• The phylogenetic framework depends on the postulation that sleep states emerged early in animal evolution

• Certain functional aspects are probably conserved from an ancestral sleep state

• Sleep evolved fundamentally as a metabolic state of the animal and serves functions outside the nervous system

• Sleep serves metabolic roles in humans

Sleep Across Phylogeny

• Some animals sleep more deeply, whereas others extend the duration of their sleep or sleep at inappropriate times

• Behavioural response to sleep deprivation provides evidence of sleep’s importance

• Sleep during lethargus has been termed developmentally timed sleep

• Sleep can be found in an animal that has a mere 302 neurons and that lacks overt circadian behavioural rhythms

• Jellyfish show sleep behaviour, demonstrating that neither a brain nor a CNS is required for sleep

Animal Examples

• Cockroach: when forced to continue locomotion during its resting time, showed an increase in subsequent immobility → suggests homeostatic guarding of the resting behavioural state

• Honeybee: reduced arousability was associated with decreased responsiveness of visual interneurons, demonstrating a physiological basis to this behaviour

• Fruit flies: prolonged immobility during the night, are less responsive to stimulation during their quiescent period and, following forced movement during the sleep period, display immobility during the early day

  • Have a clearly defined CNS with a brain with an approximately 24h circadian periodicity

• Jellyfish: the frequency of their pulsations is higher during the day than during the night, their responsiveness is reduced at night, and forced movement at night results in reduced activity and reduced responsiveness during the subsequent day

Evidence for an Ancestral Sleep State

• There is more evidence supporting that sleep existed in a common ancestor than that sleep evolved convergently

• Evolutionarily distance species share common sleep functions

• Claims of a wholly sleepless animal must be viewed with scepticism

REM and NREM Sleep

• REM and NREM sleep occur in mammals and birds and may also be present in reptiles, suggesting that among vertebrates it was present at least as early as when amniotes evolved more than 300 million years ago

Neural Requirements for Sleep

• Brain neurons are top-down regulators of sleep–wake states in mammals

• There is evidence that there is a bottom-up organization

  • As electrical activity of neurons within local neural groups becomes synchronized with the activity of neurons in other local neural groups, behavioural sleep emerges at the organismal level

• The local sleep-like state during wake might interfere with the role of the network in normal wake behaviour and is not as effective as organismal sleep at achieving global sleep functions

• When local neural groups eventually become coordinated, the organism shows sleep behaviour

• Sleep and wake lie on a continuum

• Neither central regulatory neurons nor an intact organism are needed to generate sleep states

Is Sleep Need Driven Only by Neurons?

• The influence of signals from non-neuronal tissues on sleep regulation suggests that the ancestral function of sleep might have resided in non-neuronal cells

Are Neurons Necessary for Sleep?

• Sleep and wake might be controlled by endocrine signals

• Non-neuronal cells producing endocrine signals might also be able to influence motor behaviour and reduce sensitivity to external stimuli, resulting in sleep behaviour

• There is sleep in animals that lack neurons

• If, at its core, sleep were serving a metabolic function, it is not inconceivable that plants, algae and single-cell prokaryotes will also ultimately be considered to sleep

Sleep and Metabolism

Sleep During Development and Sickness

• In humans and other terrestrial mammals that are born in an underdeveloped state, sleep need is greatest during development

• Increased sleep is apparently coupled to somatic and neural growth and development

• Mammals, arthropods and nematodes also all sleep more in the setting of either an infectious or non-infectious illness

Sleep-Wake Cycles as Temporal Metabolic Compartmentalization?

• Metabolic temporal compartmentalization may serve not only to separate chemically incompatible reactions but also to divert energetic resources used in neural processing to other uses, whether in the brain or in the body

• Overall metabolic costs may be reduced by restricting such processes to run at high capacity for a limited portion of the day

• The more waste that has been accumulated, the more that can and will be cleared

• Emergence of numerous tissue-specific and organism-specific molecular changes during both sleep and wake

• Sleep is a time for anabolic activity and the building of macromolecules in all cell types

• Within the brain, different regions and cell types show unique patterns of sleep-modulated transcription

• Sleep-induced savings in neuronal energy and anabolic metabolism may be conducive to neural plasticity

Summary and Conclusions

• Sleep emerged early in animal evolution

• Metabolic demands are a key driver of sleep regulation

• Sleep itself serves primarily metabolic roles

• Once the essential function of sleep is understood, it may come to be appreciated in organisms that lack the behavioural features that once defined it

• It is likely that in the future, we can add more specific biochemical or molecular parameters to our definition of sleep

• Several genes that affect both metabolism and sleep have been identified in mammals