The objective of this course is to give students the most up-to-date information on the biological, personal, and societal relevance of sleep. Personal relevance is emphasized by the fact that the single best predictor of daytime performance is the quality of the previous night's sleep. The brain actively generates sleep, and the first section of the course is an overview of the neurobiological basis of sleep control. The course provides cellular-level understanding of how sleep deprivation, jet lag, and substances such as alcohol, ,caffeine, and nicotine alter sleep and wakefulness. The second section of the course covers sleep-dependent changes in physiology and sleep disorders medicine. Particular emphasis will be placed on disorders of excessive sleepiness, insomnia, and sleep-dependent changes in autonomic control. Chronic sleep deprivation impairs immune function and may promote obesity. Deaths due to all causes are most frequent between 4:00 and 6:00 a.m., and this second section of the class highlights the relevance of sleep for preventive medicine. The societal relevance of sleep will be considered in the final section of the class. In an increasingly complex and technologically oriented society, operator-error by one individual can have a disastrous negative impact on public health and safety. Fatigue-related performance decrements are known to have contributed as causal factors to nuclear power plant failures, transportation disasters, and medical errors.
11.02 - Sleep Occurs as a Circadian Rhythm
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來自 University of Michigan 的課程
Sleep: Neurobiology, Medicine, and Society
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Unit 11 - Society: Circadian Rhythms, Sleep, and Health - (Standard Track)
Unit 11 kicks off the Society section of the course with a lecture on Circadian Rhythms, Sleep, and Health from Theresa Lee, Ph.D.
與講師見面
Ralph Lydic, Ph.D.Professor Emeritus, Molecular and Integrative Physiology, Professor Emeritus, Anesthesiology
University of Michigan Medical School
Helen Baghdoyan, Ph.D.Professor Emeritus, Anesthesiology, Professor Emeritus, Pharmacology, Professor of Psychiatry
University of Michigan Medical School
All right, I'm back, and now we're going to look at the way in which sleep is
rhythmic and why that is important for understanding how sleep works.
So first of all,
understand that this is a graph that shows whether you're awake or asleep.
This line is showing your wakefulness, up is awake and down is asleep.
And you could see that during the daylight hours, you tend to be awake and
where this red arrow is, is a dip in your alertness that occurs
usually in the afternoon depending on when your wake up time is.
And in many, many cultures, this is a natural time for people to sleep, and
certainly children take afternoon naps, this is when they would happen.
Then we become alert again later in the afternoon, and then at night,
we become unalert and we've sleep.
What I'm showing at the bottom is the circadian alerting signal that helps
makes this occur.
So when you first wake up in the morning, you don't need anything to keep you awake.
But humans are unusual in being a species that has a consolidated period of
wakefulness and a consolidated period of sleep.
And during the time when we are awake,
as we go through the day, we become less and less wakeful.
That is we're developing fatigue and we need something to press us to stay awake.
How is it that what you see in children is you're awake and you go to sleep or
you're awake and go to sleep, and many, many organisms that is what's typical.
But humans, we consolidate our awake for
period by having a circadian signal which is preventing sleep, right?
So these purple errors at the bottom are showing how the part of
the brain that controls circadian rhythm that is the suprachiasmatic nucleus and
other related areas.
Which control the ability of the sleep mechanism to be on or
off, is preventing that shift out of wakefulness and into sleep.
At sometime after it becomes dark typically,
the circadian signal will rapidly shut off.
And the fact that you've been awake for many hours, say 16, takes over and
you go into a sleep phase.
Okay, so this is the circadian rhythm of sleep.
So what is a circadian rhythm?
What I just showed you, one could describe as being a daily rhythm of sleep.
But I know that it's circadian, because like other circadian rhythms,
it is a self sustained or an endogenous biological rhythm.
What that means is without any information about time of day,
without being able to see the sun rise and set, without having any clocks or
anything that tells you the time of day.
You will still, at an approximately 24 hour period,
go through a natural change from being wakeful to being asleep.
Very much like what your body would normally do
even with the light dark cycle there.
Now normally, our endogenous circadian rhythm, these rhythms which are self
generated are entrained or synchronized with the outside world to be 24 hours.
If you don't have that timing system, you don't have the sun rise and
set, or a clock telling you time of day, are endogenous period.
That is the period at which this change happens is only an approximation
of 24 hours.
In the case of humans, it's a little bit longer, in the case of some species,
it's a little bit shorter.
But in the case of all organisms, the outside world,
that is the light dark cycle in particular.
Entrains or synchronizes that endogenous rhythm to the exact 24 hour period.
This is an example of what an organism looks like,
their circadian rhythm looks like, if they don't have access to external signals.
So on the top, we have an example of a pig tail monkey, and
each line represents when the animal is active.
And you're looking at a double plotted curve, so there's 24 hours and
then a repeat of 24 hours again, and then each line is a different day going.
So you have day one, day two, day two, day three, day three,
day four and so on down the page.
Now if you're entrained, this would be a straight line,
if you had a 24 hour period.
But in the case of this monkey,
it's been put into a condition where it has no information about time.
And so every day, it is waking up and
becoming active a little bit earlier than the day before.
And so it has a free running rhythm and
an underlying endogenous rhythm that runs a little bit shorter than 24 hours.
And the lower example is that of a human, and you have exactly the opposite pattern.
In this case, a human wakes up every day a little bit later, and so
the endogenous rhythm is running longer than 24 hours.
So what are the criteria for circadian rhythms?
First of all, they must persist in the absence of any periodic signals.
So if I go back to this previous slide, you see that with no outside signals
everyday, these individuals are waking up and restarting their active period.
They retain near 24 hour periods when the environment adopts a different period.
So if I put the animal into an environment where the periods happen at eight hour
intervals, the lights turn on for eight hours, turn off for
eight hours, and so forth and so on.
Well, they're going to actually stay close to 24 hours,
because our underlying endogenous circadian system runs near 24 hours.
There's that the range in which you're able entrain is from about
23 hours to about 25.
And once you get beyond that range with this signaling about time of day,
you're not going to be able to entrain any longer.
So this is why when they maybe used to have people work for
[COUGH] eight hour shifts, sleep for eight hour shifts, come back to work for
eight hour shifts when they worked in submarines.
They ended up with people who were quit
had great deal of problems with their sleep and circadian rhythms.
After a change in the light dark cycle, that entraining signal,
you change your entrainment slowly, it doesn't happen immediately.
If it happened immediately, we would know that you weren't adjusting the underlying
endogenous clock, but rather you were just responding to the signal.
It does not revert after entraining to a new signal and it drifts away.
So I'm going to show you from 24 hours without synchronizer.
So here's an example, a diagram of this.
So under the entrained signal, this is an individual, it's an animal
that is alert during the night, so think about a mouse or a rat or a bat.
And so the activity period is showing activity during the night and
very little activity during the day.
You could also think of this as sleep in a diurnal animal like ourselves.
And so you're looking at sleep here during the night and
very little sleep during the day.
And the next section what I show is we shift the light dark cycles.
So here whether which ever rhythm you want to talk about is happening during
the dark phase.
And when the lights come on six hours earlier then they had before.
Then you have to shift your active phase or
your sleep phase to back to the dark phase and it takes several days.
And in fact for a six hour shift, they'll show you that it took about three days.
In reality for most individuals, most species, it would take six or
seven days to make such a shift.
So in this case, imagine if you made a trip to Europe,
the sun comes up six hours earlier than you're use to.
That in fact, is going to take you between three and
seven days to adjust to the local time zone.
If I put you into a conditions where there's no light cycles, so
there's no information about time of day.
Then you begin to drift away from this 24 hour period, and if you're a human in this
sleep, then you're going to sleep every night, a little later than you did before.
If you're a [COUGH] dufour kind of animal that's active during the day,
you're getting active every day a little later than you did before.
So you can measure any rhythm you want, but they're all going to be doing the same
thing of drifting away from where you were before.
And we know that the brain is particularly important for this process,
because if I lesion an area of the brain called the suprachiasmatic nucleus.
I completely disrupt the circadian or
daily entrained aspect of this, and the endogenous aspect goes away.
What you have is you sleep for a little while, you're awake a little while,
you're asleep a little while, you're awake a little while.
And you're alternating back and forth between these states,
because there's no circadian signal that is prompting you to stay awake any longer.
So this has led to people developing a sleep model,
which is often called the two stage model.
I'm calling it the Three Part Sleep Model here,
because although the first two graphs that have the blue color in them.
Explain the relationship between the development of fatigue and
the circadian clock.
It's also the case that we have an underlying ultradian rhythm,
that is a rhythm that is less than 24 hours.
And for the purposes of what we're talking about, this is a rhythm that generally
runs between 90 and 110 minutes, which is underlying our circadian changes as well.
So sleep is thought to be the process of needing to sleep and
having a drive to sleep at a specific time of day.
It's hard to be a combination of the homeostatic drive to sleep,
which develops because you are awake for a number of hours.
So let's imagine that you woke up 7 in the morning and all day long,
if you're never taking a nap, the need to sleep is building.
As chemicals in the brain, for example, are building, for example, adenosine but
also others.
And until you get rid of those, your brain is keeping
track of the fact that you've been awake for a number of hours.
And at some point, you're going to go to sleep, right?
If you're a small animal, you may go to sleep every couple of hours for
little while.
But in humans, where we have this extended wakeful period and
then extend the sleep period there is a point where you make that shift.
Now, why does that happen when it happens?
Well, that were the circadian system becomes involved, and
as I showed you in the earlier graph during the day,
the circadian drive is fairly low for sleep.
And therefore you're awake, and it's a low for
sleep because the drive is forcing wakefulness.
And then as you get towards the end of the night when the head of your wakeful period
when the homeostatic drive is very high, and
the circadian drive to keep you awake falls.
Then you're going to go into a sleep phase, and
we describe this as a sleep gate.
The switch off between circadian drive to stay awake, and
the homeostatic drive is in place to cause sleep.
Underlying that is this during the time that you're asleep between this 2300 and
700 hours of between, say 11 at night and 7 in the morning.
There's this ultradian rhythm, which actually goes on through the day as well.
But during the night, we begin to have these doubts of REM sleep,
the rapid eye movement sleep, every 90 to 110 minutes.
And the duration of this 90 to 110 minute cycle, say from trough to trough to
trough how much of it contains REM is varying across the eight hour sleep phase.
So let's put these together, so at the top of this graph,
I'm showing you the sleep homeostasis.
That is the growing need to sleep, because you've been awake for
16 hours, for example.
And then when you sleep, the fact that, that homeostatic need is reduced.
And so you're more likely to be awake when the homeostatic drive is low and
to be asleep when it's high.
In the middle, we still have our circadian graph showing wakefulness is high during
the day and wakefulness goes down during the night, and therefore, you sleep.
And then we have the circadian signal which is helping
keep you awake fighting this homeostatic drive.
Now one more feature comes into play that is particularly important in humans and
other diurnal animals.
As you get into the dark phase and the circadian drive drops off and
the homeostatic drive is relatively high,
the hormone melatonin is also released at that point.
And melatonin's released in all mammals during the dark phase,
whether they're an awake animal like a rat, or a sleeping animal like ourselves.
But for those of us who are active during the light phase and
sleep during the dark phase, melatonin serves a purpose of helping us sleep.
It helps us to fall asleep quickly, so it helps decrease the time of
onset to sleep, and it also helps us consolidate our sleep across the night.
And this will become important when we talk about some of the variations that
occur in the very young, the adolescent and the elderly.
But the melatonin rhythm is an important piece of helping our sleep and
humans have this very consolidated pattern.
So as you look at the homeostatic rise in the circadian gaining mechanism,
which is keeping you awake until late into the evening say 11 o'clock at night.
About an hour or so before that shift happens where you go to sleep,
you'll going to have a narrow window of time where you begin to get very sleepy.
So for example, in this individual's case,
it might be around 10 o'clock in the evening.
You get very tired and groggy, you have a hard time focusing on what you're doing
and you're thinking, it's time to wrap it up and get myself to bed.
Now interestingly, if you make yourself stay awake,
in humans we have that ability.
We can be highly motivated, we're studying for the test, I'm driving a car and
I gotta get home, I can make myself stay awake.
And you can get a little bit past this point and you're not as sleepy.
So there's a gating window of time when the combination of your melatonin rising,
this falling rapidly and
your homeostatic drive being high is going to want to make you sleep.
Eventually you're going to sleep regardless, and
what you're seeing here is the homeostatic drive dropping
while the circadian drive is low, and you will wake in here.
Another variety of other things that are happening at the same time, your body
temperature is higher during the day and it drops and is low during the night.
And your body temperature will begin to rise
just before you're reaching this minimum wake, and it helps wake you up.
It helps bring you out of the sleep, and
that's driven by your circadian underlying mechanism as well.
So although the circadian mechanism is not so involved at this time of day and
causing you to wake up directly.
It's indirectly affecting it, because your body temperature starts to rise,
cortisol rises, melatonin falls.
So a variety of metabolic activities begin to occur that are going to
get your body ready to be active once you awaken.
And this repeats itself every 24 hours, if you are sleeping in a regular time and
paying attention, allowing the homeostatic mechanisms to work the way they should.
Now just one more detail to layer on top of this, so
going back to that ultradian rhythm that I was telling you about.
As you go to sleep at night, so your sleep need has risen,
the circadian rhythms are falling, the circadian drive.
And so now you're going to start to sleep,
and what you're seeing here is the fall and sleep need overall.
But you're alternating between non REM or slow wave sleep,
which you've already learned about.
And the non REM sleep, and at the beginning of the night most of these 90 to
110 minute that cycles between non REM and REM and back and forth.
It's going to be slow wave sleep, and if you're young and
you're healthy, it's going to be stage three and four slee.
And it's going to take up most of this period, and
you're going to have a brief period of REM.
But as the night goes on,
those 100 minute cycles become less slow wave sleep and more REM.
So when you short yourself of sleep, what are shorting yourself of?
You're actually shorting yourself of the part of the night's sleep,
which is mostly rapid eye movement sleep.
Which is, we now understand important for
a number of specific functions, it helps consolidate memory.
It's the time of night,
we've just recently learned, where the blood vessels open up.
And the cerebral spinal fluid washes out much of
the chemicals in the brain that are associated with the sensation of fatigue.
So this alternation between sleep, we're doing different things.
During the non REM phase, we're doing some aspects of brain maintenance and
repair and restoration, and during REM, we're doing different ones.
And if you sleep only four or five hours, you're shorting yourself of that
rapid eye movement sleep, that is very critical for some functions of our brain.
So this is why it's really important,
that we're going to talk about it now in a few minutes.
To get the right number of hours of sleep, and to allow the circadian system to help
you have this appropriate timing and alteration between stages of sleep.
And we're going to take a break now, and in a minute, we will go on and
talk about sleep and how it changes across the lifespan.
