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The Mysterious Science of Sleep

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Most of our bodily functions and daily processes are well-understood. We have a pretty good grasp of why the heart beats, why we need to breathe and the purpose of our kidneys. The same cannot be said for sleep. Despite spending nearly one-third of our lives asleep, the fundamental function of sleep remains a mystery.

We do understand what happens when we are not able to sleep. There is a decline in our cognitive ability, our mood deteriorates, and if the period of sleeplessness is long enough, psychotic behavior may emerge. Rats will actually die in about three weeks if not allowed to sleep. However, such studies tell us little about the real biological role of sleep.

There have been many proposed explanations for why virtually all creatures on this planet must sleep. Some believe sleep to be an evolutionary step born from the need to stay out of harm's way when it grows dark outside.

Our understanding of sleep science has grown significantly more complex over time. Now, experts generally agree that sleep is all about the brain and serves to maximize brain function.

There are two hypotheses with the most scientific support:

  • The Adenosine Hypothesis: Sleep serves to control neural chemistry or regulate the level of certain substances in the brain that cannot be regulated during constant wakefulness.
  • The Synaptic Homeostasis Hypothesis: Sleep reduces the number or strength of synapses or connections between brain cells, which steadily increase during wakefulness and cannot be maintained. Thus, sleep serves to prune these neural connections.

The first hypothesis states one of the functions of sleep can be to regulate a molecule named adenosine (1,2). Adenosine bound to phosphorus is the primary source of energy, which allows cells to function normally. As cells are active and discharging over time, there is an accumulation of of the molecule adenosine.

Certain nerve cells in the brain (neurons) have been observed to be quite active (firing frequently) during wakefulness and become less active or completely silent during sleep. One example would be neurons in the basal forebrain. These neurons connect to many other nerve cells in the brain and are believed to at least partially dictate whether the organism (man or animal) is awake (basal forebrain neurons active) or asleep (neurons less active or silent).

Investigators promoting this hypothesis believe that as basal forebrain neurons are active over time (wakefulness), adenosine accumulates outside the cell and ultimately binds a receptor on the surface of the cell (called an A1 receptor), which inhibits activity of the cell (yielding sleep). After brain cells have been active for a long time over the course of the day, this accumulation of adenosine provides a mechanism to let the cells (and the organism) rest.

At least two lines of evidence support this hypothesis. First, if adenosine levels are continuously monitored in the basal forebrain, they steadily rise during wakefulness and fall during sleep, suggesting that sleep is important in the regulation of this molecule (1). Second, caffeine, the most widely used stimulant in the world, is an adenosine antagonist. This means that caffeine blocks the ability of adenosine to "turn off" these cells and promote sleep. As a result, you stay awake or receive a short energy burst.

The second hypothesis is quite different and focuses on synapses -- connections between nerve cells in the brain (3,4). According to this line of thinking, the net strength of these synapses accumulates steadily over the course of the day (wakefulness). While awake, your cells must learn new functions by strengthening connections between cells. For example, if we learn how to execute a task during the day, many synapses strengthen and some new ones may form in specific areas of the brain. This helps to establish memory. However, learning through strengthening synapses comes at a price; stronger synapses require energy to be maintained, occupy more space on the cell surface, consume supplies needed for cells to function, and eventually saturate the capacity to learn.

So, every day connections must be reduced and returned to a baseline level or vital cellular and brain processes could be compromised. Sleep serves as an ideal time when such synapses can be pruned since the brain is "offline" and new learning is not occurring. This is how new memories formed during the day are integrated with older ones, and the brain can figure out which synapses are more important, reducing or eliminating the others.

Ample evidence in support of this hypothesis shows synapses build up during the day and are reduced during sleep (3.4). Additionally, studies show that a unique kind of brain activity that occurs during sleep, called slow waves, becomes especially intense over very specific brain areas where learning has occurred, likely indicating synaptic pruning during sleep (4).

In all likelihood there may not be a single function for sleep, but multiple neural processes that can only occur when the brain is largely disconnected from the environment. While our understanding of sleep science continues to grow, there continues to be a strong consensus on the need for a good night's rest.

References:

1) Porkka-Heiskanen T, Strecker RE, Thakkar M, Bjorkum AA, Greene RW, McCarley RW Adenosine: a mediator of the sleep-inducing effects of prolonged wakefulness. Science. 1997 May 23;276(5316):1265-8.

2) Basheer R, Strecker RE, Thakkar MM, McCarley RW. Adenosine and sleep-wake regulation. Prog Neurobiol. 2004 Aug;73(6):379-96.

3) Massimini M, Ferrarelli F, Huber R, Esser SK, Singh H, Tononi G. Breakdown of cortical effective connectivity during sleep. Science. 2005 Sep 30;309(5744):2228-32.

4) Huber R, Ghilardi MF, Massimini M, Tononi G. Local sleep and learning. Nature. 2004 Jul 1;430(6995):78-81.

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