Download Biological Rhythms

Biological Rhythms:
Circadian rhythms
Aims
To know the biological clock in control of the
Circadian Rhythm
To understand the difference between Endogeous
Pacemakers and Exogenous Zeitgebers
To be able to explain research into Circadian rhythms
Biorhythms
• A biological rhythm is any change in a
biological activity that repeats periodically.
Often synchronised: Daily, Monthly and
annual.
Circadian = 24 hour cycle; S/W cycle
Infradian = 24+ hour cycle; Menstrual
cycle
Ultradian = <24 hours; Sleep
Biological rhythms
• Circadian = 24 hour cycle; S/W cycle
• Infradian = 24+ hour cycle; Menstrual cycle
• Ultradian = <24 hours; Sleep
Key concepts
• Biological clocks
• The SCN: the Master Circadian Pacemaker
• Clock genes
– Human= CLK+BLMAL1=PER+CRY=negative feedback loop
• Circadian = 24 hour cycle; S/W cycle
• Endogenous Pacemakers regulated by Exogenous
Zeitgebers
• Human isolation studies: Siffre
• Chronotherapeutics: Aspirin
• Individual differences: Owl/Larks
• Animal research ethics
The SCN:
Supra Chiasmatic Nucleus
• In humans pathways are more complicated. The
main biological clock seems to be a small area in
the hypothalamus (involved in motivation,
temperature control) the (SCN) Suprachiasmatic
nucleus. The neurons of the SCN has an inbuilt
circadian rhythmic firing pattern.
• When the SCN of a Rat is lesioned the circadian
rhythm including sleep and feeding patterns is
totally disrupted for the animal (Stephen and
AO2
Zucker 1972)
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Task 1: Brain and Name
• Label your model with the following concepts
• P.171
• SCN, Optic Chiasm, Light, Pineal Gland, Optic
Nerve, branches from the optic nerve
M
• A neural pathway connects
the retina of each eye to
the SCN.
• This allows the amount of
Light falling on the retina
to influence the activity of
the SCN neurons.
• Thus indirectly affecting
the release of Melatonin
from the Pineal gland.
• When the SCN is intact it
regulates the manufacture
and secretion of
melatonin that takes place
in the Pineal Gland.
Controlling Circadian rhythms
• Why is the circadian rhythm 24 hours?
• The sun rises and sets every 24 hours.
• In humans the light level is detected in the eyes
and passed on to retinal ganglion cells, which also
contain a light sensitive pigment. These cells
release (NT) acetylcholine and have several effects.
They activate the neurones that cause dreaming
and some also connect to the SCN. Blind Rats lose
their cyclical behaviour. They sleep the same
amount of time but they do not have a clear
defined sleep phase. This confirms visual
information is needed to set the pattern. This is
also seen in the Miles Blind man case study.
SCN-Pineal Gland-Light/Dark-Melatonin
• The SCN responds to day length with neural
messages from the Pineal gland. The SCN is light
insensitive. The Pineal gland is light sensitive. The
cells of the pineal gland are similar to the
photoreceptors of the retina. So their interaction is
essential.
• Information from the SCN about darkness causes
the pineal gland to secrete melatonin, whilst
daylight inhibits its production. Melatonin
continues to rise and fall daily even when free
running. But the destruction of the SCN prevents
this rhythm.
Areas of the SCN (s)
• The neurons of the ventral SCN are now believed to function not
so much as clocks but rather as the location in the SCN that
receives and responds to external inputs,
• while the neurons of the dorsal SCN are believed to constitute
the SCN’s actual robust, endogenous clock. This view is
supported by certain jet-lag experiments which have shown that
in rats, the process by which a light stimulus resets the internal
clock occurs far more rapidly in the ventral SCN than in the
dorsal SCN.
• Scientists have now discovered that the neurotransmitter GABA
excites the cells of the dorsal SCN but inhibits those of the
ventral SCN. These opposing effects might influence the differing
reaction times of these two sub-regions when someone travels
across several time zones. This discovery thus opens new
insights into the mechanisms behind the disturbing symptoms
of jet lag.
• Ventral SCN influenced by external cues (Light)
• Dorsal SCN less affected by light
The Biological Clock - How does it work?

• Thought mainly to be an endogenous
(internal) mechanism
Our internal rhythms are thought to be
generated by protein synthesis within the
SCN. Protein is produced for a period of
hours until it reaches a level that inhibits
further production. Over the next few
hours the protein level gradually falls,
when it drops to a certain ‘threshold’ level
then production of the protein re-starts.
This generates an internal (endogenous)
biological rhythm – in humans of between
24 ½ and 25 hours. This is what happens inside the SCN
Protein synthesis takes place over a 24 hour period
THE TICKING OF THE BIOLOGICAL CLOCK
Suprachiasmatic Nucleus (SCN)
The basis of the circadian rhythm lies in interactions between certain proteins,
creating the ‘tick’ of the biological clock; it is an ingenious negative feedback
loop.
Darlington et al. (1998) first identified such proteins in the fruit fly, drospholia. In
the morning, two proteins, CLOCK and CYCLE (CLK-CYC) bind together. Once
joined, CLK-CYC produce two other proteins, PERIOD and TIME (PER-TIM). PERTIM has the effect of rendering the CLK-CYC proteins inactive, so that, as PERTIM increases, CLK-CYC decreases and therefore PER-TIM starts to decrease too
(negative feedback). This loop takes about 24 hours and, hey presto, you have
the biological clock!
The actual proteins vary from animal to animal. In humans the main pairs are
CLOCK-BMAL1 and PER-CRY (BMAL1 and CRY are also proteins). This protein
mechanism is present in the SCN (the central oscillator), and is also present in
cells throughout the body (peripheral oscillators). The presence of peripheral
oscillators explains why there are different rhythms for different functions such
as hormone secretion, urine production, blood circulation and so on.
THE TICKING OF THE BIOLOGICAL CLOCK
Suprachiasmatic Nucleus (SCN)
The basis of the circadian rhythm lies in interactions between certain proteins,
creating the ‘tick’ of the biological clock; it is an ingenious negative feedback
loop.
In humans the main pairs are CLOCK-BLMAL1 and PER-CRY (BMAL1 and CRY are
also proteins).
This protein mechanism is present in the SCN (the central oscillator), and is also
present in cells throughout the body (peripheral oscillators).
The presence of peripheral oscillators explains why there are different rhythms
for different functions such as hormone secretion, urine production, blood
circulation and so on.
The role of the Pineal gland
• In birds and reptiles the most important EP
(Endogenous Pacemakers) is the Pineal gland. This
structure contains receptors that respond to external
Light. Penetrating the thin layer of skull that lies above
the pineal gland.
• In turn these light receptors influence the activity of
neurons in the Pineal Gland. These neurons have a
natural rhythmic activity and also convert the NT
serotonin into the hormone Melatonin. Melatonin is
then released into the general circulation which acts on
many of the body’s organs and glands, and seems to be
responsible for the rhythmic nature of many activities
including the sleep/wake cycle.
AO1
For instance
• Melatonin acts on the brainstem sleep mechanisms
to help synchronise the phases of sleep and waking
(s/w), and it has been shown that injections of AO2
melatonin can produce sleep in sparrows.
/3
• The manufacture and release of Melatonin is
regulated by the amount of Light falling upon the
Pineal gland, decreasing as light increases.
• e.g Chickens wake and become active at dawn and
Melatonin secretions falls. This means that waking is
controlled by the biological clock in the Pineal
gland, it is adjusted to the actual time that morning
begins, which varies through out the year. This is a
good example of how EPs interact wit EZs.
AO1
Free running
• When biological clocks are allowed to run free
the S/W cycle extends. Daily exposure to light
or social cues such as a telephone call at the
same time each day is sufficient to keep the
human clock in time (Empson, 1993)
• Environmental factors other than light can
entrain (‘set’) the clock of animals such as
Hamsters. They will maintain a 24 hour cycle
without light in response to feeding, exercise or
social interaction.
Michel Siffre
• A French cave explorer
• Six months living in a cave
• His biological clock was allowed
to ‘free-run’,
• He was wired and monitored
• Erratic sleep-wake pattern at
first
• Then averaged just over 25
hours
• When he emerged it was the
179th day but in his days it was
only the 151st.
Folkard (1996) case study of Kate Aldcroft
• 25 days without access to
time
• She played amazing grace on
the bagpipes twice a day, on
what she believed was the
same time each occasion.
• The time at which she played
became later as the study
progressed.
• She began to sleep for longer
(up to 16 hours at a time) and
her sleep wake cycle extended
to 30 hours.
Folkard (1996) case study of Kate
Aldcroft
• Kate Aldcroft, a university student, was housed in a
laboratory for 25 days without any access to cues
about the time of day. To indicate her perception
of the passage of time she was asked to play
amazing grace on the bagpipes twice a day, on
what she believed was the same time each
occasion. The time at which she played became
later as the study progressed. She began to sleep
for longer (up to 16 hours at a time) and her sleep
wake cycle extended to 30 hours. This shows how
EZ’s help the human body coordinate with their
environment, and rhythmic activity maintains in
the absence of Ez’s. Jet Lag symptoms
Research to biological rhythms
• Generally it is shown that the light/dark rhythm of
the outside world synchronises the pineal gland and
the SCN. The French Cave man.
• Michel Siffre in 1972 went to live in a cave for 6
months. When he was awake the lights in the cave
were on, when he went to bed the lights were off.
His sleep/wake cycle regulated between 25 and 30
hrs (more than 24 hrs). When he reached the 179th
day, his days were only 151 since he started living
underground
Siffre
• Michel Siffre, a French cave explorer, spent over six months living
in a cave in Texas, deep under the ground, with no light, or
anything else to tell him what time of day it was. His biological
clock was allowed to ‘free-run’, that is, he just followed his body’s
inclinations, eating and sleeping whenever he chose, with no
fixed timetable. He was wired up so that some of his body
functions could be recorded; he had a telephone link to the
outside world, and was monitored by video camera. Siffre had a
fairly erratic sleep-wake pattern at first, but it settled down to a
pattern that averaged just over 25 hours, instead of 24 hours. We
do have an internal mechanism that regulates our sleep/wake
cycle, but it shifts to a length of approximately 25 hours if we do
not have external zeitgebers to reset it. When he emerged it was
the 179th day but in his days it was only the 151st.
Commentary
• Case study – Siffre is the study of one individual and
therefore has unique features. His body behaviour may
not be typical of all people and, also, living in a cave
may have particular effects due to, for example, the fact
that it is cold.
• Experiment – Siffre’s study was also an experiment ; he
controlled key variables (exogenous zeitgebers) to
observe the effects on the sleep-wake cycle. The
experimental approach (Scientific method) allows us to
demonstrate causal relationships.
• However, this level of control makes this research
reductionist.
Artificial lighting
Artificial Lighting
However, in the past psychologists did not think
that dim artificial lighting would effect the
Circadian rhythm (like sunlight). Therefore the
participants in these isolation studies were not
totally isolated from EZ’s.
Recent research suggests that this may not be
true; for example, Czeisler et al. (1999) altered
participants’ circadian rhythms down to 22 hours
and up to 28 hours just using dim lighting.
Evaluation:
• This is a one-participant study, so may not be
generalisable to all humans. Also Siffre’s living
conditions were unusual in other ways than simply
lacking time signals, and other factors such as
loneliness could have affected his behaviour.
• Similar studies have been done with rats, isolating
them from daylight (Groblewski), and found a similar
increase in the sleep-wake cycle, which supports the
findings from the Siffre study. A strength of the
study is that it lasted a long time, allowing Siffre’s
rhythms to settle down into a natural pattern.
Freewill and determinism
• On the other hand, there is evidence that we
can ‘will’ our biological rhythms to change.
One study found that people who were told to
wake up at earlier times of the night than
usual had higher levels of the stress hormone
ACTH than normal at the designated time and
they woke up earlier (Born, 1999).
• However, …….
Freewill and Determinism
EZ’s could not help him to adjust
Miles et al’s (1977) study of a blind
man. The man blind from birth had a
circadian rhythm of 24.9 hours. He
had to use stimulants and sedatives
to adjust his sleep-waking cycle to
the standard 24 hours. This shows
that light is the main exogenous
factor, as it reduces the natural 25
hour rhythm to 24 hours.
He could not over ride his biological
impairment. This also indicates that
visual information is important
Luce and Segal Artic Circle study (1966)
People who live within the
Artic circle sleep for 7 hours
per night despite the fact
that during the summer the
sun never sets. This shows
that light is not the only
zeitgeber, nor is the
biological clock only
influenced by light. Other
exogenous factors such as
social customs and
psychological factors
Aschoff and Wever (1976)
WWII Bunker
• Placed ppts in an underground WWII bunker
in the absence of environmental and social
time cues. They found that most people
displayed circadian rhythms between 24-25
hours, though some rhythms were as long as
29 hours.
Effected by
individual
differences
3 Week Cave study
• Folkard (1985) 12 participants lived in ‘temporal
isolation’ for 3 weeks…isolated from natural light
and other time cues. They agreed to go to bed at
11.45pm and get up when it said 7.45am. The
clock initially ran to time but gradually quickened
until it indicated a passing of 24hrs for 22hrs. All
but 1 of the participants kept pace with the
clock…thus demonstrating a strong free-running
rhythm. After the experiments it only took a few
days for the ppts to resynchronise their cycles to
the available time cues (clocks/light), showing the
importance of external cues.
Research to biological rhythms
• Kleitman (1963): Student participants went to
live to an underground bunker, with no cues of
light or dark. They had to choose their own
sleep/wake times. Their circadian rhythms
were extended between 25 to 27 hrs
Melatonin
• If you take 0.5mg of melatonin you will fall
asleep earlier and wake earlier (phase advance).
This is called phase advance because we advance
the sleep phase (sooner).
• If we are exposed to bright light in the evening,
the opposite occurs: we sleep and wake later –
phase delay.
– Phase advance – early bird – Older people
– Phase delay – owl – Teenagers/young adults
AO2/3: Individual differences
A relationship
• The SCN effects melatonin
production but also there are
receptors in the SCN that respond
to Melatonin.
• Which explains why melatonin
can reset the biological clock.
Light does not always effect free
running clocks
• Sometimes light is inefficient to over
ride free running clocks. Kelly et al
(1999) researched free running clocks
of submariners living on a US nuclear
submarine. These submariners live on
a 18 hours day. All cues, such as light
and social cues, do not shift the
rhythmic nature of melatonin
production on to the new 18 hour day.
It remains 24 hours.
Cryptochromes detect light
• Hall (2000) suggest that certain proteins
(Cryptochromes) in the body detect light ...
Explaining that by shining light on the back of
participants knees changed their rhythms
(Campbell and Hughes, 1988)
Why do we sleep in darkness and wake
in light?
• Conserve energy
• Protect from predators (insensitive to
movement, sensation and pain whilst asleep –
so not awaken by nocturnal predators)
• See next section Sleep and Theories of sleep
Essay
• Discuss the role of
endogenous
pacemakers and
exogenous
zeitgebers in
circadian rhythms
(25m)
• Studies such as these show that humans with
free running biological clocks settle into a
rhythmic s/w pattern of between 25-27 hours,
that is slightly longer than under normal
conditions. So we can draw 2 conclusions:
– Endogenous mechanisms can control s/w cycles in
the absence of light
– Light as an EZ is necessary to reset the clock
everyday so that the biological rhythm is
coordinated with the external world.
The physiology of sleep
Darkness
SCN sends message to pineal gland
Pineal gland responds to light levels and releases the
hormone melatonin, Cortisol decreases
Stages of sleep occur
Dawn breaks, light increases Cortisol rises & melatonin
levels drop
Noradrenaline is released
Arousal
Chronobiologists
Chronotherapeutics
 The symptoms of many illnesses fluctuate
over the 24hr cycle, such as hay fever, and are
worst around dawn; heart attacks are likely to
happen in the morning when blood is more
prone to clotting (thickened blood). Aspirin
can be used to treat heart attacks. This is most
effective around 11.00 pm which allows time
for the aspirin to peak in the blood (it takes 24 hours).
Hw
• Describe the human endogenous pacemaker (biological
clock) in control of the sleep wake cycle (6m).
• Describe one study of circadian rhythms (8m).
• What application to the real world has biological rhythm
research got? (4m)
• Explain individual difference effects on Circadian Rhythm
research (8m)
• Describe research and or explanations of the disruptions
to Circadian rhythms (8m)
• Discuss research and explanations of the disruption to
Circadian rhythms (16m) AO2/3 Evaluation/commentary
Essay plan: Explain the role of EPs and EZs in Circadian
rhythms (25 marks)
AO1
AO2/3/IDA
Circadian – 24 hours
Individual differences – onset and peak – Duffy
2000 moring/evening, owls and larks
EP and EZ
Individual differences- siffre personality, pop
validity, generalise
In humans SCN-PG-M
Case studies – idiographic
In Birds/reptiles PG-M
Artificial light – Boivin, Czeisler
Hamsters: Ralph (1990) and
Morgan (1995)
Miles Blind man, Artic study
DeCoursey (2000) Chipmunks
IDA: Ethics with animals (in depth discussion)
Siffre – 6 months, 25 hours
Generalisation/extrapolation
Aschoff and Wever (1976)
Practical application: Chronotherapeutics