Light Slow Wave Sleep Research Articles

Effect of quinolinic acid on wakefulness and sleep in the rabbit

Quinolinic acid (QUIN), an endogenous neuroactive metabolite of tryptophan, administered i.c.v. in doses of 45, 90, 180, and 270 nmol in rabbits, demonstrated an excitatory action on the sleep-wake cycle and behaviour. Doses of 90 and 180 nmol completely abolished the paradoxical sleep phase and induced a 5-fold decrease in the duration of deep slow wave sleep (dSWS) in the first hour of the experiment. Light slow wave sleep (1SWS) duration was not altered. Sniffing behaviour was markedly activated by 180 nmol of QUIN. A dose of 270 nmol completely blocked sleep, diminished the restoration of sleep, induced panic behaviour and, in some animals, induced generalized tonic seizures. Data suggest an excitatory action of QUIN on NMDA receptors involved in the regulation of the sleep-wake cycle in the rabbit.

Differential effects of the new antipsychotic risperidone on sleep and wakefulness in the rat

The effects of risperidone, a new antipsychotic with potent 5-hydroxytryptamine 2 (5-HT 2) and dopamine-D 2 (DA-D 2) antagonistic properties, were studied on sleep-wakefulness patterns in rats. Administration of low doses (0.01–0.16 mg/kg i.p.) resulted in a significant increase of deep slow wave sleep (SWS2) and a decrease of wakefulness (W) and light slow wave sleep (SWSl). High doses (0.63–2.5 mg/kg) produced opposite effects. Paradoxical sleep (PS) was significantly reduced over the dose range tested. The increase of SWS2 after low doses of risperidone could be related to a predominant and potent 5-HT 2 receptor blocking activity.

The light-dark cycle modulates the effects of ritanserin on sleep-wakefulness patterns in the rat

The 5-HT2 receptor antagonist ritanserin (0.63 mg/kg IP) produced differential effects on sleep-wakefulness patterns in rats when administered during the light or dark period: an increase in the duration of deep slow wave sleep at the expense of light slow wave sleep, paradoxical sleep and wakefulness when injected during the light period, and no major sleep alteration when given at dark onset. Since circadian variations in serotonin receptor density might modulate the sleep response, we examined the effects of ritanserin on sleep in rats exposed to continuous light for 10 days, and whether 5-HT2 receptors were affected in separate groups of rats exposed to similar conditions. No significant changes in the KD- and Bmax -values of various receptors were found. However, ritanserin produced greater effects in continuous light conditions than when given during the light period in the 12-hr light-dark condition. This suggests a possible role of 5-HT2 receptors in the organization of sleep when the environmental photoperiod is disturbed.

Functional role of 5-HT2 receptors in the regulation of sleep and wakefulness in the rat

Recently developed agents specifically acting on different 5-hydroxytryptamine (5-HT) receptor populations were used to analyze the functional role of 5-HT2 receptor subtypes in the sleep-wakefulness cycle of the rat. The 5-HT2 receptor antagonist ritanserin injected intraperitoneally (IP) (0.04-2.5 mg/kg) induced an increase in deep slow wave sleep (SWS2) duration at the expense of wakefulness (W), light slow wave sleep (SWS1) and paradoxical sleep (PS). The stimulation of 5-HT2 receptors by 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced a dose-related increase in W and a dose-dependent decrease in both SWS2 and PS. Pretreatment with ritanserin (0.16-2.5 mg/kg) or with cinanserin (2.5-5 mg/kg), another 5-HT2 receptor antagonist, dose-dependently reversed the W enhancement and the SWS2 deficit produced by DOM, but not the PS deficit. Sleep-wakefulness alterations (increase in W and SWS1 combined with a suppression of SWS2 and PS) observed after IP injection of two putative 5-HT1 receptor agonists, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) (2.5 mg/kg) and 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole (RU 24969) (0.63 mg/kg), were not modified by ritanserin pretreatment (0.16-2.5 mg/kg). These results further support the hypothesis that the serotonergic system plays an active role in the regulation of the sleep-wakefulness cycle in the rat and that 5-HT2 receptors are involved in this action. In addition, it is suggested that 5-HT1 receptor subtypes are unlikely to interact with 5-HT2 receptors in the sleep-wakefulness modulation mediated through 5-HT2 receptors.

Long-lasting insomnia induced by preoptic neuron lesions and its transient reversal by muscimol injection into the posterior hypothalamus in the cat

In order to analyse the role of the anterior hypothalamus in the regulation of the sleep-waking cycle we made bilateral neuronal lesions at different levels of the anterior hypothalamus in cats, by means of microinjections of a cell-specific neurotoxin: ibotenic acid. These lesions resulted in severe insomnia in eight cats. This insomnia was characterized by a large decrease or even disappearance of paradoxical sleep and deep slow wave sleep and, to a lesser extent, by a decrease of light slow wave sleep, for 2–3 weeks. In the other five animals, we observed a large reduction of deep slow wave sleep (0–40% of control level), but a less intensive decrease of time spent in paradoxical sleep (50–75% of control level) and no marked effect on light slow wave sleep. During the first 3–6 postoperative days we also noticed hyperthermia in all cats; thereafter, the animals presented only a slight increase in brain temperature which did not appear to trigger the sleep impairment. Histological analysis of the different lesions revealed that the insomnia could be attributed to neuronal cell body destruction in the mediobasal part of the anterior hypothalamus covering: the medial preoptic area and a narrow portion of the lateral preoptic area as well as a restricted part of the anterior hypothalamic nucleus. In order to investigate the putative role of the posterior hypothalamic structures in the mechanism of insomnia after lesion of the mediobasal preoptic area neurons we injected an agonist of GABA into the ventrolateral part of the posterior hypothalamus to locally depress the neuronal activity. The bilateral intracerebral microinjection of muscimol (0.5–5 μg) induced a transient intensive hypersomnia (slow wave sleep and paradoxical sleep). These findings indicate that neuronal cell loss in the mediobasal preoptic area induced a long lasting insomnia. Thus, it may be hypothesized that the integrity of this structure is necessary for sleep appearance. Finally, our data are in keeping with an intrahypothalamic regulation of the sleep-waking cycle.

Evidence for histaminergic arousal mechanisms in the hypothalamus of cat

Polygraphic 23-hr recordings were carried out in 25 adult cats in order to examine the effects of both systemic and local injections of various histaminergic and antihistaminergic drugs on sleep-waking cycles. α-Fluroromethylhistidine (α-FMH), a specific inhibitor of histidine decarboxylase, when injected intraperitoneally at a dose of 20 mg/kg, induced a significant increase in deep slow wave sleep (S2) and a decrease in wakefulness (W), without modifying light slow wave sleep (S1) and paradoxical sleep (PS). Intraperitoneal injections of mepyramine (1 mg and 5 mg/kg), a well-known histamine H 1-receptor antagonist, increased deep slow wave sleep and decreased wakefulness, as well as paradoxical sleep. Bilateral injections of α-FMH (50 μg/l μl) into the ventrolateral posterior hypothalamus, where histamine immunoreactive neurones have been recently identified, resulted in a significant decrease in wakefulness and increase in deep slow wave sleep. Similarly, injections of mepyramine (120 μg/1 μl) in the same structures caused a significant decrease in wakefulness and an increase in deep slow wave and paradoxical sleep as well. In contrast, local injections of SKF-91488 (50 μg/l μl), a specific inhibitor of histamine- N-methyltransferase, led to a significant increase in wakefulness and decrease in both slow wave sleep (SWS) and paradoxical sleep. Injections of histamine, at doses of 5, 30 and 60 μg/1 μl, also increased wakefulness and decreased slow wave sleep dose dependently, while these effects were completely blocked by pretreatment with mepyramine. The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H 1-receptors.

The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat

The effect of a single injection of synthetic delta-sleep-inducing peptide (DSIP, 7 nmol/kg) into the lateral ventricle of 10 cats was investigated by monitoring the sleep-wake cycle during an 8 h period. A significant decrease in sleep latency and a significant increase in total sleep and in total slow wave sleep (SWS) was found following DSIP administration. The increase in sleep resulted exclusively from a significant increase in deep slow wave sleep (S 2), while light slow wave sleep (S 1) was significantly decreased. Neither the total amount of REM sleep, nor hourly values of REM sleep were affected by DSIP application. Additional measures of REM sleep, like REM sleep latency, mean episode number and mean episode length were not different from those found in control conditions. DSIP was immediately effective since the amount of S 2 increased to more than 50% in the first postinjection hour and the difference from the control value was highly significant. The increase in S 2 was maintained over 7 h, and disappeared by the eighth hour. The increase in S 2 was caused by a prolongation of S 2 episodes and not by their more frequent occurrence. The results obtained suggest a sleep-facilitating property of DSIP.

Modulation during sleep of the cat trigeminal neurons responding to tooth pulp stimulation

Sleep-induced changes in the trigeminal neuron responses to electrical stimulation of the cat tooth pulp were studied. Two parameters were adopted: One was the evoked spike number at two times the threshold intensity (2×T response magnitude), which would reveal the level shifting of the neuronal response by the sleep-regulatory system. Another was the rate of change in the response intensity when the stimulus was raised to a level of 0.7 time the arousal threshold during light slow wave sleep (sensitivity gradient), which would reflect the influences of the pain-modulatory system driven by strong noxious inputs. It was found that during sleep the two indexes tended to show a correlated change; the neurons which came to have a greater 2×T response magnitude tended to have a smaller sensitivity gradient than during wakefulness, and vice versa. It was suggested that two contrasting populations of tooth pulp neurons might be differentiated, and that the sleep-regulatory system and the pain-modulatory system would have differential but correlated controls over these two kinds of neurons.

Electrophysiological evaluation of three paradoxical sleep deprivation techniques in rats

Three different techniques were used to study the effects of 72 hr deprivation of paradoxical sleep on percentages total sleep, light slow wave sleep, deep slow wave sleep and paradoxical sleep during deprivation and recovery periods in rats. The paradoxical sleep deprivation methods used were the classical platform, the pendulum and the multiple platform techniques. The different groups were continuously recorded over a base-line day, three deprivation days and four recovery days. All three groups showed clear suppression of paradoxical sleep throughout the deprivation period, although small differences between the pendulum and the multiple platform technique emerged. The distribution of sleep across the day and the amount of deep slow wave sleep were affected differently. Besides an exception immediately after deprivation, no important differences were detected on the recovery days. The recovery is characterized by an immediate rebound of paradoxical sleep, completed within two days, as well as rapid re-normalization of sleep percentages. A small rebound of deep slow wave sleep was recorded at the end of the dark period during the first three recovery days. Various sleep and non-sleep related variables of the PS deprivation techniques are discussed. It is improbable that the platform-pendulum controversy is due to differences in the amount of PS deprivation or the other sleep parameters measured here. Rather it looks as though non-specific platform effects override the effects of PS deprivation.

Interaction sleep and epilepsy.

In order to improve the diagnosis of epilepsy, a routine EEG recording can be supplemented with a long-lasting sleep recording or with an ambulatory EEG recording. In this paper we compare the all-night polygraphic sleep recording with the 3- to 5-hour recording after 1 night total sleep deprivation, and we discuss the outcome with each. In the first part we have analyzed the relationship between the clinical form of epilepsy and the kind and depth of sleep and we have tried to determine the optimal registration time (in hours) to obtain a maximum diagnostic gain. In the second part we have evaluated the changes in the sleep composition induced by the occurrence of epileptic EEG phenomena and by the intake of antiepileptic drugs. In the third part we have analyzed the changes in the morphological aspects of the epileptic EEG phenomena which can occur under influence of light (NREM 1-2) and deep (NREM 3-4) slow-wave sleep and REM sleep. A sufficient knowledge of these changes is very important to avoid misinterpretations.

Platform sleep deprivation affects deep slow wave sleep in addition to REM sleep

Rats were sleep deprived by the platform method to look for differential effects on light and deep slow wave sleep depending on platform size. Diameters of large and small platforms were 15 cm and 5.1 cm respectively. Sleep was recorded during a baseline light period (09.00–19.00 h), continuously during 48 h of sleep deprivation and during the first lights on recovery period (09.00–19.00 h). In both platform conditions REM sleep was virtually abolished during the first light period (hours 0–10 of sleep deprivation), while NREM sleep was reduced to approximately half of control values. During the second light period (hours 22–34 of sleep deprivation) REM sleep recovered somewhat in the large platform group. Light slow wave sleep (SWS-1) was comparable to baseline while deep slow wave sleep (SWS-2) was still significantly reduced. In the small platform group both SWS-2 and REM sleep was considerably reduced on day 2. Over the whole deprivation period there was an effect of platform size on SWS-1 (higher in the small platform group), and on SWS-2 and REM sleep (lower in the small platform group). During the 9 h light-time recovery sleep there was an REM sleep rebound in both groups. SWS-1 was reduced in both groups while SWS-2 was not significantly increased. The ratio SWS-2 SWS-1 was, however, significantly increased only in the small platform group recovery sleep. The results suggest that platform sleep deprivation deprives the animals of deep slow wave sleep in addition to REM sleep. This has implications for conclusions on REM sleep function based upon REM sleep deprivation.

Reduced sleep in cats after intraperitoneal injection of δ-sleep-inducing peptide (DSIP)

The effect of intraperitoneally injected δ-sleep-inducing peptide (DSIP) on sleep-wakefulness in cats was studied using EEG, EMG and EOG recording for 10 h following 30 nmol/kg DSIP or control saline i.p. injections. DSIP reduced the amount of sleep, specifically light slow-wave sleep and REM sleep, and REM sleep latency was increased. The results suggest that in cats with redundancy sleep DSIP increases wakefulness at the cost of light slow-wave sleep, and in addition it has a specific REM-reducing effect.

Physiological sleep myoclonus in baboons

Physiological sleep myoclonus (sleep onset myoclonus and myoclonus during paradoxical sleep) was recorded from the tails of 6 baboons (2 Papio hamadryas and 4 Papio papio) and its relationship with spontaneously occurring EEG paroxysmal discharges was studied. It was observed that during light slow wave sleep tail myoclonus (sleep onset myoclonus) was almost always associated with EEG paroxysmal discharges predominating in the fronto-rolandic cortex. During deep slow wave sleep the number of EEG paraxysmal discharges decreased and tail myoclonus disappeared. In contrast, during paradoxical sleep tail myoclonus became more frequent even in the absence of cortical paroxysmal discharges. Though at present we do not know whether sleep onset myoclonus is triggered or not by cortical paroxysmal discharges, we propose that sleep myoclonus (sleep onset myoclonus and myoclonus of paradoxical sleep) is independent of these discharges but that, at a given moment, the two phenomena may be coupled by a hypothetical subcortical pacemaker.

Effects of delta sleep inducing peptide on sleep cycle of cats deprived of paradoxical sleep

The effect of synthetic delta sleep inducing peptide (DSIP) on sleep was investigated in cat. DSIP (7 nmol/kg was administered intracerebroventricularly to cats deprived of paradoxical sleep (PS) for 72 h and immediately after termination of PS deprivation an injection of either Ringer or DSIP solution was given. Eight h of recovery sleep was then recorded. DSIP failed to affect the duration of slow-wave sleep, PS and total sleep time. There was, however, significant decrease of wakefulness and light slow-wave sleep (S1) while deep slow-wave sleep (S2) was significantly increased. There was also no change in the latency to the first episode of S2 sleep and PS. Thus, we conclude that DSIP altered the relative amounts of S1 and S2 sleep, causing more S2 (delta) sleep at the time when pressure for sleep was at its highest due to prior sleep deprivation.

An EEG averaging technique for automated sleep-wake stage identification in the rat

An automated on-line sleep-wake classification system based on an averaging technique of the running EEG is described. It operates for three rats simultaneously and is able to discriminate every 5 sec between wakefulness, light slow-wave sleep, deep slow-wave sleep, and paradoxical sleep. The hippocampal EEG and nuchal EMG are used as input parameters. The EEG is bandpass filtered after which a microcomputer samples and averages the filtered EEG and constructs spectrograms. The variability, the theta-delta ratio and the amplitude of the delta waves are obtained from these spectrograms. Together with the amplitude index of the EMG, these three EEG indices are subjected to decision rules for the identification of sleep-wake states. A first evaluation study showed 93% agreement between visual inspection and computer classification. In a second evaluation study 24-hr recordings were made. Clear circadian patterns emerged especially during the light period: deep slow-wave sleep was enhanced during the initial hours, while paradoxical sleep tended to increase over the latter hours. The outcome of these studies is compared with the results obtained with other automated sleep identification procedures.

Modulation of postsynaptic activities of thalamic lateral geniculate neurons by spontaneous changes in number of retinal inputs in chronic cats. 1. Input-output relations

The experiments were designed to explore the role of retinal inputs compared with that of the behavioral state in the modulation of the output of thalamic lateral geniculate neurons during sleep and wakefulness in cats with intact visual pathways. We made the following assumptions: the retinal dark discharge, while showing spontaneous pauses in activity, does not vary with the behavioral state; the optic tract inputs postsynaptically elicit subthreshold activities called S-potentials which in turn generate spikes, the degree of transformation being dependent on the level of alertness. On the basis of these assumptions, it could be expected that changes in retinal input frequency would modify the rate of the S-potentials. Therefore the effect of spontaneous decreases in frequency of S-potentials on the spike rate and pattern was examined in juxta- and intracellular recordings from chronically implanted cats during natural sleep and wakefulness. During quiet wakefulness and light slow-wave sleep, lateral geniculate relay neurons normally displayed numerous S-potentials associated with a moderate firing rate. Many neurons occasionally showed transient reductions in frequency of the S-potentials and an oversimplification of the discharges which combined a decreased rate with a prevalent rhythmical burst pattern. Antidromic responsiveness remained unchanged. The oscillatory periods recurred two to six times without any alteration in the control state level. They were not observed throughout wakefulness and paradoxical sleep, during which neuronal activity combined a high spike rate with a low S-potential rate. The modifications were confirmed by computation of the mean rates and of the inter-event intervals. The transfer ratio (spikes/S-potentials + spikes) significantly increased both during the oscillatory periods poor in S-potentials of quiet wakefulness and during active wakefulness. But the correlation between the transfer ratio and the spike frequency, which was high throughout the control behavioral states, faded during the periods poor in S-potentials. Thus the transient falls in the frequency of S-potentials which occurred spontaneously during quiet wakefulness caused burst discharges in lateral geniculate relay neurons, which resembled a sleep deepening, but also paralleled the effect of experimental deaflerentation. The data indicate that the iterative spikes grouped in well spaced bursts which persisted during decreases in subthreshold postsynaptic activities result in an enhanced signal-to-noise ratio. It is suggested that these impulses would maintain a minimal level of information to the visual cortex despite low rates in retinal presynaptic inputs. Therefore the results provide new insights on the regulating function of the lateral geniculate relay neuron in the visual processing during the sleep-wake cycle.

Diazepam and midazolam increase light slow-wave sleep (SWS1) and decrease wakefulness in rats

Rats implanted with electrodes for polygraphic recordings were injected with diazepam (5 mg/kg, i.p.) or midazolam, (10 mg/kg, i.p.) and recorded for 6 h during the 8 h of darkness of a 16 h light/8 h dark cycle. The results show that administration of diazepam reduced SWS1 latency by 92%, and increased SWS1 and total sleep by 255% and 59%, respectively, in comparison to control. Administration of midazolam increased SWS1 by 158% and total sleep by 57% when compared to control. These findings correlate well with the effects of benzodiazepines on sleep stage 2 in humans and indicate that benzodiazepine hypnotics increase only the behaviorally lighter stage of SWS in rats as well as in human subjects.

Breathing During Sieep in Normal Young and Elderly Subjects: Hypopneas, Apneas, and Correlated Factors

Polysomnograms were obtained from two groups of normal subjects (20 medical students and 20 elderly persons). The recordings included the usual sleep parameters (electroencephalograph, electrooculograph, and electromyograph of chin muscles) and respiratory data obtained by means of a pneumotachygraph (tidal volumes and respiratory frequency) and thoracic and abdominal strain gauges. In the older group, sleep was more disturbed and respiratory events (hypopneas and apneas) were more frequent both in non-rapid eye movement (NREM) and in REM sleep. The apneas were predominantly of the obstructive type. A correspondence analysis carried out on the 40 subjects showed that a high frequency of hypopneas and obstructive apneas was linked to old age and age-related parameters (disturbed sleep and obesity) both during NREM and REM sleep. A high frequency of central apneas during light slow-wave sleep was linked to the male sex; a high frequency of central apneas during REM sleep was linked to the amount of REM sleep. No relationship could be demonstrated between the decrease of minute ventilation from wakefulness to steady sleep and the incidence of sleep respiratory events.

Serotonergic mechanisms and sleep rebound

The administration of p-chlorophenylalanine (PCPA), an inhibitor of serotonin (5-HT) biosynthesis, at the end of a 48 h sleep deprivation does not impair the subsequent rebound of deep slow wave sleep (SWS2) and paradoxical sleep (PS). On the contrary, the administration of PCPA during a 48 h sleep deprivation is followed by a great decrease of light slow wave sleep (SWS1) and by total disappearance of SWS2 while some rebound of PS still occurs in narcoleptic-like attacks. These experiments provide evidence that sleep inducing materials are accumulated during sleep deprivation. Serotonergic processes appear to be involved in the regulatory mechanisms of the biosynthesis and the accumulation of SWS2 and PS factors.

Circadian rhythm of electrical activity and motility of the stomach in cats and their relation to sleep--wakefulness stages.

Polysomnographic recordings were done over continuous 3 days together with those of electrical and mechanical activities of the stomach using chronically implanted electrodes and force-transducer in unanesthetized and unrestrained state of 4 adult cats. Circadian rhythm of the basic electric rhythm (BER) and mechanical activity in the stomach accustomed to feeding schedule of once a day was divided into the two; the fed state from the end of feeding to 8 to 11 hr later and the succeeding fasting state. However, differentiation of the fasting state into the contractile and noncontractile periods, which is known in dogs, was not evident in cats. The mean BER interval was longer and the standard deviation was smaller in the fed state than in the fasting state. Among stages of wakefulness (W), drowsiness (D), light slow wave sleep (LS), deep slow wave sleep (DS) and REM sleep, the mean BER intervals in every total time during the fed state were compared with one another. A definite unidirectional finding obtained in all 4 cats was only that the mean BER intervals in the stage D were longer significantly than those in the stage W.