To Sleep or to Stay up Studying, That Is the Question

An Independent Project by Monika Nemcova ’19
Part 3 of 9

In my Spanish class, one of the girls summarized the universal student’s dilemma: we can either study, have a social life, or sleep – and as our time is not infinite, we manage to do only two of the three options. Well, most of us do not consider eliminating friends and becoming a hermit a viable life option. And at Andover, studying is really not optional – which leaves sleep as the least important activity. Nights thus become an endless reservoir of time which is spent either by writing that English essay or Snapchating with a well-meaning friend. For my whole year at PA, I have never met someone saying that getting a good night of sleep was their priority. Yet, as I try to argue in my series of posts about the importance of sleep, sleeping well is one of the biggest factors that influence our behavior and our performance in life. In this article, I would like to show you that the distinct choice between studying and sleeping does not exist – as the latter directly enables the former. In order to learn, the brain simply requires sleep.

When thinking about the role of sleep in learning, I remembered my dad’s childhood story that has never ceased to fascinate me. Back in the seventies, the Czech Republic still had a communist government, that made Russian a compulsory subject in all schools (as a nod to the USSR, which backed the regime). My dad, never one for learning languages, hated his Russian lessons with a passion. When he was in sixth grade, his Russian teacher insisted on learning long, lyric poetry by heart as a part of the curriculum. No one expected much of my dad. But he surprised everyone by a fluent recitation. He explained to me that he had found out that if he studied the poem straight before going to sleep, he then slept very poorly but dreamt about the poem. In the morning, he could recall it without problems. In fact, as he was telling me the story, he was still able to recite the poem, thirty years after.

The story of my dad might be an extreme case, but the relationship between dreaming about a task and improvement in that activity has been experimentally established [1]. In 2010, researchers taught two groups of people how to navigate a 3D maze. After the learning session, one of the groups went to sleep and the second one remained awake. In the napping group, the subjects who reported dreaming about things associated with the maze fared significantly better in the re-testing of the navigation. In contrast, no such distinction appeared in the awake group – the performance of the subjects was not affected by thinking about the maze. The researchers were careful not to generalize the findings as direct causation between dream experience and memory consolidation. Instead, they proposed that both the dreaming and the improvement of the task were the results of the processes of “memory reactivation and consolidation in sleep” [1]. So dreaming about the task would be just a side product of an efficiently learning brain.

However, that still does not explain how do these “processes” function, nor, for that matter, why was my dad’s learning technique effective only when he studied directly before going to bed. In order to understand that, we need to know a bit about how learning functions. The neurons in our brains are connected in intricate nets and pathways – one neuron always receives inputs from many others and based on the type and strength of the signal it receives, it either fires as well or stays silent. However, this system is not static. Both external (seeing a member of your tribe get eaten by a tiger because he was too loud) and internal (feeling pain after trying to touch fire) stimuli can affect the strength between the individual neurons. So in my first case, the connection between the neural pathway responsible for being stealthy and the pathway recognizing tiger territories strengthens. In the second case, the pathways for “great things to touch” and “fire” become less connected. It is not that easy but that is the basic principle. When the connection between two neurons strengthens, the neuroscientists say that long-term potentiation (LTP) has occurred. Weakening connection is called depotentiation. The last thing we need to know about learning is that the strengthening of the neural connections can be either short-term or long-term. A new experience evokes a short-term change, which, if it were left so, would disappear after four to six hours [2]. The brain needs to further strengthen the connection to make it last. And that is where sleep comes in.

connections
Figure 1. The connections and firing patterns of neurons are vital in learning (Retrieved from https://www.thegreatcoursesdaily.com/the-neuron-doctrine/)

Last remainder: LTP and depotentiation are chemical processes and as such depend on the brain’s own levels of chemicals, called neurotransmitters. I talked about neurotransmitters at length last time, so just a quick review relevant to learning. In REM sleep, the most prominent neurotransmitter is acetylcholine and the levels of other chemicals are low (for our context are important norepinephrine and serotonin). In NREM sleep, acetylcholine is low and both norepinephrine and serotonin occur at moderate to low levels. The neurotransmitters occurring in the brain in different sleep phases determine whatever and how the synapses can be strengthened [2].

REM Sleep

It has been experimentally established that when we learn something new, the proportion of REM in our overall sleep increases. This effect appears only when we actually learn and improve, not just all the time when we try to learn [2]. When we master that task, the amount of REM falls to normal [3]. That alone would be a good indicator that REM sleep somehow contributes to the learning process. However, there is also another proof in favor of that theory – the presence of the before-mentioned neurotransmitter acetylcholine. Acetylcholine makes the synapses (connections between neurons) especially plastic, which allows them to undergo either LTP or depotentiation [2].

LTP occurs when the neuron at the synapse fires in accordance with the general firing pattern of the brain – that EEG diagram pattern which I talked about last time (during REM, the firing pattern looks very much like the pattern of wakefulness). Depotentiation, a process as equally important for learning as LTP, is the result of a neuron firing in-between the pattern seen on the EEG. Also, depotentiation appears only in the absence of both norepinephrine and serotonin – which, again, makes the REM phase of sleep ideal for this process, as the levels of these neurotransmitters are at their lowest during REM [2, 3].

NREM Sleep

We have known for a long time that NREM sleep is also important for memory consolidation – the neurons which fired during the learning process were recorded firing again in the same order, albeit in an accelerated pattern (up to 300x). However, there is one obvious obstacle to proposing that NREM sleep also contributes to LTP – namely the absence of acetylcholine. Without acetylcholine, the short-term LTP potentiation, which happens during REM, cannot be initiated. However, it appears that NREM sleep allows the short-term LTP previously established during the REM phase to be consolidated into the more permanent long-term LTP. In favor of this hypothesis speaks the fact that protein synthesis necessary for long-term LTP notably accelerates during the NREM [2].

In addition, NREM sleep seems to contribute to depotentiation of the unused or even obstructive synapses [2].

sleepinggirl
Figure 2. Sleeping properly is key in the learning process (Retrieved from https://www.sciencedaily.com/releases/2018/08/180806104242.htm)

Now we can finally determine the real-life consequences of insufficient sleep. Because the REM phase is the only time when brain has high levels of acetylcholine and simultaneously low levels of other, obstructive neurotransmitters, it is the only time when LTP can be initiated fully. Experiments determined that subjects that were sleep deprived after a learning session showed no performance improvement following day [3]. That is one thing to consider – if we do not get enough REM sleep, learning simply does not occur. Going to sleep might thus be the most effective thing to do before a test, instead of trying to revise the material one more time. Also, subjects allowed to go to sleep immediately after a learning session had especially enhanced performance [3] – which probably explains my childhood mystery concerning my dad’s miraculous technique of poetry memorization. So I hope that the relationship between sleep and learning is less mysterious now (also, do not trust it when someone claims to learn something new while sleeping – it is a myth originating in faulty data analysis during the early twentieth century and as such was debunked in the 50’s [4]). Next time, I would like to focus on circadian rhythms and how do they affect both our sleep and our daily routines.

 

References

[1] Wamsley, E. J., Tucker, M., Payne, J. D., Benavides, J., & Stickgold, R. (2010). Dreaming of a Learning Task is Associated with Enhanced Sleep-Dependent Memory Consolidation. Current Biology, 20(9), 850-855. https://doi.org/10.1016/j.cub.2010.03.027

[2] Poe, G. R., Walsh, C. M., & Bjorness, T. E. (2010). Cognitive Neuroscience of Sleep. Progress in Brain Research, 185, 1-19. https://doi.org/10.1016/B978-0-444-53702-7.00001-4

[3] Maquet, P. (2001). The Role of Sleep in Learning and Memory. Science, 294(5544), 1048-1052. https://doi.org/10.1126/science.1062856

[4] Kang, S. (2018, October 28). Can you learn in your sleep? [Blog post]. Retrieved from Brainy Sundays website: https://scanberlin.com/2018/10/28/can-you-learn-in-your-sleep/

 

Neurobiology of Sleep

An Independent Project by Monika Nemcova ’19
Part 2 of 9

My first week of studying the mechanisms behind sleep revolved mainly around how different neurotransmitters create and affect the three basic states of the brain: wakefulness, REM sleep, and NREM sleep. But firstly, we should define what exactly these states mean. Neuroscientists recognize three standard, easy-to-measure characteristics that are used to define the brain states: EEG in the cortex, eye movement, and muscle tone. They are in the picture below. All of them measure electrical activity in certain areas. The first line, EEG, shows the activity of the brain. It is easy to spot the strange similarity between wakefulness and REM sleep in that first line: both have low voltage (seen as shorter marks on the graph) and high-frequency (the marks are close to each other) discharge patterns. It makes sense: dreaming, which happens during REM, often resembles our waking hours, so similar circuits are used to process it [1]. However, there is one interesting exception – our prefrontal cortex, active during wakefulness, is turned-off in the REM phase. The prefrontal cortex is the part of the brain that is responsible for decision making and behavior modulation. So, as it turns off during REM, in dreams we often do things that we would never, ever do awake [2].

 

REM Chart
Figure 1. Copied from Vazquez et al. J Neurosci 22:5597 – 5605, 2002

 

The second characteristic used to distinguish between the three brain states are the eye movements, noted as EOG in the picture. Eyes move the most when we are awake (even when we do not change their position conscientiously) and are still during NREM. During REM (which stands for rapid eye movement), they occasionally twitch under eyelids – that could be seen as irregularity on the otherwise flat graph [1].

The third line stands for muscle tone – how much does the body move; the less it moves, the lower the muscle tone. Quite obviously, the biggest is during wakefulness. After that, we are the most active in NREM – that is the phase when we move in the bed. Or, in the case of the less popular individuals for bed-sharing (such as myself), the phase when we steal all the pillows and kick any unfortunate person sleeping nearby. During REM, muscle activity is actively inhibited – probably as a preventive measure so that we could not act on our dreams [1].

While these three characteristics are useful in classifying the state the brain is in, it does not tell us what caused it to be so. As in many other cases in the body, the regulation of the sleep-wake cycle depends upon releasing site-specific chemicals, which, in turn, promote or inhibit the release of other chemicals. In the context of the brain, they are called neurotransmitters. Many neurotransmitters fulfill also other roles than only regulating sleep, so an average student has at least heard the name of many of them – serotonin, norepinephrine (also called noradrenaline), dopamine, acetylcholine, etc. When the electrical signal within a neuron is strong enough, it prompts the release of neurotransmitter – each neuron can do that only with one. So if the neuron releases serotonin, it is called serotonergic; if acetylcholine, cholinergic. The neurotransmitter then acts as a messenger between two neurons – the second neuron can fire more or less rapidly as the result of the chemical. It is important to note that naturally, the neurotransmitters occur only in the small space between two neurons.

 

neurotransmitters
Figure 2. How neurotransmitters allow the signal transduction between two neurons. Copied from https://www.doctorsbeyondmedicine.com/listings/neurotransmitters-and-your-health

 

That allows them to be site-specific. For example, one neurotransmitter called GABA is normally the chief promoter of NREM sleep. However, if it is released in a specific region of the brainstem called the pontine reticular formation, it inhibits REM and promotes wakefulness. When we take sleep medications (or any other drugs affecting the central neural system), our whole brain suddenly bathes in the neurotransmitters. That can account for some counter-intuitive results of some sleep medication. Most of the sleep drugs as well as the drugs used to induce general anesthesia work by promoting the effects of the beforementioned GABA. It works very well in most of the cases. However, in some patients, the drugs can promote GABA activity in the pontine reticular formation, which eliminates sleep. That is extremely unfortunate especially in children when instead of calming down before an operation, the stressed offspring becomes even more agitated [3].

The chemical cocktail of the brain is complicated but fairly well-understood. Studying sleep has the imminent advantage that it is an all-animal phenomenon, so a lot of studies could be accurately done using animal models. To simplify it, the three categories of brain states correspond with increased levels of certain neurotransmitters. The state of wakefulness is associated with high amounts of released monoamines – a group of chemical compounds where belong also serotonin and norepinephrine. They play a permissive role in sleep occurrence – it basically means that sleep can begin when their levels are low. Some anti-depressants, which work on the basis of increasing serotonin levels, can thus cause insomnia as a side effect [4]. Another important neurotransmitter is called acetylcholine. It occurs in the brain in high concentrations during both wakefulness and REM sleep. In fact, from the chemical point of view, the main difference between the REM sleep and wakefulness is the ratio of monoamines to acetylcholine. When we are awake, their levels are roughly similar. During REM sleep, the monoamines level plummet but the acetylcholine levels stay consistent [1]. I am saying levels – again, do not imagine brain bathing in acetylcholine; the neurotransmitters are released between two neurons and immediately recycled. The fact that the brain uses acetylcholine (and, therefore, the same circuits) in both wakefulness and REM sleep, again provides some rational basis why dreams resemble our waking reality so much.

As for the NREM phase – the traditional, if not a bit boring, sleep in which we spend the majority of our sleeping time, the main neurotransmitter there is the beforementioned GABA. However, I would like to talk mainly about another neurotransmitter associated with NREM sleep, adenosine. Adenosine, as in adenosine triphosphate,  is the breakdown product of the famous energy-storing molecule ATP. It is relevant to us because caffeine acts by blocking the receptors for this sleep-promoting neurotransmitter. As we are awake, increasing amounts of adenosine are released. It effectively determines the length of time we can be alert – as adenosine builds up, we become to feel tired. When we go to sleep, the adenosine levels gradually decrease – the more we sleep, the bigger the decrease. That is the biological basis why we feel more rested and alert after a night full of sleep. Caffeine blocks the adenosine receptors and thus keeps us awake [5, 1]. That is maybe something to think about – caffeine does not make us less tired, it just blocks our ability to recognize how tired we are.

So that is all from me about the neurobiology of learning. Next time, I would like to focus on circadian rhythms and something important for all students: the biological basis of learning and how is that affected by sleep.

 

References

[1] Brown, R. E., Basheer, R., McKenna, J. T., Strecker, R. E., & McCarley, R. W. (2012). Control of Sleep and Wakefulness. Physiological Review, 92(3), 1087-1187. https://doi.org/10.1152/physrev.00032.2011

[2] Baghdoyan, H. A. (n.d.). Historical Overview: Brainstem & Forebrain [Video file]. Retrieved from https://www.coursera.org/learn/sleep/lecture/hRTfO/02-03-historical-overview-brainstem-forebrain

[3] Baghdoyan, H. A. (n.d.). Wake & REM: GABA [Video file]. Retrieved from https://www.coursera.org/learn/sleep/lecture/bBMkF/02-06-wake-rem-gaba

[4] Baghdoyan, H. A. (n.d.). Wake & REM: Monoamines [Video file]. Retrieved from https://www.coursera.org/learn/sleep/lecture/Vuu3a/02-04-wake-rem-monoamines

[5] Baghdoyan, H. A. (n.d.). NREM: Adenosine [Video file]. Retrieved from https://www.coursera.org/learn/sleep/lecture/I0u9B/02-09-nrem-adenosine

Vazque, J., Lydic, R., & Baghdoyan, H. A. (2002). The Nitric Oxide Synthase InhibitorNG-Nitro-l-Arginine Increases Basal Forebrain Acetylcholine Release during Sleep and Wakefulness. Journal of Neuroscience, 22(13), 5597-5605. https://doi.org/10.1523/JNEUROSCI.22-13-05597.2002

Why Do All Animals Need to and How Do They Sleep

An Independent Project by Monika Nemcova ’19
Part 1 of 9

Even though sleep theoretically comprises a third of one’s life, an educated layperson knows basically nothing about it. I personally got through almost twelve years of rigorous formal education without getting to know more than that sleep is healthy (but why is it healthy I couldn’t tell) and that its amount per night should approach the magical number eight. I have, like everyone else at Andover, experimentally determined that if one doesn’t get enough of sleep, the next day feels like personal hell. Somewhere at the corners of my brain hovered information that there are two kinds of sleep – REM (as in “rapid eye movement” – that is when dreaming happens and eyes move rapidly below the eyelids – hence the name) and NREM (“non-rapid eye movement” – the peaceful slumber we don’t remember). This spring, I have decided to end this ignorance of mine and do an IP on sleep to finally understand this elusive phenomenon, which probably influences our day-to-day lives more anybody thought. Because I think that it is important that people know more about sleep, I will post here the weekly summaries of my readings, so everyone could see it.

Even though humanity has slept from its very beginnings, the study of sleep by itself is a very young field. Sleep came to the attention of the scientists in the early twentieth century when Sigmund Freud put forth that dreams contained messages about one’s suppressed desires and that they are crucial in unlocking one’s unconsciousness. While his claim is now generally regarded as pseudoscience (because it is impossible to prove or disprove it), it foreshadowed the efforts of future scientists to understand sleep. The breakthrough came in 1950 when a British physicist Robert Lawson during a long train ride noticed that the eyes of sleeping people were twitching under their eyelids [1]. He then spent the rest of the ride observing the sleeping passengers and the frequency of the rapid eye movements. Later, he wrote about this unorthodox experiment in a short letter to Nature [2]. A researcher at the University of Chicago, Nathaniel Kleitman and his graduate student Eugene Aserinsky decided to verify and quantify Lawson’s observations. In 1953, they proposed a relationship between the rapid eye motility observed during the sleep and dreaming, setting thus the now widely-known distinction between REM and NREM sleep. When they awoke sleeping people in the middle of their REM cycle, the vast majority of them was able to recall the dream they had or at least knew they were dreaming. In contrast, when they awoke subjects in the NREM phase, the overwhelming majority of the people could not remember their dream. Kleitman and Aserinsky also measured the interval between the individual REM phases and concluded that “An eye movement period first appears about 3 hr after going to sleep, recurs 2 hr later, and then emerges at somewhat closer intervals a third or fourth time shortly prior to awakening.” [3] When our sleeping cycle ends with the REM phase, we are able to recall the last dream. Their research also showed one of the reasons why it is so important to have a night of uninterrupted long sleep, as opposed to a few hours at night and a handful of naps – the REM phase starts only after several hours of sleep. The REM phase is crucial for learning and memory consolidation (I will discuss why is it so at some later point) [4].

 

SleepCircle
Figure 1. Copied from https://sleepcouncil.org.uk/how-much-sleep-do-we-need/

 

However, even after more than half a century of study, some aspects of sleep remain a mystery. For example, no one is sure why sleep evolved in the first place. Sleep seems like an evolutionary disadvantage – a period of time when an individual is vulnerable to the attacks of predators and cannot look for food or potential mates. Yet all animals sleep one way or another and mammals have the same sleep patterns as we do, complete with the REM and NREM phases. There must be a definitive evolutionary advantage of sleeping.

 

SleepTheories
Figure 2. Copied from https://backyardbrains.com/experiments/sleep#prettyPhoto/1/

 

Some propose that animals have evolved to eliminate the time spent by running around and being vulnerable to predators. Asleep, they are hidden, quiet and thus better protected. However, the counterargument presents itself very readily here – the individuals are less likely to escape the predators while asleep. Another theory proposes that sleep evolved to conserve energy – while we sleep, our metabolism, body temperature, and caloric demand all decrease [1]. That is, by the way, the reason why we do not even notice that we regularly do not eat up to ten hours because of sleep. If we don’t go to sleep, the body demand energy as usual – everyone has probably experienced gnawing hunger around two in the morning while desperately trying to finish an essay. Sleep also might have evolved as a time when the body could repair itself [1]. Personally, I have noticed that when I don’t sleep enough, my skin roughens, I’m more prone to acne, and I get sick easily. An important topic for students is also the role of sleep for memory consolidation [1]. We probably cannot determine a single reason why sleeping evolved but we can be sure that now it serves several different important functions and when we do not get enough of it, the body suffers greatly. Next week, I will focus on the neurobiology of sleep.

 

References

[1] Mar’i, J. (n.d.). Experiment: Sleep. Retrieved March 25, 2019, from https://backyardbrains.com/experiments/sleep

[2] Lawson, R. (1950). Blinking and Sleep. Nature, 165, 81-82. Retrieved from https://backyardbrains.com/experiments/files/Lawson-first-REM-1950.pdf

[3]   Aserinsky, E., & Kleitman, N. (1953). Regularly Occurring Periods of Eye Motility, and Concomitant Phenomena, During Sleep. Science, 118(3062), 273-274. https://doi.org/10.1126/science.118.3062.273

[4] What is REM Sleep? (2016, December 1). Retrieved March 25, 2019, from https://www.nichd.nih.gov/health/topics/sleep/conditioninfo/rem-sleep

The A-MAZE-ing Chicks…

Take On The Labyrinths of Room 103!

GUEST POST BY EMMA BROWN ’19

After a successful relay race last Monday— though some chicks were a tad distractible— Animal Behavior students have spent the past week studying associative learning and spatial cognition. This was achieved through two experiments: teaching our chicks to turn in a circle on command, and determining their learning abilities in the context of navigating a simple Y-maze.

Pictured below is Jan’s chick, Colonel Sanders, who was the only triumphant twirler in our class.

For the second experiment, my group constructed a Y-maze out of shoeboxes wherein one path from the fork would lead to food and freedom, and the other to a dead end. We tested the accuracy of Ferdi, Colonel Sanders, and a third chick over the course of five runs.

Our data depicted a significant decrease in time taken from Run 1 to Run 2 immediately followed by an outlier increase for all three birds in Run 3. Then, as the timing decreased for all birds aside from Ferdinand (who got distracted) in Runs 4 and 5 respectively, the data appeared to indicate that chicks can retain their learning of a Y-maze for a short amount of time, needing to “re-learn” the route before gaining any form of proficiency.

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Like a Chick in a Maze

Animal Behavior Continues Working with Chicks

Guest Post by Carley Kukk ’19

During our last week with the chicks, we focused on teaching them how to get through a maze using associative learning. We constructed a simple Y maze with leftover shoeboxes and placed a small pile of food at the end.

Picture1

The food acted as a positive reinforcement if the chicks successfully completed the maze. Hopefully, they would later associate the correct end of the maze with the food.

In our experiment, we used 2 chicks to strengthen our data. Each chick surprisingly ran their fastest time through the maze on their first try. This was probably a fluke as later proved in the data where the chicks always explored the other end of the maze before completing it.

Eventually it took around 30 seconds each to complete the maze. There were in total around 7 trials for each chick. They finally began to associate the ending with food and ultimately learned through operate conditioning the correct way to complete our y-maze.

The Herring Are Coming!

Bio100 Visits the Shawsheen River

This year’s Bio100 class had the unique opportunity to visit the Shawsheen River last week and learn a bit about habitat change. Each period piled into a bus and drove down to near Whole Foods in Andover to a bridge overlooking the Shawsheen River.

There, they met Jon Honea, a professor at Emerson College in Boston whose research involves making computer models to see how habitat change effects different communities. In this particular spot, two dams that were built approximately 200 years ago were taken down to allow the migratory fish to return to the area. He is now monitoring the return of the fish that used to be native to this area, namely the River Herring. These fish are silver in color and about a foot long. Mr. Honea and his team are watching the river for about 10 minutes at a time to see how many of these fish are spotted. This data will help to estimate the fish’s spawning population time.

Mr. Honea talked to them a bit about why it is so important for us to repopulate the river with this Herring. They play an important role in the ecosystem as food for many animals. They spawn in fresh water rivers and then move to the ocean to grow up. Mr. Mundra also talked a bit about the two dams that were removed from the area. These dams were preventing the fish from coming back to spawn in the river. These dams were built approximately 200 years ago as a source of energy for the Powder Mills in the area. Mr. Honea also said that the downstream dam was purely ornamental – the owner of the Mills wanted a gurgling sound for his administrative staff to feel comfortable working in the building.

The class then helped Mr. Honea to count the fish in the river. They took some basic data down, the weather and temperature of the air and water, and began to look for the fish. We are looking for the stray fish who are now able to make it upstream, to see how many make it up now that the dams are gone. Unfortunately, in the 10 minutes that we were there, no one saw a fish, but the hope is that within the next three or four years the population will be thriving!