Sleep Flashcards
Definition of sleep:
- 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
Definition of sleep 2:
- Sleep is controlled mainly by two processes:
- Homeostatic (S) - if we do not sleep we accumulate sleep debt
- Circadian (C) – sleep tends to happen at a particular time during the 24-hour cycle
- 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)
The study of sleep - polysomnography:
- 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
Polysomnography:
- 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.
Brain activity during wakefulness:
- During wakefulness, different types of neuronal activity are observed in the EEG recording:
- Beta waves consist of irregular activity of 13–30 Hz.
- 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
Brain activity during sleep:
· 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
REM sleep:
· A sleep phase characterized by increased brain activity and asynchrony in brain waves accompanied by muscle atonia
· Aserinsky and Kleitman,1953: Sleep characterized by rapid eye movements - Rapid Eye Movement sleep (REM)
· Michel Juvet, 1959: deep sleep, in terms of muscle activity but light sleep, in terms of brain activity - Paradoxical sleep
· Facial twitches, erections, vaginal secretions and dreaming occur during this stage
Brain activity during sleep 2:
· 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
Dreams:
· Discovered by Dement and Kleitman, 1957 when participants were awakened from REM sleep. They tended to report vivid dreams
· Considered important in psychoanalysis:
- Freud thought of dreams as the ‘royal route to the unconscious’ and an opportunity to realize our secret wishes
- Jung viewed dreams as a glimpse into the collective unconscious
· Most dreams are related to events that happen in a person’s life
· 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
Contemporary views on dreaming - J. Allan Hobson (2004) – 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 organize the content into a logical story when awake
· There is no meaning in dreaming although dreams are based on each person’s experiences
Contemporary views on dreaming - Valli and Revonsuo (2009) – argued that dreams are biologically adaptive and they lead to enhanced coping strategies:
· Coping Hypothesis (also known as Clinico-Anatomical Hypothesis) (top-down view on dreams)
· People dream about events that they find threatening in their lives
· Support for this hypothesis is the evidence that problem solving occurs during sleep (“sleep on it”)
The neural basis of sleep:
· 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
Adenosine:
· Accumulates during the day, after prolonged wakefulness and promotes sleep
· Caffeine antagonizes the effects of adenosine and decreases sleepiness
Observations and discovery:
· Constantine von Economo early 20th century observed patients with encephalitis
- 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
· This area of the anterior hypothalamus was later identified as the ventro-lateral 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
Brain areas involved in wakefulness and arousal:
· 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
· 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)
- Tuberomammillary nucleus (TMN-Histamine) * antihistamines
- Nucleus basalis of Maynert (NBM-Ach) * also high during REM sleep
Orexin or hypocretin:
· It is a peptide released from the lateral hypothalamus (LH)
· Highly responsible for the maintenance of wakefulness
· Implicated in narcolepsy
Circadian rhythms:
· Circadian “circa” and “dies” - 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)
· 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
Early discoveries:
· 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
In humans - Aschoff (1965):
· Humans were placed in an underground bunker where no external cues
· Allowed to select their light-dark cycle and turn the lights on and off at will
· The participants continued to show daily sleep-activity rhythms, even though they drifted to >24hrs
· Concluded that humans have an endogenous biological clock which governs sleep-wake behaviour
Setting and resetting the biological clock - entrainment:
· 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.
Resetting the biological clock - jet lag:
· 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 “phase-delays” our circadian rhythms whereas traveling east “phase-advances” our circadian rhythms – people find it more difficult
Variability in our circadian rhythms:
· Circadian rhythms may differ between people and can lead to different patterns of wakefulness and alertness - chronotypes
· Morning people “larks” and evening people “owls”
· Rhythms have a genetic basis, but they also change as a function of age and other external factors (lifestyle, social factors etc).
Chronotypes across the lifespan:
· 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”
· Morning people report to be happier than evening people
Suspecting its existence:
· 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
· He performed electrical lesions in various parts of their brain in order to locate the biological clock
· The rats lost their rhythmic behaviour after damage to the hypothalamus
· In his book “Biological Clocks in Medicine and Psychiatry” (1965) he hypothesized that many disorders may result from disruption of the biological clock
The suprachiasmatic nucleus is the clock:
· 1972: Independent discovery by researchers in two different laboratories: Moore & Eichler and Stephan & Zucker
· The primary biological clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus
· Lesions of this nucleus disrupted circadian rhythms of wheel running, drinking, and hormonal secretion, and was thus named “the master clock”
The SCN:
· 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
How does light reach the SCN?:
· 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
What makes this clock tick?:
· 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
Transcription-translation-inhibition-feedback loop:
· 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
SCN effects on the pituitary and the pineal gland:
· The SCN regulates waking and sleeping by controlling activity levels in other areas and secretory glands such as the pituitary and the pineal gland
Other effects of the SCN:
· 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
Why do we sleep?:
· A very important question which is partially answered
· Sleep is ubiquitous. All animals engage in sleep or a rest state comparable to sleep
· What if we decide to stay awake and not go to sleep
Sleep deprivation in rats:
· 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
Why do we sleep 2?:
· Adaptive
· Restorative
· Developmental
· Cognitive processes
Sleep is adaptive:
· 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
Sleep is restorative:
· 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
Sleep promotes development:
· 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
Sleep facilitates cognition:
· 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
Consolidation and systems consolidation:
· 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
