The role of the medial preoptic area in the organization of paradoxical sleep

Influence of electrical stimulation of the medial preoptic area of cats on characteristics of paradoxical sleep and activity of medial preoptic neurons were studied in the course of sleep-waking cycle. Low-frequency stimulation of this structure in the state of slow-wave sleep evoked short-latency electrocortical desynchronization and induced transition to paradoxical sleep or paradocical sleep-like state. The same stimulation during the whole period of paradoxical sleep results in a reduction of its duration, practically complete disappearance of tonic stage, and increase in the density of rapid eye movements in phasic stage. The vast majority of meurons in the medial preoptic area decreased their firing rates during quiet waking and slow-wave sleep and dramatically increased their activity during paradoxical sleep. More than 50% of such neurons displayed activation 20-70 s prior to the appearance of electrocorticographic correlates of paradoxical sleep. Some neurons were selectively active during paradoxical sleep. Approximately 50% of cells increased their firing rates a few seconds prior to and/or during series of rapid eye movements. The results suggest that the medial preoptic area contains the units of the executive system (network) of paradoxical sleep and are involved in the mechanisms of neocortical desynchronization.     

Dynamics of neuronal activity in the posterior hypothalamus during alternating phases of the sleep-wake cycle

The dynamics of neuronal activity in the posterior hypothalamus in different phases of the sleep-wake cycle were investigated during experiments on free-ranging cats. The highest frequency discharges were found to occur in 89.3% of neurons belonging to this region during the stages of active wakefulness and emotionally influenced paradoxical sleep. These neurons become less active during restful wakefulness and the unemotional stage of paradoxical sleep; this reduced activity can be most clearly observed in the context of slow-wave sleep. It was found that 7.1% of test neurons discharged at the highest rate during the stage of active wakefulness. They did not achieve an activity level characteristic of active wakefulness during the period of paradoxical sleep, although activity level was higher than during other states. Only 3.6% of neurons followed the opposite pattern, with discharges succeeding more frequently in slow-wave sleep and activity reduced to an equal degree during wakefulness and paradoxical sleep. The neurophysiological mechanisms governing the sleep-wake cycle and how the posterior hypothalamus contributes to these mechanisms are discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 160–167, March–April, 1988.     

The effects of electrical stimulation of posterior hypothalamus on activity of the nucleus pontis oralis' neurons

The nucleus pontis oralis' neurons were responsive to electrical stimulation of posterior hypothalamus. PS-on neurons showed an inhibitory response, and PS-off cells demonstrated an excitatory response. Neurons that discharged in association with phasic paradoxical sleep phenomena were found to have both the excitatory and the inhibitory responses. Evoked responses changed across sleep-waking cycle. The findings suggest that posterior hypothalamus is involved in the control of paradoxical sleep generation mechanisms located in the nucleus pontis oralis.     

Dynamics of neuronal activity in the lateral preoptic area of hypothalamus in the course of sleep-waking cycle

Frequency and patterns of activity of 106 neurons in the lateral preoptic area of unanesthetized cats were studied under conditions of indolent head fixation. It was shown that this structure contains two somnogenic neuronal populations with different functions. Neurons increasing their discharge frequency during transition from active to quiet wakefulness and subsequent sleep development to the point of phasic stage of paradoxical sleep development are considered as elements of an anti-waking system, which is involved in the mechanisms of sleep onset and deepening by means of inactivation of the arousal system. Neurons displaying the highest firing rates during light slow-wave sleep and synchronization of discharges with sleep spindles are considered as elements of a slow-wave sleep network.     

Hyperoxia causes increased albumin permeability of cultured endothelial monolayers

The effect of phasic eye movement activity on ventilation during rapid-eye-movement (REM) sleep was studied in seven healthy young adults by use of the respiratory inductive plethysmograph. Mean ventilation (VE) and ventilatory components during REM sleep were not significantly different from that seen in either stages 1-2 or 3-4 sleep. The percent of rib cage contribution to ventilation in REM sleep, 29.3 +/- 5.1%, was reduced compared with 54.4 +/- 5.8% in stage 1-2 and 52.2 +/- 4.3% in stage 3-4 sleep (P less than 0.005). When one separated breaths by the degree of associated phasic eye movement activity, it became apparent that breathing during REM sleep is very heterogeneous. Increasing eye movement activity was associated with inhibition of ventilation with a reduction in VE from 5.1 +/- 0.3 to 3.8 +/- 0.3 l/min. Tidal volume and frequency both fell, whereas inspiratory duration was unchanged. Compartmental ventilation was also affected, with the fall in the rib cage contribution from 37.8 +/- 6.4 to 15.3 +/- 5.6%. Chest wall and abdominal movement became more asynchronous as phasic-eye-movement activity increased and frank paradoxical breathing was seen.     

Influences of NREM sleep on the activity of tonic vs. inspiratory phasic muscles in normal men.

Studies of sleep influences on human pharyngeal and other respiratory muscles suggest that the activity of these muscles may be affected by non-rapid-eye-movement (NREM) sleep in a nonuniform manner. This variable sleep response may relate to the pattern of activation of the muscle (inspiratory phasic vs. tonic) and peripheral events occurring in the airway. Furthermore, the ability of these muscles to respond to respiratory stimuli during NREM sleep may also differ. To systematically investigate the effect of NREM sleep on respiratory muscle activity, we studied two tonic muscles [tensor palatini (TP), masseter (M)] and two inspiratory phasic ones [genioglossus (GG), diaphragm (D)], also measuring the response of these muscles to inspiratory resistive loading (12 cmH2O.l-1.s) during wakefulness and NREM sleep. Seven normal male subjects were studied on a single night with intramuscular electrodes placed in the TP and GG and surface electrodes placed over the D and M. Sleep stage, inspiratory airflow, and moving time average electromyograph (EMG) of the above four muscles were continuously recorded. The EMG of both tonic muscles fell significantly (P less than 0.05) during NREM sleep [TP awake, 4.3 +/- 0.05 (SE) arbitrary units, stage 2, 1.1 +/- 0.2; stage 3/4, 1.0 +/- 0.2. Masseter awake, 4.8 +/- 0.6; stage 2, 3.3 +/- 0.5; stage 3/4, 3.1 +/- 0.5]. On the other hand, the peak phasic EMG of both inspiratory phasic muscles (GG and D) was well maintained.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrical responses of olfactory structures and amygdala of dogs in the paradoxical phase of sleep

Electrical activity of the olfactory bulb, olfactory tubercle, amygdala, hippocampus, hypothalamus, and neocortex in the various phases of natural sleep was studied in chronic experiments on dogs under conditions close to those of free behavior. During paradoxical sleep it was found that a high-frequency synchronized rhythm of sinusoidal waves with a frequency of 36–42 Hz arises in the olfactory structures and amygdala. Generation of this activity during paradoxical sleep, by contrast with wakefulness, was unconnected with stimulation of the olfactory receptors and was probably purely central in origin. A study of the dynamics of the olfacto-amygdaloid rhythm during the paradoxical phase, and its comparison with somatic, autonomic, and EEG correlates of sleep, led to the conclusion that this rhythm is a specific EEG correlate of the paradoxical phase of sleep in dogs.     

Blood flow and pO2 in the posterior hypothalamus of cats during paradoxical sleep

In chronic experiments on cats it has been found by recording of the brain local blood flow (BLBF) and of oxygen tension (pO2) in the posterior and anterior hypothalamus, that at sleep phases alternation, the changes of these parameters are differently directed: during the paradoxical sleep the level of BLBF and pO2 oscillations frequency increased in the posterior hypothalamus and decreased in the anterior one. During slow-wave sleep opposite relations were observed. Opposite directions of changes of BLBF level and pO2 oscillations frequency in one and the same phase of sleep show that they are of local origin and must be determined by functional-metabolic shifts. In particular, the increase of BLBF level and frequency of pO2 oscillations must reflect a rise of posterior hypothalamus functional-metabolic activity during paradoxical sleep.     

Geniohyoid muscle activity in normal men during wakefulness and sleep

Reduction in the activity of upper airway "dilator" muscles during sleep may allow the pharyngeal airway to collapse in some individuals. However, quantitative studies concerning the effect of sleep on specific upper airway muscles that may influence pharyngeal patency are sparse and inconclusive. We studied seven normal men (mean age 27, range 22-37 yr) during a single nocturnal sleep study and recorded sleep staging parameters, ventilation, and geniohyoid muscle electromyogram (EMGgh) during nasal breathing throughout the night. Anatomic landmarks for placement of intramuscular geniohyoid recording electrodes were determined from a cadaver study. These landmarks were used in percutaneous placement of wire electrodes, and raw and moving-time-averaged EMGgh activities were recorded. Sleep stage was determined using standard criteria. Stable periods of wakefulness and non-rapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep were selected for analysis. The EMGgh exhibited phasic inspiratory activity during wakefulness and sleep in all subjects. In six of seven subjects, mean and peak inspiratory EMGgh activities were significant (P less than 0.05) reduced during stages 2 and 3/4 NREM sleep and REM sleep compared with wakefulness. This reduction of EMGgh activity was shown to result from a sleep-related decline in the level of tonic muscle activity. Phasic inspiratory EMGgh activity during all stages of sleep was not significantly different from that during wakefulness. Of interest, tonic, phasic, and peak EMGgh activities were not significantly reduced during REM sleep compared with any other sleep stage in any subject. In addition, the slope of onset of phasic EMGgh activity was not different during stage 2 NREM and REM sleep compared with wakefulness in these subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Sleep and wakefulness in Greenland seal pups

ECoG of both hemispheres, EOG, neck EMG and EKG were recorded in 2 white (age 10 days) and 2 gray pups (age 1 month) of harp seal. The active wakefulness occupied 23.4 +/- 3.8% of total recording time, the relaxed wakefulness--32.6 +/- 3.6%, drowsiness--4.8 +/- 1.1%, slow wave sleep--31.5 +/- 3.0%, paradoxical sleep--7.7 +/- 0.8%. The sleep cycle averaged 18.2 +/- 1.4 min. Interhemispheric asymmetry of the ECoG was not seen in all 4 pups. The respiration was fast and regular in the relaxed wakefulness, then long respiration pauses were alternated with episodes of hyperventilation during slow wave sleep and there was rare and irregular respiration in the paradoxical sleep. The heart rate was lowest during the paradoxical sleep. It is suggested that this pattern of sleep, allowing seals to delay their breathing during sleep for a long time may be considered as an adaptation to existence in freezing seas.     

The interhemispheric brain asymmetry of the rabbit in a state of "animal hypnosis"]

By the method of forced immobilization the rabbits were brought into the state of "animal hypnosis" (immobilization reflex), and their ECoG was recorded, which was further processed on the computer. It was found that during hypnosis a functional interhemispheric brain asymmetry was developed in rabbits with activity predominance in the right hemisphere. The "animal hypnosis" is a phasic process: in the ECoG of the rabbit under hypnosis a regular alternation of delta and theta activity takes place. Electrophysiological reconstructions in the rabbit brain during the change of its functional state correlate with the brain thermal reactions, revealed earlier.     

Temporal patterns of unit activity of mesencephalic reticular nuclei during sleep and waking

Temporal patterns of unit activity in the mesencephalic reticular nuclei (n. cuneiformis, n. parabrachialis) were studied in unrestrained rats during the sleep-waking cycle; activity was derived by means of movable metallic microelectrodes. Analysis of the data showed that most neurons of these mesencephalic reticular nuclei (76 and 66% respectively) generate activity with the highest frequency during active waking and the emotional stage of paradoxical sleep; they discharge with lower frequency during passive wakefulness and the nonemotional stage of paradoxical sleep, and they exhibit least activity during slow-wave sleep. Comparatively few neurons (24 and 15%) demonstrate the opposite kind of temporal pattern of activity: They discharge more intensively during slow-wave sleep and more slowly during active wakefulness and the emotional stage of paradoxical sleep. Activity of these neurons during quiet wakefulness and the nonemotional stage of paradoxical sleep reaches the level of activity observed during slow-wave sleep. Neurons discharging intensively during active wakefulness were found in n. parabrachialis; their discharge frequency during passive wakefulness and slow-wave sleep and its frequency was least during paradoxical sleep. The similarity and differences of the neurophysiological mechanisms of regulation of the phases and stages of the sleepwaking cycle are discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 16, No. 5, pp. 678–690, September–October, 1984.     

Tonic and phasic modifications of viscerosensory evoked potentials during sleep in cats

Modification of the viscerosensory evoked potentials (EPs) were studied during the sleep-wakefulness cycle of the rat. Electrical stimuli of various intensity were delivered either to the mucosal surface of a fistula of the small intestine or to the left splanchnic nerve during wakefulness (W), drowsiness (D), slow-wave-sleep (SWS), and paradoxical sleep (PS). The average EPs were recorded from the somatosensory (SI and SII) and associative (AS) areas of the cortex, the ventrobasal complex of the thalamus (VPL), the posterior hypothalamus (HPT) and the dorsal hippocampus (HPC). The amplitude of each component of the EPs in all explored structures were the largest in SWS and the smallest in W. A phasic increase in amplitude was observed in the EPs recorded immediately before the appearance of the spindles of SWS and during the REM episodes of PS. The peak latencies of the late components were the longest in SWS. These changes of the amplitudes and latencies were greater in the responses to weak stimulation than in EPs to strong ones. The possible synaptic events of the sleep-dependent control of viscerosensory activity are discussed.     

Control of activity of the diaphragm in rapid-eye-movement sleep

Respiration in rapid-eye-movement sleep (REMS) is known to be highly variable. The purpose of this study was to investigate the source of this variability and to determine which ordering principles remained operative in REM sleep. In unrestrained, naturally sleeping cats we recorded the electroencephalogram, electrooculogram, neck electromyogram, and diaphragmatic electromyogram (EMG) and computed its moving average (MAdi). As a reference, we first examined MAdi during "tonic" REMS, since breathing is fairly regular in this state. "Control" ranges for peak amplitude (PEMG), inspiratory time (TI), duration of postinspiratory inspiratory activity, expiratory time, and the calculated inspiratory slope (PEMG/TI) were determined by overlaying individual breath traces of the time course of MAdi during tonic REMS to form a composite tracing. Next, the time course of the EMG during individual breaths in slow-wave sleep (SWS) and a complete period of consecutive breaths in REMS (both tonic and phasic) were compared with this tonic REMS composite. The number of eye movements per breath was tabulated as an index of phasic activity. The inspiratory slopes during SWS and tonic REMS were similar. However, during phasic REMS, many breaths displayed either increases (excitation) or decreases (inhibition) in slope compared with the "typical" breaths seen in tonic REMS. The occurrence of these altered slopes increased with the frequency of phasic events. TI was inversely related to the slope of the EMG, which tended to minimize changes in PEMG.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impulse activity of neurons in the nucleus pontis oralis in cats during sleep--wakefulness cycle

The nucleus pontis oralis contains several populations of neurons showing distinct sleep-waking discharge patterns. PS-on, PS-off cells, and neurons that discharged in association with phasic movements during paradoxical sleep and/or waking, were found. The findings suggest that different populations of the nucleus pontis oralis neurons take a distinct part in paradoxical sleep control.     

Role of the hypothalamus in organizing the wakefulness-primary sleep cycle in the frog Rana temporaria

New data are presented on the role of the hypothalamus in re-arrangement of tonus of the vegetative nervous system during three forms of rest of the primary sleep in the frog. Temporal organization of the cycle " awakefulness -primary sleep" depends on interaction of the anterior and posterior hypothalamus. The anterior hypothalamus is responsible for manifestation of two forms of rest of the primary sleep, i.e. diurnal resting form (P-1) which is associated with the increase in plastic tone of skeletal muscles, and the other resting form (P-3) which is associated with the decrease in muscle tonus. These forms of rest are accompanied by the predominance of parasympathetic tonus of the vegetative nervous system. The posterior hypothalamus is associated with manifestation of the resting form which includes the increase in the rigidity of muscle tonus (P-2) and transient phasic increase in the heart rate, the latter being observed at all forms of the primary sleep. Statistical treatment of the ECG revealed specific pattern of two-dimensional density of distribution of probabilities of R-R intervals for the resting forms of the primary sleep which is important for identification of different phases in the " awakefulness -primary sleep" cycle in vertebrates.     

Developmental changes in the complexity of the electrocortical activity in foetal sheep.

The foetal sheep brain develops organised sleep states from 115-120 d gestational age (dGA, term 150 dGA) alternating between REM and NREM sleep. We aimed to investigate whether maturation of REM or NREM sleep generating structures leads to the development of distinct sleep states. The electrocorticogram (ECoG) was recorded from five unanaesthetised chronically instrumented foetal sheep in utero and was analysed every 5th day between 115-130 dGA by two different non-linear methods. We calculated a non-linear prediction error which quantifies the causality of the ECoG and applied bispectral analysis which quantifies non-linear interrelations of single frequency components within the ECoG signal. The prediction error during REM sleep was significantly higher than during NREM sleep at each investigated age (P<0.0001) coincidental with poor organisation of the rhythmic pattern in the ECoG during REM sleep. At 115 dGA, organised sleep states defined behaviourally were not developed yet. The prediction error, however, showed already different states of electrocortical activity that were not detectable using power spectral analysis. The prediction error of the premature NREM sleep ECoG decreased significantly during emergence of organised sleep states between 115 and 120 dGA and continued to decrease after the emergence of distinct sleep states (P<0.05). The prediction error of the premature REM sleep ECoG did not change until 120 dGA and began to increase at 125 dGA (P<0.05). Using bispectral analysis, we showed couplings between delta waves (1.5-4 Hz) and frequencies in the range of spindle waves (4-8 and 8-12 Hz) during NREM sleep that became closer during development. The results show that maturation of ECoG synchronisation mediating structures is important for the development of organised sleep states. The further divergence of the prediction error of NREM and REM sleep after development of organised sleep states reveals continuous functional development. Thus, complementary application of non-linear ECoG analysis to power spectral analysis provide new insights in the collective behaviour of the neuronal network during the emergence of sleep states.     

Changes in the oxygen tension level in different brain structures of rats in the waking-sleep cycle

Changes of oxygen tension level (pO2) in the visual cortex, dorsal hippocampus, lateral hypothalamus and central grey substance were studied during wake-sleep cycle in rats. The dependence was established of pO2 level changes on the character of behavioural reactions and on the accompanying hippocampal EEG activity: during orienting-investigatory and active defensive behaviour and also during paradoxical sleep, accompanied by hippocampal theta rhythm, pO2 level increased; during passive-defensive behaviour "freezing" reaction accompanied by desynchronization of the hippocampal rhythmic, the level of pO2 decreased. The obtained data confirm Routtenberg hypothesis about two relatively independent systems of ascending activation with different types of hippocampal EEG activity and supplement it with a thesis that the activity of these systems is accompanied by different shifts of brain oxidative metabolism.     

Posterior cricoarytenoid muscle activity during wakefulness and sleep in normal adults

Six normal adults were studied 1) to compare respiratory-related posterior cricoarytenoid (PCA) muscle activity during wakefulness and sleep and 2) to determine the effect of upper airway occlusions during non-rapid-eye-movement (NREM) sleep on PCA activity. A new electromyographic technique was developed to implant hooked-wire electrodes into the PCA by using a nasopharyngoscope. A previously described technique was used to induce upper airway occlusions during NREM sleep (Kuna and Smickley, J. Appl. Physiol. 64: 347-353, 1988). The PCA exhibited phasic inspiratory activity during quiet breathing in wakefulness and sleep in all subjects. Discounting changes in tonic activity, peak amplitude of PCA inspiratory activity during stage 3-4 NREM sleep decreased to 77% of its value in wakefulness. Tonic activity throughout the respiratory cycle was present in all subjects during wakefulness but was absent during state 3-4 NREM sleep. In this sleep stage, PCA phasic activity abruptly terminated near the end of inspiration. During nasal airway occlusions in NREM sleep, PCA phasic activity did not increase significantly during the first or second occluded effort. The results, in combination with recent findings for vocal cord adductors in awake and sleeping adults, suggest that vocal cord position during quiet breathing in wakefulness is actively controlled by simultaneously acting antagonistic intrinsic laryngeal muscles. In contrast, the return of the vocal cords toward the midline during expiration in stage 3-4 NREM sleep appears to be a passive phenomenon.     

Effects of broad-spectrum monoamine oxidase inhibitors on the structure and ratio of stages in in the cat sleep-wake cycle

Monoamine oxidase (MAO) inhibitors disturb the structure of the sleep-wake cycle and its ultradian rhythms by extending total slow-wave sleep, completely suppressing paradoxical sleep, and reducing total waking period considerably. Once the synchrony induced by MAO inhibitors has stopped, a rebound effect of increased waking occurs preceding and during partial restoral of paradoxical sleep. This fact is viewed as an indication of a waking requirement accumulating during the aforementioned partial deprivation under the effects of MAO inhibitors. Especially marked effects are exerted by MAO inhibitors on paradoxical sleep, in which they produce long-term suppression of tonic and phasic components. It is suggested that inhibition of paradoxical sleep is brought about by selective impairment of functional state of its neurophysiological trigger mechanisms.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 4, July–August, 1988, pp. 463–470.