Paradoxical Sleep - A Study of its Nature and Mechanisms
Michel Jouvet
Progress In Brain Research Vol. 18 Sleep Mechanisms 1965
TABLE OF CONTENTS
Introduction
Evidence of the duality of the states of sleep

(a) EEG and behavioural findings

(b) Phylogenetic findings

(c) Ontogenetic findings

(d) Functional findings

(e) Structural findings

Mechanisms of paradoxical sleep

(a) Producing P.S. as a reflex

(b) Results of deafferentations

(c) Role of the hypothalamus and pituitary

(d) Deprivation of P.S. in the pontile animal

(e) Effects of temperature on P.S. in the pontile animal

(f) Action of gamma-butyrolactone (G.B.L.)

(g) Osmolarity of the blood and paradoxical sleep

Discussion

(a) Duality of the states of sleep

(b) Mechanisms underlying the appearance of P.S.

Summary and Conclusions

Discussion

Figures

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Discussion

(a) Duality of the states of sleep

The first section will be limited to positive evidence of the duality of the states of sleep and thus of the specificity and autonomy of paradoxical sleep in relation to slow sleep.

(i) Structural duality of the two states of sleep

It is difficult to explain the totality of the results we have just described on the basis of a 'unitary' theory of behavioural sleep, according to which similar mechanisms and identical structures are responsible for the two states of sleep. To explain the desynchronization of P.S. following synchronization of slow sleep in accordance with this theory, it has been necessary to presume the existence of a single progressively ascending inhibitory process, which attacks first the ascending activating reticular system and secondarily the thalamic synchronizing structures (Hernandez Peon, 1963). In point of fact, the structural details we have described necessarily imply different nervous structures responsible for the two states of sleep. The results of experiments with section and coagulation all make it possible to localize the structures triggering off P.S. in the pons (M. Jouvet, 1961; Cadilhac and Passouant-Fontaine, 1962; Rossi et al. 1963). We have discussed elsewhere (M. Jouvet, 1962a) the different arguments in favour of a descending origin of slow sleep from the telencephalon. But the initiation of this slow activity has not been finally cleared up. Some results indicate that synchronizing structures which could be responsible for slow sleep are to be found in the medulla oblongata (Moruzzi, 1960; Magnes et al., 1961). It has been suggested ( Rossi et al., 1963) that these structures are situated immediately behind those responsible for P.S. (in the caudal part of the pontine reticular formation). This hypothesis does not however take into account the fact that coagulation directly behind the nucleus reticularis pontis caudalis at the level of the anterior part of the nucleus gigantocellularis does not suppress slow sleep. Also there is no intermediary phase of sleep between wakefulness and P.S. in pontile animals as shown by either EEG or behaviour. If the synchronizing structures were situated in the lower portion of the brain stem, at the level of the pons and the medulla oblongata, we would have to assume that they could produce no EEG or behavioural manifestations in pontile animals. Moreover, the ascending synchronizing influences would have to act on structures rostral to the pons to produce behavioural sleep of an intermediary type between wakefulness and P.S. without slow activity, as occurs in decorticate animals (M. Jouvet, 1962a), whilst the cortex would be necessary to produce slow subcortical activity in intact animals.

(ii) Duality of the mechanisms of the states of sleep (Fig. 25)

Like the structural findings, the EEG, phylogenetic and ontogenetic data speak for a duality of mechanisms. The results of cortical and subcortical recordings which show the fundamental difference between P.S. and slow sleep are in fact confirmed by other methods. Thus, the cortical D.C. potential (Dement, 1964; Wurtz, 1964) in cats shows a sudden negative shift at the beginning of P.S., following the positive shift of slow sleep. The variations in cerebral impedance ( Birzis and Tachibana, 1964) and cerebral blood flow ( Kanzow et al., 1962) are similar to those observed during wakefulness and contrary to those observed during slow sleep. Lastly, studies with electrodes have shown a sudden increase in cortical (Evarts, 1962) or reticular activity (Huttenlocher, 1961) compared with that of slow sleep.

Variations in both the autonomic and somatic spheres show that P.S. is indeed a state qualitatively different from slow sleep, for blood pressure drops suddenly at the beginning of the former, while there is little change in the course of the latter (Candia et al., 1962). Finally, the monosynaptic spinal reflexes change little during slow sleep, and disappear entirely in P.S. (Giaquinto et al., 1964). All the results reviewed here cannot be explained on the basis of a 'unitary' theory of sleep.

Such a theory also necessarily implies that slow sleep (considered as a phase of light sleep) precedes P.S. (deep sleep). If the hypothesis is to be accepted, there ought to be a parallelism between the phylogenic and ontogenic evolution of the two states of sleep. But this is not in fact the case. Whereas slow sleep appears to be a characteristic of all vertebrate species studied polygraphically up to the present time (from reptiles to mammals), P.S. does not appear to be related to slow sleep in their phylogenic evolution. What is more, the absence of P.S. in chelonians, and its very rudimentary form in birds, contrast with its constancy and relative importance in all mammals. The number of species so far studied is too small to permit definite conclusions to be drawn, but it does appear that P.S. occurs from birds upwards on the evolutionary scale. It may therefore be presumed that with its appearance a new function came into being which is not necessarily related to sleep, since it does not appear in reptiles.

Ontogenic aspects also make a differentiation between the two states of sleep possible. At birth, in fact, P.S. occurs relatively more often and is less dependent on slow sleep than in later life. Periods of sleep with rapid eye movements have also been observed in newborns (Roffwarg et al., 1963; Delange et al., 1961). These phases of sleep similar to P.S. can also follow immediately on wakefulness. Thus in the newborn mammal, slow sleep is not a prerequisite of P.S. Until now, sleep states have been investigated primarily in animals that are very immature at birth and it is therefore diffficult when analysing the greater amounts and autonomy of P.S. compared with slow sleep to know what to attribute to the immaturity of the nervous system and what to the conditions of early life - milk diet, etc. Nevertheless, one fact stands out: in the cat the average duration of P.S. is almost from the first identical with that in the adult animals. It is only by a reduction in frequency that the proportion of P.S. versus total sleep diminishes. It must therefore be assumed that the P.S. mechanism is already at birth what it will be later in the adult, whereas slow sleep requires further deve]opment. In other words, P.S. depends on an 'innate' mechanism, whereas the mechanism of slow sleep is acquired after birth.

Whilst in adulthood a behavioural distinction can be made polygraphically between the two states of sleep, the fact that slow sleep habitually precedes P.S. would permit the conclusion that the former is a prerequisite of the latter. But our technique of selective deprivation makes it very easy to separate them. Our results confirm those of Dement (1960) in humans and show that a need for P.S. appears as soon as an attempt is made to suppress it. This suggests that a particular function is connected with the appearance of P.S. It is interesting to note in this context that a cat deprived of P.S. for more than 72 h resembles a newborn kitten in its recuperative sleep. In both cases P.S. constitutes the greater part of behavioural sleep (up to 80% of the first hour of recuperative sleep), phasic phenomena and periodicity are very much increased and, especially, P.S. can follow immediately on wakefulness, without being preceded by a phase of slow sleep. P.S. following directly on a state of wakefulness has also been observed in adult man during narcoleptic attacks (Rechtschaffen et al., 1963). Thus under particular conditions - selective deprivation of P.S., narcolepsy—not yet fully understood, it is possible to distinguish between the mechanisms of P.S. and slow sleep in adults.

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BIBLIOGRAPHY
  1. Adey, W. R.
    (1964) ; L'élaboration et le stockage de l'information dans le système nerveux
    Actualités Neurophysiologiques, V série. M. Monnier, Editor. Masson, Paris.
  2. Bard, P., And Macht, M. B.
    (1958) ; The behaviour of chronically decerebrate cats
    Neurological Basis of Behaviour. Churchill London (p. 55-71).
  3. Berlucchi, G., Moruzzi, G., Salvi, G., And Strata, P.
    (1964) ; Pupil behaviour and ocular movements during synchronized and desynchronized sleep
    Arch. Ital. Biol., 102, 230-245.
  4. Bessman, S. P., And Skolnik, S. J.
    (1964) ; Gamma hydroxybutyrate and gamma butyrolactone. Concentration in rat tissues during anesthesia
    Science, 143, 1045-1047.
  5. Birzis, L., And Tachibana, S.
    (1964) ; Local cerebral impedance and blood flow during sleep and arousal
    Exp. Neurol., 9, 269 285.
  6. Brodal, A.
    (1957) ; The Reticular Formation of the Brain Stem. Anatomical Aspects and Functional Correlations
    Edinburgh, Oliver and Boyd.
  7. Brooks, D. C., And Bizzi, E.
    (1963) ; Brain stem electrical activity during deep sleep
    Arch. Ital. Biol., 101, 648 665.
  8. Cadilhac, J., And Passouant-Fontaine, T.
    (1962) ; Décharges épileptiques et activité électrique de veille et de sommeil dans l'hippocampe au cours de l'ontogenèse
    Physiologie de l'Hippocampe. P. Passouant, Editor. C.N.R.S. (p. 429 442).
  9. Cadilhac, J., Passouant-Fontaine, T., And Passouant, P.
    (1961) ; Modifications de l'activité de l'hippocampe suivant les divers stades du sommeil spontané chez le chat
    Rev. Neurol., 105, 171 176.
  10. Candia, O., Favale, E., Giussani, A., And Rossi, G. F.
    (1962) ; Blood pressure during natural sleep and during sleep induced by electrical stimulation of the brain stem reticular formation
    Arch. Ital. Biol., 100, 216-233.
  11. Delange, M., Castan, P., Cadilhac, J., And Passouant, P.
    (1961) ; Etude E.E.G. des divers stades du sommeil de nuit chez l'enfant. Considérations sur le stade IV ou d'activité onirique
    Rev. Neurol., 105, 176-181.
  12. Dement, W. C.
    (1958) ; The occurrence of low voltage, fast, electroencephalogram patterns during behavioral sleep in the cat
    Electroenceph. clin. Neurophysiol., 10, 291-296.
  13. Dement, W. C.
    (1960) ; The effect of dream deprivation
    Science, 13t, 1705-1707.
  14. Dement, W. C.
    (1964) ; Eye movements during sleep
    The Oculomotor System. M. B. Bender, Editor. Harper and Row, New York (p. 366-416).
  15. Dement, W. C.
    (1964) ; Does rapid eye movement sleep have a function ?
    lnternat. Symp. on the Anatomo Functional Aspects of Sleep. Lyons, 9-11 Sept. 1963; Edition C.N.R.S., in the press.
  16. Dement W. C., And Kleltman, N.
    (1957) ; The relation of eye movements during sleep to dream activity: an objective method for the study of dreaming
    J. exp. Psychol., 53, 339 346.
  17. De Robertis, E., And Gerschenfeld, H. M.
    (1961) ; Submicroscopic morphology and function of glial cells
    Int. Rev. Neurobiol., 3, 1.
  18. Edstrom, R.
    Recent developments of the blood brain barrier concept
    Int. Rev. Neurobiol. (in the press).
  19. Evarts, E. V.
    (1962) ; Activity of neurons in visual cortex of cat during sleep with low voltage fast activity
    J. Neurophysiol., 25, 812 816.
  20. Faure, J.
    (1962) ; La phase paradoxale du sommeil chez le lapin. (Ses relations neurohormonales)
    Rev. Neurol., 106, 190 197.
  21. Gerschenfeld, H. M., Wald, F., Zadunaisky, J. A., And De Robertis, E.
    (1959) ; Function of astroglia in the water-ion metabolism of the central nervous system
    Neurology, 9, 412 425.
  22. Giaquinto, S., Pompeiano, O., And Somogyi, I.
    (1964) ; Descending inhibitory influences on spinal reflexes during natural sleep
    Arch. Ital. Biol., 102, 282-308.
  23. Giarman, N. J., And Roth, R. H.
    (1964) ; Differential estimation of gamma-butyrolactone and gamma-hydroxybutyric acid in rat blood and brain
    Science, 145, 583 584.
  24. Giarman, N. J., And Schmidt, K. F.
    (1963) ; Some neurochemical aspects of the depressant action of gamma-butyrolactone on the central nervous system
    Brit. J. Pharmacol., 20, 563 568.
  25. Hermann, H., Jouvet, M., And Klein, M.
    (1964) ; Etude polygraphique du sommeil chez la tortue
    C.R. Acad. Sci. (Paris), 258, 2175 2178.
  26. Hernandez-Peon, R.
    (1963) ; Sleep induced by localized electrical or chemical stimulation of the forebrain
    Electroenceph. clin. Neurophysiol., 24, Suppl., 188-198.
  27. Hobson, J. A.
    The effect of chronic brain stem lesions on cortical and muscular activity in the cat
    Electroenceph. clin. Neurophysiol. in the press.
  28. Hobson, J. A.
    (1964) ; L'activité électrique phasique du cortex et du thalamus au cours du sommeil désynchronisé chez le chat
    C. R. Soc. Biol. (Paris), in the press.
  29. Hubel, D. H.
    (1960) ; Electrocorticograms in cats during natural sleep
    Arch. Ital. Biol., 98. 171-181.
  30. Huttenlocher, P. R.
    (1961) ; Evoked and spontaneous activity in single units of medial brain stem during natural sleep and waking
    J. Neurophysiol., 24, 451-468.
  31. Hyden, H., And Pigon, A.
    (1960) ; A cytophysiological study of the functional re]ationship between Oligodendrogial Cells and nerve cells of Deiters' nucleus
    J. Neurochem., 6, 57-72.
  32. Jeannerod, M., And Mouret, J.
    (1963) ; Etude comparative des mouvements oculaires observés chez ]e chat au cours de la veille et du sommeil
    J. Physiol. (Paris), 55, 268.
  33. Jeannerod, M., Mouret, J., And Jouvet, M.
    (1965) ; Etude de la motricité oculaire au cours de la phase paradoxale du sommeil chez le chat
    Electroenceph. clin. Neurophysiol., in the press.
  34. Jouvet, D.
    (1962) ; La phase rbombencéphalique du sommeil. Ses rapports avec l'activité onirique
    Thesis, Lyons.
  35. Jouvet, D., Valatx, J. L., And Jouvet, M.
    (1961) ; Etude polygraphique du sommeil du chaton
    C.R. Soc. Biol. (Paris), 155, 1660 1664.
  36. Jouvet, D., Vimont, P., Delorme, J. F., And Jouvet, M.
    (1964) ; Etude de la privation de phase paradoxa]e du sommei] chez le chat
    C.R. Soc. Biol. (Paris), 158, 756-759.
  37. Jouvet, M.
    (1961) ; Telencepha]ic and rhombencephalic sleep in the cat
    The Nature of Sleep, G. E. W. Wolstenholme and M. O'Connor, Editors, London (p. 188-208).
  38. Jouvet, M.
    (1962a) ; Recherches sur ]es structures nerveuses et les mécanismes responsab]es des différentes phases du sommeil physiologique
    Arch. Ital. Biol., 100, 125-206.
    TEXTE-INTEGRAL
  39. Jouvet, M.
    (1962b) ; Un appareil enregistreur automatique des phases rhombencépha]iques du sommeil chez l'animal: l'onirographe
    Rev. Neurol., 107, 269 271.
  40. Jouvet, M., Cier, A., Mounier, D., And Valatx, J. L.
    (1961) ; Effets du 4 butyrolactone et du 4 hydroxybutyrate de sodium sur l'E.E.G. et ]e comportement du chat
    C. R. Soc. Biol. (Paris) , 155, 1313 1316.
  41. Jouvet, M., And Jouvet, D.
    (1964) ; Le sommeil et les rêves chez les animaux.
    Psychiatrie animale. H. Ey, Editor. Desclée de Brovwe.
  42. Jouvet, M., Jouvet, D., And Valatx, J. L.
    (1963) ; Etude du sommeil chez le chat pontique chronique: sa suppression automatique
    C. R. Soc. Biol. (Paris), 157, 845-849.
  43. Jouvet, M., Michel, F., And Courjon, J.
    (1959) ; Sur un stade d'activité é]ectrique cérébrale rapide au cours du sommeil physio]ogique
    C.R. Soc. Biol. (Paris), 153, 1024-1028.
  44. Kanzow, E., Krause, D., And Kuehnel, H.
    (1962) ; The vasomotor system of the cerebral cortex in the phases of desynchronized E.E.G. activity during natural sleep in cats
    Pflugers Arch. ges. Physiol., 274, 593 607.
  45. Kawakami, M., And Sawyer, C. H.
    (1962) ; Effects of hormones on 'paradoxical' sleep in the rabbit
    Fed. Proc., 21, 354-359.
  46. Klein, M.
    (1963) ; Etude polygraphique et phylogénétique des différents États de Sommeil
    Thesis. Lyon, Bosc Edit.
  47. Klein, M., Michel, F., And Jouvet, M.
    (1964) ; Etude polygraphique du sommeil chez les oiseaux
    C.R. Soc. Biol. (Paris), 158, 99-103.
  48. Koch, E
    (1932) ; Die Irradiation der pressoreceptorischen Kreislaufreflexe. Klin. Wschr., 2, 225227.
  49. Lissak, K., Karmos, G., And Grastyan, E.
    (1962) ; The importance of muscular afferentation in the organization of the 'paradoxical phase' of sleep
    Abstract XXII Int. Physiol. Congr., Excerpta Medica, No. 932. Leiden.
  50. Magnes, J., Moruzzi, G., And Pompeiano, O.
    (1961) ; Synchronization of the E.E.G. produced by low-frequency electrical stimulation of the region of the solitary tract
    Arch. Ital. Biol., 99, 33-67.
  51. Magoun, H. W.
    (1950) ; Caudal and cephalic influences of the brain stem reticular formation
    Physiol. Rev., 30, 459 474.
  52. Magoun, H. W., And Rhines, R.
    (1946) ; An inhibitory mechanism in the bulbar reticular formation
    J. Neurophysiol., 9, 165-171.
  53. Michel, F., Jeannerod, M., Mouret, J., Rechtschaffen, A., And Jouvet, M.
    (1964a) ; Sur les mécanismes de l'activité de pointes au niveau du système visuel au cours de la phase paradoxale du sommeil
    C.R. Soc. Biol. (Paris), 158, 103-106.
  54. Michel, F., Rechtschaffen, A., And Vimont, P.
    (1964b) ; Activité électrique des muscles oculaires extrinsèques au cours du cycle veille sommeil
    C. R. Soc. Biol. (Paris), 158, 1 06-109.
  55. Mikiten, T., Niebyl, P., And Hendley, C.
    (1961) ; E.E.G. desynchronization during behavioural sleep associated with spike discharge from the thalamus of the cat
    Fed. Proc., 20, 327.
  56. Moruzzi, G.
    (1960) ; Synchronizing influences of the brain stem and the inhibitory mechanisms underlying the production of sleep by sensory stimulation
    Electroenceph. clin. Neurophysiol., 13 Suppl., 231-253.
  57. Moruzzi, G.
    (1964) ; Reticular influences On the E.E.G.
    Electroenceph. clin. Neurophysiol., 16, 2-17.
  58. Moruzzi, G., And Magoun, H. W.
    (1949) ; Brain stem reticular formation and activation of the E.E.G.
    Electroenceph. clin. Neurophysiol., 1, 455 473.
  59. Mouret, J., Jeannerod, M., And Jouvet, M.
    (1963) ; L'activité électrique du système visuel au cours de la phase paradoxale du sommeil chez le chat
    J. Physiol. (Paris), 55, 305-306.
  60. Naquet, R., Denavit, M., Lanoir, J., And Albe-Fessard D.
    Altérations transitoires ou définitives de zones diencéphaliques chez le chat. Leurs effets sur l'activité électrique corticale et le sommeil
    Internat. Symp. on the Anatomo-Functional Aspects of Sleep. Lyons 9 11 Sept. 1963. Edition C.N.R.S., in the press.
  61. Nauta, W. J. H.
    (1946) ; Hypothalamic regulation of sleep in rats. An experimental study
    J. Neurophysiol., 9, 285-316.
  62. Pompeiano, O.
    Ascending and descending influences of somatic afferent volleys in unrestrained cats: supraspinal inhibitory control of spinal reflexes during natural and reflexly induced sleep
    Internat. Symp. on the Anatomo-Functional Aspects of Sleep. Lyons 9-11 Sept. 1963. Edition C.N.R.S., in the press.
  63. Pompeiano, O., And Swett, J. E.
    (1962a) ; E.E.G. and behavioral manifestations of sleep induced by cutaneous nerve stimulation in normal cats
    Arch. Ital. Biol., 100, 311-342.
  64. Pompeiano, O., And Swett, J. E.
    (1962b) ; Identification of cutaneous and muscular afferent fibers producing E.E.G. synchronization or arousal in normal cats
    Arch. Ital. Biol., 100, 343-380.
  65. Pompeiano, O., And Swett, J. E.
    (1963) ; Actions of graded cutaneous and muscular afferent volleys on brain stem units in the decerebrate cerebellectomized cat
    Arch. Ital. Biol., 101, 552-583.
  66. Rechtschaffen, A., Wolpert, E. A., Dement, W. C., Mitchell, S. A., And Fisher, C.
    (1963) ; Nocturnal Sleep of Narcoleptics
    Electroenceph. clin. Neurophysiol., 15, 599 609.
  67. Reinoso-Suarez, F.
    (1961) ; Topographischer Hirnatlas der Katze.
    Darmstadt, Merck.
  68. Roffwarg, H. P., Dement, W. C., And Fisher, C.
    (1963) ; A sleep E.E.G. rapid eye movement cycle in new born infants associated with specific physiological variations
    Report of Curr. Res. Assoc. for the Psychophysiol. Study of Sleep.
  69. Rossi, G. F., Favale, E., Hara, T., Gtussani, A., And Sacco, G.
    (1961) ; Researches on the nervous mechanisms underlying deep sleep in the cat
    Arch. Ital. Biol., 99, 270 292.
  70. Rossi, G. F., Minobe, K., And Candia, O.
    (1963) ; An experimental study of the hypnogenic mechanisms of the brain stem
    Arch. Ital. Biol., 101, 470 492.
  71. Scheibel, M. E., And Scheibel, A. B.
    (1957) ; Structural substrates for integrative patterns in the brain stem reticular core. Reticular Formation of the Brain
    Henry Ford HospItal. Symposium. Boston, Little Brown and Co. (p. 31-55).
  72. Snyder, R. S., And Niemer, W. T.
    (1961) ; A Stereotaxic Atlas of the Cat Brain
    Univ. of Chic. Press.
  73. Stern, E. W., And Coxon, R. V.
    (1964) ; Osmolarity of brain tissues and its relation to brain bulk
    Anrer. J. Physiol., 206, 1-7.
  74. Tschirgt, R. D.
    (1958) ; The blood brain barrier. Biology of Neuroglia
    W. F. Windle, Editor. Springfield, C. Thomas (p. 130-138).
  75. Valatx, J. L.
    (1963) ; Ontogenèse des différents États de Sommeil. Etude comportementale E.E.G. et polygraphique chez le Chaton
    Thesis. Lyons, Annequin Edit.
  76. Valatx, J. L., Jouvet, D., And Jouvet, M.
    (1964) ; Evolution électroencéphalographique des différents états de sommeil chez le chaton
    Electroenceph. clin. Neurophysiol., 17, 218-233.
  77. Von Economo, C.
    (1929) ; Schlaftheorie
    Ergebn. Physiol., 28, 312-339.
  78. Wurtz, R. H.
    Steady potential shifts during arousal and deep sleep in the cat
    Submitted to J. Neurophysiol.