Sleep Centers

What, and where, are the sleep-inducing centers that act on the RAS ? Our suspicions are now focused on a collection of nerve cells at the midline of the brainstem that are known as the "nuclei of raphe" (from a Greek word meaning "seam" and signifying the juncture of the two halves of the brain). In Sweden, Annica Dahlstrom and Kzell Fuxe have shown that under ultraviolet light these cells emit a yellow fluorescence that shows they are rich in the hormone-like substance serotonin, which is known to have a wide spectrum of powerful effects on the brain and other organs of the body [see "Serotonin," by Irvine H. Page; SCIENTIFIC AMERICAN, December, 1957]. Suspecting from various preliminary pharmacological experiments that serotonin might play a role in sleep, we decided to test the effects of destroying the raphe cells, which are the principal source of the serotonin supply in the brain. We found that when we destroyed 80 percent of these cells at the level of the medulla in cats (the animals could not have survived destruction of a larger percentage), the cats became even more sleepless than those on which Moruzzi had performed his operation. In more than 100 hours of continuous observation with electrical recording instruments, our animals slept less than 10 percent of the time. Our results were closely related to those of Moruzzl's. His operation dividing the brainstem cut through the raphe system. We found that when we destroyed only the raphe cells on one side or the other of the site of his cut, our animals were reduced to the same amount of sleep (20 percent) as those on which he had performed his experiment. This gives us further reason to believe the raphe system may indeed be the main center responsible for bringing on sleep in cats.

These new developments bring serotonin into a prominent place in the research picture and offer an avenue for biochemical attack on the mysteries of sleep. The fact that the raphe cells are chiefly notable for their production of serotonin seems to nominate this substance for an important role in producing the onset of sleep. We have recently been able to demonstrate a significant correlation between the extent of the lesion of the raphe system, the decrease in sleep and the decrease in the amount of serotonin in the brain as measured by means of spectrofluorescent techniques. In physiological terms we can begin to see the outlines of the system of brain structures involved in initiating the on set of sleep and maintaining the first stage of light slumber. At the level of the brainstem, probably within the raphe system, there are structures that apparently counteract the RAS and by their braking action cause the animal to fall asleep. Associated with these structures there presumably are nearby structures that account for the modulations of electrical activity (notably the slow brain waves) that have been observed to accompany light sleep. This slow activity seems to depend primarily, however, on the higher brain structures, particularly the cortex and the thalamus; in a decorticated animal the pattern characteristic of light sleep does not make its appearance. We must therefore conclude that the set of mechanisms brought into play during the process of falling asleep is a complicated one and that a number of steps in the process still remain to be discovered.

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