ANAT 322 Lecture Notes - Lecture 19: Wild Type, Cryptochrome, Bioluminescence
7 Jun 2018
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ANAT 322 Winter 2017
Lectures
Lecture 19:
→ Circadian Rhythms and Neuroendocrine Regulation
1. In the general population, many people when thinking about circadian rhythms think about the
sleep/wake cycle. Sleep is only one of the many things regulated by a circadian rhythm in physiology.
Many different things in the body ae regulated in a daily or circadian manner or 24-hour cycle manner.
Rhythm refers to the beat or the recurring nature of a sound in music for example. In biology it is the
same and a biological rhythm is anything that will vary over time in a recurring fashion, in cycles.
There are many different types of biological rhythms and circadian rhythms is only one of them. They
are classified according to the duration of the cycle. If you have a hormone that varies with a rhythm in
that between each peak you have 2 hours, in this case the period of the rhythm is two hours.
2. We can assess the period in a rhythm which is the duration of a cycle or the time it takes to go from
one point of the sample up to the point that reaches the same level. It is important because it allows us
to classify biological rhythms.
The amplitude is how high or what is the level of variation of a hormone for example.
The phase refers to when the rhythm peaks in time or at what time does the peak occurs.
Ultradian rhythm are those that are less than a day such as heart beats (period of 1s), neurons in the
brain that shows spikes of electrical activity (ms range).
Infradian rhythm can be over days, weeks or years and year-long rhythms are normal in the
physiology of many animals that mimic changes in the environment.
Circadian rhythms (circa=about, dian = diem or day) have a period of a day in duration.
3. Bottom right shows melatonin rhythm in sheep which is circadian and it is high during the night and
very low during the day in the blood. In both winter and summer there is a rhythm of melatonin but the
shape of the rhythm is different.
We can see LH for three different sheep and the spikes have different periods. When infradian
rhythms last a year they are also called circannual rhythms.
If you keep under a constant photoperiod or duration of the day, you will still see these rhythms of
prolactin that are seen in the wild. Between two peaks there are 15 weeks so the rhythm lasts about a
year and so these are circannual rhythms.
4. At the top right corner there is melatonin which has a circadian rhythm and it is high during the night
and down during the day.
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6-sulfatoxymelatonin is a breakdown product of melatonin that can be found in the urine so you can
collect the urine at different times and it has a rhythm with the same phase as melatonin.
Body temperature is not constant and varies during 24 hours by about 1 degree and it is highest by
the end of the afternoon and it is at its lowest point by the end of the night.
Plasma cortisol also varies and it is high at the beginning of the day and goes down until the evening
and goes up during the night. The peak of cortisol in the morning is not simply a response to light
because it is low in the evening and goes up and is high already even before the subject wakes up which
is an indication that these circadian rhythms are not simply a response to the dark-light cycle. They are
endogenous or intrinsic to the body and those that are not cannot be called circadian.
We can also see somatotropin (growth hormone) has a peak during the night.
5. Jetlag occurs when you go quickly to another cycle and outside you have a different day/night cycle
but within you have your own endogenous rhythms that contradict or are not at the same phase as the
environment.
A person in London goes to Hong Kong and suddenly the day/night cycle has changed by 8 hours but
the circadian rhythm of body temperature has not moved. The consequences are that the maximum of
the temperature will no longer be in the afternoon but at the beginning of the night and the minimum
will occur in the early afternoon. If the person goes to LA, the core body temperature minimum will be
in the day and the peak will be during the night.
The environment is able to reset our biological rhythms such that when we have jetlag we only have
it for several days until the clocks are reset.
6. If you look at someone in the lab and you want to look at temperature or melatonin rhythm, there are
things you need to remove from the environment of the subject to see endogenous rhythms.
Melatonin is high during the night and low during the day. However, if you flash lights for half an hour
after midnight, you can see that melatonin drops vey suddenly in the blood and when you turn off the
light melatonin levels recover. This is not because of a circadian rhythm of melatonin but because of the
topical external application of light which will have through some mechanisms effects on melatonin
leels. So if ou at to look at soeoe’s elatoi leels, ou eed to hae o light or er dim light
during the night otherwise melatonin will be masked (left panel)
Temperature is high in afternoon and low in the night. In this experiment, the subjects were isolated
in the lab and were put on short days of half an hour of dark and one hour of light and the subject was
only allowed to sleep during the dark half hour for two full days. Despite the fact that they do not see a
real dark/light cycle and do not sleep for 8 hours, you can still see the 24 hour cycle of core body
temperature with the maximum at about 3pm and minimum at night. Every time the subject sleeps, the
temperature drops by maybe two or three decimals which is because sleep does some masking of
temperature. During the night the temperature goes down but because you sleep it will go further down
so if you want to look at the true endogenous cycle then you need to prevent the subject form sleeping.
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7. Speleologist that goes into underground caves decided to combine his passion for caves with
questions he had about biological rhythms and he wanted to know if these persisted in underground
caves where there is no life/dark cycles and temperature and humidity is constant.
He went two months underground and started in late June until august and recorded different values
for sleep, temperature and so on. He had contact with the surface to get things for live but they were
not telling him what time it was or what day it was. Overall, he was able to see in his sleep diary that he
had about 24 circadian rhythms and he confused some naps he was having with actual sleep and so
there was an error in the date. Overall, this showed that in constant conditions circadian rhythms.
He wanted to study the effect of age on biological rhythms when he went back and there are effects
on this.
8. The first example of a real human chronobiology lab was in Germany and it was the work of one of
the founders of the field of the biology of time or rhythms.
This as i the earl ’s, ad there ere i Gera a lot of shelters that ere unused so he used
all of these to make these labs where you can control the lights. The person is isolated there of extended
periods of life and the sleep, temperature and other parameters are recorded and controlled.
9. They do experiments that allow them to look at physiological phenomena such as temperature,
hormones or even genes in conditions where rhythms will not be masked by the environment or
entrained (reset to another time) by environmental cues as with jetlag.
To do that they will remove as much as possible anything that can mask a rhythm and they will
remove exposure of subject to time cues. The person in the room will not know what time of the day is
or the day it is and experimenters coming into the room are trained to not tell time or day.
There are two types of experiments, the constant routine and the forced desynchrony.
10. Constant routine consists of keeping the subject in the lab with conditions that will mask as little as
possible the circadian rhythms.
Sleep can mask core body temperature which goes further down so you will keep the subject awake
but you cannot be awake for more than about 2-3 days so these usually last maximum 30-35 hours.
Movement can also affect some biological rhythms so activity in the morning can mask cortisol and
there is an extra burst when you are active. This is why the person is maintained in a semi-recumbent
posture which is of about 45 degrees. Melatonin can be masked by light as well as gene expression so
you want to have very dim light that do not impact the measurements. Food can mask different
hormones, metabolic values, rhythm of glucose, so you need constant feeding.
These for characteristics will make sure you minimize masking of circadian rhythms.
In the graphs we can see different measurements for entrained conditions which means regular
sleep/wake cycle or light/dark cycle and constant routine which are the conditions that are controlled.
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Document Summary
Circadian rhythms and neuroendocrine regulation: in the general population, many people when thinking about circadian rhythms think about the sleep/wake cycle. Sleep is only one of the many things regulated by a circadian rhythm in physiology. Many different things in the body ae regulated in a daily or circadian manner or 24-hour cycle manner. Rhythm refers to the beat or the recurring nature of a sound in music for example. In biology it is the same and a biological rhythm is anything that will vary over time in a recurring fashion, in cycles. There are many different types of biological rhythms and circadian rhythms is only one of them. They are classified according to the duration of the cycle. It is important because it allows us to classify biological rhythms. The amplitude is how high or what is the level of variation of a hormone for example.
