Circadian Rhythms

An Independent Project by Monika Nemcova ’19

Part 4 of 4

Circadian Rhythms

This is the final blog post on my series about sleep. Last time, I wrote about the relationship between sleep and learning. Today, I would like to focus on why do we, as mammals, tend to become sleepy at roughly the same time every day. So, what makes us want to go to sleep? And what keeps us awake during the day?

The intricate system in charge of our sleep-and-wake patterns comprises of two so-called drives, homeostatic and circadian. The drives (sets of processes promoting an action) act in opposition [1], balancing each other – in the same way as the two conflicting forces, the gravitational and the centrifugal, balance the Earth on its orbit. However, unlike the forces affecting the Earth, the homeostatic and circadian drives change in size throughout the day – which allows us to transition between sleep and wakefulness.

Homeostatic drive

Homeostatic are any processes that organisms use to maintain stable conditions in their bodies. Homeostatic processes, for example, keep the blood levels of oxygen and sugar stable or maintain the optimal body temperature. Our bodies naturally strive to keep the inner conditions consistent and if an unusual spike in any chemical occurs, there are mechanisms that return said chemical on its normal level [2].

But how does that concern our sleep? Enter adenosine, the neurotransmitter I already wrote about in my second blog post (quick reminder: it makes us sleepy and caffeine functions by blocking it). Adenosine, alongside with other chemicals, builds up in the brain as we are awake – the longer we stay awake the more adenosine there is and, in turn, the sleepier we are. As you can see in Fig. 1, when adenosine levels reach a certain point, we feel sleepy enough to go to bed. During sleep (shown as the purple field), the adenosine levels get flushed out of the brain. That is why it is called the homeostatic drive – when there is too much adenosine, the body employs mechanisms to get rid of the chemical [1].

In addition, adenosine build-up explains how does sleep debt work. In the picture, you can see that after a night full of sleep, the adenosine levels are fairly low. But what happens when we do not allow ourselves enough time in the bed to get rid of all of the adenosine? Well, it just stays in the brain – and as the day progresses, the build-up starts at the levels left there from the previous night, not zero. That is the reason why we feel so horribly tired the day following insufficient sleep or even an all-nighter. Longer time in the bed effectively erases the sleep debt by decreasing the adenosine levels. Nevertheless, if we, once more, do not sleep enough, the morning baseline amount of adenosine increases again. That continues until the body cannot put up with the adenosine levels anymore. Then it just forces us to sleep [1] – and that is all the missed first periods and slept-through films, classed or ASM.

Picture1
Fig. 1 Homeostatic and Circadian Drives (https://www.coursera.org/learn/sleep/lecture/TWyO7/11-02-sleep-occurs-as-a-circadian-rhythm)

Circadian drive

However, if sleep was determined only by the homeostatic drive, the time when we go to sleep and wake up would not matter. Yet very few of us thrive in a regime with a supposed activity peak around 4 a. m. and time for sleep around midday. Why do we naturally tend to sleep during the night and be awake during the day? And how does the brain regulate it?

The answer lies in the second cycle that drives sleep and wakefulness – the circadian rhythm. “Circadian” comes from the Latin words for “around” and “day”, so it won’t come as a big surprise that the circadian rhythm acts as an inner clock for many species, from plants and bacteria to animals. So while the homeostatic drive tells us that we are sleepy when we stayed up for late, the circadian rhythm tells that is is time to go to bed because it is past midnight [3]. The fact that we have inbuilt time makers that go beyond detecting the outward cues (such as the amount of sunlight outside) has been experimentally proven. A group of volunteers was left to live in total darkness for several weeks and their sleep-wake cycle still exhibited periodicity. However, without the outward visual clues, the average length of “one day” (period of wakefulness followed by a period of sleep) was about 25 hours. As a result of that, the volunteers went to sleep about one hour later every day – so after 6 days the difference between the time outside and their inner clock was the same as between the East Coast and Europe [1]. In normal conditions, the human inner clock synchronizes itself daily with environmental clues. This agility marks the second important characteristics of the circadian rhythm: it can adapt to various outward signal. That is what happens when we travel to a country in a different time zone – the inner clock slowly shifts so that the perceived clues match the intrinsic signals. Another peculiar thing our inner clock can do is to change the ratio of “night” and “day” – in the past, people in the Northern Hemisphere slept more during the long winter nights and less in summer. And last but not least, even the length of the circadian period can change. I already talked about the shift from the natural 25 hours period to the 24 hours period we exhibit normally, but, in fact, human beings can be entrained to accept anything between 23 to 25 hours as the length of a “day.” [1] Interestingly, a day on Mars lasts 25 hours [4], so at least our internal clock wouldn’t pose a barrier for possible future colonization of the red planet. I have never realized how important that is – it would be very inconvenient and unhealthy for the first colonists to cycle out of rhythm with the outward cues.

So, returning to the Fig. 1, circadian rhythm prompts our brain to go to sleep roughly around the same time every day. In mammals, the center for keeping track of the circadian rhythms is called the suprachiasmatic nucleus (SCN) [3]. But keeping track of time is not something impressive in the terms of our body – experiments showed that a wide array of cells are able to do that, from the cells of lungs and liver to the ones of skin. What is truly unique about SCN is its position next to the ending of the optical nerves. SCN’s timekeeping system is the only one in the body that can actively respond to visual cues and thus synchronize the inner time with the perceived outward time [3].

In addition, SCN helps to maintain a healthy sleep-wake cycle in other way: by initiating the circadian drive. I started talking about the circadian drive as the opposing force to the homeostatic drive but then went on about the circadian rhythm. It was necessary to understand the periodicity of the process but now I can finally explain how exactly does the circadian drive influence wakefulness. The circadian drive allows us to have a single period of consolidated wakefulness [1]. It is basically a signal from SCN to neurons that release wakefulness-promoting neurotransmitters, such as monoamines or acetylcholine [3]. If we did not have the circadian drive, we would be able to remain awake only for a few hours – after that the homeostatic drive would force us to go to sleep. After short rest, we would wake, be active for a while, and had a need to go to sleep again [1]. One can surely imagine that hunting, foraging or any other complicated activity would be severely hindered by that. So the circadian drive, which acts as the opposing force promoting wakefulness, is very important for the success of human or and many other bigger species. As you can see in Fig. 2, even though the upper arrows symbolizing adenosine levels increase as the day progresses, the wakefulness levels (the blue line) remains constant. That is because the circadian drive (lower arrows) gradually increases as well. In the evening, the circadian drive decreases but the homeostatic drive stays strong – as a result, we become tired and fall asleep. In the morning, the situation is reversed – the adenosine levels have decreased and the circadian drive, timed by the circadian rhythm in SCN, wakes us up [1].

Fig. 2 Intrinsic factors influencing the sleep-wake cycle
Fig. 2 Intrinsic factors influencing the sleep-wake cycle (https://cdn.mednet.co.il/2015/12/0950_%D7%92%D7%91%D7%A2%D7%AA%D7%99.pdf)

I hope that you have found the mechanism of the sleep-wake cycle as fascinating as I have.

References

[1] Lee, T. (n.d.). Sleep occurs as a circadian rhythm [Video file]. Retrieved from https://www.coursera.org/learn/sleep/lecture/TWyO7/11-02-sleep-occurs-as-a-circadian-rhythm

[2] Rodolfo, K. (2000, January 3). What is homeostasis? Scientific American. Retrieved from https://www.scientificamerican.com/article/what-is-homeostasis/

[3] Wright, K. P., Lowry, C. A., & LeBourgeois, M. K. (2012). Circadian and wakefulness-sleep modulation of cognition in humans. Frontiers in Molecular Neuroscience, 5(50). https://doi.org/10.3389/fnmol.2012.00050

[4] Mars Facts [Fact sheet]. (n.d.). Retrieved May 8, 2019, from Mars Exploration website: https://mars.nasa.gov/allaboutmars/facts/#?c=inspace&s=distance

 

Author: pascienceblog

Administrative Assistant, Division of Natural Sciences

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