Vol. 2, # 43
November 5, 2005

Q: What is the circadian rhythm (system) and what does it do? - Layperson

A: Circadian rhythm is the name given to the roughly 24 hour cycles shown by physiological processes in plants and animals. (The term circadian comes from the Latin circa, meaning "around" and dies, "day", meaning literally, "around a day.") It was initially discovered in the movement of plant leaves in the 1700s by the French scientist Jean-Jacques d'Ortous de Mairan.

The circadian rhythm is neither fully dependent on nor fully independent of external cues such as sunlight and temperature. Early researchers identified that some sort of "internal" rhythm must exist, because plants and animals did not react immediately to artificially-induced changes in daily rhythms. However it has been well established that a mechanism for adjustment also exists, as plants and animals will eventually adjust their internal clock to a new pattern (if it is sufficiently regular).

Circadian rhythms are important in determining the sleeping and feeding patterns of all animals, including humans. There are clear patterns of brain wave activity, hormone production, cell regeneration and other biological activities linked to this 24 hour cycle.

The circadian rhythm is linked to the light/dark cycle. Animals kept in total darkness for extended periods eventually function with a "free running" rhythm. Each "day" their sleep cycle is pushed back- or forward (depending whether they are nocturnal or diurnal animals) by approximately one hour. The human free-running circadian rhythm is close to 25 hours - cues from our environment help keep us on a 24 hour track. Free running organisms still have a consolidated sleep/wake cycle when in environment shielded from external cues, but the rhythm is not entrained and may become out of phase with other circadian, or ultradian rhythms (e.g. temperature and digestion). This research has influenced the design of spacecraft environments, as systems that mimic the light/dark cycle have been found to be highly beneficial to astronauts.

The circadian "clock" in mammals is located in the suprachiasmatic nucleus (SCN), a distinct group of cells located in the hypothalamus. Destruction of the SCN results in the complete absence of a regular sleep/wake rhythm. Contributing to this clock are light receptors found in the retina which have a pathway, (called the retinohypothalamic tract), leading to the SCN. Interestingly, if cells from the SCN are removed and cultured, they will maintain their own rhythm in the absence of external cues.

Sleep is controlled by neurotransmitters, which act on neurons in the brainstem and in the spinal cord. Signals produced by the SCN travel to different regions of the brain. It regulates other functions associated with the sleep cycle such as body temperature, hormone secretion, urine production, and changes in blood pressure. The sleep/wake cycle in humans is dependent on light and temperature. A change in these could shift or disrupt the cycle. External factors that affect the circadian rhythm are called zeitgebers. These could be anything from an alarm clock to meal times.

There are many health problems associated with a disturbance in the sleep circadian rhythm. These can be temporary or due to a lack in the circadian rhythm in the body. These include Seasonal Affective Disorder (SAD) where the rhythm is disturbed due to the change in length of day, delayed sleep phase syndrome (DSPS) which is caused by a circadian rhythm abnormality causing the sufferers body to want to sleep later than normal. More temporary problems include jet lag and problems caused to those working late shifts.

Melatonin is an internal factor affecting the circadian clock. Melatonin is produced by the pineal gland and it has a day/night function. It peaks during darkness and lowers during the day. Melatonin has been shown to shift biological rhythms. There is a correlation with the circadian rhythm so melatonin can be used to shift the rhythm in terms of therapeutic measures. This not only includes human health problems but other cycles such as in sheep to control breeding cycles.

Circadian rhythms seem to fit the profile of brain equals behavior when looked at through the human perspective. The brain takes in inputs along with signals it creates to create an output. What is left unexplained can be seen when thinking backwards. Are circadian rhythms controlled by the brain if organisms without brains posses them? Cyanobacteria lack brains but still respond to circadian rhythms. Aside from cyanobacteria it can be said that plants have a circadian clock which controls photosynthesis and flowering. If this is true what part of the rhythm is controlled by the brain. Could it be that the basic function of circadian rhythms lacks the need of a brain, which is used for only higher functions of rhythms? If this is so where do the rhythms come from.

It appears that the SCN takes the information on day length from the retina, interprets it, and passes it on to the pineal gland (a pea-like structure found on the epithalamus), which then secretes the hormone melatonin in response. Secretion of melatonin peaks at night and ebbs during the day. The SCN does not appear to be able to react rapidly to changes in the light/dark cues.

Recently, evidence has emerged that circadian rhythms are found in many cells in the body--outside of the SCN "master clock." Liver cells, for example, appear to respond to feeding rather than light. Cells from many parts of the body appear to have "free-running" rhythms.

Disruption to rhythms usually have a negative effect in the short term. Many travelers have experienced the condition known as jet lag, with its associated symptoms of fatigue, disorientation and insomnia. A number of other sleep disorders are associated with irregular or pathological functioning of the circadian rhythms.

Scientists have long known that light plays an important role in regulating the human body's daily biological rhythms ”also known as circadian rhythms” including the sleep-wake cycle, alertness, and hormone production. At night and under conditions of darkness, the pineal gland produces melatonin, a hormone closely related to the body's master clock. Using techniques from visual psychophysics, LRC researchers are gaining a better understanding of the mechanisms that convert light into neural signals in the human circadian system. A recently published LRC study is the first to show evidence of a "color" mechanism in the circadian system that controls melatonin suppression when humans are exposed to light.

Normally, melatonin levels rise in the evening, remain high for most of the night while we sleep, then drop in the morning as we awaken. In recent years, researchers have learned that bright white light suppresses melatonin. Previous studies have also suggested that melatonin suppression reacts differently to light of varying wavelengths, specifically showing a maximum sensitivity to short-wavelength ("blue") light. Further research has shown that the cones and rods of the eye, which receive and transmit signals about light to the brain and body, get help from a photoactive substance named melanopsin when it comes to melatonin suppression in humans. Melanopsin is found in a subset of retinal ganglion cells.

A recent study published in NeuroReport by LRC researchers, with Professor Robert Parsons of Rensselaer's biology department, shows that 18 lux of blue light from light-emitting diodes is more effective at suppressing melatonin levels than 450 lux of clear mercury white light because a "spectral opponent mechanism" likely contributes to the circadian system's response to light, also known as circadian phototransduction.

"Our preliminary evidence shows that opponency of some kind is involved in the suppression of melatonin by light in humans, making white light found in buildings much less effective at suppressing melatonin than was previously thought," said Dr. Mariana Figueiro, LRC Light and Health researcher.

For color vision, three types of cones (short, middle and long wavelength) process color information in the retina. The visual system separates cone responses into color information processed by two opponent channels, the red vs. green and the blue vs. yellow channels.

In these opponent channels, light in one wavelength region (e.g., blue) increases a neural response, while light in the opposing region (e.g., yellow) decreases it. The right balance of energy in the opposing wavelength regions will result in a null response in that channel, signaling that there is no color, and indeed that there is no light at all.

Though biologists understand how opponency works for color vision, the LRC study is the first to find the existence of spectral opponency in circadian phototransduction. Figueiro explains the concept of opponency for the circadian system: "Similarly, in the case of the circadian system, it seems that a sufficient balance of light in each wavelength region results in a null response by the circadian system, just as if there is no light at all." As part of their study, Figueiro, Parsons, and LRC researchers John Bullough and Mark Rea showed that a spectral opponent mechanism was consistent with their data, as well as with other previously published data on the suppression of melatonin by light in humans.

"In the past, we thought the human circadian system was additive, meaning if a certain amount of blue light and a certain amount of yellow light each produced the same level of melatonin suppression, then half of these amounts of blue and yellow added together would produce the same level of melatonin suppression," said Figueiro. However, this theory is contradicted by study results showing a small amount of blue light producing a stronger suppression than a much greater amount of white light (blue plus yellow), suggesting the existence of spectral opponency in the human circadian system.

"It seems that the circadian system in diurnal (active during the day) humans is preferentially sensitive to blue light, presumably the blue sky," said Mark Rea, LRC director.

These findings show promise for a number of practical applications, including improving sleep quality in patients with Alzheimer's disease, advancing treatments for seasonal affective disorder, and studying effects of light on night-shift workers and premature infants.

In short, various internal and external factors are at play in regulating the circadian rhythm.

The paper, "Preliminary Evidence for Spectral Opponency in the Suppression of Melatonin by Light in Humans" by Figueiro, Bullough, Parsons and Rea, is published in the February 9, 2004 issue (Volume 15, Number 2) of NeuroReport.

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© 2002 Nature's Corner