Biological Rhythms: Circadian rhythms

1. 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

2. IDEAs Disadvantages of the Biological approach • The Synoptic Tool Kit • (Synoptic - presenting a summary or general view of a whole)

3. 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

4. Biological rhythms • Circadian = 24 hour cycle; S/W cycle • Infradian = 24+ hour cycle; Menstrual cycle • Ultradian = <24 hours; Sleep

6. 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

8. The SCN: Supra ChiasmaticNucleus • 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 Zucker 1972) AO2/3

9. 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

10. 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. M

11. 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.

12. 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.

14. 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 GABAexcites 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

15. 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

16. THE TICKING OF THE BIOLOGICAL CLOCKSuprachiasmatic 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-CYCproduce two other proteins, PERIOD and TIME (PER-TIM). PER-TIM has the effect of rendering the CLK-CYC proteins inactive, so that, as PER-TIM 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.

17. THE TICKING OF THE BIOLOGICAL CLOCKSuprachiasmatic 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.

18. The role of the Pineal gland AO1 • 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.

19. For instance AO1 • 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 melatonin can produce sleep in sparrows. • The manufacture and release of Melatonin is regulated by the amount of Light falling upon the Pineal gland, decreasing as light increases. • e.gChickens 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. AO2/3

20. 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.

21. 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.

22. 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.

23. 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

24. 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

25. 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.

26. 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.

27. Artificial lighting

28. 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.

29. 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.

30. Freewill anddeterminism • 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, …….

31. FreewillandDeterminism 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

33. 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

34. 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

35. 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.

36. 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

37. 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

38. 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.

39. 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.

40. 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)

41. 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

42. Essay • Discuss the role of endogenous pacemakers and exogenous zeitgebers in circadian rhythms (25m)

43. IDA Disadvantages of the Biological approach • The Synoptic Tool Kit • (Synoptic - presenting a summary or general view of a whole)

44. 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.

45. 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

46. Chronobiologists

47. 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 2-4 hours).

48. 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

49. Essay plan: Explain the role of EPs and EZs in Circadian rhythms (25 marks)