Sleep and Circadian Rhythms Flashcards

1
Q

Information surrounding sleep

A
  • Sleep is a natural, periodic state that involves reduced responses to environmental stimuli and decreased mobility
  • It is a behaviour observed in all humans across cultures and numerous other species, even in unicellular organisms – humans spend a third of their lives sleeping
  • Sleep is a type of behaviour that always fascinated people, especially because it involves dreaming (mythology, Sigmund Freud etc)
  • In the last few years there has been a renewed interest in the scientific study of sleep
  • Sleep differs from states such as coma (extended period of unconsciousness), vegetative state or brain death (no sign of brain activity and no response to stimuli)
  • Sleeping is very different to resting
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2
Q

What are the 2 processes sleep is controlled by?

A

Homeostatic (S) if we do not sleep we accumulate sleep debt (the more we’re awake the more we want to go to sleep)

Circadian (C) – sleep tends to happen at a particular time during the 24-hour cycle

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3
Q

Two-process model of sleep

A

Circadian rhythm is regular, we are active during the day then we are less active during the night and this has a regular pattern.

For the homeostatic drive we start off with very little of this homeostatic drive and when we wake up we’re very alert but this drive accumulates the more we stay awake and then theres a point we want to go to sleep.

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4
Q

The Study of Sleep
Polysomnography

A
  • The ‘gold standard’ of sleep research
  • Discovered by Hans Berger 1929
  • Used initially in cats but now it is used for research and for clinical purposes
  • Involves recordings of electrical activity from multiple sources “poly” somnography
  • Recordings revealed a specific sleep architecture (the way that things are changing)
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5
Q

Polysomnography: list the types of recordings

A
  • EEG recordings (electroencephalogram): recordings of activity of populations of neurons in the brain underneath the skull
  • EOG recordings (electrooculogram): recordings of activity of the muscles around the eyes to decipher eye movements
  • EMG recordings (electromyogram): recordings of the activity of the muscles in the body
  • These recordings can be combined with others such as heart rate, temperature, breathing (O2) etc.
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6
Q

During wakefulness, what are the different types of neuronal activity which are observed in the EEG recording?

A

Beta waves consist of irregular activity of 13–30 Hz.
- fast activity
- Beta activity takes place when the brain is processing information
- The person is alert and attentive to events in the environment or engaging in cognitive processes

Alpha waves consist of activity of 8–12 Hz.
- Occur when a person is resting quietly, not particularly aroused or excited and not engaged in strenuous mental activity

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7
Q

Stages of brain activity during sleep

A
  • Sleep begins with a state of relaxation, feeling drowsy
  • Stage 1 (3.5–7.5 Hz): presence of theta activity - it is a transition between sleep and wakefulness
  • Stage 2: Sleep begins – characterized by irregular activity and also sleep spindles (12-14Hz) although these occur in other stages of sleep and K complexes which are only found during stage 2.
  • Stage 3: High-amplitude and low-frequency delta activity (less than 3.5 Hz)
    – Synchronized, regular waves, reflecting synchrony and coordination in the activity of neurons in underlying brain areas
    – There is a slowing down of brain activity as well as other bodily functions, such as heart rate, breathing, temperature, kidney function, etc
    – Sometimes referred to as slow-wave sleep (SWS), or deep sleep.
    – hard to wake people up when they are in this stage
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8
Q

REM Sleep
1- what is and and characterised by?
2- what did Aserinsky and Kleitman,1953 find?
3- what did Michel Juvet, 1959 find?
4- what happens

A

1- A sleep phase characterized by increased brain activity and asynchrony in brain waves accompanied by muscle atonia

2- Aserinsky and Kleitman,1953: Sleep characterized by rapid eye movements - Rapid Eye Movement sleep (REM)

3- Michel Juvet, 1959: deep sleep, in terms of muscle activity but light sleep, in terms of brain activity (he thought the more we sleep the more our muscles relax)- Paradoxical sleep

4- Facial twitches, erections, vaginal secretions and dreaming occur during this stage

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9
Q

Brain activity during sleep

A
  • Sleep recordings revealed four distinct patterns of activity, three stages of sleep (NREM), 1, 2, 3 and an additional REM sleep episode
  • We cycle through each stage and back, with each cycle lasting approximately 90 minutes
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10
Q

Findings in other species?

A

SIMILAR FINDINGS

In other species/ mammals we can get very similar activity and similar recodings from EEG, EMG and EOG.

We can distinguish the 3 stages of sleep- in slow wave sleep we have little muscle activity and slowing of brain activity where as in REM we have more theta activity and brain is more active but very little recording in EMG.

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11
Q

Cycle of sleep on a typical night

A

Starts with wakefulness then goes through the different stages (stage 1 then stage 2), going into deeper levels of sleep (slow wave sleep) at stage 3. Then we come up to stage 2 and stage 1 then we might get a short REM episode and then go down again into deeper stages of sleep, then come up again and have another REM episode a bit longer this time. This processes repeats throughout the night.

Things to point out:
- we spend more time in slow wave/ deeper stages of sleep earlier in the night where as we may not even go to the slow wave sleep phase later in the night. (circadian component). It does make a difference what time we go to bed because we may miss some circadian patterns.
- the opposite happens for REM sleep- it starts off with short episodes but then we start to spend more time in REM sleep when closer to wakefulness.

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12
Q

Dreams:
1- discovered by?
2- considered important in?
3- what are most dreams related to?
4- what did Calvin Hall et al (1982) find?

A

1- Discovered by Dement and Kleitman, 1957 when participants were awakened from REM sleep. They tended to report vivid dreams

2- Considered important in psychoanalysis:
- Freud thought of dreams as the ‘royal route to the unconscious’ and an opportunity to realise our secret wishes
- Jung viewed dreams as a glimpse into the collective unconscious

3- Most dreams are related to events that happen in a person’s life

4- Calvin Hall et al (1982): analyzed 10,000 dreams of healthy people and found that more than 64% are associated with sadness, anxiety or anger whereas 18% are happy dreams and only 1% involved sexual content

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13
Q

Contemporary views on dreaming
Allan Hobson (2004)

A

Activation-synthesis hypothesis (bottom-up view on dreams)

  • The brainstem is activated during REM and sends signals to the cortex which creates images with actions and emotions from memory
  • The frontal cortex is less activated during dreaming so there is no logic in the timing or the sequence of events, although the person tries to organise the content into a logical story when awake
  • There is no meaning in dreaming although dreams are based on each person’s experiences
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14
Q

Contemporary views on dreaming
Valli and Revonsuo (2009)

A

Argued that dreams are biologically adaptive and they lead to enhanced coping strategies

  • Coping Hypothesis (also known as ClinicoAnatomical Hypothesis) (top-down view on dreams)
  • People dream about events that they find threatening in their lives and this helps to find solutions to their problems
  • Support for this hypothesis is the evidence that problem solving occurs during sleep (“sleep on it”)
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15
Q

The neural basis of sleep
1- idea of?
2- what produce sleep-wake cycles?
3- _____ secreted by ____ during _____ promotes sleepiness

A
  • Idea of a sleep-inducing substance perhaps due to the fact that many natural substances cause sleep i.e. morphine
  • Neurochemicals and hormones produce sleep-wake cycles
  • Melatonin secreted by the pineal gland during the dark promotes sleepiness but it is not the only one
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16
Q

Adenosine

A
  • Accumulates during the day, after prolonged wakefulness and promotes sleep
  • Caffeine antagonises the effects of adenosine and decreases sleepiness
  • Released by astrocytes and it is a way to signal that there is very little energy. So astrocytes start to release adenosine to slow down the activity of our neurons. When we go to sleep (especially during slow wave sleep) the adenosine gets moved away and then we are able to function well. We have discovered that is we drink caffeine when we are really sleepy, we’re able to extend our wakefulness.
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17
Q

Observations and Discovery:
What did Constantine von Economo early 20th century observe and findings

A
  • observed patients with encephalitis

findings:
- Most had continuous sleepiness and would wake up only to eat and drink and these had damage in the base of the brain
- Fewer patients displayed insomnia and they had damage in an area of the anterior hypothalamus

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18
Q

Observations and Discovery
- what brain area was discovered and what does it contain?
- what does damage to this area cause?
- what does electrical stimulation to this area cause?

A
  • This area of the anterior hypothalamus was later identified as the ventrolateral preoptic area (vlPOA) which contains inhibitory neurotransmitters such as GABA
  • Damage to this area causes insomnia in rats and they eventually die
  • Electrical stimulation of this area causes sleepiness and sleep
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19
Q

Brain Areas involved in Wakefulness and Arousal
- who discovered these regions accidentally?
- what did they do?
- what resulted in waking the animal?

A
  • Moruzzi and Mogoun (1949) discovered these regions accidentally
  • While recording from anaesthetized cats they stimulated the cat’s brainstem and noticed that the delta waves were replaced by beta waves
  • Stimulating the brainstem in a sleeping cat resulted in waking the animal
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20
Q

Brain Areas involved in Wakefulness and Arousal
- what brain area promotes arousal?
- list the neurotransmitters important

A

The reticular formation (Reticular Activating System-RAS) is comprised by several nuclei in the brainstem that extend to the forebrain to promote arousal

  • Locus coeruleus (LC - NE/NA)
  • Raphé nucleus (RN – 5HT) - producing serotionin
  • Tuberomammillary nucleus (TMN-Histamine) antihistamines
  • Nucleus basalis of Maynert (NBM-Ach) also high during REM sleep
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21
Q

Key components of ascending arousal system and key projections from the VlPOA to areas of the ascending arousal system

A

The ventral lateral pre-optic area is inhibiting/ shutting down this arousal system using GABA because we want to sleep

The arousal system is doing the opposite, it is activating, releasing the neuron transmitters. They’re all promoting their individual neurotransmitters and sending projections to different brain areas and the cortex because we want to be alert and processing information.

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22
Q

The flip-flop switch Cliff Saper 2001

A
  • This processes is a battle between the two brain systems (sleep system and arousal system)
  • These systems are mutually inhibitory (they are trying to shut each other down)

Flip-flop is “on”:
- arousal areas are active and they are releasing all the neurotransmitters
- they are inhibiting the sleep promoting region, which is the ventral other optic area.
- this during the day is easier to do, they are managing to inhibit the ventral optic.

Flip-flop is “off”:
- happens at night time
- vlPOA is active
- It is inhibiting the arousal brain areas and we are able to go to sleep

23
Q

Orexin or Hypocretin

A
  • It is a peptide released from the lateral hypothalamus (LH)
  • Highly responsible for the maintenance of wakefulness (arousal)
  • Implicated in narcolepsy (we don’t have maintenance of arousal and this is because orexin is not there)
  • activation holds flip-flop “on”
24
Q

Circadian rhythms
- what is circadian split into
- what are rhythms of regualr patterns of activity associated with?
- what cycles
- what rhythms?

A
  • Circadian “circa” (around) and “dies” (day) - rhythms or regular patterns of activity associated with a 24h-cycle such as day and night
  • Endogenous cycles (“generated from within”) - our brain and body spontaneously generate their own rhythms based on the earth’s rotation
  • Endogenous rhythms can also be annual (migration) or seasonal (breeding)
25
Q

Circadian rhythms:
- what are humans?
- what does the 24h rhythm control?

A
  • Humans are diurnal (vs nocturnal)
  • This 24h rhythm not only controls sleep and wakefulness but also other important functions such as body temperature, secretion of hormones, urination, etc
26
Q

Average Body Temperature

A

There seems to be a major dive in temperature when we are asleep. Temperature then starts to climb up right before we wake up.

27
Q

Early Discoveries:
- what are not unique to humans and animals
- what did French geologist, Jean Jacque d’Ortous de Mairan (1729) experiment with

A
  • Biorhythms are not unique to humans and animals
    – flowers may open during the day and close during the night
  • 1729: French geologist, Jean Jacque d’Ortous de Mairan experimented with the mimosa plant
    – Even if isolated from light, dark or temperature cues the leaves continued their rhythmic behaviour
28
Q

In humans: Aschoff (1965)
1- where were humans placed?
2- what were pp’s allowed to do?
3- what did pp’s show?
4- what did they conclude?

A

1- Humans were placed in an underground bunker where no external cues
2- Allowed to select their light-dark cycle and turn the lights on and off at will
3- The participants continued to show daily sleep-activity rhythms, even though they drifted to >24hrs
4- Concluded that humans have an endogenous biological clock which governs sleep-wake behaviour

(free running- not entrained to have fixed rhythmicity in our clock)

29
Q

Setting and Resetting the Biological Clock: Entrainment
What are eternal cues that serve to set our biological clock called? + explain about them

A
  • External cues that serve to set our biological clock are called Zeitgebers
    (“time givers”)
  • The most potent zeitgeber for humans is light although there are others (meals, activity, temperature, etc)
  • When a zeitgeber resets a biorhythm, that rhythm is said to be entrained.
30
Q

Resetting the Biological Clock: Jet lag
- what is jet lag?
- what does it stem from?
- impacts?
- travelling west vs east?

A
  • Jet lag - a disruption of the circadian rhythms due to crossing time zones

– Stems from a mismatch of the internal circadian clock and external time

– Sleepiness during the day, sleeplessness at night, and impaired concentration

  • Traveling west (eg. US) “phase-delays” our circadian rhythms whereas traveling east “phase-advances” (few hours ahead eg. Cyprus) our circadian rhythms – people find it more difficult
31
Q

Variability in our circadian rhythms
1- what do circadian rhythms differ between?
2- name for morning vs evening people?
3- what about rhythms?

A

1- Circadian rhythms may differ between people and can lead to different patterns of wakefulness and alertness - chronotypes
2- Morning people “larks” and evening people “owls”
3- Rhythms have a genetic basis, but they also change as a function of age and other external factors (lifestyle, social factors etc).

32
Q

Chronotypes across the lifespan

A
  • We all start off (infancy and childhood) and finish off (adulthood and old age) as morning people “larks”
  • During adolescence there is an increasing shift towards “eveningness” – teenagers become “owls”, which is particularly difficult given that school starts early in the morning

– Some schools in the US have changed their curriculum to a later start in order to accommodate teenagers (A. Carskadon)

  • Differences in chronotype may result in “social jet lag”- sleeping at different times due to socialising
  • Morning people report to be happier than evening people
33
Q

The neural basis of the biological clock
Suspecting its existence
1- What did Curt Paul Richter, Prof. of Psychobiology at Johns Hopkins (1927) introduce?
2- what did he perform?
3- what happened to the rats?
4- what did he hypothesise in his book?

A

1- Curt Paul Richter, Prof. of Psychobiology at Johns Hopkins (1927): Introduced the concept that the brain generates its own rhythms, so it must have a biological clock which he attempted to locate in the brain of wild rats
2- He performed electrical lesions in various parts of their brain in order to locate the biological clock
3- The rats lost their rhythmic behaviour after damage to the hypothalamus
4- In his book “Biological Clocks in Medicine and Psychiatry” (1965) he hypothesised that many disorders may result from disruption of the biological clock

34
Q

What is the clock?

A

Suprachiasmatic nucleus

35
Q

The suprachiasmatic nucleus is the clock:
1- independent discovery by?
2- where is the primary biological clock located?
3- implications of lesions of this nucleus?

A

1- 1972: Independent discovery by researchers in two different laboratories: Moore & Eichler and Stephan & Zucker

2- The primary biological clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus

3- Lesions of this nucleus disrupted circadian rhythms of wheel running, drinking, and hormonal secretion, and was thus named “the master clock”

36
Q

The suprachiasmatic nucleus (SCN)

A

supra on top of chiasm

2 black circles are the biological structures of the SCN

37
Q

The SCN
1- what does recording electrodes in the SCN confirm?
2- what continues to function in a rhythmic pattern
3- what does transplantation of an SCN into a donor organism result in?

A
  • Recording electrodes in the SCN confirm that neurons are more active during the light period than during the dark period
  • A single cell extracted from the SCN and raised in tissue culture continues to function in a rhythmic pattern
  • Transplantation of an SCN into a donor organism results in the recipient following the donor’s rhythm
38
Q

How does light reach the SCN?

A
  • The SCN receives information about light through the retinohypothalamic tract, formed by a special population of ganglion cells (photosensitive retinal ganglion cells-PRGCs) which make up ~1-3% of ganglion cells (Berson et al 2002)
  • These PRGCs have their own photopigment called melanopsin and can respond directly to light, especially blue light (Provencio et al 2000)

– They do not rely on rods and cones which explains the fact that blind people remain entrained
– Experiments where rods and cones were inactivated had no effect on circadian rhythms
- Part of this tract terminates in the midbrain to control the size of the pupil in response to light

39
Q

The Retinohypothalamic Tract

A

retina is in the back of our eye

Referring to a special group of ganglion cells which are not giving information about the objects we see but the presence or absence of light. These ganglion cells are going to feed in the information into the superchiasmatic nucleus. Then this will feed information on to other areas of the brain such as the pineal gland for example in order to produce melatonin because there is absence of light outside.

40
Q

What makes this clock tick?
What did Jeffrey Hall & Michael Rosbash and Michael Young discover

A

Jeffrey Hall & Michael Rosbash (Brandeis Univ, Mass)
- Studied the SCN in Drosophila (fruit flies)
- 1984: Discovered the “per” gene and the “PER” protein (period)

Michael Young (Rockefeller Univ)
- 1994: Discovered the gene “tim” that produces the “TIM” protein (timeless)
- When TIM meets PER they combine and shut the period gene down

  • 2017 Nobel prize in physiology and medicine
41
Q

The Molecular Mechanism
Drosophila vs mammals

A

In drosophila, we have 2 proteins which are referred to as activators. So we have the clock and the cycle that come together on the enhancer box (E-box) and they initiate the transcription of certain genes. (eg. per gene into PER protein). When Per and Tim accumulate in the cytoplasm they start to form dimers (they pair up). So together they go back and translocate into the nucleus and they inhibit the transcription of more of themselves until all these proteins/ dimers are cleared out. This cycle takes place in a 24 hour window.

In mammals we have the same processes but it involves slightly different genes. Have the clock gene and the BMAL1 which are activating this processes. SO have the activation of Per1-3 and Cry1,2 that are also produced. When they meet, they dimerise and together they go back into the nucleus and inhibit the transcription of themselves.

42
Q

Transcription-Translation-Inhibition- Feedback Loop

A
  • A few genes and their protein products are involved in this clock
  • Transcription from DNA to mRNA, to translation into proteins which form dimers
  • These dimers enter the nucleus in order to inhibit transcription and then they decay
  • The cycle begins again in a daily rhythm
43
Q

SCN effects on the pituitary and the pineal gland

A

Pituitary Gland:
Glucocorticoid Release
Light phase
Arousal activities

Pineal Gland
Melatonin Release
Dark phase
Rest activities

44
Q

Other effects of the SCN

A
  • Breeding of animals is controlled by the SCN via the pineal gland
    – During winter, the increased melatonin produced at night inhibits the gonads which shrink
    – During spring, there is less melatonin produced which allows the gonads to enlarge, to produce testosterone and support mating behaviours
  • The time of day affects performance in humans on a wide range of cognitive tasks measuring attention, executive functions and memory
  • Treatment of disease can be influenced by circadian rhythms i.e. surgery outcome or pharmacotherapy
    – Toxicity of a drug varies from 20-80% depending on the time of day (not necessarily considered in drug studies)
    – Risk for illness also changes depending on the time of day, i.e. there is a higher likelihood of a stroke or heart attack in the morning
45
Q

SCN linked to timing

A

The SCN drives a number of slave oscillators, each responsible for the timing of a different type of behavior i.e. drinking, sleeping, body temperature, activity etc

Important that we do things in a systematic, orchestrated way.

46
Q

Sleep deprivation in rats

A
  • Rechtschaffen et al 1983: Sleep-deprived rats
  • The animals looked sick, they stopped grooming, became weak and lost their ability to thermoregulate.
  • They were losing weight although they were eating more and eventually, they died
  • In human studies there are restrictions due to ethical reasons but sleep deprivation is associated with increases in body weight
47
Q

Why do we sleep?

A
  • Adaptive
  • Restorative
  • Developmental
  • Cognitive processes
48
Q

A. Sleep is Adaptive
- what was the original function of sleep
- what is there a decrease/ increase in?
- how much energy does our brain normally spend?
- what is this and especially for?

A
  • The original function of sleep was probably to conserve energy
    – Decrease in body temperature of about 1-2 degrees Celsius in mammals
    – Decrease in muscle activity
    – Increase in sleep time when there is scarcity of food
  • Normally our brain spends ~20% of our energy even though it is very small (2%) compared to our body weight
  • This is true especially for NREM sleep, particularly SWS where metabolic rate and blood flow to the brain decrease, but not for REM sleep
49
Q

B. Sleep is Restorative

A
  • Sleep takes place at night, at the end of a busy day and helps us to feel refreshed and energized the next day
  • Activity during wakefulness results in the accumulation of free radicals (oxidative stress) and potentially toxic waste (such as amyloid beta).

– During sleep, restorative mechanisms take place to remove the free radicals and toxic waste

50
Q

C. Sleep Promotes Development

A
  • The first clue that perhaps sleep has a role in brain development comes from the fact that infants sleep a lot more than adults
    – REM sleep in adults accounts for about 20-25% of total sleep whereas in infants it takes up about 50% of total sleep time
  • During stage 3 sleep (SWS), Growth Hormone (GH) release is at its peak which is important for growth
51
Q

Sleep across the lifespan

A
  • Shows sleep across the lifespan
  • Non rem sleep is greater in childhood
  • Rem sleep is greater in infancy
  • We spend more time awake as we get older
52
Q

D. Sleep Facilitates Cognition
What does sleep enhance?

A
  • Sleep enhances learning & memory

– Performance on a newly learned task is often better the next day if adequate sleep is achieved during the night whereas deficits are evident following sleep-deprivation

– During sleep, neurons replay the previous experience to retain the information (Wilson and McNaughton, 1994).

– Evidence that possibly different types of learning may be supported by the different stages of sleep (SWS vs REM and declarative vs non-declarative)

  • Problem-solving and Creativity

– During sleep, the brain continues to process material and enables the solution to problems, as evidenced by the “aha” phenomenon upon waking

53
Q

Consolidation and Systems Consolidation:
- what dis Müller and Pilzecker (1900) find?
- memory trace storage?
- what happens to memory traces which are thought to be unnecessary?
- what helps to reinstate the brain?

A
  • Müller and Pilzecker 1900: consolidation helps to establish memories in our brains for future use
    – It involves the synthesis of new proteins and the formation of new synapses
  • The memory traces themselves are not stored in the hippocampus forever. Instead, they are transferred to areas of the cortex, known as systems consolidation
  • Memory traces that are thought to be unnecessary are removed Synaptic homeostasis hypothesis (Tononi & Cirelli 2014)
    – synaptic pruning during sleep helps to reinstate the brain so that it can be able to function and learn more the next day