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Dr. David White, M.D.

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The Mysterious Science of Sleep

Posted: 07/05/2012 7:40 am

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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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...
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...
 
 
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02:20 PM on 08/24/2012
It is strange that there is only theories about this issue and I am also not sure if they are correct.
There are people that cannot sleep and they doesn't need it at all.
I sleep 2 hours a day and I don't need more, I feel like back of my brain working and I am more concentrated and have much more abilities during the time when I sleep only 2 hours a day and I don't want to sleep at all.
When I sleep 6-8 I feel horrible and sleepy! I have difficulties in concentration and always trying to switch brain activity to left side of my brain, because it is working much better.
klepysik
07:49 AM on 07/11/2012
So...I work 12hrs night's, 3 days on, 3 off, 4 on, 4 off. I tend to switch to a 'normal' life on my days off as I am married w/4 kids. I'm lucky to get 5hrs of sleep a day..anyday, or night, working or off, 5hrs and I'm up. I'd give anything to get 7-8 hrs at a time. !! Even the OTC sleep aids don't extend my sleep.
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realitytrumpsbull
Two 'alves of coconut!
02:05 AM on 07/07/2012
I think the body is roughly analogous to a machine, except for the part where when you park your body, it starts to fix itself. If you always run it, you will eventually 'crash', and not just your adrenal glands or whatever, but also literally, your car. Get your Z's. Whoever/whatever is trying to keep you from doing it, tell em to @#$@ off. It really is saving your own life. Don't forget to tell the Idiot Box to take a hike, too, computer also. Down, sleep thieves! Begone!
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Claire Redfern
blogger, mom...
10:01 PM on 07/06/2012
I know this, I don't sleep well. narcolepsy is a bi&&ch to live with . I wake several time a night.. or never really fall asleep. I have good sleep meds, and do sleep but once I am up I am up.. if I fall back to sleep I am out for hours.. the problem is I fall back to sleep around 3 or 4 am.... sleep until around 9 or so and feel like hell. I am working with a sleep doc to get my circadian rhythm back. I can live with getting up at 5a, but not if you just went to sleep at 3a. If I get good sleep I am fine... Usually if I fall back to sleep I have the worst nightmares too.. I can give Wes Craven ideas for the next horror flick.....
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Susan Shaffer
watching you...
09:34 PM on 07/06/2012
I have had some extraordinarily bright people work for me over the years. A common thread is that they slept less. This gave them more time to study and of course get good marks. Of course you have to want to study.
Anyway one question that has perplexed me about sleep is why we sleep less and less as we age. The spare time left over from sleep time should mean our elderly are our most productive. Yet that is the age that people start to slow down. I can understand physical decline since we are at our physical peak at 25 and it's downhill from there but from a mental point of view they should be the most productive.
04:44 PM on 07/06/2012
I had to quit coffee when I was working ... it was keeping me awake on the job.
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Susan Shaffer
watching you...
09:35 PM on 07/06/2012
reminds me of a post card I got
"Coffee, there is plenty of time to sleep when you are dead"
02:38 PM on 07/06/2012
With all scientific information aside, if I don't get enough sleep, I tend to get lethargic and moody. And, because I have low blood pressure, it seems like that too works in conjunction with lack of sleep making me even less in tune with my surroundings. So as not to go against anything stated in the article, I believe sleep is something we all need just like eating, exercise, etc. - there doesn't necessarily have to be a reason behind it - it's just a normal process like all other activities.
09:29 AM on 07/06/2012
One thing to remember about our bodies is that they evolve according to external conditions, and learn to take advantage of external conditions. At night, it's dark outside. It's dangerous to be wandering around, more dangerous to be running, or lost, or in the presence of predators. So we take advantage of that time to rest.

Over time, our bodies, and the bodies of all animals learn that there are rest periods and active periods. Many bodily functions can take advantage of this balance for process that include recovery, consolidation, etc. Some processes are 'important' but not 'urgent'. It's valuable to shuffle some of these into the night time for efficiency. I suspect there is not a single reason for sleep, but that as our bodies evolved they learned to take advantage of the night and the day - for different aspects of healthiness.
to your health, tracy
http://personalhealthfreedom.blogspot.ca/p/subject-index.html
08:40 AM on 07/06/2012
hohum.... I'm sleepy
01:17 PM on 07/05/2012
Sleep is practice for death.
ka9vmp
No Hazbrat Endorsements
05:57 PM on 07/06/2012
Is that where the phrase "dead tired" came from?
04:19 AM on 07/07/2012
Mebbe
11:32 AM on 07/05/2012
While adenosine and synaptic homeostatis regulate sleep, does the contribution of sleep to biological rhythm help explain why sleep is essential to health? Disturbing the timing, duration, or quality of sleep impairs the strength of biological rhythm (the orderly coordination of hormones and cellular functions in nearly every tissue; in fact genomic circadian rhythm is a characteristic of nearly every cell and life form on the planet including plants). Like a car engine with ignition "timing" off by even a little bit, the lifestyles associated with reduced rhythm strength will keep you running/ticking but not as long as those whose rhythm is well-tuned. In studies of elderly populations and "shift workers", impaired biological rhythm has been associated with a 2-3 fold increase risk of mortality independent of age and other common risk factors. Enough said.