ANAT 322 Lecture Notes - Lecture 21: Synaptic Plasticity, Orexigenic, Astrocyte
7 Jun 2018
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ANAT 322 Winter 2017
Lectures
Lecture 21:
→ Circadian and Homeostatic Regulation of Sleep
1. Sleep is not only regulated by the circadian system and there are two main aspects of regulation of
sleep. There is a regulation by the circadian clock that will time when it is the good time to sleep and
there is also a homeostatic regulation of sleep which is that we sleep when we need sleep and have not
slept for a lot time and there is a sleep pressure that builds up in our brains.
2. Sleep can be defined by different parameters such as behavioral criteria in the sense that when we
sleep we do not move but sleep is not simply being quite so it is not only a matter of not moving.
Another important behavioral criteria that defines sleep is that the arousal threshold is really high which
means that what you need as a stimulation in order to make the animal active is higher. It is regulated
homeostatically as well in that when you have been awake for a longer time, you are more likely to fall
into the quiescence state.
Sleep can be defined in other ways such as with electrical criteria through EEG. There is also
pharmacological criteria during different sleep stages as we have different neurotransmitters secreted
that regulate different aspects of sleep. There are also molecular criteria or genes that are
downregulated or upregulated during different sleep stages (ongoing research).
3. Sleep is seen in many different organisms, including humans or mammals, fish and many of these
aspects of sleep have been studied in different organisms so it is widespread among animals so it must
have some importance or advantage for the organism.
It must be important because if you prevent someone form sleeping there are big adverse effects and
eventually death so it does not take so many dies until someone will die.
It probably have some role in energy conservation as we do not use as much resources when we
sleep and you can replenish some of the stores that you have such as glycogen in the brain. Some
animals will be resting at night when it is colder so they do not have to spend so much energy. It has
been known for a while that sleep is important for memory consolidation. More recently, synaptic
homeostasis is when we make new synapses and clean the ones that we are not using or do not need
any more so there is space for more learning.
4. There are different recordings you can do in a subject in order to study sleep. There is
electrooculography that allows you to put devices close to the eye and record the eye movements.
There is electromyography that tells about muscle activity. Electroencephalography through electrodes
put on the scalp that allow you to study electrical activity in the cortex.
If you do experiments and record in individual neurons, you will see that each of these neurons have
their own trace of electrical activity. The EGG shows high electrical activity when the neurons have
synchronized electrical activity by averaging all the individual activities. On the other hand, if the
different neurons are not synchronized, you get more of a flat line when averaging so low amplitude
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ANAT 322 Winter 2017
Lectures
activity. You can assess from an electron whether the neurons are synchronized or not and you can
assess the different types of waves of the average electrical activity.
There are different types of electrical waves seen in the brain that depend on the frequency or period
of the electrical activity and these are measured as oscillations per second or Hertz. There are alpha,
theta (6-8 Hz), delta (1-4 Hz), among others.
Polysomnography means that you are using all of these measurements (EOG, EMG and EEG) in order
to assess different sleep states.
5. Throughout the night we go between different stages of sleep that last about an hour and a half in
length and repeat many times during the night (4 to 6 times).
Non-REM sleep comprises four different stages including the slow wave sleep. During the stage 1 of
non-REM sleep, it is similar to being awake in that the EGG is mainly theta (fast rhythm, low amplitude,
desynchronized neurons and slow eye movement) and the EMG is high so there is still movement in the
muscle.
6. In stage 2, the eye movements have reduced a lot and the EMG is a bit smaller than in stage 1. Stage 1
is the stage where you start to enter into sleep and are easy to wake up whereas in stage 2 you are
entering a deeper sleep so it is harder to wake the person up.
The EGG still has slow amplitude and fast theta rhythm but you start to see some different activity
like the sleep spindles which are fast rhythms for a few seconds. You also have the K complexes which
are big high amplitude, slow wave rhythms that occur infrequently.
7. Stages 3 and 4 are the slow wave sleep because the main characteristic of the stage is to have very
slow waves in that the period is larger, higher amplitude and frequency is lower which are called delta
waves (1-4Hz). There is limited eye movement and the EMG has gone down more than in stages 1 and 2.
The neurons are well synchronized in the cortex.
8. In the REM sleep, is where we have the most vivid dreams and is also called paradoxical sleep. There
is rapid eye movement so there is high amplitude and movement of the eyeballs. The eye muscles are
one of the only muscles in the body that are still active together with breathing muscles whereas the
rest of the body is almost paralyzed as seen in the EMG which is very flat.
The EEG is similar to the wake or stage 1 because we see the theta rhythms that are very fast and low
amplitude so there is synchronization of neurons in the cortex.
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ANAT 322 Winter 2017
Lectures
9. Slow wave sleep depends a lot on the homeostatic process so when we sleep deprive someone there
is a large rebound in slow wave sleep. On the other hand, REM sleep is more regulated by the circadian
clock.
Learning, memory and synaptic equilibrium occur a lot during slow wave sleep as well as growth
hormone secretion that peaks at the beginning of the night due to sleep that would not be seen if a
person is not sleeping.
10. If we put side by side the stages that are repeated throughout the night, you have a hypnogram. At
the top you have wake, then REM sleep and then stages that are lower in the diagram.
Slow wave sleep is mainly at the beginning of the night which is when we need to recuperate from
the day so it is restorative sleep. The longer you have been asleep, the longer you have REM sleep and
the circadian clock will tell the regions in the brain when it is the time to do REM sleep which is in the
early morning hours. This is why when we wake up around the end of the night of sleep, we have the
impression that we are dreaming than when we wake up at the beginning of the night.
Sleep and the shape of the stages of sleep changes throughout life and children spend more time into
non-REM sleep and less time in REM sleep but they sleep more. Older adults go less into REM sleep and
have more times during the night where they wake up.
11. One century ago in the 1916, there was a disease called lethargic encephalopathy that spread
through Europe and North America and the cause was not known. They had severe sleep phenotypes so
neurologists were interested in trying to find the source of this. A neurologist from Vienna saw many of
these patients that suffered from the disease and for some of them, because they died, he was able to
describe what region of the brain had a lesion. A lesion in the brain led to the defect in sleep/wake cycle
ut ost sujets ould reoer after a ouple of oths. After the ’s, the disease disappeared
without people knowing the causes of the problem. In the majority of subjects, they had lesions that
caused sleepiness and these people would sleep about 20 hours per day and were always very tire.
The lesioned occurred in the brainstem or at the boundary between the hypothalamus and the
brainstem which led to the high sleepiness phenotype. In a good number of other patients the reverse
occurred, they had very severe insomnia and they would sleep short time and would have a hard time
going to sleep even if feeling tired.
Narcolepsy consist of sleep attacks during the day but instability between sleep/night throughout the
day. It appears than in some subjects, narcolepsy was associated with a lesion in part of the lateral or
posterior hypothalamus.
It is known that there are different centers in the brain that control sleep and wake. There is an
ascending arousal system whereby a number of brain nuclei in the hypothalamus, the thalamus and the
brainstem will project to the cortex and activate the cortex to stimulate wake. The pathway from the
brainstem through the hypothalamus and thalamus to the cortex is very important in stimulating wake.
This is why in subjects with lesions in those regions result in reduction of stimulation of sleep.
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Document Summary
Circadian and homeostatic regulation of sleep: sleep is not only regulated by the circadian system and there are two main aspects of regulation of sleep. Another important behavioral criteria that defines sleep is that the arousal threshold is really high which means that what you need as a stimulation in order to make the animal active is higher. It is regulated homeostatically as well in that when you have been awake for a longer time, you are more likely to fall into the quiescence state. Sleep can be defined in other ways such as with electrical criteria through eeg. There is also pharmacological criteria during different sleep stages as we have different neurotransmitters secreted that regulate different aspects of sleep. It must be important because if you prevent someone form sleeping there are big adverse effects and eventually death so it does not take so many dies until someone will die.
