The science of sleep: Part I

This post is gonna be about a passion of mine. Something I can indulge in anytime, anywhere, for any amount of time. Something I would choose over diamonds and Michelin restaurants. I now realise the punchline of this joke would have been better if the title hasn’t already disclosed that it’s gonna be around sleeping. Oh well.

Sleep, as mysterious as it is necessary, still puzzles scientists -- and they have been researching it for decades (and people have been sleeping for thousands of years). What exactly happens when we sleep? Why do we do it? Can we stop sleeping at all? What happens then? Got you curious enough? Then read on and find out how close we are to answering all of these questions.

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1. Some theoretical background: the what’s and when’s of snoozing

Everyone has heard about REM sleep: either because of its connection to dreams or because of how important it is or just because you liked “Losing My Religion”. But there is more to sleep: it also contains three non-REM stages with different characteristics and functions (and differing probabilities you will be grumpy when woken up during this stage).

Stage 1 sleep (N1) is the drowsy sleep phase when you drift between waking and sleeping. Your muscles are not fully inhibited yet and you can experience the “I’m falling”-sensation, a sudden muscle contraction which is called “myoclonic jerk” (some scientists have assumed it might stem from brains of our primate ancestors making us confuse muscle relaxation with falling from a tree1). Moreover, there is a change in your brain waves, synchronised electrical pulses resulting from tons of neurons communicating with each other (see Fig. 1 for a visualisation of all the possible brain waves). In a waking state your brain produces a lot of brain waves called beta and gamma. Both are rather jerky and high-frequency and are either connected to concentration (beta) or theorized to play a role in creating consciousness (gamma). In this first sleep stage instead of beta and gamma your brain starts showing slower and more synchronized alpha waves (associated with relaxation and peacefulness) and even more slower theta waves (associated with deep relaxation and daydreaming) -- keyword: slowing down. This stage lasts between 1 and 10 minutes. 3, 4

 Fig 1. A short intro into what brain waves happen in your head.

Fig 1. A short intro into what brain waves happen in your head.

Stage 2 sleep (N2): Here, your consciousness has drifted away. Heart rate and breathing slow down, temperature decreases, you prepare to enter the deep sleep and theta waves are still very prominent. This stage together with the previous one comprise what is known as “light sleep”. We spend most of our (around 45% of the night) snoozing time in this stage. Light sleep is the best phase to wake up in as you won’t feel groggy or disoriented but rather refreshed and ready to take on the day.2, 3

Stage 3 sleep (N3): This is when things get serious: the deep sleep stage. It is also called slow-wave-sleep because -- you guessed it -- the brain waves slow down and become larger. Now delta waves, the slowest one your brain can produce, rule the party. You are unresponsive to any outside sounds, hard to wake up and your muscles are completely relaxed. This sleep stage is called restorative as your tissue gets repaired, energy gets restored, your kidneys clean your blood, you get the picture.2, 3 Waking up during a deep sleep phase leads to this state (a scientifically proven fact, no citation needed).

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REM sleep + sleep paralysis: The arguably most intriguing feature of sleep -- dreams -- mostly happen during this stage, being vivid and elaborate. The defining feature is the random and rapid side-to-side eye movements. The purpose of these movements is not completely clarified yet (what in neuroscience is, after all?), but theories include scanning of the scenes we see in our dreams4, 5, 6 and memory formation 7, 8, 9 (we’re gonna talk more about the sleep functions later). Your blood pressure and breathing rate rise to almost the waking level and your brain waves resemble waking state too -- there are even high-concentration beta-waves present!2 Due to all this weird stuff REM sleep has earned the title of “Paradoxical Sleep”. A bit scary but worth knowing is that your muscles become completely paralyzed during this stage -- neurotransmitters called GABA and glycine prevent your muscles from receiving brain signals and protect you from acting out on your dreams and potentially hurting yourself10. So basically we’re just laying there completely paralysed while our eyes uncontrollably dart from side to side. Lovely. Scientists believe that when the transition from and to REM sleep doesn’t go smoothly it may lead to sleep paralysis -- a frightening state when you’re already aware but still can’t move your body 11 . In this limbo between wakefulness and vivid dreams people often report seeing scary stuff which can be mostly categorized as either an incubus (you experience chest pressure and problems breathing which you might perceive to be caused by a demonic entity sitting on your chest), an intruder (you sense an unwanted presence of some fearful creature) or an out-of-body experiences 12 . This might explain a lot of reports of seeing paranormal activity 13 or being abducted by aliens 14 (sorry, Agent Mulder!). Approximately 7,6% of the general population suffers from sleep paralysis, while the rate increases drastically for students, 28% of whom have reported experiencing it. 15
During an average night, you would go through several complete sleep cycles (one cycle lasting ca. 90 minutes) with REM stages getting longer towards morning.

 A short overview of what is going on during the night. As you can see, slow wave sleep dominates the beginning of the night while REM sleep becomes more prominent in the second half of the sleeping period.

A short overview of what is going on during the night. As you can see, slow wave sleep dominates the beginning of the night while REM sleep becomes more prominent in the second half of the sleeping period.

2. How does your brain fall asleep?

It is impossible to pinpoint the exact moment of falling asleep. One moment you are still going through all the dumb stuff you did five years ago and another moment you’re already drifting away towards the second sleep stage. So what happens in your brain when you fall asleep?

There is a tiny thing deep in your brain called suprachiasmatic nucleus (SCN) which is the mastermind behind our 24-hour sleep-wake cycle. Directly from your eyes it receives information about how much light exposure you’re getting. It uses this information to reset your internal clock to correspond to the normal day-night cycle. In turn, the internal clock accordingly regulates multiple bodily functions, such as temperature, hormone release and, interestingly for us, sleep and wakefulness 16 . Interestingly, even in a complete absence of light, our internal clock still functions in a roughly 24-hour rhythmus. 17, 18 It has been found that it is due to a cyclical activity of certain genes (fittingly called “clock genes”) 19 . These genes produce different levels of various "clock proteins" depending on the time of the day -- and these proteins then regulate your daily rhytmus (such as what your body tempreture is, how much melatonin is secreted, how alert you are etc etc).
SCN is intricately connected to the -- prepare for another long name -- ventrolateral preoptic nucleus (VLPO) 20 -- a structure which is active during sleep 21 . These connections are thought to activate VLPO and thus to promote the onset of sleep -- ‘cause when VLPO neurons are activated, they release inhibitory chemicals (called GABA and galanin) which, in turn, suppress our arousal system. So through a long chain of command a switch is turned and your arousal slowly goes to zero. VLPO neurons can also be activated by a chemical called adenosine. Adenosine builds up during the day after glycogen, the body’s principal store of energy, breaks down, and after enough of it has accumulated it starts to promote tiredness and nudge you towards a more restful state. 22, 23 This is called a homeostatic regulation as the brain strives to balance out the tiredness that builds up with some rest.

 A short overview of the chain of command. From https://www.medscape.org/viewarticle/703161_2

A short overview of the chain of command. From https://www.medscape.org/viewarticle/703161_2

Another sleep related chemical is the one you will see as a supplement in a supermarket: melatonin. It is produced by the pineal gland and its production, as so many other things, is regulated by our circadian clock. When the sun goes down, SCN commands the pineal gland to start producing melatonin (whose levels are barely detectable during the day) which is then released into your bloodstream and induces sleep. Recently, scientists have been warning us against using smartphones, TVs and other kinds of light-emitting devices before bad as it is supposed to mess with our melatonin levels. The light from our electronic devices has a much higher concentration of blue light than the natural light does, and this treacherous blue light suppresses the melatonin production more than any other wavelength 24, 25 . This throws off the sleep-wake cycle and can lead to a poorer quantity and quality of sleep as the brain is confused about what time of the day it is right now. So do yourself a favor and read a book before sleep instead. Or do some mindfulness meditation. Or have sex. Anything without a blue light.

 Suppressed melatonin production due to the bright light exposure vs. high melatonin production when wearing goggles blocking out blue light (and obviously high melatonin production when only being subjected to the dim light).  From https://academic.oup.com/jcem/article/90/5/2755/2836826

Suppressed melatonin production due to the bright light exposure vs. high melatonin production when wearing goggles blocking out blue light (and obviously high melatonin production when only being subjected to the dim light).  From https://academic.oup.com/jcem/article/90/5/2755/2836826

3. Why do we sleep? Why is sleep important?

This is a really good question. And unfortunately there is no definite answer. As William Dement, the founder of Stanford Sleep Research Center said, "As far as I know, the only reason we need to sleep that is really, really solid is because we get sleepy." So… Let’s see what we already know (besides this grain of wisdom).

Memory

The romance between sleep and memory consolidation (that is, its stabilization) has long been suspected and numerous studies in the last decades, if not even centuries, have solidified it (but none have set the record completely straight). There is a distinction between two memory types: declarative (fact-based information, “what”-memories) and procedural (“how”-memories, like a muscle memory of how to drive a bike or play a new song on a guitar). It would be very convenient to have a clear distinction like “slow wave sleep is responsible for this and REM is responsible for that”, but unfortunately the reality is a less clear-cut mess.

Generally, sleep helps memory: people who sleep after learning something tend to remember this newly learnt stuff better than their counterparts who stayed awake after the learning session. 26 Learning word lists 27, 28 , complex finger moving skills 29, 30 or even gaining insight into complex hidden rules 31 : all that benefited from a sleeping session following the learning.

Slow wave sleep (SWS), dominating the first part of the night, was theorized to help specifically with the consolidation of declarative memories 32, 33, 34 . The process behind the stabilisation of newly acquired memories is believed to be their reactivation in hippocampus, our memory center, during sleep. By “replaying” the memories their traces would become more stable and less likely to perish away 35, 36 . One study found that if you learned something while smelling rose odour and then were exposed to the same smell during your SWS sleep, then your hippocampal activity increased and your memories next day were stronger 37 . So,

  1. Stronger hippocampal reactivation during SWS.
  2. Better memories.
  3. ???
  4. Profit!
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REM sleep, on the other hand, was associated with procedural memory whose consolidation does not depend on hippocampus (but rather on rehearsing the movement commands in parts of the brain concerned with muscle control, such as cerebellum, basal ganglia and motor cortex). 38, 39, 40 Not that much is known about the exact consolidation mechanisms of this kind of memory so we’re gonna keep this paragraph short. However, there are studies speaking against such a clear cut distinction (or if you wanna be scientific, against “dual-process hypothesis”). For instance, it was shown that SWS sleep can also help to consolidate memories for movements (=procedural) 41, 42 , whereas REM sleep had some part in stabilizing memories about events and facts 43, 44 . A not so clear separation of responsibilities after all, it seems. This rather indicates that both stages are important for both types of memory (this theory is called “sequential hypothesis”, again, if you wanna be scientific): they complement each other rather than compete. It just so happens that one stage (SWS) might contribute more to one type of memory (declarative) and vice versa.

But of course this is not the end of the story. There is -- surprise -- another theory trying to describe how memories are consolidated (oh boy, was it fun to learn for the exam on memory). It is called “synaptic homeostasis” and it basically says that when you’re awake and you acquire all the new memories and experiences, the connections between your brain cells (=synapses) get stronger (and even new ones are created) and that when you sleep the brain tries to downscale all this huge daytime increase to a reasonable level by removing the unnecessary synapses. 45 So you could almost say you sleep to forget….in order to lift signal over noise and to start a new day refreshed and ready to learn again. Unnecessary connections and random memories get removed, while the important ones get stronger by being replayed. A recent study has provided a direct visual proof for this hypothesis: using extremely high-resolution microscopy the researchers first identified size and shape of 6920 synapses and then have shown that after a few hours of sleep 80% of the synapses shrank by ca. 18%. 46

    Large synapses in an awake mouse vs. shrunken synapses of a mouse who indulged in some sleep (Image Credit: med.wisc.edu)

   Large synapses in an awake mouse vs. shrunken synapses of a mouse who indulged in some sleep (Image Credit: med.wisc.edu)

Of course there is no one correct answer -- the truth is somewhere in the middle, all these theories explaining some part of what is really going on. But now you know that you should think twice before pulling an all-nighter before an exam -- stressing out with Red Bull won’t make you remember stuff better, but some hours of restful ZZZ’s just might.

Housekeeping

Another theoreticized function of sleep is doing a little housekeeping. While you are sleeping the brain puts on the janitor robe and takes off to clear out all the junk that has accumulated there during all your daytime thinking. In a series of mice studies, researchers have discovered a system that drains waste products from the brain during sleep. 47 A brain equivalent of lymphatic system, a network of tiny channels flushing out waste by-products with cerebrospinal fluid, is responsible for that. Scientists called it a “glymphatic system” because, well, it functions like a lymphatic system but with the help of supportive brain cells: glial cells. See what they did there? When mice were asleep, the system went into overdrive (the awake flow was just 5% of the sleep flow!) and the brain cells even shrank in size to make the spaces around them easier to clean. The by-products that get flushed out include beta-amyloid protein, the criminal mind behind Alzheimer’s disease (it gets cleared out twice as fast during sleep as compared to wakefulness!), and other things associated with neurodegenerative disorders. So if you wanna to pull an all-nighter think about all these toxins that accumulate in your brain and hit the hay for a couple of hours instead.

So while it is still not completely clear why we spend a third of our lives sleeping we seem to have pretty good pointers.

Stay tuned for part II which will include fascinating infos on dreams, what can go wrong with our sleep and some advice on optimal sleeping practice!