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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III. State of sleep characterized by fast cortical activity paradoxical sleep

B. Electrophysiological Aspects

Paradoxical sleep (see Fig. 1) in an unrestrained normal adult cat takes place after a variable period of slow sleep. It appears then periodically during slow sleep, and mean duration is 6 min (but periods from 15 to 20 min can be frequently recorded). Its percentage in comparison with the duration of be havioral sleep is from 20 to 25% (about 15% for a period of 24 hr) (120) (see Table I). As in the behavioral aspects, it is also possible to recognize in the electrical cerebral activity during PS two major components tonic (fast cortical ac tivity and regular theta hippocampal activity) and phasic (monophasic ponto geniculo-occipItal. spike activity associated with rapid eye movements).

TABLE 1. Stability of sleep patterns of the cat calculated with method of continuous polygraphic recordings

  Awake Slow sleep Paradodixal sleep
% total time 31.5+-7 (28+-4.2) 52.5+-7 (56.5+-5.3) 16+-2 (15.5+-2.2)
% total sleep time - 77+-4 (72.4+-4.2) 23+-4 (27.5+-4.2)
Mean duration - (107.2+-12.9) 5.8+-1.3 (5.8+-1.3)

Modified from refs. 120 and 413 (in parentheses). Means and SD were obtained in g animals (120) and in 8 animals (413).

Tonic activity

Tonic activity is characterized by a neocortical diencephalic and mesence phalic low-voltage fast activity (20-30 cycles/sec), which is similar to the cortical desynchronization that usually accompanies intense arousal or attention states (analysis of cortical EEG frequencies does not always allow a discrimination between both types of activity) (79, 342, 420). However, some electrical local cortical and subcortical activity enables us to discriminate the electric cerebral activity of PS from that of behavioral arousal. The appearance of a continuous theta rhythm at the level of the ventral and dorsal hippocampus is most characteristic (85, 188, 240, 288, 289, 342, 350, 351). It is steadier and faster (5-7 cycles/ sec) than that observed during intense wakefulness (4-4.5 cycles/sec) at the level of the dorsal hippocampus (but it can be recorded also in the ventral hippocampus where theta rhythm occurs only occasionally during intense arousal). The hippocampal activity seems to have an autonomous reactivity. Indeed, the sensory stimulations may involve a fast hippocampal activity without any shift of cortical activity. Yet sometimes a short burst of cortical spindles may accompany the archeocortical activation. Theta rhythm has been also recorded at the level of the pulvinar (12), the periacqueductal grey matter (240), and the anterior part of the pons at the level of the limbic midbrain area (242). The olfactory bulb activity shifts also in a characteristic way, for the sinusoid rhythm from so to 60 cycles/sec, observed during arousal, disappears during PS (154, 263, 270).

Unit activity and steady potential. The PS cortico-subcortical fast activity is accompanied by an important increase of unit activity compared with slow sleep and even with arousal.

At the level of the cerebral cortex, the frequency of the discharges increases (139, 140). Evarts (142) has studied the discharges of the pyramidal tract neurons. Their total statistical activity remains the same during arousal and PS (just as the integrated background of pyramidal tract activity increases at the same level as wakefulness during PS) (20). Yet the bursts of increasing unit activity occurring during the phasic movements of PS are different from those of arousal. Evarts suggests this difference in pattern indicates a disinhibition of the inhibitory cortical interneurons even more important than that occurring during slow sleep, which would involve a "disorganization" of the cortical unit activity during PS (139), At the level of the mesencephalic tegmentum, the increased unit activity is important too (often twice as much as during a relaxed wakefulness). According to Huttenlocher (223, 224), occlusion but not inhibition would account for the decrease in unit responses to clicks in the RF during PS. The results concerning the steady cortical potentials are not in agreement. In the rat, Caspers (97) observes a positive shift at the onset of PS (therefore in the same direction as slow sleep). On the other hand, Dement (125), Rossi et al. (385), and Wurtz (442) in the cat and Kawamura and Sawyer (265) in the rabbit have noticed a negative shift (therefore in the same direction as in cortical arousal). These last findings agree with the shifts of cortical and subcortical impedance (50), which are similar to those observed in arousal. Thus PS seems to be the appearance of a state qualitatively different from that of slow sleep.

Phasic activity

The very close relationship between the electrical phasic activity and the visual system makes it necessary to study these in the same section.

Rapid eye movements. Rapid eye movements (REM) appear at the onset of the cortical activation. From 60 to 70 movements a minute, their rapidity and frequency, their "pattern," enables us to distinguish them from the movements of observation during waking (229-231). Either isolated or in groups of small bursts of less than 5 movements (as can be noticed also during observation), they are mainly characterized by the presence of bursts including more than 5 movements (up to 50 closely following one another). The ratio between the total number of the movements and those within the bursts is constant in every animal (50 %) during PS (231). The myosis is maximal most of the time (240), whereas the nictitating membranes are relaxed. Yet, at times, a sudden mydriasis with retraction of the nictitating membranes may accompany the volleys of ocular movements (46, 47, 212). This phasic pupillary dilatation remains even after ablation of the superior cervical ganglia and therefore must be ascribed to an inhibition of the tonic activity of the Edinger-Westphal nucleus (46, 47). The analysis of the structures responsible for the appearance of eye movements isolated and in bursts has given the following results (231) the pontine cat (superior colliculus destroyed) has only isolated lateral and external movements (depending on the VIth nerve); in the mesencephalic cat (superior colliculus intact) more important bursts of ocular movements persist. On the contrary, the coagulation of a zone located at the level of the superior colliculus and of the mesencephalic tegmentun in the intact animal suppresses the bursts. These bursts, in turn, are much increased in the decorticate animal. But the role of the cortex is not unequivocal, because the removal of the visual cortex strikingly reduces the isolated eye movements and the bursts, whereas a frontal decortication or a frontal leucotomy produces a very marked increase in these bursts.

It has recently been shown that the destruction of the medial and descending vestibular nuclei suppressed also the burst of REM, whereas isolated eye movements were still present during PS. Those nuclei in which unit activity is increased during PS (53) apparently control most of the phasic phenomena of PS (322).

Thus, the REM of PS belong to mechanisms different from those of wake fulness since they still exist in preparations utterly incapable of ocular movements during arousal (such as decorticate or pontine cats) just as they are present during PS in newborn kittens that are still blind (422, 423). The results support the hypothesis that these ocular movements are triggered at the level of the vestibular nuclei and that a growing "complexity" is involved at the level of the superior colliculi and of the mesencephalic tegmentum, whereas processes of "cortical integration" (facilitating visual cortex and inhibitory frontal cortex) would impinge back on the latter zone (231).

Phasic electrical ponto-geniculo-occipItal. activity. The difficulties and delays of a wide and systematic exploration of the cortical and subcortical structures in chronic experiments explain why it took several years before a link was obvious between the "spontaneous" phasic potentials observed during PS. First described at the level of the pontine RF (254), 200- to 300-,uv monophasic spikes 100 msec in duration, often occurring in groups of 5-6 (hence their look of pseudo-spindles), could be observed later at the level of the lateral geniculate nucleus (74, 196, 315) (Fig. 2) and at the level of the occipItal. cortex (334), the superior colliculus and the nucleus of III (74, 312), the pulvinar and the parietal cortex afterward (207). Pontine and geniculate phasic spikes are the first electric signs heralding the appearance of a PS episode. They may appear 1-2 min before the cortical activation and the disappearance of the neck EMG (74, 312) and sometimes occur erratically during slow sleep. They may occur sporadically during 5 % of slow sleep time (429), and usually during PS they have a frequency of 60-70 min.

The latency between the monophasic pontine potentials and the geniculate potentials is very short (5 msec) (52). Geniculate evoked responses having the same pattern as spontaneous spikes can be evoked (gating effect) through stimulation of the pontine RF during PS (then they have a 25- to 35-msec latency) (52). But it is impossible to evoke geniculate responses through stimulation of the pons during arousal or slow sleep. The selective triggering of the ponto-geniculo-occipItal. (PGO) activity by reserpine (119) has recently allowed the study of the organization of the PGO activity in acute experiments using Flaxedil (227, 248) (see below).

The relationship between this phasic activity and the REM is not simple neither darkness nor coagulation of the retina (47), nor even complete removal of the eyes and of the extraocular muscles (312), suppresses these PGO spikes (at least during the 2 or 3 days after the operation). Therefore, this activity cannot be considered a possible feedback of a retinal "on and off" effect of extrinsic muscular origin. Moreover, this phasic activity appears 30 or go sec before the ocular movements at the onset of PS. There sometimes may be ocular movements without any recorded activity of spikes, but in most cases there is a close time relationship between the phasic PGO spikes and the muscular activity of the extrinsic muscles (314); the latter mainly occurs in phasic bursts, whereas there is a tonic component during arousal.

These data are in favor of there being an ascending pontine extraretinal projection at the level of the lateral geniculate and the occipItal. cortex. Similar extraretinal input to the lateral geniculate body has been noticed after stimulation of the mesencephalic reticular formation or the labyrinth (258). Besides, lesions of the occipItal. cortex can show signs of degeneration at the level of the pontine RF [raphe nucleus and nucleus reticularis pontis caudalis (136)], thus favoring the existence of a system of projection between the pons and the visual cortex.

Whatever the complex organization of the extraretinal input to the lateral geniculate body might be, it is very likely that the optic tract terminals are in volved in the genesis of geniculate monophasic spikes. Indeed these spikes disappear some 6 days after enucleation of both orbits (232, 333) or retinal photocoagulation (51) though REM's and pontine spikes persist (333). The time course of wave disappearance corresponds to that of optic nerve degeneration. The hypothesis that PGO spikes could be induced by the release of monoamines at monoaminergic terminals impinging on pontine neurons or on optic tract terminals in the lateral geniculate is summarized below (119, 248).

Unit activity. The unit activity of the occipItal. cortex strikingly increases during PS in comparison with slow sleep. This increase of the discharges reaches its peak during eye movements, even while the animal is in the dark. It can be compared then to the discharges recorded during visual observation (140). These unit discharges during PS may be the unitary translation of the monophasic spikes recorded with macroelectrodes, although the latter were not recorded. On the other hand, at the level of the optic nerve, there is an important decrease of unit activity during slow sleep and PS (41) that contrasts with the increase of activity at the level of the lateral geniculate nucleus and of the mesencephalic reticular formation during PS (224). However, a transitory arrest of the spon taneous activity of l2 % of geniculate units belonging to on-off and off-on cells) was observed during monophasic spikes by Bizzi (51).

Evoked responses

Though the interpretation of the various components (early or late) of the evoked cortical responses is still a matter of discussion, the purpose of many experiments has been to analyze their shifts during the various states of sleep. The results are different according to the specific systems that have been stimulated, the nature of the stimuli, the cortical areas studied, and the methods used to estimate the results. The use of automatic techniques, which is rapidly spreading, to record averages by means of a "memory computer" has greatly simplified the task of experimenters. But in working out an average amplitude (founded on series of 50-100 responses) some significant short-lasting shifts may be concealed (for example, during some phasic events of PS). We shall briefly survey the responses evoked by physiological stimuli at the level of the receptors (shocks, clicks, flashes) and those evoked by electric stimulation of the afferent specific or non specific pathways or relays during the two states of sleep.

Responses evoked by stimulation of receptors.

AUDITORY SYSTEM. The decrease and variability of the primary (fast) and secondary (late) responses during slow sleep compared to arousal have long been known (68). There is no noticeable variation in amplitude at the level of the ascending relays. On the other hand, the responses decrease in amplitude in the mesencephalic RF compared with relaxed wakefulness (440)

During PS the amplitude of the cortical responses shows a decrease (240, 440) comparable to the one observed in intense arousal. The decrease in amplitude is also noticeable at the level of the mesencephalic tegmentum and has been ascribed to an occlusion phenomenon (223). At the level of the cochlear nucleus the responses may disappear, especially during REM bursts (240). This amplitude reduction is not noticed after section of the middle-ear muscles and must therefore be ascribed to a peripheral phenomenon (34, 13l ) and not to the intervention of a possible central control of afferent activity.

SOMESTHETIC SYSTEM. Whereas the cortical evoked responses to the radial nerve stimulation increase during slow sleep (the associative responses, mainly), in PS the amplitude of the responses increases during the early phase in comparison with slow sleep, but decreases in the late phase (16, 342).

VISUAL SYSTEM. A decrease in cortical evoked responses to flashes of light has been observed during PS, and a total depression of evoked responses was described whenever spontaneous geniculo-occipItal. spikes occurred (51, 334).

Responses evoked by stimulation of specific afferent pathways. The most permanent fact is the increase in the cortical response to the stimulation of an afferent pathway or of a specific thalamic nucleus [optic nerve, lateral geniculate nucleus, medial lemniscus, nucleus ventralis postero lateralis (VPL), medial geniculate nucleus] in comparison with slow sleep. This phenomenon is similar to the facilitation of the cortical responses by reticular stimulation (69, 134). According to some authors, the increase of the responses is similar to those observed during intense arousal (106, 110, 342, 346). For others, on the contrary, this facilitation is even more dramatic (357, 385). All the findings reveal an increase in the first phase of the responses compared with slow sleep, whereas contradictory results are obtained concerning the late phase of the visual response (110, 145). Some experiments suggest that the facilitation of the responses may take place at the thalamic level (155, 156), whereas others favor facilitation at the cortical level (26, 110, 342, 385). The most interesting results concern the interaction between the spontaneous phasic geniculo-occipItal. activity and orthodromic and antidromic responses of the optic tract. A reduction in optic tract orthodromic response and an increase in optic tract antidromic response to lateral geniculate stimulation (whereas flash-evoked responses were depressed in the lateral geniculate and in the cortex, though not in the optic tract) are consistent with the occurrence of presynaptic inhibition at optic tract terminals during the monophasic spikes that occur during REM (51,226). On the other hand, the increase in the postsynaptic component of the evoked lateral geniculate responses during the spontaneous spikes favors the existence of facilitation at the postsynaptic side (226). This mechanism may explain why the decrease in flash-evoked cortical responses is observed during PS at the same time that a facilitation of the geniculate-induced cortical responses is obtained.

Responses evoked by stimulation of nonspecific systems. The recruiting response elicited by a low frequency stimulation of the diffuse thalamic system (increasing a great deal during slow sleep) is very much reduced in PS (342,385,444). This reduction is achieve to alevel comparable to (385) or even lower than that during arousal (420,446).

The data of theses experiments have been discussed in detail elsewhere (110,385). They enable us to draw a rather surprising conclusion : that the cortical excitabitiliy would be much enhanced during PS to alevel that may even be superior to that of intense arousal.

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