![]() ![]() March 4, 2025 |
PSY 340 Brain and Behavior Class 20: Rhythms of Waking and Sleeping |
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Chronobiology = how time and seasons affect the biological functioning of living organisms
Consider what the rhythms of your life are like in this time of your life.
- What time do you usually go to bed?
- What is sleep like for you? Do you toss & turn? Awaken at night? Dream?
- What time do you usually get up?
- How do you feel when you get up?
- What time of day are you usually the most awake & alert?
- What time of day are you usually the least alert & able to concentrate?
- What season of the year do you like the most? Why?
A. Endogenous Rhythms
What rhythms (or cycles) do you experience?
- Each year = circannual (circum = "about" + annus = "year)
- Each month = circamensual (circum = "about" + mensis = "month")
- Each day = circadian (circum = "about" + dies = "day")
Circadian rhythms are patterns of biological activities and responsiveness that occur on a recurring 24-hour cycle as described in the next section.
Are there any other ways in which you are affected by the change of seasons or time of the year?
- If changes happen because of mechanisms in the body = endogenous ("born from within")
- If changes happen because of mechanisms outside the body = exogenous ("born from outside")
B. Setting & Resetting the "Biological Clock"
- The brain itself generates its own rhythms of change [= biological clock] which is quite steady and not subject to many outside influences. That time is about 24 hours long. See below some of the general rhythms of our biological clock
Multiple systems in the body follow a circadian cycle as shown above.
- Research reported in 2013 noted that the genes in epidermal stem cells (in our skin) follow distinctive patterns to protect their DNA during periods of peak ultraviolet radiation during the day and replace old/worn-out cells during the night.
- Similarly, cells in the liver follow a circadian rhythm of activity/metabolism (Xi & Chen, 2014) which may be disrupted by age and lead to various physical disorders.
Zeitgeber ("time giver" or "synchronizer" in German) = (1) daily environmental signals or stimuli that reset the circadian rhythm or (2) seasonal environmental signals that set the circannual rhythm (e.g., migration, mating, hibernation) of an animal. This process of resetting the biological clock of an animal is known as "entrainment"
- Light plays a critical role in setting/resetting the biological clock of land animals, especially humans (Rouyer et al, 2015). Note that we know much more about the role of light than temperature in the biological clock.
- In humans, fluctuations in the body's internal temperature is normally regulated by the suprachiasmatic nucleus (SCN, see below). Multiple cells in the body, in turn, respond to these fluctuations with increased or decreased levels of activity.
- Tides may serve as a zeitgeber for marine animals.
- Other though less-important stimuli are noise, activity level (exercise), and environmental/ambient temperature. In humans, light seems to be more important although since most people live in reasonably warm, insulated, and comfortable housing in the modern world, other zeitgebers may now be less important than they were before the Industrial Revolution.
- Recent research points to food as another zeitgeber regarding feeding and metabolism and affects the circadian rhythm of the liver in particular. "Because peripheral tissues communicate back to the brain via ghrelin, leptin, glucose, insulin, etc., circadian feeding contributes to an intertwining of the clock and metabolism that appears to be crucial for metabolic homeostasis" (Eckel-Mahan & Sassone-Corsi, 2013)
Jet Lag = disruption of circadian rhythms due to travel across time zones
Jet lag often leads to stress and elevates levels of the hormone cortisol. Prolonged exposure to cortisol harms memory and undermines the body's immune system.
- If you want to stay awake, keep light bright or exercise
- If you want to go to sleep, keep room dark & quiet & do not exercise
- Most people find it easier to travel from east to west across time zones rather than west to east.
Shift Work
- Individuals whose job requires frequent changes in sleep times may frequently have trouble sleeping in the afternoon or early evening.
- Night workers may not experience enough bright light at work to reliably shift their biological clock. Artificial light at work is often not strong enough to do the job. Such workers ought to sleep in very dark rooms during the day and have very bright lights at work.
- Shift workers, especially those at night, appear to have greater accident levels than day workers.
Jet Lag & shift work may be causing obesity and other metabolic problems by disrupting the daily rhythms of gut microbe (not in book)
- Research has identified a distinctive relationship between the microbes in our intestines ("microbiome") and their response to changes in human circadian rhythms.
- For example, Thaiss et al (2014) point to the daily rhythm of the microbiome as crucial in maintaining a balance in the metabolic system (how food is processed, used, stored, etc. in the body). By impairing or altering the usual circadian clock, the microbiome tends to lose its rhythmicity and this may lead toward both obesity and Type-II diabetes.
"Social Jet Lag"
- “Social jetlag (SJL), the difference in sleep timing between work and free days is a consequence of the discrepancy between the individual’s circadian rhythm and the social clock. SJL is considered a chronic stress factor and has been linked to various health problems" (Sűdy et al., 2019, p. 1)
- Many people must be at work or at school at a certain time before their body’s circadian rhythm is attuned to the demands of the office or classroom. On days in which people do not HAVE to go to work or school, they tend to get more sleep (see graphic showing this pattern in a sample of Europeans).
Two Forms of Human Circadian Rhythms = "Chronotypes"
There are significantly different patterns of how individuals experience their circadian rhythms. Most people fall somewhere between these two chronotypes ("chronos" in Greek means "time):
- Early rising are "morning people" or "larks": as day progresses they tend to become less productive
- Tend generally to report being happier than "owls".
- Late rising are "evening people" or "owls": they take time to reach their peak in the late afternoon or evening
- Among teenagers, strong evening people tend to get lower grades because they often must be in school earlier than their circadian rhythm would prefer (see diagram.) There tends to be a higher level of alcohol use, overeating, and engagement in other risky behaviors by these "owls" as adolescents.
Sleeping patterns change with age with infants and children going to bed early and waking early However, adolescents tend to go to bed later and to wake up later (if they are free to do so). This pattern tends to change around age 20 and to reverse.
In contemporary society, the time we MUST get up for work, school, etc. is often different and much shorter than the time our bodies would like to get up. The difference between these times has recently been termed "social jetlag" and may be associated with the same physical problems mentioned earlier: obesity, etc.
C. Mechanisms of the Biological Clock
1. Superchiasmatic Nucleus (SCN)
- Main control for internal body temperature and sleep resides in the superchiasmatic nucleus (SCN) of the hypothalamus (located just above the optic chiasm; Buhr et al. 2010)
- Cells of the SCN depend upon a genetically-based control system to follow a 24-hour cycle. Individual cells of the SCN by themselves will do so.
- Light hits special retinal ganglion cells which use a different photopigment (melanopsin) than the regular photopigments in the the rods & cones. They are found mostly in the retina near the nose. The photopigments in these cells are maximally sensitive to light of ca. 460-480 nm wavelengths, that is, violet to blue.
- These melanopsin ganglion (M-G) cells (usually called intrinsically-photosensitive Retinal Ganglion Cells or ipRGCs) transmit information about ambient light along the retinohypothalamic tract to the SCN. The M-G cells/ipRGCs appear not to be sensitive to rapid or small changes in light, but to the average or overall light level which changes very gradually, for example, at dawn or dusk. The M-G cells/ipRGCs do not now appear to be related to the parvo-, magno-, or koniocellular ganglion pathways, but communicate directly to the SCN.
- The SCN sends a signal (via a very complicated route) which ends up at the pineal gland. This gland secretes melatonin (see below).
- Note that this can create significant difficulty for people who have total blindness, but for others there are enough M-G cells/ipRGCs that there is no disruption of their circadian rhythms. The difficulty is called Non-24 Hour Sleep-Wake Disorder
2. The Biochemistry of the Circadian Rhythm
- The circuitry by which the circadian rhythm is biochemically maintained is quite complex, e.g.,
- In Drosophila (fruit flies) they include genes which produce 2 proteins (called the PER [= period]) and TIM [= timeless] proteins) that interact with a third protein (CLOCK) to cause sleepiness in these insects. At the beginning of the day, the levels of PER and TIM are low but gradually increase. There is a feedback loop which causes the genes producing PER and TIM to slow down as the concentrations increase until the production stops.
- In humans the pattern is quite similar though the genes involved produce the proteins including hTIM (human TIMELESS), CLOCK, PER1, PER2, PER3, & BMAL (brain muscle ARNT-like protein).The diagram on the left shows the circadian rhythm of Per-Tim-CLOCK.
- Since light tends to stop TIM production and even break down TIM, bright lights at night stop TIM and we do not feel as sleepy as we should.
- Additionally, all of these interactions appear to involve not only a "feed forward" influence (light->SCN->pineal gland), but also negative feedback loops as well. The overall system is finely attuned both to the onset of light in the morning and the decrease of light with the coming of nighttime/darkness.
- A human PER genetic mutation is associated with getting sleepy earlier in the evening & awakening earlier than normal in the morning. Circadian rhythm for such people is less than 24 hours.
3. M
elatonin (https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know)
- The SCN controls the activity level of the pineal gland (an endocrine [hormone-releasing] gland) in the posterior of the thalamus.
- The pineal gland releases melatonin, a hormone that increases sleepiness. In humans, pineal gland begins to secrete melatonin at night about 1-3 hours before we normally go to bed although the highest amount of melatonin is actually secreted in the middle of the night.
- Melatonin pills (one moderate dose of 0.5 mg) in the afternoon tends to reset the biological clock by advancing it, i.e., person sleeps earlier and wakes up earlier the next morning.
- Sleep medical advice generally says that the "short term" use of melatonin (1-2 months) is reasonably safe for problems with sleep (it should not be used in chronic insomnia).
- Meta-analytic study of multiple research findings (Fetemeh et al. (2022)) concludes that melatonin may be
- particularly helpful in adults with respiratory, metabolic, and sleep disorders.
- but shows little effect in adults who are coping with mental disorders, neurodegenerative diseases, other diseases such as breast cancer, migraine, patients under methadone maintenance treatment, alcohol use disorder, cirrhosis, IBS (irritable bowel syndrome), or brain injury.
- High doses of melatonin are problematic:
- In rats, they cause a Parkinsonian-like movement disorder, lowers reproductive fertility, and harms developing fetus.
- No government agency in the US regulates production of melatonin & quality may be questionable (in Europe, you need a prescription for melatonin). Indeed, in a 2017 study of 31 brands of melatonin supplements (ranging in doses from 1 to 10 mg), researchers found that the actual amount of melatonin in the supplement varied between −83% to +478% of the labelled content. Furthermore, in 8 of the 31 samples, an identifiable level of serotonin (5-HT) was found in the supplement (Erlend & Saxena, 2017)
- Many over-the-counter melatonin capsules contain very high single doses, e.g., 3-5-10 mg. (10 or more times the normal level in humans)
References
Buhr, E. D., Yoo, S.-H., & Takahasi, J. S. (2010). Temperature as a universal resetting cue for mammalian circadian oscillators. Science, 330, 376-385. https://doi.org/10.1126/science.1195262
Eckel-Mahan, K., & Sassone-Corsi, P. (2013). Metabolism and the circadian clock converge. Physiological Reviews, 93(1), 107-135. https://doi.org/10.1152/physrev.00016.2012
Erland, L. A., & Saxena, P. K. (2017) Melatonin natural health products and supplements: Presence of serotonin and significant variability of melatonin content. Journal of Clinical Sleep Medicine, 13(2), 275-281. https://doi.org/10.5664/jcsm.6462
Fatemeh, G. Sajjad, M., Niloufar, R., Neda, S., Leila, S., & Khadijeh, M. (2022). Effect of melatonin supplementation on sleep quality: A systematic review and meta‑analysis of randomized controlled trials. Journal of Neurology, 269, 205-215. https://doi.org/10.1007/s00415-020-10381-w
Foster, R. G., Peirson, S. N., Wulff, K., Winnebeck, Vetter, C., & Roenneberg, T. (2013). Sleep and circadian rhythm disruption in social jetlag and mental illness. Progress in Molecular Biology and Translational Science, 119, 325-346. https://doi.org/10.1016/B978-0-12-396971-2.00011-7
Gooley, J. J., Lu, J., Chou, T. C., Scammell, T. E., & Saper, C. B. (2001). Melanopsin in cells of origin of the retinohypothalamic tract. Nature Neuroscience, 4(12), 1165. Abstract retrieved 3/2/05 from the Web site: http://www.nature.com/cgi-taf/DynaPage.taf?file=/neuro/journal/v4/n12/abs/nn768.html&dynoptions=doi1109910898
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NIMH (2007, May 4). Cell networking keeps brain's master clock ticking. National Institutes of Mental Health. Retrieved 3/13/08 from http://www.nimh.nih.gov/science-news/2007/cell-networking-keeps-brains-master-clock-ticking.shtml
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Rouyer, F., & Chatterjee, A. (2015). A receptor for subtle temperature changes. Nature, 527, 449-450. https://doi.org/10.1038/nature16316
Sűdy, A. K., Ella, K., Bódizs, R., & Káldi, K. (2019). Association of social jetlag with sleep quality and autonomic cardiac control during sleep in young healthy men. Frontiers in Neuroscience. https://dx.doi.org/10.3389/fnins.2019.00950
Thaiss, C. A., Zeevi, D., Levy, M., Zilberman-Schapira, G., Suez, J., Tengeler, A. C., ... & Kuperman, Y. (2014). Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell, 159(3), 514-529. https://doi.org/10.1016/j.cell.2014.09.048
Xi, Y., & Chen, D. (2014). Partitioning the circadian clock. Science, 345(6201), 1122-1123. https://doi.org/10.1126/science.1259601
The first version of this page was posted on March 2, 2005.