Neurophysiology of the States of Sleep
Michel Jouvet
Physiological Reviews 47 (2) pp : 117-177 (1967)


Definitions and Abbreviations

State of Sleep Characterized by Slow Cortical Activity Slow Sleep

Behavioral aspect

Electrophysiological aspect

Structures and mechanisms responsible for slow sleep

State of Sleep Characterized by Fast Cortical Activity-Paradoxical Sleep

Behavioral aspects

Electrophysiological aspects

Structures and mechanisms responsible for paradoxical sleep

A synthesis of paradoxical sleep mechanisms

Relationship with oneiric activity in man

Phylogenesis of the States of Sleep

Ontogenesis of the States of Sleep

Relationship Between Slow Sleep and Paradoxical Sleep Unicity or Duality of Sleep Mechanisms

A Possible Monoaminergic Theory of Sleep

Figure 1

Figure 2


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II. State of sleep chacterized by slow cortical activity slow sleep

B. Electrophysiological Aspects

The EEG aspects of slow sleep (see Fig. 1) have been known for a long time (130, 204, 274, 371). They consist of the appearance of 11- to 16-cycles/sec spindles of large amplitude predominant at the level of the frontal and associative areas, whereas the synchronized activity is less important at the level of the auditory and visual areas, the olfactory bulb (154, 200), and the pyriform cortex (162). The spindles are also recorded in bipolar derivation at the level of the mesencephalic reticular formation (RF) (204, 251) and the pyramidal tract (20). They are often, though not always, synchronous with the cortical spindles. They are usually followed by 1- to 4-cycles/sec high-voltage slow waves that are also recorded at the level of the subcortical structures. The spindles and slow waves are of lesser amplitude and may be absent (then a low-voltage fast activity may prevail) at the level of the specific thalamic nuclei (240), the pulvinar (12), and the caudal part of the brain stem. Yet no systematic analysis of the topography of the distribution of slow waves at the level of the subcortical structures has been made by using methods of quantitative integration such as those already used in acute (399) or chronic experiments (23).

Some local peculiarities of brain activity during sleep must be pointed out. At the level of the dorsal or ventral hippocampus and at the level of the structures in efferent relationship with the hippocampus (7), high-voltage spikes (500-900,microv) appear (253). These have also been described during barbiturate narcosis (73, 370). Such an activity still exists at the level of the limbic structures in the animal deprived of the neocortex (240). It is then the only electrical index of the appearance of slow sleep. Thus in the cat only two EEG consecutive aspects, spindles and slow waves, can be recorded during slow sleep. It appears that in carnivora falling asleep there is no stage similar to the first stage of sleep in man (127), during which there is a flattening of alpha activity with a fast activity. A similar short-lasting stage has been described in the chimpanzee (5, 372).

Unitary activity during spontaneous sleep

The mechanisms of sleep would obviously be better known if we could understand the intimate nature of the unit activity shifts at the cortical level, the limbic system, and the reticular formation level; these are the three structures in which, a priori, the most important information may be recorded. In this field chronic experimentation is just beginning and certain interpretations must be borrowed from the results of acute experimentation. Two ways of exploring unit activity have been worked out.

1) The first method investigates the behavior of only one neuron (or of a small group of neurons). In some cases, the shifts of the unit discharges during slow sleep (compared with arousal) are statistically studied, but unfortunately no time correlation is possible with the changes of the EEG within sleep, which lessens the value of the results. Infrequently, the modality of the unit cortical discharges is studied in relation to the two characteristic EEG patterns, spindles and slow waves, and thus more fruitful results are obtained on the influences exerted on the neurons (input).

2) The second method is to study the general activity level of the neurons with techniques of integration. Hence this enables us to learn more of the results of the neuronal activity (output).

Unitary behavior of the neurons during slow sleep.

CORTEX. When the unitary activity is not studied in close temporal relationship with the pattern of sleep EEG, but is compared statistically with the activity of the waking state, the results obtained at the level of the visual (137-139, 215), suprasylvian (143), or auditory (335) cortex show an increase of unit discharges in comparison with waking [which was compared to an increase of noise and so to a decrease of the signal-to-noise ratio (137)]. The statistical analysis of the intervals between unit discharges suggests that a change in the pattern of the discharges occurs rather than a general increase (137). This change in pattern is accompanied by other phenomena supporting a reduction of inhibitory processes the recovery cycle of the visual cortical evoked responses shows a decrease in comparison with waking (144), and the inhibition of spontaneous discharges that are evoked by stimulation of the lateral geniculate nucleus is less important than during waking (141). How ever, the study of the unitary activity of sensory cortices does not always allow us to distinguish between the fiber discharges and the neuron discharges and it might be interesting to know the cortical efferent activity.

Evarts (142) has studied the pyramidal tract (PT) neurons located by antidromic stimulation at the level of the pyramids. During slow sleep the total activity is slightly lower than during waking, while bursts of discharges and silent periods occur in turns. The bursts, which probably but not obviously accompany cortical spindles, are attributed to the "reduction in the effectiveness of a mechanism limiting the frequency of the discharges during waking," and the hypothesis of a disinhibition of some central inhibitory interneurons during sleep has been set forth (142). In this connection it must be pointed out that, in preparations with important lesions of the mesencephalic reticular formation, Martin and Branch (308) have also recorded bursts of unitary activity at the level of PT neurons, and they hypothesize that the reticular lesion suppresses an inhibitory process responsible for the regular discharge of the units during waking. All these data favor existence of a decrease in the inhibitory cortical processes through disinhibition of inhibition during the stage of the spindles. Such unit discharges in bursts had already been described by Adrian and Moruzzi (8) in the spindles of cats under Dial anesthesia. They have also been observed, during physiological sleep, at the level of the lateral geniculate nucleus (216).

The study of the temporal relationship between the different patterns of unit discharges and of general EEG activity is more valuable for it enables us to distinguish two different processes during slow sleep that a total statistical analysis might fail to recognize and might even set aside. The results obtained in acute experiments (18, 111-113, 262) have shown that the gathering in bursts of the units (in sequence when recorded with several microelectrodes) (425, 426) accompanies barbiturate spindles, whereas the slow waves of hypoglycemia may, on the contrary, involve a reduction of discharges (113). Contradictory results nevertheless have been found often (215, 335).

Recently the technique of transcortical bipolar recording, in chronic conditions, revealed a very close correlation between the physiological sleep EEG and the unitary activity of the different generators of the cortex during their stratigraphic analysis (87, 88). Thus the surface-positive or surface-negative spindles are accompanied by bursts of discharges occurring at the level of the superficial dendritic and deep (somato-dendritic) units, whereas surface-negative slow waves (typical of slow sleep) are accompanied by a suppression of the unit activity (due to hyperpolarization of the membrane of neuronal bodies of the deep layers). This recently published study is the only one in which a relationship was found between spindles, slow waves, and cortical unit activity in chronic animals.

RETICULAR FORMATION. Although the reticular formation (RF) activity has been studied in acute conditions (326, 327, 397), the analysis of reticular units in chronic conditions has just started. Strumwasser (416) has described an increase in the unitary activity of the mesencephalic reticular formation during slow sleep contrasting with a surprising reduction of activity during waking. Huttenlocher (223, 224) studied 50 units at the level of the mesencephalic tegmentum during waking and slow sleep. Unfortunately, he did not distinguish between spindles and slow waves, which makes it difficult to interpret his findings. Most of the units of the dorsal part of the mesencephalic tegmentum showed increased activity in bursts during slow sleep, but a small group of units, situated at the level of the ventral part of the tegmentum, showed reduced activity, compared to that during waking. However, Caspers (98, 99) found in the rat that 20% of the mesencephalic reticular units showed a decreasing activity at the beginning of the slowing of the EEG, whereas 80 % showed a complete rest when high-voltage cortical slow waves appeared. On the other hand, at the level of the medulla Caspers (97) found an increased unit activity at the onset of slow sleep. As yet there does not appear to be any study of the relationship between reticular unit activity and slow activity recorded with macroelectrodes at the same level during sleep.

In spite of the large amount of work on the rhinencephalon, there is not a single reference concerning hippocampal unit activity during sleep. Only the amygdala has been studied (393); at this level, the unit activity decreases and shows a tendency to cluster in bursts. The correlation of these bursts with cortical activity has not been studied.

Background activity level. This technique (23) allows us to quantify the high frequency activity recorded with electrodes 20-80 micron in diameter, and it also enables us to evaluate the intensity of the background activity of the neurons (23, 398). Used lately in chronic conditions at the level of the pyramidal tract (pes pedunculi) (20), this method emphasizes that there is a close correlation between the appearance of cortical spindles, the increase of the background level of pyramidal activity, and, on occasion, the existence of bursts of phasic muscular activity in the neck muscles. The level of pyramidal activity, on the contrary, reaches its minimum during the intervals between the spindles. This observation is consonant with that of Adrian and Moruzzi (8) on cats during Dial anesthesia and proves the existence of descending pyramidal volleys during slow sleep. Though this method has not yet been used for other parts of the brain during sleep, it seems of interest to summarize the results of Schlag and Balvin (398, 399) in acute experiments on encephale isole or on the cat under curare. At the level of the motor cortex the results are similar to those obtained by Arduini et al. (20) at the level of the pyramidal tract-reduction of the general level of activity between the spindles and increased activity during the spindles. On the other hand, no one has recorded an increase in the activity level of the mesencephalic reticular formation during spindles; indeed, a decrease in the reticular activity level appeared whenever periods of spindles and cortical slow waves occurred. [On the contrary, the recruiting response elicited by stimulation of the diffuse thalamic system (129, 321) (see 83) involves an increase in the reticular activity level, thus revealing the different natures of the recruiting response and of the spindles of physiological sleep.] So the curve of the background reticular activity level seems to be the opposite of that of the frontal cortex and the pyramidal tract during slow sleep, and during the transition between wakefulness and sleep the background cortical and reticular activity levels decrease in a way parallel to that of waking.

It is too early to synthesize all these results, because most of the investigators unfortunately have made no distinction between spindles and slow waves and also because there are important gaps in our knowledge about the limbic system and the caudal parts of the brain stem. Yet it seems possible to draw a few tentative inferences. During the manifestation of the surface-positive or surface-negative spindles typical when falling asleep, the thalamic origin of which seems unquestionable (see below), the unit activity of superficial and deeper layers of the cortex is subject to a phasic enhancement. This increase of discharge is attributed either to a negative feedback responsible for keeping a certain level of cortical tone (142) or to the manifestation of a disinhibition of cortical inhibitory interneurons ~(still to be demonstrated). Whatever their detailed mechanism, the spindles are accompanied by a phasic increase in the level of background cortical activity at the level of the sensory and motor areas and the pyramidal tract and by a decrease of the background activity level in the midbrain reticular formation. There are no data, however, that allow us to say whether the appearance of these spindles is secondary to the reduction of the reticular activity level or whether it is the actual cause of such a reduction. The decreased background activity of the reticular formation, however, may explain a few peripheral signs of sleep the reduction of muscular tone, in spite of the amount of pyramidal impulses at every spindle, would then appear as a decrease in the tonic activity of the reticular facilitatory descending system (301).

During cortical slow waves, when slow sleep reveals its most typical EEG manifestation, it seems possible to assume that the cortical unitary activity decreases (probably through hyperpolarization at the level of the deeper layers). At this stage too, the reticular activity seems to decrease.

It is undeniably of much interest to know the relationship between the reticular unit activity and the activity recorded with macroelectrodes during sleep, but nevertheless its importance must not be overestimated in attempts to explain the mechanism of sleep. As a matter of fact, in spite of the complete lack of variation of the electrical activity at the brain-stem level (which remains fast and of low voltage), the chronic decorticate animal keeps on presenting short but un deniable episodes of sleep, behaviorally resembling slow sleep. Thus it would be very important to know, in such chronically decorticate animals, what are the shifts of the background activity level of the mesencephalic reticular formation and then to study their possible correlations with the hippocampal unit activity or with that of the brain-stem caudal structures.

Cortical steady potential and other electrical parameters

The appearance of spindles and slow waves of physiological sleep, whether they occur spontaneously or are provoked by phenomena of habituation (389), is accompanied by a shift of the cortical steady potential to the positive side (96, 97, 390, 442), whereas waking is accompanied by a negative shift (22). A reduction of the resistance of superficial layers of the cortex and an increase of the capacitance have been observed during slow sleep by Aladjanova (15). Such changes are attributed to a "moderating influence of the dendritic potentials over the excitability of the neurons through extra-cellular currents." The hypothalamic impedance (reflecting, in a way, the blood flow) decreases, whereas cortical and reticular impedance shows a tendency to increase at the onset of slow sleep, which is attributed to a relaxation of vasomotor tone (50). The temperature of the preoptic area and of the hypothalamus falls by 0.5 C during slow sleep (2, 4).

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