[CHANGES IN BRAIN ELECTRICAL ACTIVITY PATTERNS IN RATS WITH DIFFERENT SUSCEPTIBILITY TO SEIZURES IN LITHIUM-PILOCARPINE MODEL OF STATUS EPILEPTICUS].

The intracranial EEG was continuously registered in Krushinskii-Molodkina rats with inherited susceptibility to audiogenic seizures and in Wistar rats, which are resistant to the audiogenic convulsions in the lithium-pilocarpine model of status epilepticus (SE). The recordings were done from somatosensory, auditory and visual cortical areas, caudate nucleus, hippocampus and dorso-medial nucleus of thalamus. We found that SE was induced in Krushinskii-Molodkina rats by intramuscular injections of pilocarpine at a minimum dose of 15 mg/kg, while in Wistar rats with a dose of 25 mg/kg. We describe six successive EEG patterns during SE. We identified behavioral convulsive manifestations associated with each phase of the SE. Rats of both strains had the same sequence and the main properties of EEG patterns, except the latency of phase 1 (Krushinskii-Molodkina rats 13 + 3 min vs. Wistar rats 23 + 2 min). In conclusion, the rats with susceptibility to audiogenic seizures have increased sensitivity to the pilocarpine, but the development and time-course of SE in rats of both strains did not differ.

[EFFECTS OF ELECTRICAL STIMULATION OF NUCLEUS RETICULARIS PONTIS ORALIS ON THE SLEEP-WAKING STATES IN KRUSHINSKII-MOLODKINA STRAIN RATS].

The effects of electrical stimulation of nucleus reticularis pontis oralis on the behavior and brain electrical activity during all phases of the sleep-waking cycle was studied in Krushinskii-Molodkina strain rats, which have an inherited predisposition to audiogenic seizures. Electrical stimulation with 7 Hz frequency in the deep stage of slow-wave sleep cause appearance the fast-wave sleep. Similar stimulation during fast-wave sleep periods did not effects on the electrographic patterns and EEG spectral characteristics of hippocampus, visual, auditory and somatocnen nrnrenc nf the cnrtey ThPe sfimul1stinns did nnt break a fast-wave sleenhut increased almost twice due the duration of these sleep episodes. After electrical stimulation by same frequency during the wakeftlness and superficial slow-wave sleep states, the patterns and spectral characteristics of brain electrical activity in rats showed no significant changes as compared with controls. The results of this study indicate that the state of the animals sleep-waking cycle at the time of stimulation is a critical variable that influences the responses which are induced by electrical stimulation of the nucleus reticularis pontis oralis.

[Inferior colliculus stimulation effects in KrushinskiI-Molodkina strain rats].

The effects of the central nucleus of the inferior colliculus chemical and electrical stimulation on the producing and forming the convulsive manifestations, as well as on the organization of sleep, was studied in Krushinskii-Molodkina strain rats, which have an inherited predisposition to audiogenic seizures. Microinjections of quinolinic acid (10 micrograms) or electrical stimulation with 70 Hz frequency produced the paroxysmal manifestations in the form of intensive circular excursions coincident wild running behaviors on the initial nonseizures motor exitation stage of audiogenic seizures. The results suggest that in Krushinskii-Molodkina strain rats the inferior colliculus is involved in the neuronal network, responsible for initiation and realization to the scampering stage of the evoked convulsive reactions to sound. The reduction of fast-wave (paradoxical) sleep total duration after the given actions it was observed. However, the inferior colliculus electrical stimulation with 7 Hz frequency during slow-wave sleep cause appearance the episodes fast-wave sleep. A significant (almost twice due) increase of the total time of fast-wave sleep by increasing the quantity, but not the duration of these episodes after 3-4 sessions of such sort stimulations were observed. These results showed that the inferior colliculus rats can produce the modulating action on the brain system responsible for triggering fast-wave sleep.

[The action of ionotropic glutamate receptor channel blockers on effects of sleep deprivation in rats].

The action of non-competitive glutamate receptor antagonists on the effects of sleep deprivation has been studied on Krushinskii-Molodkina rats having an inherited predisposition to audiogenic seizures and Wistar rats deprived to this respond. Two types of glutamate receptor open channels blockers were used: the selective blockers of NMDA-receptors (memantine and IEM-1921) and blockers of mixed type, impacting both on the NMDA- and presumably Ca(2+)-permeable AMPA/kainate receptors (IEM-1754 and IEM 1925). Rats were subjected to 12 hours long sleep deprivation. Immediatly after that memantine and IEM-1921 were injected, and during the first 3 hours the total or partial reduction of fast-wave (paradoxical) sleep and a significant increase of the representation of wakefulness at the cost of reducing the total time of slow-wave sleep were observed. These effects are most likely to be a consequence of the blockade of NMDA-receptors functioning in the systems of the rat brain responsible for the launch and maintenance of fast-wave sleep. Injection of IEM-1754 and IEM-1925 on background of sleep deprivation did not affect the organization of sleep during the first 3 hours of their action. During the second three-hour period the rebound effect was observed. The obtained results indicate the involvement of NMDA glutamate receptors in the functioning of various parts of the sleep system of both rat lines.

[Effects of ionotropic glutamate receptor channel blockers ON sleep-waking organization in rats].

The effects of non-competitive glutamate receptor antagonists on sleep-waking organization have been studied on Krushinskii-Molodkina rats having an inherited predisposition to audiogenic seizures and Wistar ones which are resistant to this action of sound. Two types of blockers of glutamate receptor open channels were used: selective blockers of NMDA receptors (memantine and IEM-1921) and blockers of mixed type, impacting both on the NMDA and Ca-permeable AMPA/ kainate receptors (IEM-1754 and IEM 1925). During the first 3 hours after administration of these glutamate antagonists the total or partial deprivation of fast-wave sleep was provoked. Additionally the selective NMDA receptor blocking drugs (memantine, IEM-1921) induced in the same period a significant increase of the representation of wakefulness at the cost of reducing of the total time of slow-wave sleep. These effects are most likely to be a consequence of the blockade of NMDA receptors responsible for the launch and maintenance of wakefulness, slow- and fast-wave sleep. In the same first 3 hours period after the administration of IEM-1754 and IEM-1925 the organization of sleep was not significantly affected. The evident reduction of wakefulness, total duration and increase of slow-wave sleep impact was observed, during the second three-hour period. It, apparently, can be caused by the blockade of AMPA/kainate receptors. The obtained results indicate the involvement of NMDA and AMPA/kainate receptors in the functioning of various parts of the sleep system of rats belonging to both lines.

[Effects of ionotropic glutamate receptor channel blockers on the development of audiogenic seizures in Krushinski-Molodkina rats].

The action of noncompetitive blockers of glutamate receptors has been investigated on Krushinski-Molodkina rats genetically-prone to audiogenic seizures. The selective blockers of NMDA receptor channels, memantine and IEM-1921, and their dicationic homologues, IEM-1925 and IEM-1754, capable of blocking in varying degrees both NMDA and Ca-permeable AMPA receptor channels, were studied. The drugs were injected intramuscularly to rats with the different time intervals (30 min, 1, 2 or 3 hours) before sound signal. The effects of the drugs on latent period of initial locomotor activity provoked by audio stimulation (8 kHz sine-wave tone, 90 dB volume), the appearance of clonic convulsions of different intensities, and, finally, tonic convulsions with limb and tail extension were evaluated. Within 30 min after injection IEM-1921 at a dose of 5 mg/kg, 33% of rats manifested a complete absence of convulsive reactions to sound, and in 59% of rats audiogenic seizures occured only in the form of motor excitation without a generalized clonic-tonic convulsions. Memantine at a dose of 5 mg/kg did not cause a complete blockade of seizures, but after 1 h of injection in 50% of the rats and after 2 h in 70% of rats a weakening of the audiogenic seizures to the level of motor excitation only was observed. After 3 hrs after administration of blockers its anticonvulsive action weakened significantly (p < 0.01). Dicationic blockers that block both NMDA and AMPA/kainate receptors, IEM-1925 (in doses of 0.001-20.0 mg/kg) and IEM-1754 (0.025-50.0 mg/kg), did not affect audiogenic clonic-tonic convulsive reactions. The involvement of activation of NMDA and calcium permeable AMPA/kainate receptors in the pathogenesis of audiogenic seizures is discussed.

[The effect of ionotropic glutamate receptor antagonist on pentylenetetrazole-indused seizures in Krushinsky-Molodkina rats].

Krushinsky-Molodkina (KM) rats exhibit inherited susceptibility to audiogenic seizures and auditory stimuli induce generalized tonic-clonic seizures that resemble human epilepsy. The aim of this study was to compare the neurological manifestations of pentylenetetrazole (PTZ)-induced seizures in Wistar and KM rats to clarify the contribution of inherited susceptibility to audiogenic seizures, and to assess the anticonvulsant activity of NMDA receptor blockers memantine and IEM-1921 (1-phenylcyclohexylamine) in the PTZ-induced seizure model in KM rats. KM rats exhibited increased seizure severity relative to Wistar rats, and the death of KM rats was observed in 2.1 times more likely. Both NMDA receptor blockers showed anticonvulsant activity in the PTZ-induced seizure model, however IEM-1921 was more potent than memantine. IEM-1921 reduced the average intensity of the seizures by 2 points on a 5-point scale, and the total duration of generalized seizures was decreased by 41 times. IEM-1921 completely prevented the death of animals, while memantine only slightly decreased the mortality (68% in control conditions vs. 50% with administration of memantine). The results of the present study suggest that NMDA receptors are involved in the molecular mechanisms of seizures of different etiologies.

[About evolution of sleep-wakefulness cycle in vertebrates].

Data about behavioral, somato-vegetative and neurophysiological parameters of sleep and wakefulness in insects, cold- and warm-blooded vertebrates are provided. Hypotheses existing now about evolutionary formation of separate sleep phases and stages in vertebrates are considered. In the review are shown the data about correlations of quantitative characteristics of sleep and wake in some mammals with basic metabolic rate, lifestyle, environmental habits. The original experimental results at formation of neurophysiological characteristics of sleep and wake in vertebrates, phylogeny and in ontogeny of mature and immature mammals are provided in detail. On the basis of own concepts about evolutionary development of sleep-wakefulness cycle in vertebrates the interactions of telencephalic, diencephalic and rhombencepalic parts of brain in the processes of cycle wakefulness cycle integration are discussed.

[On filo- and ontogenetic development of dopaminergic regylation of wakefulness-sleep cycle in vertabrates].

The comparative immunohistochemical researches of dofamine containing neurons and fibers are carried uot in telencephalic and diencephalic departments of the brain in different vertebratts (adults rats, rats aged 14 and 30 days and frogs). For analysis of quantitative changes dynamics in thyrozinhydroxylase, D1 and D2 immunoreactive material in sleep-wakefulness cycle the model of sleepdeprivation is used. There are found the facts of morphofunctional correlations in the reactions of dophaminergic system during ontogeny and phylogeny. Besides, the pharmacological effects of dofamine agonist and antagonists on the sleep-wakefulness cycle in young rats and in frogs are shown. So, dopamine and its agonist apomorphine increase in sleep-wakefulness cycle duration of sleep-like state ofcataplexy (homolog of the sleep) in frogs, in 30-day-old rats it increase the share of wakefulness and catalepsy. D1 receptors antagonist (SCH 23390) adminisrated to frogs, caused increase of wakefulness and catatonic type states duration, where as D2 receptors antagonist (apomorphine) increased cataleptic condition. Administration of dopamine antagonist (haloperidol) to 30-day-old rats previously causes the increase of cataleptic state, after which the slow wave sleep state is enhanced. The questions of phylo-, ontogenetic formation of dopaminergic system regulating role in sleep-wakefulness cycle, when transition mainly from neurosecretory diencephalic influences of dophamine to the mainly neurotransmittory functins of telencephalic regions occured, is discussed.

[The evolution of sleep circadian cycle and telencephalo-diencephalic interaction in vertebrates].

The modem representations of wakefulness-sleep cycle evolution and the data about dynamics of reactivity of activating and inhibition neurotransmitter systems of the forebrain, converging in striatum, in cold- and warm-blooded vertebrates are considered. The data about dynamics of immune reactivity of vasopressin- and oxytocinergic cells of paraventricular and supraoptical hypothalamic nuclei is presented. On the basis of the obtained results, the idea of the leading role of telencephalo-diencephalic interactions in activation of somnogenic processes and their possible mechanisms is advanced.

Effects of memantine on convulsive reactions and the organization of sleep in krushinskii-molodkina rats with an inherited predisposition to audiogenic convulsions.

Krushinskii-Molodkina rats, which have a genetic predisposition to audiogenic convulsions, are used as a natural animal model for studies of the actions of anticonvulsants. It is important to understand the extent to which changes in glutamatergic synaptic transmission is involved in the mechanisms producing convulsive states and in the functional organization of the sleep-waking cycle in rats of this strain. The present report describes experiments addressing this, in which i.m. doses of 5 and 10 mg/kg of a noncompetitive NMDA glutamate receptor antagonist of the memantine type were given at different times (30 min, 1, 2, and 3 h) before presentation of sound stimuli (sine-wave tones at 8 kHz, 90 dB). Effects on the latent periods of the initial motor excitation, the appearance of clonic convulsions of different intensities, and, finally, tonic convulsions with limb and tail extension were evaluated. The greatest attenuation of convulsive seizures, to a level consisting only of motor excitation, was obtained in 60% of the rats between 1 and 2 h after administration. There were no differences between the effects of doses of 5 and 10 mg/kg. When doses were given 3 h before sound provocation, convulsive reactions became more marked than at 2 h, though they were nevertheless more marked than in controls. Krushinskii-Molodkina rats with chronically implanted electrodes for recording brain electrical activity were used to study the effects of memantine on the organization of sleep. These experiments showed that the rats' sleep during the first hour after dosage consisted only of short episodes of superficial slow-wave sleep, and that even this sleep disappeared completely 54.4 +/- 4.9 and 39.9 +/- 5.2 min after administration of the agent at doses of 5 and 7 mg/kg, respectively. Rats showed a complete absence of sleep for 2 and 2.5 h, respectively, after which episodes of slow-wave sleep reappeared. The first episodes of REM sleep was seen in rats only after 3.3 +/- 0.2 and 3.7 +/- 0.2 h after memantine injections. The appearance of these episodes provided evidence that the effects of memantine on the activity of the somnogenic system of the animals' brains were complete and that recovery of the normal organization of the sleep-waking cycle had started. The synchronicity and codirectionality of the blocking action of memantine on sleep organization and measures of audiogenic convulsions in Krushinskii-Molodkina rats is evidence for the involvement of glutamatergic synapses with NMDA receptors in both the regulation of the somnogenic systems and the pathogenesis of epileptiform manifestations in rats.

[The sleep organization in the Krushinskii-Molodkina strain rats after sleep deprivation and different intensity audiogenic seizures].

Organization of sleep after different intensity audiogenic paroxysmal seizures evoked in animals under normal diurnal wakefulness-sleep cycle and after 12-hour fast-wave sleep deprivations or 6-hour total sleep deprivation was studied in Krushinskii-Molodkina strain rats with an inherited predisposition to audiogenic convulsions. Under all specified conditions, intensive audiogenic clonic or clonic-tonic convulsions caused long-lasting and pronounced sleep disorders in rats associated with disorganization of the mechanisms of starting the fast-wave sleep phase in the first place. But after experimental deprivations of sleep the audiogenic paroxysmal seizures run only as initial motor excitement without obvious convulsions. Such sort of seizures promote a faster beginning of recovery process after deprivations and did not cause any disorganization of the function of the brain systems responsible for starting and shaping (maintenance) fast-wave sleep.

[Effects of memantine on convulsive reactions and sleep-waking cycle in Krushinskii-Molodkina strain rats with the inherited predisposition to audiogenic convulsions].

Krushinskii-Molodkina strain rats have an inherited predisposition to audiogenic convulsions and are used as a natural animal model in the anticonvulsive drugs studies. We have investigated whether changes in the glutamatergic synaptic transmission are involved in the mechanism of audiogenic convulsions and functional organization of sleep-waking cycle observed in rats of this line. For this purpose Memantine, a selective uncompetitive blocker of NMDA receptors was used. Memantine was injected i.m. at the dose 5 or 10 mg/kg injected 30 min, 1, 2 or 3 hours before the sound stimulus (the sine-wave tone 8 kHz, 90 db). We evaluated the latent period of initial enhanced motor activity, the appearance and intensity of clonic seizures, and thereafter the tonic seizures accompanied by extension of limbs and tail. The maximal attenuation of convulsive attack to the level of initial motor excitement only was occurred in 60% of rats between 1 and 2 hours after memantine pretreatment. No difference between the doses 5 and 10 mg/kg was observed. The effect of memantine began to decrease when memantine was injected 3 h before convulsion provocation. The recording of EEG by chronically implanted electrodes was performed from the rats of Krushinsky-Molodkina line for the study of memantine effects on the sleep organization. The sleep of these rats during the first hour after 5 or 7 mg/kg memantine injection exhibited as the short periods of slow-wave sleep only which disappeared completely thereafter 54.4 +/- 4.9 and 39.9 +/- 5.2 min correspondingly. The complete sleep loss was observed approximately 2-2.5 hours later and followed by appearance of episodes of slow-wave sleep. The first episodes of fast-wave sleep occurred 3-4 hours later. Their reappearance evidenced of the completion of memantine action on the somnogenic brain systems and the beginning of recovery of normal sleep-waking organization. Thus the manifestations of unidirectional and synchronous memantine action on audiogenic seizures and disturbances of sleep-waking mechanisms may speak about involvement of NMDA receptors in both of epileptogenesis and somnogenic system of Krushinsky-Molodkina rats line.

[Effects of transliquoral electrical brain stimulation on the wakefulness-sleep cycle in rats].

Peculiarities of natural behavior in unanesthesired Wistar strain rats, and their electrogram patterns under the liquor brainstem electrical stimulation were in the focus of present study. Analysis of the electrogram specters of somatosensory and auditory areas of the cortex, hippocampus, mediodorsal thalamic nucleus, lateral periaqueductal gray and fastigial cerebellar nucleus revealed authentic increasing of teta-waves most significantly during slow-wave sleep period under the electrostimulation. The increasing of complete wakefulness-sleep cycles was found after multiple (15-20 per hour) stimulations. Possible homeostatic effect of the liquor brainstem electrical stimulation on somnogenic mechanisms are discussed.

The phenomenon of reduced convulsive readiness in Krushinskii-Molodkina rats after multiple audiogenic convulsive seizures.

Spectral analysis of activity in a number of brain structures (sensorimotor, visual and auditory cortex, hippocampus, caudate nucleus, medial central nucleus of the thalamus) was performed during the sleep-waking cycle in Krushinskii-Molodkina rats, which have an inherited predisposition to audiogenic convulsions; studies were performed on the background of the long-lasting, stable decrease in the level of convulsive readiness seen in these animals after multiple generalized audiogenic tonic-clonic convulsive seizures. The results showed that the decrease in the sensitivity of the rats to the convulsive action of sound correlates with a decrease in the intensity of the theta rhythm and an increase in alpha waves on the electroencephalogram in the state of calm waking. Possible rearrangements of the functioning of ascending brain systems in conditions of stable reductions in reactivity to sound after multiple convulsive seizures are discussed.

[Electroencephalographic analysis of manifestations of latent forms of paroxysmal syndrome in the wakefulness-sleep cycle in rats].

An electroencephalographic study of the brain activity in the wakefulness-sleep cycle was carried out on rats of Krushinskii-Molodkina line (KM) with hereditary predisposition to audiogenic convulsions and on Wistar rats that were insensitive to the convulsiogenic sound effect, but with epileptiform manifestations appearing on the background of cadmium intoxication and administration of kainic acid into the caudate nucleus head. There were revealed several EEG patterns whose presence was an indicator of formation of disorders of the CNS activity of the paroxysmal character in the animals. It has been established that in the phase of the rat rapid-wave sleep, a high representation of episodes with predominance of a-diapason EEG oscillations can be considered a specific non-paroxysmal abnormality due to the presence of convulsive syndrome in these animals. It was shown the long steady decrease of sensitivity of KM rats to the convulsiogenic sound effect, which appeared after multiple audiogenic generalized tonicoclonic convulsive attacks, correlated with a decrease of the degree of theta-diapason oscillations and with an increase of representation of alpha-diapason waves on EEG in the state of the animal quiet consciousness. A role of disintegration in activity of the ascending activating brain systems in the animal and human paroxysmal syndromes is discussed.

The effects of repeated audiogenic convulsions on the organization of sleep in rats.

The organization of sleep in Krushinskii-Molodkina rats, with an inherited predisposition to audiogenic convulsions, was studied during and after repeated audiogenic convulsions consisting of two, three, or five relatively rare (separated by intervals of 90 min) or three, five, or nine relatively frequent (separated by intervals of 45 min) generalized clonic-tonic convulsions. In rats subjected to repeated seizures with rare convulsions, behavior in the periods between individual convulsions was dominated by passive waking (75.2 +/- 4.6% of the time), with a low level (24.8 +/- 4.3%) of slow-wave and a complete absence of fast-wave sleep, i.e., there was selective removal of the fast-wave sleep phase from the sleep-waking cycle of the rats. In rats subjected to frequent seizures with frequent convulsions, the period between convulsions showed only passive waking, with complete loss of slow-wave and fast-wave sleep, i.e., total sleep deprivation took place. The minimal latent period before the appearance of the first episodes of slow-wave sleep after repeated convulsions was 59.9 +/- 10.8 min; that for fast-wave sleep was 158.2 +/- 13.4 min. However, the first episodes of slow-wave and fast-wave sleep had an essentially normal structure, though episodes shorter than those in controls were seen, albeit more rarely. Despite the prolonged (up to 7 h) absence of slow-wave sleep during seizures and the prolonged (8.5 h) decrease in fast-wave sleep, there was no compensatory increase in the levels of these states in the sleep-waking cycle during the 12 h of recovery after seizures. Overall, the recovery period after repeated seizures was characterized by an increase (compared with controls) in the total proportion of waking in the behavior of the rats, with a decrease in the total duration of slow-wave and fast-wave sleep. It is concluded that the paroxysmal status significantly disorganizes the operation of the sleep-generating structures of the brain. The functioning of the systems responsible for slow-wave sleep is less affected, while impairments of the activity of the systems responsible for the formation of fast-wave sleep are more significant, affecting primarily the mechanisms triggering this sleep phase.

[The phenomenon of lowering a seizure readiness level after frequent audiogenic seizures in Krushinskii-Molodkina rats].

The spectral analysis of the EEG activity of several brain structures (somatosensory, visual and auditory areas of the cortex, hippocampus, caudate nucleus and central medial thalamic nucleus) in the wakefulness-sleep cycle in Krushinskii--Molodkina strain rats with inherited predisposition to audiogenic seizures using long-lastint reducing of the seizure readiness level revealed in these animals after frequentative audiogenic generalized tonicclonic seizures, was performed. The reducing susceptibility to convulsiogenic sound stimuli in rats correlated with a decrease of the theta-range' waves level and increase of the expression alpha-range waves in the EEG during wakefulness. Probable role of reorganized functions of ascending activating brain systems in origination of the long reduction of susceptibility to the sound after frequentative audiogenic convulsions in rats is discussed.

[The effect of multiple audiogenic seizures upon the sleep organization in rats].

The organization of sleep during and after frequentative convulsions, consisting of 2, 3, or 5 comparatively rare seizures (following one another with a 90-minute interval) or of 3, 5 or 9 comparatively frequent seizures (following one another with a 45-minute interval) of generalized tonic-clonic character in Krushinskii-Molodkina strain rats with inherited predisposition to audiogenic convulsions, was studied. In frequentative convulsions with rare seizures, between separate seizures, passive wakefulness (75.2 +/- 4.6% time) prevailed under low (24.8 +/- 4.3%) slow-wave sleep and full absence of fast-wave sleep. In rats under frequentative convulsions with frequent seizures, in interictal period, only passive wakefulness was observed under reduction of slow-wave sleep and fast-wave sleep, i.e. total sleep deprivation. Minimal latensy of first episodes of the slow-wave sleep after frequentative convulsions was 59.9 +/- 10.8, and of fast-wave sleep: 158.2 +/- 13.4 min. First episodes of slow-wave sleep and fast-wave sleep had normal structure, though they were lesser and shorter than in control experiments. In spite of long-lasting (up to 7 hrs) absence of slow-wave sleep during seizure and prolonged (8.5 hrs) reduction of fast-wave sleep with no subsequent compensatory increase, these conditions occurred in the wakefulness-sleep cycle during 12-hour reconstruction after convulsions. The reconstruction period after frequentative convulsions was characterized by increase in general share of wakefulness and reduction of total slow-wave and fast-wave sleep as compared with control data. Paroxysmal status seems to disorganize work of the brain somnogenic structures. The function of systems responsible for slow-wave sleep are affected to a lesser extent, but disorganization of the system responsible for fast-wave sleep is more significant and associated with mechanisms of starting the phase of sleep in the first place.