Suffering from insomnia? Fruit flies do as well...

Familiar as it is, sleep is still rather mysterious. No one doubts it is important for good health, and amongst its functions is probably the processing of memories. Sleep is best studied in humans and other mammals, where it is characterised by a number of behavioural traits. These include quiescence, reduced body movement and muscle tonus, a characteristic posture, a high arousal threshold and compensatory sleep after sleep deprivation. In human sleep, five distinct stages are recognised – REM (rapid eye movement) sleep and four stages of non-REM sleep. These stages differ in their behavioural and physiological parameters and are characterised by certain patterns of brain activity. NREM1 and NREM2 are considered light sleep and NREM3 and NREM4 deep sleep, whilst REM sleep is typically associated with high brain activity and vivid dreams.

However, sleep is convergent and has evolved many times. In many, and perhaps all, of these cases the animals involved have complex behaviours, and typically show capacities for memory and learning. The overall similarities in sleep behaviour are striking in many respects and even include such features as changes in sleep during the life of the animal, responses to sleep deprivation, and parallels in arousal.

Cubozoans

In some ways one of the most remarkable examples is in the box jellyfish (Cubozoa), which are celebrated for their extraordinary camera eyes.There is no doubt that these highly venomous animals are by far the most sophisticated of the cnidarians, showing not only the advanced eyes, but also an active mode of life, courtship and copulation, and a complex internal anatomy, which includes a digestive tissue that is surprisingly similar to that of the mammals. Even more astonishing is that, when applying a novel tagging technique to study jellyfish behaviour, Jamie Seymour and colleagues observed periods of “inactivity”. During these, “the jellyfish lie motionless on the sea floor, with no bell pulsation occurring and with tentacles completely relaxed and in contact with the sea floor” (Seymour et al. 2004, Medical Journal of Australia, vol. 181, p. 707). It is difficult not to interpret this as sleep, and the researchers suggested that it might be related to cubozoan feeding behaviour. As active visual hunters of vertebrates, the jellyfish are likely to benefit from being inactive at night when vision is limited anyway.

Nematodes

Prior to each of its four moults, the roundworm Caenorhabditis elegans enters a period referred to as “lethargus”, which is associated with a quiescent behavioural state. The evidence that this state is indeed sleep-like is even more convincing than in the box jellyfish. Lethargus shows properties typically associated with sleep, such as reduced sensory responsiveness and homeostasis. The gene egl-4, which encodes a cGMP-dependent protein kinase (PKG), was shown to operate in sensory neurons and to regulate the sleep-like behaviour of C. elegans. Mutant worms with lower and higher PKG levels showed decreased and increased behavioural quiescence, respectively. Due to the association with larval moult, it has been suggested that sleep might have evolved to enable developmental change.

Arthropods

Sleep is found in a number of arthropods, notably in some insects, scorpions and also crustaceans such as crayfish. Amongst the insects, it is best documented in fruit flies (Drosophila) and honeybees (Apis mellifera).

Fruit flies

Drosophila melanogaster is the best-studied invertebrate sleep model, being well suited for behavioural, neurophysiological and genetic analyses. Fly sleep resembles mammalian sleep in a number of ways. Not only are there homeostatically regulated periods when the fly is immobile and has an elevated arousal threshold (and this does not require a functioning circadian clock), but there is also characteristic electrical activity in the brain as well as a distinctive signature of gene expression in the brain. Intriguingly, antihistamines increase sleep, whilst stimulants such as caffeine reduce it. Sleep seems to be regulated by the mushroom bodies, the higher brain centres involved in memory and learning. In accordance with this, it was shown that sleep is reduced and memory is poor in hyperkinetic mutants, and sleep deprivation leads to a loss of long-term courtship memories. Research in Drosophila not only helps to understand the mechanisms of sleep-related learning, but might also provide insights into causes and consequences of insomnia and perhaps narcolepsy. Whole-genome profiling in a line of flies that share several traits with humans suffering from insomnia revealed that genes implicated in metabolism, neuronal activity and sensory perception are modified in these flies and might also play a role in human insomnia.

Honeybees

Honeybees, which display considerable evidence of cognitive competence, show all the hallmarks of sleep: a characteristic posture, limited movement, reduced muscle tone, a decrease in body temperature and a raised reaction threshold (i.e. they can be prodded). Sleeping bees also ventilate discontinuously, with abdominal pumping being interrupted by extended ventilation pauses. Honeybee sleep has some striking similarities to mammalian sleep, including distinct sleep stages (from light to deep sleep) and compensatory mechanisms for sleep deprivation. Sleep deprivation in humans has various negative consequences, including imprecise or irrational communication. Similarly, sleep-deprived honeybees showed a deteriorated ability to communicate the position of a food source to nest mates through the waggle dance. This is likely to reduce the colony’s foraging efficiency. Another detrimental effect of sleep deprivation in bees is that the consolidation of certain (but not of other) forms of memory is affected (which indicates that different forms of memory are possibly mediated by different mechanisms).

Interestingly, honeybee sleep is highly plastic. Similar to human shift workers, bee foragers were shown to have flexible sleep schedules. The worker bees sleep primarily at night, but shifted the timing of sleep in relation to when food was available. In an experiment, the same bees were presented with a food source either in early morning or late afternoon – in the former case, they slept in the afternoon, while in the latter scenario the same individuals slept more in the morning. Thus, sleep displays temporal plasticity, depending on the ecological conditions. It remains to be seen whether this shift impairs health and performance of the bees, as has been demonstrated in humans. It is likely that sleep helps foragers consolidate their memories of the food sources they have recently used, thus maximising the benefits of foraging. Young bees do not show such strong circadian rhythms, but they do sleep as well and their sleep patterns show quite a few similarities to those of foragers. However, there are certain differences in sleep architecture, for example young bees remain in the lightest sleep stage for longer than foragers. This plasticity might be due to variation in the sleep-regulating neuronal network, which could be developmental or environmentally induced.

Even more intriguing are bursts of antennal movement in sleeping bees – could they be analogous to REM, i.e. do bees dream? Certainly they show characteristic electrical activity…

Cephalopods

Octopuses, which due to numerous similarities can be regarded as “honorary vertebrates”, extend the striking list of convergence in sleep. These extraordinary cephalopods have been observed to spend much of the day in their dens, with narrowed pupils and a particular skin colouration. Nor do they react to external stimuli during these times. When kept awake, they slept for longer the following day. It was shown that the activity of the vertical lobe, a brain region involved in visual learning, is higher during these behavioural rest cycles. It was even suggested that there might be an octopus equivalent of mammalian REM sleep, the period linked with memory consolidation. This would not come as too big a surprise, as octopuses are known for their exceptional learning abilities. Sleep in octopus, together with other features such as brain lateralisation, has been interpreted as evidence for a form of primary consciousness. In squid, similar periods of inactivity have been noted, but they still need to be confirmed as sleep.

Vertebrates

There is evidence of sleep in all vertebrate groups, but most is known about sleep in mammals, and this shows intriguing convergences with sleep in birds. For example, both birds and mammals have independently evolved slow wave sleep (SWS, a part of non-REM sleep in humans) and REM sleep, neither of which is observed in sleeping amphibians and reptiles. SWS is characterised by slow brain waves of high amplitude, while fast brain waves of low amplitude are recorded during REM sleep. There are remarkable similarities in the electroencephalogram (EEG) patterns during mammalian and avian SWS and REM sleep, but other aspects differ between the two groups. For example, different brain regions are involved in the regulation of these sleep patterns, the pallium in birds and the neocortex in mammals. Furthermore, SWS is probably involved in the transfer of memories from the hippocampus to the prefrontal cortex in mammals, but this does not seem to be the case in birds. It has therefore been suggested that the slow oscillation occurring during SWS might have another, more general, function that could be related to maintaining optimal brain function.

Intriguingly, sleep patterns are different in monotremes, which are considered the most basal mammals. Here, only a single stage of sleep has been demonstrated, which combines elements of REM sleep and SWS. A recent study on brain activity on ostriches (Struthio camelus), a basal bird, has revealed considerable similarities to the monotreme sleep pattern. Furthermore, in both monotremes and ostriches, the amount of REM sleep is greater than in other mammals and birds. The sleep pattern found in these two basal groups could thus represent an early stage in the evolution of REM sleep.