pacing dependent. The indication of PPM in these 8 patients was complete AVB. In conclusion, in our center, the rate of PPM implantation was 16%, which is lower than that reported in the published works. Only 29% of those patients implanted with PPM were pacemaker dependent. Further studies are necessary to define reliable predictors for long-term pacing. PMID:23998348

Goldenberg, Gustavo; Kusniec, Jairo; Kadmon, Ehud; Golovchiner, Gregory; Zabarsky, Ronit; Nevzorov, Roman; Vaknin, Hana; Assali, Abed; Kornowski, Ran; Haim, Moti; Strasberg, Boris

2013-11-15

433

Animal activity around the clock with no overt circadian rhythms: patterns, mechanisms and adaptive value  

PubMed Central

Circadian rhythms are ubiquitous in many organisms. Animals that are forced to be active around the clock typically show reduced performance, health and survival. Nevertheless, we review evidence of animals showing prolonged intervals of activity with attenuated or nil overt circadian rhythms and no apparent ill effects. We show that around-the-clock and ultradian activity patterns are more common than is generally appreciated, particularly in herbivores, in animals inhabiting polar regions and habitats with constant physical environments, in animals during specific life-history stages (such as migration or reproduction), and in highly social animals. The underlying mechanisms are diverse, but studies suggest that some circadian pacemakers continue to measure time in animals active around the clock. The prevalence of around-the-clock activity in diverse animals and habitats, and an apparent diversity of underlying mechanisms, are consistent with convergent evolution. We suggest that the basic organizational principles of the circadian system and its complexity encompass the potential for chronobiological plasticity. There may be trade-offs between benefits of persistent daily rhythms versus plasticity, which for reasons still poorly understood make overt daily arrhythmicity functionally adaptive only in selected habitats and for selected lifestyles. PMID:23825202

Bloch, Guy; Barnes, Brian M.; Gerkema, Menno P.; Helm, Barbara

2013-01-01

434

Dopaminergic Regulation of Circadian Food Anticipatory Activity Rhythms in the Rat  

PubMed Central

Circadian activity rhythms are jointly controlled by a master pacemaker in the hypothalamic suprachiasmatic nuclei (SCN) and by food-entrainable circadian oscillators (FEOs) located elsewhere. The SCN mediates synchrony to daily light-dark cycles, whereas FEOs generate activity rhythms synchronized with regular daily mealtimes. The location of FEOs generating food anticipation rhythms, and the pathways that entrain these FEOs, remain to be clarified. To gain insight into entrainment pathways, we developed a protocol for measuring phase shifts of anticipatory activity rhythms in response to pharmacological probes. We used this protocol to examine a role for dopamine signaling in the timing of circadian food anticipation. To generate a stable food anticipation rhythm, rats were fed 3h/day beginning 6-h after lights-on or in constant light for at least 3 weeks. Rats then received the D2 agonist quinpirole (1 mg/kg IP) alone or after pretreatment with the dopamine synthesis inhibitor ?-methylparatyrosine (AMPT). By comparison with vehicle injections, quinpirole administered 1-h before lights-off (19h before mealtime) induced a phase delay of activity onset prior to the next meal. Delay shifts were larger in rats pretreated with AMPT, and smaller following quinpirole administered 4-h after lights-on. A significant shift was not observed in response to the D1 agonist SKF81297. These results provide evidence that signaling at D2 receptors is involved in phase control of FEOs responsible for circadian food anticipatory rhythms in rats. PMID:24312417

Smit, Andrea N.; Patton, Danica F.; Michalik, Mateusz; Opiol, Hanna; Mistlberger, Ralph E.

2013-01-01

435

Development of the Circadian Timing System in Rat Pups Exposed to Microgravity during Gestation  

NASA Technical Reports Server (NTRS)

Ten pregnant Sprague Dawley rat dams were exposed to spaceflight aboard the Space Shuttle (STS-70) for gestational days 11-20 (G 11-20; FILT group). Control dams were maintained in either a flight-like (FIDS group) or vivarium cage environment (VIV group) on earth. All dams had ad lib access to food and water and were exposed to a light-dark cycle consisting of 12 hours of light (- 30 lux) followed by 12 hours of darkness. The dams were closely monitored from G 22 until parturition. All pups were cross-fostered at birth; each foster dam had a litter of 10 pups. Pups remained with their foster dam until post-natal day 21 (PN 21). Pup body mass was measured twice weekly. At PN14 FILT pups had a smaller body mass than did the VIV pups (p < 0.01). Circadian rhythms of body temperature and activity of pups from two FILT dams (n = 8), two FIDS dams (n = 9) and two VIV dams (n = 7) were studied starting from age PN 21. All pups had circadian rhythms of temperature and activity at this age. There were no significant differences in rhythms between groups that could be attributed to microgravity exposure. We also examined the development of neural structures involved in circadian rhythmicity: the retina, the intergeniculate leaflet (IGL) and the circadian pacemaker, the suprachiasmatic nucleus (SCN). There were small differences between the flight and control groups at very early stages of development (G 20 and PN3) which indicated that the development of both the SCN and the IGL. These results indicate that exposure to the microgravity environment of spaceflight during this embryonic development period does not affect the development of the circadian rhythms of body temperature and activity, but may affect the early development of the neural structures involved in circadian timing.

Fuller, Charles A.

2000-01-01

436

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.  

Code of Federal Regulations, 2013 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3640 Indirect pacemaker generator function analyzer. (a) Identification. An indirect...

2013-04-01

437

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.  

Code of Federal Regulations, 2012 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3640 Indirect pacemaker generator function analyzer. (a) Identification. An indirect...

2012-04-01

438

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.  

Code of Federal Regulations, 2010 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3640 Indirect pacemaker generator function analyzer. (a) Identification. An indirect...

2010-04-01

439

21 CFR 870.3640 - Indirect pacemaker generator function analyzer.  

Code of Federal Regulations, 2011 CFR

...ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CARDIOVASCULAR DEVICES Cardiovascular Prosthetic Devices § 870.3640 Indirect pacemaker generator function analyzer. (a) Identification. An indirect...

2011-04-01

440

Disrupted reproduction, estrous cycle, and circadian rhythms in female vasoactive intestinal peptide deficient mice  

PubMed Central

The female reproductive cycle is gated by the circadian timing system and may be vulnerable to disruptions in the circadian system. Prior work suggests that vasoactive intestinal peptide (VIP) expressing neurons in the suprachiasmatic nucleus (SCN) are one pathway by which the circadian clock can influence the estrous cycle but the impact of the loss of this peptide on reproduction has not been assessed. In the present study, we first examine the impact of the genetic loss of the neuropeptide VIP on the reproductive success of female mice. Significantly, mutant females produced about half the offspring of their wild type sisters even when mated to the same males. We also find that VIP-deficient females exhibit a disrupted estrous cycle i.e. ovulation occurs less frequently and results in the release of fewer oocytes compared to controls. Circadian rhythms of wheel running activity are disrupted in the female mutant mice as are the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibit lower amplitude oscillations with altered phase relationships between the SCN and peripheral oscillators as measured by PER2-driven bioluminescence. The simplest explanation of our data is that the loss of VIP results in a weakened SCN oscillator which reduces the synchronization of the female circadian system. These results clarify one of the mechanisms by which disruption of the circadian system reduces female reproductive success. PMID:25252712

Loh, Dawn Hsiao-Wei; Kuljis, Dika Ana; Azuma, Lauren; Wu, Yingfei; Truong, Danny; Wang, Huei-Bin; Colwell, Christopher Scott

2015-01-01

441

Daily variation in the electrophysiological activity of mouse medial habenula neurones  

PubMed Central

AbstractIntrinsic daily or circadian rhythms arise through the outputs of the master circadian clock in the brain's suprachiasmatic nuclei (SCN) as well as circadian oscillators in other brain sites and peripheral tissues. SCN neurones contain an intracellular molecular clock that drives these neurones to exhibit pronounced day–night differences in their electrical properties. The epithalamic medial habenula (MHb) expresses clock genes, but little is known about the bioelectric properties of mouse MHb neurones and their potential circadian characteristics. Therefore, in this study we used a brain slice preparation containing the MHb to determine the basic electrical properties of mouse MHb neurones with whole-cell patch clamp electrophysiology, and investigated whether these vary across the day–night cycle. MHb neurones (n = 230) showed heterogeneity in electrophysiological state, ranging from highly depolarised cells (? ?25 to ?30 mV) that are silent with no membrane activity or display depolarised low-amplitude membrane oscillations, to neurones that were moderately hyperpolarised (?40 mV) and spontaneously discharging action potentials. These electrical states were largely intrinsically regulated and were influenced by the activation of small-conductance calcium-activated potassium channels. When considered as one population, MHb neurones showed significant circadian variation in their spontaneous firing rate and resting membrane potential. However, in recordings of MHb neurones from mice lacking the core molecular circadian clock, these temporal differences in MHb activity were absent, indicating that circadian clock signals actively regulate the timing of MHb neuronal states. These observations add to the extracellularly recorded rhythms seen in other brain areas and establish that circadian mechanisms can influence the membrane properties of neurones in extra-SCN sites. Collectively, the results of this study indicate that the MHb may function as an intrinsic secondary circadian oscillator in the brain, which can shape daily information flow in key brain processes, such as reward and addiction. PMID:24247982

Sakhi, Kanwal; Belle, Mino D C; Gossan, Nicole; Delagrange, Philippe; Piggins, Hugh D

2014-01-01

442

Circadian gene variants in cancer.  

PubMed

Humans as diurnal beings are active during the day and rest at night. This daily oscillation of behavior and physiology is driven by an endogenous circadian clock not environmental cues. In modern societies, changes in lifestyle have led to a frequent disruption of the endogenous circadian homeostasis leading to increased risk of various diseases including cancer. The clock is operated by the feedback loops of circadian genes and controls daily physiology by coupling cell proliferation and metabolism, DNA damage repair, and apoptosis in peripheral tissues with physical activity, energy homeostasis, immune and neuroendocrine functions at the organismal level. Recent studies have revealed that defects in circadian genes due to targeted gene ablation in animal models or single nucleotide polymorphism, deletion, deregulation and/or epigenetic silencing in humans are closely associated with increased risk of cancer. In addition, disruption of circadian rhythm can disrupt the molecular clock in peripheral tissues in the absence of circadian gene mutations. Circadian disruption has recently been recognized as an independent cancer risk factor. Further study of the mechanism of clock-controlled tumor suppression will have a significant impact on human health by improving the efficiencies of cancer prevention and treatment. PMID:24901356

Kettner, Nicole M; Katchy, Chinenye A; Fu, Loning

2014-06-01

443

Casein Kinase 1 Promotes Synchrony of the Circadian Clock Network  

PubMed Central

Casein kinase 1, known as DOUBLETIME (DBT) in Drosophila melanogaster, is a critical component of the circadian clock that phosphorylates and promotes degradation of the PERIOD (PER) protein. However, other functions of DBT in circadian regulation are not clear, in part because severe reduction of dbt causes preadult lethality. Here we report the molecular and behavioral phenotype of a viable dbtEY02910 loss-of-function mutant. We found that DBT protein levels are dramatically reduced in adult dbtEY02910 flies, and the majority of mutant flies display arrhythmic behavior, with a few showing weak, long-period (?32 h) rhythms. Peak phosphorylation of PER is delayed, and both hyper- and hypophosphorylated forms of the PER and CLOCK proteins are present throughout the day. In addition, molecular oscillations of the circadian clock are dampened. In the central brain, PER and TIM expression is heterogeneous and decoupled in the canonical clock neurons of the dbtEY02910 mutants. We also report an interaction between dbt and the signaling pathway involving pigment dispersing factor (PDF), a synchronizing peptide in the clock network. These data thus demonstrate that overall reduction of DBT causes long and arrhythmic behavior, and they reveal an unexpected role of DBT in promoting synchrony of the circadian clock network. PMID:24820422

Zheng, Xiangzhong; Sowcik, Mallory; Chen, Dechun

2014-01-01

444

Translational Profiling of Clock Cells Reveals Circadianly Synchronized Protein Synthesis  

PubMed Central

Abstract Genome-wide studies of circadian transcription or mRNA translation have been hindered by the presence of heterogeneous cell populations in complex tissues such as the nervous system. We describe here the use of a Drosophila cell-specific translational profiling approach to document the rhythmic “translatome” of neural clock cells for the first time in any organism. Unexpectedly, translation of most clock-regulated transcripts—as assayed by mRNA ribosome association—occurs at one of two predominant circadian phases, midday or mid-night, times of behavioral quiescence; mRNAs encoding similar cellular functions are translated at the same time of day. Our analysis also indicates that fundamental cellular processes—metabolism, energy production, redox state (e.g., the thioredoxin system), cell growth, signaling and others—are rhythmically modulated within clock cells via synchronized protein synthesis. Our approach is validated by the identification of mRNAs known to exhibit circadian changes in abundance and the d