These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

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, Raphaelle; Emery, Patrick

2012-01-01

2

Lmo Mutants Reveal a Novel Role for Circadian Pacemaker Neurons in Cocaine-Induced Behaviors  

PubMed Central

Drosophila has been developed recently as a model system to investigate the molecular and neural mechanisms underlying responses to drugs of abuse. Genetic screens for mutants with altered drug-induced behaviors thus provide an unbiased approach to define novel molecules involved in the process. We identified mutations in the Drosophila LIM-only (LMO) gene, encoding a regulator of LIM-homeodomain proteins, in a genetic screen for mutants with altered cocaine sensitivity. Reduced Lmo function increases behavioral responses to cocaine, while Lmo overexpression causes the opposite effect, reduced cocaine responsiveness. Expression of Lmo in the principal Drosophila circadian pacemaker cells, the PDF-expressing ventral lateral neurons (LNvs), is sufficient to confer normal cocaine sensitivity. Consistent with a role for Lmo in LNv function, Lmo mutants also show defects in circadian rhythms of behavior. However, the role for LNvs in modulating cocaine responses is separable from their role as pacemaker neurons: ablation or functional silencing of the LNvs reduces cocaine sensitivity, while loss of the principal circadian neurotransmitter PDF has no effect. Together, these results reveal a novel role for Lmo in modulating acute cocaine sensitivity and circadian locomotor rhythmicity, and add to growing evidence that these behaviors are regulated by shared molecular mechanisms. The finding that the degree of cocaine responsiveness is controlled by the Drosophila pacemaker neurons provides a neuroanatomical basis for this overlap. We propose that Lmo controls the responsiveness of LNvs to cocaine, which in turn regulate the flies' behavioral sensitivity to the drug. PMID:15550987

2004-01-01

3

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

4

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

PubMed

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, Agata; Gorostiza, E Axel; Herrero, Anastasia; Castaño, Eduardo M; Ceriani, M Fernanda

2014-10-01

5

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; Fernandez-Gamba, Agata; Gorostiza, E. Axel; Herrero, Anastasia; Castano, Eduardo M.; Ceriani, M. Fernanda

2014-01-01

6

Caffeine increases light responsiveness of the mouse circadian pacemaker.  

PubMed

Caffeine is the most commonly used psychoactive stimulant worldwide. It reduces sleep and sleepiness by blocking access to the adenosine receptor. The level of adenosine increases during sleep deprivation, and is thought to induce sleepiness and initiate sleep. Light-induced phase shifts of the rest-activity circadian rhythms are mediated by light-responsive neurons of the suprachiasmatic nucleus (SCN) of the hypothalamus, where the circadian clock of mammals resides. Previous studies have shown that sleep deprivation reduces circadian clock phase-shifting capacity and decreases SCN neuronal activity. In addition, application of adenosine agonists and antagonists mimics and blocks, respectively, the effect of sleep deprivation on light-induced phase shifts in behaviour, suggesting a role for adenosine. In the present study, we examined the role of sleep deprivation in and the effect of caffeine on light responsiveness of the SCN. We performed in vivo electrical activity recordings of the SCN in freely moving mice, and showed that the sustained response to light of SCN neuronal activity was attenuated after 6 h of sleep deprivation prior to light exposure. Subsequent intraperitoneal application of caffeine was able to restore the response to light. Finally, we performed behavioural recordings in constant conditions, and found enhanced period lengthening during chronic treatment with caffeine in drinking water in constant light conditions. The data suggest that increased homeostatic sleep pressure changes circadian pacemaker functioning by reducing SCN neuronal responsiveness to light. The electrophysiological and behavioural data together provide evidence that caffeine enhances clock sensitivity to light. PMID:25196050

van Diepen, Hester C; Lucassen, Eliane A; Yasenkov, Roman; Groenen, Inske; Ijzerman, Adriaan P; Meijer, Johanna H; Deboer, Tom

2014-11-01

7

Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons  

Microsoft Academic Search

The mammalian suprachiasmatic nucleus (SCN) is a master circadian pacemaker. It is not known which SCN neurons are autonomous pacemakers or how they synchronize their daily firing rhythms to coordinate circadian behavior. Vasoactive intestinal polypeptide (VIP) and the VIP receptor VPAC2 (encoded by the gene Vipr2) may mediate rhythms in individual SCN neurons, synchrony between neurons, or both. We found

Sara J Aton; Christopher S Colwell; Anthony J Harmar; James Waschek; Erik D Herzog

2005-01-01

8

Circadian Pacemaking in Cells and Circuits of the Suprachiasmatic Nucleus  

PubMed Central

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 ([Ca2+]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/[Ca2+]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

9

Differentially timed extracellular signals synchronize pacemaker neuron clocks.  

PubMed

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

2014-09-01

10

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

11

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

12

Cyclic AMP Signaling Control of Action Potential Firing Rate and Molecular Circadian Pacemaking in the Suprachiasmatic Nucleus  

Microsoft Academic Search

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

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

2011-01-01

13

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

14

Development of the Mouse Circadian Pacemaker: Independence from Environmental Cycles*  

PubMed Central

Summary The freerunning period (?) of the circadian pacemaker underlying the wheel-running activity rhythm of Mus musculus was found to be unaffected by the periods of environmental cycles (maternal and light/dark) under which the mice are raised. Mice born to mothers entrained to periods (T) of 28 or 20 h (ratio of light to dark of 14/10) and maintained on those cycle until beyond puberty showed only a temporary difference in freerunning period when placed into constant darkness. Such temporary ‘after-effects ‘ of entrainment were shown, as had been previously, to occur in animals exposed to non-24-h cycles as adults only.After-effects on the ratio of activity to rest (?/?) were not even temporarily different in animals raised on T = 28 or T = 20.Rearing on T = 28 or T = 20 did not affect the abilities of animals to entrain to these cycles later in life.Measurements from young and old animals as well as remeasurement of the young animals later in their lives revealed several effects of age on the pacemaker: a) After-effects on freerunning period after T = 28 or T = 20 are not greater but last longer in older animals; b) Freerunning period is shorter in younger animals; and c) The ratio of activity to rest changes over time in constant darkness and is greater in young animals. Together these suggest that pacemaker ‘plasticity’ reflected in changes in ? and ?/? over time in constant darkness decreases with age.The length of gestation measured in ‘real’ time was the same in mice entrained to T = 28 or T = 20, demonstrating that gestation is not measured in circadian cycles.

Davis, Fred C.; Menaker, Michael

2013-01-01

15

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

16

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, Maria Luisa

2013-01-01

17

Putative pacemakers in the eyestalk and brain of the crayfish Procambarus clarkii show circadian oscillations in levels of mRNA for crustacean hyperglycemic hormone.  

PubMed

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

18

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

19

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-Castaneda, Julio Cesar; Vigueras-Villasenor, Rosa Maria; Rojas, Patricia; Chavez-Saldana, Margarita; Perez, Oscar Gutierrez; Montes, Sergio; Rios, Camilo

2011-01-01

20

Light and Diurnal Cycle Affect Human Heart Rate: Possible Role for the Circadian Pacemaker  

Microsoft Academic Search

Humans and animals demonstrate diurnal rhythms in physiology and behavior, which are generated by the circadian pacemaker, located in the supra-chiasmatic nucleus (SCN). The endogenous diurnal rhythm of the SCN is synchronized to the diurnal cycle most effectively by light. However, light also influences the SCN and its output instantaneously, as is demonstrated for the immediate effects of light on

Frank A. J. L. Scheer; Lorenz J. P. van Doornen; Ruud M. Buijs

1999-01-01

21

Retrograde Bone Morphogenetic Protein Signaling Shapes a Key Circadian Pacemaker Circuit  

PubMed Central

The neuropeptide pigment-dispersing factor (PDF) synchronizes molecular oscillations within circadian pacemakers in the Drosophila brain. It is expressed in the small ventral lateral neurons (sLNvs) and large ventral lateral neurons, the former being indispensable for maintaining behavioral rhythmicity under free-running conditions. How PDF circuits develop the specific connectivity traits that endow such global behavioral control remains unknown. Here, we show that mature sLNv circuits require PDF signaling during early development, acting through its cognate receptor PDFR at postsynaptic targets. Yet, axonal defects by PDF knockdown are presynaptic and become apparent only after metamorphosis, highlighting a delayed response to a signal released early on. Presynaptic expression of constitutively active bone morphogenetic protein (BMP) receptors prevents pdfr mutants misrouting phenotype, while sLNv-restricted downregulation of BMP signaling components phenocopied pdf01. Thus, we have uncovered a novel mechanism that provides an early “tagging” of synaptic targets that will guide circuit refinement later in development. PMID:23303947

Gorostiza, E. Axel; Ceriani, M. Fernanda

2013-01-01

22

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

23

Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording 1 Published on the World Wide Web on 20 October 1998. 1  

Microsoft Academic Search

The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological mechanisms underlying the circadian rhythm in firing activity. Circadian rhythmicity could not be detected either in spontaneous firing rate or in

Jeroen Schaap; Nico P. A Bos; Marcel T. G de Jeu; Alwin M. S Geurtsen; Johanna H Meijer; Cyriel M. A Pennartz

1999-01-01

24

Entrainment of the human circadian pacemaker to longer-than-24-h days  

PubMed Central

Entrainment of the circadian pacemaker to the light:dark cycle is necessary for rhythmic physiological functions to be appropriately timed over the 24-h day. Nonentrainment results in sleep, endocrine, and neurobehavioral impairments. Exposures to intermittent bright light pulses have been reported to phase shift the circadian pacemaker with great efficacy. Therefore, we tested the hypothesis that a modulated light exposure (MLE) with bright light pulses in the evening would entrain subjects to a light:dark cycle 1 h longer than their own circadian period (?). Twelve subjects underwent a 65-day inpatient study. Individual subject's circadian period was determined in a forced desynchrony protocol. Subsequently, subjects were released into 30 longer-than-24-h days (daylength of ? + 1 h) in one of three light:dark conditions: (i) ?25 lux; (ii) ?100 lux; and (iii) MLE: ?25 lux followed by ?100 lux, plus two 45-min bright light pulses of ?9,500 lux near the end of scheduled wakefulness. We found that lighting levels of ?25 lux were insufficient to entrain all subjects tested. Exposure to ?100 lux was sufficient to entrain subjects, although at a significantly wider phase angle compared with baseline. Exposure to MLE was able to entrain the subjects to the imposed sleep–wake cycles but at a phase angle comparable to baseline. These results suggest that MLE can be used to entrain the circadian pacemaker to non-24-h days. The implications of these findings are important because they could be used to treat circadian misalignment associated with space flight and circadian rhythm sleep disorders such as shift-work disorder. PMID:17502598

Gronfier, Claude; Wright, Kenneth P.; Kronauer, Richard E.; Czeisler, Charles A.

2007-01-01

25

Computational model of electrically coupled, intrinsically distinct pacemaker neurons.  

PubMed

Electrical coupling between neurons with similar properties is often studied. Nonetheless, the role of electrical coupling between neurons with widely different intrinsic properties also occurs, but is less well understood. Inspired by the pacemaker group of the crustacean pyloric network, we developed a multicompartment, conductance-based model of a small network of intrinsically distinct, electrically coupled neurons. In the pyloric network, a small intrinsically bursting neuron, through gap junctions, drives 2 larger, tonically spiking neurons to reliably burst in-phase with it. Each model neuron has 2 compartments, one responsible for spike generation and the other for producing a slow, large-amplitude oscillation. We illustrate how these compartments interact and determine the dynamics of the model neurons. Our model captures the dynamic oscillation range measured from the isolated and coupled biological neurons. At the network level, we explore the range of coupling strengths for which synchronous bursting oscillations are possible. The spatial segregation of ionic currents significantly enhances the ability of the 2 neurons to burst synchronously, and the oscillation range of the model pacemaker network depends not only on the strength of the electrical synapse but also on the identity of the neuron receiving inputs. We also compare the activity of the electrically coupled, distinct neurons with that of a network of coupled identical bursting neurons. For small to moderate coupling strengths, the network of identical elements, when receiving asymmetrical inputs, can have a smaller dynamic range of oscillation than that of its constituent neurons in isolation. PMID:15728775

Soto-Treviño, Cristina; Rabbah, Pascale; Marder, Eve; Nadim, Farzan

2005-07-01

26

A Functional analysis of circadian pacemakers in nocturnal rodents  

Microsoft Academic Search

Summary 1Phase response curves for 15' bright light pulses of four species of nocturnal rodents are described. All show delay phase shifts early in the subjective night, advance shifts in the late subjective night, and relative insensitivity during the subjective day.2The broad scatter in measured phase-shifts is largely due to error of measurement: the response of the pacemakers to light

Serge Daan; Colin S. Pittendrigh

1976-01-01

27

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

28

Drosophila ATF-2 regulates sleep and locomotor activity in pacemaker neurons.  

PubMed

Stress-activated protein kinases such as p38 regulate the activity of transcription factor ATF-2. However, the physiological role of ATF-2, especially in the brain, is unknown. Here, we found that Drosophila melanogaster ATF-2 (dATF-2) is expressed in large ventral lateral neurons (l-LN(v)s) and also, to a much lesser extent, in small ventral lateral neurons, the pacemaker neurons. Only l-LN(v)s were stained with the antibody that specifically recognizes phosphorylated dATF-2, suggesting that dATF-2 is activated specifically in l-LN(v)s. The knockdown of dATF-2 in pacemaker neurons using RNA interference decreased sleep time, whereas the ectopic expression of dATF-2 increased sleep time. dATF-2 knockdown decreased the length of sleep bouts but not the number of bouts. The ATF-2 level also affected the sleep rebound after sleep deprivation and the arousal threshold. dATF-2 negatively regulated locomotor activity, although it did not affect the circadian locomotor rhythm. The degree of dATF-2 phosphorylation was greater in the morning than at night and was enhanced by forced locomotion via the dp38 pathway. Thus, dATF-2 is activated by the locomotor while it increases sleep, suggesting a role for dATF-2 as a regulator to connect sleep with locomotion. PMID:18694958

Shimizu, Hideyuki; Shimoda, Masami; Yamaguchi, Terumi; Seong, Ki-Hyeon; Okamura, Tomoo; Ishii, Shunsuke

2008-10-01

29

A functional analysis of circadian pacemakers in nocturnal rodents  

Microsoft Academic Search

Summary 1.In a preceding paper (Pittendrigh and Daan, 1976a) differences in the lability of the freerunning circadian period (t) in constant darkness (DD) were described among four species of rodents. This lability (i) is strongly correlated with the responses of t to (ii) D2O-administration and to (iii) constant light (LL) of various intensities. The question is raised whether these are

Serge Daan; Colin S. Pittendrigh

1976-01-01

30

Pacemakers  

MedlinePLUS Videos and Cool Tools

... www.X-Plain.com] ct150109 Last reviewed: 01/17/2013 1 This reference summary explains how pacemakers ... www.X-Plain.com] ct150109 Last reviewed: 01/17/2013 2 A pacemaker is an electronic device ...

31

Light-mediated TIM degradation within Drosophila pacemaker neurons (s-LNvs) is neither necessary nor sufficient for delay zone phase shifts.  

PubMed

Circadian systems are entrained and phase shifted by light. In Drosophila, the model of light-mediated phase shifting begins with photon capture by CRYPTOCHROME (CRY) followed by rapid TIMELESS (TIM) degradation. In this study, we focused on phase delays and assayed TIM degradation within individual brain clock neurons in response to light pulses in the early night. Surprisingly, there was no detectable change in TIM staining intensity within the eight pacemaker s-LNvs. This indicates that TIM degradation within s-LNvs is not necessary for phase delays, and similar assays in other genotypes indicate that it is also not sufficient. In contrast, more dorsal circadian neurons appear light-sensitive in the early night. Because CRY is still necessary within the s-LNvs for phase shifting, the results challenge the canonical cell-autonomous molecular model and raise the question of how the pacemaker neuron transcription-translation clock is reset by light in the early night. PMID:20471351

Tang, Chih-Hang Anthony; Hinteregger, Erica; Shang, Yuhua; Rosbash, Michael

2010-05-13

32

Pacemaker Heterogeneity in the Suprachiasmatic Nucleus: Origins and Network Implications  

Microsoft Academic Search

In mammals, the suprachiasmatic nuclei (SCN) in the ventral hypothalamus function as a circadian pacemaker, controlling daily rhythms in behavior and physiology. Together the SCN contain approximately 20,000 neurons that maintain rhythms in firing rate and gene expression. Previous studies led to the assumption that single SCN neurons are capable of self-sustained circadian rhythms. Whether and which SCN neurons can

Alexis Webb

2010-01-01

33

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 transcription. Genetic deletion of these repressors abolishes circadian rhythms in behavior and physiology (2

Huettner, James E.

34

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

35

Optic lobe circadian pacemaker sends its information to the contralateral optic lobe in the cricket Gryllus bimaculatus  

Microsoft Academic Search

The bilaterally paired optic lobe pacemakers of the cricket Gryllus bimaculatus are mutually coupled. In the present study we recorded the neural activity conveyed from the brain toward the optic lobe with a suction electrode to examine the coupling signals. The results demonstrated that the brain efferents to the optic lobe encode the circadian information: Both in constant light (LL)

K. Tomioka; M. Nakamichi; M. Yukizane

1994-01-01

36

Pacemaker phase control versus masking by light: setting the circadian chronotype in dual Octodon degus.  

PubMed

There are two main processes involved in the expression of circadian rhythmicity: entrainment and masking. Whereas the first operates via the central pacemaker to anticipate predictable environmental conditions, masking (mainly induced by light) functions as a direct modulator of the circadian output signal induced by nonpredictable events. The Chilean rodent Octodon degus presents both diurnal and nocturnal chronotypes when given free access to an exercise wheel. Two steady-entrainment phases and graded masking by light seem to generate the wide variability of chronotypes in this species. The aim of this study was to characterize the differential masking by light according to the individual chronotypes, their stability over time, and the influence of wheel running availability and ambient temperature upon the degus' nocturnality. To this end, diurnal and nocturnal degus were subjected to ultradian cycles (1:1-h light-dark [LD]), with and without wheel running availability, and under both normal and high diurnal ambient temperature cycles. The present results show that diurnal and nocturnal degus present a stable masking by light, each according to its respective chronotype. Thus, whereas diurnal animals increased their activity with light, in nocturnal degus light induced a sharp drop in wheel running activity. These two types of masking responses appeared not only when the animals were synchronized to the 12:12-h LD cycle, but also under ultradian cycles. Different masking effects persisted when wheel running was made unavailable and when the animals shifted their circadian activity patterns in response to ultradian cycles or to diurnal exposure to high temperatures. In conclusion, our results show that the positive and negative masking effects of light on diurnal and nocturnal degus, respectively, seem to occur independently of relative phase control by the central pacemaker or the negative masking induced by high environmental temperatures. PMID:20795881

Vivanco, Pablo; Rol, Maria Angeles; Madrid, Juan Antonio

2010-08-01

37

Computational Modeling of the Regulation of Pacemaker Frequency in Dopamine Neurons Marco Huertas and Carmen Canavier  

E-print Network

Computational Modeling of the Regulation of Pacemaker Frequency in Dopamine disorder and drug addiction. The firing pattern of dopamine neurons in behaving a real time interface between a computer and a living neuron. We show

Ullmer, Brygg

38

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

39

Circadian Regulation of the Na+/K+-Atpase Alpha Subunit in the Visual System Is Mediated by the Pacemaker and by Retina Photoreceptors in Drosophila Melanogaster  

PubMed Central

We investigated the diurnal oscillation in abundance of the catalytic ? subunit of the sodium/potassium pump (ATP?) in the brain of Drosophila melanogaster. This rhythm is bimodal and is particularly robust in the glia cells of the lamina, the first optic neuropil. We observed loss of ATP? cycling in lamina glia in behaviourally arrhythmic per01 and tim01 mutants and in flies overexpressing the pro-apoptotic gene hid in the PDF-positive clock neurons. Moreover, the rhythm of ATP? abundance was altered in cry01 and Pdf0 mutants, in flies with a weakened clock mechanism in retina photoreceptor cells and in those subject to downregulation of the neuropeptide ITP by RNAi. This complex, rhythmic regulation of the ? subunit suggests that the sodium/potassium pump may be a key target of the circadian pacemaker to impose daily control on brain activities, such as rhythmic changes in neuronal plasticity, which are best observed in the visual system. PMID:24040028

Damulewicz, Milena; Rosato, Ezio; Pyza, Elzbieta

2013-01-01

40

Circadian regulation of the Na+/K+-ATPase alpha subunit in the visual system is mediated by the pacemaker and by retina photoreceptors in Drosophila melanogaster.  

PubMed

We investigated the diurnal oscillation in abundance of the catalytic ? subunit of the sodium/potassium pump (ATP?) in the brain of Drosophila melanogaster. This rhythm is bimodal and is particularly robust in the glia cells of the lamina, the first optic neuropil. We observed loss of ATP? cycling in lamina glia in behaviourally arrhythmic per(01) and tim(01) mutants and in flies overexpressing the pro-apoptotic gene hid in the PDF-positive clock neurons. Moreover, the rhythm of ATP? abundance was altered in cry(01) and Pdf(0) mutants, in flies with a weakened clock mechanism in retina photoreceptor cells and in those subject to downregulation of the neuropeptide ITP by RNAi. This complex, rhythmic regulation of the ? subunit suggests that the sodium/potassium pump may be a key target of the circadian pacemaker to impose daily control on brain activities, such as rhythmic changes in neuronal plasticity, which are best observed in the visual system. PMID:24040028

Damulewicz, Milena; Rosato, Ezio; Pyza, Elzbieta

2013-01-01

41

Intrinsically Active and Pacemaker Neurons in Pluripotent Stem Cell-Derived Neuronal Populations  

PubMed Central

Summary Neurons generated from pluripotent stem cells (PSCs) self-organize into functional neuronal assemblies in vitro, generating synchronous network activities. Intriguingly, PSC-derived neuronal assemblies develop spontaneous activities that are independent of external stimulation, suggesting the presence of thus far undetected intrinsically active neurons (IANs). Here, by using mouse embryonic stem cells, we provide evidence for the existence of IANs in PSC-neuronal networks based on extracellular multielectrode array and intracellular patch-clamp recordings. IANs remain active after pharmacological inhibition of fast synaptic communication and possess intrinsic mechanisms required for autonomous neuronal activity. PSC-derived IANs are functionally integrated in PSC-neuronal populations, contribute to synchronous network bursting, and exhibit pacemaker properties. The intrinsic activity and pacemaker properties of the neuronal subpopulation identified herein may be particularly relevant for interventions involving transplantation of neural tissues. IANs may be a key element in the regulation of the functional activity of grafted as well as preexisting host neuronal networks. PMID:24672755

Illes, Sebastian; Jakab, Martin; Beyer, Felix; Gelfert, Renate; Couillard-Despres, Sebastien; Schnitzler, Alfons; Ritter, Markus; Aigner, Ludwig

2014-01-01

42

Acceleratory Synapses on Pacemaker Neurons in the Heart Ganglion of a Stomatopod, Squilla Oratoria.  

National Technical Information Service (NTIS)

The pacemaker neurons of the heart ganglion are innervated from the CNS through two pairs of acceleratory nerves. The effect of acceleratory nerve stimulation was examined with intracellular electrodes from the pace-maker cells. The major effects on the p...

A. Watanabe, S. Obara, T. Akiyama

1969-01-01

43

Reduction of scale invariance of activity fluctuations with aging and Alzheimer's disease: Involvement of the circadian pacemaker  

Microsoft Academic Search

Human motor control systems orchestrate complex scale-invariant patterns of activity over a wide range of time scales (minutes to hours). The neural mechanisms underlying scale-invariance are unknown in humans. In rats, the master circadian pacemaker [suprachiasmatic nucleus (SCN)] is crucially involved in scale-invariant activity fluctuations over multiple time scales from minutes to 24 h. Aging and Alzheimer's disease (AD) are

Kun Hu; Eus J. W. van Someren; Steven A. Shea; Frank A. J. L. Scheer

2009-01-01

44

The Clock Input to the First Optic Neuropil of Drosophila melanogaster Expressing Neuronal Circadian Plasticity  

PubMed Central

In the first optic neuropil (lamina) of the fly's visual system, two interneurons, L1 and L2 monopolar cells, and epithelial glial cells show circadian rhythms in morphological plasticity. These rhythms depend on clock gene period (per) and cryptochrome (cry) expression. In the present study, we found that rhythms in the lamina of Drosophila melanogaster may be regulated by circadian clock neurons in the brain since the lamina is invaded by one neurite extending from ventral lateral neurons; the so-called pacemaker neurons. These neurons and the projection to the lamina were visualized by green fluorescent protein (GFP). GFP reporter gene expression was driven by the cry promotor in cry-GAL4/UAS-GFP transgenic lines. We observed that the neuron projecting to the lamina forms arborizations of varicose fibers in the distal lamina. These varicose fibers do not form synaptic contacts with the lamina cells and are immunoreactive to the antisera raised against a specific region of Schistocerca gregaria ion transport peptide (ITP). ITP released in a paracrine way in the lamina cortex, may regulate the swelling and shrinking rhythms of the lamina monopolar cells and the glia by controlling the transport of ions and fluids across cell membranes at particular times of the day. PMID:21760878

Damulewicz, Milena; Pyza, Elzbieta

2011-01-01

45

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

46

Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons.  

PubMed

The discovery of genetic variants in the cholinergic receptor nicotinic CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula-interpeduncular axis as a critical relay circuit in the control of nicotine dependence. Although clear roles for ?3, ?4, and ?5 receptors in nicotine aversion and withdrawal have been established, the cellular and molecular mechanisms that participate in signaling nicotine use and contribute to relapse have not been identified. Here, using translating ribosome affinity purification (TRAP) profiling, electrophysiology, and behavior, we demonstrate that cholinergic neurons, but not peptidergic neurons, of the medial habenula (MHb) display spontaneous tonic firing of 2-10 Hz generated by hyperpolarization-activated cyclic nucleotide-gated (HCN) pacemaker channels and that infusion of the HCN pacemaker antagonist ZD7288 in the habenula precipitates somatic and affective signs of withdrawal. Further, we show that a strong, ?3?4-dependent increase in firing frequency is observed in these pacemaker neurons upon acute exposure to nicotine. No change in the basal or nicotine-induced firing was observed in cholinergic MHb neurons from mice chronically treated with nicotine. We observe, however, that, during withdrawal, reexposure to nicotine doubles the frequency of pacemaking activity in these neurons. These findings demonstrate that the pacemaking mechanism of cholinergic MHb neurons controls withdrawal, suggesting that the heightened nicotine sensitivity of these neurons during withdrawal may contribute to smoking relapse. PMID:24082085

Görlich, Andreas; Antolin-Fontes, Beatriz; Ables, Jessica L; Frahm, Silke; Slimak, Marta A; Dougherty, Joseph D; Ibañez-Tallon, Inés

2013-10-15

47

PDFR and CRY Signaling Converge in a Subset of Clock Neurons to Modulate the Amplitude and Phase of Circadian Behavior in Drosophila  

PubMed Central

Background To synchronize their molecular rhythms, circadian pacemaker neurons must input both external and internal timing cues and, therefore, signal integration between sensory information and internal clock status is fundamental to normal circadian physiology. Methodology/Principal Findings We demonstrate the specific convergence of clock-derived neuropeptide signaling with that of a deep brain photoreceptor. We report that the neuropeptide PDF receptor and the circadian photoreceptor CRYPTOCROME (CRY) are precisely co-expressed in a subset of pacemakers, and that these pathways together provide a requisite drive for circadian control of daily locomotor rhythms. These convergent signaling pathways influence the phase of rhythm generation, but also its amplitude. In the absence of both pathways, PER rhythms were greatly reduced in only those specific pacemakers that receive convergent inputs and PER levels remained high in the nucleus throughout the day. This suggested a large-scale dis-regulation of the pacemaking machinery. Behavioral rhythms were likewise disrupted: in light?dark conditions they were aberrant, and under constant dark conditions, they were lost. Conclusions/Significance We speculate that the convergence of environmental and clock-derived signals may produce a coincident detection of light, synergistic responses to it, and thus more accurate and more efficient re-setting properties. PMID:21559487

Im, Seol Hee; Li, Weihua; Taghert, Paul H.

2011-01-01

48

Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording.  

PubMed

The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological mechanisms underlying the circadian rhythm in firing activity. Circadian rhythmicity could not be detected either in spontaneous firing rate or in other membrane properties when whole-cell measurements were made following an initial phase shortly after membrane rupture. However, this apparent lack of rhythmicity was not due to an unhealthy slice preparation or to seal formation, as a clear day/night difference in firing rate was found in cell-attached recordings. Furthermore, in a subsequent series of whole-cell recordings, membrane properties were assessed directly after membrane rupture, and in this series we did find a significant day/night difference in spontaneous firing rate, input resistance and frequency adaptation. As concerns the participation of different subpopulations of suprachiasmatic nucleus neurons expressing circadian rhythmicity, cluster I neurons exhibited strong rhythmicity, whereas no day/night differences were found in cluster II neurons. Vasopressin-containing cells form a subpopulation of cluster I neurons and showed a more pronounced circadian rhythmicity than the total population of cluster I neurons. In addition to their strong rhythm in spontaneous firing rate they also displayed a day/night difference in membrane potential. PMID:9974136

Schaap, J; Bos, N P; de Jeu, M T; Geurtsen, A M; Meijer, J H; Pennartz, C M

1999-01-01

49

Setting clock speed in mammals: the CK1? tau mutation in mice accelerates the circadian pacemaker by selectively destabilizing PERIOD proteins  

PubMed Central

Summary The intrinsic period of circadian clocks is their defining adaptive property. To identify the biochemical mechanisms whereby casein kinase1 (CK1) determines circadian period in mammals, we created mouse null and tau mutants of Ck1 epsilon. Circadian period lengthened in CK1??/?, whereas CK1?tau/tau shortened circadian period of behaviour in vivo and suprachiasmatic nucleus firing rates in vitro, by accelerating PERIOD-dependent molecular feedback loops. CK1?tau/tau also accelerated molecular oscillations in peripheral tissues, revealing its global role in circadian pacemaking. CK1?tau acted by promoting degradation of both nuclear and cytoplasmic PERIOD, but not CRYPTOCHROME, proteins. Together, these whole animal and biochemical studies explain how tau, as a gain-of-function mutation, acts at a specific circadian phase to promote degradation of PERIOD proteins, and thereby accelerate the mammalian clockwork in brain and periphery. PMID:18400165

Gallego, Monica; Lebiecki, Jake; Brown, Timothy M.; Sladek, Martin; Semikhodskii, Andrei S.; Glossop, Nicholas R.J.; Piggins, Hugh D.; Chesham, Johanna E.; Bechtold, David A.; Yoo, Seung-Hee; Takahashi, Joseph S; Virshup, David M.; Boot-Handford, Raymond P.; Hastings, Michael H.; Loudon, Andrew S.I.

2013-01-01

50

Specific brainstem neurons switch each other into pacemaker mode to drive movement by activating NMDARs  

PubMed Central

Rhythmic activity is central to brain function. In the vertebrate central nervous system, the neuronal circuits for breathing and locomotion involve inhibition and also neurons acting as pacemakers, but identifying the neurons responsible has proven difficult. By studying simple hatchling Xenopus laevis tadpoles, we have already identified a population of electrically coupled hindbrain neurons (dINs) which drive swimming. During rhythm generation dINs release glutamate to excite each other and activate NMDA receptors (NMDARs). The resulting depolarization enables a network mechanism for swimming rhythm generation which depends on reciprocal inhibition between antagonistic right and left sides. Surprisingly, a surgically isolated hemi-CNS without inhibition can still generate swimming-like rhythms. We have now discovered that activation of NMDARs transforms dINs, which normally fire singly to current injection, into pacemakers firing within the normal swimming frequency range (10-25 Hz). When dIN firing is blocked pharmacologically, this NMDAR activation produces 10 Hz membrane potential oscillations which persist when electrical coupling is blocked but not when the voltage-dependent gating of NMDARs by Mg2+ is removed. The NMDA-induced oscillations and pacemaker firing at swimming frequency are unique to the dIN population and do not occur in other spinal neurons. We conclude that NMDAR-mediated self-resetting switches critical neurons which drive swimming into pacemaker mode only during locomotion where it provides an additional, parallel mechanism for rhythm generation. This allows rhythm generation in a half CNS and raises the possibility that such concealed pacemaker properties may be present underlying rhythm generation in other vertebrate brain networks. PMID:21148000

Li, W.-C.; Roberts, A.; Soffe, S. R.

2010-01-01

51

Neuronal influence on peripheral circadian oscillators in pupal Drosophila prothoracic glands  

PubMed Central

Rhythmic expression of period (per) and timeless (tim) genes in central circadian pacemaker neurons and prothoracic gland cells, part of the peripheral circadian oscillators in flies, may synergistically control eclosion rhythms, but their oscillatory profiles remain unclear. Here we show differences and interactions between peripheral and central oscillators using per-luciferase and cytosolic Ca2+ reporter (yellow cameleon) imaging in organotypic prothoracic gland cultures with or without the associated central nervous system. Isolated prothoracic gland cells exhibit light-insensitive synchronous per-transcriptional rhythms. In prothoracic gland cells associated with the central nervous system, however, per transcription is markedly amplified following 12-h light exposure, resulting in the manifestation of day–night rhythms in nuclear PER immunostaining levels and spontaneous Ca2+ spiking. Unlike PER expression, nuclear TIM expression is associated with day–night cycles that are independent of the central nervous system. These results demonstrate that photoreception and synaptic signal transduction in/from the central nervous system coordinate molecular 'gears' in endocrine oscillators to generate physiological rhythms. PMID:22713751

Morioka, Eri; Matsumoto, Akira; Ikeda, Masayuki

2012-01-01

52

Temporal Precision in the Mammalian Circadian System: A Reliable Clock from Less Reliable Neurons  

Microsoft Academic Search

The mammalian SCN contains a biological clock that drives remarkably precise circadian rhythms in vivo and in vitro. This study asks whether the cycle-to-cycle variability of behavioral rhythms in mice can be attributed to precision of individual circadian pacemakers within the SCN or their interactions. The authors measured the standard deviation of the cycle-to-cycle period from 7-day recordings of running

Erik D. Herzog; Sara J. Aton; Rika Numano; Yoshiyuki Sakaki; Hajime Tei

2004-01-01

53

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

54

Hypoxia-activated Ca2+ currents in pacemaker neurones of rat rostral ventrolateral medulla in vitro.  

PubMed Central

We examined the effects of brief periods of hypoxia or application of cyanide on the discharge and membrane properties of medullary pacemaker neurones in slices of the rostral ventrolateral reticular nucleus (RVL) of the medulla oblongata of rats. Stable intracellular recordings were obtained from seventy-nine neurones within the RVL which exhibited spontaneous rhythmic discharge in the absence of excitatory postsynaptic potentials (EPSPs). The membrane potential cycles of these neurones could be reset with an evoked spike without eliciting EPSPs or inhibitory postsynaptic potentials and hence met criteria of RVL pacemaker neurones. Hypoxia, produced by reducing O2 from 95 to 20% for 40 s or exposure to cyanide (30-300 microM for 40 s), reversibly increased neuronal discharge 1.6-fold (20% O2) or 2.6-fold (300 microM cyanide), respectively, in association with membrane depolarization and a significant fall in membrane resistance. The membrane responses to hypoxia and cyanide were observed in the presence of tetrodotoxin (TTX) at a concentration (10 microM) which eliminated spontaneous spikes or spikes evoked by intracellular depolarization. When recorded at a holding potential of -70 mV by single-electrode voltage clamp, hypoxia or cyanide (300 microM) elicited inward currents of 0.44 +/- 0.06 and 0.58 +/- 0.08 nA, respectively, which are attenuated by reducing the concentration of extracellular Ca2+ ions, and abolished by 2 mM CoCl2 and 100 microM NiCl2, but not affected by 50 microM CdCl2, replacement of 83% extracellular Na+, or adenosine deaminase (2U ml-1). We conclude that hypoxia and cyanide directly excite RVL pacemaker neurones in vitro by a common mechanism: activation of Ca2+ channel conductance. Images Figure 5 PMID:8046626

Sun, M K; Reis, D J

1994-01-01

55

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

56

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

PubMed

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. PMID:24939987

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

2014-01-01

57

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

58

Circadian Gene Expression in Individual Fibroblasts  

Microsoft Academic Search

The mammalian circadian timing system is composed of a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain and subsidiary oscillators in most peripheral cell types. While oscillators in SCN neurons are known to function in a self-sustained fashion, peripheral oscillators have been thought to damp rapidly when disconnected from the control exerted by the SCN. Using two reporter

Emi Nagoshi; Camille Saini; Christoph Bauer; Thierry Laroche; Felix Naef; Ueli Schibler

2004-01-01

59

In vivo Circadian Rhythms in Gonadotropin-Releasing Hormone Neurons  

Microsoft Academic Search

Although it is generally accepted that the circadian clock provides a timing signal for the luteinizing hormone (LH) surge, mechanistic explanations of this phenomenon remain underexplored. It is known, for example, that circadian locomotor output cycles kaput (clock) mutant mice have severely dampened LH surges, but whether this phenotype derives from a loss of circadian rhythmicity in the suprachiasmatic nucleus

Jason R. Hickok; Shelley A. Tischkau

2010-01-01

60

Persistent sodium current drives conditional pacemaking in CA1 pyramidal neurons under muscarinic stimulation.  

PubMed

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 (I(NaP)) 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 I(NaP), which then depolarizes the cell from -70 mV to spike threshold. We quantified the relative contributions of I(NaP), hyperpolarization-activated cation current (I(h)), 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 I(NaP) in a positive feedback loop starting near -70 mV and providing increasing inward current to threshold. These results show that the pacemaking "engine" from I(NaP) 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; Bean, Bruce P

2013-09-18

61

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

62

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

63

Circadian and dark-pulse activation of orexin/hypocretin neurons  

PubMed Central

Temporal control of brain and behavioral states emerges as a consequence of the interaction between circadian and homeostatic neural circuits. This interaction permits the daily rhythm of sleep and wake, regulated in parallel by circadian cues originating from the suprachiasmatic nuclei (SCN) and arousal-promoting signals arising from the orexin-containing neurons in the tuberal hypothalamus (TH). Intriguingly, the SCN circadian clock can be reset by arousal-promoting stimuli while activation of orexin/hypocretin neurons is believed to be under circadian control, suggesting the existence of a reciprocal relationship. Unfortunately, since orexin neurons are themselves activated by locomotor promoting cues, it is unclear how these two systems interact to regulate behavioral rhythms. Here mice were placed in conditions of constant light, which suppressed locomotor activity, but also revealed a highly pronounced circadian pattern in orexin neuronal activation. Significantly, activation of orexin neurons in the medial and lateral TH occurred prior to the onset of sustained wheel-running activity. Moreover, exposure to a 6 h dark pulse during the subjective day, a stimulus that promotes arousal and phase advances behavioral rhythms, activated neurons in the medial and lateral TH including those containing orexin. Concurrently, this stimulus suppressed SCN activity while activating cells in the median raphe. In contrast, dark pulse exposure during the subjective night did not reset SCN-controlled behavioral rhythms and caused a transient suppression of neuronal activation in the TH. Collectively these results demonstrate, for the first time, pronounced circadian control of orexin neuron activation and implicate recruitment of orexin cells in dark pulse resetting of the SCN circadian clock. PMID:19055781

Marston, Oliver J; Williams, Rhîannan H; Canal, Maria M; Samuels, Rayna E; Upton, Neil; Piggins, Hugh D

2008-01-01

64

Glial cells physiologically modulate clock neurons and circadian behavior in a calcium-dependent manner  

PubMed Central

Summary Background An important goal of contemporary neuroscience research is to define the neural circuits and synaptic interactions that mediate behavior. In both mammals and Drosophila, the neuronal circuitry controlling circadian behavior has been the subject of intensive investigation, but roles for glial cells in the networks controlling rhythmic behavior have only begun to be defined in recent studies. Results Here, we show that conditional, glial-specific genetic manipulations affecting membrane (vesicle) trafficking, the membrane ionic gradient or calcium signaling lead to circadian arrhythmicity in adult behaving Drosophila. Correlated and reversible effects on a clock neuron peptide transmitter (PDF) and behavior demonstrate the capacity for glia-to-neuron signaling in the circadian circuitry. These studies also reveal the importance of a single type of glial cell – the astrocyte – and glial internal calcium stores in the regulation of circadian rhythms. Conclusions This is the first demonstration in any system that adult glial cells can physiologically modulate circadian neuronal circuitry and behavior. A role for astrocytes and glial calcium signaling in the regulation of Drosophila circadian rhythms emphasizes the conservation of cellular and molecular mechanisms that regulate behavior in mammals and insects. PMID:21497088

Ng, Fanny S.; Tangredi, Michelle M.; Jackson, F. Rob

2011-01-01

65

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

66

Glia-related circadian plasticity in the visual system of Diptera  

PubMed Central

The circadian changes in morphology of the first visual neuropil or lamina of Diptera represent an example of the neuronal plasticity controlled by the circadian clock (circadian plasticity). It is observed in terminals of the compound eye photoreceptor cells, the peripheral oscillators expressing the clock genes. However, it has been found also in their postsynaptic partners, the L1 and L2 monopolar cells, in which the activity of the clock genes have not yet been detected. The circadian input that the L1 and L2 receive seems to originate not only from the retina photoreceptors and from the circadian pacemaker neurons located in the brain, but also from the glial cells that express the clock genes and thus contain circadian oscillators. This paper summarizes the morphological and biochemical rhythms in glia of the optic lobe, shows how they contribute to circadian plasticity, and discusses how glial clocks may modulate circadian rhythms in the lamina. PMID:23986707

Górska-Andrzejak, Jolanta

2012-01-01

67

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

68

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

69

Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons  

PubMed Central

Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day-night cycle. They are orchestrated by a central circadian clock in the brain, the suprachiasmatic nucleus (SCN). Transcription of clock genes is sensitive to metabolic changes in reduction and oxidation (redox); however, circadian cycles in protein oxidation have been reported in anucleate cells, where no transcription occurs. We tested whether the SCN also expresses redox cycles and how such metabolic oscillations might affect neuronal physiology. We detected self-sustained circadian rhythms of SCN redox state that required the molecular clockwork. The redox oscillation could determine the excitability of SCN neurons through non-transcriptional modulation of multiple K+ channels. Thus, dynamic regulation of SCN excitability appears to be closely tied to metabolism that engages the clockwork machinery. PMID:22859819

Wang, Tongfei A.; Yu, Yanxun V.; Govindaiah, Gubbi; Ye, Xiaoying; Artinian, Liana; Coleman, Todd P.; Sweedler, Jonathan V.; Cox, Charles L.; Gillette, Martha U.

2012-01-01

70

Circadian rhythm of redox state regulates excitability in suprachiasmatic nucleus neurons.  

PubMed

Daily rhythms of mammalian physiology, metabolism, and behavior parallel the day-night cycle. They are orchestrated by a central circadian clock in the brain, the suprachiasmatic nucleus (SCN). Transcription of clock genes is sensitive to metabolic changes in reduction and oxidation (redox); however, circadian cycles in protein oxidation have been reported in anucleate cells, where no transcription occurs. We investigated whether the SCN also expresses redox cycles and how such metabolic oscillations might affect neuronal physiology. We detected self-sustained circadian rhythms of SCN redox state that required the molecular clockwork. The redox oscillation could determine the excitability of SCN neurons through nontranscriptional modulation of multiple potassium (K(+)) channels. Thus, dynamic regulation of SCN excitability appears to be closely tied to metabolism that engages the clockwork machinery. PMID:22859819

Wang, Tongfei A; Yu, Yanxun V; Govindaiah, Gubbi; Ye, Xiaoying; Artinian, Liana; Coleman, Todd P; Sweedler, Jonathan V; Cox, Charles L; Gillette, Martha U

2012-08-17

71

[Multilayered control of the Mammalian circadian system].  

PubMed

All mammals show daily rhythms in their physiological activity, for example, sleep-wake cycles. This rhythmicity is endogenously generated by a system called the circadian clock, and is composed of reactions occurring in several neural/cellular layers of multicellular organisms. Inter-cellular and inter-organ communication is important for the synchronous action of circadian rhythmicity across the whole body. The heart of the circadian system lies in the rhythmic neuronal activity of the suprachiasmatic nuclei (SCN) in the brain. The oscillation emerges as cell-autonomous rhythmic gene expression observed in individual SCN neurons. Inter-neuronal communication synchronizes the circadian phase of each neuron within the SCN. The integrated rhythmic SCN activity works as a pacemaker for the circadian clocks of non-SCN cells, each of which also rhythmically express clock genes. The -24-h period length of the circadian rhythm is predominantly determined by reactions at the molecular level. Cell-autonomous circadian oscillation is driven by a negative feedback loop of transcription regulation, where CRY/PER heterodimers act as the transcriptional repressors of their own genes. One of the rate limiting steps of circadian cycling is a phosphorylation of CRY and PER proteins followed by proteasome-mediated degradation of those proteins. Pharmacological and genetic perturbation of the phosphorylation or degradation pathways alters the circadian period length. This review provides a hierarchical view of the circadian system, which is important to uncover the different effects of medical or social perturbations on circadian regulation of inter-cellular synchronization, or cell-autonomous oscillation. PMID:24899350

Ode, Koji L; Ueda, Hiroki R

2014-06-01

72

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

73

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

74

Role of the axodendritic tree in the functioning of Helix bursting neurons: generation of pacemaker activity and propagation of action potentials along the axon  

Microsoft Academic Search

The purpose of this study was to determine the role of the axodendritic tree in the generation of bursting pacemaker activity in the identified Helix RPa1 neuron, which is homologous to the Aplysia R15 cell, and propagation of action potentials along the axons. In doing so, I used recording of RPa1 neuron electrical activity after cutting off the right or

N. I Kononenko

2000-01-01

75

Neuropeptidergic input pathways to the circadian pacemaker center of the Madeira cockroach analysed with an improved injection technique.  

PubMed

Light entrainment pathways synchronize the circadian clock of almost all species of the animal and plant kingdom to the daily light dark cycle. In the Madeira cockroach Rhyparobia (Leucophaea) maderae, the circadian clock is located in the accessory medulla of the brain's optic lobes. The clock has abundant neuropeptides with unknown functions. Previous studies suggested that myoinhibitory peptides (MIPs), orcokinins (ORCs), and allatotropin (AT) take part in light input pathways to the circadian clock. As the sequences of AT and ORCs of R. maderae have not yet been determined, with matrix-assisted laser desorption/ionization-time of flight mass spectrometry, the respective Rhyparobia peptides were characterized. To search for light-like phase-shifting inputs to the circadian clock, Rhyparobia-MIP-1, Rhyparobia-AT, and Rhyparobia-ORC were injected at different circadian times, combined with locomotor activity assays. An improved, less invasive injection method was developed that allowed for the analysis of peptide effects within <2 weeks after injection. Rhyparobia-MIP-1 and Rhyparobia-AT injections resulted in dose-dependent monophasic phase response curves with maximum delays at the beginning of the subjective night, similar to light-dependent phase delays. In contrast to Manduca sexta-AT, Rhyparobia-AT did not phase advance locomotor activity rhythms. Only injections of Rhyparobia-ORCs resulted in a biphasic light-like phase response curve. Thus, it is hypothesized that Rhyparobia-MIP-1 and -AT are candidates for relaying light-dependent delays and/or non-photic inputs to the clock, whereas Rhyparobia-ORCs might be part of the light-entrainment pathways relaying phase delays and advances to the circadian clock of the Madeira cockroach. PMID:23802608

Schulze, Julia; Schendzielorz, Thomas; Neupert, Susanne; Predel, Reinhard; Stengl, Monika

2013-09-01

76

Circadian rhythms in Drosophila.  

PubMed

We discuss some historical features of the circadian in Drosophila melanogaster. We then describe some recent progress from our laboratory in three different areas. First, we discuss the regulation of circadian gene expression as assayed with microarrays. Results are discussed that verify and extend published data, both with respect to the previously identified cycling mRNAs as well as some clustering within the genome of some of the genes that give rise to these circadian transcripts. Also discussed are experiments that attempt to identify transcripts that are enriched in lateral neurons, the key circadian pacemaker cells in the Drosophila brain. Second, the issue of damping within the brain is addressed, by assaying molecular oscillations after many days in constant darkness. Third, the identification of a new circadian mutant is described, which is a fully recessive allele of the gene Clock. The previous allele in flies, as well as the single mutant allele in mice, is a dominant allele. This limits the conclusions that can be drawn from the genetic and molecular analyses in these mutant strains. Results with the new recessive allele not only support the notion that Clock is an important clock gene but also indicate that it contributes more to the amplitude of the rhythm rather than the period. PMID:14712924

Rosbash, Michael; Allada, Ravi; McDonald, Mike; Peng, Ying; Zhao, Jie

2003-01-01

77

A Constant Light-Genetic Screen Identifies KISMET as a Regulator of Circadian Photoresponses  

PubMed Central

Circadian pacemakers are essential to synchronize animal physiology and behavior with the day?night cycle. They are self-sustained, but the phase of their oscillations is determined by environmental cues, particularly light intensity and temperature cycles. In Drosophila, light is primarily detected by a dedicated blue-light photoreceptor: CRYPTOCHROME (CRY). Upon light activation, CRY binds to the pacemaker protein TIMELESS (TIM) and triggers its proteasomal degradation, thus resetting the circadian pacemaker. To understand further the CRY input pathway, we conducted a misexpression screen under constant light based on the observation that flies with a disruption in the CRY input pathway remain robustly rhythmic instead of becoming behaviorally arrhythmic. We report the identification of more than 20 potential regulators of CRY-dependent light responses. We demonstrate that one of them, the chromatin-remodeling enzyme KISMET (KIS), is necessary for normal circadian photoresponses, but does not affect the circadian pacemaker. KIS genetically interacts with CRY and functions in PDF-negative circadian neurons, which play an important role in circadian light responses. It also affects daily CRY-dependent TIM oscillations in a peripheral tissue: the eyes. We therefore conclude that KIS is a key transcriptional regulator of genes that function in the CRY signaling cascade, and thus it plays an important role in the synchronization of circadian rhythms with the day?night cycle. PMID:20041201

Dubruille, Raphaelle; Murad, Alejandro; Rosbash, Michael; Emery, Patrick

2009-01-01

78

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

79

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

80

Spike firing pattern of output neurons of the Limulus circadian clock.  

PubMed

The lateral eyes of the horseshoe crab (Limulus polyphemus) show a daily rhythm in visual sensitivity that is mediated by efferent nerve signals from a circadian clock in the crab's brain. How these signals communicate circadian messages is not known for this or other animals. Here the authors describe in quantitative detail the spike firing pattern of clock output neurons in living horseshoe crabs and discuss its possible significance to clock organization and function. Efferent fiber spike trains were recorded extracellularly for several hours to days, and in some cases, the electroretinogram was simultaneously acquired to monitor eye sensitivity. Statistical features of single- and multifiber recordings were characterized via interval distribution, serial correlation, and power spectral analysis. The authors report that efferent feedback to the eyes has several scales of temporal structure, consisting of multicellular bursts of spikes that group into clusters and packets of clusters that repeat throughout the night and disappear during the day. Except near dusk and dawn, the bursts occur every 1 to 2 sec in clusters of 10 to 30 bursts separated by a minute or two of silence. Within a burst, each output neuron typically fires a single spike with a preferred order, and intervals between bursts and clusters are positively correlated in length. The authors also report that efferent activity is strongly modulated by light at night and that just a brief flash has lasting impact on clock output. The multilayered firing pattern is likely important for driving circadian rhythms in the eye and other target organs. PMID:21775292

Liu, Jiahui S; Passaglia, Christopher L

2011-08-01

81

Circadian rhythmicity and light sensitivity of the zebrafish brain.  

PubMed

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

82

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

83

Interplay between myogenic pacemakers and enteric neurons determine distinct motor patterns in the rat colon.  

PubMed

Waxing and waning of slow waves amplitude has been recently associated with a segmentation motor pattern in the murine small intestine. The 'wax and wane' phenomenon in this area of the gastrointestinal tract seems to be the result of modulation of slow waves by a second pacemaker of a lower frequency displayed by the interstitial cells of Cajal near the deep muscular plexus (ICC-DMP). In the rat colon, smooth muscle cyclic depolarizations causing low-frequency (LF) contractions (0.9 ± 0.1 cpm) occur together with slow wave activity associated to high-frequency (HF) contractions (14 ± 0.3 cpm; ripples). In the present manuscript, we demonstrate the presence of 'wax and wane' in rat colonic slow waves. Depolarization from the 'wax' to the 'wane' was 7.6 ± 1.2 mV, i.e., smooth muscle cells went from a resting membrane potential (RMP) of -50.0 mV to a RMP of -42.4 mV. The amplitude of the slow wave decreased from 14.0 ± 2.2 mV to 3.4 ± 0.7 mV. The wax and wane phenomenon occurred at 0.9 ± 0.1 cpm, coinciding with the frequency of cyclic depolarizations. Therefore, we hypothesized that the 'wax and wane' of slow waves in the rat colon could be the result of their interaction with the LF pacemaker. We describe three different myogenic motor patterns that depend on the level of smooth muscle and ICC excitation: (i) LF propulsive contractions, (ii) regular slow waves causing ripples, and (iii) a wax and wane pattern that may lead to segmentation. Different intra- and extra-luminal inputs probably determine the dominating motor pattern in each area through the enteric nervous system. PMID:25088991

Mañé, N; Jimenez, M

2014-10-01

84

Circadian rhythms: basic neurobiology and clinical applications.  

PubMed

Circadian rhythms are major features of adaptation to our environment. In mammals, circadian rhythms are generated and regulated by a circadian timing system. This system consists of entertainment pathways, pacemakers, and pace-maker output to effector systems that are under circadian control. The primary entertainment pathway is the retinohypothalamic tract, which terminates in the circadian pacemakers, the suprachiasmatic nuclei of the hypothalamus. The output of the suprachiasmatic nuclei is principally to the hypothalamus, the midline thalamus, and the basal forebrain. This provides a temporal organization to the sleep-wake cycle, to many physiological and endocrine functions, and to psychomotor performance functions. Disorders of circadian timing primarily affect entertainment and pacemaker functions. The pineal hormone, melatonin, appears to be promising agent for therapy of some circadian timing disorders. PMID:9046960

Moore, R Y

1997-01-01

85

Correlation with behavioral activity and rest implies circadian regulation by SCN neuronal activity levels.  

PubMed

The SCN of the hypothalamus contains a major pacemaker, which exhibits 24-h rhythms in electrical impulse frequency. Although it is known that SCN electrical activity is high during the day and low during the night, the precise relationship between electrical activity and behavioral rhythms is almost entirely unknown. The authors performed long-term recordings of SCN multiple unit activity with the aid of implanted microelectrodes in parallel with the drinking activity in freely moving mice. The animals were kept in a 12h:12h light-dark cycle (LD 12:12) and in short-day (LD 8:16) and long-day photoperiods (LD 16:8). Onsets and offsets of behavioral activity occurred when SCN discharge was around half-maximum value. Of the onsets 80%, and of the offsets 62%, occurred when SCN electrical activity differed less than 15% from the half-maximum electrical activity levels. Transitions between rest and activity could be described by a sigmoid shaped probability curve with Hill coefficients of 7.0 for onsets and 5.7 for offsets. The similarity in the onset and offset levels shows an absence of hysteresis in the control of behavioral activity by the SCN. Exposure to short- or long-day photoperiods induced significant alterations in the waveform of electrical activity but did not affect SCN electrical activity levels at which behavioral transitions occurred. In all photoperiods, the SCN signal was skewed with more rapid discharge changes during onsets (19% per hour) than offsets (11% per hour). The precision of the circadian system appears optimized, as transitions between behavioral activity and rest occur when the change in SCN electrical activity is maximal, both during the declining and rising phase. The authors conclude that transitions in behavioral state can be described by a probability function around half-maximum electrical activity levels and that the parameters of the SCN, predicting onset and offset of behavior, are remarkably insensitive to environmental conditions. PMID:19926807

Houben, Thijs; Deboer, Tom; van Oosterhout, Floor; Meijer, Johanna H

2009-12-01

86

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

87

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

88

The blue-light photoreceptor CRYPTOCHROME is expressed in a subset of circadian oscillator neurons in the Drosophila CNS.  

PubMed

In the fruit fly Drosophila melanogaster, CRYPTOCHROME (CRY) functions as a photoreceptor to entrain circadian oscillators to light-dark cycles and as a transcription factor to maintain circadian oscillator function in certain peripheral tissues. Given the importance of CRY to circadian clock function, we expected this protein to be expressed in all oscillator cells, yet CRY cellular distribution and subcellular localization has not been firmly established. Here we investigate CRY spatial expression in the brain using a newly developed CRY antibody and a novel set of cry deletion mutants. We find that CRY is expressed in s-LNvs, l-LNvs, and a subset of LNds and DN1s, but not DN2s and DN3s. CRY is present in both the nucleus and the cytoplasm of these neurons, and its subcellular localization does not change over the circadian cycle. Although CRY is absent in DN2s and DN3s, cry promoter activity and/or cry mRNA accumulation can be detected in these neurons, suggesting that CRY levels are regulated posttranscriptionally. Oscillators in DN2s and DN3s entrain to environmental light-dark cycles, which implies that they are entrained indirectly by retinal photoreceptors, extraretinal photoreceptors, or other CRY-expressing cells. PMID:18663237

Benito, Juliana; Houl, Jerry H; Roman, Gregg W; Hardin, Paul E

2008-08-01

89

Solitary and gregarious locusts differ in circadian rhythmicity of a visual output neuron.  

PubMed

Locusts demonstrate remarkable phenotypic plasticity driven by changes in population density. This density dependent phase polyphenism is associated with many physiological, behavioral, and morphological changes, including observations that cryptic solitarious (solitary-reared) individuals start to fly at dusk, whereas gregarious (crowd-reared) individuals are day-active. We have recorded for 24-36 h, from an identified visual output neuron, the descending contralateral movement detector (DCMD) of Schistocerca gregaria in solitarious and gregarious animals. DCMD signals impending collision and participates in flight avoidance maneuvers. The strength of DCMD's response to looming stimuli, characterized by the number of evoked spikes and peak firing rate, varies approximately sinusoidally with a period close to 24 h under constant light in solitarious locusts. In gregarious individuals the 24-h pattern is more complex, being modified by secondary ultradian rhythms. DCMD's strongest responses occur around expected dusk in solitarious locusts but up to 6 h earlier in gregarious locusts, matching the times of day at which locusts of each type are most active. We thus demonstrate a neuronal correlate of a temporal shift in behavior that is observed in gregarious locusts. Our ability to alter the nature of a circadian rhythm by manipulating the rearing density of locusts under identical light-dark cycles may provide important tools to investigate further the mechanisms underlying diurnal rhythmicity. PMID:22653888

Gaten, Edward; Huston, Stephen J; Dowse, Harold B; Matheson, Tom

2012-06-01

90

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

91

Requirement of Mammalian Timeless for Circadian  

E-print Network

a circadian rhythm in neuronal firing rate with a peak near circadian time (CT) 7 over two cycles (22) In control slices, the SCN maintained a circadian rhythm in neuronal firing rate with a peak near circadianRequirement of Mammalian Timeless for Circadian Rhythmicity Jessica W. Barnes,1 * Shelley A

Gillette, Martha U.

92

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

93

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

PubMed

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. 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

94

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

95

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

96

Disruption of Cryptochrome partially restores circadian rhythmicity to the arrhythmic period mutant of Drosophila.  

PubMed

The Drosophila melanogaster circadian clock is generated by interlocked feedback loops, and null mutations in core genes such as period and timeless generate behavioral arrhythmicity in constant darkness. In light-dark cycles, the elevation in locomotor activity that usually anticipates the light on or off signals is severely compromised in these mutants. Light transduction pathways mediated by the rhodopsins and the dedicated circadian blue light photoreceptor cryptochrome are also critical in providing the circadian clock with entraining light signals from the environment. The cry(b) mutation reduces the light sensitivity of the fly's clock, yet locomotor activity rhythms in constant darkness or light-dark cycles are relatively normal, because the rhodopsins compensate for the lack of cryptochrome function. Remarkably, when we combined a period-null mutation with cry(b), circadian rhythmicity in locomotor behavior in light-dark cycles, as measured by a number of different criteria, was restored. This effect was significantly reduced in timeless-null mutant backgrounds. Circadian rhythmicity in constant darkness was not restored, and TIM protein did not exhibit oscillations in level or localize to the nuclei of brain neurons known to be essential for circadian locomotor activity. Therefore, we have uncovered residual rhythmicity in the absence of period gene function that may be mediated by a previously undescribed period-independent role for timeless in the Drosophila circadian pacemaker. Although we do not yet have a molecular correlate for these apparently iconoclastic observations, we provide a systems explanation for these results based on differential sensitivities of subsets of circadian pacemaker neurons to light. PMID:16361445

Collins, Ben H; Dissel, Stephane; Gaten, Edward; Rosato, Ezio; Kyriacou, Charalambos P

2005-12-27

97

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

98

Circadian rhythm of temperature preference and its neural control in Drosophila  

PubMed Central

A daily body temperature rhythm (BTR) is critical for the maintenance of homeostasis in mammals. While mammals use internal energy to regulate body temperature, ectotherms typically regulate body temperature behaviorally [1]. Some ectotherms maintain homeostasis via a daily temperature preference rhythm (TPR) [2], but the underlying mechanisms are largely unknown. Here, we show that Drosophila exhibit a daily circadian clock dependent TPR that resembles mammalian BTR. Pacemaker neurons critical for locomotor activity are not necessary for TPR; instead, the dorsal neuron 2s (DN2s), whose function was previously unknown, is sufficient. This indicates that TPR, like BTR, is controlled independently from locomotor activity. Therefore, the mechanisms controlling temperature fluctuations in fly TPR and mammalian BTR may share parallel features. Taken together, our results reveal the existence of a novel DN2- based circadian neural circuit that specifically regulates TPR; thus, understanding the mechanisms of TPR will shed new light on the function and neural control of circadian rhythms. PMID:22981774

Kaneko, Haruna; Head, Lauren M.; Ling, Jinli; Tang, Xin; Liu, Yilin; Hardin, Paul E.; Emery, Patrick; Hamada, Fumika N.

2012-01-01

99

Mammalian Circadian Rhythms: A Neural Network Model,  

National Technical Information Service (NTIS)

A neural network model provides behavioral, physiological, and anatomical predictions of how circadian rhythms are generated by the suprachiasmatic nuclei (SCN) of the mammalian hypothalamus. The 4-dimensional basic gated pacemaker model is defined in ter...

G. A. Carpenter, S. Grossberg

1987-01-01

100

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

101

Circadian regulation of intracellular G-protein signalling mediates intercellular synchrony and rhythmicity in the suprachiasmatic nucleus  

PubMed Central

Synchronous oscillations of thousands of cellular clocks in the suprachiasmatic nucleus (SCN), the circadian centre, are coordinated by precisely timed cell–cell communication, the principle of which is largely unknown. Here we show that the amount of RGS16 (regulator of G protein signalling 16), a protein known to inactivate G?i, increases at a selective circadian time to allow time-dependent activation of intracellular cyclic AMP signalling in the SCN. Gene ablation of Rgs16 leads to the loss of circadian production of cAMP and as a result lengthens circadian period of behavioural rhythm. The temporally precise regulation of the cAMP signal by clock-controlled RGS16 is needed for the dorsomedial SCN to maintain a normal phase-relationship to the ventrolateral SCN. Thus, RGS16-dependent temporal regulation of intracellular G protein signalling coordinates the intercellular synchrony of SCN pacemaker neurons and thereby defines the 24?h rhythm in behaviour. PMID:21610730

Doi, Masao; Ishida, Atsushi; Miyake, Akiko; Sato, Miho; Komatsu, Rie; Yamazaki, Fumiyoshi; Kimura, Ikuo; Tsuchiya, Soken; Kori, Hiroshi; Seo, Kazuyuki; Yamaguchi, Yoshiaki; Matsuo, Masahiro; Fustin, Jean-Michel; Tanaka, Rina; Santo, Yasuko; Yamada, Hiroyuki; Takahashi, Yukari; Araki, Michihiro; Nakao, Kazuki; Aizawa, Shinichi; Kobayashi, Masaki; Obrietan, Karl; Tsujimoto, Gozoh; Okamura, Hitoshi

2011-01-01

102

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

103

Mitogen-activated protein kinase is a functional component of the autonomous circadian system in the suprachiasmatic nucleus.  

PubMed

The suprachiasmatic nucleus (SCN) is the master circadian pacemaker driving behavioral and physiological rhythms in mammals. Circadian activation of mitogen-activated protein kinase [MAPK; also known as ERK (extracellular signal-regulated kinase)] is observed in vivo in the SCN under constant darkness, although the biological significance of this remains unclear. To elucidate this question, we first examined whether MAPK was autonomously activated in ex vivo SCN slices. Moreover, we investigated the effect of MAPK inhibition on circadian clock gene expression and neuronal firing rhythms using SCN-slice culture systems. We show herein that MAPK is autonomously activated in the SCN, and our data demonstrate that inhibition of the MAPK activity results in dampened rhythms and reduced basal levels in circadian clock gene expression at the SCN single-neuron level. Furthermore, MAPK inhibition attenuates autonomous circadian neuronal firing rhythms in the SCN. Thus, our data suggest that light-independent MAPK activity contributes to the robustness of the SCN autonomous circadian system. PMID:18448638

Akashi, Makoto; Hayasaka, Naoto; Yamazaki, Shin; Node, Koichi

2008-04-30

104

Aging decreases L-type calcium channel currents and pacemaker firing fidelity in substantia nigra dopamine neurons.  

PubMed

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; Beckstead, Michael J

2014-07-01

105

A riot of rhythms: neuronal and glial circadian oscillators in the mediobasal hypothalamus  

Microsoft Academic Search

BACKGROUND: In mammals, the synchronized activity of cell autonomous clocks in the suprachiasmatic nuclei (SCN) enables this structure to function as the master circadian clock, coordinating daily rhythms in physiology and behavior. However, the dominance of this clock has been challenged by the observations that metabolic duress can over-ride SCN controlled rhythms, and that clock genes are expressed in many

Clare Guilding; Alun TL Hughes; Timothy M Brown; Sara Namvar; Hugh D Piggins

2009-01-01

106

Ontogeny of Circadian Organization in the Rat  

Microsoft Academic Search

The mammalian circadian system is orchestrated by a master pacemaker in the brain, but many peripheral tissues also contain independent or quasi-independent circadian oscillators. The adaptive significance of clocks in these structures must lie, in large part, in the phase relationships between the constituent oscillators and their micro- and macroenvironments. To examine the relationship between postnatal development, which is dependent

Shin Yamazaki; Tomoko Yoshikawa; Elizabeth W. Biscoe; Rika Numano; Lauren M. Gallaspy; Stacy Soulsby; Evagelia Papadimas; Pinar Pezuk; Susan E. Doyle; Hajime Tei; Yoshiyuki Sakaki; Gene D. Block; Michael Menaker

2009-01-01

107

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

108

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

109

Mauthner Cell-Initiated Electromotor Behavior Is Mediated via NMDA and Metabotropic Glutamatergic Receptors on Medullary Pacemaker Neurons in a Gymnotid Fish  

Microsoft Academic Search

Weakly electric fish generate meaningful electromotor behav- iors by specific modulations of the discharge of their medullary pacemaker nucleus from which the rhythmic command for each electric organ discharge (EOD) arises. Certain electromo- tor behaviors seem to involve the activation of specific neuro- transmitter receptors on particular target cells within the nu- cleus, i.e., on pacemaker or on relay cells.

Sebastian Curti; Atilio Falconi; Francisco R. Morales; Michel Borde

1999-01-01

110

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

111

GABA and $G_{io}$ Differentially Control Circadian Rhythms and Synchrony in Clock Neurons  

Microsoft Academic Search

Neurons in the mammalian suprachiasmatic nuclei (SCN) generate daily rhythms in physiology and behavior, but it is unclear how they maintain and synchronize these rhythms in vivo. We hypothesized that parallel signaling pathways in the SCN are required to synchronize rhythms in these neurons for coherent output. We recorded firing and clock-gene expression patterns while blocking candidate signaling pathways for

Sara J. Aton; James E. Huettner; Martin Straume; Erik D. Herzog

2006-01-01

112

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

113

Parent-of-origin genetic background affects the transcriptional levels of circadian and neuronal plasticity genes following sleep loss.  

PubMed

Sleep homoeostasis refers to a process in which the propensity to sleep increases as wakefulness progresses and decreases as sleep progresses. Sleep is tightly organized around the circadian clock and is regulated by genetic and epigenetic mechanisms. The homoeostatic response of sleep, which is classically triggered by sleep deprivation, is generally measured as a rebound effect of electrophysiological measures, for example delta sleep. However, more recently, gene expression changes following sleep loss have been investigated as biomarkers of sleep homoeostasis. The genetic background of an individual may affect this sleep-dependent gene expression phenotype. In this study, we investigated whether parental genetic background differentially modulates the expression of genes following sleep loss. We tested the progeny of reciprocal crosses of AKR/J and DBA/2J mouse strains and we show a parent-of-origin effect on the expression of circadian, sleep and neuronal plasticity genes following sleep deprivation. Thus, we further explored, by in silico, specific functions or upstream mechanisms of regulation and we observed that several upstream mechanisms involving signalling pathways (i.e. DICER1, PKA), growth factors (CSF3 and BDNF) and transcriptional regulators (EGR2 and ELK4) may be differentially modulated by parental effects. This is the first report showing that a behavioural manipulation (e.g. sleep deprivation) in adult animals triggers specific gene expression responses according to parent-of-origin genomic mechanisms. Our study suggests that the same mechanism may be extended to other behavioural domains and that the investigation of gene expression following experimental manipulations should take seriously into account parent-of-origin effects. PMID:24446504

Tinarelli, Federico; Garcia-Garcia, Celina; Nicassio, Francesco; Tucci, Valter

2014-03-01

114

Circadian Control of Neuroendocrine Circuits Regulating Female Reproductive Function  

PubMed Central

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

115

PDP1? functions downstream of the circadian oscillator to mediate behavioral rhythms Abbreviated title: PDP1? function in the circadian clock  

PubMed Central

The Drosophila circadian oscillator is comprised of autoregulatory period/timeless (per/tim) and Clock (Clk) feedback loops that control rhythmic transcription. In the Clk loop, CLOCK-CYCLE (CLK-CYC) heterodimers activate vrille (vri) and PAR domain protein 1? (Pdp1?) transcription, then sequential repression by VRI and activation by PDP1? mediate rhythms in Clk transcription. Since VRI and PDP1? bind the same regulatory element, the VRI/PDP1? ratio is thought to control the level of Clk transcription. Thus, constant high or low PDP1? levels in clock cells should eliminate Clk mRNA cycling and disrupt circadian oscillator function. Here we show that reducing PDP1? levels in clock cells by ~70% via RNA interference or increasing PDP1? levels by ~10-fold in clock cells does not alter Clk mRNA cycling or circadian oscillator function. However, constant low or high PDP1? levels in clock cells disrupt locomotor activity rhythms despite persistent circadian oscillator function in brain pacemaker neurons that extend morphologically normal projections into the dorsal brain. These results demonstrate that the VRI/PDP1? ratio neither controls Clk mRNA cycling nor circadian oscillator function, and argue that PDP1? is not essential for Clk activation. PDP1? is nevertheless required for behavioral rhythmicity, which suggests that it functions to regulate oscillator output. PMID:17344391

Benito, Juliana; Zheng, Hao; Hardin, Paul E.

2007-01-01

116

A Gq-Ca2+ Axis Controls Circuit-Level Encoding of Circadian Time in the Suprachiasmatic Nucleus  

PubMed Central

Summary The role of intracellular transcriptional/post-translational feedback loops (TTFL) within the circadian pacemaker of the suprachiasmatic nucleus (SCN) is well established. In contrast, contributions from G-coupled pathways and cytosolic rhythms to the intercellular control of SCN pacemaking are poorly understood. We therefore combined viral transduction of SCN slices with fluorescence/bioluminescence imaging to visualize GCaMP3-reported circadian oscillations of intracellular calcium [Ca2+]i alongside activation of Ca2+/cAMP-responsive elements. We phase-mapped them to the TTFL, in time and SCN space, and demonstrated their dependence upon G-coupled vasoactive intestinal peptide (VIP) signaling. Pharmacogenetic manipulation revealed the individual contributions of Gq, Gs, and Gi to cytosolic and TTFL circadian rhythms. Importantly, activation of Gq-dependent (but not Gs or Gi) pathways in a minority of neurons reprogrammed [Ca2+]i and TTFL rhythms across the entire SCN. This reprogramming was mediated by intrinsic VIPergic signaling, thus revealing a Gq/[Ca2+]i-VIP leitmotif and unanticipated plasticity within network encoding of SCN circadian time. PMID:23623697

Brancaccio, Marco; Maywood, Elizabeth S.; Chesham, Johanna E.; Loudon, Andrew S.I.; Hastings, Michael H.

2013-01-01

117

Distinct visual pathways mediate Drosophila larval light avoidance and circadian clock entrainment  

PubMed Central

Visual organs perceive environmental stimuli required for rapid initiation of behaviors and can also entrain the circadian clock. The larval eye of Drosophila is capable of both functions. Each eye contains only 12 photoreceptors (PRs), which can be subdivided into two subtypes. Four PRs express blue-sensitive rhodopsin5 (rh5) and eight express green-sensitive rhodopsin6 (rh6). We found that either PR-subtype is sufficient to entrain the molecular clock by light, while only the Rh5-PR subtype is essential for light avoidance. Acetylcholine (ACh) released from PRs confers both functions. Both subtypes of larval PRs innervate the main circadian pacemaker neurons of the larva, the PDF-expressing lateral neurons (LNs), providing sensory input to control circadian rhythms. However, we show that PDF-expressing LNs are dispensable for light avoidance, and a distinct set of three clock neurons is required. Thus we have identified distinct sensory and central circuitry regulating light avoidance behavior and clock entrainment. Our findings provide insights into the coding of sensory information for distinct behavioral functions and the underlying molecular and neuronal circuitry. PMID:21525293

Keene, Alex C.; Mazzoni, Esteban O.; Zhen, Jamie; Younger, Meg A.; Yamaguchi, Satoko; Blau, Justin; Desplan, Claude; Sprecher, Simon G.

2011-01-01

118

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

119

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

E-print Network

), 91198 Gif-sur-Yvette, France Keywords: circadian clock, disconnected mutant, PDF neuropeptide, tetanus by overexpressing per and to block synaptic transmission with the tetanus toxin light chain (TeTxLC). Genetic

Rouyer, Francois

120

Adolescent Sleep Deficits Invite Innovative Researc h: The Study of Circadian Phase Preference Delay  

Microsoft Academic Search

Abstract A lack of sufficient sleep is a rampant problem amo ng adolescents today. The effects of sleep deprivation entail the disruption of an indiv idual’s circadian rhythm. The circadian timing system,is the internal mechanism,or pacemaker,that organizes daily biological processes in mammals.,The brain’s circadian timing,system,switches on,later at night as pubertal development,progresses. These changes,in adolescents’ circadian timing systems produce,a pattern of

Kerry Morrison

121

Augmentation of bursting pacemaker activity by serotonin in an identified Achatina fulica neurone: an increase in sodium- and calcium-activated negative slope resistance via cyclic-AMP-dependent protein phosphorylation.  

PubMed

The mechanism of serotonin (5-HT) action on bursting activity was examined in a bursting pacemaker neurone of the snail Achatina fulica. 5-HT augmented both the depolarizing and post-burst-hyperpolarizing phases of the bursting cycle in a dose-dependent manner. This biogenic amine also enhanced the negative slope resistance (NSR), which was normally detectable at membrane potentials between -40 and -20 mV, and produced another NSR at voltages between -20 and 0 mV. The former NSR disappeared in Na(+)-free saline and the latter was abolished by replacement with Co(2+)-substituted Ca(2+)-free saline. Both isobutylmethylxanthine, extracellular applied, and intracellularly applied cyclic AMP simulated a 5-HT effect on the current-voltage relationships. In contrast, the 5-HT effect was suppressed in a dose-dependent manner by prior treatment with a cyclic-AMP-dependent protein kinase inhibitor, isoquinoline sulphonamide. Similar suppression was observed after intracellular injection of a cyclic-AMP-dependent protein kinase inhibitor isolated from bovine muscle. These results suggest that 5-HT may augment the bursting pacemaker activity by its stimulatory effect on both the slow Na+ channels and the Ca2+ channels through cyclic-AMP-dependent protein phosphorylation. PMID:8382731

Funase, K; Watanabe, K; Onozuka, M

1993-02-01

122

Circadian dysfunction may be a key component of the non-motor symptoms of Parkinson's disease: insights from a transgenic mouse model  

PubMed Central

Sleep disorders are nearly ubiquitous among patients with Parkinson’s disease (PD), and they manifest early in the disease process. While there are a number of possible mechanisms underlying these sleep disturbances, a primary dysfunction of the circadian system should be considered as a contributing factor. Our laboratory’s behavioral phenotyping of a well-validated transgenic mouse model of PD reveals that the electrical activity of neurons within the master pacemaker of the circadian system, the suprachiasmatic nuclei (SCN), is already disrupted at the onset of motor symptoms, although the core features of the intrinsic molecular oscillations in the SCN remain functional. Our observations suggest that the fundamental circadian deficit in these mice lies in the signaling output from the SCN, which may be caused by known mechanisms in PD etiology: oxidative stress and mitochondrial disruption. Disruption of the circadian system is expected to have pervasive effects throughout the body and may itself lead to neurological and cardiovascular disorders. In fact, there is much overlap in the non-motor symptoms experienced by PD patients and in the consequences of circadian disruption. This raises the possibility that the sleep and circadian dysfunction experienced by PD patients may not merely be a subsidiary of the motor symptoms, but an integral part of the disease. Furthermore, we speculate that circadian dysfunction can even accelerate the pathology underlying PD. If these hypotheses are correct, more aggressive treatment of the circadian misalignment and sleep disruptions in PD patients early in the pathogenesis of the disease may be powerful positive modulators of disease progression and patient quality of life. PMID:23353924

Willison, L. David; Kudo, Takashi; Loh, Dawn H.; Kuljis, Dika; Colwell, Christopher S.

2014-01-01

123

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

124

Antidepressants and food restriction cycles: evidence for multiple pacemakers in rodents.  

PubMed

Studies involving the suprachiasmatic nuclei (SCN) provide insufficient evidence to support the SCN as master pacemaker(s) in the rodent circadian system. Restricted feeding (RF) cycles act as strong zeitgebers for activity and corticosterone rhythms and provide support for the existence of important secondary pacemakers. These proposed pacemakers show anticipatory behavior, a limited range of entertainment for RF cycles, and prolonged free runs under certain circumstances. Additional evidence supporting a multiple pacemaker model of rodent circadian organization comes from studies involving antidepressants. Lithium treatment lengthens the free-running tau of rat activity rhythms and shifts the range of entrainment towards longer zeitgeber cycles. Lithium also phase delays many rodent rhythms but does not appear to affect the SCN-pineal axis. These data are difficult to explain without involving more than one pacemaker. Models of the rodent system can be developed incorporating multiple pacemakers. To test these models, a multivariate approach will be required. Combining the labeled 2-deoxyglucose method for metabolic mapping and the procedures of fractional desynchronization with antidepressant psychopharmacology and RF cycles may prove to be an important multivariate approach. PMID:3306700

McEachron, D L

1987-01-01

125

The Intergeniculate Leaflet Partially Mediates Effects of Light on Circadian Rhythms  

Microsoft Academic Search

Photic signals affect circadian activity rhythms by both phasic and tonic mechanisms that modulate pacemaker phase and period. In mammals, the effects of light on circadian activity are mediated by the retina, which communicates with the suprahiasmatic nucleus (SCN) by two different anatomical routes: the retino-hypothalamic tract (RHT), originating in the retina, and the geniculo-hypothalamic tract (GHT), arising from a

Gary E. Pickard; Martin R. Ralph; Michael Menaker

1987-01-01

126

Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction  

PubMed Central

Previously, we investigated the role of neuropeptide Y and leptin-sensitive networks in the mediobasal hypothalamus in sleep and feeding and found profound homeostatic and circadian deficits with an intact suprachiasmatic nucleus. We propose that the arcuate nuclei (Arc) are required for the integration of homeostatic circadian systems, including temperature and activity. We tested this hypothesis using saporin toxin conjugated to leptin (Lep-SAP) injected into Arc in rats. Lep-SAP rats became obese and hyperphagic and progressed through a dynamic phase to a static phase of growth. Circadian rhythms were examined over 49 days during the static phase. Rats were maintained on a 12:12-h light-dark (LD) schedule for 13 days and, thereafter, maintained in continuous dark (DD). After the first 13 days of DD, food was restricted to 4 h/day for 10 days. We found that the activity of Lep-SAP rats was arrhythmic in DD, but that food anticipatory activity was, nevertheless, entrainable to the restricted feeding schedule, and the entrained rhythm persisted during the subsequent 3-day fast in DD. Thus, for activity, the circuitry for the light-entrainable oscillator, but not for the food-entrainable oscillator, was disabled by the Arc lesion. In contrast, temperature remained rhythmic in DD in the Lep-SAP rats and did not entrain to restricted feeding. We conclude that the leptin-sensitive network that includes the Arc is required for entrainment of activity by photic cues and entrainment of temperature by food, but is not required for entrainment of activity by food or temperature by photic cues. PMID:23986359

Li, Ai-Jun; Dinh, Thu T.; Jansen, Heiko T.; Ritter, Sue

2013-01-01

127

Circadian light  

PubMed Central

The present paper reflects a work in progress toward a definition of circadian light, one that should be informed by the thoughtful, century-old evolution of our present definition of light as a stimulus for the human visual system. This work in progress is based upon the functional relationship between optical radiation and its effects on nocturnal melatonin suppression, in large part because the basic data are available in the literature. Discussed here are the fundamental differences between responses by the visual and circadian systems to optical radiation. Brief reviews of photometry, colorimetry, and brightness perception are presented as a foundation for the discussion of circadian light. Finally, circadian light (CLA) and circadian stimulus (CS) calculation procedures based on a published mathematical model of human circadian phototransduction are presented with an example. PMID:20377841

2010-01-01

128

Relationships between the circadian system and Alzheimer's disease-like symptoms in Drosophila.  

PubMed

Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer's disease (AD), are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-? (A?) peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing A? peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per01). No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived A? peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic A? peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of A? peptides causes rhythm degradation downstream from the central clock mechanism. PMID:25171136

Long, Dani M; Blake, Matthew R; Dutta, Sudeshna; Holbrook, Scott D; Kotwica-Rolinska, Joanna; Kretzschmar, Doris; Giebultowicz, Jadwiga M

2014-01-01

129

The role of circadian rhythm in breast cancer  

PubMed Central

The circadian rhythm is an endogenous time keeping system shared by most organisms. The circadian clock is comprised of both peripheral oscillators in most organ tissues of the body and a central pacemaker located in the suprachiasmatic nucleus (SCN) of the central nervous system. The circadian rhythm is crucial in maintaining the normal physiology of the organism including, but not limited to, cell proliferation, cell cycle progression, and cellular metabolism; whereas disruption of the circadian rhythm is closely related to multi-tumorigenesis. In the past several years, studies from different fields have revealed that the genetic or functional disruption of the molecular circadian rhythm has been found in various cancers, such as breast, prostate, and ovarian. In this review, we will investigate and present an overview of the current research on the influence of circadian rhythm regulating proteins on breast cancer. PMID:23997531

Li, Shujing; Ao, Xiang

2013-01-01

130

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

131

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

132

Cerebral temperature varies across circadian phases in humans  

Microsoft Academic Search

The 24-hour rhythm of core body temperature (CBT) is commonly used in humans as a tool to assess the oscillation of the central endogenous circadian pacemaker. The invasive nature of the rectal sensor used to collect CBT makes it difficult to use in ambulatory conditions. Here we validate the use of a newly developed brain temperature (BT) sensor against that

Philippe Boudreau; Ari Shechter; Andre Dittmar; Claudine Gehin; Georges Delhomme; Ronald Nocua; Guy Dumont; Diane B. Boivin

2008-01-01

133

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

134

Glial Cell Modulation of Circadian Rhythms  

PubMed Central

Studies of Drosophila and mammals have documented circadian changes in the morphology and biochemistry of glial cells. In addition, it is known that astrocytes of flies and mammals contain evolutionarily conserved circadian molecular oscillators that are similar to neuronal oscillators. In several sections of this review, I summarize the morphological and biochemical rhythms of glia that may contribute to circadian control. I also discuss the evidence suggesting that glia-neuron interactions may be critical for circadian timing in both flies and mammals. Throughout the review, I attempt to compare and contrast findings from these invertebrate and vertebrate models so as to provide a synthesis of current knowledge and indicate potential research avenues that may be useful for better understanding the roles of glial cells in the circadian system. PMID:21732426

JACKSON, F. ROB

2011-01-01

135

The extraretinal eyelet of Drosophila: development, ultrastructure, and putative circadian function.  

PubMed

Circadian rhythms can be entrained by light to follow the daily solar cycle. In Drosophila melanogaster a pair of extraretinal eyelets expressing immunoreactivity to Rhodopsin 6 each contains four photoreceptors located beneath the posterior margin of the compound eye. Their axons project to the region of the pacemaker center in the brain with a trajectory resembling that of Bolwig's organ, the visual organ of the larva. A lacZ reporter line driven by an upstream fragment of the developmental gap gene Krüppel is a specific enhancer element for Bolwig's organ. Expression of immunoreactivity to the product of lacZ in Bolwig's organ persists through pupal metamorphosis and survives in the adult eyelet. We thus demonstrate that eyelet derives from the 12 photoreceptors of Bolwig's organ, which entrain circadian rhythmicity in the larva. Double labeling with anti-pigment-dispersing hormone shows that the terminals of Bolwig's nerve differentiate during metamorphosis in close temporal and spatial relationship to the ventral lateral neurons (LN(v)), which are essential to express circadian rhythmicity in the adult. Bolwig's organ also expresses immunoreactivity to Rhodopsin 6, which thus continues in eyelet. We compared action spectra of entrainment in different fly strains: in flies lacking compound eyes but retaining eyelet (so(1)), lacking both compound eyes and eyelet (so(1);gl(60j)), and retaining eyelet but lacking compound eyes as well as cryptochrome (so(1);cry(b)). Responses to phase shifts suggest that, in the absence of compound eyes, eyelet together with cryptochrome mainly mediates phase delays. Thus a functional role in circadian entrainment first found in Bolwig's organ in the larva is retained in eyelet, the adult remnant of Bolwig's organ, even in the face of metamorphic restructuring. PMID:12417651

Helfrich-Förster, Charlotte; Edwards, Tara; Yasuyama, Kouji; Wisotzki, Barbara; Schneuwly, Stephan; Stanewsky, Ralf; Meinertzhagen, Ian A; Hofbauer, Alois

2002-11-01

136

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

137

Effect of network architecture on synchronization and entrainment properties of the circadian oscillations in the suprachiasmatic nucleus.  

PubMed

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus constitutes the central circadian pacemaker. The SCN receives light signals from the retina and controls peripheral circadian clocks (located in the cortex, the pineal gland, the liver, the kidney, the heart, etc.). This hierarchical organization of the circadian system ensures the proper timing of physiological processes. In each SCN neuron, interconnected transcriptional and translational feedback loops enable the circadian expression of the clock genes. Although all the neurons have the same genotype, the oscillations of individual cells are highly heterogeneous in dispersed cell culture: many cells present damped oscillations and the period of the oscillations varies from cell to cell. In addition, the neurotransmitters that ensure the intercellular coupling, and thereby the synchronization of the cellular rhythms, differ between the two main regions of the SCN. In this work, a mathematical model that accounts for this heterogeneous organization of the SCN is presented and used to study the implication of the SCN network topology on synchronization and entrainment properties. The results show that oscillations with larger amplitude can be obtained with scale-free networks, in contrast to random and local connections. Networks with the small-world property such as the scale-free networks used in this work can adapt faster to a delay or advance in the light/dark cycle (jet lag). Interestingly a certain level of cellular heterogeneity is not detrimental to synchronization performances, but on the contrary helps resynchronization after jet lag. When coupling two networks with different topologies that mimic the two regions of the SCN, efficient filtering of pulse-like perturbations in the entrainment pattern is observed. These results suggest that the complex and heterogeneous architecture of the SCN decreases the sensitivity of the network to short entrainment perturbations while, at the same time, improving its adaptation abilities to long term changes. PMID:22423219

Hafner, Marc; Koeppl, Heinz; Gonze, Didier

2012-01-01

138

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.; Ozkaya, Ozge; Hemsley, Matthew; Kyriacou, Charalambos P.; Rosato, Ezio

2014-01-01

139

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

140

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

141

Myopotential interference inducing pacemaker tachycardia in a DVI programmed pacemaker.  

PubMed

A 67-year-old male, suffering from ventricular tachycardia unresponsive to drug therapy, received a universal AV sequential pacemaker (DDD,M). The pacemaker was programmed in the DVI mode, pacing rate 100 bpm, AV interval 250 ms. After implantation, the patient experiences two episodes of tachycardia that proved to be pacemaker tachycardia with a rate of 150 bpm. The first period was self-terminating, and the second had to be stopped by reprogramming the pulse generator. Pacemaker tachycardia could easily be provoked by instructing the patient to contract the pectoral muscle adjacent to the pulse generator. To our knowledge, this is the first report of pacemaker tachycardia provoked by myopotentials in a pulse generator programmed in the DVI mode. PMID:6209636

van Gelder, L M; El Gamal, M I

1984-11-01

142

Trends in Cardiac Pacemaker Batteries  

PubMed Central

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

143

Plasticity of the intrinsic period of the human circadian timing system.  

PubMed

Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol), which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light ( approximately 450 lux; approximately 1.2 W/m(2)) for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration. PMID:17684566

Scheer, Frank A J L; Wright, Kenneth P; Kronauer, Richard E; Czeisler, Charles A

2007-01-01

144

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

145

Distribution of circadian clock-related proteins in the cephalic nervous system of the silkworm, Bombyx mori.  

PubMed

In the circadian timing systems, input pathways transmit information on the diurnal environmental changes to a core oscillator that generates signals relayed to the body periphery by output pathways. Cryptochrome (CRY) protein participates in the light perception; period (PER), Cycle (CYC), and Doubletime (DBT) proteins drive the core oscillator; and arylalkylamines are crucial for the clock output in vertebrates. Using antibodies to CRY, PER, CYC, DBT, and arylalkylamine N-acetyltransferase (aaNAT), the authors examined neuronal architecture of the circadian system in the cephalic ganglia of adult silkworms. The antibodies reacted in the cytoplasm, never in the nuclei, of specific neurons. A cluster of 4 large Ia(1) neurons in each dorsolateral protocerebrum, a pair of cells in the frontal ganglion, and nerve fibers in the corpora cardiaca and corpora allata were stained with all antibodies. The intensity of PER staining in the Ia(1) cells and in 2 to 4 adjacent small cells oscillated, being maximal late in subjective day and minimal in early night. No other oscillations were detected in any cell and with any antibody. Six small cells in close vicinity to the Ia(1) neurons coexpressed CYC-like and DBT-like, and 4 to 5 of them also coexpressed aaNATlike immunoreactivity; the PER- and CRY-like antigens were each present in separate groups of 4 cells. The CYC- and aaNAT-like antigens were further colocalized in small groups of neurons in the pars intercerebralis, at the venter of the optic tract, and in the subesophageal ganglion. Remaining antibodies reacted with similarly positioned cells in the pars intercerebralis, and the DBT antibody also reacted with the cells in the subesophageal ganglion, but antigen colocalizations were not proven. The results imply that key components of the silkworm circadian system reside in the Ia(1) neurons and that additional, hierarchically arranged oscillators contribute to overt pacemaking. The retrocerebral neurohemal organs seem to serve as outlets transmitting central neural oscillations to the hemolymph. The frontal ganglion may play an autonomous function in circadian regulations. The colocalization of aaNAT- and CYC-like antigens suggests that the enzyme is functionally linked to CYC as in vertebrates and that arylalkylamines are involved in the insect output pathway. PMID:15523109

Sehadová, Hana; Markova, Elitza P; Sehnal, Frantisek; Takeda, Makio

2004-12-01

146

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

147

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

148

Circadian Timekeeping in BALB\\/c and C57BL\\/6 Inbred Mouse Strains  

Microsoft Academic Search

Circadian rhythms of locomotion (wheel-running activity) in 12 inbred mouse strains were recorded for interstrain dif- ferences in 7DD, the endogenous (free-running) period of the circadian pacemaker measured in constant environmental darkness. The results indicate that 1 or more genetic loci influence the value of Tag, and a large (50 min) difference in mean rDD between 2 of the strains,

William J. Schwartz; Pamela Zimmerman

1990-01-01

149

Circadian and CLOCK-Controlled Regulation of the Mouse Transcriptome and Cell Proliferation  

Microsoft Academic Search

Circadian rhythms of cell and organismal physiology are controlled by an autoregulatory transcription-translation feedback loop that regulates the expression of rhythmic genes in a tissue-specific manner. Recent studies have suggested that components of the circadian pacemaker, such as the Clock and Per2 gene products, regulate a wide variety of processes, including obesity, sensitization to cocaine, cancer susceptibility, and morbidity to

Brooke H. Miller; Erin L. McDearmon; Satchidananda Panda; Kevin R. Hayes; Jie Zhang; Jessica L. Andrews; Marina P. Antoch; John R. Walker; Karyn A. Esser; John B. Hogenesch; Joseph S. Takahashi

2007-01-01

150

Scheduled Voluntary Wheel Running Activity Modulates Free-Running Circadian Body Temperature Rhythms in Octodon degus  

Microsoft Academic Search

Entrainment of the circadian pacemaker to nonphotic stimuli, such as scheduled wheel-running activity, is well characterized in nocturnal rodents, but little is known about activity-dependent entrainment in diurnal or crepuscular species. In the present study, effects of scheduled voluntary wheel-running activity on circadian timekeeping were investigated in Octodon degus,a hystricomorph rodent that exhibits robust crepuscular patterns of wakefulness. When housed

Martien J. H. Kas; Dale M. Edgar

2001-01-01

151

Plasticity of Circadian Behavior and the Suprachiasmatic Nucleus Following Exposure to Non24Hour Light Cycles  

Microsoft Academic Search

Period aftereffects are a form of behavioral plasticity in which the free-running period of circadian behavior undergoes experience-dependent changes. It is unclear whether this plasticity is age dependent and whether the changes in behavioral period relate to changes in the SCN or the retina, 2 known circadian pacemakers in mammals. To determine whether these changes vary with age, Per1-luc transgenic

Sara J. Aton; Gene D. Block; Hajime Tei; Shin Yamazaki; Erik D. Herzog

2004-01-01

152

Cryptochrome-positive and -negative clock neurons in Drosophila entrain differentially to light and temperature.  

PubMed

The blue-light photoreceptive protein Cryptochrome (CRY) plays an important role in the light synchronization of the Drosophila circadian clock. Previously, we found that among the approximately 150 clock neurons, many but not all neurons express CRY. We speculated that the CRY-positive pacemaker neurons may be especially important for light entrainment, whereas the CRY-negative neurons may be important for other environmental cues, for example, temperature. To investigate this hypothesis, we tested the entrainability of the clock neurons to out-of-phase light and temperature cycles. When light-dark or light-dim light cycles were shifted by 12 h with respect to temperature cycles, behavioral rhythms of wild-type flies were re-entrained by the light cycles. In this condition, we found that TIMELESS (TIM) level was strongly influenced by the temperature cycles in many CRY-negative clock neurons, suggesting that the CRY-negative neurons have higher sensitivity to temperature. Under the same conditions, cry-null mutants entrained to the temperature cycles or very slowly re-entrained to light-dark cycles. Our results suggest that there are 2 types of clock neurons having differential sensitivities to light and temperature, and CRY is a key component for the preferential entrainment to light. PMID:21135155

Yoshii, Taishi; Hermann, Christiane; Helfrich-Förster, Charlotte

2010-12-01

153

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

154

Candidates for the light entrainment pathway to the circadian clock of the Madeira cockroach Rhyparobia maderae.  

PubMed

The circadian pacemaker controlling locomotor activity rhythms in the Madeira cockroach is located at the accessory medulla (AMe). The ipsi- and contralateral compound eyes provide light input to the AMe, possibly via the ?-aminobutyric acid (GABA)-immunoreactive (-ir) distal tract, which connects the glomeruli of the AMe to the ipsilateral medulla and lamina. To identify possible light-entrainment pathways, double-label immunocytochemistry was performed employing antibodies against GABA, myoinhibitory peptide (MIP), allatotropin (AT) and orcokinin (ORC). While all antisera tested, except the anti-ORC, prominently stained the glomeruli of the AMe, colocalization with anti-GABA was detected neither in the glomeruli nor in the distal tract. However, one median neuron that colocalized GABA-, AT- and MIP-immunoreactivity appeared to connect all glomeruli of the AMe to the medulla and lamina. Furthermore, one distal-frontoventral local neuron with arborizations in all glomeruli of the AMe colocalized anti-AT- and anti-MIP immunoreactivity. As candidates for contralateral light entrainment pathways, one ventromedian and one ventral neuron colocalized MIP- and ORC immunoreactivity, projecting via posterior and anterior commissures. Both branched in the interglomerular region of the AMe, where arborizations co-labeled with anti-ORC- and anti-MIP antisera. A possible role for MIP in light entrainment is supported also by injections of Rhyparobia maderae-specific MIP-2, which generated an all-advance phase-response curve late at night. Future experiments will challenge our hypothesis that GABA-, MIP- and AT-ir neurons provide ipsilateral light entrainment to all glomeruli, while MIP- and ORC-ir neurons carry contralateral light entrainment to the AMe's interglomerular region, either delaying or advancing AMe neurons light-dependently. PMID:24322392

Schendzielorz, Julia; Stengl, Monika

2014-02-01

155

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); Didier Y. R. Stainier (University of California;Department of Biochemistry and Biophysics and Cardiovascular Research Institute); Herwig Baier (University of California;Department of Physiology); Jan Huisken (University of California; Max Planck Institute of Molecular Cell Biology and Genetics;Department of Biochemistry and Biophysics and Cardiovascular Research Institute)

2010-11-12

156

Runaway atrioventricular sequential pacemaker after radiation therapy.  

PubMed

Pacemaker malfunction manifested as a runaway circuitry occurred in two patients after they received radiation therapy for treatment of carcinoma. Both pacemakers were programmable atrioventricular sequential units (DVI) with complementary metal oxide semiconductor circuitry. One pacemaker was directly in the radiation field, whereas the other was not directly within the radiation port. Thus, direct irradiation of an implanted pacemaker should be avoided. It is advisable that a pacemaker be shielded even when the pacemaker is not in the direct field of radiation. PMID:3776991

Lee, R W; Huang, S K; Mechling, E; Bazgan, I

1986-11-01

157

Spontaneous Synchronization of Coupled Circadian Oscillators Didier Gonze,*y  

E-print Network

Spontaneous Synchronization of Coupled Circadian Oscillators Didier Gonze,*y Samuel Bernard, 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 28 h

Bernard, Samuel

158

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

159

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

160

CROSS-DISCIPLINARY PHYSICS AND RELATED AREAS OF SCIENCE AND TECHNOLOGY: Modelling of intercellular synchronization in the Drosophila circadian clock  

NASA Astrophysics Data System (ADS)

In circadian rhythm generation, intercellular signaling factors are shown to play a crucial role in both sustaining intrinsic cellular rhythmicity and acquiring collective behaviours across a population of circadian neurons. However, the physical mechanism behind their role remains to be fully understood. In this paper, we propose an indirectly coupled multicellular model for the synchronization of Drosophila circadian oscillators combining both intracellular and intercellular dynamics. By simulating different experimental conditions, we find that such an indirect coupling way can synchronize both heterogeneous self-sustained circadian neurons and heterogeneous mutational damped circadian neurons. Moreover, they can also be entrained to ambient light-dark (LD) cycles depending on intercellular signaling.

Wang, Jun-Wei; Chen, Ai-Min; Zhang, Jia-Jun; Yuan, Zhan-Jiang; Zhou, Tian-Shou

2009-03-01

161

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.

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

2014-01-01

162

Circadian System, Sleep and Endocrinology  

PubMed Central

Levels of numerous hormones vary across the day and night. Such fluctuations are not only attributable to changes in sleep/wakefulness and other behaviors but also to a biological timing system governed by the suprachiasmatic nucleus of the hypothalamus. Sleep has a strong effect on levels of some hormones such as growth hormone but little effect on others which are more strongly regulated by the biological timing system (e.g., melatonin). Whereas the exact mechanisms through which sleep affects circulating hormonal levels are poorly understood, more is known about how the biological timing system influences the secretion of hormones. The suprachiasmatic nucleus exerts its influence on hormones via neuronal and humoral signals but it is also now apparent that peripheral cells can rhythmically secrete hormones independent of signals from the suprachiasmatic nucleus. Under normal circumstances, behaviors and the biological timing system are synchronized and consequently hormonal systems are exquisitely regulated. However, many individuals (e.g., shift-workers) frequently undergo circadian misalignment by desynchronizing their sleep/wake cycle from the biological timing system. Recent experiments indicate that circadian misalignment has an adverse effect on metabolic and hormonal factors such as glucose and insulin. Further research is needed to determine the underlying mechanisms that cause the negative effects induced by circadian misalignment. Such research could aid the development of countermeasures for circadian misalignment. PMID:21939733

Morris, Christopher J.; Aeschbach, Daniel; Scheer, Frank A.J.L.

2011-01-01

163

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

164

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

165

Ethanol consumption in mice: relationships with circadian period and entrainment.  

PubMed

A functional connection between the circadian timing system and alcohol consumption is suggested by multiple lines of converging evidence. Ethanol consumption perturbs physiological rhythms in hormone secretion, sleep, and body temperature; and conversely, genetic and environmental perturbations of the circadian system can alter alcohol intake. A fundamental property of the circadian pacemaker, the endogenous period of its cycle under free-running conditions, was previously shown to differ between selectively bred high- (HAP) and low- (LAP) alcohol preferring replicate 1 mice. To test whether there is a causal relationship between circadian period and ethanol intake, we induced experimental, rather than genetic, variations in free-running period. Male inbred C57Bl/6J mice and replicate 2 male and female HAP2 and LAP2 mice were entrained to light:dark cycles of 26 or 22 h or remained in a standard 24 h cycle. On discontinuation of the light:dark cycle, experimental animals exhibited longer and shorter free-running periods, respectively. Despite robust effects on circadian period and clear circadian rhythms in drinking, these manipulations failed to alter the daily ethanol intake of the inbred strain or selected lines. Likewise, driving the circadian system at long and short periods produced no change in alcohol intake. In contrast with replicate 1 HAP and LAP lines, there was no difference in free-running period between ethanol naïve HAP2 and LAP2 mice. HAP2 mice, however, were significantly more active than LAP2 mice as measured by general home-cage movement and wheel running, a motivated behavior implicating a selection effect on reward systems. Despite a marked circadian regulation of drinking behavior, the free-running and entrained period of the circadian clock does not determine daily ethanol intake. PMID:20880659

Trujillo, Jennifer L; Do, David T; Grahame, Nicholas J; Roberts, Amanda J; Gorman, Michael R

2011-03-01

166

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

167

Interactions of the Circadian CLOCK System and the HPA Axis  

PubMed Central

Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli. These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks, the circadian CLOCK and stress systems, which respectively consist of oscillating molecular pacemakers, the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal (HPA) axis and its end-effector, the glucocorticoid receptor. These systems communicate with each other at different signaling levels, and dysregulation of either system may lead to development of pathologic conditions. In this review, we summarize the mutual physiologic interactions between the circadian CLOCK system and the HPA axis, and discuss their clinical implications. PMID:20106676

Nader, Nancy; Chrousos, George P.; Kino, Tomoshige

2010-01-01

168

Cerebral temperature varies across circadian phases in humans.  

PubMed

The 24-hour rhythm of core body temperature (CBT) is commonly used in humans as a tool to assess the oscillation of the central endogenous circadian pacemaker. The invasive nature of the rectal sensor used to collect CBT makes it difficult to use in ambulatory conditions. Here we validate the use of a newly developed brain temperature (BT) sensor against that of a standard rectal temperature sensor using a 72-hour ultra-rapid sleep-wake (URSW) cycle procedure. A significant circadian variation of both body temperature recordings was observed from which a phase and amplitude was reliably determined. These results indicate that BT can be refined as a non-invasive alternative to CBT measurements in the evaluation of circadian phase in field conditions. PMID:19163804

Boudreau, Philippe; Shechter, Ari; Dittmar, Andre; Gehin, Claudine; Delhomme, Georges; Nocua, Ronald; Dumont, Guy; Boivin, Diane B

2008-01-01

169

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

170

Electrical interference in non-competitive pacemakers  

PubMed Central

Patients with 41 implanted non-competitive pacemakers were investigated. A variety of domestic electrical equipment, a motor-car, and a physiotherapy diathermy apparatus were each operated in turn at various ranges from the patient. Interference effects on pacemaker function were assessed on the electrocardiograph. Medtronic demand 5841 pacemakers were stopped by diathermy while Cordis Ectocor pacemakers developed a fast discharge rate. Cordis triggered pacemakers (both Atricor and Ectocor) were sensitive to interference from many items of domestic equipment and the motor car. The Elema EM153 ran at an increased rate when an electric razor was running close to the pacemaker. The Devices demand 2980 and the Medtronic demand 5841 were not affected by the domestic equipment tested. The significance of interference effects is discussed in relation to pacemaker design. Images PMID:5470044

Sowton, E.; Gray, K.; Preston, T.

1970-01-01

171

[Wide QRS tachycardia preceded by pacemaker spikes].  

PubMed

The differential diagnosis and therapeutic management of wide QRS tachycardia preceded by pacemaker spike is presented. The pacemaker-mediated tachycardia, tachycardia fibrillo-flutter in patients with pacemakers, and runaway pacemakers, have a similar surface electrocardiogram, but respond to different therapeutic measures. The tachycardia response to the application of a magnet over the pacemaker could help in the differential diagnosis, and in some cases will be therapeutic, as in the case of a tachycardia-mediated pacemaker. Although these conditions are diagnosed and treated in hospitals with catheterization laboratories using the application programmer over the pacemaker, patients presenting in primary care clinic and emergency forced us to make a diagnosis and treat the haemodynamically unstable patient prior to referral. PMID:23768570

Romero, M; Aranda, A; Gómez, F J; Jurado, A

2014-04-01

172

Circadian Period Integrates Network Information Through Activation of the BMP Signaling Pathway  

PubMed Central

Living organisms use biological clocks to maintain their internal temporal order and anticipate daily environmental changes. In Drosophila, circadian regulation of locomotor behavior is controlled by ?150 neurons; among them, neurons expressing the PIGMENT DISPERSING FACTOR (PDF) set the period of locomotor behavior under free-running conditions. To date, it remains unclear how individual circadian clusters integrate their activity to assemble a distinctive behavioral output. Here we show that the BONE MORPHOGENETIC PROTEIN (BMP) signaling pathway plays a crucial role in setting the circadian period in PDF neurons in the adult brain. Acute deregulation of BMP signaling causes period lengthening through regulation of dClock transcription, providing evidence for a novel function of this pathway in the adult brain. We propose that coherence in the circadian network arises from integration in PDF neurons of both the pace of the cell-autonomous molecular clock and information derived from circadian-relevant neurons through release of BMP ligands. PMID:24339749

Beckwith, Esteban J.; Gorostiza, E. Axel; Berni, Jimena; Rezaval, Carolina; Perez-Santangelo, Agustin; Nadra, Alejandro D.; Ceriani, Maria Fernanda

2013-01-01

173

Modeling some properties of circadian rhythms.  

PubMed

Mathematical models have been very useful in biological research. From the interaction of biology and mathematics, new problems have emerged that have generated advances in the theory, suggested further experimental work and motivated plausible conjectures. From our perspective, it is absolutely necessary to incorporate modeling tools in the study of circadian rhythms and that without a solid mathematical framework a real understanding of them will not be possible. Our interest is to study the main process underlying the synchronization in the pacemaker of a circadian system: these mechanisms should be conserved in all living beings. Indeed, from an evolutionary perspective, it seems reasonable to assume that either they have a common origin or that they emerge from similar selection circumstances. We propose a general framework to understand the emergence of synchronization as a robust characteristic of some cooperative systems of non-linear coupled oscillators. In a first approximation to the problem we vary the topology of the network and the strength of the interactions among oscillators. In order to study the emergent dynamics, we carried out some numerical computations. The results are consistent with experiments reported in the literature. Finally, we proposed a theoretical framework to study the phenomenon of synchronization in the context of circadian rhythms: the dissipative synchronization of nonautonomous dynamical systems. PMID:24245720

Lara-Aparicio, Miguel; Barriga-Montoya, Carolina; Padilla-Longoria, Pablo; Fuentes-Pardo, Beatriz

2014-04-01

174

Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes  

PubMed Central

Circadian pacemaking requires the orderly synthesis, posttranslational modification, and degradation of clock proteins. In mammals, mutations in casein kinase 1 (CK1) ? or ? can alter the circadian period, but the particular functions of the WT isoforms within the pacemaker remain unclear. We selectively targeted WT CK1? and CK1? using pharmacological inhibitors (PF-4800567 and PF-670462, respectively) alongside genetic knockout and knockdown to reveal that CK1 activity is essential to molecular pacemaking. Moreover, CK1? is the principal regulator of the clock period: pharmacological inhibition of CK1?, but not CK1?, significantly lengthened circadian rhythms in locomotor activity in vivo and molecular oscillations in the suprachiasmatic nucleus (SCN) and peripheral tissue slices in vitro. Period lengthening mediated by CK1? inhibition was accompanied by nuclear retention of PER2 protein both in vitro and in vivo. Furthermore, phase mapping of the molecular clockwork in vitro showed that PF-670462 treatment lengthened the period in a phase-specific manner, selectively extending the duration of PER2-mediated transcriptional feedback. These findings suggested that CK1? inhibition might be effective in increasing the amplitude and synchronization of disrupted circadian oscillators. This was tested using arrhythmic SCN slices derived from Vipr2?/? mice, in which PF-670462 treatment transiently restored robust circadian rhythms of PER2::Luc bioluminescence. Moreover, in mice rendered behaviorally arrhythmic by the Vipr2?/? mutation or by constant light, daily treatment with PF-670462 elicited robust 24-h activity cycles that persisted throughout treatment. Accordingly, selective pharmacological targeting of the endogenous circadian regulator CK1? offers an avenue for therapeutic modulation of perturbed circadian behavior. PMID:20696890

Meng, Qing-Jun; Maywood, Elizabeth S.; Bechtold, David A.; Lu, Wei-Qun; Li, Jian; Gibbs, Julie E.; Dupre, Sandrine M.; Chesham, Johanna E.; Rajamohan, Francis; Knafels, John; Sneed, Blossom; Zawadzke, Laura E.; Ohren, Jeffrey F.; Walton, Kevin M.; Wager, Travis T.; Hastings, Michael H.; Loudon, Andrew S. I.

2010-01-01

175

Control of rat hypothalamic pro-opiomelanocortin neurons by a circadian clock that is entrained by the daily light-off signal  

Microsoft Academic Search

Previous studies have clearly demonstrated that the immediate-early gene, c-fos can regulate, through its protein product Fos, the expression of the pro-opiomelanocortin gene. In the present study, immunohistochemistry for Fos and ?-endorphin was used to assess the basal activity of hypothalamic pro-opiomelanocortin-producing neurons throughout a 12h light\\/12h dark cycle. Here, we showed that Fos is undetectable in most ?-endorphin neurons

K. A Jamali; G Tramu

1999-01-01

176

Changing the Waveform of Circadian Rhythms: Considerations for Shift-Work  

PubMed Central

Circadian disruption in shift-work is common and has deleterious effects on health and performance. Current efforts to mitigate these harms reasonably focus on the phase of the circadian pacemaker, which unfortunately in humans, shifts slowly and often incompletely. Temporal reorganization of rhythmic waveform (i.e., the shape of its 24?h oscillation), rather than phase, however, may better match performance demands of shift-workers and can be quickly and feasibly implemented in animals. In fact, a bifurcated pacemaker waveform may permit stable entrainment of a bimodal sleep/wake rhythm promoting alertness in both night and daylight hours. Although bifurcation has yet to be formally assessed in humans, evidence of conserved properties of circadian organization and plasticity predict its occurrence: humans respond to conventional manipulations of waveform (e.g., photoperiodism); behaviorally, the sleep/wake rhythm is adaptable; and finally, the human circadian system likely derives from the same multiple cellular oscillators that permit waveform flexibility in the rodent pacemaker. In short, investigation into untried manipulations of waveform in humans to facilitate adjustment to challenging schedules is justified. PMID:22557994

Harrison, Elizabeth M.; Gorman, Michael R.

2012-01-01

177

Bioimpedance in the pacemaker clinic.  

PubMed

Thoracic electrical bioimpedance (TEB) provides a rapid, accurate, cost-effective method of optimizing the atrioventricular delay in dual-chamber pacemakers. In addition to measurements of cardiac output, TEB provides other hemodynamic indices such as systolic time interval, left cardiac work index, and end diastolic index. The availability of this additional data can assist the clinician in the objective determination of the optimal atrioventricular delay for individual patients. Thoracic electrical bioimpedance is completely noninvasive and takes only minutes to perform. PMID:10745711

Belott, P

1999-08-01

178

21 CFR 870.3620 - Pacemaker lead adaptor.  

...2014-04-01 2014-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a...

2014-04-01

179

21 CFR 870.3620 - Pacemaker lead adaptor.  

Code of Federal Regulations, 2011 CFR

...2011-04-01 2011-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a...

2011-04-01

180

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 870.3620...Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a...

2012-04-01

181

21 CFR 870.3620 - Pacemaker lead adaptor.  

Code of Federal Regulations, 2010 CFR

...2010-04-01 2010-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a...

2010-04-01

182

21 CFR 870.3620 - Pacemaker lead adaptor.  

Code of Federal Regulations, 2013 CFR

...2013-04-01 2013-04-01 false Pacemaker lead adaptor. 870.3620 Section 870.3620...Prosthetic Devices § 870.3620 Pacemaker lead adaptor. (a) Identification. A pacemaker lead adaptor is a device used to adapt a...

2013-04-01

183

The enigma of behavioral inputs to the circadian clock: a test of function using restraint.  

PubMed

Wheel running stimulated during the daily rest period can acutely shift circadian rhythms in Syrian hamsters. Spontaneous running, defining the active phase of the circadian rest-activity cycle, can shorten the circadian periodicity in constant light or dark in several nocturnal rodent species. The adaptive significance of these behavioral effects on pacemaker phase and period is unclear. Here we consider a hypothesis that behavioral inputs to the circadian pacemaker serve primarily to enhance the precision of light-dark entrainment and maintain daily activity onset close to lights-off (i.e., dusk) by stabilizing entrainment on a steeper portion of the delay zone of the phase-response curve to light. This hypothesis rests on the evidence that spontaneous activity early in the active period feeds back on the pacemaker to advance its motion. If so, then preventing activity at this time should induce a phase delay shift. Such delay shifts have been reported in Syrian hamsters physically restrained early in the active period. We show here that restraint can induce phase delays but that, using the Aschoff Type 2 procedure for measuring shifts, these delays are very small, are inversely related to behavioral sleep during restraint, and are positively correlated with 'rebound' increases in running following restraint, at a circadian time when stimulated running is known to induce phase delay shifts. Repeated bouts of restraint, to promote habituation, were associated with strong attenuation of 'rebound' running and no significant delay shifts. These results suggest that, in Syrian hamsters, spontaneous activity early at night has little effect on pacemaker motion, and argue against the stated hypothesis. PMID:16580032

Mistlberger, Ralph E; Antle, Michael C

2006-05-30

184

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

185

The crayfish Procambarus clarkii CRY shows daily and circadian variation.  

PubMed

The circadian rhythms of crayfish are entrained by blue light, through putative extra retinal photoreceptors. We investigated the presence and daily variation of CRY, a protein photosensitive to blue light spectra and ubiquitous in animals and plants, in the putative pacemakers of Procambarus clarkii, namely the eyestalk and brain, at different times of the 24 h light:dark cycles. Using different experimental light protocols and by means of qualitative/quantitative immunofluorescence anatomical and biochemical methods, we identified CRY immunoreactivity in cells located in the medulla-terminalis-hemiellipsoidal complex (MT-HB) and the anterior margin of the median protocerebrum (PR). The immunoreaction varied with the time of day and the two neural structures showed a semi-mirror image. The results of the biochemical analysis matched these variations. Western blotting demonstrated statistically significant circadian rhythms in brain CRY abundance, but no daily circadian CRY abundance oscillations in the eyestalk. These immunocytochemical and biochemical results link a specific photoreceptor molecule to circadian rhythmicity. We propose that CRY may be linked to the photoreception of the clock and to the generation of circadian rhythmicity. PMID:15037639

Fanjul-Moles, María Luisa; Escamilla-Chimal, Elsa G; Gloria-Osorio, Andrea; Hernández-Herrera, Gabriela

2004-04-01

186

Entraining signals initiate behavioral circadian rhythmicity in larval zebrafish.  

PubMed

The authors show that a circadian clock that regulates locomotor activity in larval zebrafish develops gradually over the first 4 days of life and that exposure to entraining signals late in embryonic development is necessary for initiation of robust behavioral rhythmicity. When zebrafish larvae were transferred from a light-dark (LD) cycle to constant darkness (DD) on the third or fourth day postfertilization, the locomotor activity of almost all fish was rhythmic on days 5 to 9 postfertilization, with peak activity occurring during the subjective day. Rhythm amplitude was higher after four LD cycles than after three LD cycles. When embryos were transferred from LD to DD on the second day postfertilization, only about half of the animals later displayed statistically significant activity rhythms. These rhythms were noisier and of lower amplitude, but phased normally. When zebrafish were raised in DD beginning at 14 h postfertilization, only 22% of them expressed significant circadian rhythmicity as larvae. These rhythms were of low amplitude and phase-locked to the time of handling on the third day rather than to the maternal LD cycle. These results show that behavioral rhythmicity in zebrafish is regulated by a pacemaking system that is sensitive to light by the second day of embryogenesis but continues to develop into the fourth day. This pacemaking system requires environmental signals to initiate or synchronize circadian rhythmicity. PMID:12164247

Hurd, Mark W; Cahill, Gregory M

2002-08-01

187

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

188

Dissociation of Circadian and Circatidal Timekeeping in the Marine Crustacean Eurydice pulchra  

PubMed Central

Summary Background Tidal (12.4 hr) cycles of behavior and physiology adapt intertidal organisms to temporally complex coastal environments, yet their underlying mechanism is unknown. However, the very existence of an independent “circatidal” clock has been disputed, and it has been argued that tidal rhythms arise as a submultiple of a circadian clock, operating in dual oscillators whose outputs are held in antiphase i.e., ?12.4 hr apart. Results We demonstrate that the intertidal crustacean Eurydice pulchra (Leach) exhibits robust tidal cycles of swimming in parallel to circadian (24 hr) rhythms in behavioral, physiological and molecular phenotypes. Importantly, ?12.4 hr cycles of swimming are sustained in constant conditions, they can be entrained by suitable stimuli, and they are temperature compensated, thereby meeting the three criteria that define a biological clock. Unexpectedly, tidal rhythms (like circadian rhythms) are sensitive to pharmacological inhibition of Casein kinase 1, suggesting the possibility of shared clock substrates. However, cloning the canonical circadian genes of E. pulchra to provide molecular markers of circadian timing and also reagents to disrupt it by RNAi revealed that environmental and molecular manipulations that confound circadian timing do not affect tidal timing. Thus, competent circadian timing is neither an inevitable nor necessary element of tidal timekeeping. Conclusions We demonstrate that tidal rhythms are driven by a dedicated circatidal pacemaker that is distinct from the circadian system of E. pulchra, thereby resolving a long-standing debate regarding the nature of the circatidal mechanism. PMID:24076244

Zhang, Lin; Hastings, Michael H.; Green, Edward W.; Tauber, Eran; Sladek, Martin; Webster, Simon G.; Kyriacou, Charalambos P.; Wilcockson, David C.

2013-01-01

189

Serotonin modulates circadian entrainment in Drosophila.  

PubMed

Entrainment of the Drosophila circadian clock to light involves the light-induced degradation of the clock protein timeless (TIM). We show here that this entrainment mechanism is inhibited by serotonin, acting through the Drosophila serotonin receptor 1B (d5-HT1B). d5-HT1B is expressed in clock neurons, and alterations of its levels affect molecular and behavioral responses of the clock to light. Effects of d5-HT1B are synergistic with a mutation in the circadian photoreceptor cryptochrome (CRY) and are mediated by SHAGGY (SGG), Drosophila glycogen synthase kinase 3beta (GSK3beta), which phosphorylates TIM. Levels of serotonin are decreased in flies maintained in extended constant darkness, suggesting that modulation of the clock by serotonin may vary under different environmental conditions. These data identify a molecular connection between serotonin signaling and the central clock component TIM and suggest a homeostatic mechanism for the regulation of circadian photosensitivity in Drosophila. PMID:15996552

Yuan, Quan; Lin, Fangju; Zheng, Xiangzhong; Sehgal, Amita

2005-07-01

190

Weakly Circadian Cells Improve Resynchrony  

PubMed Central

The mammalian suprachiasmatic nuclei (SCN) contain thousands of neurons capable of generating near 24-h rhythms. When isolated from their network, SCN neurons exhibit a range of oscillatory phenotypes: sustained or damping oscillations, or arrhythmic patterns. The implications of this variability are unknown. Experimentally, we found that cells within SCN explants recover from pharmacologically-induced desynchrony by re-establishing rhythmicity and synchrony in waves, independent of their intrinsic circadian period We therefore hypothesized that a cell's location within the network may also critically determine its resynchronization. To test this, we employed a deterministic, mechanistic model of circadian oscillators where we could independently control cell-intrinsic and network-connectivity parameters. We found that small changes in key parameters produced the full range of oscillatory phenotypes seen in biological cells, including similar distributions of period, amplitude and ability to cycle. The model also predicted that weaker oscillators could adjust their phase more readily than stronger oscillators. Using these model cells we explored potential biological consequences of their number and placement within the network. We found that the population synchronized to a higher degree when weak oscillators were at highly connected nodes within the network. A mathematically independent phase-amplitude model reproduced these findings. Thus, small differences in cell-intrinsic parameters contribute to large changes in the oscillatory ability of a cell, but the location of weak oscillators within the network also critically shapes the degree of synchronization for the population. PMID:23209395

Thoroughman, Kurt A.; Doyle, Francis J.; Herzog, Erik D.

2012-01-01

191

Circadian Clocks and Metabolism  

PubMed Central

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

2014-01-01

192

Usability assessment of pacemaker programmers.  

PubMed

There is a perception among clinicians of usability differences in the user interface of pacemaker programmers, but there is an absence of literature in this area. The purpose of this study was to describe usability differences in pacemaker programmers. Forty-two programmer users completed self-administered questionnaires and two usability experts independently performed heuristic evaluation to identify features that violated general usability principles. Programmers from seven manufacturers (coded A-G) were evaluated. There was a balanced representation of users: nurses (58%) versus technologists (40%) who are employed in community (50%) versus academic (45%) hospitals, novice versus expert users based on the median users' programming experience of 60 months (range 1-300 months). Significant differences between programmers were found in overall user satisfaction and ease of programmer use (P < 0.0001) in the display, controls, operation, and physical dimension of the programmers (P < 0.05). Heuristic evaluations showed frequent violations of usability principles in all programmers. Problematic areas include reliance on user recall, inconsistency in operation of critical controls, poor readability, and not anticipating user wants or action. Programmer interface designs do not consistently meet user needs or general usability principles. This impacts on the safe and effective use of programmers. Guidelines in programmer design should be established, particularly with respect to labeling, location, and operation of critical controls. PMID:15511248

Chiu, Christine C; Vicente, Kim J; Buffo-Sequeira, Ilan; Hamilton, Robert M; McCrindle, Brian W

2004-10-01

193

differentially control circadian rhythms and synchrony in clock neuronsi/oGABA and G Sara J. Aton, James E. Huettner, Martin Straume, and Erik D. Herzog  

E-print Network

differentially control circadian rhythms and synchrony in clock neuronsi/oGABA and G Sara J. Aton, see: Notes: #12;GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons. GABAA and GABAB antagonism increased circadian peak firing rates and rhythm precision of cultured SCN

Huettner, James E.

194

Phase shifting the circadian rhythm of neuronal activity in the isolated Aplysia eye with puromycin and cycloheximide. Electrophysiological and biochemical studies  

PubMed Central

The effects of pulse application of puromycin (PURO) or cycloheximide (CHX) were tested on the circadian rhythm (CR) of spontaneous compound action potential (CAP) activity in the isolated Aplysia eye. CAP activity was recorded from the optic nerve in constant darkness at 15degreesC. PURO pulses (6, 12 h; 12--134 mug/ml) and CHX pulses (12 h, 500--2,000 mug/ml) caused dose-dependent phase delays in the CR when administered during projected night. PURO pulses (6 h, 125 mug/ml) caused phase advances when given during projected day and caused phase delays when given during projected night. In biochemical experiments PURO (12 h, 20 mug/ml) and CHX (12 h, 500 mug/ml) inhibited leucine incorporation into the eye by about 50%. PURO (12 h; 50, 125 mug/ml) also changed the molecular weight distribution of proteins synthesized by the eye during the pulse. The effect of PURO (12 h, 125 mug/ml) on the level of incorporation was almost completely reversible within the next 12 h but the phase-shifted eye showed an latered spectrum of proteins for up to 28 h after the pulse. In electrophysiological experiments spontaneous CAP activity and responses to light were measured before, during, and after drug treatments. In all, eight parameters in three periods were analyzed quantitatively. Of these 24 indices, only 3 showed significant changes. PURO increased spontaneous CAP frequency by 67% 0-7 h after the drug pulse and increased the CAP amplitude of the tonic light response by 23% greater than 7 h after the pulse. CHX increased the intraburst spontaneous CAP frequency by 33% during the pulse and CAP frequency of the tonic light response by 32% 0- 7 h after the pulse. The above data indicate that phase-shifting doses of PURO and CHX inhibit protein synthesis in the eye without causing adverse electrophysiological effects, and suggest that protein synthesis is involved in the production of the CR of the isolated Aplysia eye. PMID:993764

1976-01-01

195

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

196

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

197

The Arabidopsis Circadian System  

PubMed Central

Rhythms with periods of approximately 24 hr are widespread in nature. Those that persist in constant conditions are termed circadian rhythms and reflect the activity of an endogenous biological clock. Plants, including Arabidopsis, are richly rhythmic. Expression analysis, most recently on a genomic scale, indicates that the Arabidopsis circadian clock regulates a number of key metabolic pathways and stress responses. A number of sensitive and high-throughput assays have been developed to monitor the Arabidopsis clock. These assays have facilitated the identification of components of plant circadian systems through genetic and molecular biological studies. Although much remains to be learned, the framework of the Arabidopsis circadian system is coming into focus. Dedication This review is dedicated to the memory of DeLill Nasser, a wonderful mentor and an unwavering advocate of both Arabidopsis and circadian rhythms research. PMID:22303209

McClung, C. Robertson; Salome, Patrice A.; Michael, Todd P.

2002-01-01

198

The role of the circadian system in fractal neurophysiological control  

PubMed Central

Many neurophysiological variables such as heart rate, motor activity, and neural activity are known to exhibit intrinsic fractal fluctuations - similar temporal fluctuation patterns at different time scales. These fractal patterns contain information about health, as many pathological conditions are accompanied by their alteration or absence. In physical systems, such fluctuations are characteristic of critical states on the border between randomness and order, frequently arising from nonlinear feedback interactions between mechanisms operating on multiple scales. Thus, the existence of fractal fluctuations in physiology challenges traditional conceptions of health and disease, suggesting that high levels of integrity and adaptability are marked by complex variability, not constancy, and are properties of a neurophysiological network, not individual components. Despite the subject's theoretical and clinical interest, the neurophysiological mechanisms underlying fractal regulation remain largely unknown. The recent discovery that the circadian pacemaker (suprachiasmatic nucleus) plays a crucial role in generating fractal patterns in motor activity and heart rate sheds an entirely new light on both fractal control networks and the function of this master circadian clock, and builds a bridge between the fields of circadian biology and fractal physiology. In this review, we sketch the emerging picture of the developing interdisciplinary field of fractal neurophysiology by examining the circadian system’s role in fractal regulation. PMID:23573942

Pittman-Polletta, Benjamin R.; Scheer, Frank A.J.L.; Butler, Matthew P.; Shea, Steven A.; Hu, Kun

2013-01-01

199

Assessment of circadian rhythms in humans: comparison of real-time fibroblast reporter imaging with plasma melatonin  

PubMed Central

We compared the period of the rhythm of plasma melatonin, driven by the hypothalamic circadian pacemaker, to in vitro periodicity in cultured peripheral fibroblasts to assess the effects on these rhythms of a polymorphism of PER3 (rs57875989), which is associated with sleep timing. In vitro circadian period was determined using luminometry of cultured fibroblasts, in which the expression of firefly luciferase was driven by the promoter of the circadian gene Arntl (Bmal1). The period of the melatonin rhythm was assessed in a 9-d forced desynchrony protocol, minimizing confounding effects of sleep-wake and light-dark cycles on circadian rhythmicity. In vitro periods (32 participants, 24.61±0.33 h, mean±sd) were longer than in vivo periods (31 participants, 24.16±0.17 h; P<0.0001) but did not differ between PER3 genotypes (P>0.4). Analyses of replicate in vitro assessments demonstrated that circadian period was reproducible within individuals (intraclass correlation=0.62), but in vivo and in vitro period assessments did not correlate (P>0.9). In accordance with circadian entrainment theory, in vivo period correlated with the timing of melatonin (P<0.05) at baseline and with diurnal preference (P<0.05). Individual circadian rhythms can be reliably assessed in fibroblasts but may not correlate with physiological rhythms driven by the central circadian pacemaker.—Hasan, S., Santhi, N., Lazar, A.S., Slak, A., Lo, J., von Schantz, M., Archer, S. N., Johnston, J. D., Dijk, D.-J. Assessment of circadian rhythms in humans: comparison of real-time fibroblast reporter imaging with plasma melatonin. PMID:22371527

Hasan, Sibah; Santhi, Nayantara; Lazar, Alpar S.; Slak, Ana; Lo, June; von Schantz, Malcolm; Archer, Simon N.; Johnston, Jonathan D.; Dijk, Derk-Jan

2012-01-01

200

Pacemaker twiddler's syndrome (rotation of the pacemaker around the electrode cable, a rare complication of pacemaker therapy).  

PubMed

Rotation of the pacemaker generator around the electrode cable (i.e. twiddler's syndrome) was observed by the authors in six cases during the implantation of 4250 pacemakers. Twiddler's syndrome developed in three cases following implantation and in three cases after the replacement of the pacemaker. As a result of the rotation of the device, displacement of the electrode occurred in all cases. The factors predisposing to rotation of the device were as follows: (i) a loose, dilated pocket in 5 cases; (ii) seroma formation around the device in 2 cases; (iii) manipulation with the pacemaker in one case. For treating twiddler's syndrome, reimplantation was performed, fashioning a small and tight pocket for the device and fixing it by transfixing sutures. After reimplantation, the patients became complaint free, no recurrences occurred. PMID:2596244

Solti, F; Moravcsik, E; Rényi-Vámos, F; Szabó, Z

1989-01-01

201

How Will a Pacemaker Affect My Lifestyle?  

MedlinePLUS

... check for changes in your heart's electrical activity. Battery Replacement Pacemaker batteries last between 5 and 15 years (average 6 ... doctor will replace the generator along with the battery before the battery starts to run down. Replacing ...

202

Biophotonics: Circadian photonics  

NASA Astrophysics Data System (ADS)

A growing body of medical evidence suggests that disrupting the body's biological clock can have adverse effects on health. Researchers are now creating the photonic tools to monitor, predict and influence the circadian rhythm.

Rea, Mark S.

2011-05-01

203

Circadian Rhythm Sleep Disorders  

MedlinePLUS

... Circadian Rhythm Sleep Disorders • Delayed sleep phase disorder (DSP): DSP occurs when a person regularly goes to ... in the general population is unknown. Risk Groups • DSP is more common in teens and young adults , ...

204

Are pacemaker properties required for respiratory rhythm generation in adult turtle brain stems in vitro?  

PubMed

The role of pacemaker properties in vertebrate respiratory rhythm generation is not well understood. To address this question from a comparative perspective, brain stems from adult turtles were isolated in vitro, and respiratory motor bursts were recorded on hypoglossal (XII) nerve rootlets. The goal was to test whether burst frequency could be altered by conditions known to alter respiratory pacemaker neuron activity in mammals (e.g., increased bath KCl or blockade of specific inward currents). While bathed in artificial cerebrospinal fluid (aCSF), respiratory burst frequency was not correlated with changes in bath KCl (0.5-10.0 mM). Riluzole (50 microM; persistent Na(+) channel blocker) increased burst frequency by 31 +/- 5% (P < 0.05) and decreased burst amplitude by 42 +/- 4% (P < 0.05). In contrast, flufenamic acid (FFA, 20-500 microM; Ca(2+)-activated cation channel blocker) reduced and abolished burst frequency in a dose- and time-dependent manner (P < 0.05). During synaptic inhibition blockade with bicuculline (50 microM; GABA(A) channel blocker) and strychnine (50 muM; glycine receptor blocker), rhythmic motor activity persisted, and burst frequency was directly correlated with extracellular KCl (0.5-10.0 mM; P = 0.005). During synaptic inhibition blockade, riluzole (50 microM) did not alter burst frequency, whereas FFA (100 microM) abolished burst frequency (P < 0.05). These data are most consistent with the hypothesis that turtle respiratory rhythm generation requires Ca(2+)-activated cation channels but not pacemaker neurons, which thereby favors the group-pacemaker model. During synaptic inhibition blockade, however, the rhythm generator appears to be transformed into a pacemaker-driven network that requires Ca(2+)-activated cation channels. PMID:17522127

Johnson, Stephen M; Wiegel, Liana M; Majewski, David J

2007-08-01

205

Neurospora WC-1 Recruits SWI/SNF to Remodel frequency and Initiate a Circadian Cycle.  

PubMed

In the negative feedback loop comprising the Neurospora circadian oscillator, the White Collar Complex (WCC) formed from White Collar-1 (WC-1) and White Collar-2 (WC-2) drives transcription of the circadian pacemaker gene frequency (frq). Although FRQ-dependent repression of WCC has been extensively studied, the mechanism by which the WCC initiates a circadian cycle remains elusive. Structure/function analysis of WC-1 eliminated domains previously thought to transactivate frq expression but instead identified amino acids 100-200 as essential for frq circadian expression. A proteomics-based search for coactivators with WCC uncovered the SWI/SNF (SWItch/Sucrose NonFermentable) complex: SWI/SNF interacts with WCC in vivo and in vitro, binds to the Clock box in the frq promoter, and is required both for circadian remodeling of nucleosomes at frq and for rhythmic frq expression; interestingly, SWI/SNF is not required for light-induced frq expression. These data suggest a model in which WC-1 recruits SWI/SNF to remodel and loop chromatin at frq, thereby activating frq expression to initiate the circadian cycle. PMID:25254987

Wang, Bin; Kettenbach, Arminja N; Gerber, Scott A; Loros, Jennifer J; Dunlap, Jay C

2014-09-01

206

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

PubMed Central

Summary 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 transcription of the two major circadian regulators, BMAL1 and CLOCK. This activation itself 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 levels 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 pheno-copy these aging-dependent circadian changes, while mice that over-express SIRT1 in 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

2013-01-01

207

Neurospora WC-1 Recruits SWI/SNF to Remodel frequency and Initiate a Circadian Cycle  

PubMed Central

In the negative feedback loop comprising the Neurospora circadian oscillator, the White Collar Complex (WCC) formed from White Collar-1 (WC-1) and White Collar-2 (WC-2) drives transcription of the circadian pacemaker gene frequency (frq). Although FRQ-dependent repression of WCC has been extensively studied, the mechanism by which the WCC initiates a circadian cycle remains elusive. Structure/function analysis of WC-1 eliminated domains previously thought to transactivate frq expression but instead identified amino acids 100–200 as essential for frq circadian expression. A proteomics-based search for coactivators with WCC uncovered the SWI/SNF (SWItch/Sucrose NonFermentable) complex: SWI/SNF interacts with WCC in vivo and in vitro, binds to the Clock box in the frq promoter, and is required both for circadian remodeling of nucleosomes at frq and for rhythmic frq expression; interestingly, SWI/SNF is not required for light-induced frq expression. These data suggest a model in which WC-1 recruits SWI/SNF to remodel and loop chromatin at frq, thereby activating frq expression to initiate the circadian cycle. PMID:25254987

Wang, Bin; Kettenbach, Arminja N.; Gerber, Scott A.; Loros, Jennifer J.; Dunlap, Jay C.

2014-01-01

208

The selective tachykinin neurokinin 1 (NK1) receptor antagonist, GR 205,171, stereospecifically inhibits light-induced phase advances of hamster circadian activity rhythms.  

PubMed

Circadian rhythms in mammals are generated by master pacemaker cells located within the suprachiasmatic nucleus of the hypothalamus. In hamsters, the suprachiasmatic nucleus contains a small collection of cells immunoreactive for substance P, the endogenous ligand of tachykinin neurokinin 1 (NK1) receptors. In addition, two other nuclei which form part of the circadian system, the intergeniculate leaflet of the thalamus and the raphe nuclei, also contain fibers and/or cell bodies immunoreactive for substance P. In light of these observations, we evaluated the influence of the selective tachykinin NK1 receptor antagonist, GR 205,171, upon circadian activity rhythms in the hamster. Systemic injection of GR 205,171 dose-dependently (2.5-40.0 mg/kg, i.p.) inhibited light-induced phase advances in hamster circadian wheel running activity rhythms by approximately 50%. In contrast, GR 226,206, the less active enantiomer of GR 205,171, failed to affect light-induced phase advances. In addition, we examined the potential ability of GR 205,171 to induce non-photic phase shifts in hamster wheel running rhythms when injected at mid-day to late night circadian times. However, GR 205,171 (40 mg/kg) did not elicit non-photic phase shifts at these times indicating that tachykinin NK1 receptor antagonists are only effective when a light stimulus is applied to the pacemaker. Although GR 205,171 may, in theory, activate several sites within the circadian system, we suggest that GR 205,171 acts in the raphe nuclei to increase inhibitory serotonergic input to pacemaker cells in the suprachiasmatic nuclei, thereby suppressing photic modulation of the pacemaker. These findings have important implications for the use of tachykinin NK1 receptor antagonists in the treatment of depression and other central nervous system disorders. PMID:16307740

Gannon, Robert L; Millan, Mark J

2005-12-19

209

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

210

Analysis method and experimental conditions affect computed circadian phase from melatonin data.  

PubMed

Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of analyzing the plasma melatonin rhythm can be grouped into three categories: curve-fitting, threshold-based and physiologically-based linear differential equations. To determine which method provides the most accurate assessment of circadian phase, we compared the ability to fit the data and the variability of phase estimates for seventeen different markers of melatonin phase derived from these methodological categories. We used data from three experimental conditions under which circadian rhythms - and therefore calculated melatonin phase - were expected to remain constant or progress uniformly. Melatonin profiles from older subjects and subjects with lower melatonin amplitude were less likely to be fit by all analysis methods. When circadian drift over multiple study days was algebraically removed, there were no significant differences between analysis methods of melatonin onsets (P = 0.57), but there were significant differences between those of melatonin offsets (P<0.0001). For a subset of phase assessment methods, we also examined the effects of data loss on variability of phase estimates by systematically removing data in 2-hour segments. Data loss near onset of melatonin secretion differentially affected phase estimates from the methods, with some methods incorrectly assigning phases too early while other methods assigning phases too late; missing data at other times did not affect analyses of the melatonin profile. We conclude that melatonin data set characteristics, including amplitude and completeness of data collection, differentially affect the results depending on the melatonin analysis method used. PMID:22511928

Klerman, Hadassa; St Hilaire, Melissa A; Kronauer, Richard E; Gooley, Joshua J; Gronfier, Claude; Hull, Joseph T; Lockley, Steven W; Santhi, Nayantara; Wang, Wei; Klerman, Elizabeth B

2012-01-01

211

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

212

Pacemaker leads: performance and progress.  

PubMed

Pacing leads remain the "weaker link" of the permanent pacing system. Lead failure has been an issue since the beginning of implantable pacemaker therapy. Modern electronics have brought about considerable progress in pacing technology, but lead design has been slower to evolve and problems persist. IS-1 standardization must be considered a significant advance, but some issues regarding IS-1 standardization persist and have been the cause of some compatibility problems. With respect to lead insulation, silicone has proved to offer total reliability for > 30 years. In the search for better handling characteristics, polyurethane 80A was employed for bipolar leads, but it failed to demonstrate satisfactory insulating properties. New insulation materials, such as ethylene-fluoro-ethylene (ETFE), and coated wire technology look promising, having shown 99.32% survival at 5-year follow-up. Reliability is the main objective in lead design, but leads should provide low battery consumption as well. Low coil resistance, with high electrode impedance in steroid-eluting leads, is the standard at present. Low polarization is a desirable property for 2 main reasons: (1) in conjunction with low-threshold leads, it decreases battery consumption; and (2) it allows capture detection and, therefore, safer pacing at low battery consumption. Lead tip design as well as pacing pulse configuration can influence polarization. PMID:10089864

de Voogt, W G

1999-03-11

213

Two steady-entrainment phases and graded masking effects by light generate different circadian chronotypes in Octodon degus.  

PubMed

Processes involved in the operation of the circadian pacemaker are well characterized; however; little is known about what mechanisms drive the overt diurnal, nocturnal, or crepuscular behavior in a species. In this context, dual-phasing rodents, such as Octodon degus, emerge as a useful model to decipher these keys. Two main chronotypes, nocturnal and diurnal, have been traditionally described in laboratory-housed degus based on the percentage of activity displayed by the animals during the scotophase or photophase. However, if one considers also the entrainment phase angle during the first days following a change from LD to DD conditions, a third chronotype (intermediate)-or more properly, a continuous grading of circadian expressions between diurnal and nocturnal chronotype-can be observed. Our experiments suggest the pacemaker of the diurnal animal is entrained to the photophase, and light does not exert a negative masking effect. The pacemaker of the nocturnal degus, on the other hand, is entrained to the scotophase, and light exerts a strong negative masking effect. Finally, the intermediate chronotype is characterized by variable negative masking effect of light overlapping a pacemaker entrained to the photophase. The phase shift inversion from diurnal to nocturnal chronotype is related to the availability of a wheel in the cage, and the effect may be located downstream from the clock. However, body temperature rhythm recordings, less affected by masking effects, point to an involvement of the circadian pacemaker in chronotype differentiation, as transient entrainment cycles, and not an abrupt phase shift, were detected after providing access to the wheel. The diurnality of degus seems to be the result of a variety of mechanisms, which may explain how different processes can lead to similar chronotypes. PMID:19212838

Vivanco, Pablo; Rol, Maria Angeles; Madrid, Juan Antonio

2009-02-01

214

Precision of the pacemaker nucleus in a weakly electric fish: network versus cellular influences.  

PubMed

We investigated the relative influence of cellular and network properties on the extreme spike timing precision observed in the medullary pacemaker nucleus (Pn) of the weakly electric fish Apteronotus leptorhynchus. Of all known biological rhythms, the electric organ discharge of this and related species is the most temporally precise, with a coefficient of variation (CV = standard deviation/mean period) of 2 x 10(-4) and standard deviation (SD) of 0.12-1.0 micros. The timing of the electric organ discharge is commanded by neurons of the Pn, individual cells of which we show in an in vitro preparation to have only a slightly lesser degree of precision. Among the 100-150 Pn neurons, dye injection into a pacemaker cell resulted in dye coupling in one to five other pacemaker cells and one to three relay cells, consistent with previous results. Relay cell fills, however, showed profuse dendrites and contacts never seen before: relay cell dendrites dye-coupled to one to seven pacemaker and one to seven relay cells. Moderate (0.1-10 nA) intracellular current injection had no effect on a neuron's spiking period, and only slightly modulated its spike amplitude, but could reset the spike phase. In contrast, massive hyperpolarizing current injections (15-25 nA) could force the cell to skip spikes. The relative timing of subthreshold and full spikes suggested that at least some pacemaker cells are likely to be intrinsic oscillators. The relative amplitudes of the subthreshold and full spikes gave a lower bound to the gap junctional coupling coefficient of 0.01-0.08. Three drugs, called gap junction blockers for their mode of action in other preparations, caused immediate and substantial reduction in frequency, altered the phase lag between pairs of neurons, and later caused the spike amplitude to drop, without altering the spike timing precision. Thus we conclude that the high precision of the normal Pn rhythm does not require maximal gap junction conductances between neurons that have ordinary cellular precision. Rather, the spiking precision can be explained as an intrinsic cellular property while the gap junctions act to frequency- and phase-lock the network oscillations. PMID:10669509

Moortgat, K T; Bullock, T H; Sejnowski, T J

2000-02-01

215

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

216

[Infective endocarditis in patients with permanent pacemaker].  

PubMed

Five patients who had permanent pacemaker and infective endocarditis were analyzed. Diagnose was confirmed by a positive blood cultures in all patients and 2 of them had identifiable vegetation in the echocardiogram too. The etiologic agent was Staphylococcus aureus in 3, Staphylococcus epidermidis in 1 and Staphylococcus viridans in 1. Three patients were treated with antibiotics alone: one had no clinical conditions to be operated, one died before surgery and one had good response to antimicrobial therapy alone. Two patients were submitted to antibiotic therapy and surgical removal of the pacemaker system, without complications. It was concluded that the surgical removal of the pacemaker system, as soon as possible, is the choice's therapy. PMID:7998851

Jorge, S do C; Kormann, D D; Medeiros, P; Mateos, J C; Zamorano, M M; Silva, L M; Zambonini, M N; Arnoni, A S; Assef, J E; Magalhães, H M

1994-04-01

217

Inappropriate ventricular blanking in a DDI pacemaker.  

PubMed

The DDI mode is a new pacing mode with potential advantages over DVI pacing. We describe anomalous post R wave ventricular pacing due to the presence of inappropriate ventricular blanking periods in a pacemaker programmed to the DDI mode. Although no adverse consequences were seen in our patients, potentially dangerous R-on-T pacing could occur, particularly if long atrioventricular delays are programmed. A method for eliminating this pacing anomaly is described. Patients programmed to the DDI mode with the pacemaker model described should be evaluated for post R wave ventricular pacing and corrective measures should be taken. PMID:2426670

Erlebacher, J A; Stelzer, P

1986-07-01

218

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

PubMed Central

Animals and humans are able to predict and synchronize their daily activity to signals present in their environments. Environmental cues are most often associated with signaling the beginning or the end of a daily activity cycle but they can also be used to time the presentation or availability of scarce resources. If the signal occurs consistently, animals can begin to anticipate its arrival and ultimately become entrained to its presence. While many stimuli can produce anticipation for a daily event, these events rarely lead to changes in activity patterns during the rest of the circadian cycle. We demonstrate that performance of a task requiring sustained attention not only produces entrainment, but produces a robust modification in the animals’ activity throughout the entire circadian cycle. In particular, normally nocturnal rats, when trained during the light phase (ZT 4) adopted a significant and reversible diurnal activity pattern. Importantly, control experiments demonstrated that this entrainment could not be attributed to the non-cognitive components of task performance, such as handling, water deprivation, access to water used as a reward, or animal activity associated with operant training. These findings additionally indicate that levels of cognitive performance are modulated by the circadian cycle and that such activity can act as a highly effective entrainment signal. These results form the basis for future research on the role of neuronal systems mediating interactions between cognitive activity and circadian rhythms. PMID:19824760

Gritton, Howard J.; Sutton, Blair C.; Martinez, Vicente; Sarter, Martin; Lee, Theresa M.

2010-01-01

219

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

220

Spatial and circadian regulation of cry in Drosophila.  

PubMed

In Drosophila, cryptochrome (cry) encodes a blue-light photoreceptor that mediates light input to circadian oscillators and sustains oscillator function in peripheral tissues. The levels of cry mRNA cycle with a peak at approximately ZT5, which is similar to the phase of Clock (Clk) mRNA cycling in Drosophila. To understand how cry spatial and circadian expression is regulated, a series of cry-Gal4 trans-genes containing different portions of cry upstream and intron 1 sequences were tested for spatial and circadian expression. In fly heads, cry upstream sequences drive constitutive expression in brain oscillator neurons, a novel group of nonoscillator cells in the optic lobe, and peripheral oscillator cells in eyes and antennae. In contrast, cry intron 1 drives rhythmic expression in eyes and antennae, but not brain oscillator neurons. These results demonstrate that intron 1 is sufficient for high-amplitude cry mRNA cycling, show that cry upstream sequences are sufficient for expression in brain oscillator neurons, and suggest that cry spatial and circadian expression are regulated by different elements. PMID:18663236

Hao Zheng; Ng, Fanny; Yixiao Liu; Hardin, Paul E

2008-08-01

221

Photic responses of suprachiasmatic area neurons in diurnal degus ( Octodon degus) and nocturnal rats ( Rattus norvegicus)  

Microsoft Academic Search

Photic sensitivity of cells in the suprachiasmatic nuclei (SCN), the principal pacemaker of the mammalian circadian system, has been documented in several species. In nocturnal rodents, the majority of photically responsive SCN cells are activated by retinal illumination. One report identified mostly photic suppressions among SCN cells in a diurnal rodent, studied under somewhat different conditions. We examined photic sensitivity

Yong-Yi Jiao; Theresa M. Lee; Benjamin Rusak

1999-01-01

222

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 significant circadian rhythms with a peak at the circadian phase corresponding to 5­9 p.m. ( 9 h later than a circadian rhythm. These findings suggest that endogenous circadian-mediated activity vari- ations

Stanley, H. Eugene

223

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, Antonio M; Costa, Francisco; Tralhao, Antonio; Marques, Hugo; Cardim, Nuno; Adragao, Pedro

2014-01-01

224

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

225

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

226

An Intelligent System for Pacemaker Reprogramming  

E-print Network

cardiac pacemakers and the excitatory and conductive system of the heart have a clear physical structure, model�based reasoning, abductive reasoning. 1 Introduction Cardiac disease in a patient may cause the excitatory and conductive system of the heart to fail, resulting in an abnormal cardiac rhythm, usually

Utrecht, Universiteit

227

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

228

Circadian Clock Regulation of the Cell Cycle in the Zebrafish Intestine  

PubMed Central

The circadian clock controls cell proliferation in a number of healthy tissues where cell renewal and regeneration are critical for normal physiological function. The intestine is an organ that typically undergoes regular cycles of cell division, differentiation and apoptosis as part of its role in digestion and nutrient absorption. The aim of this study was to explore circadian clock regulation of cell proliferation and cell cycle gene expression in the zebrafish intestine. Here we show that the zebrafish gut contains a directly light-entrainable circadian pacemaker, which regulates the daily timing of mitosis. Furthermore, this intestinal clock controls the expression of key cell cycle regulators, such as cdc2, wee1, p21, PCNA and cdk2, but only weakly influences cyclin B1, cyclin B2 and cyclin E1 expression. Interestingly, food deprivation has little impact on circadian clock function in the gut, but dramatically reduces cell proliferation, as well as cell cycle gene expression in this tissue. Timed feeding under constant dark conditions is able to drive rhythmic expression not only of circadian clock genes, but also of several cell cycle genes, suggesting that food can entrain the clock, as well as the cell cycle in the intestine. Rather surprisingly, we found that timed feeding is critical for high amplitude rhythms in cell cycle gene expression, even when zebrafish are maintained on a light-dark cycle. Together these results suggest that the intestinal clock integrates multiple rhythmic cues, including light and food, to function optimally. PMID:24013905

Peyric, Elodie; Moore, Helen A.; Whitmore, David

2013-01-01

229

Circadian rhythms of glucocorticoid hormone actions in target tissues: potential clinical implications.  

PubMed

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. PMID:23033538

Kino, Tomoshige

2012-10-01

230

SLEEPAND CIRCADIAN NEUROBIOLOGY (SCN)  

E-print Network

.D.) at the Stanford University Sleep Clinic (Director: Jed Black, M.D.). MISSION FOR THE SCN LAB The SCN lab has beenSTANFORD SLEEPAND CIRCADIAN NEUROBIOLOGY (SCN) LABORATORY STANFORD SLEEP DISORDERS CLINIC AND RESEARCH CENTER DEPARTMENT OF PSYCHIATRY AND BEHAVIORAL SCIENCES STANFORD UNIVERSITY SCHOOL OF MEDICINE

Kay, Mark A.

231

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

232

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

233

Development of the circadian clockwork in the kidney.  

PubMed

The circadian molecular clock is an internal time-keeping system composed of centrally synchronized tissue-level pacemakers. Here, we explored the ontogeny of the clock machinery in the developing kidney. Pregnant rats were housed at 12-12?h light-dark cycles. Offsprings were killed at 4-h intervals on embryonic day 20 and at postnatal weeks 1, 4, and 12. Canonical clock gene (Clock, Bmal1, Rev-erb?, Cry1, Cry2, Per1, Per2) and kidney-specific clock-controlled gene (?ENaC, SGK1, NHE3, AVPR2) expression was profiled by RT-PCR. To investigate the role of nutritional cues, the feeding pattern was modified postpartum. Clock, Rev-erb?, Per2, ?ENaC, SGK1, NHE3, and AVPR2 showed circadian expression at the end of intrauterine development. By 1 week, all genes oscillated with a distinct acrophase shift toward the time of peak feeding activity. Daily 4-hour withdrawal of mothers induced a 12-hour phase shift of Clock and Bmal1 expression, while disrupting oscillations of the other genes. After weaning, oscillation phases shifted back toward the adult pattern, which was fully expressed at 12 weeks. Thus, functional circadian molecular clockwork evolves in the late fetal and early postnatal kidney. During the nursing period, oscillations are entrained by nutritional cues. The coupling of the circadian expression of tubular regulators of fluid and electrolyte excretion to the feeding-entrained clockwork may be important to maintain homeostasis during this critical period. PMID:24897033

Mészáros, Krisztina; Pruess, Linda; Szabó, Attila J; Gondan, Matthias; Ritz, Eberhard; Schaefer, Franz

2014-11-01

234

Melatonin signaling controls circadian swimming behavior in marine zooplankton.  

PubMed

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

2014-09-25

235

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

236

Neurobiology of Stomotoca. II. Pacemakers and conduction pathways.  

PubMed

Evidence is presented for separate conduction pathways for swimming and for tentacle coordination in the marginal nerves of the jellyfish Stomotoca. The effector muscles are fired through junctions sensitive to excess Mg++, probably represented by the neuromuscular synapses observed by electron microscopy. The swimming effector (striated muscle) fires one-to-one with nerve input signals and myoid conduction occurs. Tentacle responses (smooth muscle contractions) involve facilitation, presumably at the neuro-effector junction; responses are graded and nonpropagating. Electrical correlates of two further conducting systems using the marginal nerves have been recorded. Their functions are unknown. One, the bridge system, extends up the four radii and encircles the peduncle; the other (ring system) is confined to the margin. A fifth conducting system is inferred in the case of the pointing response and its distribution is plotted. Signals have not been obtained from it. Pointing is accompanied by a burst of muscle potentials in the radial smooth muscles and is exhibited after a lengthy latency, indicating a local pacemaker. A sixth conducting pathway is the epithelial system, which mediates crumpling, a response involving the radial muscles without pacemaker intervention. Characteristic conduction velocities and wave forms are noted for the first four systems and for epithelial pulses. All systems, except perhaps the pointing conduction system, through-conduct under excess Mg++. Spontaneous activity patterns are described for the swimming, tentacle pulse, and ring systems. Abrupt increases in light intensity inhibit spontaneous activity, sudden decreases augmenting it. In the absence of specialized photoreceptors, light is presumed to act directly on central neurons. Epithelial pulses inhibit swimming, apparently by blocking the generation or conduction of the primary nervous events. This observation, taken in conjunction with evidence of feedback inhibition of the primary swimming system by the cells it fires, is discussed in relation to possible mechanisms whereby the output of nerve cells might be altered by activity in the excitable epithelial cells which envelop them. PMID:241778

Mackie, G O

1975-07-01

237

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

238

Melatonin for Circadian Rhythm Disturbances in Dementia  

E-print Network

Melatonin for Circadian Rhythm Disturbances in Dementia Available from: http. Describe the pathophysiology of circadian rhythm disturbances in dementia 2. Evaluate current treatment options for circadian rhythm disturbances in dementia 3. Review available literature on the use

Pillow, Jonathan

239

Circadian Regulation of Glutathione Levels and Biosynthesis in Drosophila melanogaster  

PubMed Central

Circadian clocks generate daily rhythms in neuronal, physiological, and metabolic functions. Previous studies in mammals reported daily fluctuations in levels of the major endogenous antioxidant, glutathione (GSH), but the molecular mechanisms that govern such fluctuations remained unknown. To address this question, we used the model species Drosophila, which has a rich arsenal of genetic tools. Previously, we showed that loss of the circadian clock increased oxidative damage and caused neurodegenerative changes in the brain, while enhanced GSH production in neuronal tissue conferred beneficial effects on fly survivorship under normal and stress conditions. In the current study we report that the GSH concentrations in fly heads fluctuate in a circadian clock-dependent manner. We further demonstrate a rhythm in activity of glutamate cysteine ligase (GCL), the rate-limiting enzyme in glutathione biosynthesis. Significant rhythms were also observed for mRNA levels of genes encoding the catalytic (Gclc) and modulatory (Gclm) subunits comprising the GCL holoenzyme. Furthermore, we found that the expression of a glutathione S-transferase, GstD1, which utilizes GSH in cellular detoxification, significantly fluctuated during the circadian day. To directly address the role of the clock in regulating GSH-related rhythms, the expression levels of the GCL subunits and GstD1, as well as GCL activity and GSH production were evaluated in flies with a null mutation in the clock genes cycle and period. The rhythms observed in control flies were not evident in the clock mutants, thus linking glutathione production and utilization to the circadian system. Together, these data suggest that the circadian system modulates pathways involved in production and utilization of glutathione. PMID:23226288

Beaver, Laura M.; Klichko, Vladimir I.; Chow, Eileen S.; Kotwica-Rolinska, Joanna; Williamson, Marisa; Orr, William C.; Radyuk, Svetlana N.; Giebultowicz, Jadwiga M.

2012-01-01

240

Pacemakers and implantable cardioverter defibrillators--general and anesthetic considerations.  

PubMed

A pacemaking system consists of an impulse generator and lead or leads to carry the electrical impulse to the patient's heart. Pacemaker and implantable cardioverter defibrillator codes were made to describe the type of pacemaker or implantable cardioverter defibrillator implanted. Indications for pacing and implantable cardioverter defibrillator implantation were given by the American College of Cardiologists. Certain pacemakers have magnet-operated reed switches incorporated; however, magnet application can have serious adverse effects; hence, devices should be considered programmable unless known otherwise. When a device patient undergoes any procedure (with or without anesthesia), special precautions have to be observed including a focused history/physical examination, interrogation of pacemaker before and after the procedure, emergency drugs/temporary pacing and defibrillation, reprogramming of pacemaker and disabling certain pacemaker functions if required, monitoring of electrolyte and metabolic disturbance and avoiding certain drugs and equipments that can interfere with pacemaker function. If unanticipated device interactions are found, consider discontinuation of the procedure until the source of interference can be eliminated or managed and all corrective measures should be taken to ensure proper pacemaker function should be done. Post procedure, the cardiac rate and rhythm should be monitored continuously and emergency drugs and equipments should be kept ready and consultation with a cardiologist or a pacemaker-implantable cardioverter defibrillator service may be necessary. PMID:24907883

Rapsang, Amy G; Bhattacharyya, Prithwis

2014-01-01

241

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

242

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

243

Circadian clocks and neurodegenerative diseases: time to aggregate??  

PubMed Central

The major neurodegenerative diseases are characterised by a disabling loss of the daily pattern of sleep and wakefulness, which may be reflective of a compromise to the underlying circadian clock that times the sleep cycle. At a molecular level, the canonical property of neurodegenerative diseases is aberrant aggregation of otherwise soluble neuronal proteins. They can thus be viewed as disturbances of proteostasis, raising the question whether the two features — altered daily rhythms and molecular aggregation — are related. Recent discoveries have highlighted the fundamental contribution of circadian clocks to the correct ordering of daily cellular metabolic cycles, imposing on peripheral organs such as the liver a strict programme that alternates between anabolic and catabolic states. The discovery that circadian mechanisms are active in local brain regions suggests that they may impinge upon physiological and pathological elements that influence pro-neurodegenerative aggregation. This review explores how introducing the dimension of circadian time and the circadian clock might refine the analysis of aberrant aggregation, thus expanding our perspective on the cell biology common to neurodegenerative diseases. PMID:23797088

Hastings, Michael H; Goedert, Michel

2013-01-01

244

Circadian clocks and neurodegenerative diseases: time to aggregate?  

PubMed

The major neurodegenerative diseases are characterised by a disabling loss of the daily pattern of sleep and wakefulness, which may be reflective of a compromise to the underlying circadian clock that times the sleep cycle. At a molecular level, the canonical property of neurodegenerative diseases is aberrant aggregation of otherwise soluble neuronal proteins. They can thus be viewed as disturbances of proteostasis, raising the question whether the two features - altered daily rhythms and molecular aggregation - are related. Recent discoveries have highlighted the fundamental contribution of circadian clocks to the correct ordering of daily cellular metabolic cycles, imposing on peripheral organs such as the liver a strict programme that alternates between anabolic and catabolic states. The discovery that circadian mechanisms are active in local brain regions suggests that they may impinge upon physiological and pathological elements that influence pro-neurodegenerative aggregation. This review explores how introducing the dimension of circadian time and the circadian clock might refine the analysis of aberrant aggregation, thus expanding our perspective on the cell biology common to neurodegenerative diseases. PMID:23797088

Hastings, Michael H; Goedert, Michel

2013-10-01

245

Homeostatic, circadian, and emotional regulation of sleep.  

PubMed

A good night's sleep is one of life's most satisfying experiences, while sleeplessness is stressful and causes cognitive impairment. Yet the mechanisms that regulate the ability to sleep have only recently been subjected to detailed investigation. New studies show that the control of wake and sleep emerges from the interaction of cell groups that cause arousal with other nuclei that induce sleep such as the ventrolateral preoptic nucleus (VLPO). The VLPO inhibits the ascending arousal regions and is in turn inhibited by them, thus forming a mutually inhibitory system resembling what electrical engineers call a "flip-flop switch." This switch may help produce sharp transitions between discrete behavioral states, but it is not necessarily stable. The orexin neurons in the lateral hypothalamus may help stabilize this system by exciting arousal regions during wakefulness, preventing unwanted transitions between wakefulness and sleep. The importance of this stabilizing role is apparent in narcolepsy, in which an absence of the orexin neurons causes numerous, unintended transitions in and out of sleep and allows fragments of REM sleep to intrude into wakefulness. These influences on the sleep/wake system by homeostatic and circadian drives, as well as emotional inputs, are reviewed. Understanding the pathways that underlie the regulation of sleep and wakefulness may provide important insights into how the cognitive and emotional systems interact with basic homeostatic and circadian drives for sleep. PMID:16254994

Saper, Clifford B; Cano, Georgina; Scammell, Thomas E

2005-12-01

246

Application of an ex vivo cellular model of circadian variation for bipolar disorder research: a proof of concept study  

PubMed Central

Objectives Disruption of circadian function has been observed in several human disorders, including bipolar disorder (BD). Research into these disorders can be facilitated by human cellular models that evaluate external factors (zeitgebers) that impact circadian pacemaker activity. Incorporating a firefly luciferase reporter system into human fibroblasts provides a facile, bioluminescent readout that estimates circadian phase, while leaving the cells intact. We evaluated whether this system can be adapted to clinical BD research and whether it can incorporate zeitgeber challenge paradigms. Methods Fibroblasts from patients with bipolar I disorder (BD-I) (n = 13) and controls (n = 12) were infected ex vivo with a lentiviral reporter incorporating the promoter sequences for Bmal1, a circadian gene to drive expression of the firefly Luciferase gene. Following synchronization, the bioluminescence was used to estimate period length. Phase response curves (PRC) were also generated following forskolin challenge and the phase response patterns characterized. Results Period length and PRCs could be estimated reliably from the constructs. There were no significant case–control differences in period length, with a nonsignificant trend for differences in PRCs following the phase setting experiments. Conclusions An ex vivo cellular fibroblast-based model can be used to investigate circadian function in BD-I. It can be generated from specific individuals and this could usefully complement ongoing circadian clinical research. PMID:23782472

Bamne, Mikhil N; Ponder, Christine A; Wood, Joel A; Mansour, Hader; Frank, Ellen; Kupfer, David J; Young, Michael W; Nimgaonkar, Vishwajit L

2013-01-01

247

[Delayed atrial excitation following bifocal pacemaker stimulation].  

PubMed

A patient with drug-resistant ventricular tachycardia due to ischemic heart disease with severe left ventricular failure was successfully treated by the implantation of a DDD pacemaker system pacing at a rate of 90 beats/min (overdrive suppression). Additional therapy with high doses of beta-blockers was necessary. The ECG demonstrated a delay of 100 ms between atrial spike and p-wave. The hemodynamic effects of this ineffective atrial contraction were assessed by jugular venous puls tracing, phonocardiography, echocardiography, and radionuclide-ventriculography. The desired positive effects of physiological pacing could only be achieved by further prolongation of the A-V interval by these 100 ms. This observation shows that, with DDD pacemakers, AV intervals of varying length may be necessary with VAT or VDD and DVI modes in individual cases. PMID:6868743

Alt, E; Wirtzfeld, A; Seidl, K; Haller, F; von Bibra, H; Sauer, E

1983-04-01

248

Uncovering the Proteome Response of the Master Circadian Clock to Light Using an AutoProteome System*  

PubMed Central

In mammals, the suprachiasmatic nucleus (SCN) is the central circadian pacemaker that governs rhythmic fluctuations in behavior and physiology in a 24-hr cycle and synchronizes them to the external environment by daily resetting in response to light. The bilateral SCN is comprised of a mere ?20,000 neurons serving as cellular oscillators, a fact that has, until now, hindered the systematic study of the SCN on a global proteome level. Here we developed a fully automated and integrated proteomics platform, termed AutoProteome system, for an in-depth analysis of the light-responsive proteome of the murine SCN. All requisite steps for a large-scale proteomic study, including preconcentration, buffer exchanging, reduction, alkylation, digestion and online two-dimensional liquid chromatography-tandem MS analysis, are performed automatically on a standard liquid chromatography-MS system. As low as 2 ng of model protein bovine serum albumin and up to 20 ?g and 200 ?g of SCN proteins can be readily processed and analyzed by this system. From the SCN tissue of a single mouse, we were able to confidently identify 2131 proteins, of which 387 were light-regulated based on a spectral counts quantification approach. Bioinformatics analysis of the light-inducible proteins reveals their diverse distribution in different canonical pathways and their heavy connection in 19 protein interaction networks. The AutoProteome system identified vasopressin-neurophysin 2-copeptin and casein kinase 1 delta, both of which had been previously implicated in clock timing processes, as light-inducible proteins in the SCN. Ras-specific guanine nucleotide-releasing factor 1, ubiquitin protein ligase E3A, and X-linked ubiquitin specific protease 9, none of which had previously been implicated in SCN clock timing processes, were also identified in this study as light-inducible proteins. The AutoProteome system opens a new avenue to systematically explore the proteome-wide events that occur in the SCN, either in response to light or other stimuli, or as a consequence of its intrinsic pacemaker capacity. PMID:21859948

Tian, Ruijun; Alvarez-Saavedra, Matias; Cheng, Hai-Ying M.; Figeys, Daniel

2011-01-01

249

76 FR 47085 - Effective Date of Requirement for Premarket Approval for a Pacemaker Programmer  

Federal Register 2010, 2011, 2012, 2013

...information submitted in response to the 515(i...This Proposal--Pacemaker Programmers (21...at an improper rate. 3. Misdiagnosis...ability to sense pacemaker function can lead...including adaptive rate pacemakers (LWP);...

2011-08-04

250

77 FR 37570 - Effective Date of Requirement for Premarket Approval for a Pacemaker Programmer  

Federal Register 2010, 2011, 2012, 2013

...been no 510(k) submissions for pacemaker programmers since 1995 with the...implantable cardiac devices including pacemakers and defibrillators. Because these...product codes including adaptive rate pacemakers (LWP); implantable...

2012-06-22

251

Transvenous Pacemaker Lead Removal in Pacemaker Lead Endocarditis with Large Vegetations: A Report of Two Cases  

PubMed Central

Pacemaker lead endocarditis is treated with total removal of the infected device and proper antibiotics. The outcomes of patients undergoing percutaneous lead extraction for large vegetations (>2 cm) have not yet been shown. In this case report, we present two patients with pacemaker lead endocarditis with large vegetations of maximum diameter 2.4 cm and 3.2 cm. The first patient had multiple vegetations attached to the tricuspid and mitral valves and developed septic emboli to the brain, lung, and liver. The second patient had a large, persistent vegetation on the tricuspid valve, even two weeks after complete removal of the leads. Both patients were successfully treated with transvenous pacemaker lead removal and antibiotics. PMID:24653742

Cho, Hyunsoo; Kim, Mihyun; Uhm, Jae-Sun; Pak, Hui-Nam; Lee, Moon-Hyoung

2014-01-01

252

Transvenous pacemaker lead removal in pacemaker lead endocarditis with large vegetations: a report of two cases.  

PubMed

Pacemaker lead endocarditis is treated with total removal of the infected device and proper antibiotics. The outcomes of patients undergoing percutaneous lead extraction for large vegetations (>2 cm) have not yet been shown. In this case report, we present two patients with pacemaker lead endocarditis with large vegetations of maximum diameter 2.4 cm and 3.2 cm. The first patient had multiple vegetations attached to the tricuspid and mitral valves and developed septic emboli to the brain, lung, and liver. The second patient had a large, persistent vegetation on the tricuspid valve, even two weeks after complete removal of the leads. Both patients were successfully treated with transvenous pacemaker lead removal and antibiotics. PMID:24653742

Cho, Hyunsoo; Kim, Mihyun; Uhm, Jae-Sun; Pak, Hui-Nam; Lee, Moon-Hyoung; Joung, Boyoung

2014-03-01

253

Gene therapy: Biological pacemaker created by gene transfer  

NASA Astrophysics Data System (ADS)

The pacemaker cells of the heart initiate the heartbeat, sustain the circulation, and dictate the rate and rhythm of cardiac contraction. Circulatory collapse ensues when these specialized cells are damaged by disease, a situation that currently necessitates the implantation of an electronic pacemaker. Here we report the use of viral gene transfer to convert quiescent heart-muscle cells into pacemaker cells, and the successful generation of spontaneous, rhythmic electrical activity in the ventricle in vivo. Our results indicate that genetically engineered pacemakers could be developed as a possible alternative to implantable electronic devices.

Miake, Junichiro; Marbán, Eduardo; Nuss, H. Bradley

2002-09-01

254

Myopotential inhibition of unipolar AV sequential (DVI) pacemaker.  

PubMed

Whereas myopotential inhibition of QRS-inhibited (VVI) pacemakers is well known, its occurrence in patients with AV sequential (DVI) pacemakers has not been reported. The present communication deals with spontaneous and induced myopotential inhibition of a multiprogrammable Intermedics unipolar AV sequential (DVI) pacemaker. The bedside maneuvers that were performed in the patient exposed the problem, therefore serving to establish the diagnosis. Although external adjustment of the sensitivity was the simple, non-invasive solution in this case, more studies are required to determine the success rate of this approach as well as the incidence and clinical significance of myopotential inhibition of unipolar DVI pacemakers. PMID:6181468

Echeverria, H J; Luceri, R M; Thurer, R J; Castellanos, A

1982-01-01

255

Responses of a bursting pacemaker to excitation reveal spatial segregation between bursting and spiking mechanisms  

PubMed Central

Central pattern generators (CPGs) frequently include bursting neurons that serve as pacemakers for rhythm generation. Phase resetting curves (PRCs) can provide insight into mechanisms underlying phase locking in such circuits. PRCs were constructed for a pacemaker bursting complex in the pyloric circuit in the stomatogastric ganglion of the lobster and crab. This complex is comprised of the Anterior Burster (AB) neuron and two Pyloric Dilator (PD) neurons that are all electrically coupled. Artificial excitatory synaptic conductance pulses of different strengths and durations were injected into one of the AB or PD somata using the Dynamic Clamp. Previously, we characterized the inhibitory PRCs by assuming a single slow process that enabled synaptic inputs to trigger switches between an up state in which spiking occurs and a down state in which it does not. Excitation produced five different PRC shapes, which could not be explained with such a simple model. A separate dendritic compartment was required to separate the mechanism that generates the up and down phases of the bursting envelope (1) from synaptic inputs applied at the soma, (2) from axonal spike generation and (3) from a slow process with a slower time scale than burst generation. This study reveals that due to the nonlinear properties and compartmentalization of ionic channels, the response to excitation is more complex than inhibition. PMID:21360137

Maran, Selva K; Sieling, Fred H; Demla, Kavita; Prinz, Astrid A; Canavier, Carmen C

2011-01-01

256

"False inhibition" of demand pacemaker due to leakage of fluid into the pacemaker lead socket.  

PubMed

"False inhibition" of a demand pacemaker usually occurs with a microfracture of the lead system resulting in a galvanic potential at the site of the fracture or with sensing of myopotential with exercise. An increase in the slope of the leading half edge of the pulse contour is generally considered diagnostic of lead fracture. We report the case of a patient in whom "false inhibition" at rest and an increase in the slope of the leading half edge of the pulse contour were caused by leakage of fluid into the pacemaker lead socket. PMID:642574

Chandra, M S; Patel, M R; Laughlin, D E; Rossi, N P

1978-05-01

257

CHAPTER SEVEN Circadian Rhythms, Sleep  

E-print Network

CHAPTER SEVEN Circadian Rhythms, Sleep Deprivation, and Human Performance Namni Goel*, Mathias Basner*, Hengyi Rao*, , David F. Dinges* *Division of Sleep and Chronobiology, Department of Psychiatry, Philadelphia, Pennsylvania, USA Contents 1. Introduction 156 2. Sleep­Wake and Circadian Regulation: Two

Pennsylvania, University of

258

Making Circadian Cancer Therapy Practical  

Microsoft Academic Search

Practical circadian therapy for the cancer patient involves 3 spheres of intervention—improving lifestyle, optimizing internal biochemical milieu, and adjusting treatment times. The potential value of improving overall circadian functioning is shown in the work of Mormont et al in which pronounced rest—activity rhythms were associated with better survival in colorectal cancer patients receiving chronomodulated chemotherapy. Lifestyle interventions that may improve

Keith I. Block; Penny B. Block; Susan Reynolds Fox; Jamie Stouffer Birris; April Y. Feng; Michael de la Torre; Deva Nathan; Peter Tothy; Amanda K. Maki; Charlotte Gyllenhaal

2009-01-01

259

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

260

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

261

Circadian KaiC Phosphorylation: A Multi-Layer Network  

PubMed Central

Circadian KaiC phosphorylation in cyanobacteria reconstituted in vitro recently initiates a series of studies experimentally and theoretically to explore its mechanism. In this paper, we report a dynamic diversity in hexameric KaiC phosphoforms using a multi-layer reaction network based on the nonequivalence of the dual phosphorylation sites (S431 and T432) in each KaiC subunit. These diverse oscillatory profiles can generate a kaleidoscopic phase modulation pattern probably responsible for the genome-wide transcription rhythms directly and/or indirectly in cyanobacteria. Particularly, our model reveals that a single KaiC hexamer is an energy-based, phosphorylation-dependent and self-regulated circadian oscillator modulated by KaiA and KaiB. We suggest that T432 is the main regulator for the oscillation amplitude, while S431 is the major phase regulator. S431 and T432 coordinately control the phosphorylation period. Robustness of the Kai network was examined by mixing samples in different phases, and varying protein concentrations and temperature. Similar results were obtained regardless of the deterministic or stochastic method employed. Therefore, the dynamic diversities and robustness of Kai oscillator make it a qualified core pacemaker that controls the cellular processes in cyanobacteria pervasively and accurately. PMID:19936045

Li, Congxin; Chen, Xiaofang; Wang, Pengye; Wang, Weichi

2009-01-01

262

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

263

Systems Biology of the Mammalian Circadian Clock  

E-print Network

Molecular Chronobiology #12;The circadian oscillator Circadian rhythm Oster et al., 2002 Feedback loops rhythms disrupted -TrCP1-Mediated Degradation of PERIOD2 Is Essential for Circadian Dynamics Reischl et alSystems Biology of the Mammalian Circadian Clock Hanspeter Herzel Institute for Theoretical Biology

Spang, Rainer

264

Human skin keratinocytes, melanocytes, and fibroblasts contain distinct circadian clock machineries.  

PubMed

Skin acts as a barrier between the environment and internal organs and performs functions that are critical for the preservation of body homeostasis. In mammals, a complex network of circadian clocks and oscillators adapts physiology and behavior to environmental changes by generating circadian rhythms. These rhythms are induced in the central pacemaker and peripheral tissues by similar transcriptional-translational feedback loops involving clock genes. In this work, we investigated the presence of functional oscillators in the human skin by studying kinetics of clock gene expression in epidermal and dermal cells originating from the same donor and compared their characteristics. Primary cultures of fibroblasts, keratinocytes, and melanocytes were established from an abdominal biopsy and expression of clock genes following dexamethasone synchronization was assessed by qPCR. An original mathematical method was developed to analyze simultaneously up to nine clock genes. By fitting the oscillations to a common period, the phase relationships of the genes could be determined accurately. We thereby show the presence of functional circadian machinery in each cell type. These clockworks display specific periods and phase relationships between clock genes, suggesting regulatory mechanisms that are particular to each cell type. Taken together, our data demonstrate that skin has a complex circadian organization. Oscillators are present not only in fibroblasts but also in epidermal keratinocytes and melanocytes and are likely to act in coordination to drive rhythmic functions within the skin. PMID:22627494

Sandu, Cristina; Dumas, Marc; Malan, André; Sambakhe, Diariétou; Marteau, Clarisse; Nizard, Carine; Schnebert, Sylvianne; Perrier, Eric; Challet, Etienne; Pévet, Paul; Felder-Schmittbuhl, Marie-Paule

2012-10-01

265

Photorefractoriness in mammals: dissociating a seasonal timer from the circadian-based photoperiod response.  

PubMed

In seasonal animals, prolonged exposure to constant photoperiod induces photorefractoriness, causing spontaneous reversion in physiology to that of the previous photoperiodic state. This study tested the hypothesis that the onset of photorefractoriness is correlated with a change in circadian expression of clock genes in the suprachiasmatic nucleus (circadian pacemaker) and the pars tuberalis (PT, a melatonin target tissue). Soay sheep were exposed to summer photoperiod (16-h light) for either 6 or 30 wk to produce a photostimulated and photorefractory physiology, and seasonal changes were tracked by measuring the long-term prolactin cycles. Animals were killed at 4-h intervals throughout 24 h. Contrary to the hypothesis, the 24-h rhythmic expression of clock genes (Rev-erbalpha, Per1, Per2, Bmal1, Cry1) in the suprachiasmatic nucleus and PT reflected the ambient photoperiod/melatonin signal and not the changing physiology. Contrastingly, the PT expression of alpha-glycoprotein hormone subunit (alphaGSU) and betaTSH declined in photorefractory animals toward a short day-like endocrinology. We conclude that the generation of long-term endocrine cycles depends on the interaction between a circadian-based, melatonin-dependent timer that drives the initial photoperiodic response and a non-circadian-based timer that drives circannual rhythmicity in long-lived species. Under constant photoperiod the two timers can dissociate, leading to the apparent refractory state. PMID:15919753

Lincoln, Gerald A; Johnston, Jonathan D; Andersson, Hakan; Wagner, Gabriela; Hazlerigg, David G

2005-09-01

266

The relationship between FRQ-protein stability and temperature compensation in the Neurospora circadian clock.  

PubMed

Temperature compensation is an important property of all biological clocks. In Neurospora crassa, negative-feedback regulation on the frequency (frq) gene's transcription by the FRQ protein plays a central role in the organism's circadian pacemaker. Earlier model calculations predicted that the stability of FRQ should determine the period length of Neurospora's circadian rhythm as well as the rhythm's temperature compensation. Here, we report experimental FRQ protein stabilities in frq mutants at 20 degrees C and 25 degrees C, and estimates of overall activation energies for mutant FRQ protein degradation. The results are consistent with earlier model predictions, i.e., temperature compensation of Neurospora's circadian rhythm is a highly regulated process where the stability of FRQ is an important factor in determining Neurospora's circadian period as well as the clock's temperature compensation. The partial loss of temperature compensation in frq7 and frq(S513I) mutants can be described by a simple negative-feedback model (the Goodwin oscillator) when the experimentally obtained activation energies of FRQ degradation for theses mutants are incorporated into the model. PMID:16314576

Ruoff, Peter; Loros, Jennifer J; Dunlap, Jay C

2005-12-01

267

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

268

The Output Signal of Purkinje Cells of the Cerebellum and Circadian Rhythmicity  

PubMed Central

Measurement of clock gene expression has recently provided evidence that the cerebellum, like the master clock in the SCN, contains a circadian oscillator. The cerebellar oscillator is involved in anticipation of mealtime and possibly resides in Purkinje cells. However, the rhythmic gene expression is likely transduced into a circadian cerebellar output signal to exert an effective control of neuronal brain circuits that are responsible for feeding behavior. Using electrophysiological recordings from acute and organotypic cerebellar slices, we tested the hypothesis whether Purkinje cells transmit a circadian modulated signal to their targets in the brain. Extracellular recordings from brain slices revealed the typical discharge pattern previously described in vivo in single cell recordings showing basically a tonic or a trimodal-like firing pattern. However, in acute sagittal cerebellar slices the average spike rate of randomly selected Purkinje cells did not exhibit significant circadian variations, irrespective of their specific firing pattern. Also, frequency and amplitude of spontaneous inhibitory postsynaptic currents and the amplitude of GABA- and glutamate-evoked currents did not vary with circadian time. Long-term recordings using multielectrode arrays (MEA) allowed to monitor neuronal activity at multiple sites in organotypic cerebellar slices for several days to weeks. With this recording technique we observed oscillations of the firing rate of cerebellar neurons, presumably of Purkinje cells, with a period of about 24 hours which were stable for periods up to three days. The daily renewal of culture medium could induce circadian oscillations of the firing rate of Purkinje cells, a feature that is compatible with the behavior of slave oscillators. However, from the present results it appears that the circadian expression of cerebellar clock genes exerts only a weak influence on the electrical output of cerebellar neurons. PMID:23505510

Mordel, Jerome; Karnas, Diana; Pevet, Paul; Isope, Philippe; Challet, Etienne; Meissl, Hilmar

2013-01-01

269

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

270

Utility of isoproterenol in unmasking latent escape rhythm in pacemaker dependent patients undergoing pacemaker replacement.  

PubMed

Pacemaker generator replacement in dependent patients may be managed with a bridging temporary pacing lead or by replacing the generator very expediently. The 2 options involve a small risk, and temporary pacing introduces additional cost. This study was conducted to explore the utility of a graduated rate-decrease protocol with isoproterenol support in unmasking an intrinsic rhythm that would obviate the 2 strategies. The protocol was used in 100 consecutive pacemaker-dependent patients (mean age 74.4 +/- 13.7 years, 56% men) who underwent permanent pacemaker replacement. Device lower rates were decremented in 1-minute intervals to 60, 50, 40, and 30 beats/min. If no intrinsic rhythm of > or =30 beats/min was observed after 1 minute, isoproterenol was infused at 1 microg/min for 2 minutes, followed by 2 microg/min for 2 minutes. Of the 100 patients, 59 demonstrated intrinsic rhythm during pacing step-down alone. Of the remaining 41 patients, 28 (68.3%) demonstrated intrinsic rhythm during isoproterenol infusion. The escape rhythm was junctional in 29%, idioventricular in 23%, conducted atrial fibrillation in 16%, and sinus in 15%. Only 13 of 100 patients (13%) failed to demonstrate adequate intrinsic rhythm after the protocol. In conclusion, this suggests that a standardized protocol to elicit an underlying rhythm in patients previously assessed as pacemaker dependent effectively minimizes the need for temporary pacing during device replacement. PMID:18308011

Chihrin, Stephen M; Mohamed, Uwais; Yee, Raymond; Gula, Lorne J; Klein, George J; Skanes, Allan C; Krahn, Andrew D

2008-03-01

271

Autonomic control and innervation of the atrioventricular junctional pacemaker  

E-print Network

the junctional rate, and parasympathetic and sympathetic com- ponents can be separated with atropine system; Junctional rhythm; Junctional pacemaker (Heart Rhythm 2007;4:1326­1335) © 2007 Heart Rhythm junction may be- come the pacemaker of the heart. Unlike the well-characterized sinoatrial node (SAN

272

[A new program-controlled telemetry technology for pacemakers].  

PubMed

This thesis is about a new technology of program-controlled telemetry for pacemakers. The system utilizes digital logic circuit design, and the program-controlled part uses single chip to control for display and debug. PWM and reflectance telemetry may improve the preciseness and correctness of signal transmission, and reduce the power consumption of pacemakers and prolong the lifetime. PMID:16104257

Wang, Yu; Huang, Xin-ming; Fang, Zu-xinag

2002-09-01

273

Disrupted reproduction, estrous cycle, and circadian rhythms in female mice deficient in vasoactive intestinal Peptide.  

PubMed

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 produce 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; that is, ovulation occurs less frequently and results in the release of fewer oocytes compared with controls. Circadian rhythms of wheel-running activity are disrupted in the female mutant mice, as is the spontaneous electrical activity of dorsal SCN neurons. On a molecular level, the VIP-deficient SCN tissue exhibits 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, D H; Kuljis, D A; Azuma, L; Wu, Y; Truong, D; Wang, H B; Colwell, C S

2014-10-01

274

GW182 controls Drosophila circadian behavior and PDF-Receptor signaling  

PubMed Central

The neuropeptide PDF is crucial for Drosophila circadian behavior: it keeps circadian neurons synchronized. Here, we identify GW182 as a key regulator of PDF signaling. Indeed, GW182 downregulation results in phenotypes similar to those of Pdf and Pdf-receptor (Pdfr) mutants. gw182 genetically interacts with Pdfr and cAMP signaling, which is essential for PDFR function. GW182 mediates miRNA-dependent gene silencing through its interaction with AGO1. Consistently, GW182's AGO1 interaction domain is required for GW182's circadian function. Moreover, our results indicate that GW182 modulates PDFR signaling by silencing the expression of the cAMP phosphodiesterase DUNCE. Importantly, this repression is under photic control, and GW182 activity level - which is limiting in circadian neurons - influences the responses of the circadian neural network to light. We propose that GW182's gene silencing activity functions as a rheostat for PDFR signaling, and thus profoundly impacts the circadian neural network and its response to environmental inputs. PMID:23583112

Zhang, Yong; Emery, Patrick

2013-01-01

275

Electrocution induced symptomatic bradycardia necessitating pacemaker implantation.  

PubMed

Electrical or electrocution injury is a common accidental occurrence and mostly workplace related. Fatal arrhythmias, skin injury and sudden death may ensue. However, it is rare for electrocution to result in permanent low rate sinus bradycardia, incompatible with an active lifestyle. The probable mechanisms for this pathological sinus bradycardia are sinus node dysfunction and autonomic dysfunction with vagal predominance. We describe a young patient who suffered a non fatal electrocution with resultant low rate sinus bradycardia and its successful treatment with a dual chamber rate responsive pacemaker. PMID:25104983

Yew, Kuan Leong

2014-04-01

276

Electrocution Induced Symptomatic Bradycardia Necessitating Pacemaker Implantation  

PubMed Central

Electrical or electrocution injury is a common accidental occurrence and mostly workplace related. Fatal arrhythmias, skin injury and sudden death may ensue. However, it is rare for electrocution to result in permanent low rate sinus bradycardia, incompatible with an active lifestyle. The probable mechanisms for this pathological sinus bradycardia are sinus node dysfunction and autonomic dysfunction with vagal predominance. We describe a young patient who suffered a non fatal electrocution with resultant low rate sinus bradycardia and its successful treatment with a dual chamber rate responsive pacemaker. PMID:25104983

Yew, Kuan Leong

2014-01-01

277

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

278

The photoperiodic clock is blackheaded buntings (Emberiza melanocephala) is mediated by a self-sustaining circadian system.  

PubMed

Three experimental protocols were employed to clarify whether the circadian system is involved in photoperiodic time-measurement in the blackheaded bunting, Emberiza melanocephala. In a single-pulse paradigm, one 8-h light pulse was delivered at different times to groups of birds across three days of constant darkness (DD). Photoperiodic induction, as measured by a rise in plasma luteinizing hormone (LH), showed clear circadian rhythmicity. The second experiment examined the LH responses in birds exposed to lighting cycles using a Nanda-Hamner type of protocol and confirmed full photostimulation under 6L:30D. The third experiment measured the time of the first photoinduced rise in LH in birds subjected to 30 h of continuous light following entrainment under short days (6L:18D). This experiment aimed to identify the position of the photoinducible phase (phi i). LH first rose at hour 18 following dawn indicating that phi i lies in the middle of the day. Plasma concentrations of melatonin were also measured under 6L:18D and 6L:30D light cycles as another physiological marker of the circadian systems in buntings. The pattern of melatonin secretion with the driving oscillator being circadian in nature. It is concluded that the circadian pacemaker driving the photoinducible rhythm in blackheaded bunting is strongly self-sustaining and free-runs under constant conditions. PMID:8965259

Kumar, V; Jain, N; Follett, B K

1996-01-01

279

Biological Clocks and Circadian Rhythms  

NSDL National Science Digital Library

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 rhythms, they are provided with opportunities to connect learning to experiences and observations from their own lives. This article describes how to reset the biological clock of a shamrock plant while shedding light on its circadian rhythms.

Robertson, Laura; Jones, M. G.

2009-02-01

280

An Effect of Castration and Testosterone Replacement on a Circadian Pacemaker in Mice (Mus musculus)  

Microsoft Academic Search

Castration of mice in freerunning conditions (total darkness, DD) causes a reduction of running wheel activity in the beginning of the active period (alpha ) and stimulates activity at the end of alpha . Simultaneously, the period (tau ) of the freerunning rhythm is increased. Both effects are abolished by implantation of a Silastic capsule from which a physiological dose

Serge Daan; David Damassa; Colin S. Pittendrigh; Erla R. Smith

1975-01-01

281

Fixed interval feeding does not entrain the circadian pacemaker in blind rats.  

PubMed

Male and female rats were blinded by orbital enucleation at 1 or 21 days of age and were housed along with intact controls in a temperature- and light-controlled room (22 +/- 2 degrees C, LD 12:12). At 40 days of age the rats were transferred to running wheel cages connected to an event recorder and their activity patterns were monitored for the next 11--16 wk. After 4--6 wk in the running wheels, the rats were subjected to a fixed interval feeding (FIF) schedule lasting 23 days followed by 4--6 wk of ad libitum feeding and watering. Of 19 blind rats with interpretable activity records, 14 showed no change in their activity patterns associated with the FIF other than the addition of a large component of activity before and after the feeding period every day. It was concluded that, in contrast to the squirrel monkey, FIF is not an important zeitgeber for blind rats. PMID:443404

Gibbs, F P

1979-05-01

282

Electrophysiological and Ionic Properties of Intrinsic Circadian Pacemakers in the Vertebrate Pineal Gland.  

National Technical Information Service (NTIS)

Cyclic GMP-activated channels of the chick pineal gland are not altered by physiological concentrations of cytoplasmic Ca2+ ions. They are partially blocked by physiological levels of Mg2+. Changes in intracellular pH over a range of 6.2-8.2 do not affect...

S. E. Dryer

1994-01-01

283

The frequency preference of neurons and synapses in a recurrent oscillatory network.  

PubMed

A variety of neurons and synapses shows a maximal response at a preferred frequency, generally considered to be important in shaping network activity. We are interested in whether all neurons and synapses in a recurrent oscillatory network can have preferred frequencies and, if so, whether these frequencies are the same or correlated, and whether they influence the network activity. We address this question using identified neurons in the pyloric network of the crab Cancer borealis. Previous work has shown that the pyloric pacemaker neurons exhibit membrane potential resonance whose resonance frequency is correlated with the network frequency. The follower lateral pyloric (LP) neuron makes reciprocally inhibitory synapses with the pacemakers. We find that LP shows resonance at a higher frequency than the pacemakers and the network frequency falls between the two. We also find that the reciprocal synapses between the pacemakers and LP have preferred frequencies but at significantly lower values. The preferred frequency of the LP to pacemaker synapse is correlated with the presynaptic preferred frequency, which is most pronounced when the peak voltage of the LP waveform is within the dynamic range of the synaptic activation curve and a shift in the activation curve by the modulatory neuropeptide proctolin shifts the frequency preference. Proctolin also changes the power of the LP neuron resonance without significantly changing the resonance frequency. These results indicate that different neuron types and synapses in a network may have distinct preferred frequencies, which are subject to neuromodulation and may interact to shape network oscillations. PMID:25232127

Tseng, Hua-An; Martinez, Diana; Nadim, Farzan

2014-09-17

284

Casein kinase 1 promotes synchrony of the circadian clock network.  

PubMed

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 dbt(EY02910) loss-of-function mutant. We found that DBT protein levels are dramatically reduced in adult dbt(EY02910) 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 dbt(EY02910) 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; Sehgal, Amita

2014-07-01

285

[Infections secondary to implantation of cardiac pacemakers].  

PubMed

Infectious complications of pacemaker implantation are not common but may be particularly severe. Localised wound infections at the site of implantation have been reported in 0.5% of cases in the most recent series with an average of about 2%. The incidence of septicaemia and infectious endocarditis is lower, about 0.5% of cases. The operator's experience, the duration of the procedure and repeat procedures are considered to be predisposing factors. The main cause of these infections is though to be local contamination during the implantation. The commonest causal organism is the staphylococcus (75 to 92%), the staphylococcus aureus being the cause of acute infections whereas the staphylococcus epidermis is associated with cases of secondary infection. The usual clinical presentation is infection at the site of the pacemaker but other forms such as abscess, endocarditis, rejection of the implanted material, septic emboli and septic phlebitis have been described. The diagnosis is confirmed by local and systemic biological investigations and by echocardiography (especially transoesophageal echocardiography) in cases of right heart endocarditis. There are two axes of treatment: bactericidal double antibiotherapy and surgical ablation of the infected material either percutaneously or by cardiotomy. Though controversial, and unsupported by scientific evidence, the role of systematic, preoperative, prophylactic antibiotic therapy in the prevention of these complications seems to be increasing. PMID:9749192

Da Costa, A; Kirkorian, G; Chevalier, P; Cerisier, A; Chalvidan, T; Obadia, J F; Etienne, J; Isaaz, K; Touboul, P

1998-06-01

286

Permanent cardiac pacemakers: issues relevant to the emergency physician, part I  

Microsoft Academic Search

Many people benefit from the implantation of cardiac pacemakers for management of certain cardiac dysrhythmias. These patients are seen regularly in the emergency department with a variety of pacemaker complications and malfunctions. The presence of a pacemaker may also affect management of unrelated medical problems. This two-part series reviews the medical issues related to patients with permanent pacemakers. Part I

Taylor Y Cardall; Theodore C Chan; William J Brady; James C Perry; Gary M Vilke; Peter Rosen

1999-01-01

287

Altered Dynamics in the Circadian Oscillation of Clock Genes in Dermal Fibroblasts of Patients Suffering from Idiopathic Hypersomnia  

PubMed Central

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues – mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep – wake rhythms in IH. PMID:24454829

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Rohr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

288

Altered dynamics in the circadian oscillation of clock genes in dermal fibroblasts of patients suffering from idiopathic hypersomnia.  

PubMed

From single cell organisms to the most complex life forms, the 24-hour circadian rhythm is important for numerous aspects of physiology and behavior such as daily periodic fluctuations in body temperature and sleep-wake cycles. Influenced by environmental cues - mainly by light input -, the central pacemaker in the thalamic suprachiasmatic nuclei (SCN) controls and regulates the internal clock mechanisms which are present in peripheral tissues. In order to correlate modifications in the molecular mechanisms of circadian rhythm with the pathophysiology of idiopathic hypersomnia, this study aimed to investigate the dynamics of the expression of circadian clock genes in dermal fibroblasts of idiopathic hypersomniacs (IH) in comparison to those of healthy controls (HC). Ten clinically and polysomnographically proven IH patients were recruited from the department of sleep medicine of the University Hospital of Muenster. Clinical diagnosis was done by two consecutive polysomnographies (PSG) and Multiple Sleep Latency Test (MSLT). Fourteen clinical healthy volunteers served as control group. Dermal fibroblasts were obtained via punch biopsy and grown in cell culture. The expression of circadian clock genes was investigated by semiquantitative Reverse Transcriptase-PCR qRT-PCR analysis, confirming periodical oscillation of expression of the core circadian clock genes BMAL1, PER1/2 and CRY1/2. The amplitude of the rhythmically expressed BMAL1, PER1 and PER2 was significantly dampened in dermal fibroblasts of IH compared to HC over two circadian periods whereas the overall expression of only the key transcriptional factor BMAL1 was significantly reduced in IH. Our study suggests for the first time an aberrant dynamics in the circadian clock in IH. These findings may serve to better understand some clinical features of the pathophysiology in sleep - wake rhythms in IH. PMID:24454829

Lippert, Julian; Halfter, Hartmut; Heidbreder, Anna; Röhr, Dominik; Gess, Burkhard; Boentert, Mathias; Osada, Nani; Young, Peter

2014-01-01

289

Proton Beam Therapy Interference With Implanted Cardiac Pacemakers  

SciTech Connect

Purpose: To investigate the effect of proton beam therapy (PBT) on implanted cardiac pacemaker function. Methods and Materials: After a phantom study confirmed the safety of PBT in patients with cardiac pacemakers, we treated 8 patients with implanted pacemakers using PBT to a total tumor dose of 33-77 gray equivalents (GyE) in dose fractions of 2.2-6.6 GyE. The combined total number of PBT sessions was 127. Although all pulse generators remained outside the treatment field, 4 patients had pacing leads in the radiation field. All patients were monitored by means of electrocardiogram during treatment, and pacemakers were routinely examined before and after PBT. Results: The phantom study showed no effect of neutron scatter on pacemaker generators. In the study, changes in heart rate occurred three times (2.4%) in 2 patients. However, these patients remained completely asymptomatic throughout the PBT course. Conclusions: PBT can result in pacemaker malfunctions that manifest as changes in pulse rate and pulse patterns. Therefore, patients with cardiac pacemakers should be monitored by means of electrocardiogram during PBT.

Oshiro, Yoshiko [Department of Radiation Oncology, University of Tsukuba, Ibaraki (Japan)], E-mail: ooyoshiko@pmrc.tsukuba.ac.jp; Sugahara, Shinji [Department of Radiation Oncology, University of Tsukuba, Ibaraki (Japan); Noma, Mio; Sato, Masato; Sakakibara, Yuzuru [Department of Cardiovascular Surgery, University of Tsukuba, Ibaraki (Japan); Sakae, Takeji [Proton Medical Research Center, University of Tsukuba, Ibaraki (Japan); Hayashi, Yasutaka [Department of Radiation Oncology, University of Tsukuba, Ibaraki (Japan); Nakayama, Hidetsugu; Tsuboi, Koji; Fukumitsu, Nobuyoshi [Department of Radiation Oncology, University of Tsukuba, Ibaraki (Japan); Proton Medical Research Center, University of Tsukuba, Ibaraki (Japan); Kanemoto, Ayae [Department of Radiation Oncology, University of Tsukuba, Ibaraki (Japan); Hashimoto, Takayuki [Division of Radiation Oncology, Shizuoka Cancer Center Hospital, Shizuoka (Japan); Tokuuye, Koichi [Department of Radiation Oncology, University of Tsukuba, Ibaraki (Japan); Proton Medical Research Center, University of Tsukuba, Ibaraki (Japan)

2008-11-01

290

Resynchronization of circadian sleep-wake and temperature cycles in the squirrel monkey following phase shifts of the environmental light-dark cycle  

NASA Technical Reports Server (NTRS)

Circadian rhythms in physiological and behavioral functions gradually resynchronize after phase shifts in environmental time cues. In order to characterize the rate of circadian resynchronization in a diurnal primate model, the temperature, locomotor activity, and polygraphically determined sleep-wake states were monitored in squirrel monkeys before and after 8-h phase shifts of an environmental light-dark cycle of 12 h light and 12 h dark (LD 12:12). For the temperature rhythm, resynchronization took 4 d after phase delay shift and 5 d after phase advance shift; for the rest-activity cycle, resynchronization times were 3 d and 6 d, respectively. The activity acrophase shifted more rapidly than the temperature acrophase early in the post-delay shift interval, but this internal desynchronization between rhythms disappeared during the course of resynchronization. Further study of the early resynchronization process requires emphasis on identifying evoked effects and measuring circadian pacemaker function.

Wexler, D. B.; Moore-Ede, M. C.

1986-01-01

291

Recurrent pulmonary embolization following implantation of transvenous pacemaker.  

PubMed

A 44-year-old man developed recurrent pulmonary embolization after implantation of a permanent transvenous DVI pacemaker connected to polyurethane leads. Thrombus was found in the left innominate and subclavian veins around the pacemaker leads, but not in the right atrium or in the venous system of the pelvis and the lower extremities. The recurrence of pulmonary embolization followed discontinuation of treatment with Coumadin. This case demonstrates that lifelong anticoagulation is indicated in patients who have had pulmonary embolization and/or venous thrombosis around the pacemaker leads. PMID:6207489

Pasquariello, J L; Hariman, R J; Yudelman, I M; Feit, A; Gomes, J A; El-Sherif, N

1984-09-01

292

Bimodal Oscillations of Cyclic Nucleotide Concentrations in the Circadian System of the Madeira Cockroach Rhyparobia maderae.  

PubMed

Pigment-dispersing factor (PDF) is the most important coupling factor of the circadian system in insects, comparable to its functional ortholog vasoactive intestinal polypeptide of the mammalian circadian clock. In Drosophila melanogaster, PDF signals via activation of adenylyl cyclases, controlling circadian locomotor activity rhythms at dusk and dawn. In addition, PDF mediates circadian rhythms of the visual system and is involved in entrainment to different photoperiods. We examined whether PDF daytime-dependently elevates cAMP levels in the Madeira cockroach Rhyparobia maderae and whether cAMP mimics PDF effects on locomotor activity rhythms. To determine time windows of PDF release, we searched for circadian rhythms in concentrations of cAMP and its functional opponent cGMP in the accessory medulla (AMe), the insect circadian pacemaker controlling locomotor activity rhythms, and in the optic lobes, as the major input and output area of the circadian clock. Enzyme-linked immunosorbent assays detected PDF-dependent increases of cAMP in optic lobes and daytime-dependent oscillations of cAMP and cGMP baseline levels in the AMe, both with maxima at dusk and dawn. Although these rhythms disappeared at the first day in constant conditions (DD1), cAMP but not cGMP oscillations returned at the second day in constant conditions (DD2). Whereas in light-dark cycles the cAMP baseline level remained constant in other optic lobe neuropils, it oscillated in phase with the AMe at DD2. To determine whether cAMP and cGMP mimic PDF-dependent control of locomotor activity rhythms, both cyclic nucleotides were injected at different times of the circadian day using running-wheel assays. Whereas cAMP injections generated delays at dusk and advances at dawn, cGMP only delayed locomotor activity at dusk. For the first time we found PDF-dependent phase advances at dawn in addition to previously described phase delays at dusk. Thus, we hypothesize that PDF release at dusk and dawn controls locomotor activity rhythms and visual system processing cAMP-dependently. PMID:25231947

Schendzielorz, Julia; Schendzielorz, Thomas; Arendt, Andreas; Stengl, Monika

2014-10-01

293

Multiple Amidated Neuropeptides Are Required for Normal Circadian Locomotor Rhythms in Drosophila  

Microsoft Academic Search

In Drosophila, the amidated neuropeptide pigment dispersing factor (PDF) is expressed by the ventral subset of lateral pace- maker neurons and is required for circadian locomotor rhythms. Residual rhythmicity in pdf mutants likely reflects the activity of other neurotransmitters. We asked whether other neuropep- tides contribute to such auxiliary mechanisms. We used the gal4\\/UAS system to create mosaics for the

Paul H. Taghert; Randall S. Hewes; Jae H. Park; Martha A. O'Brien; Mei Han; Molly E. Peck

2001-01-01

294

A mechanosensory pathway to the Drosophila circadian clock.  

PubMed

Circadian clocks attune the physiology of virtually all living organisms to the diurnal cycles of their environments. In metazoan animals, multiple sensory input pathways have been linked to clock synchronization with the environmental cycle (entrainment). Extrinsic entrainment cues include light and temperature. We show that (12-hour:12-hour) cycles of vibration and silence (VS) are sufficient to synchronize the daily locomotor activity of wild-type Drosophila melanogaster. Behavioral synchronization to VS cycles required a functional clock and functional chordotonal organs and was accompanied by phase-shifts of the daily oscillations of PERIOD protein concentrations in brain clock neurons. The feedback from mechanosensory-and particularly, proprioceptive-organs may help an animal to keep its circadian clock in sync with its own, stimulus-induced activities. PMID:24482478

Simoni, Alekos; Wolfgang, Werner; Topping, Matthew P; Kavlie, Ryan G; Stanewsky, Ralf; Albert, Joerg T

2014-01-31

295

CIRCADIAN GENES AND BREAST CANCER SUSCEPTIBILITY IN ROTATING SHIFT WORKERS  

PubMed Central

Rotating night shift work is associated with increased risk of breast cancer, likely via circadian disruption. We hypothesized that circadian pathway genes influence breast cancer risk, particularly in rotating night shift workers. We selected 178 common variants across 15 genes pertinent to the circadian system. Using a mixed candidate- and tag-single nucleotide polymorphism approach, we tested for associations between these variants and breast cancer risk in 1,825 women within the Nurses’ Health Study II cohort and investigated potential interactions between genotype and rotating shift-work in a subset of 1,318 women. Multiple-testing-adjusted p-values were obtained by permutation (n=10,000). None of the selected variants was significantly associated with breast cancer risk. However, when accounting for potential effect modification, rs23051560 (Ala394Thr) in the largest circadian gene, Neuronal PAS domain protein 2 (NPAS2) was most strongly associated with breast cancer risk (nominal test for interaction p-value=0.0005; 10,000-permutation-based main-effects p-value among women with <24 months of shift-work=0.003). The observed multiplicative association with breast cancer risk per minor allele (A) was 0.65 (95%CI=0.51–0.82) among women with <24 months of shift-work, and 1.19 (95%CI=0.93–1.54) with ?24 months of shift-work. Women homozygous for the minor allele (AA) with ?24 months of shift-work had a 2.83-times higher breast cancer risk compared to homozygous AA women with <24 months of shift-work (95%CI=1.47–5.56). In smmary, common variation in circadian genes plays at most a small role in breast cancer risk among women of European ancestry. The impact of NPAS2 Ala394Thr in the presence of rotating shift-work requires further investigation. PMID:22473669

Monsees, Genevieve M.; Kraft, Peter; Hankinson, Susan E.; Hunter, David J.; Schernhammer, Eva S.

2012-01-01

296

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2010 CFR

...electronic circuits that produce a periodic electrical pulse to stimulate the heart. This device, which is used outside the body, is used as a temporary substitute for the heart's intrinsic pacing sytem until a permanent pacemaker can be...

2010-04-01

297

Sexual dimorphism in the complexity of cardiac pacemaker activity  

NSDL National Science Digital Library

Journal article titled "Sexual Dimorphism in the Complexity of Cardiac Pacemaker Activity" from The American Journal of PhysiologyÃÂHeart and Circulatory Physiology, by Terry B. J. Kuo, and Cheryl C. H. Yang.

Terry B. Kuo (Tzu Chi Buddhist General Hospital Department of Neurology); Cheryl C.H. Yang (Tzu Chi University Department of Physiology)

2007-10-03

298

21 CFR 870.3600 - External pacemaker pulse generator.  

...permanent pacemaker can be implanted, or to control irregular heartbeats in patients following cardiac surgery or a myocardial infarction. The device may have adjustments for impulse strength, duration, R-wave sensitivity, and other pacing variables....

2014-04-01

299

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2013 CFR

...permanent pacemaker can be implanted, or to control irregular heartbeats in patients following cardiac surgery or a myocardial infarction. The device may have adjustments for impulse strength, duration, R-wave sensitivity, and other pacing variables....

2013-04-01

300

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2011 CFR

...permanent pacemaker can be implanted, or to control irregular heartbeats in patients following cardiac surgery or a myocardial infarction. The device may have adjustments for impulse strength, duration, R-wave sensitivity, and other pacing variables....

2011-04-01

301

21 CFR 870.3600 - External pacemaker pulse generator.  

Code of Federal Regulations, 2012 CFR

...permanent pacemaker can be implanted, or to control irregular heartbeats in patients following cardiac surgery or a myocardial infarction. The device may have adjustments for impulse strength, duration, R-wave sensitivity, and other pacing variables....

2012-04-01

302

Magnetic Resonance Imaging Conditional Pacemakers: Rationale, Development and Future Directions  

PubMed Central

Pacemakers and other cardiac implantable electronic devices (CIEDs) have long been considered an absolute contraindication to magnetic resonance imaging (MRI), a crucial and growing imaging modality. In the last 20 years, protocols have been developed to allow MR scanning of CIED patients with a low complication rate. However, this practice has remained limited to a relatively small number of centers, and many pacemaker patients continue to be denied access to clinically indicated imaging. The introduction of MRI conditional pacemakers has provided a widely applicable and satisfactory solution to this problem. Here, the interactions of pacemakers with the MR environment, the results of MR scanning in patients with conventional CIEDs, the development and clinical experience with MRI conditional devices, and future directions are reviewed. PMID:23071382

Cronin, Edmond M; Wilkoff, Bruce L

2012-01-01

303

Atrial trigeminy induced by a normally functioning DVI pacemaker.  

PubMed

Atrial trigeminy was seen in a patient with a normally functioning DVI pacemaker (Byrel-5992). Atrial competition resulted from coincidence of sinus and atrial escape rates together with late ventricular sensing. This resulted in atrial output stimuli occurring within the QRS complex. Alternate impulses occurred late enough to conduct to the ventricle after recovery of the AV node. Reprogramming the pacemaker to either a faster DVI rate or to VVI abolished the arrhythmia. PMID:6200856

Millar, R N; Obel, I W

1984-03-01

304

Protein Phosphatase 1 (PP1) Is a Post-Translational Regulator of the Mammalian Circadian Clock  

PubMed Central

Circadian clocks coordinate the timing of important biological processes. Interconnected transcriptional and post-translational feedback loops based on a set of clock genes generate and maintain these rhythms with a period of about 24 hours. Many clock proteins undergo circadian cycles of post-translational modifications. Among these modifications, protein phosphorylation plays an important role in regulating activity, stability and intracellular localization of clock components. Several protein kinases were characterized as regulators of the circadian clock. However, the function of protein phosphatases, which balance phosphorylation events, in the mammalian clock mechanism is less well understood. Here, we identify protein phosphatase 1 (PP1) as regulator of period and light-induced resetting of the mammalian circadian clock. Down-regulation of PP1 activity in cells by RNA interference and in vivo by expression of a specific inhibitor in the brain of mice tended to lengthen circadian period. Moreover, reduction of PP1 activity in the brain altered light-mediated clock resetting behavior in mice, enhancing the phase shifts in either direction. At the molecular level, diminished PP1 activity increased nuclear accumulation of the clock component PER2 in neurons. Hence, PP1, may reduce PER2 phosphorylation thereby influencing nuclear localization of this protein. This may at least partially influence period and phase shifting properties of the mammalian circadian clock. PMID:21712997

Schmutz, Isabelle; Wendt, Sabrina; Schnell, Anna; Kramer, Achim; Mansuy, Isabelle M.; Albrecht, Urs

2011-01-01

305

Pet-1 Deficiency Alters the Circadian Clock and Its Temporal Organization of Behavior  

PubMed Central

The serotonin and circadian systems are two important interactive regulatory networks in the mammalian brain that regulate behavior and physiology in ways that are known to impact human mental health. Previous work on the interaction between these two systems suggests that serotonin modulates photic input to the central circadian clock (the suprachiasmatic nuclei; SCN) from the retina and serves as a signal for locomotor activity, novelty, and arousal to shift the SCN clock, but effects of disruption of serotonergic signaling from the raphe nuclei on circadian behavior and on SCN function are not fully characterized. In this study, we examined the effects on diurnal and circadian behavior, and on ex vivo molecular rhythms of the SCN, of genetic deficiency in Pet-1, an ETS transcription factor that is necessary to establish and maintain the serotonergic phenotype of raphe neurons. Pet-1?/? mice exhibit loss of rhythmic behavioral coherence and an extended daily activity duration, as well as changes in the molecular rhythms expressed by the clock, such that ex vivo SCN from Pet-1?/? mice exhibit period lengthening and sex-dependent changes in rhythmic amplitude. Together, our results indicate that Pet-1 regulation of raphe neuron serotonin phenotype contributes to the period, precision and light/dark partitioning of locomotor behavioral rhythms by the circadian clock through direct actions on the SCN clock itself, as well as through non-clock effects. PMID:24831114

Axley, John C.; Deneris, Evan S.; McMahon, Douglas G.

2014-01-01

306

244 Dispatch Circadian rhythms: Partners in time  

E-print Network

244 Dispatch Circadian rhythms: Partners in time Russell N. Van Gelder* and Mark A. Krasnow of the rhythms he discovered. Circadian rhythms -- self- sustained, nearly 24 hour rhythms of behavior in insects. Despite intensive analysis of the physiological properties of circadian rhythms, no clear insight

Krasnow, Mark A.

307

Cognitive performance as a zeitgeber: cognitive oscillators and cholinergic modulation of the SCN entrain circadian rhythms.  

PubMed

The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF) cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s) outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior. PMID:23441168

Gritton, Howard J; Stasiak, Ashley M; Sarter, Martin; Lee, Theresa M

2013-01-01

308

Effects of restricted feeding schedules on circadian organization in squirrel monkeys  

NASA Technical Reports Server (NTRS)

Free running circadian rhythms of motor activity, food-motivated lever-pressing, and either drinking (N = 7) or body temperature (N = 3) were recorded from 10 squirrel monkeys maintained in constant illumination with unlimited access to food. Food availability was then restricted to a single unsignaled 3-hour interval each day. The feeding schedule failed to entrain the activity rhythms of 8 monkeys, which continued to free-run. Drinking was almost completely synchronized by the schedule, while body temperature showed a feeding-induced rise superimposed on a free-running rhythm. Nonreinforced lever-pressing showed both a free-running component and a 24-hour component that anticipated the time of feeding. At the termination of the schedule, all recorded variables showed free-running rhythms, but in 3 animals the initial phase of the postschedule rhythms was advanced by several hours, suggesting relative coordination. Of the remaining 2 animals, one exhibited stable entrainment of all 3 recorded rhythms, while the other appeared to entrain temporarily to the feeding schedule. These results indicate that restricted feeding schedules are only a weak zeitgeber for the circadian pacemaker generating free-running rhythms in the squirrel monkey. Such schedules, however, may entrain a separate circadian system responsible for the timing of food-anticipatory changes in behavior and physiology.

Boulos, Z.; Frim, D. M.; Dewey, L. K.; Moore-Ede, M. C.

1989-01-01

309

Circadian performance of suprachiasmatic nuclei (SCN)-lesioned antelope ground squirrels in a desert enclosure.  

PubMed

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 site of origin, including 12 intact control animals and 10 animals whose circadian timing had been disrupted by SCN-lesioning. Time of activity was recorded continuously for 15 days in a large outdoor enclosure by a motion detector, a microchip transponder detector, and video surveillance. An unplanned nighttime attack by a feral cat resulted in the death of 60% of the SCN-lesioned animals and 29% of the control animals in the enclosure. Surface activity of SCN-lesioned animals at the food cache occurred both in daytime and at night, ranging from 16.0% nighttime activity for one partially lesioned individual to 52.1% for one completely lesioned animal. Controls were strongly day-active, with nighttime surface trips constituting only 0-1.3% of all excursions to the cache. Nine wild free-ranging individuals, including one with a radiotransmitter collar, were exclusively day-active. One of the functions of the SCN in mammals may be to reduce activity of animals during times that are unfavorable for activity. PMID:9333206

DeCoursey, P J; Krulas, J R; Mele, G; Holley, D C

1997-11-01

310

The role of retinal photoreceptors in the regulation of circadian rhythms  

PubMed Central

The circadian clock is an evolutionarily, highly conserved feature of most organisms. This internal timing mechanism coordinates biochemical, physiological and behavioral processes to maintain synchrony with the environmental cycles of light, temperature and nutrients. Several studies have shown that light is the most potent cue used by most organisms (humans included) to synchronize daily activities. In mammals, light perception occurs only in the retina; three different types of photoreceptors are present within this tissue: cones, rods and the newly discovered intrinsically photosensitive retinal ganglion cells (ipRGCs). Researchers believe that the classical photoreceptors (e.g., the rods and the cones) are responsible for the image-forming vision, whereas the ipRGCs play a key role in the non-image forming vision. This non-image-forming photoreceptive system communicates not only with the master circadian pacemaker located in the suprachiasmatic nuclei of the hypothalamus, but also with many other brain areas that are known to be involved in the regulation of several functions; thus, this non-image forming system may also affect several aspects of mammalian health independently from the circadian system. PMID:19777353

Paul, Ketema N.; Saafir, Talib B.; Tosini, Gianluca

2010-01-01

311

A Role for Id2 in Regulating Photic Entrainment of the Mammalian Circadian System  

PubMed Central

Summary Inhibitor of DNA binding genes (Id1–Id4) encode helix-loop-helix (HLH) transcriptional repressors associated with development and tumorigenesis [1, 2], but little is known concerning the function(s) of these genes in normal adult animals. Id2 was identified in DNA microarray screens for rhythmically expressed genes [3–5], and further analysis revealed a circadian pattern of expression of all four Id genes in multiple tissues including the suprachiasmatic nucleus. To explore an in vivo function, we generated and characterized deletion mutations of Id2 and of Id4. Id2?/? mice exhibit abnormally rapid entrainment and an increase in the magnitude of the phase shift of the pacemaker. A significant proportion of mice also exhibit disrupted rhythms when maintained under constant darkness. Conversely, Id4?/? mice did not exhibit a noticeable circadian phenotype. In vitro studies using an mPer1 and an AVP promoter reporter revealed the potential for ID1, ID2, and ID3 proteins to interact with the canonical basic HLH clock proteins BMAL1 and CLOCK. These data suggest that the Id genes may be important for entrainment and operation of the mammalian circadian system, potentially acting through BMAL1 and CLOCK targets. PMID:19217292

Duffield, Giles E.; Watson, Nathan P.; Mantani, Akio; Peirson, Stuart N.; Robles-Murguia, Maricela; Loros, Jennifer J.; Israel, Mark A.; Dunlap, Jay C.

2009-01-01

312

Cognitive Performance as a Zeitgeber: Cognitive Oscillators and Cholinergic Modulation of the SCN Entrain Circadian Rhythms  

PubMed Central

The suprachiasmatic nucleus (SCN) is the primary circadian pacemaker in mammals that can synchronize or entrain to environmental cues. Although light exerts powerful influences on SCN output, other non-photic stimuli can modulate the SCN as well. We recently demonstrated that daily performance of a cognitive task requiring sustained periods of attentional effort that relies upon basal forebrain (BF) cholinergic activity dramatically alters circadian rhythms in rats. In particular, normally nocturnal rats adopt a robust diurnal activity pattern that persists for several days in the absence of cognitive training. Although anatomical and pharmacological data from non-performing animals support a relationship between cholinergic signaling and circadian rhythms, little is known about how endogenous cholinergic signaling influences SCN function in behaving animals. Here we report that BF cholinergic projections to the SCN provide the principal signal allowing for the expression of cognitive entrainment in light-phase trained animals. We also reveal that oscillator(s) outside of the SCN drive cognitive entrainment as daily timed cognitive training robustly entrains SCN-lesioned arrhythmic animals. Ablation of the SCN, however, resulted in significant impairments in task acquisition, indicating that SCN-mediated timekeeping benefits new learning and cognitive performance. Taken together, we conclude that cognition entrains non-photic oscillators, and cholinergic signaling to the SCN serves as a temporal timestamp attenuating SCN photic-driven rhythms, thereby permitting cognitive demands to modulate behavior. PMID:23441168

Gritton, Howard J.; Stasiak, Ashley M.; Sarter, Martin; Lee, Theresa M.

2013-01-01

313

Intermittent pacemaker syndrome: revision of VVI pacemaker to a new cardiac pacing mode for tachy-brady syndrome.  

PubMed

A patient with tachy-brady syndrome manifested by paroxysmal atrial fibrillation and symptomatic sinus bradycardia and treated by VVI pacing developed pacemaker syndrome during episodes of ventricular pacing. His cardiac pacemaker was revised to a dual chamber system utilizing the new AV sequential DDI pacing mode which eliminated pacemaker-related tachycardias and totally abolished the pacemaker syndrome symptoms. There have been no further episodes of atrial fibrillation, possibly due to elimination of temporal dispersion of refractory periods during bradycardia. The propensity for atrial fibrillation has also been minimized by excluding competitive atrial stimulation during DVI pacing. The DDI mode provides the clinician increased utility and flexibility in the use of AV sequential pacing therapy. PMID:2437541

McCormick, D J; Shuck, J W; Ansinelli, R A

1987-03-01

314

Standards of evidence in chronobiology: critical review of a report that restoration of Bmal1 expression in the dorsomedial hypothalamus is sufficient to restore circadian food anticipatory rhythms in Bmal1-/- mice  

PubMed Central

Daily feeding schedules generate food anticipatory rhythms of behavior and physiology that exhibit canonical properties of circadian clock control. The molecular mechanisms and location of food-entrainable circadian oscillators hypothesized to control food anticipatory rhythms are unknown. In 2008, Fuller et al reported that food-entrainable circadian rhythms are absent in mice bearing a null mutation of the circadian clock gene Bmal1 and that these rhythms can be rescued by virally-mediated restoration of Bmal1 expression in the dorsomedial nucleus of the hypothalamus (DMH) but not in the suprachiasmatic nucleus (site of the master light-entrainable circadian pacemaker). These results, taken together with controversial DMH lesion results published by the same laboratory, appear to establish the DMH as the site of a Bmal1-dependent circadian mechanism necessary and sufficient for food anticipatory rhythms. However, careful examination of the manuscript reveals numerous weaknesses in the evidence as presented. These problems are grouped as follows and elaborated in detail: 1. data management issues (apparent misalignments of plotted data), 2. failure of evidence to support the major conclusions, and 3. missing data and methodological details. The Fuller et al results are therefore considered inconclusive, and fail to clarify the role of either the DMH or Bmal1 in the expression of food-entrainable circadian rhythms in rodents. PMID:19323828

Mistlberger, Ralph E; Buijs, Ruud M; Challet, Etienne; Escobar, Carolina; Landry, Glenn J; Kalsbeek, Andries; Pevet, Paul; Shibata, Shigenobu

2009-01-01

315

Synaptic Depression Mediates Bistability in Neuronal Networks with Recurrent Inhibitory Connectivity  

E-print Network

Synaptic Depression Mediates Bistability in Neuronal Networks with Recurrent Inhibitory, New Jersey 07102 When depressing synapses are embedded in a circuit com- posed of a pacemaker neuron the synapses are mostly depressed, and the oscillations are dominated by the properties of the oscillating

Nadim, Farzan

316

Dynamics and transitions of firing patterns in deterministic and stochastic neuronal systems  

Microsoft Academic Search

Some recent work on experimental and theoretical studies on complex firing patterns of neurons and their dynamical mechanisms is reviewed. At first, experimental results on various neural firings and the bifurcation scenarios of ISI series are discovered in neural pacemakers. Next, a thorough analysis on dynamical behaviour and transitions of neuronal firing patterns, including the period-adding bursting sequence without chaos,

Qishao Lu; Zhuoqin Yang; Lixia Duan; Huaguang Gu; Wei Ren

2009-01-01

317

Disruption of circadian clocks has ramifications for metabolism, brain, and behavior.  

PubMed

Circadian (daily) rhythms are present in almost all plants and animals. In mammals, a brain clock located in the hypothalamic suprachiasmatic nucleus maintains synchrony between environmental light/dark cycles and physiology and behavior. Over the past 100 y, especially with the advent of electric lighting, modern society has resulted in a round-the-clock lifestyle, in which natural connections between rest/activity cycles and environmental light/dark cycles have been degraded or even broken. Instances in which rapid changes to sleep patterns are necessary, such as transmeridian air travel, demonstrate negative effects of acute circadian disruption on physiology and behavior. However, the ramifications of chronic disruption of the circadian clock for mental and physical health are not yet fully understood. By housing mice in 20-h light/dark cycles, incongruous with their endogenous ?24-h circadian period, we were able to model the effects of chronic circadian disruption noninvasively. Housing in these conditions results in accelerated weight gain and obesity, as well as changes in metabolic hormones. In the brain, circadian-disrupted mice exhibit a loss of dendritic length and decreased complexity of neurons in the prelimbic prefrontal cortex, a brain region important in executive function and emotional control. Disrupted animals show decreases in cognitive flexibility and changes in emotionality consistent with the changes seen in neural architecture. How our findings translate to humans living and working in chronic circadian disruption is unknown, but we believe that this model can provide a foundation to understand how environmental disruption of circadian rhythms impacts the brain, behavior, and physiology. PMID:21220317

Karatsoreos, Ilia N; Bhagat, Sarah; Bloss, Erik B; Morrison, John H; McEwen, Bruce S

2011-01-25

318

The biological clock of an hematophagous insect: locomotor activity rhythms, circadian expression and downregulation after a blood meal.  

PubMed

Despite the importance of circadian rhythms in vector-borne disease transmission, very little is known about its molecular control in hematophagous insect vectors. In Drosophila melanogaster, a negative feedback loop of gene expression has been shown to contribute to the clock mechanism. Here, we describe some features of the circadian clock of the sandfly Lutzomyia longipalpis, a vector of visceral leishmaniasis. Compared to D. melanogaster, sandfly period and timeless, two negative elements of the feedback loop, show similar peaks of mRNA abundance. On the other hand, the expression of Clock (a positive transcription factor) differs between the two species, raising the possibility that the different phases of Clock expression could be associated with the observed differences in circadian activity rhythms. In addition, we show a reduction in locomotor activity after a blood meal, which is correlated with downregulation of period and timeless expression levels. Our results suggest that the circadian pacemaker and its control over the activity rhythms in this hematophagous insect are modulated by blood intake. PMID:16337945

Meireles-Filho, Antonio C A; da S Rivas, Gustavo B; Gesto, João S M; Machado, Ricardo C; Britto, Constança; de Souza, Nataly A; Peixoto, Alexandre A

2006-01-01

319

Monitoring Cell-autonomous Circadian Clock Rhythms of Gene Expression Using Luciferase Bioluminescence Reporters  

PubMed Central

In mammals, many aspects of behavior and physiology such as sleep-wake cycles and liver metabolism are regulated by endogenous circadian clocks (reviewed1,2). The circadian time-keeping system is a hierarchical multi-oscillator network, with the central clock located in the suprachiasmatic nucleus (SCN) synchronizing and coordinating extra-SCN and peripheral clocks elsewhere1,2. Individual cells are the functional units for generation and maintenance of circadian rhythms3,4, and these oscillators of different tissue types in the organism share a remarkably similar biochemical negative feedback mechanism. However, due to interactions at the neuronal network level in the SCN and through rhythmic, systemic cues at the organismal level, circadian rhythms at the organismal level are not necessarily cell-autonomous5-7. Compared to traditional studies of locomotor activity in vivo and SCN explants ex vivo, cell-based in vitro assays allow for discovery of cell-autonomous circadian defects5,8. Strategically, cell-based models are more experimentally tractable for phenotypic characterization and rapid discovery of basic clock mechanisms5,8-13. Because circadian rhythms are dynamic, longitudinal measurements with high temporal resolution are needed to assess clock function. In recent years, real-time bioluminescence recording using firefly luciferase as a reporter has become a common technique for studying circadian rhythms in mammals14,15, as it allows for examination of the persistence and dynamics of molecular rhythms. To monitor cell-autonomous circadian rhythms of gene expression, luciferase reporters can be introduced into cells via transient transfection13,16,17 or stable transduction5,10,18,19. Here we describe a stable transduction protocol using lentivirus-mediated gene delivery. The lentiviral vector system is superior to traditional methods such as transient transfection and germline transmission because of its efficiency and versatility: it permits efficient delivery and stable integration into the host genome of both dividing and non-dividing cells20. Once a reporter cell line is established, the dynamics of clock function can be examined through bioluminescence recording. We first describe the generation of P(Per2)-dLuc reporter lines, and then present data from this and other circadian reporters. In these assays, 3T3 mouse fibroblasts and U2OS human osteosarcoma cells are used as cellular models. We also discuss various ways of using these clock models in circadian studies. Methods described here can be applied to a great variety of cell types to study the cellular and molecular basis of circadian clocks, and may prove useful in tackling problems in other biological systems. PMID:23052244

Ramanathan, Chidambaram; Khan, Sanjoy K.; Kathale, Nimish D.; Xu, Haiyan; Liu, Andrew C.

2012-01-01

320

Chronic electromyographic analysis of circadian locomotor activity in crayfish.  

PubMed

Animals generally exhibit circadian rhythms of locomotor activity. They initiate locomotor behavior not only reflexively in response to external stimuli but also spontaneously in the absence of any specific stimulus. The neuronal mechanisms underlying circadian locomotor activity can, therefore, be based on the rhythmic changes in either reflexive efficacy or endogenous activity. In crayfish Procambarus clarkii, it can be determined by analyzing electromyographic (EMG) patterns of walking legs whether the walking behavior is initiated reflexively or spontaneously. In this study, we examined quantitatively the leg muscle activity that underlies the locomotor behavior showing circadian rhythms in crayfish. We newly developed a chronic EMG recording system that allowed the animal to freely behave under a tethered condition for more than 10 days. In the LD condition in which the animals exhibited LD entrainment, the rhythmic burst activity of leg muscles for stepping behavior was preceded by non-rhythmic tonic activation that lasted for 1323±488ms when the animal initiated walking. In DD and LL free-running conditions, the pre-burst activation lasted for 1779±31 and 1517±39ms respectively. In the mechanical stimulus-evoked walking, the pre-burst activation ended within 79±6ms. These data suggest that periodic changes in the crayfish locomotor activity under the condition of LD entrainment or free-running are based on activity changes in the spontaneous initiation mechanism of walking behavior rather than those in the sensori-motor pathway connecting mechanoreceptors with leg movements. PMID:23631885

Tomina, Yusuke; Kibayashi, Akihiro; Yoshii, Taishi; Takahata, Masakazu

2013-07-15

321

Scientists Use Gene Therapy to Create 'Biological Pacemaker' in Pig Hearts  

MedlinePLUS

... enable JavaScript. Scientists Use Gene Therapy to Create 'Biological Pacemaker' in Pig Hearts Technique might one day ... transform ordinary pig heart muscle cells into a "biological pacemaker," a feat that might one day lead ...

322

Biasing the pacemaker in the behavioral theory of timing  

PubMed Central

In the behavioral theory of timing, pacemaker rate is determined by overall rate of reinforcement. A two-alternative free-operant psychophysical procedure was employed to investigate whether pacemaker period was also sensitive to the differential rate of reinforcement. Responding on a left key during the first 25 s and on a right key during the second 25 s of a 50-s trial was reinforced at variable intervals, and variable-interval schedule values during the two halves of the trials were varied systematically. Responding on the right key during the first 25 s and on the left key during the second 25 s was not reinforced. Estimates of pacemaker period were derived from fits of a function predicted by the behavioral theory of timing to right-key response proportions in consecutive 5-s bins of the 50-s trial. Estimates of pacemaker period were shortest when the differential reinforcer rate most strongly favored right-key responses, and were longest when the differential reinforcer rate most strongly favored left-key responses. The results were consistent with the conclusion that pacemaker rate is influenced by relative reinforcer rate. PMID:16812769

Bizo, Lewis A.; White, K. Geoffrey

1995-01-01

323

Laparoscopic-assisted retrieval of migrated intra-abdominal pacemaker generator.  

PubMed

A 5-year-old boy born with a congenital heart defect had insertion of an epicardial pacemaker that was found on routine evaluation to have been displaced into the rectovesical pouch. He underwent transvenous insertion of another pacemaker, and the displaced pacemaker was successfully retrieved by laparoscopy without incident. PMID:21479910

Kravarusic, Dragan; Chirdan, Lohfa; Freud, Enrique

2011-12-01

324

Effectiveness evaluation of shielding material for reducing electromagnetic interference of cardiac pacemaker by portable information terminals  

Microsoft Academic Search

A shielding technique is an effective means to protect implanted cardiac pacemaker users from portable information terminals, whereas no evaluation methods for this aim have been established. In this paper, an FDTD model for predicting EMI levels in the pacemakers was introduced for numerical shielding effectiveness evaluation. In the model the pacemaker acted as a receiving antenna, which resulted in

Jianqing Wang; Takeshi Ohshima; Osamu Fujiwara

2001-01-01

325

Noninvasive evaluation of retrograde conduction times to avoid pacemaker-mediated tachycardia.  

PubMed

Pacemaker-mediated tachycardia is a potential complication of atrioventricular (AV) universal DDD pacemakers when retrograde ventriculoatrial (VA) conduction is slower than the postventricular-atrial refractory period of the pulse generator. The propensity for pacemaker-mediated tachycardia was noninvasively assessed in 17 patients with a unipolar DDD pacemaker using chest wall stimulation. Low amplitude stimuli were delivered to chest wall electrodes through a programmed stimulator. Using this method, 13 of the 17 patients were found to have absent VA conduction or VA conduction time less than the postventricular-atrial refractory period. In the four patients with noninvasively measured VA conduction time greater than the postventricular-atrial refractory period, sustained pacemaker-mediated tachycardia was induced. Reprogramming of pacemaker parameters prevented repeat induction of pacemaker-mediated tachycardia in only one of four patients. The three remaining patients had clinical pacemaker-mediated tachycardia and underwent pacemaker programming to the DVI mode. A total of 13 patients continue to use DDD mode after a mean follow-up period of 9.5 +/- 5.4 months. Invasive measurement of VA conduction was performed in 13 of the 17 patients. The noninvasive method accurately predicted the invasive measurement in each case. Noninvasive evaluation of VA conduction accurately predicts the propensity for pacemaker-mediated tachycardia under a variety of clinical conditions. Serial testing can be performed after pacemaker reprogramming or drug intervention. Noninvasive evaluation of retrograde VA conduction should predict most clinical episodes of pacemaker-mediated tachycardia. PMID:3998322

Greenspon, A J; Greenberg, R M

1985-06-01

326

Experimental observation of transition from chaotic bursting to chaotic spiking in a neural pacemaker  

NASA Astrophysics Data System (ADS)

The transition from chaotic bursting to chaotic spiking has been simulated and analyzed in theoretical neuronal models. In the present study, we report experimental observations in a neural pacemaker of a transition from chaotic bursting to chaotic spiking within a bifurcation scenario from period-1 bursting to period-1 spiking. This was induced by adjusting extracellular calcium or potassium concentrations. The bifurcation scenario began from period-doubling bifurcations or period-adding sequences of bursting pattern. This chaotic bursting is characterized by alternations between multiple continuous spikes and a long duration of quiescence, whereas chaotic spiking is comprised of fast, continuous spikes without periods of quiescence. Chaotic bursting changed to chaotic spiking as long interspike intervals (ISIs) of quiescence disappeared within bursting patterns, drastically decreasing both ISIs and the magnitude of the chaotic attractors. Deterministic structures of the chaotic bursting and spiking patterns are also identified by a short-term prediction. The experimental observations, which agree with published findings in theoretical neuronal models, demonstrate the existence and reveal the dynamics of a neuronal transition from chaotic bursting to chaotic spiking in the nervous system.

Gu, Huaguang

2013-06-01

327

Experimental observation of transition from chaotic bursting to chaotic spiking in a neural pacemaker.  

PubMed

The transition from chaotic bursting to chaotic spiking has been simulated and analyzed in theoretical neuronal models. In the present study, we report experimental observations in a neural pacemaker of a transition from chaotic bursting to chaotic spiking within a bifurcation scenario from period-1 bursting to period-1 spiking. This was induced by adjusting extracellular calcium or potassium concentrations. The bifurcation scenario began from period-doubling bifurcations or period-adding sequences of bursting pattern. This chaotic bursting is characterized by alternations between multiple continuous spikes and a long duration of quiescence, whereas chaotic spiking is comprised of fast, continuous spikes without periods of quiescence. Chaotic bursting changed to chaotic spiking as long interspike intervals (ISIs) of quiescence disappeared within bursting patterns, drastically decreasing both ISIs and the magnitude of the chaotic attractors. Deterministic structures of the chaotic bursting and spiking patterns are also identified by a short-term prediction. The experimental observations, which agree with published findings in theoretical neuronal models, demonstrate the existence and reveal the dynamics of a neuronal transition from chaotic bursting to chaotic spiking in the nervous system. PMID:23822491

Gu, Huaguang

2013-06-01

328

Epigenetic regulation of axonal growth of Drosophila pacemaker cells by histone acetyltransferase tip60 controls sleep.  

PubMed

Tip60 is a histone acetyltransferase (HAT) enzyme that epigenetically regulates genes enriched for neuronal functions through interaction with the amyloid precursor protein (APP) intracellular domain. However, whether Tip60-mediated epigenetic dysregulation affects specific neuronal processes in vivo and contributes to neurodegeneration remains unclear. Here, we show that Tip60 HAT activity mediates axonal growth of the Drosophila pacemaker cells, termed "small ventrolateral neurons" (sLNvs), and their production of the neuropeptide pigment-dispersing factor (PDF) that functions to stabilize Drosophila sleep-wake cycles. Using genetic approaches, we show that loss of Tip60 HAT activity in the presence of the Alzheimer's disease-associated APP affects PDF expression and causes retraction of the sLNv synaptic arbor required for presynaptic release of PDF. Functional consequence of these effects is evidenced by disruption of the sleep-wake cycle in these flies. Notably, overexpression of Tip60 in conjunction with APP rescues these sleep-wake disturbances by inducing overelaboration of the sLNv synaptic terminals and increasing PDF levels, supporting a neuroprotective role for dTip60 in sLNv growth and function under APP-induced neurodegenerative conditions. Our findings reveal a novel mechanism for Tip60 mediated sleep-wake regulation via control of axonal growth and PDF levels within the sLNv-encompassing neural network and provide insight into epigenetic-based regulation of sleep disturbances observed in neurodegenerative diseases like Alzheimer's disease. PMID:22982579

Pirooznia, Sheila K; Chiu, Kellie; Chan, May T; Zimmerman, John E; Elefant, Felice

2012-12-01

329

Magnetic Resonance Imaging in patients with ICDs and Pacemakers  

PubMed Central

Magnetic resonance (MR) imaging has unparalleled soft-tissue imaging capabilities. The presence of devices such as pacemakers and implantable cardioverter/defibrillators (ICDs), however, is historically considered a contraindication to MR imaging. These devices are now smaller, with less magnetic material and improved electromagnetic interference protection. This review summarizes the potential hazards of the device-MR environment interaction, and presents updated information regarding in-vivo and in-vitro experiments. Recent reports on patients with implantable pacemakers and ICDs who underwent MR scan shows that under certain conditions patients with these implanted systems may benefit from this imaging modality. The data presented suggests that certain modern pacemaker and ICD systems may indeed be MR safe. This may have major clinical implications on current imaging practice. PMID:16943868

Nair, Prashant; Roguin, Ariel

2005-01-01

330

OPTIMIZATION OF WORK SCHEDULES BASED ON CIRCADIAN RHYTHMS KERI HAGERMAN  

E-print Network

OPTIMIZATION OF WORK SCHEDULES BASED ON CIRCADIAN RHYTHMS By KERI HAGERMAN A SENIOR RESEARCH PAPER.2. Circadian Rhythms----------------------------------------------------------------------------- 1.2.1. A Circadian Rhythm Model---------------------------------------------------------- 1.3. Shift Work

Miles, Will

331

Influence of short-term constant light on phase shift of mouse circadian locomotor activity rhythm induced by agonist and antagonist of serotonin  

Microsoft Academic Search

Despite the large body evidence from a variety of studies, the role of the serotonergic projection in the circadian system is still unclear. Previous work suggested that 5-HT is involved in both the response of SCN neurons to light and the phase-resetting properties of nonphotic stimuli. In hamsters, short exposure to constant light potentiates circadian phase-shifting caused by nonphotic stimuli,

Renata Bartoszewicz; Daria Chmielewska; Magdalena Domo?; Gra?yna Barbacka-Surowiak

2010-01-01

332

Angiosarcoma-like presentation of pacemaker-related vascular proliferation.  

PubMed

A 90-year-old man presented with a rapidly growing vascular lesion after a pacemaker generator change. The rapid growth suggested a possible angiosarcoma. A less dramatic presentation of vascular proliferation has been described as reticular telangiectatic erythema, which has been reporting following insertion of pacemakers, implantable cardioverter defibrillators, and drug-delivery devices. The onset of the disorder is described as weeks to years after implantation or generator change. It is a benign condition that generally remains static or regresses over time. The vascular proliferation noted in this case resolved almost completely over a period of 1 year. PMID:22106983

Ringrose, J S; Banerjee, T; Hull, P R

2012-03-01

333

Femoral approach: an exceptional alternative for permanent pacemaker implantation.  

PubMed

The classic transvenous implantation of a permanent pacemaker in a pectoral location may be precluded by obstruction of venous access through the superior vena cava or recent infection at the implant site. When these barriers to the procedure are bilateral and there are also contraindications or technical difficulties to performing a thoracotomy for an epicardial approach, the femoral vein, although rarely used, can be a viable alternative. We describe the case of a patient with occlusion of both subclavian veins and a high risk for mini-thoracotomy or videothoracoscopy, who underwent implantation of a permanent single-chamber pacemaker via the right femoral vein. PMID:24931177

Tereno Valente, Bruno; Conceição, José M; Nogueira da Silva, Manuel; M Oliveira, Mário; S Cunha, Pedro; Lousinha, Ana; Galrinho, Ana; C Ferreira, Rui

2014-05-01

334

Cardiac arrest caused by undersensing of a temporary epicardial pacemaker.  

PubMed

The R-on-T phenomenon is a well-known entity that predisposes to dangerous arrhythmias. Typically, a premature ventricular complex occurring at the critical time during the T wave of the preceding beat precipitates ventricular tachycardia and fibrillation. This phenomenon can occur not only in asynchronous ventricular pacemakers, but also in synchronous pacemakers, if loss of sensing of the intrinsic rhythm becomes evident. A patient who was fitted with a temporary epicardial wire, following cardiac surgery and experienced repeated episodes of polymorphic ventricular tachycardia caused by the R-on-T phenomenon, is described. PMID:20101359

Chemello, D; Subramanian, A; Kumaraswamy, N

2010-01-01

335

A Novel Protein, CHRONO, Functions as a Core Component of the Mammalian Circadian Clock  

PubMed Central

Circadian rhythms are controlled by a system of negative and positive genetic feedback loops composed of clock genes. Although many genes have been implicated in these feedback loops, it is unclear whether our current list of clock genes is exhaustive. We have recently identified Chrono as a robustly cycling transcript through genome-wide profiling of BMAL1 binding on the E-box. Here, we explore the role of Chrono in cellular timekeeping. Remarkably, endogenous CHRONO occupancy around E-boxes shows a circadian oscillation antiphasic to BMAL1. Overexpression of Chrono leads to suppression of BMAL1–CLOCK activity in a histone deacetylase (HDAC) –dependent manner. In vivo loss-of-function studies of Chrono including Avp neuron-specific knockout (KO) mice display a longer circadian period of locomotor activity. Chrono KO also alters the expression of core clock genes and impairs the response of the circadian clock to stress. CHRONO forms a complex with the glucocorticoid receptor and mediates glucocorticoid response. Our comprehensive study spotlights a previously unrecognized clock component of an unsuspected negative circadian feedback loop that is independent of another negative regulator, Cry2, and that integrates behavioral stress and epigenetic control for efficient metabolic integration of the clock. PMID:24736997

Myung, Jihwan; Kim, Jae Kyoung; Yoritaka, Takashi; Tanoue, Shintaro; Abe, Takaya; Kiyonari, Hiroshi; Fujimoto, Katsumi; Kato, Yukio; Todo, Takashi; Matsubara, Akio; Forger, Daniel; Takumi, Toru

2014-01-01

336

[Body movement as pacemaker induction value: comparison of 2 activity-triggered pacemakers].  

PubMed

This article compares the rate behavior of the activity-triggered pacemakers, the Activitrax (A) and the Sensolog (S), during bench tests as well as in patients under defined ergometric conditions and during every day life with special reference to the susceptibility of both systems to external noise. In the bench tests both pacemakers were mounted on a swingbord and subjected to controlled vibrational force. In the first experiment the frequency, in the second experiment the energy was varied. In two groups, one with S, one with A implanted, each consisting of 10 patients, the discriminating power of workload changes was examined under defined treadmill exercise. Furthermore in 5 patients of each group the rate behavior of S and A under daily life conditions and during common environmental noise was registered using Holter-ECG. In the bench tests S and A displayed a frequency-selective mode of operation between 2 Hz and 70 Hz with the highest sensitivity (resonance frequency) at 10 Hz. In patients, S showed a significantly higher discriminating power to changes of workload under treadmill exercise. According to y = 0.27x + 85.8 (r = 0.92) the relationship between the pacing rate of S and the power was linear whereas with y = 0.04x + 89.8 (r = 0.2) the pacing rate of A was almost independent of the given power. The susceptibility to external noise occurring during riding a car, streetcar or train with rate increases between 7 ppm and 12 ppm did not significantly differ in both systems.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3388936

Stangl, K; Wirtzfeld, A; Lochschmidt, O; Basler, B; Mittnacht, A

1988-04-01

337

Intrinsic and extrinsic cues regulate the daily profile of mouse lateral habenula neuronal activity.  

PubMed

The epithalamic lateral habenula (LHb) is implicated as part of the mammalian brain's circadian system. Anatomical evidence suggests that the LHb receives extrinsic circadian timing cues from retinal ganglion cells and the master clock in the suprachiasmatic nuclei (SCN). Intriguingly, some LHb neurones contain the molecular circadian clock, but it is unclear if and how intrinsic and extrinsic circadian processes influence neuronal activity in the mouse LHb. Here, using an in vitro brain slice preparation isolating the LHb from the SCN, we show through whole-cell patch-clamp recordings that LHb neurones exhibit heterogeneity in their resting state, but the majority spontaneously fire action potentials (APs). Discharge rate of APs varied from low firing in the early day to higher firing later in the day and was absent in LHb brain slices prepared from Cry1(-/-)Cry2(-/-) mice that lack a functional molecular clock. Low amplitude circadian oscillations in the molecular circadian clock were also monitored in LHb brain slices, but were absent in Cry1(-/-)Cry2(-/-) LHb brain tissue. A putative neurochemical output signal of the SCN, prokineticin 2 (PK2), inhibited some LHb neurones by elevating the frequency of GABA release in the LHb. Using multi-electrode recordings in vivo, we found that LHb neurones sluggishly respond to retinal illumination, suggesting that they receive such information through polysynaptic processes. In summary, our results show for the first time that intrinsic circadian signals are important for regulating LHb neuronal state, while the SCN-derived signal PK2 is less influential. Moreover, we demonstrate that mouse LHb neurones have access to and can respond to visual input, but such signals are unlikely to be directly communicated to the LHb. Broadly, these findings raise the possibility that intrinsic circadian signals are likely to be influential in shaping LHb contributions to cognition and emotionality. PMID:25194046

Sakhi, Kanwal; Wegner, Sven; Belle, Mino D C; Howarth, Michael; Delagrange, Philippe; Brown, Timothy M; Piggins, Hugh D

2014-11-15

338

Pacemaker patient-triggered event recording: accuracy, utility, and cost for the pacemaker follow-up clinic.  

PubMed

Many pacemaker patients have vague symptoms following implantation. It is often difficult for the physician to ascertain if they are cardiac in origin. A new pacemaker feature has been introduced, Patient-Triggered Event Records (PTER), to help the physician with this diagnosis. The PTER is a continuously running event record which stores the cardiac rhythm and rate. Brief application of a magnet will transfer the record into the device's memory. The data recorded will be the 97 events prior to the magnet application and the 30 events following magnet removal. The exact state of pacing (atrial and ventricular sensing/pacing, or premature ventricular events) and the rate of the ventricular events will be graphically displayed by the programmer for all 127 events. Thus, the exact pacer and cardiac rhythm can be determined during the period of the symptomatic episode. A total of three PTER's can be stored within the device. If a fourth is recorded, it will replace the oldest record. Three pacemakers with the PTER feature were tested in vitro with five different simulated cardiac rhythms. A beat-by-beat comparison between the PTER and the 15 simulated test rhythms revealed a 100% accurate documentation by PTER. Sixteen pacemaker patients which have the PTER feature were monitored using a King of Hearts for a total of 43 symptomatic events. The PTER records produced clinically relevant information 98% of the time while the King of Hearts produced clinically relevant information 81% of the time. A comparison of costs of the two different methods of monitoring these patients, was $2,432 versus $4,480 for the PTER and loop event monitor respectively. The PTER is an accurate, lower cost method for monitoring and diagnosing symptomatic pacemaker patients. The PTER can be used as the first diagnostic tool in troubleshooting patients with paroxysmal symptoms in the pacemaker clinic population. PMID:8945047

Machado, C; Johnson, D; Thacker, J R; Duncan, J L

1996-11-01

339

Circadian clocks, rhythmic synaptic plasticity and the sleep-wake cycle in zebrafish  

PubMed Central

The circadian clock and homeostatic processes are fundamental mechanisms that regulate sleep. Surprisingly, despite decades of research, we still do not know why we sleep. Intriguing hypotheses suggest that sleep regulates synaptic plasticity and consequently has a beneficial role in learning and memory. However, direct evidence is still limited and the molecular regulatory mechanisms remain unclear. The zebrafish provides a powerful vertebrate model system that enables simple genetic manipulation, imaging of neuronal circuits and synapses in living animals, and the monitoring of behavioral performance during day and night. Thus, the zebrafish has become an attractive model to study circadian and homeostatic processes that regulate sleep. Zebrafish clock- and sleep-related genes have been cloned, neuronal circuits that exhibit circadian rhythms of activity and synaptic plasticity have been studied, and rhythmic behavioral outputs have been characterized. Integration of this data could lead to a better understanding of sleep regulation. Here, we review the progress of circadian clock and sleep studies in zebrafish with special emphasis on the genetic and neuroendocrine mechanisms that regulate rhythms of melatonin secretion, structural synaptic plasticity, locomotor activity and sleep. PMID:23378829

Elbaz, Idan; Foulkes, Nicholas S.; Gothilf, Yoav; Appelbaum, Lior

2012-01-01

340

Circadian rhythmometry of mammalian radiosensitivity  

NASA Technical Reports Server (NTRS)

In the case of human bone marrow, the largest number of mitoses is seen in the evening in diurnally active men, mitotic activity being at a minimum in the morning. The opposite pattern is observed for nocturnal animals such as rats and mice on a regimen of light during the daytime alternating with darkness during the night hours. The entirety of these rhythms plays an important role in the organism's responses to environmental stimuli, including its resistance to potentially harmful agents. Conditions under which circadian rhythms can be observed and validated by inferential statistical means are discussed while emphasizing how artifacts of the laboratory environment can be shown to obscure circadian periodic variations in radiosensitivity.

Haus, E.; Halberg, F.; Loken, M. K.; Kim, Y. S.

1974-01-01

341

Circadian Clocks in the Ovary  

PubMed Central

Clock gene expression has been observed in tissues of the hypothalamic-pituitary-gonadal (HPG) axis. While the contribution of hypothalamic oscillators to the timing of reproductive biology is well known, the role of peripheral oscillators like those in the ovary is less clear. Circadian clocks in the ovary may play a role in the timing of ovulation. Disruption of the clock in ovarian cells or desynchrony between ovarian clocks and circadian oscillators elsewhere in the body may contribute to the onset and progression of various reproductive pathologies. Here we review evidence for clock function in the ovary across multiple species and offer a novel perspective on the role of this clock in normal ovarian physiology and in diseases that negatively impact fertility. PMID:20599392

Sellix, Michael T.; Menaker, Michael

2010-01-01

342

Circadian clocks are designed optimally  

E-print Network

Circadian rhythms are acquired through evolution to increase the chances for survival by synchronizing to the daylight cycle. Reliable synchronization is realized through two trade-off properties: regularity to keep time precisely, and entrainability to synchronize the internal time with daylight. Since both properties have been tuned through natural selection, their adaptation can be formalized in the framework of mathematical optimization. By using a succinct model, we found that simultaneous optimization of regularity and entrainability entails inherent features of the circadian mechanism irrespective of model details. At the behavioral level we discovered the existence of a dead zone, a time during which light pulses neither advance nor delay the clock. At the molecular level we demonstrate the role-sharing of two light inputs, phase advance and delay, as is well observed in mammals. We also reproduce the results of phase-controlling experiments and predict molecular elements responsible for the clockwork...

Hasegawa, Yoshihiko

2014-01-01

343

Circadian Rhythm Control: Neurophysiological Investigations  

NASA Technical Reports Server (NTRS)

The suprachiasmatic nucleus (SCN) was implicated as a primary component in central nervous system mechanisms governing circadian rhythms. Disruption of the normal synchronization of temperature, activity, and other rhythms is detrimental to health. Sleep wake disorders, decreases in vigilance and performance, and certain affective disorders may result from or be exacerbated by such desynchronization. To study the basic neurophysiological mechanisms involved in entrainment of circadian systems by the environment, Parylene-coated, etched microwire electrode bundles were used to record extracellular action potentials from the small somata of the SCN and neighboring hypothalamic nuclei in unanesthetized, behaving animals. Male Wistar rats were anesthetized and chronically prepared with EEG ane EMG electrodes in addition to a moveable microdrive assembly. The majority of cells had firing rates 10 Hz and distinct populations of cells which had either the highest firing rate or lowest firing rate during sleep were seen.

Glotzbach, S. F.

1985-01-01

344

Circadian rhythms: glucocorticoids and arthritis.  

PubMed

Circadian rhythms are driven by biological clocks and are endogenous in origin. Therefore, circadian changes in the metabolism or secretion of endogenous glucocorticoids are certainly responsible in part for the time-dependent changes observed in the inflammatory response and arthritis. More recently, melatonin (MLT), another circadian hormone that is the secretory product of the pineal gland, has been found implicated in the time-dependent inflammatory reaction with effects opposite those of cortisol. Interestingly, cortisol and MLT show an opposite response to the light. The light conditions in the early morning have a strong impact on the morning cortisol peak, whereas MLT is synthesized in a strictly nocturnal pattern. Recently, a diurnal rhythmicity in healthy humans between cellular (Th1 type) or humoral (Th2 type) immune responses has been found and related to immunomodulatory actions of cortisol and MLT. The interferon (IFN)-gamma/interleukin (IL)-10 ratio peaked during the early morning and correlated negatively with plasma cortisol and positively with plasma MLT. Accordingly, the intensity of the arthritic pain varies consistently as a function of the hour of the day: pain is greater after waking up in the morning than in the afternoon or evening. The reduced cortisol and adrenal androgen secretion, observed during testing in rheumatoid arthritis (RA) patients not treated with glucocoticoids, should be clearly considered as a "relative adrenal insufficiency" in the presence of a sustained inflammatory process, and allows Th1 type cytokines to be produced in higher amounts during the late night. In conclusion, the right timing (early morning) for the glucocorticoid therapy in arthritis is fundamental and well justified by the circadian rhythms of the inflammatory mechanisms. PMID:16855156

Cutolo, Maurizio; Sulli, Alberto; Pizzorni, Carmen; Secchi, Maria Elena; Soldano, Stefano; Seriolo, Bruno; Straub, Rainer H; Otsa, Kati; Maestroni, Georges J

2006-06-01

345

Apparent pacemaker failure due to reversion circuitry within the programming device.  

PubMed

While being evaluated for a recurrent tachyarrhythmia, a patient with a permanent pacemaker underwent reprogramming of the unit from the DVI to the VVI mode for assessment of the underlying rhythm. Subsequent reprogramming of the pacemaker to the DVI or DDD mode was impossible despite multiple attempts and the use of multiple programmers. The problem was considered to be a malfunction of the pacemaker circuitry, and plans were made for the pacemaker to be explanted and a replacement unit implanted. Before the procedure, the pacemaker company was notified of the explantation. We subsequently learned that a special programming sequence had to be carried out because of reversion circuitry present in the pacemaker but not described in the available literature. This report emphasizes the need for familiarity with each of the individual pacemakers being implanted and the need for the manufacturer to be as specific as possible given the complexity of current units. PMID:6200849

Hayes, D L; Holmes, D R; Merideth, J; Osborn, M J; Bardsley, W T

1984-03-01

346

Arteriovenous fistula following pacemaker lead removal: CT diagnosis  

Microsoft Academic Search

  \\u000a Arteriovenous fistula formation is a very rare complication of pacemaker lead extraction. Rapid diagnosis is essential due\\u000a to the life-threatening nature of this complication. CT angiography provides a noninvasive and quick method for assessment.

Preet Kang; Diego B. Nunez Jr

2003-01-01

347

Supplementary Materials to Pace-Makers Lost: Shifting Spatial  

E-print Network

Supplementary Materials to Pace-Makers Lost: Shifting Spatial Epidemiology of Reemerging Pertussis of time chara- caterizing the US pertussis notification case time series, we performed our analyses on two of pertussis incidence of each state (one state per line), where the states are ordered by longitude. To ease

Choisy, Marc

348

Hydrogen-induced microelectronic capacitor failure in pacemakers.  

PubMed

Ceramic chip capacitors used in hybrid microelectronics for cardiac pacemakers are usually highly reliable. However, under certain conditions of capacitor construction, capacitor materials, mounting techniques, and environmental conditions, high failure rates may occur. A specific example is presented in which a ceramic capacitor used in an implanted pacemaker delaminated and failed approximately 30 days after being implanted. The failed capacitor caused a pulse rate rise, but due to circuit design techniques, the rate increase was limited to an acceptable value. The capacitor that failed was from an isolated lot of capacitors that was manufactured using pure palladium plates. The circuit containing this capacitor was hermetically sealed within a titanium case by welding. During the welding, a small amount of hydrogen was released from the titanium which, over a period of 2 to 4 weeks, was absorbed by the palladium plates in the capacitor. By absorbing the hydrogen, the palladium plates exhibit a volumetric expansion of sufficient magnitude to crack and delaminate the capacitor to the point of failure. Subsequently, the recurrence of this failure mode has been avoided by using capacitors containing special palladium alloys that cannot absorb hydrogen. This phenomenon is of interest to pacemaker designers since mercury batteries used in conventional pacemakers generate large amounts of hydrogen and potentially may be responsible for complications when used in conjunction with capacitors containing palladium. PMID:958043

Rainer, W G; Kolenik, S A; Whittaker, R E; Sadler, T R; Lapin, E S

1976-01-01

349

Electromagnetic interference with implantable cardiac pacemakers by video capsule  

Microsoft Academic Search

Methods: A total of 100 consecutive patients (70 men, 30 women) with an implanted pacemaker (95 on bipolar mode) were studied. The testing was performed with a functional testing device (Test Cap) for the Given Diagnostic System that reproduces the effect of the video capsule by transmitting at exactly the same frequency. During continuous electrocardiographic monitoring and recording, 100 tests

Sergio Dubner; Yael Dubner; Sebastian Gallino; Liliana Spallone; David Zagalsky; Horacio Rubio; Joseph Zimmerman; Eran Goldin

350

Contribution of Visual and Circadian Neural Circuits to Memory for Prolonged Mating Induced by Rivals  

PubMed Central

Rival exposure causes Drosophila melanogaster males to prolong mating. Longer-Mating-Duration (LMD) may enhance reproductive success, but its underlying mechanism is currently unknown. Here we report that LMD is context-dependent and can be induced solely via visual stimuli. We further show that LMD involves neural circuits important for visual memory, including central neurons in the ellipsoid body but not the mushroom bodies or the fan-shaped bodies, and may rely on the rival exposure memory lasting several hours. LMD is affected by a subset of learning and memory mutants. LMD depends on the circadian clock genes timeless and period but not Clock or cycle, and persists in many arrhythmic conditions. Moreover, LMD critically depends on a subset of pigment dispersing factor (PDF) neurons rather than the entire circadian neural circuit. Our study thus delineates parts of the molecular and cellular basis for LMD – a plastic social behavior elicited by visual cues. PMID:22561453

Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

2012-01-01

351

Circadian variation in sports performance.  

PubMed

Chronobiology is the science concerned with investigations of time-dependent changes in physiological variables. Circadian rhythms refer to variations that recur every 24 hours. Many physiological circadian rhythms at rest are endogenously controlled, and persist when an individual is isolated from environmental fluctuations. Unlike physiological variables, human performance cannot be monitored continuously in order to describe circadian rhythmicity. Experimental studies of the effect of circadian rhythms on performance need to be carefully designed in order to control for serial fatigue effects and to minimise disturbances in sleep. The detection of rhythmicity in performance variables is also highly influenced by the degree of test-retest repeatability of the measuring equipment. The majority of components of sports performance, e.g. flexibility, muscle strength, short term high power output, vary with time of day in a sinusoidal manner and peak in the early evening close to the daily maximum in body temperature. Psychological tests of short term memory, heart rate-based tests of physical fitness, and prolonged submaximal exercise performance carried out in hot conditions show peak times in the morning. Heart rate-based tests of work capacity appear to peak in the morning because the heart rate responses to exercise are minimal at this time of day. Post-lunch declines are evident with performance variables such as muscle strength, especially if measured frequently enough and sequentially within a 24-hour period to cause fatigue in individuals. More research work is needed to ascertain whether performance in tasks demanding fine motor control varies with time of day. Metabolic and respiratory rhythms are flattened when exercise becomes strenuous whilst the body temperature rhythm persists during maximal exercise. Higher work-rates are selected spontaneously in the early evening. At present, it is not known whether time of day influences the responses of a set training regimen (one in which the training stimulus does not vary with time of day) for endurance, strength, or the learning of motor skills. The normal circadian rhythms can be desynchronised following a flight across several time zones or a transfer to nocturnal work shifts. Although athletes show all the symptoms of 'jet lag' (increased fatigue, disturbed sleep and circadian rhythms), more research work is needed to identify the effects of transmeridian travel on the actual performances of elite sports competitors. Such investigations would need to be chronobiological, i.e. monitor performance at several times on several post-flight days, and take into account direction of travel, time of day of competition and the various performance components involved in a particular sport. Shiftwork interferes with participation in competitive sport, although there may be greater opportunities for shiftworkers to train in the hours of daylight for individual sports such as cycling and swimming. Studies should be conducted to ascertain whether shiftwork-mediated rhythm disturbances affect sports performance. Individual differences in performance rhythms are small but significant. Circadian rhythms are larger in amplitude in physically fit individuals than sedentary individuals. Athletes over 50 years of age tend to be higher in 'morningness', habitually scheduling relatively more training in the morning and selecting relatively higher work-rates during exercise compared with young athletes. These differences should be recognised by practitioners concerned with organising the habitual regimens of athletes. PMID:8726347

Atkinson, G; Reilly, T

1996-04-01

352

Harmonics of Circadian Gene Transcription in Mammals  

Microsoft Academic Search

The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of

Michael E. Hughes; Luciano DiTacchio; Kevin R. Hayes; Christopher Vollmers; S. Pulivarthy; Julie E. Baggs; Satchidananda Panda; John B. Hogenesch

2009-01-01

353

Bright light affects human circadian rhythms  

Microsoft Academic Search

The relative effectiveness of external zeitgebers synchronizing circadian rhythms can be evaluated by mesuring the size of the range of entrainment. The experimental approach to measure entrainment limits is the application of an artificial zeitgeber with slowly and steadily changing period. In human circadian rhythms, an absolute light-dark (LD) cycle with a light intensity during L of 100 lux or

Rtitger A. Wever; Jan Polášek; Christina M. Wildgruber

1983-01-01

354

[Relation between dementia and circadian rhythm disturbance].  

PubMed

Dementia and circadian rhythm disturbance are closely linked. First, dementia patient shows circadian rhythm disorders (e.g. insomnia, night wandering, daytime sleep). These symptoms are a burden for caregivers. Circadian rhythm disturbance of dementia relates ADL and cognitive impairment, and diurnal rhythm disorder of blood pressure and body temperature. Some study shows that circadian rhythm disorders in dementia are a disturbance of neural network between suprachiasmatic nucleus and cerebral white matter, and involvement of both frontal lobes, left parietal and occipital cortex, left temporoparietal region. The first-line treatment of circadian rhythm disturbance should be non-drug therapy (e.g. exercise, bright light exposure, reduce caffeine intake, etc.). If physician prescribe drugs, keep the rule of low-dose and short-term and avoid benzodiazepines. Atypical antipsychotic drugs like risperidone and some antidepressants are useful for treatment of insomnia in dementia. But this usage is off-label. So we must well inform to patient and caregiver, and get consent about treatment. Second, some study shows circadian rhythm disorder is a risk factor of dementia. However, we should discuss that circadian rhythm disturbance is "risk factor of dementia" or "prodromal symptom of dementia". If a clinician finds circadian rhythm disorder in elderly people, should be examined cognitive and ADL function, and careful about that patients have dementia or will develop dementia. PMID:24724422

Nakamura, Kei; Meguro, Kenichi

2014-03-01

355

Circadian systems: different levels of complexity.  

PubMed Central

After approximately 50 years of circadian research, especially in selected circadian model systems (Drosophila, Neurospora, Gonyaulax and, more recently, cyanobacteria and mammals), we appreciate the enormous complexity of the circadian programme in organisms and cells, as well as in physiological and molecular circuits. Many of our insights into this complexity stem from experimental reductionism that goes as far as testing the interaction of molecular clock components in heterologous systems or in vitro. The results of this enormous endeavour show circadian systems that involve several oscillators, multiple input pathways and feedback loops that contribute to specific circadian qualities but not necessarily to the generation of circadian rhythmicity. For a full appreciation of the circadian programme, the results from different levels of the system eventually have to be put into the context of the organism as a whole and its specific temporal environment. This review summarizes some of the complexities found at the level of organisms, cells and molecules, and highlights similar strategies that apparently solve similar problems at the different levels of the circadian system. PMID:11710975

Roenneberg, T; Merrow, M

2001-01-01

356

Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis  

PubMed Central

To investigate the role of the circadian clock in the development of alcohol-induced fatty liver disease we examined livers of mice chronically alcohol-fed over 4-weeks that resulted in steatosis. Here we show time-of-day specific changes in expression of clock genes and clock-controlled genes, including those associated with lipid and bile acid regulation. Such changes were not observed following a 1-week alcohol treatment with no hepatic lipid accumulation. Real-time bioluminescence reporting of PERIOD2 protein expression suggests that these changes occur independently of the suprachiasmatic nucleus pacemaker. Further, we find profound time-of-day specific changes to the rhythmic synthesis/accumulation of triglycerides, cholesterol and bile acid, and the NAD/NADH ratio, processes that are under clock control. These results highlight not only that the circadian timekeeping system is disturbed in the alcohol-induced hepatic steatosis state, but also that the effects of alcohol upon the clock itself may actually contribute to the development of hepatic steatosis. PMID:24430730

Zhou, Peng; Ross, Ruth A.; Pywell, Cameron M.; Liangpunsakul, Suthat; Duffield, Giles E.

2014-01-01

357

Alterations in endogenous circadian rhythm of core temperature in senescent Fischer 344 rats  

NASA Technical Reports Server (NTRS)

We assessed whether alterations in endogenous circadian rhythm of core temperature (CRT) in aging rats are associated with chronological time or with a biological marker of senescence, i.e., spontaneous rapid body weight loss. CRT was measured in male Fischer 344 (F344) rats beginning at age 689 days and then continuously until death. Young rats were also monitored. The rats were housed under constant dim red light at 24-26 degrees C, and core temperature was recorded every 10 min via biotelemetry. The CRT amplitude of the body weight-stable (presenescent) old rats was significantly less than that of young rats at all analysis periods. At the onset of spontaneous rapid weight loss (senescence), all measures of endogenous CRT differed significantly from those in the presenescent period. The suprachiasmatic nucleus (a circadian pacemaker) of the senescent rats maintained its light responsiveness as determined by an increase in c-fos expression after a brief light exposure. These data demonstrate that some characteristics of the CRT are altered slowly with chronological aging, whereas others occur rapidly with the onset of senescence.

McDonald, R. B.; Hoban-Higgins, T. M.; Ruhe, R. C.; Fuller, C. A.; Horwitz, B. A.

1999-01-01

358

Genetic Basis of Human Circadian Rhythm Disorders  

PubMed Central

Circadian rhythm disorders constitute a group of phenotypes that usually present as altered sleep-wake schedules. Until a human genetics approach was applied to investigate these traits, the genetic components regulating human circadian rhythm and sleep behaviors remained mysterious. Steady advances in the last decade have dramatically improved our understanding of the genes involved in circadian rhythmicity and sleep regulation. Finding these genes presents new opportunities to use a wide range of approaches, including in vitro molecular studies and in vivo animal modeling, to elevate our understanding of how sleep and circadian rhythms are regulated and maintained. Ultimately, this knowledge will reveal how circadian and sleep disruption contribute to various ailments and shed light on how best to maintain and recover good health. PMID:22849821

Jones, Christopher R.; Huang, Angela L.; Ptacek, Louis J.; Fu, Ying-Hui

2012-01-01

359

Metabolic consequences of sleep and circadian disorders.  

PubMed

Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome, and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance, and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

Depner, Christopher M; Stothard, Ellen R; Wright, Kenneth P

2014-07-01

360

The Circadian Clock Coordinates Ribosome Biogenesis  

PubMed Central

Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis. PMID:23300384

Symul, Laura; Martin, Eva; Atger, Florian; Naef, Felix; Gachon, Frederic

2013-01-01

361

Robustness of circadian rhythms with respect to molecular noise  

E-print Network

Robustness of circadian rhythms with respect to molecular noise Didier Gonze, Jose´ Halloy molecular model capable of generating circadian rhythms to assess the robustness of circadian oscillations stochastic simulations model Drosophila Neurospora Circadian rhythms characterized by a period close to 24 h

Goldbeter, Albert

362

Mice deficient of glutamatergic signaling from intrinsically photosensitive retinal ganglion cells exhibit abnormal circadian photoentrainment.  

PubMed

Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light. PMID:25357191

Purrier, Nicole; Engeland, William C; Kofuji, Paulo

2014-01-01

363

Gonadal- and sex-chromosome-dependent sex differences in the circadian system.  

PubMed

Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system. PMID:23439698

Kuljis, Dika A; Loh, Dawn H; Truong, Danny; Vosko, Andrew M; Ong, Margaret L; McClusky, Rebecca; Arnold, Arthur P; Colwell, Christopher S

2013-04-01

364

Cocaine modulates pathways for photic and nonphotic entrainment of the mammalian SCN circadian clock.  

PubMed

Cocaine abuse is highly disruptive to circadian physiological and behavioral rhythms. The present study was undertaken to determine whether such effects are manifest through actions on critical photic and nonphotic regulatory pathways in the master circadian clock of the mouse suprachiasmatic nucleus (SCN). Impairment of SCN photic signaling by systemic (intraperitoneal) cocaine injection was evidenced by strong (60%) attenuation of light-induced phase-delay shifts of circadian locomotor activity during the early night. A nonphotic action of cocaine was apparent from its induction of 1-h circadian phase-advance shifts at midday. The serotonin receptor antagonist, metergoline, blocked shifting by 80%, implicating a serotonergic mechanism. Reverse microdialysis perfusion of the SCN with cocaine at midday induced 3.7 h phase-advance shifts. Control perfusions with lidocaine and artificial cerebrospinal fluid had little shifting effect. In complementary in vitro experiments, photic-like phase-delay shifts of the SCN circadian neuronal activity rhythm induced by glutamate application to the SCN were completely blocked by cocaine. Cocaine treatment of SCN slices alone at subjective midday, but not the subjective night, induced 3-h phase-advance shifts. Lidocaine had no shifting effect. Cocaine-induced phase shifts were completely blocked by metergoline, but not by the dopamine receptor antagonist, fluphenazine. Finally, pretreatment of SCN slices for 2 h with a low concentration of serotonin agonist (to block subsequent serotonergic phase resetting) abolished cocaine-induced phase shifts at subjective midday. These results reveal multiple effects of cocaine on adult circadian clock regulation that are registered within the SCN and involve enhanced serotonergic transmission. PMID:22218419

Glass, J David; Brager, Allison J; Stowie, Adam C; Prosser, Rebecca A

2012-03-15

365

Gonadal- and Sex-Chromosome-Dependent Sex Differences in the Circadian System  

PubMed Central

Compelling reasons to study the role of sex in the circadian system include the higher rates of sleep disorders in women than in men and evidence that sex steroids modulate circadian control of locomotor activity. To address the issue of sex differences in the circadian system, we examined daily and circadian rhythms in wheel-running activity, electrical activity within the suprachiasmatic nucleus, and PER2::LUC-driven bioluminescence of gonadally-intact adult male and female C57BL/6J mice. We observed greater precision of activity onset in 12-hour light, 12-hour dark cycle for male mice, longer activity duration in 24 hours of constant darkness for female mice, and phase-delayed PER2::LUC bioluminescence rhythm in female pituitary and liver. Next, in order to investigate whether sex differences in behavior are sex chromosome or gonadal sex dependent, we used the 4 core genotypes (FCG) mouse model, in which sex chromosome complement is independent of gonadal phenotype. Gonadal males had more androgen receptor expression in the suprachiasmatic nucleus and behaviorally reduced photic phase shift response compared with gonadal female FCG mice. Removal of circulating gonadal hormones in adults, to test activational vs organizational effects of sex revealed that XX animals have longer activity duration than XY animals regardless of gonadal phenotype. Additionally, we observed that the activational effects of gonadal hormones were more important for regulating activity levels in gonadal male mice than in gonadal female FCG mice. Taken together, sex differences in the circadian rhythms of activity, neuronal physiology, and gene expression were subtle but provide important clues for understanding the pathophysiology of the circadian system. PMID:23439698

Kuljis, Dika A.; Truong, Danny; Vosko, Andrew M.; Ong, Margaret L.; McClusky, Rebecca; Arnold, Arthur P.; Colwell, Christopher S.

2013-01-01

366

Mice Deficient of Glutamatergic Signaling from Intrinsically Photosensitive Retinal Ganglion Cells Exhibit Abnormal Circadian Photoentrainment  

PubMed Central

Several aspects of behavior and physiology, such as sleep and wakefulness, blood pressure, body temperature, and hormone secretion exhibit daily oscillations known as circadian rhythms. These circadian rhythms are orchestrated by an intrinsic biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus which is adjusted to the daily environmental cycles of day and night by the process of photoentrainment. In mammals, the neuronal signal for photoentrainment arises from a small subset of intrinsically photosensitive retinal ganglion cells (ipRGCs) that send a direct projection to the SCN. ipRGCs also mediate other non-image-forming (NIF) visual responses such as negative masking of locomotor activity by light, and the pupillary light reflex (PLR) via co-release of neurotransmitters glutamate and pituitary adenylate cyclase-activating peptide (PACAP) from their synaptic terminals. The relative contribution of each neurotransmitter system for the circadian photoentrainment and other NIF visual responses is still unresolved. We investigated the role of glutamatergic neurotransmission for circadian photoentrainment and NIF behaviors by selective ablation of ipRGC glutamatergic synaptic transmission in mice. Mutant mice displayed delayed re-entrainment to a 6 h phase shift (advance or delay) in the light cycle and incomplete photoentrainment in a symmetrical skeleton photoperiod regimen (1 h light pulses between 11 h dark periods). Circadian rhythmicity in constant darkness also was reduced in some mutant mice. Other NIF responses such as the PLR and negative masking responses to light were also partially attenuated. Overall, these results suggest that glutamate from ipRGCs drives circadian photoentrainment and negative masking responses to light. PMID:25357191

Purrier, Nicole; Engeland, William C.; Kofuji, Paulo

2014-01-01

367

Regulation of gustatory physiology and appetitive behavior by the circadian clock in Drosophila melanogaster  

PubMed Central

Summary Background Circadian regulation of chemosensory processes is common in animals, but little is known about how circadian clocks control chemosensory systems or the consequences of rhythms in chemosensory system function. Taste is a major chemosensory gate used to decide whether or not an animal will eat, and the main taste organ in Drosophila, the proboscis, harbors autonomous circadian oscillators. Here we examine gustatory physiology, tastant-evoked appetitive behavior, and food ingestion to understand clock-dependent regulation of the Drosophila gustatory system. Results Here we report that single-unit responses from labellar gustatory receptor neurons (GRNs) to attractive and aversive tastants show diurnal and circadian rhythms in spike amplitude, frequency and duration across different classes of gustatory sensilla. Rhythms in electrophysiological responses parallel behavioral rhythms in proboscis extension reflex (PrER). Molecular oscillators in GRNs are necessary and sufficient for rhythms in gustatory responses, and drive rhythms in G protein coupled receptor kinase 2 (GPRK2) expression that mediate rhythms in taste-sensitivity. Eliminating clock function in certain GRNs increases feeding and locomotor activity, mimicking a starvation response. Conclusions Circadian clocks in GRNs control neuronal output and drive behavioral rhythms in taste responses that peak at a time of day when feeding is maximal in flies. Our results argue that oscillations in GPRK2 levels drive rhythms in gustatory physiology and behavior, and that GRN clocks repress feeding. The similarity in gustatory system organization and feeding behavior in flies and mammals, and diurnal changes in taste sensitivity in humans, suggest that our results are relevant to the situation in humans. PMID:20153192

Chatterjee, Abhishek; Tanoue, Shintaro; Houl, Jerry H.; Hardin, Paul E.

2014-01-01

368

Loss of dopamine disrupts circadian rhythms in a mouse model of Parkinson's disease.  

PubMed

Although a wide range of physiological functions regulated by dopamine (DA) display circadian variations, the role of DA in the generation and/or modulation of these rhythms is unknown. In Parkinson's disease (PD) patients, in addition to the classical motor symptoms, disturbances of the pattern of daily rest/wake cycles are common non-motor symptoms. We investigated daily and circadian rhythms of rest/activity behaviors in a transgenic MitoPark mouse model with selective inactivation of mitochondrial transcription factor A (Tfam) resulting in a slow and progressive degeneration of DA neurons in midbrain structures. Correlated with this, MitoPark mice show a gradual reduction in locomotor activity beginning at about 20weeks of age. In a light-dark cycle, MitoPark mice exhibit a daily pattern of rest/activity rhythms that shows an age-dependent decline in both the amplitude and the stability of the rhythm, coupled with an increased fragmentation of day/night activities. When the circadian system is challenged by exposure to constant darkness or constant light conditions, control littermates retain a robust free-running circadian locomotor rhythm, whereas in MitoPark mice, locomotor rhythms are severely disturbed or completely abolished. Re-exposure to a light/dark cycle completely restores daily locomotor rhythms. MitoPark mice and control littermates express similar masking behaviors under a 1h light/1h dark regime, suggesting that the maintenance of a daily pattern of rest/activity in arrhythmic MitoPark mice can be attributed to the acute inhibitory and stimulatory effects of light and darkness. These results imply that, in addition to the classical motor abnormalities observed in PD, the loss of the midbrain DA neurons leads to impairments of the circadian control of rest/activity rhythms. PMID:25171792

Fifel, Karim; Cooper, Howard M

2014-11-01

369

JOURNAL OF BIOLOGICAL RHYTHMS / June 1999Olde Scheper et al. / MOLECULAR CIRCADIAN CLOCKS A Model of Molecular Circadian Clocks  

E-print Network

JOURNAL OF BIOLOGICAL RHYTHMS / June 1999Olde Scheper et al. / MOLECULAR CIRCADIAN CLOCKS A Model, the Netherlands Abstract A fundamental question in the field of circadian rhythms concerns the biochemical of the intricate molecu- lar interactions governing circadian rhythmogenesis. Key words circadian rhythm

van Pelt, Jaap

370

The role of the funny current in pacemaker activity.  

PubMed

Abstract: Pacemaking is a basic physiological process, and the cellular mechanisms involved in this function have always attracted the keen attention of investigators. The "funny" (I(f)) current, originally described in sinoatrial node myocytes as an inward current activated on hyperpolarization to the diastolic range of voltages, has properties suitable for generating repetitive activity and for modulating spontaneous rate. The degree of activation of the funny current determines, at the end of an action potential, the steepness of phase 4 depolarization; hence, the frequency of action potential firing. Because I(f) is controlled by intracellular cAMP and is thus activated and inhibited by beta-adrenergic and muscarinic M2 receptor stimulation, respectively, it represents a basic physiological mechanism mediating autonomic regulation of heart rate. Given the complexity of the cellular processes involved in rhythmic activity, an exact quantification of the extent to which I(f) and other mechanisms contribute to pacemaking is still a debated issue; nonetheless, a wealth of information collected since the current was first described more than 30 years ago clearly agrees to identify I(f) as a major player in both generation of spontaneous activity and rate control. I(f)- dependent pacemaking has recently advanced from a basic, physiologically relevant concept, as originally described, to a practical concept that has several potentially useful clinical applications and can be valuable in therapeutically relevant conditions. Typically, given their exclusive role in pacemaking, f-channels are ideal targets of drugs aiming to pharmacological control of cardiac rate. Molecules able to bind specifically to and block f-channels can thus be used as pharmacological tools for heart rate reduction with little or no adverse cardiovascular side effects. Indeed a selective f-channel inhibitor, ivabradine, is today commercially available as a tool in the treatment of stable chronic angina. Also, several loss-of-function mutations of HCN4 (hyperpolarization-activated, cyclic-nucleotide gated 4), the major constitutive subunit of f-channels in pacemaker cells, are known today to cause rhythm disturbances, such as for example inherited sinus bradycardia. Finally, gene- or cell-based methods for in situ delivery of f-channels to silent or defective cardiac muscle represent novel approaches for the development of biological pacemakers eventually able to replace electronic devices. PMID:20167941

DiFrancesco, Dario

2010-02-19

371

Circadian clock gene Per2 is not necessary for the photoperiodic response in mice.  

PubMed

In mammals, light information received by the eyes is transmitted to the pineal gland via the circadian pacemaker, i.e., the suprachiasmatic nucleus (SCN). Melatonin secreted by the pineal gland at night decodes night length and regulates seasonal physiology and behavior. Melatonin regulates the expression of the ?-subunit of thyroid-stimulating hormone (TSH; Tshb) in the pars tuberalis (PT) of the pituitary gland. Long day-induced PT TSH acts on ependymal cells in the mediobasal hypothalamus to induce the expression of type 2 deiodinase (Dio2) and reduce type 3 deiodinase (Dio3) that are thyroid hormone-activating and hormone-inactivating enzymes, respectively. The long day-activated thyroid hormone T3 regulates seasonal gonadotropin-releasing hormone secretion. It is well established that the circadian clock is involved in the regulation of photoperiodism. However, the involvement of the circadian clock gene in photoperiodism regulation remains unclear. Although mice are generally considered non-seasonal animals, it was recently demonstrated that mice are a good model for the study of photoperiodism. In the present study, therefore, we examined the effect of changing day length in Per2 deletion mutant mice that show shorter wheel-running rhythms under constant darkness followed by arhythmicity. Although the amplitude of clock gene (Per1, Cry1) expression was greatly attenuated in the SCN, the expression profile of arylalkylamine N-acetyltransferase, a rate-limiting melatonin synthesis enzyme, was unaffected in the pineal gland, and robust photoperiodic responses of the Tshb, Dio2, and Dio3 genes were observed. These results suggested that the Per2 clock gene is not necessary for the photoperiodic response in mice. PMID:23505514

Ikegami, Keisuke; Iigo, Masayuki; Yoshimura, Takashi

2013-01-01

372

Circadian rhythms, sleep deprivation, and human performance.  

PubMed

Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep-wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F

2013-01-01

373

Circadian Rhythms, Sleep Deprivation, and Human Performance  

PubMed Central

Much of the current science on, and mathematical modeling of, dynamic changes in human performance within and between days is dominated by the two-process model of sleep–wake regulation, which posits a neurobiological drive for sleep that varies homeostatically (increasing as a saturating exponential during wakefulness and decreasing in a like manner during sleep), and a circadian process that neurobiologically modulates both the homeostatic drive for sleep and waking alertness and performance. Endogenous circadian rhythms in neurobehavioral functions, including physiological alertness and cognitive performance, have been demonstrated using special laboratory protocols that reveal the interaction of the biological clock with the sleep homeostatic drive. Individual differences in circadian rhythms and genetic and other components underlying such differences also influence waking neurobehavioral functions. Both acute total sleep deprivation and chronic sleep restriction increase homeostatic sleep drive and degrade waking neurobehavioral functions as reflected in sleepiness, attention, cognitive speed, and memory. Recent evidence indicating a high degree of stability in neurobehavioral responses to sleep loss suggests that these trait-like individual differences are phenotypic and likely involve genetic components, including circadian genes. Recent experiments have revealed both sleep homeostatic and circadian effects on brain metabolism and neural activation. Investigation of the neural and genetic mechanisms underlying the dynamically complex interaction between sleep homeostasis and circadian systems is beginning. A key goal of this work is to identify biomarkers that accurately predict human performance in situations in which the circadian and sleep homeostatic systems are perturbed. PMID:23899598

Goel, Namni; Basner, Mathias; Rao, Hengyi; Dinges, David F.

2014-01-01

374

In vitro circadian period is associated with circadian/sleep preference  

PubMed Central

Evaluation of circadian phenotypes is crucial for understanding the pathophysiology of diseases associated with disturbed biological rhythms such as circadian rhythm sleep disorders (CRSDs). We measured clock gene expression in fibroblasts from individual subjects and observed circadian rhythms in the cells (in vitro rhythms). Period length of the in vitro rhythm (in vitro period) was compared with the intrinsic circadian period, ?, measured under a forced desynchrony protocol (in vivo period) and circadian/sleep parameters evaluated by questionnaires, sleep log, and actigraphy. Although no significant correlation was observed between the in vitro and in vivo periods, the in vitro period was correlated with chronotype, habitual sleep time, and preferred sleep time. Our data demonstrate that the in vitro period is significantly correlated with circadian/sleep preference. The findings suggest that fibroblasts from individual patients can be utilized for in vitro screening of therapeutic agents to provide personalized therapeutic regimens for CRSD patients. PMID:23797865

Hida, Akiko; Kitamura, Shingo; Ohsawa, Yosuke; Enomoto, Minori; Katayose, Yasuko; Motomura, Yuki; Moriguchi, Yoshiya; Nozaki, Kentaro; Watanabe, Makiko; Aritake, Sayaka; Higuchi, Shigekazu; Kato, Mie; Kamei, Yuichi; Yamazaki, Shin; Goto, Yu-ichi; Ikeda, Masaaki; Mishima, Kazuo

2013-01-01

375

Immunoreactivities to three circadian clock proteins in two ground crickets suggest interspecific diversity of the circadian clock structure.  

PubMed

The closely related crickets Dianemobius nigrofasciatus and Allonemobius allardi exhibit similar circadian rhythms and photoperiodic responses, suggesting that they possess similar circadian and seasonal clocks. To verify this assumption, antisera to Period (PER), Doubletime (DBT), and Cryptochrome (CRY) were used to visualize circadian clock neurons in the cephalic ganglia. Immunoreactivities referred to as PER-ir, DBT-ir, and CRY-ir were distributed mainly in the optic lobes (OL), pars intercerebralis (PI), dorsolateral protocerebrum, and the subesophageal ganglion (SOG). A system of immunoreactive cells in the OL dominates in D. nigrofasciatus, while immunoreactivities in the PI and SOG prevail in A. allardi. Each OL of D. nigrofasciatus contains 3 groups of cells that coexpress PER-ir and DBT-ir and send processes over the frontal medulla face to the inner lamina surface, suggesting functional linkage to the compound eye. Only 2 pairs of PER-ir cells (no DBT-ir) were found in the OL of A. allardi. Several groups of PER-ir cells occur in the brain of both species. The PI also contains DBT-ir and CRY-ir cells, but in A. allardi, most of the DBT-ir is confined to the SOG. Most immunoreactive cells in the PI and in the dorsolateral brain send their fibers to the contralateral corpora cardiaca and corpora allata. The proximity and, in some cases, proven identity of the PER-ir, DBT-ir, and CRY-ir perikarya are consistent with presumed interactions between the examined clock components. The antigens were always found in the cytoplasm, and no diurnal oscillations in their amounts were detected. The photoperiod, which controls embryonic diapause, the rate of larval development, and the wing length of crickets, had no discernible effect on either distribution or the intensity of the immunostaining. PMID:16603676

Shao, Qi-Miao; Sehadová, Hana; Ichihara, Naoyuki; Sehnal, Frantisek; Takeda, Makio

2006-04-01

376

Design and Testing of a Percutaneously Implantable Fetal Pacemaker  

PubMed Central

We are developing a cardiac pacemaker with a small, cylindrical shape that permits percutaneous implantation into a fetus to treat complete heart block and consequent hydrops fetalis, which can otherwise be fatal. The device uses off-the-shelf components including a rechargeable lithium cell and a highly efficient relaxation oscillator encapsulated in epoxy and glass. A corkscrew electrode made from activated iridium can be screwed into the myocardium, followed by release of the pacemaker and a short, flexible lead entirely within the chest of the fetus to avoid dislodgement from fetal movement. Acute tests in adult rabbits demonstrated the range of electrical parameters required for successful pacing and the feasibility of successfully implanting the device percutaneously under ultrasonic imaging guidance. The lithium cell can be recharged inductively as needed, as indicated by a small decline in the pulsing rate. PMID:22855119

Loeb, Gerald E.; Zhou, Li; Zheng, Kaihui; Nicholson, Adriana; Peck, Raymond A.; Krishnan, Anjana; Silka, Michael; Pruetz, Jay; Chmait, Ramen; Bar-Cohen, Yaniv

2012-01-01

377

The circadian timing system in clinical oncology.  

PubMed

The circadian timing system (CTS) controls several critical molecular pathways for cancer processes and treatment effects over the 24 hours, including drug metabolism, cell cycle, apoptosis, and DNA damage repair mechanisms. This results in the circadian time dependency of whole-body and cellular pharmacokinetics and pharmacodynamics of anticancer agents. However, CTS robustness and phase varies among cancer patients, based on circadian monitoring of rest- activity, body temperature, sleep, and/or hormonal secretion rhythms. Circadian disruption has been further found in up to 50% of patients with metastatic cancer. Such disruption was associated with poor outcomes, including fatigue, anorexia, sleep disorders, and short progression-free and overall survival. Novel, minimally invasive devices have enabled continuous CTS assessment in non-hospitalized cancer patients. They revealed up to 12-hour differences in individual circadian phase. Taken together, the data support the personalization of chronotherapy. This treatment method aims at the adjustment of cancer treatment delivery according to circadian rhythms, using programmable-in-time pumps or novel release formulations, in order to increase both efficacy and tolerability. A fixed oxaliplatin, 5-fluorouracil and leucovorin chronotherapy protocol prolonged median overall survival in men with metastatic colorectal cancer by 3.3 months as compared to conventional delivery, according to a meta-analysis (P=0.009). Further analyses revealed the need for the prevention of circadian disruption or the restoration of robust circadian function in patients on chronotherapy, in order to further optimize treatment effects. The strengthening of external synchronizers could meet such a goal, through programmed exercise, meal timing, light exposure, improved social support, sleep scheduling, and the properly timed administration of drugs that target circadian clocks. Chrono-rehabilitation warrants clinical testing for improving quality of life and survival in cancer patients. PMID:24915535

Innominato, Pasquale F; Roche, Véronique P; Palesh, Oxana G; Ulusakarya, Ayhan; Spiegel, David; Lévi, Francis A

2014-06-01

378

Pacemakers in a Reaction-Diffusion Mechanics System  

Microsoft Academic Search

Non-linear waves of excitation are found in various biological, physical and chemical systems and are often accompanied by\\u000a deformations of the medium. In this paper, we numerically study wave propagation in a deforming excitable medium using a two-variable\\u000a reaction-diffusion system coupled with equations of continuum mechanics. We study the appearance and dynamics of different\\u000a excitation patterns organized by pacemakers that

R. H. Keldermann; M. P. Nash; A. V. Panfilov

2007-01-01

379

SCN5A and sinoatrial node pacemaker function  

Microsoft Academic Search

The SCN5A gene encodes specific voltage-dependent Na+ channels abundant in cardiac muscle that open and close at specific stages of cardiac activity in response to voltage change, thereby controlling the magnitude and timecourse of voltage-dependent Na+ currents (iNa )i n cardiac muscle cells. Although iNa has been recorded from sinoatrial (SA) node pacemaker cells, its precise role in SA node

Ming Lei; Henggui Zhang; Andrew A. Grace; H. Huang

2007-01-01

380

Plethyzmography in assessment of hemodynamic results of pacemaker functions programming  

NASA Astrophysics Data System (ADS)

The paper presents potential role of plethyzmography in optimization of heart hemodynamic function during pacemaker programming. The assessment of optimal stroke volume in patients, with implanted dual chamber pacemaker (DDD), by plethyzmography was a goal of the study. The data were collected during pacing rhythm. 20 patients (8 female and 12 male, average 77.4+/-4.6 years) with dual chamber pacemaker (DDD) and with pacing rhythm during routine pacemaker control and study tests were incorporated in the study group. Hemodynamic parameters were assessed during modification of atrio-ventricular delay (AVD) for pacing rhythm of 70 bpm and 90 bpm. The time of atrioventricular was programmed with 20 ms steps within range 100-200 ms and data were recorded with two minutes delay between two consecutive measurements. Stroke volume (SV) and cardiac output (CO) were calculated from plethyzmographic signal by using Beatscope software (TNO Holand). Highest SV calculated for given pacing rhythm was named optimal stroke volume (OSV) and consequently highest cardiac output was named maximal cardiac output (MCO). The time of atrio-ventricular delay for OSV was named optimal atrioventricular delay (OAVD). The results have showed: mean values of OAVD for 70 bpm - 152+/-33 ms and for 90 bpm -149+/-35 ms, shortening of the mean OAVD time caused by increase of pacing rate from 70 bpm to 90 bpm what resulted in statistically significant decrease of OSV with not statistically significant increase of MCO. The analysis of consecutive patients revealed three types of response to increase of pacing rhythm: 1. typical-shortening of OAVD, 2. neutral-no change of OAVD and 3.atypical-lengthening of OAVD.

Wojciechowski, Dariusz; Sionek, Piotr; Peczalski, Kazimierz; Janusek, Dariusz

2011-01-01

381

The MAP Kinase p38 Is Part of Drosophila melanogaster's Circadian Clock  

PubMed Central

All organisms have to adapt to acute as well as to regularly occurring changes in the environment. To deal with these major challenges organisms evolved two fundamental mechanisms: the p38 mitogen-activated protein kinase (MAPK) pathway, a major stress pathway for signaling stressful events, and circadian clocks to prepare for the daily environmental changes. Both systems respond sensitively to light. Recent studies in vertebrates and fungi indicate that p38 is involved in light-signaling to the circadian clock providing an interesting link between stress-induced and regularly rhythmic adaptations of animals to the environment, but the molecular and cellular mechanisms remained largely unknown. Here, we demonstrate by immunocytochemical means that p38 is expressed in Drosophila melanogaster's clock neurons and that it is activated in a clock-dependent manner. Surprisingly, we found that p38 is most active under darkness and, besides its circadian activation, additionally gets inactivated by light. Moreover, locomotor activity recordings revealed that p38 is essential for a wild-type timing of evening activity and for maintaining ?24 h behavioral rhythms under constant darkness: flies with reduced p38 activity in clock neurons, delayed evening activity and lengthened the period of their free-running rhythms. Furthermore, nuclear translocation of the clock protein Period was significantly delayed on the expression of a dominant-negative form of p38b in Drosophila's most important clock neurons. Western Blots revealed that p38 affects the phosphorylation degree of Period, what is likely the reason for its effects on nuclear entry of Period. In vitro kinase assays confirmed our Western Blot results and point to p38 as a potential “clock kinase” phosphorylating Period. Taken together, our findings indicate that the p38 MAP Kinase is an integral component of the core circadian clock of Drosophila in addition to playing a role in stress-input pathways. PMID:25144774

Dusik, Verena; Senthilan, Pingkalai R.; Mentzel, Benjamin; Hartlieb, Heiko; Wulbeck, Corinna; Yoshii, Taishi; Raabe, Thomas; Helfrich-Forster, Charlotte

2014-01-01

382

TrkB-mediated protection against circadian sensitivity to noise trauma in the murine cochlea.  

PubMed

Noise-induced hearing loss (NIHL) is a debilitating sensory impairment affecting 10%-15% of the population, caused primarily through damage to the sensory hair cells or to the auditory neurons. Once lost, these never regenerate [1], and no effective drugs are available [2, 3]. Emerging evidence points toward an important contribution of synaptic ribbons in the long-term coupling of the inner hair cell and afferent neuron synapse to maintain hearing [4]. Here we show in nocturnal mice that night noise overexposure triggers permanent hearing loss, whereas mice overexposed during the day recover to normal auditory thresholds. In view of this time-dependent sensitivity, we identified a self-sustained circadian rhythm in the isolated cochlea, as evidenced by circadian expression of clock genes and ample PERIOD2::LUCIFERASE oscillations, originating mainly from the primary auditory neurons and hair cells. The transcripts of the otoprotecting brain-derived neurotrophic factor (BDNF) showed higher levels in response to day noise versus night noise, suggesting that BDNF-mediated signaling regulates noise sensitivity throughout the day. Administration of a selective BDNF receptor, tropomyosin-related kinase type B (TrkB), in the night protected the inner hair cell's synaptic ribbons and subsequent full recovery of hearing thresholds after night noise overexposure. The TrkB agonist shifted the phase and boosted the amplitude of circadian rhythms in the isolated cochlea. These findings highlight the coupling of circadian rhythmicity and the TrkB receptor for the successful prevention and treatment of NIHL. PMID:24583017

Meltser, Inna; Cederroth, Christopher R; Basinou, Vasiliki; Savelyev, Sergey; Lundkvist, Gabriella S; Canlon, Barbara

2014-03-17

383

Copper chelation and exogenous copper affect circadian clock phase resetting in the suprachiasmatic nucleus in vitro.  

PubMed

Light stimulates specialized retinal ganglion cells to release glutamate (Glu) onto circadian clock neurons of the suprachiasmatic nucleus (SCN). Glu resets the phase of the SCN circadian clock by activating N-methyl-d-aspartate receptors (NMDAR) causing either delays or advances in the clock phase, depending on early- or late-night stimulation, respectively. In addition, these Glu-induced phase shifts require tropomyosin receptor kinase B (TrkB) receptor activity. Previous studies show that copper (Cu) released at hippocampal synapses can inhibit NMDAR activity, and application of exogenous Cu likewise inhibits NMDAR activity. We investigated the effects of Cu in acute SCN brain slices prepared from C57BL/6Nhsd adult, male mice using treatments that decrease or increase available Cu levels in vitro and recorded neuronal activity on the following day. When bath-applied for 10 min at zeitgeber time (ZT) 16 (where ZT0=lights-on in the donor animal colony), the Cu-specific chelators tetrathiomolybdate (TTM) and bathocuproine disulfonate each induce ?2.5-3-h phase delays in circadian neuronal activity rhythms, similarly to Glu-induced phase delays. Co-application of 10 ?M CuCl2, but not 10 ?M CoCl? blocks TTM-induced phase delays. Furthermore, TTM causes phase advances when applied at ZT23. At both application times, TTM-induced phase shifts are blocked by NMDA or TrkB receptor antagonists. Surprisingly, bath-application of 10 ?M Cu alone also induces phase shifts in analogous experiments at ZT16 and ZT23. Inhibiting NMDAR does not block Cu-induced phase shifts. TrkB inhibition blocks Cu-induced phase delays but not phase advances. Thus, increasing and decreasing Cu availability appear to shift the SCN clock phase through different mechanisms, at least at the receptor level. We propose that Cu plays a role in the SCN circadian clock by modulating Glu signaling. PMID:24161278

Yamada, Y; Prosser, R A

2014-01-01

384

Management of tachyarrhythmias with dual-chamber pacemakers.  

PubMed

Multiprogrammable dual-demand AV sequential (DVI, MN) pacemakers were implanted in twenty-three patients (in one of them a DVI, MN unit was used as a VVI, MN with the aid of an atrial plug) with supraventricular tachycardias after electrophysiological studies revealed a great variety of AV reentry circuits. The latter included tachycardias involving accessory pathways of the Kent type, manifest or concealed Wolff-Parkinson-White syndromes, nodo-ventricular (Mahaim) tracts, "enhanced" AV node (or extra AV nodal) pathways and dual AV pathways. In addition, multiprogrammable "non-committed" AV sequential (DVI, MN and DDD, M) pacemakers were permanently implanted to treat different forms of ventricular tachyarrhythmias that included: torsade de pointes in the Romano-Ward syndrome and Chagas' cardiomyopathy, ventricular tachycardia which is bradycardia-dependent (in Chagas' cardiomyopathy) and reciprocal beats induced by, and producing severe hemodynamic derangements in a patient with a conventional VVI unit. With small-size multiprogrammable units, arrhythmias may be treated by changing parameters non-invasively. By temporary inhibition, one may analyze the underlying rhythm and pacemaker dependency. In patients without chronic atrial flutter/fibrillation who require pacing and possibly tachyarrhythmia control, our experience with multiprogrammable "non-committed" AV sequential pacing has been very satisfactory. The evolution toward newer pacing modes which provide atrial sensing and tracking (DDD), and thus preserve AV synchrony over a wider range of atrial rates, may contribute even further to successful patient management. This may be applicable to pediatric patients as well. PMID:6189076

Medina-Ravell, V; Castellanos, A; Portillo-Acosta, B; Maduro-Maytin, C; Rodriguez-Salas, L; Hernandez-Arenas, M; La Salle-Toro, R; Mendoza-Mujica, I; Ortega-Maldonado, M; Berkovits, B V

1983-03-01

385

Cryptochrome restores dampened circadian rhythms and promotes healthspan in aging Drosophila.  

PubMed

Circadian clocks generate daily rhythms in molecular, cellular, and physiological functions providing temporal dimension to organismal homeostasis. Recent evidence suggests two-way relationship between circadian clocks and aging. While disruption of the circadian clock leads to premature aging in animals, there is also age-related dampening of output rhythms such as sleep/wake cycles and hormonal fluctuations. Decay in the oscillations of several clock genes was recently reported in aged fruit flies, but mechanisms underlying these age-related changes are not understood. We report that the circadian light-sensitive protein CRYPTOCHROME (CRY) is significantly reduced at both mRNA and protein levels in heads of old Drosophila melanogaster. Restoration of CRY using the binary GAL4/UAS system in old flies significantly enhanced the mRNA oscillatory amplitude of several genes involved in the clock mechanism. Flies with CRY overexpressed in all clock cells maintained strong rest/activity rhythms in constant darkness late in life when rhythms were disrupted in most control flies. We also observed a remarkable extension of healthspan in flies with elevated CRY. Conversely, CRY-deficient mutants showed accelerated functional decline and accumulated greater oxidative damage. Interestingly, overexpression of CRY in central clock neurons alone was not sufficient to restore rest/activity rhythms or extend healthspan. Together, these data suggest novel anti-aging functions of CRY and indicate that peripheral clocks play an active role in delaying behavioral and physiological aging. PMID:23692507

Rakshit, Kuntol; Giebultowicz, Jadwiga M

2013-10-01

386

Circadian Modulation of Anxiety: A Role for Somatostatin in the Amygdala  

PubMed Central

Pharmacological evidence suggests that the neuropeptide somatostatin (SST) exerts anxiolytic action via the amygdala, but findings concerning the putative role of endogenous SST in the regulation of emotional responses are contradictory. We hypothesized that an endogenous regulation of SST expression over the course of the day may determine its function and tested both SST gene expression and the behavior of SST knock out (SST-/-) mice in different aversive tests in relation to circadian rhythm. In an open field and a light/dark avoidance test, SST-/- mice showed significant hyperactivity and anxiety-like behavior during the second, but not during the first half of the active phase, failing to show the circadian modulation of behavior that was evident in their wild type littermates. Behavioral differences occurred independently of changes of intrinsically motivated activity in the home cage. A circadian regulation of SST mRNA and protein expression that was evident in the basolateral complex of the amygdala of wild type mice may provide a neuronal substrate for the observed behavior. However, fear memory towards auditory cue or the conditioning context displayed neither a time- nor genotype-dependent modulation. Together this indicates that SST, in a circadian manner and putatively via its regulation of expression in the amygdala, modulates behavior responding to mildly aversive conditions in mice. PMID:24376834

Albrecht, Anne; Thiere, Marlen; Bergado-Acosta, Jorge Ricardo; Poranzke, Janine; Müller, Bettina; Stork, Oliver

2013-01-01

387

Effects of Tetraethylammoni um on Potassium Currents in a Molluscan Neuron  

Microsoft Academic Search

The effects of tetraethylammoni um (TEA) on the delayed K + current and on the Ca2+-activated K + current of the Aplysia pacemaker neurons R-15 and L-6 were studied. The delayed outward K + current was measured in Ca2+-free ASW containing tetrodotoxin (TTX), using brief depolarizing clamp pulses. External TEA blocks the delayed K + current reversibly in a dose-

A. HERMANN; A. L. F. GORMAN

1981-01-01

388

Optogenetic Stimulation of MCH Neurons Increases Sleep  

PubMed Central

Melanin concentrating hormone (MCH) is a cyclic neuropeptide present in the hypothalamus of all vertebrates. MCH is implicated in a number of behaviors but direct evidence is lacking. To selectively stimulate the MCH neurons the gene for the light-sensitive cation channel, channelrhodopsin-2, was inserted into the MCH neurons of wild-type mice. Three weeks later MCH neurons were stimulated for 1 min every 5 min for 24 h. A 10 Hz stimulation at the start of the night hastened sleep onset, reduced length of wake bouts by 50%, increased total time in non-REM and REM sleep at night, and increased sleep intensity during the day cycle. Sleep induction at a circadian time when all of the arousal neurons are active indicates that MCH stimulation can powerfully counteract the combined wake-promoting signal of the arousal neurons. This could be potentially useful in treatment of insomnia. PMID:23785141

Konadhode, Roda Rani; Pelluru, Dheeraj; Blanco-Centurion, Carlos; Zayachkivsky, Andrew; Liu, Meng; Uhde, Thomas; Glen, W. Bailey; van den Pol, Anthony N.; Mulholland, Patrick J.

2013-01-01

389

Testing of Common Electromagnetic Environments for Risk of Interference with Cardiac Pacemaker Function  

PubMed Central

Background Cardiac pacemakers are known to be susceptible to strong electromagnetic fields (EMFs). This in vivo study investigated occurrence of electromagnetic interference with pacemakers caused by common environmental sources of EMFs. Methods Eleven volunteers with a pacemaker were exposed to EMFs produced by two mobile phone base stations, an electrically powered commuter train, and an overhead high voltage transmission lines. All the pacemakers were programmed in normal clinically selected settings with bipolar sensing and