SNOOZE OR LOSE

Here we go again. In order to finish my term paper on time, I must pull an “all-nighter”. It is a tactic I employ increasingly often despite knowing the consequences: I will be a zombie the next day, with my eyes drooping and my head embarrassingly bobbing as I ride the bus or ‘attend’ Powerpoint presentations. The complaint of “not enough hours in the day” is heard from
many people, not only last-minute students such as myself [1,2]. This frustration begs the question, what is the evolutionary reason I need to sleep for 8 of the 24 hours in a day?

Sleep has been studied in over 150 animal species, including invertebrates, fish, amphibians, reptiles, birds, and 14 orders of mammals [3], however fundamental questions of what sleep is doing and why remain largely a mystery[4]. Recent studies are making discoveries that reveal what happens during sleep, and allow for exciting theories to be proposed regarding the need for sleep.

What is sleep?

Most of us would recognize someone who is sleeping. It is generally characterized by a reduction in body movement, unresponsiveness, and a lack of consciousness. In 1953, Nathan Kleitman of the University of Chicago provided some of the first evidence of brain activity during sleep by discovering that during sleep, people experience periods of rapid eye movement, now commonly known as REM sleep [5]. In fact, all terrestrial mammals examined to this date exhibit REM sleep in alternating cycle with non-REM sleep [3]. Through technological achievements in neural imaging and micro-scale wire probes, sleep is studied at the cellular (neurons in particular) level [4]. Non-REM sleep is marked by synchronous, low frequency neuron activity in the cortex. In contrast, brain activity during REM sleep resembles wakefulness [6]. It is during REM phase, that we most commonly experience dreams. Dreaming is accompanied by excitation of the brain’s motor control systems, causing muscle twitches that give REM sleep its characteristic eye movements. In order to inhibit most body movement during REM sleep, the brain stops releasing the chemicals that would activate motoneurons (brain cells that control muscle cells) [4,6]. These chemicals are known as neurotransmitters, and are responsible for carrying signals from one neuron to another. Additionally, the brain releases a different set of neurotransmitters that actively shut down motorneurons [6].

Sleep has also been shown to affect brain systems that control internal organs [7,8]. Heart rate, body temperature, hormone levels, and breathing are all regulated differently during REM and non-REM sleep (and compared to being awake) [7,8]. The precise signals that induce the onset of sleep are not completely understood, however a small group of brain cells have been discovered at the base of the forebrain appear active only during non-REM sleep [4,6]. These cells are called sleep-on neurons, and are known to be partly activated by increased body heat. In REM sleep, specialized cells called REM sleep-on neurons become especially active [4,6].

The ubiquity of sleep throughout the animal kingdom suggests that it appears early in the evolutionary tree (of mammals), and that it serves an essential function (or many) [8]. Classification schemes for sleep are challenged to deal with the impressive variety of sleep behaviours exhibited in different animals. Perhaps most curious from a human perspective are whales and dolphins, which are able to sleep while swimming. Their trick is to only shut down half of their brain (and corresponding eye). This resting half of the brain undergoes activity such as REM and non-REM sleep, while the active half (and active eye) remains attentive to predators, environment and breathing cues [9]. After approximately two hours, the animal will switch sides in order to rest both halves of the brain. Humans require (on average) approximately 8 hours of sleep per night, while the opossum needs 18, and elephants get by with only 3 [3]. A survey of sleep characteristics across taxonomy reveals that evolutionary relatedness does not determine sleep time (e.g. the range of primate sleep duration extensively overlaps the duration of sleep for rodents) [3]. Rather, it is the size of an animal that is the best indicator of the amount of sleep it needs [4]. Larger animals tend to need less sleep than smaller animals, likely a consequence of larger animals having lower body/brain temperatures and slower rates of metabolism (the chemical process of breaking down food for energy and using this energy to construct cell components such as proteins). Furthermore, all sleeping animals release (or stop releasing) neurotransmitters, which disables movement and reduces environment awareness [6]. These correlations of sleep properties to metabolism and neurotransmitters must be taken into account by any theory attempting to explain the basis for sleep.

Do we need to sleep?

Now, having reviewed the occurrence of sleep, my question remains: What is the function of sleep, and why is it needed? The obvious answer is that adequate sleep is required to be alert and awake, but this is similar to saying that eating is to prevent feelings of hunger. Just as eating evolved as a means to nourish the body’s cells (and their processes), sleeping must have a similar justification as a requirement for sustaining life.

In the past, investigations of the function of sleep have often taken the form of sleep deprivation studies. Randy Gardner holds the Guinness World Record for intentionally going the longest without sleep. In 1965, as part of a high-school science project, 18 year old Gardner stayed awake for 264 hours (11 days). During his sleep deprivation, he reportedly experienced significant deficits in concentration, motivation, perception, and problem solving, however he recovered normal cognitive function after a few nights’ sleep. Being sleepy while driving has been shown to be as dangerous driving drunk [10], and lack of sleep has been implicated in depression and obesity [1,2]. Due to the associated health risks, the Guinness Book of Records no longer sanctions sleep deprivation records. The Vietnamese news agency, Thanh Nien, has been following Tai Ngoc, who has been awake for 35 years following a fever in 1973 [11]. Ngoc is apparently mentally sound and suffers no ill effect (other than some grumpiness).

Total sleep deprivation in rats has been shown to lead to weight loss (despite increased food consumption), and ultimately death [4,6]. For reasons that are still a mystery, rats kept without sleep will die within 10 to 20 days—a faster death than if they are withheld food but sleep normally.

The drive for sleep is so strong that achieving total sleep deprivation requires repeated and intense stimulation. Such stress confounds the results of sleep function studies based on sleep deprivation, and points to the need to develop new experimental procedures that reduce stress contamination. Stress effects likely contributed to the now convincingly debunked theory that sleep deprivation leads to insanity [4].

The Function of Sleep: Current Understanding

The function and need of both REM and non-REM sleep remains unclear, and is an area of active research. Jerome Siegel, a professor of psychiatry at the Brain Research Institute of the University of California Los Angeles, is a leader in the sleep research field and a proponent of functional theories for REM and non-REM sleep. Recall the observation that small animals, with a fast metabolism, tend to sleep more than larger animals, with slower metabolisms. The processes involved in metabolism can generate free radicals, which are extremely reactive chemicals that can damage and even kill cells. High metabolic rates lead to increased free-radical damage in cells, and can impair tissue functions. Injured cells are typically replaced with fresh ones produced by cell division, however most brain regions do not continue actively dividing after birth. Siegel and his colleagues propose that during non-REM sleep the brain enters a state of slower metabolism, and lower temperature, thus providing a favourable environment for enzymes to be synthesized and repair cells [4,6].

To account for REM sleep, Siegel hypothesizes that the cessation of neurotransmitter release (which is observed during REM phase) is vital for the proper function of neurons [4,6]. Several studies support the theory that a constant release of certain neurotransmitters can desensitize neurons to that stimulus [4]. Therefore, the break in neurotransmitter release during REM sleep provides a rest period for receiving neurons to regain their sensitivity. Maintaining this sensitivity may be crucial during waking for regulating emotion (many antidepressant pharmaceuticals act on the reception of neurotransmitters).

A puzzling property of REM sleep (that may not be adequately addressed by the sensitivity theory) is that when an animal is forced to go without REM sleep, it will repay this “debt” by achieving more than the usual amount of REM sleep when it is finally allowed to reach this phase [4].

A significant amount of research is exploring the role of sleep in memory consolidation and learning[12]. An exciting result supporting this theory is reported by David Euston in this week’s edition of Science [12]. Euston records the patterns of neural activity in the prefrontal cortex of rats during a repetitive sequence task. Interestingly, these patterns of activity are also observed during sleep, but compressed in time by a factor of 6 to 7. The authors propose that when behavioural constraints are removed, the brain’s intrinsic processing speed is much faster than it is in real time, and that the observed replay may play a role in the process of memory consolidation. Furthermore, a recent study of sleep time in Drosophila showed that a rich social experience, versus an impoverished one (as in isolation), increased the duration of sleep [13].

In all animals studied, the amount of time spent in REM gradually decreases from as the subject matures [4,6]. Even more interesting, the amount of time in REM sleep for an adult in a given species is proportional to how immature the offspring are at birth [4,6]. The platypus (an early mammal, evolutionarily speaking) is born completely defenseless and blind, and achieves approximately 8 hours of REM sleep per day [3,4]. In contrast, newbord dolphins are able to swim at birth, and do almost no REM sleeping. Additionally, preventing REM sleep in cats during early development can lead to visual system abnormalities [8]. This evidence suggests that the neural activity during REM sleep plays an important role in establishing neural connections and sensory development.

Sleep and Evolution

Research on sleep has shown that it is phylogenetically ancient [3,8]. Some researchers argue that the primary function of sleep is trivial (that of rest), and that the complexity we observe is the result of evolutionary “leftovers” [14]. Characteristics such as REM sleep and thermoregulation, that are unique to mammals, may be functionally secondary. Studies looking at the sleep of reptiles (the evolutionary parent to mammals and birds) are currently underway, and may provide insight into when and whey the dual mode (REM/non-REM) of sleep evolved in mammals. What would be a phenotypic trait of sleep that could be favourably selected for through evolution? The “Preservation and Protection” theory holds that sleep serves an adaptive function by protecting the animal. Sleep forces the animal to stay quiet and hidden, helping it avoid predation. This argument has been criticized for failing to explain why the brain is required to disengage from the external environment during sleep (animals who are preyed upon typically disengage to a lesser extent) [14]. However, the “Preservation and Protection” theory does reverse the question: why are we ever awake?

Alas, the sun has risen, and my “all-nighter” must come to a close. Today I join the ranks of the tens of millions of North Americans who are affected by sleep deprivation each year [1,2]. Although I am still waiting for a complete and accurate justification for why (functionally and evolutionarily) I need to sleep for one third of my life, the findings and theories reviewed here imply that sleep likely serves multiple functions, and is essential for healthy life. I may not understand sleep, but I can’t cheat it.

References

1. Carpenter, S. Sleep deprivation may be undermining teen health. Monitor on Psychology 2001; 32:9.

2. Bettelheim, A. What is keeping Americans up at night?. CQ Researcher 1998; 8:24.

3. Campbell, S.S., and Tobler, I. Animal sleep: a review of sleep duration across phylogeny. Neurosci Biobehav Rev 1984; 8:269-300.

4. Siegel, J. Why we sleep. Scientific American 2003; 289:92-97.

5. Aserinsky, E. and Kleitman, N. Regularly Occurring Periods of Eye Motility, and Concomitant Phenomena During Sleep. Science 1953; 118: 273 – 274.

6. Siegel, J. Clues to the functions of mammalian sleep. Nature 2005; 437:1264-1271.

7. Benca, R.M., and Quintas, J. Sleep and host defenses: a review. Sleep 1997; 20:1027-37.

8. Kavanau, J. L. Origin and Evolution of Sleep: Roles of Vision and Endothermy. Brain Res Bull 1997; 42:245-264.

9. Hecker, B. How do whales and dolphins sleep without drowning? Scientific American Online. link. Retrieved November 20, 2007.

10. Horne, J. and Reyner, L. Vehicle accidents related to sleep: a review. Occup. Environ. Med. 199;56:289-294.

11. Thao, V.P. Vietnam man handles three decades without sleep. Thanh Nien, 2006-02-14

12. Ganguly-Fitzgerald, I., Donlea, J., and Shaw, P.J. Waking Experience Affects Sleep Need in Drosophila. Science 2006; 313:1775-1781.

13. Euston, D.R., et al. Fast-Forward Playback of Recent Memory Sequences in Prefrontal Cortex During Sleep. Science 2007; 318:1147-1150.

14. Rial, R.V., et al. The trivial function of sleep. Sleep Med Rev 2007;11:311-325.