When the sun rises, melatonin secretion is inhibited, and the brain's awake circuits resume. Because circadian rhythms are expressed in many physiologic and neurobehavioral variables, the phase of the pacemaker can be ascertained by using any of these variables as a marker. In humans, the core body temperature rhythm has often been a preferred marker of circadian phase because it can provide an accurate representation of the underlying pacemaker's characteristics under certain conditions. Figure 31-5 . The phase response curve to a stimulus of three consecutive daily 5-hour pulses of bright light, centered on the subjective day.
Circadian rhythms are physical, mental and behavioral changes that follow a roughly 24-hour cycle, responding primarily to light and darkness in an organism’s environment. In circadian biology, the phase response curve is used to characterize the synchronizing effects of light on a circadian pacemaker.1 3 23 60 90 To construct a phase response curve,16 discrete light stimuli are applied systematically over the entire circadian cycle; the magnitudes of the light-induced phase shifts are then plotted as a function of circadian phase at which the organism is exposed to the stimuli. In human experiments, the constant routine has been used to estimate both the initial circadian phase of the pacemaker prior to a stimulus and then the final poststimulus circadian phase.
Melatonin-suppression test in a healthy sighted subject (upper panel) and a blind patient (lower panel). In each, plasma melatonin (upper traces) and temperature (lower traces) were measured repeatedly during a constant routine (hatched bar) and subsequent episode(s) of sleep (solid bars).
Experiments in fruit flies (which may seem a far cry from humans, but actually serve as excellent models in biological clock studies) show that degeneration in the brain occurs much more rapidly when there are problems in the functioning of a key clock gene, and the lifespans of the flies are significantly shortened. Knowing more about how the clock is related to cognitive function and decline could help experts predict -- and perhaps one day prevent -- it from occurring in humans as well. The same genes that control the receptors for the sleep hormone melatonin are involved in insulin release, which could also play a role in diabetes risk. When melatonin receptor genes have mutations that damage the connection between the biological clock and insulin release people have a significantly higher risk of developing diabetes. Some of the best knowledge we have about the roles the biological clock plays in our health come from instances in which the cycle gets out of sync.
Only five inbred strains are known to produce a high-amplitude melatonin rhythm (Table 2.12.4 ). It should be pointed out that in C57BL/6 a small but significant short peak in pineal melatonin has been reported, despite the mutation in the AANAT [84–86] . Unlike other rodents and humans, mice do not excrete metabolized melatonin in the urine as 6-sulphatoxymelatonin.
Only the neurons of the SCN core receive the direct light information via the RHT [40, 55, 56] . The excitatory amino acid glutamate is the primary neurotransmitter at the synapses of the RHT [60, 61] . It is released together with the neuromodulators substance P (SP) and pituitary adenylyl cyclase activating peptide (PACAP) whereby NMDA receptors are activated, causing an influx of Ca2+, activation of MAP-kinases, and consequently the phosphorylation of cAMP-response-element-binding protein (CREB) [62, 63] .
One possible explanation might invoke principles of associative learning. If the bed represents a place for socializing, studying, eating, and so on, then it is possible that it will become a place that elicits higher levels of arousal, which would make falling asleep at the appropriate time more difficult. Answers could also consider self-perpetuating cycle referred to when describing insomnia. If an individual is having trouble falling asleep and that generates anxiety, it might make sense to remove him from the context where sleep would normally take place to try to avoid anxiety being associated with that context.
Initial phase is the number of hours after the fitted minimum of the endogenous core body temperature rhythm at which the center of the light stimulus occurred. Phase shift is the difference between the time of the pre- and post-stimulus temperature minima. A regression line has been fitted to the data points. The phase relationship between sleep and CBT rhythms at sleep onset is an important determinant of subsequent sleep latency, amount and quality. This has been most convincingly demonstrated in human subjects undergoing internal- or forced desynchronization in environments without time cues.
2. Different species have different evolutionary histories, and they have adapted to their environments in different ways.
Circadian rhythms are perhaps most famously implicated in jet lag, when passing through multiple time zones offsets your body's clock from that of your wristwatch. "Losing" or "gaining" time during air travel can leave your body feeling disoriented, especially if it is expecting daylight when it is actually dark, or vice versa. Eventually your body is able to adjust its circadian rhythms to the new environment.
When we are very young, we spend up to 16 hours a day sleeping. As we grow older, we sleep less. In fact, a meta-analysis , which is a study that combines the results of many related studies, conducted within the last decade indicates that by the time we are 65 years old, we average fewer than 7 hours of sleep per day (Ohayon, Carskadon, Guilleminault, & Vitiello, 2004). As the amount of time we sleep varies over our lifespan, presumably the sleep debt would adjust accordingly. Watch this brief video describing circadian rhythms and how they affect sleep.
The relationship between body rhythms and mood is an intricate one, and likely has to do with how the brain chemical serotoninfluctuates in relation to the light-dark cycle and throughout the year as the days become longer and shorter. Mice bred to have problems with serotonin function also have seriously altered daily rhythms. People's serotonin levels increase during the part of the day when there is more light available.
In other words, they maintain circadian periodicity over a range of physiological temperatures. Many organisms live at a broad range of temperatures, and differences in thermal energy will affect the kinetics of all molecular processes in their cell(s).
If people go extended periods of time without sleep, they will accrue a sleep debt and potentially experience a number of adverse psychological and physiological consequences. A biological clock is only of any use if internal clock time is adjusted to environmental time. The classic example of a mismatch between biological and environmental time is “jet lag.” In the natural environment, many factors could set or entrain circadian rhythms to a specific phase of the 24-h rotation of the earth.
The rhythm can be reset by exposure to external stimuli (such as light and heat), a process called entrainment. The external stimulus used to entrain a rhythm is called the Zeitgeber, or "time giver".
Perhaps humans would be most vulnerable to threats during the evening hours when light levels are low. Therefore, it might make sense to be in shelter during this time. Rodents, on the other hand, are faced with a number of predatory threats, so perhaps being active at night minimizes the risk from predators such as birds that use their visual senses to locate prey. It’s important to remember that your biological rhythms are intended to protect you. They signal when it’s time to rest.
Melatonin is also thought to feed back to the neurons of the SCN where melatonin receptors are located [77–80] . This feedback probably can fine-tune the circadian output signal from the SCN  . However, most of the commonly used inbred mouse strains are unable to synthesize melatonin in the pineal gland due to malfunctions (mutations) in either arylalkylamine-N-acetyltransferase (AANAT) or hydroxyindole-O-methyltransferase (HIOMT), the two enzymes involved in melatonin synthesis from serotonin [82–84] .
For instance, exposure to sunlight, drugs, and caffeine can affect sleep schedules. The circadian clock plays a physical, mental, and behavioral role that responds to light and dark. There are many other reasons our bodies' clocks can go out of sync, which probably involve a combination of genetic predisposition and lifestyle choices, such as alcohol consumption.
In a nocturnal species, activity onset was considered to indicate the beginning of the night and was designated circadian time (CT) 12 (the subjective night would span CT 12–24), whereas in a diurnal species the start of activity was considered to signal dawn and was designated CT 0 (the subjective day would span CT 0–12). Pittendrigh observed that light pulses given to free-running animals during their subjective day would have no marked effect on the clock, whereas light during the first half of the subjective night (CT 12–18) would phase delay the clock—the animal would start activity later the next day.
In humans, activity and feeding generally occur during the light period ( Roenneberg et al., 2012 ). However, in the present 24-h society, the synchrony between these rhythms is easily disturbed.
The superior cervical ganglia finally send postganglionic sympathetic fibres back into the brain as the nervi conarii which innervate the mammalian pineal gland. Noradrenalin is released only during darkness of the night at the synapses of these nerve endings, binds to β-adrenergic receptors, and activates the synthesis of melatonin. Melatonin is considered the ‘chemical expression of darkness’  because light acutely inhibits melatonin synthesis and the duration of the nightly melatonin peak correlates with the duration of the dark phase [75, 76] . Melatonin released from the pineal gland at night is thought to be distributed throughout the body and binds to those brain areas and peripheral organs that are equipped with melatonin receptors, thereby informing the body of the time of day, or rather, time of night  .
Since the biological clock is, in fact, a biological entity, things can go wrong with it that may have less to do with lifestyle or the environment, and more to do with the mechanisms of the clock itself. For example, there's more to the clock-diabetes link than just turning our sleep cycle around, though sleep can make a difference.
He explored the effects of short pulses of light on free-running rhythms in a variety of animals, including Drosophila, maintained in constant darkness. He showed that light had different effects on the clock at different phases of the circadian cycle. As the animals were kept under constant darkness, he used the phase of activity of the animal to determine the position of the clock.
It can also help to get into bright light as soon as possible in the morning. During slow-wave sleep, there is a significant decline in cerebral metabolic rate and cerebral blood flow. The activity falls to about 75 percent of the normal wakefulness level. The regions of the brain that are most active when awake have the highest level of delta waves during slow-wave sleep. This indicates rest is geographical.