How long have we been sleeping?
“J’ai peur du sommeil comme on a peur d’un grand trou,
Tout plein de vague horreur…”
In his phenomenal ‘Les fleurs du mal’ (‘Flowers of Evil’), Baudelaire promenades through the darkness of the night and with his characteristic gloomy brush, paints sleep as ‘a great hole’ that he fears. This myth surrounding sleep as a mysterious unknown, a darkness, an absence,‘a bottomless pit’, a break from our living-walking-eating-procreating lives, has surpassed much beyond poetry and fiction and imagination. The sleep researchers, too, are still not quite sure as to why we need to go to bed in a circadian, periodic fashion. In the simplistic view, it is seemingly futile perhaps, to imagine a third of life that we spend without feeding or having sex. The honey droplets dripping on our eyes each night, evidently, still needs a deeper scientific reflection to comprehend its meaning.
Several hypotheses are under inspection today towards deciphering the mysteries of sleep. One such theory suggests that it is perhaps beneficial to remain inactive as this reduces the possibility of encountering a predator that might be active at that given time of sleep. Another theory says that it is crucial to reduce the demand of energy and through sleep, conserve some for the next day. Associated with this, it is also thought that sleep gives the animals a chance to restore, rejuvenate and repair what is exhausted during the time of wakefulness. Probably the most highlighted notion on the biological significance of sleep revolves around the brain plasticity theory which suggests that sleep allows changes in the structural organization of the brain and by doing so, enables learning of new things and consolidation of new memories.
One way to understand the fundamental importance of sleep is to ask how far back sleep could be traced in the evolutionary landscape. Does every animal sleep? Or at least, do most animals sleep? Studies so far have reached down to the Jellyfish, which is known not to have a brain, as ancient as one could go for the signs of sleep-like states. In 2017, a group at CalTech found sleep-like immobility in the Jellyfish. These Jellyfish rhythmically contract and relax their bell-like structure, an action described as ‘pulses’; the frequency of which is less at night than during the day. Sleeping Jellyfish tell us that the brain is dispensable for sleep, but whether one could do away with the nervous system altogether and still achieve sleep is still an open question.
Researchers have reported sleep-like immobility in many other animals, including invertebrates. Some of these animals have even been used as model systems to study the molecular and neural underpinnings of sleep using the vast plethora of genetic and physiological tools that these systems offer. Fruit flies, for example, show immobile sleep-like state every night. They can be sleep-deprived, mechanically or even with genetic manipulations of wake-promoting neurons, which inevitably results in rebound sleep the following day and the return of the sleep pattern to normal in successive days; essentially attesting reversibility. Sleeping animals also have high arousal threshold. They can be woken by caffeine or pulses of light which points towards the fact that this immobility is not likely to be the result of some sort of paralysis or coma and can be reversed. These behavioral parameters to distinguish sleep from other immobilities have been widely used to establish model systems which could then be used to answer questions on sleep.
But there is a concern with identifying sleep by testing mostly for behavioral standards such as reversibility, higher arousal threshold and rebound. Some believe that sleep could only be ascribed to a given event of immobility not only through the behavioral signs but also, if the distinctive brain waves that mirror sleep, can also be found. Measurement of the electrical activity in the brain, therefore, in addition to recording behavior, is crucial for some to say that an animal is indeed sleeping. Commenting on the Jellyfish study, Nadine Gravett from the University of Witwatersrand told The Atlantic, “They can’t claim that jellyfish have a sleep-like state…The most that can be said is that under controlled laboratory conditions, they show distinct periods of immobility—and it’s possible that sleep could happen during these periods.”
The hallmark electrical signatures in the brain that parallel sleep have only been observed in mammals, reptiles and birds. Have these brain waves originated only recently in the evolutionary timescale? The abundance of sleep-like phenomena in other vertebrates like fish and invertebrates raise the question whether sleep-like states were always accompanied by these neural hallmarks. Practical difficulties in recording electrical activity through invasive methods (for example, planting an electrode in the brain) in non-mammals have been the biggest challenge standing in the path towards the answer of this question.
An article (https://www.nature.com/articles/s41586-019-1336-7.pdf) published in the journal Nature in July this year discovered a non-invasive method to tackle this issue. When neurons are active and firing, their calcium levels rise. Using this principle, the authors of this article utilized a technique in which a transgenic fluorescent protein would parallel the calcium levels in the neurons, and therefore, the fluorescence would be the surrogate of the neural activity (https://neuwritesd.org/2018/05/10/a-bright-idea-illuminating-the-brain/). This was done using a light-sheet microscope and intact, immobile and almost transparent infant Zebrafish. With this magnificent set-up with single-cell resolution spanning the whole body of an animal, the authors demonstrated that even these water-dwelling creatures show remarkable sleep signatures in their brain just like the mammals, reptiles and birds.
For example, humans show two distinct phases of sleep, which include non-REM sleep and REM (abbreviation for Rapid Eye Movement) sleep. Non-REM sleep is deep sleep where the brain activity is low and the muscles are relaxed; whereas during REM sleep, which essentially poses a paradox in which the brain activity is such as if the animal is awake. The authors studying the Zebrafish found that the Zebrafish exhibit two types of sleep similar to humans: slow burst sleep and propagating wave sleep, similar to non-REM and REM sleep, respectively. The only marked difference that they observed was a lack of rapid eye movement in the REM-equivalent phase in the Zebrafish. These otherwise massively similar sleep patterns between us and the Zebrafish put the origin of certain aspects of sleep back to at least 450 million years ago – which is impressive.
In addition to the sheer fundamental appeal of this study on the origin of sleep, it is also practically very useful to know that humans and Zebrafish are not really very different when it comes to sleep, as the sleep researchers (like many neurobiologists) are always looking towards finding the perfect animal system in which they can model a particular physiology. Obesity, many metabolic disorders, heart diseases, diabetes and many more have been linked to sleep. Studying sleep in humans, especially in order to decipher the molecular and neural aspects is evidently cumbersome and in many cases, almost impossible. On the other hand, thanks to this study, as Zebrafish and humans sleep alike, one could use Zebrafish to frame fundamental questions on sleep with much more confidence. In addition to this, unlike other animal models like mice and rats, Zebrafish are diurnal just like humans which, circadianly speaking, brings us even closer.