Sl#p Science
The physiology of sleep and circadian rhythms
Importance of sleep and circadian rhythms – Why learn about it?
• Sleep is a basic human need and critical for life
• Healthy sleep is tightly coupled to intact circadian rhythms
o If sleep goes wrong ® affects circadian rhythms (and vice versa)
• Healthy sleep + circadian rhythms promote optimal physical and mental health
• Untreated sleep and circadian rhythm disorders exacerbate other medical conditions ® increase
healthcare costs
• Understanding may driver of poor sleep = improve healthcare, sleep-related service provision and
patient outcomes
What is sleep?
• A behavioural state in which we disengage from and are unresponsive to the environment
• Accompanied by postural recumbence (resting), behavioural quiescence and closed eyes
• Controlled by multiple neuronal networks in the brain
Circadian rhythms
• In the field of chronobiology – the study of biological temporal rhythms such as daily, tidal,
weekly, seasonal and annual rhythms
o Period of repetition
• Circadian rhythm – an endogenously driven 24-hour cycle in biochemical, physiological or
behavioural processes
• Chronotype – an expression of your circadian rhythm
o Attribute reflecting one’s preference for mornings or evenings
• When we sleep, our body temperature is at its lowest
• Rises when we want to wake up, then continues to rise throughout the day
• Drops when we want to go back to sleep
Kleitman’s Mammoth Cave experiment
• 4 June to 6 July 1938
• Create an environment removing all external cues to see if physiological rhythm existed
o Does our body continue to produce these rhythms no matter what
o Uniform conditions of temperature, illumination and quiet in the cave
• Found an endogenously generated 24h body temperature cycle
• Sleepiness flowed in contingence with temperature rhythm
Sleep is critical for survival, physical health, mental well-being, cognition, and productivity
Does sleep really matter?
• It is a non-negotiable aspect of survival
• Preserved throughout evolution = therefore conclude it is beneficial to all creatures
,• Physiological correlates of Prolonged Sleep Deprivation in Rats (1983)
• Stimulus presentations were times to reduce sleep severely in experimental rats
• Disc was continuously moving, rats had to keep moving, therefore stayed awake
• Experimental rats suffered severe pathology and death
o Pathology – fluid in lungs and trachea, collapsed lung, stomach ulcers, internal
haemorrhage, severe edema in limbs, atrophied testicles, scrotal damage, enlarged
bladder etc.
o Not only the brain is affected by sleep
• Some systems were more affected by sleep deprivation relative to others
• Time of death ranged from 5 to 33 days
What we know so far
• Reverses performance loss associated with wakefulness
• Enhances neural connections
• Housekeeping function relating to the lymphatic system while we sleep
o Waste removal e.g. Amyloid-beta (relating to Alzheimer’s)
• Immune support – adaptive immunity is more dominant when we are asleep
o Creates antibodies needed to protect against inhaled immune systems
• Restore brain energy stores
• Period of reduced caloric use
Conclusion:
Þ Physical health
Þ Mental health
Þ Emotional resilience
Þ Physical performance
Þ Cognitive performance
Physiology and Measurement of Circadian Rhythms
The basic physiology of circadian rhythms
• Free running rhythm – a sleep disorder in which the intrinsic circadian
rhythm is no longer entrained to the 24-hour cycle
o 24 hours 11 minutes (±16 minutes), just longer than the light-
dark cycle
o Sleep schedule shifts late every day
o No environmental cues
, Endogenously driven
• Master clock = suprachiasmatic nucleus (SCN) of
the hypothalamus
• Interacting network clock genes = PER, CRY,
BMAL1 and REVerb-alpha
• The molecular mechanism of circadian clocks in
mammals is generated by a cell-autonomous
transcriptional autoregulatory feedback loop
o Endogenously driven circadian rhythm
• Activation: CLOCK and BMAL1 form a heterodimer that acts as a TF complex ® binds to Ebox
elements ® promoting transcription of Per1-3 and Cry1, 2
• Repression: Once PER and CRY are translated, they form complexes that translocate back to the
nucleus ® inhibit the activity of CLOCK-BMAL1 complex (negative feedback loop)
• At low enough protein levels, genes are reactivated
• Cycle of protein levels increasing then decreasing = 24 hours
Entrained
• Adjusted to the environment by external cues
• Zeitgebers – a rhythmically occurring natural phenomenon which acts as a cue in the regulation
of the body’s circadian rhythms
o Light – primary external cue
o Meal time
o Locomotor activity
o Chronobiotic drugs e.g. melatonin acts as an entrainer
• Output of internal body clock = circadian rhythm
Criteria for circadian rhythms
1. The rhythms repeat once a day
2. Endogenous – the rhythms persist in the absence of external cues
3. Entrainable – the rhythms can be adjusted to match the local time
4. Temperature compensation – the rhythms maintain circadian periodicity over a range of
physiological temperatures
Parameters of biological rhythms
• Acrophase – the time interval in which the highest levels of
activity are expected (peak)
• Nadir – the time the rhythms troughs
The physiology of sleep and circadian rhythms
Importance of sleep and circadian rhythms – Why learn about it?
• Sleep is a basic human need and critical for life
• Healthy sleep is tightly coupled to intact circadian rhythms
o If sleep goes wrong ® affects circadian rhythms (and vice versa)
• Healthy sleep + circadian rhythms promote optimal physical and mental health
• Untreated sleep and circadian rhythm disorders exacerbate other medical conditions ® increase
healthcare costs
• Understanding may driver of poor sleep = improve healthcare, sleep-related service provision and
patient outcomes
What is sleep?
• A behavioural state in which we disengage from and are unresponsive to the environment
• Accompanied by postural recumbence (resting), behavioural quiescence and closed eyes
• Controlled by multiple neuronal networks in the brain
Circadian rhythms
• In the field of chronobiology – the study of biological temporal rhythms such as daily, tidal,
weekly, seasonal and annual rhythms
o Period of repetition
• Circadian rhythm – an endogenously driven 24-hour cycle in biochemical, physiological or
behavioural processes
• Chronotype – an expression of your circadian rhythm
o Attribute reflecting one’s preference for mornings or evenings
• When we sleep, our body temperature is at its lowest
• Rises when we want to wake up, then continues to rise throughout the day
• Drops when we want to go back to sleep
Kleitman’s Mammoth Cave experiment
• 4 June to 6 July 1938
• Create an environment removing all external cues to see if physiological rhythm existed
o Does our body continue to produce these rhythms no matter what
o Uniform conditions of temperature, illumination and quiet in the cave
• Found an endogenously generated 24h body temperature cycle
• Sleepiness flowed in contingence with temperature rhythm
Sleep is critical for survival, physical health, mental well-being, cognition, and productivity
Does sleep really matter?
• It is a non-negotiable aspect of survival
• Preserved throughout evolution = therefore conclude it is beneficial to all creatures
,• Physiological correlates of Prolonged Sleep Deprivation in Rats (1983)
• Stimulus presentations were times to reduce sleep severely in experimental rats
• Disc was continuously moving, rats had to keep moving, therefore stayed awake
• Experimental rats suffered severe pathology and death
o Pathology – fluid in lungs and trachea, collapsed lung, stomach ulcers, internal
haemorrhage, severe edema in limbs, atrophied testicles, scrotal damage, enlarged
bladder etc.
o Not only the brain is affected by sleep
• Some systems were more affected by sleep deprivation relative to others
• Time of death ranged from 5 to 33 days
What we know so far
• Reverses performance loss associated with wakefulness
• Enhances neural connections
• Housekeeping function relating to the lymphatic system while we sleep
o Waste removal e.g. Amyloid-beta (relating to Alzheimer’s)
• Immune support – adaptive immunity is more dominant when we are asleep
o Creates antibodies needed to protect against inhaled immune systems
• Restore brain energy stores
• Period of reduced caloric use
Conclusion:
Þ Physical health
Þ Mental health
Þ Emotional resilience
Þ Physical performance
Þ Cognitive performance
Physiology and Measurement of Circadian Rhythms
The basic physiology of circadian rhythms
• Free running rhythm – a sleep disorder in which the intrinsic circadian
rhythm is no longer entrained to the 24-hour cycle
o 24 hours 11 minutes (±16 minutes), just longer than the light-
dark cycle
o Sleep schedule shifts late every day
o No environmental cues
, Endogenously driven
• Master clock = suprachiasmatic nucleus (SCN) of
the hypothalamus
• Interacting network clock genes = PER, CRY,
BMAL1 and REVerb-alpha
• The molecular mechanism of circadian clocks in
mammals is generated by a cell-autonomous
transcriptional autoregulatory feedback loop
o Endogenously driven circadian rhythm
• Activation: CLOCK and BMAL1 form a heterodimer that acts as a TF complex ® binds to Ebox
elements ® promoting transcription of Per1-3 and Cry1, 2
• Repression: Once PER and CRY are translated, they form complexes that translocate back to the
nucleus ® inhibit the activity of CLOCK-BMAL1 complex (negative feedback loop)
• At low enough protein levels, genes are reactivated
• Cycle of protein levels increasing then decreasing = 24 hours
Entrained
• Adjusted to the environment by external cues
• Zeitgebers – a rhythmically occurring natural phenomenon which acts as a cue in the regulation
of the body’s circadian rhythms
o Light – primary external cue
o Meal time
o Locomotor activity
o Chronobiotic drugs e.g. melatonin acts as an entrainer
• Output of internal body clock = circadian rhythm
Criteria for circadian rhythms
1. The rhythms repeat once a day
2. Endogenous – the rhythms persist in the absence of external cues
3. Entrainable – the rhythms can be adjusted to match the local time
4. Temperature compensation – the rhythms maintain circadian periodicity over a range of
physiological temperatures
Parameters of biological rhythms
• Acrophase – the time interval in which the highest levels of
activity are expected (peak)
• Nadir – the time the rhythms troughs
