Part 1 : Experimental results obtained on cats
The rhombencephalic phase of sleep
II. The neural structures responsible for RPS
A. The neural structures necessary and sufficient for the periodical triggering of the RPS
(i) The cerebellum, whose action might be strongly suspected in view of the total atony during RPS, is not involved since typical RPS appears in totally cerebellecto mized cats. In these animals, the alpha-type rigidity which distinguishes the post-operative period is abolished during RPS.
(ii) Total removal of the neocortex produces a surprising alteration in the electrical activity recorded at the level of the subcortical structures. In fact, there is a permanent lack of spindles and slow waves during the survival period of the animal (up to 6 months). Mesodiencephalic structures continuously exhibit a fast low voltage activity. However, the decorticate cats exhibit two different postures during sleep. There are short periods during which the eyes are closed. At this time, there are high voltage spikes in the limbic system. On the other hand the RPS, which constitutes 70-80 per cent of behavioral sleep, is shown by phenomena identical with those of the intact animal: appearance of "spindles" at the level of the pontile RF, theta rhinencephalic activity, disappearance of EMG activity, cardiorespiratory alterations, and appearance of eye movements almost similar to those of normal cats (Fig. 2).
(iii) Brain stem transection: chronic pontile or mesencephalic animal. The electrical activity of the cortical and diencephalic formations situated rostrally to the section, continually exhibits the classical appearance described at the level of the cerveau isole (Bremer 1935), i.e. a continuous mixing of spindles and slow waves, whatever the state of wakefulness (Fig. 3).
Behind the section, the mesencephalic activity constantly remains rapid during wakefulness. The periods of behavioral sleep are accompanied by the appearance of "spindles" at the level of the pontile RF and a complete disappearance of EMG activity in the neck. The latter change is especially remarkable if one compares it to the greatly increased muscular activity during wakefulness (decerebration hypertony). During these periods, the eye movements are slower and less frequent than in decorticate or normal animals, while the nictitating membrane is relaxed. Finally, important cardiorespiratory variations are observed. The duration of these phases is similar to that observed in intact animals, i.e. 10-15 min. The interval between phases is longer: 40-60 min. The threshold of behavioral arousal obtained by reticular electrical stimulation (shown by an increase in hypertony and midriasis) is also increased by 200 per cent during RPS compared to that observed during wakefulness. The same phenomena were observed in pontile cats in which all the brain rostral to the pons was removed (Fig. 4). In these animals the periodic appearance of RPS was similar to the "sudden postural collapse" observed by Bard and Macht (1958) in chronically decerebrate cats. These facts demonstrate that the neural structures responsible for the triggering of RPS are located behind the mesencephalon.
The determination of the posterior boundary of these structures has not been easy since it is very difficult to keep alive for several days an animal whose brain stem is transected behind the pons. Nevertheless, two cats survived for 1 week after a total removal of the cerebellum and a total transection of the brain stem made dorsally at the level of the caudal two-thirds of the nucleus reticularis pontis caudalis and ventrally at the limit between the pons and the trapezoid bodies (Fig. 5). In such a preparation two phenomena in particular appeared: behind the section there was no periodic variation in muscular activity nor in cardiac or respiratory activity (Fig. 6) analogous to that shown in the mesencephalic or pontile animals. The EMG activity remained constant throughout the survival period of the animal. Thus, medullary and spinal structures cannot trigger any periodical behavioral RPS when they are separated from the pons. Contrariwise, rostral to the section, very often, the cortical activity is fast, and is similar to the cortical activity described in the medio-pontine pretrigeminal preparation (Batini et al. 1959a, b, c).
The neural structures responsible for RPS are thus situated ahead of a pre-bulbar transection and behind a prepontine section. These structures must, therefore, necessarily be found at the level of the pons. For this reason limited lesions have been made at the level of the pontine reticular formation in order to suppress selectively the EEG and the behavioral correlates of the RPS.
(iiii) Lesions of the pontine reticular formation. Destruction of nucleus reticularis pontis caudalis suppressed the appearance of RPS in six cats (Fig. 7).
These cats were able to stand up and walk, and they could feed themselves. Some abnormality of behavior appeared in each of them, 3 or 4 days after the lesion. Periodically, they would have a fixed gaze with the head up and pupils dilated; and they would reach out with their paws as if attemping to touch an object. Such periodical "hallucinatory-like states" became more and more frequent throughout the survival period (up to I month).
In these cats, the cortical EEG was predominantly fast and the dorsal hippocampus showed a theta activity during the first days. On the 3rd day, periods of spindles and slow waves appeared during 50-60 per cent of the recorded time. The EEG and behavioral arousal were normal. On no occasion, in spite of continuous recording both day and night, was RPS observed: no fast EEG activity occurred during behavioral sleep and there was no disappearance of the EMG (Fig. 8). Nevertheless, in four cats, some RPS reappeared. But it was of very short duration (2-3 min) and had the same periodicity as before the coagulation of the pons. Its duration was only two per cent of the recorded time (compared with 25 per cent before the operation).
Thus, the destruction of the nucleus reticularis pontis caudalis suppresses the RPS. For this reason, we proposed the term RPS to describe the sleep stage characterized by fast EEG activity. This name seems more appropriate than "Paradoxical Phase" which we proposed earlier (Jouvet et al. 1959b).
B. Cerebral tracts responsible for the fast cortical EEG during RPS.
The location of the structures responsible for the triggering of RPS being established at the level of the nucleus reticularis pontis caudalis, circumscribed coagulations of the brain stem have been carried out, rostral to the pons, in order to suppress only the fast cortical and the theta hippocampal activity which are so characteristic of the RPS.
(i) Lesions of the lateral parts of the brain stem which destroy the specific ascending pathways and leave intact the mesencephalic reticular formation and the ventral part of the brain stem do not change the EEG correlates of SPS or of RPS, nor their behavioral correlates. Thus, such lesions do not affect the ascending pathways responsible for the fast cortical activity during RPS.
(ii) Lesions of the rostral part of the mesencephalic tegmentum (which leave intact the ventral part of the mesencephalon) suppress the low voltage fast cortical activity during arousal induced by nociceptive stimuli or by stimulation of the reticular formation behind the lesion (Moruzzi and Magoun 1949). Nevertheless, such lesions do not eliminate the possibility of fast cortical activity during RPS. This fact suggests that the cerebral tracts responsible for the cortical "activation" during sleep are necessarily different, at least in part, from the ascending activating reticular system which is responsible for cortical "arousal" (Moruzzi and Magoun 1949).
(iii) Lesions carried out at the level of the medial part of nucleus reticularis pontis oralis, interpeduncular nucleus and central grey matter, subthalamic region (medial hypothalamus, lateral liypothalamus, medial forebrain bundle) and septum, suppress, totally or in part, the low voltage fast cortical activity and the theta hippocampal activity during RPS without alteration of the behavioral aspects of this phase of sleep (Fig. 9). Such lesions, nevertheless, do not suppress the cortical arousal during wake fulness. Thus, lesions carried out at the level of the "limbic midbrain circuit" (Nauta and Kuypers 1957; Nauta 1958) suppress fast neocortical activity characteristic of RPS. It is possible that ascending corticopetal pathways coming from the nucleus reticularis pontis caudalis may take, at least in part, the limbic midbrain circuit (Fig. 10).