1
Q
Temperature Compensation
A
A characteristic of circadian rhythms, whereby changes in temperature do not significantly alter the period – a Q10 close to 1. Q10 – the ratio between the rates measured for (bio) chemical reactions at two temperatures differing by 10°C within the physiological range – is nearly 1 for the circadian period length (Dunlap, 1999).
This temperature compensation may be important for poikilothermic organisms, such as fish, amphibians and reptiles, in order to anticipate daytime irrespective of ambient temperature.
2
Q
Feedback Loop
A
- From a molecular standpoint, circadian rhythms are regulated by transcriptional and post-translational feedback loops generated by a set of interplaying clock proteins.
- The fundamental mechanism of the generation and maintenance of rhythms is similar in the central and the peripheral clocks; however, the output pathways elicited can be different and more tissue specific.
- The positive limb of the mammalian clock machinery is comprised of CLOCK and BMAL1, which are transcription factors that heterodimerise through the PAS domain and induce the expression of clock-controlled genes by binding to their promoters at E-boxes.
- The cryptochrome (CRY1 and CRY2) and period (PER1, PER2 and PER3) families are clock-controlled genes and encode proteins that negatively regulate the circadian machinery.
- Per and Cry proteins are thought to translocate into the nucleus and form a complex to inhibit CLOCK–BMAL1-mediated transcription, thereby closing the negative feedback loop6.
- To start a new transcription cycle, the CLOCK–BMAL1 complex needs to be de-repressed through the proteolytic degradation of Per and Cry.
- Although we have described the mammalian circadian clocks, the generation and maintenance of rhythms is conceptually conserved in other model organisms such as Drosophila melanogaster, Neurospora crassa and plants
3
Q
Phase angle
A
- The relative angular displacement between a periodic quantity and a reference angle.
- There can be a difference between the entraining cycle and the entrained rhythm. This difference can be measured by selecting a point in the entraining cycle (e.g. light on), and a phase reference point in the resulting rhythm (e.g. the onset of a particular activity).
- The difference between these two points is known as the phase angle. The phase angle is a function of photoperiod, for example it may be greater at LD 1:23 than at LD 4:20 (i.e. there may be a greater time between say light on and the start of activity at a shorter photoperiod).
- In humans the phase angle difference can be seen between the natural lights on i.e. dawn, and waking up
- Phase angle of entrainment is defined as the relationship between the timing of the biological clock and the timing of an external time cue (i.e., zeitgeber), and if the primary explanation for morningness-eveningness is circadian, then a difference in phase angle of entrainment to the light-dark cycle would be expected between the two types.
4
Q
Zeitgeber
A
- A zeitgeber is any external or environmental cue that entrains or synchronizes an organism’s biological rhythms to the Earth’s 24-hour light/dark cycle and 12 month cycle.
- It is the principal entraining signal which is usually light however some animals use different cues such as temperature.
- The term “zeitgeber” (German for literally “time giver”, i.e., “synchronizer”) was first used by Jürgen Aschoff, one of the founders of the field of chronobiology. His work demonstrated the existence of endogenous (internal) biological clocks, which synchronize biological rhythms. In addition, he found that certain exogenous (external) cues, which he called zeitgebers, influence the timing of these internal clocks.
- There are many different zeitgebers, and their relative influence on an individual at any given time depends on a number of factors, including the presence and operation of other kinds of zeitgebers.
- For example, Jürgen Aschoff showed that individuals can compensate for the absence of some zeitgebers like natural light by attending to social zeitgebers instead.
- Specifically, individuals placed in total darkness for four days did not differ on a variety of measures, including body temperature and various psychomotor tasks like time estimation and finger tapping, from individuals placed in an artificial light-dark environment when both groups were given the same strict time schedule.
- Researchers concluded that social zeitgebers, like meal times and interactions with other people, can entrain biological rhythms in ways similar to those of other common zeitgebers like light.
- Other common examples of zeitgebers include, light, temperature, social interactions, pharmacological manipulation, exercise and eating/drinking patterns.
5
Q
Zugunruhe
A
- Zugunruhe is a German compound word consisting of Zug (move, migration) and Unruhe (anxiety, restlessness).
- It describes anxious behavior in migratory animals, especially in birds during the normal migration period. When these animals are enclosed, such as in an Emlen funnel, Zugunruhe serves to study the seasonal cycles of the migratory syndrome.
- Zugunruhe involves increased activity towards and after dusk with changes in the normal sleep pattern. Researchers have been able to study the endocrine controls and navigational mechanisms associated with migration by studying Zugunruhe.
- Zugunruhe has been artificially induced in experiments by simulating long days. Some studies on White-crowned Sparrows have suggested that prolactin is involved in the pre-migratory hyperphagia (feeding), fattening and Zugunruhe however others have found that prolactin may merely be associated with lipogenesis (fat accumulation).
- The phenomenon of Zugunruhe was generally believed to be found only in migratory species; however, a study of a resident species has shown low-level Zugunruhe, including oriented activity, suggesting that the endogenous mechanisms for migratory behaviour may be present even in a resident species.
- Further suggestions for endogenous programs are provided by observations that the number of nights on which Zugunruhe is exhibited by caged migrants appears related to the distance of migration involved.
6
Q
Phase response curve (PRC)
A
- A phase response curve (PRC) illustrates the transient change in the cycle period of an oscillation induced by a perturbation as a function of the phase at which it is received.
- PRCs are used in various fields; examples of biological oscillations are the heartbeat, circadian rhythms, and the regular, repetitive firing observed in some neurons in the absence of noise.
- A PRC illustrates the relationship between a treatment’s time of administration and the treatment’s effect on a circadian rhythm.
- Normally, the body’s various physiological rhythms will be synchronized within an individual organism (human or animal).
- The sleep–wake cycle is the most familiar of these rhythms; for humans, a treatment designed to affect circadian rhythms will most often be intended to adjust sleep timing, by either delaying it to later in the day (night), or advancing it.
- Extreme morning people may want to delay their sleep timing; extreme evening chronotypes may wish to advance it.
- A PRC is a graph showing, by convention, time of the subject’s endogenous day along the x-axis and the amount of the phase shift (in hours) along the y-axis. The curve has one peak and one nadir in each 24-hour cycle. Relative circadian time is plotted vs. phase shift magnitude.
- The two common treatments used to shift the timing of sleep are light therapy, directed at the eyes, and administration of the hormone melatonin, usually taken orally. Either or both can be used daily. Each of these treatments has its own PRC which will vary according to the species being studied; its shape may also vary individually, just slightly. The magnitude is dose-dependent.
7
Q
Circannual
A
• Any biological rhythm involving a biological or psychological process that occurs or fluctuates at intervals of approximately one year, even in controlled environments from which seasonal cues have been eliminated, such as the seasonal changes in behaviour of some migratory birds, which persist even under constant laboratory conditions from which fluctuations in temperature, daylight, and other seasonal cues have been excluded.
8
Q
Retino hypothalamic tract (RHT)
A
- The retinohypothalamic tract (RHT) is a photic neural input pathway involved in the circadian rhythms of mammals.
- The origin of the retinohypothalamic tract is the intrinsically photosensitive retinal ganglion cells (ipRGC), which contain the photopigment melanopsin.
- The axons of the ipRGCs belonging to the retinohypothalamic tract project directly, monosynaptically, to the suprachiasmatic nuclei (SCN) via the optic nerve and the optic chiasm.
- The suprachiasmatic nuclei receive and interpret information on environmental light, dark and day length, important in the entrainment of the “body clock”. They can coordinate peripheral “clocks” and direct the pineal gland to secrete the hormone melatonin.
- The SCN of the hypothalamus contains an endogenous pacemaker that regulates circadian rhythms. The zeitgeber found to have the most profound effect on the SCN is light, which is the form of stimulation of which conversion is needed for it to be processed by the brain.
- Neurotransmitters that travel the RHT are responsible for delivering this message to other parts of the brain. If damage is done to this important pathway, alterations in circadian rhythms including phase shifts may occur. Studies done on rats show that even with severely degenerated photoreceptors (blind, no visible light perception), they have the ability to entrain to the light/dark cycle because they have intact RHTs.
9
Q
Oscillator coupling
A
- The circadian clock is a cell-autonomous and self-sustained oscillator with a period of about 24 h and thought to function as a cellular metronome that temporally controls key aspects of cell physiology, including metabolism, redox balance, chromatin landscapes and transcriptional states, and cell signalling.
- In growth conditions, successive divisions and progression through the cell cycle can also be considered as a periodic process. The cell cycle duration in mammalian cells typically also lasts on the order of 1 day.
- An immediate theoretical consequence is that coupling between two such oscillators may lead to synchronisation, which is also called mode-locking. In fact, depending on the relationships between the intrinsic periods of the oscillators and the strength of their coupling, the system may stabilize into a steady state in which the two cycles advance together, similar to a resonance phenomenon.
- More generally, the system may switch from asynchrony (quasi-periodicity) to synchronization characterized by a rational winding number (p:q) such that exactly p cycles of the first oscillator are completed while the second completes q cycles.
10
Q
Entrainment
A
- Entrainment, within the study of chronobiology, occurs when rhythmic physiological or behavioral events match their period and phase to that of an environmental oscillation.
- A common example is the entrainment of circadian rhythms to the daily light–dark cycle, which ultimately is determined by the Earth’s rotation. The term entrainment is justified because the biological rhythms are endogenous:
- They persist when the organism is isolated from periodic environmental cues. Of the several possible cues, called zeitgebers (German for ‘time-givers’, ‘synchronizers’), which can contribute to entrainment, bright light is by far the most effective. Exercise may also play a role.
- The activity/rest (sleep) cycle in animals is only one set of circadian rhythms that normally are entrained by environmental cues.
- In mammals, such endogenous rhythms are generated by the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. Entrainment is accomplished by altering the concentration of clock components through altered gene expression and protein stability.
- Circadian oscillations occur even in the cells of isolated organs, and it is believed that the master pacemaker in the mammalian brain, the SCN, coordinates the peripheral clocks.
- Such hierarchical relationships are not the only ones possible: Two or more oscillators may couple in order to assume the same period without either being dominant over the other(s). This situation is analogous to Huygens’ pendulum clocks.
- The phase of entrainment refers to the relative timing of any circadian event within the objective 24-hour day.
- When good sleep hygiene is insufficient, a person’s lack of synchronization to night and day can have health consequences.
- There is significant variation within normal chronotypes’ entrainment; it is normal for humans to awaken anywhere from about 5 a.m. to 9 a.m. However, patients with delayed sleep-phase disorder (DSPD), advanced sleep-phase disorder (ASPD) and non-24-hour sleep–wake disorder are improperly entrained to light/dark.
11
Q
Chronotype
A
- Chronotype refers to the behavioral manifestation of underlying circadian rhythms of myriad physical processes. A person’s chronotype is the propensity for the individual to sleep at a particular time during a 24-hour period.
- ‘Eveningness’ (delayed sleep period) and ‘morningness’ (advanced sleep period) are the two extremes with most individuals having some flexibility in the timing of their sleep period.
- However, across development there are changes in the propensity of the sleep period with pre-pubescent children preferring an advanced sleep period, adolescents preferring a delayed sleep period and many elderly preferring an advanced sleep period.
- The causes and regulation of chronotypes, including developmental change, individual propensity for a specific chronotype, and flexible versus fixed chronotypes have yet to be determined. However, research is beginning to shed light on these questions, such as the relationship between age and chronotype.
- With the exception of the most extreme and rigid chronotypes regulation is likely due to gene-environment interactions.
- Important environmental cues (zeitgebers) include light, feeding, social behavior, and work and school schedules.
- Humans are normally diurnal creatures, that is to say they are active in the daytime. As with most other diurnal animals, human activity-rest patterns are endogenously controlled by biological clocks with a circadian (~24-hour) period.
- Normal variation in chronotype encompasses sleep–wake cycles that are from about two hours earlier to about two hours later than average. Extremes outside of this range can cause a person difficulty in participating in normal work, school, and social activities. If a person’s “lark” or (more commonly) “owl” tendencies are strong and intractable to the point of disallowing normal participation in society, the person is considered to have a circadian rhythm sleep disorder.
Clocks
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