The states of sleep
Michel Jouvet
Scientific American (1967)


Brain Activities in Sleep

The Two Sleep States

The Suppression of Wakefulness

Sleep Centers

Paradoxical Sleep

The Evolution of Sleep

The Chemistry of Sleep


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The Chemistry of Sleep

All of this suggests that some chemical process takes place during the recovery period. Let us suppose that the deprivation of paradoxical sleep causes a certain substance related to the nervous system to accumulate. The excess of paradoxical sleep during the recovery period will then be occupied with elimination of this "substance," presumably through the agency of "enzymatic" factors that act only during paradoxical sleep.

There is reason to believe that certain enzymes called monoamine oxidases, which oxidize substances having a single amine group, play a crucial role in bringing about the transition from light sleep to paradoxical sleep. We have found that drugs capable of inhibiting these enzymes can suppress paradoxical sleep in cats without affecting either light sleep or wakefulness. A single injection of the drug nialamide, for example, will eliminate paradoxical sleep from the cycle for a period of hundreds of hours. We have also found that this potent drug can suppress paradoxical sleep in cats that have first been deprived of such sleep for a long period in the pool experiment.

The findings concerning the probable importance of the monoamine oxidases in the sleep mechanism raise the hope that it may soon be possible to build a bridge between neurophysiology and biochemistry in the investigation of sleep. If it is indeed a fact that these enzymes play an important role in sleep, this tends to strengthen the hypothesis that serotonin and noradrenalin, which are monoamines, are involved in the two states of sleep-serotonin in light sleep and noradrenalin in paradoxical sleep. There are other bits of chemical evidence that support the same view. For example, the drug reserpine, which is known to prevent the accumulation of monoamines at places where these compounds are usually deposited, has been found to be capable of producing some specific electrical signs of paradoxical sleep in experimental animals. Further, the injection of certain precursors involved in the synthesis of serotonin in the brain can produce a state resembling light sleep, whereas drugs that selectively depress the serotonin level in the brain produce a state of permanent wakefulness.

We can put together a tentative working hypothesis about the brain mechanisms that control sleep. It seems that, the raphe system is the seat responsible for the onset of light sleep, and that it operates through the secretion of serotonin. Similarly, the locus coeruleus harbors the system responsible for producing deep sleep, and this uses noradrenalin as its agent. In cyclic fashion these two systems apply brakes to the reticular activating system responsible for wakefulness and also influence all the other nerve systems in the brain, notably those involved in dreaming.

Dreaming itself, particularly the question of its evolutionary origin and what function it serves, is still one of the great mysteries of biology. With the discovery of its objective accompaniments and the intriguing phenomenon of paradoxical sleep, however, it seems that we have set foot on a new continent that holds promise of exciting explorations.

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