Circadian Rhythms and Biological Clocks, Part A

Zheng Eelderink-Chen , ... Martha Merrow , in Methods in Enzymology, 2015

2.one.3 Zeitgeber forcefulness and entrainment of yeast

Zeitgeber strength was contradistinct in two ways: (1) as referred to higher up, simply shifting the temperature cycle to lower mean level (18/25  °C vs. 21/28   °C) and (2) irresolute amplitude of temperature cycles (16/27, 18/25, xix/23, and 20/22   °C; Fig. 5). The 20/22   °C wheel failed to yield a rhythmic pH oscillation, suggesting that this zeitgeber condition is too weak to entrain a yeast cyclic clock (information not shown). In the entraining temperature cycles with increasing aamplitude, the stage of the pH rhythm becomes afterward. At lower temperatures, the stage of the H+ oscillation also moves afterwards than the phase in higher temperatures. This suggests that, at least within the weather tested, lower temperature (18/25   °C) is perceived as a stronger zeitgeber than the college temperature condition (21/28   °C). That is, entrainment at the lower temperature is more like the higher amplitude temperature cycles.

Figure five. Phase relationships modify with zeitgeber forcefulness. Grey panels betoken cool phase; white panels bespeak warm phase. (A) The phase of the H+ oscillation in temperature cycles with the same amplitude merely dissimilar absolute values. In lower temperature cycles (18–25   °C; lower panel), the peak of the H+ oscillation shifted to the later position than the peak in warmer cycles (21–28   °C; upper panel). (B) The phase of the H+ oscillation in temperature cycles with different amplitudes. The peak of the H+ oscillation shifted to a later on stage in the high-amplitude cycles. The information are double plotted.

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Hormone-Behavior Relations of Clinical Importance

A.J. Lewy , ... J. Crude , in Hormones, Encephalon and Beliefs (Second Edition), 2009

five.lxxx.6 Zeitgeber Fourth dimension

Another important concept is zeitgeber time (ZT). The term zeitgeber (literally, fourth dimension giver or fourth dimension cue) refers to environmental variables that are capable of interim as cyclic time cues. The calorie-free/dark cycle is the most important zeitgeber, but other stimuli such as melatonin tin can as well function equally zeitgebers. ZT is the temporal relation of the circadian rhythm, marked by the DLMO, to entraining signals such as dawn (or the first introduction of light, i.e. wake time). For example, a person whose DLMO occurs 13  h after wake time is said to have a DLMO ZT of xiii. The ZT of the DLMO tin can provide data well-nigh the length of a person'due south cyclic rhythm (tau). For example, a person whose DLMO occurs at ZT xiii almost probable has a shortened tau, peradventure less than 24   h, while a person with a DLMO of ZT fifteen most likely has an intrinsically long tau (Lewy et al., 2000).

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Cyclic Role and Therapeutic Potential of Melatonin in Humans

A.J. Lewy , ... J.S. Emens , in Encyclopedia of Neuroscience, 2009

Phase Angle of Entrainment and Circadian Period

The DLMO ZT tin be used to estimate the PAE. Yet, this assumes that the conveniently measured slumber variable, waketime, faithfully represents the stage of reference for the primary zeitgeber, the light dark bike, an assumption grounded in the fact that the sleep/wake cycle superimposes structure on the perceived low-cal dark cycle. As more is understood about the cyclic response to light (and dark), this reference stage will exist calculated with greater accurateness. At present, however, we must deal as best we can with the fact that waking upwards into bright sunlight results in a shorter PAE (DLMO ZT) than enkindling before dawn, a fact that complicates extending findings from studies in which animals with shorter intrinsic periods (taus) entrain to a 24  h zeitgeber with a shorter PAE. (Unless otherwise specified, intrinsic tau is assumed here to be greater than 24   h, which is clearly the case for the majority of humans.) The creature studies were conducted nether weather in which the light/dark bike was much more strictly controlled than the measurement of DLMO ZT in humans exposed to their usual light/dark cycles. However, under laboratory conditions, sighted humans with shorter taus accept besides been shown to have shorter PAEs, a finding consistent with what was found in blind people entraining to a daily dose (x   mg) of melatonin. PAE has also been estimated in humans using the melatonin/sleep onset interval (MSI). Another consideration is that PAD is nigh meaningful when measured nether naturalistic conditions, whereas PAE is most useful when measured under controlled lighting and stabilized sleep/wake experimental atmospheric condition.

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Psychiatric Disorders Associated with Disturbed Sleep and Circadian Rhythms

E.G. Simon , in Encyclopedia of Neuroscience, 2009

Social rhythm in bipolar disorder

The social zeitgeber hypothesis mentioned earlier in the case of MDE holds good for bipolar disorder also ( Effigy 6 ). Information technology has been noted that disruptive events (zeitstorer's) happen more than ofttimes prior to manic or hypomanic episodes when compared with euthymic periods. In RCBD, significantly decreased social rhythm has been reported. Reduced social rhythm has been plant in groups of adolescents who were at high risk of developing bipolar disorder in a sample of bipolar II patients compared to a command group. In a recent study conducted in Germany that examined social rhythm instabilities in adolescents and immature adults at risk for affective disorders, participants from the bipolar risk group were found to have reduced social rhythm scores every bit measured by the Social Rhythm Metric when compared with a control group. The Social Rhythm Metric quantifies the stability of an individual'south daily routine and lists activities that are identified as central to everyday life. The group with take a chance for unipolar depression divers by the high rigidity scores from the rigidity subscale of the Munich Personality Exam did not prove reduced social rhythm scores.

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1954 Zeitgebers (Time-Givers) for Biological Clocks

Michael D. Brood , in Conceptual Breakthroughs in Ethology and Animate being Behavior, 2017

The Caption

A biological clock is cocky-sustaining and runs using just a small corporeality of energy. What it doesn't exercise well, on its own, is go on authentic time. Animals kept in continuous dark or light go on their rhythms for a while, only their clocks do not cycle at exactly 24   h, so without an external input the clock falls out of synchrony with the environment. Xx-iv-hour rhythms are called circadian rhythms because they cycle in one case a 24-hour interval; biological clocks typically run on a daily cycle. Animals under atmospheric condition without light input take complimentary-running biological clocks that lose their synchrony with the environment and with other animals.

The German physiologist Jürgen Aschoff developed two key concepts that brought our understanding of biological clocks into our modern scientific framework: entrainment and the zeitgeber ( Aschoff 1954). Entrainment is the synchronization of the internal clock with the external world. Clocks be in many organs in an animal, and so entrainment ensures that the clocks work well together. A zeitgeber, or fourth dimension-giver, is the external cue that entrains the clock.

To understand how zeitgebers piece of work a footling background on clocks helps. Biological clocks tin can best exist imagined as working like a mechanical clock with a pendulum or a mechanical watch with a balance wheel. Protein molecules build upward and break downwards rhythmically and the information from this rhythm drives cycles in biological processes. In a mechanical picket the spring unloads a small bit of tension, causing the residual bicycle to swing and advance a ratchet, which in plough pushes gears that lead to motion of the hands of the watch. In a biological clock small bits of energy are expended in protein synthesis to keep the molecules oscillating.

Menstruation, or per, genes are found in most animals and are important in helping to drive the clock. A build-up of poly peptide products (transcripts) within the cell from the per genes feeds back to plow off the per genes. When the per gene products interruption down the per genes turn dorsum on and start production of the proteins again. Thus there is an on–off cycle for the cell.

This is where the zeitgeber comes in. Another gene, cryptochrome (cry) codes for proteins that are light-sensitive, particularly for bluish light. Weep products combine with per products, so the whole wheel can be timed with external twenty-four hours–night cycles. The cry mechanism is somewhat different in mammals and this caption is something of a simplification, but overall it helps to institute the mechanistic validity of Aschoff's concept of a zeitgeber (Reppert and Weaver, 2002). 1

Another really interesting fact most biological clocks is that they are temperature independent. Many physiological processes speed up when an animal is hot and slow downwards when an beast is common cold, but non so with circadian clocks. Given that in many habitats temperature changes with the solar day–night cycle, the temperature independence of the clock prevents physiological chaos. Clocks come up again in Chapter 34, 1971 Behavioral Genetics.

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Handbook of Sleep Research

Teresa Liu-Ambrose , Ryan S. Falck , in Handbook of Behavioral Neuroscience, 2019

III Cyclic Rhythms and Sleep in Normal Aging

The chief entraining zeitgeber for the homo biological clock is light ( Roenneberg & Foster, 1997; Sharma & Chandrashekaran, 2005), exerting its influence on retinal ganglion cells containing melanopsin (Blanks, Hinton, Sadun, & Miller, 1989; La Morgia et al., 2016; Schmidt, Chen, & Hattar, 2011; Sekaran, Foster, Lucas, & Hankins, 2003). Retinal light exposure direct stimulates the action of the SCN, which stage delays the biological clock such that the desire for sleep decreases and wakefulness increases (or is maintained); reduced retinal lite exposure results in less activeness of the SCN and increases the want to sleep by stage advancing the biological clock (Shirani & Louis, 2009). Thus, under normal circumstances, the biological clock is entrained to the solar light-dark cycle through the regulation of the SCN—which helps humans maintain a regular sleep-wake bicycle (Mistlberger, 2005).

Even so, crumbling significantly alters the functioning of circadian rhythms. Aging is associated with the biological clock initiating sleep-promoting mechanisms earlier in the day (Czeisler et al., 1992; Duffy, Dijk, Klerman, & Czeisler, 1998) and a decreased amplitude in circadian signals, which increment sleep demand (Dijk, Duffy, Riel, Shanahan, & Czeisler, 1999; van Someren, Mirmiran, & Swaab, 1993). This weakening of circadian regulation with aging likely plays a prominent role in the fragmentation of sleep-wake rhythms observed in older adults during (1) the wake maintenance zone, which occurs two–3   hours earlier habitual bedtime, and (2) the sleep maintenance zone, which occurs 2–three   hours earlier habitual wake time (Landry & Liu-Ambrose, 2014). In improver, older adults accept reduced sensitivity to light, due to age-related loss of retinal ganglion cells and axons (Harwerth, Wheat, & Rangaswamy, 2008), which leads to poorer functioning of the SCN and divergence of the biological clock from the solar light-dark cycle (Neikrug & Ancoli-Israel, 2010). Behavioral changes in older adulthood—such as spending less time outdoors—could also further decrease bright light exposure, which may be a contributing cistron to the decreased aamplitude of cyclic rhythms (Landry & Liu-Ambrose, 2014).

This age-associated weakening in circadian regulation may likewise be linked to declines in sleep quality in older machismo. Sleep changes every bit a function of normal aging, both in terms of decreased quality and quantity (Crowley, 2011; Espiritu, 2008). More one-half of adults over 65 years report at least 1 chronic slumber complaint—the almost common complaints being the inability to stay asleep at night and excessive daytime sleepiness resulting in frequent daytime naps (Foley et al., 1995). These complaints, in item the reports of excessive daytime sleepiness (a key indicator of accumulated sleep debt (Carskadon, 1986; Johns, 1991)), suggest that age-related changes in sleep are likely the result of something beyond reduced demand for sleep. The evidence therefore suggests that (1) normal aging may disrupt the function of circadian rhythms and (2) these age-related changes in the functioning of circadian rhythms may explain the declines in both slumber quality and quantity equally people historic period.

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Clock Genes and Metabolic Regulation

A. Kohsaka , J. Bass , in Encyclopedia of Neuroscience, 2009

Low-cal: Zeitgeber and Photoreception

Light is the predominant Zeitgeber signal (time giver) that entrains the biological clock of the SCN. The SCN, in turn, maintains temporal synchrony between internal periodic cycles and the external environment that is idea to enhance overall organismal function and survival. For example, the daily tiptop in the secretion of glucocorticoid promotes cardiovascular tone during the transition from sleep to wakefulness, and a ascension in growth hormone during the residuum phase may contribute to metabolic homeostasis, for instance, past promoting hepatic gluconeogenesis.

A major advance in understanding how the SCN receives photic input came from the discovery of the melanopsin photoreceptor pathway by Provencio and colleagues in 2000. In mammals, retinal photoreceptors, which comprise rods, cones, and ganglion cells, receive both visual (sight) and nonvisual (light) information. The nonvisual response, called cyclic photoreception, plays an important role in the lite entrainment of the circadian system. The discovery of melanopsin, a novel opsin, opened a new window on the detailed mechanism of circadian photoreception. A subset of retinal ganglion cells was subsequently shown to express melanopsin, and genetic ablation of melanopsin reduced the locomotor activity response to light. Melanopsin-containing ganglion cells receive input from the rod–cone system and send neural projections to multiple central nervous system (CNS) regions, including the hypothalamus and thalamus. Retinal photoreceptors project to the SCN via the retinohypothalamic tract (RHT). Recent studies also suggest that melanopsin-containing neurons may too project to broad regions of neocortex and thereby provide direct light input into regions involved in alacrity, attention, and arousal independently of the RHT input into the SCN.

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Body Clocks in Health and Disease

I.N. Karatsoreos , R. Silvery , in Conn'south Translational Neuroscience, 2017

Cyclic time (CT) versus Zeitgeber time (ZT) . Circadian time is a standard unit of time based on the endogenous complimentary-running period of a rhythm. Zeitgeber time is a unit of measurement of time based on the menstruum of a zeitgeber, such equally the 12:12 calorie-free:night wheel. By convention, in complimentary-running, abiding conditions, the onset of activity of day-agile organisms is cyclic time zero (CT0) and the onset of activeness of night-active organisms is CT12. In a light:night cycle, for diurnal organisms ZT0 (lights on) is the time of activity onset and ZT12 (lights off) defines activity onset for nocturnal animals.

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Circadian Rhythms and Biological Clocks, Role B

Matthias Schlichting , Charlotte Helfrich-Förster , in Methods in Enzymology, 2015

Abstruse

Low-cal is the nearly important Zeitgeber to entrain the cyclic clock of the fruit fly Drosophila melanogaster to the 24-h bike on globe. The fruit fly's cyclic clock is very light sensitive, mainly because about half of the 150 clock neurons in the fly's brain limited the blue-light photopigment, Cryptochrome, which provokes an immediate degradation of the clock poly peptide Timeless upon activation by lite. Consequently, Drosophila's molecular clock tin reset very fast to mensurate the changes in environmental-lighting weather condition. However, usually the responses of the molecular clock to low-cal are non direct measured, merely conclusions virtually entrainment of the circadian clock are drawn from recording the flies' locomotor activity rhythms. Here, nosotros review how the flies' locomotor activity can be recorded under dissimilar light regimes and how entrainment can exist analyzed and properly judged. Nosotros too summarize the influence of unlike recording and lighting methods on the flies' activeness pattern, highlight their advantages and disadvantages, and stress full general pitfalls.

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Bones Slumber Concepts, Scientific discipline, Impecuniousness, and Mechanisms

D. Mircsof , S.A. Brown , in Encyclopedia of Sleep, 2013

Phase Shifts and Phase Response Curves

Lite is considered the strongest Zeitgeber for the SCN. Every twenty-four hours, it resets the stage of the endogenous cyclic clock and the linked oscillations in physiology and behavior to exactly lucifer the 24-h mean solar day (up to a maximum of approximately 2  h per solar day in humans), even if the endogenous 'gratuitous-running' period of the internal clock is shorter or longer. Chiefly for this result, the effect of light on the SCN varies depending on the time at which it is perceived. Thus, resetting of the circadian organization by lite exposure at most times during the subjective day has lilliputian or no effect on the resetting of the clock. By contrast, lite exposure in the late night and early on morning leads to stage advances (and then that locomotor activeness will commencement before the next twenty-four hours) and lite exposure in the evening and early night delays the clock (and then that activity will starting time later the next mean solar day).This stage dependence of low-cal-induced phase shifts can best be visualized every bit a stage response curve (Red china), which plots phase shifts of a circadian rhythm as a function of the cyclic phase that a stimulus is given. The human China to bright light pulses is shown in Figure one(a) . Although biological mechanism may vary considerably, all known environmental factors that phase-shift the clock (both natural and artificial) do and then in a time-dependent way, though the shape of the Mainland china varies. For example, the PRC of the hormone and drug melatonin is shown in Figure 1(b) .

Effigy ane. Schematic representation of the phase response curves (PRCs) to light and melatonin. (a) Light exposure in the early on evening leads to a delay of circadian rhythms, whereas light exposure in the early morning causes phase advances. On the 10-axis, the time indicate 0 corresponds roughly to the minimum of the body temperature. For convenience, conventional time of day is besides plotted. During daytime, there exists a 'dead zone' during which light exposure has little event on circadian phase shifting. (b) The PRC to melatonin is near 12   h out of phase with that of light and exhibits less potent phase shifting, represented by the smaller amplitude.

 Adjusted from Lewy AJ, Bauer VK, Ahmed S, (1998) The human stage response bend (Red china) to melatonin is about 12 hours out of phase with the PRC to light. Chronobiology International 15: 71–83; Khalsa SB, Jewett ME, et al. (2003). A phase response curve to unmarried bright light pulses in man subjects. The Journal of Physiology 549(Pt 3): 945–952.

Natural environmental inputs to the circadian oscillator are generally divided into photic (light) and nonphotic (practise, social interaction) categories. Every bit we shall see, these stimuli reach the SCN and peripheral clocks via very different pathways, only in each case the result is rhythmic physiology and beliefs that is optimally entrained to the environment.

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