H&G Bonustoets 5
Slaap – H.8 p. 200 -229
Hormonen – H.10 p. 230 – 256
H. 8 Rhythms of Waking and Sleeping
Endogenous Rhythms
Endogenous circannual rhythm: a rhythm that prepares for seasonal changes.
- like in birds when they migrate.
Endogenous circadian rhythms: rhythms that last about a day.
- examples are: 24-hour wake-sleep rhythms, eating, drinking, urination, hormone secretion,
metabolism, sensitivity to drugs, mood and other variables.
Setting and Resetting the Biological Clock
Although circadian rhythms persist without light, your rhythm is not perfect. Unless something resets
it from time to time, it would gradually drift away from the correct time.
Zeitgeber: the stimulus that resets the circadian rhythm.
- light is by far the dominant zeitgeber for land animals, whereas the tides are important for some
marine animals.
- in addition to light, other zeitgebers include exercise, arousal of any kind, meals, and the
temperature of the environment.
Jet Lag
Jet lag: a disruption of circadian rhythms due to crossing time zones.
Problems stem from the mismatch between internal circadian clock and external time.
Phase-delay: most people find it easier to adjust to crossing time zones going west than east. Going
west, we stay awake later at night and then awaken late the next morning, already partly adjusted to
the new schedule. We phase-delay our circadian rhythms.
Phase-advance: going east, we phase-advance to sleep earlier and awaken earlier.
Adjusting to jet lag is often stressful. Stress elevates blood levels of the adrenal hormone cortisol,
and many studies have shown that prolonged elevations of cortisol damage neurons in the
hippocampus, a brain area important for memory.
Shift Work
,Problem:
People who work at night have great difficulty adjusting their circadian rhythm, because most
buildings use artificial lighting in the range of 150 to 180 lux, which is only moderately effective in
resetting the rhythm.
Solution:
People adjust best to night work if they sleep in a very dark room during the day and work under very
bright lights at night, comparable to the noonday sun. Short-wavelength (bluish) light helps to reset
the circadian rhythm better than long-wavelength light does.
Morning People and Evening People
Circadian rhythms differ among individuals.
Being a morning person or an evening person depends partly on age. It also depends on genetics and
several environmental factors, including artificial light. People who live in a big city, surrounded by
bright lights, are more likely to stay up late than are people in rural areas.
Mechanisms of the Biological Clock
The brain generates its own rhythm – a biological clock – and the biological clock is insensitive to
most forms of interference. The biological clock is a hardy, robust mechanism.
The Suprachiasmatic Nucleus (SCN)
Although cells throughout the body generate circadian rhythms, the main driver of rhythms for sleep
and body temperature is the suprachiasmatic nucleus (SCN), a part of the hypothalamus.
Suprachiasmatic nucleus (SCN): the main driver of rhythms for sleep and body temperature.
The SCN generates circadian rhythms itself in a genetically controlled manner. If SCN neurons are
disconnected from the rest of the brain or removed from the body and maintained in tissue culture,
they continue to produce a circadian rhythm of action potentials. Even a single isolated SCN cell can
maintain a circadian rhythm, although interactions among cells sharpen the accuracy of the rhythm.
The rhythms come from the SCN itself.
- SCN cells produce a circadian rhythm of activity even if they are kept in cell culture isolated
from the rest of the body.
- Also, when hamsters received transplanted SCN neurons, their circadian rhythm followed
the pattern of the donor animals.
How Light Resets the SCN
The SCN is positioned just above the optic chiasm in the human brain. A small branch of the optic
nerve, known as the retinohypothalamic path, from the retina to the SCN, alters the SCN’s settings.
Most of the input to that path, however, does not come from normal retinal receptors. The
retinohypothalamic path to the SCN comes from a special population of retinal ganglion cells that
have their own photopigment, called melanopsin, unlike the ones found in rods and cones.
,These special ganglion cells receive some input from rods and cones, but even if they do not receive
that input, they respond directly to light.
They respond to light slowly and turn of slowly when the light ceases. Therefore, they respond to the
overall average amount of light, not to instantaneous changes in light. The average intensity over a
period of time is exactly the information the SCN needs to gauge the time of day.
These ganglion cells respond mainly to short-wavelength (blue) light. For that reason, exposure to
television, video games, computers, and so forth, all of which emit mostly short-wavelength light,
tends to phase-delay the circadian rhythm and make it difficult to fall asleep at the usual time.
The Biochemistry of the Circadian Rhythm
The suprachiasmatic nucleus produces the circadian rhythm.
Fruit flies
Studies on the fruit fly found several genes responsible for a circadian rhythm.
- Period (PER)
- Timeless (TIM)
PER and TIM produce the proteins PER and TIM. The concentration of these two proteins, which
promote sleep and inactivity, oscillates over a day, based on feedback interactions among neurons.
The proteins TIM and PER remain low during most of the day and begin to increase toward evening.
They reach high levels at night, promoting sleep. They also feed back to inhibit the genes that
produce them, so that their level declines toward morning.
Because the feedback cycle is 24 hours, the flies generate a circadian rhythm even in an unchanging
environment.
However, in addition to the automatic feedback, light activates a chemical that breaks down the TIM
protein, thereby increasing wakefulness and synchronizing the internal clock to the external world.
Humans and other mammals
Mammals have three version of the PER protein and several proteins closely related to TIM.
Mutations in the genes producing PER proteins lead to alterations of sleep schedules.
Melatonin
The SCN regulates waking and sleeping by controlling activity levels in other brain areas, including
the pineal gland.
Pineal gland: an endocrine gland located just posterior to the thalamus. Releasing the hormone
melatonin.
The pineal gland releases the hormone melatonin.
Melatonin: a widespread chemical, found in nearly all animals, as well as in plants and bacteria. In all
cases, it is released mostly at night. In diurnal animals like humans, it increases sleepiness.
In nocturnal animals, it increases wakefulness.
, Melatonin secretion starts to increase about 2 or 3 hours before bedtime. Taking a melatonin pill in
the evening has little effect on sleepiness because the pineal gland produces melatonin at that time
anyway. However, people who take melatonin earlier start to become sleepy. In the process, it shifts
the circadian rhythm such that the person starts to become sleepy earlier than usual the next day
also.
Stop & Check
1. What evidence indicates that humans have an internal biological clock?
People who have lived in an environment with a light-dark schedule much different from 24 hours
fail to follow that schedule and instead become wakeful and sleepy on about a 24-hour basis.
2. Why do people at the eastern edge of a time zone awaken earlier than those at the western
edge on their weekends and holidays?
The sun rises earlier at the eastern edge than at the western edge. Evidently, the sun controls
waking-sleeping schedules even when people follow the same clock time for their work schedule.
3. What evidence strongly indicates that the SCN produces the circadian rhythm itself?
SCN cells produce a circadian rhythm of activity even if they are kept in cell culture isolated from the
rest of the body. Also, when hamsters received transplanted SCN neurons, their circadian rhythm
followed the pattern of the donor animals.
4. How does light reset the biological clock?
A branch of the optic nerve, the retinohypothalamic path, conveys information about light to the
SCN. The axons comprising that path originate from special ganglion cells that respond to light by
themselves, even if they do not receive input from rods or cones.
5. People who are blind because of cortical damage can still synchronize their circadian rhythm
to the local pattern of day and night. Why?
If the retina is intact, melanopsin-containing ganglion cells can still send messages to the SCN,
resetting its rhythm.
6. How do the proteins TIM and PER relate to sleepiness in Drosophila?
The proteins TIM and PER remain low during most of the day and begin to increase toward evening.
They reach high levels at night, promoting sleep. They also feed back to inhibit the genes that
produce them, so that their level declines toward morning.
Summary
1. Animals, including humans, have circadian rhythms – internally generated rhythms of activity
and sleep lasting about 24 hours, even in an unchanging environment. It is difficult to adjust
to a sleep schedule much different from 24 hours.
