The dynamics of spindles and EEG slow-wave activity in NREM sleep in mice

A quantitative analysis of spindles and spindle-related EEG activity was performed in C57BL/6 mice. The hypothesis that spindles are involved in sleep regulatory mechanisms was tested by investigating their occurrence during 24 h and after 6 h sleep deprivation (SD; n = 7). In the frontal derivation distinct spindle events were characterized as EEG oscillations with a dominant frequency approximately at 11 Hz. Spindles were most prominent during NREM sleep and increased before NREM-REM sleep transitions. Whereas spindles increased concomitantly with slow wave activity (SWA, EEG power between 0.5 and 4.0 Hz) at the beginning of the NREM sleep episode, these measures showed an opposite evolution prior to the transition to REM sleep. The 24-h time course of spindles showed a maximum at the end of the 12-h light period, and was a mirror image of SWA in NREM sleep. After 6 h SD the spindles in NREM sleep were initially suppressed, and showed a delayed rebound. In contrast, spindles occurring immediately before the transition to REM sleep were enhanced during the first 2 h of recovery. The data suggest that spindles in NREM sleep may be involved in sleep maintenance, while spindles heralding the transition to REM sleep may be related to mechanisms of REM sleep initiation.     

Principal components of electroencephalographic spectrum as markers of opponent processes underlying ultradian sleep cycles

Sleep-wake regulation involves reciprocal interactions between sleep- and wake-promoting processes that inhibit one another. To uncover the signatures of the opponent processes underlying ultradian sleep cycles, principal component analysis was performed on the sets of 16 single-Hz log-transformed electroencephalographic (EEG) power densities (1-16?Hz frequency range). Data were collected during unrestricted night sleep followed by 9 20-min naps (14 women aged 17-55 yrs) and during 12 20-min naps after either restriction or deprivation of sleep (9 males and 9 males, respectively, aged 18-22 yrs). It was found that any subset of power spectra could be reduced to the invariant four-principal component structure. The time courses of scores on these four components might be interpreted as the spectral EEG markers of the kinetics of two pairs of opponent chronoregulatory processes. In a sequence of ultradian sleep cycles, the 1st and 2nd components represent the alternations between competing drives for sleep and wakefulness, respectively, whereas the 3rd and 4th components reflect the alternations between light and deep sleep, respectively. The results suggest that principal component structuring of EEG spectrum can be employed for derivation of the parameters of the quantitative models conceptualizing the three major aspects of sleep-wake regulation—homeostatic, circadian, and ultradian processes.     

Asymmetry of the electroencephalographic manifestations of REM and slow-wave sleep in the cat

Studies were carried out on cats by bipolar electrodes implanted into symmetrical points of somatosensory cortical areas, caudate nuclei, hippocampus, lateral geniculate bodies, reticular formation of the midbrain after section of the half of midbrain tegmentum and commissural systems of the brain. Animals with sections usually have asymmetry of sleep EEG. The phenomenon is revealed of the coexistence of slow-wave and paradoxal sleep in different brain halves.     

Elevated variance in heart rate during slow-wave sleep after late-night physical activity

This study investigates the effect of mild physical activity before bedtime on the sleep pattern and heart rate during the night. Nine healthy subjects underwent a habituation night, a reference night, and a physical induction night. The physical induction night did not alter the sleep pattern. Physical activity before bedtime resulted in higher heart rate variance during slow-wave sleep. The low-frequency/high-frequency component (LF/HF) ratio during slow-wave sleep in the physical induction night was significantly higher than during the reference night. Increased mean heart rate and higher LF/HF ratio are related to decreased parasympathetic dominance. Exercise up to 1 h before bedtime thus seems to modify the quality of sleep.     

Role of biological membranes in slow-wave sleep

Two involvements of cellular membranes in slow-wave sleep (SWS) are discussed. In the first the endoplasmic reticulum (ER) is focussed upon, and in the second, the plasmalemma, where specific binding sites (receptors?) for promoters of slow-wave sleep are believed to be located. The study concerning the ER focusses on an enzyme in the brain, glucose-6-phosphatase, which, although present at low levels, manifests greatly increased activity during SWS compared to the waking state. The work on the plasmalemma has to do with the specific binding of muramyl peptides, inducers of slow-wave sleep, to various cells, and membrane preparations of various sorts, including those from brain tissue. Such cells as macrophages from mice, B-lymphocytes from human blood, and cells from a cell line (C-6 glioma) have been examined in this context.     

Effect of cold stimulation during slow-wave sleep on sleep cycle

To clarify the effect of cold stimulation during slow-wave sleep (SWS) on the sleep cycle, we conducted a sleep experiment. Five healthy males slept on a bedding system we developed to make the inside of bedding cooler. When the subject was sleeping deeply in the second and fourth SWS, the system cooled their bedding. When the subject's sleep condition shifted toward arousal, the cold air was stopped. As a result, all subjects’ sleep stage shifted to light sleep and reached arousal. After stopping stimulation, they immediately returned to the SWS at the first stimulation. But at the second stimulation, the sleep state did not return to the SWS.     

Effect of color temperature of light sources on slow-wave sleep

In order to examine whether the spectral compositions of light source may affect sleep quality, sleep architecture under different color temperatures of light sources was evaluated. Seven healthy males were exposed to the light sources of different color temperatures (3000 K, 5000 K and 6700 K) for 6.5 h before sleep. The horizontal illuminance level was kept at 1000 lux. Subjects slept on a bed in near darkness (< 10 lux) after extinguishing the light, and polysomnograms recorded the sleep parameters. In the early phase of the sleep period, the amount of stage-4 sleep (S4-sleep) was significantly attenuated under the higher color temperature of 6700 K compared with the lower color temperature of 3000 K. Present findings suggest that light sources with higher color temperatures may affect sleep quality in a view that S4-sleep period is important for sleep quality.     

An optimal monitor of the electroencephalographic sigma sleep state

A model has been proposed for a Markovjumping sleep depth that modulates a white-noise driven structure generating the sigma rhythm in the electroencephalogram. The corresponding maximum likelihood monitor, that continuously detects the current sleep stage from the observed electroencephalogram, has been derived and implemented. Simulations show high detection performances.     

Peptidoglycans as promoters of slow-wave sleep. I. Structure of the sleep-promoting factor isolated from human urine

Fast atom bombardment-mass spectrometry (FABMS) has been used to determine the structure of the urinary sleep-promoting factor (FSu), the nature of whose components had been reported earlier. Less than 1 nmol of the underivatized substance sufficed for the FABMS experiments. The major somnogenic constituent of the purified preparation was a peptidoglycan of Mr = 921 with the structure N-acetylglucosaminyl-N -acetylanhydromuramylalanylglutamyldiaminopimelylalanine. The anhydro linkage is between C-1 and C-6 of the muramyl entity. Two additional substances accompanied the above compound. These were the hydrated form (i.e. in which the muramyl entity had a free reducing end, and a free hydroxyl on C-6), and an anhydro analogue lacking the terminal alanine. The Mr values were 939 and 850, respectively. Methyl esters were prepared, and these were also acetylated. The mass spectra of the methyl ester of Mr = 921 displayed an increase in Mr of 42 (i.e. 3 X 14), indicating the presence, originally, of three free carboxyls. Acetylation increased Mr by a further 168 units (i.e. 4 X 42), indicating 4 hydroxyl or amino groups. These data are consistent with the structure cited above for the main entity of FSu. Similar confirmatory results were obtained for the two minor constituents described above. These operations were worked out on natural muramyl peptides of known structure, obtained from other sources, and the data are given for comparison.     

A probabilistic model for the ultradian timing of REM sleep in mice

A salient feature of mammalian sleep is the alternation between rapid eye movement (REM) and non-REM (NREM) sleep. However, how these two sleep stages influence each other and thereby regulate the timing of REM sleep episodes is still largely unresolved. Here, we developed a statistical model that specifies the relationship between REM and subsequent NREM sleep to quantify how REM sleep affects the following NREM sleep duration and its electrophysiological features in mice. We show that a lognormal mixture model well describes how the preceding REM sleep duration influences the amount of NREM sleep till the next REM sleep episode. The model supports the existence of two different types of sleep cycles: Short cycles form closely interspaced sequences of REM sleep episodes, whereas during long cycles, REM sleep is first followed by an interval of NREM sleep during which transitions to REM sleep are extremely unlikely. This refractory period is characterized by low power in the theta and sigma range of the electroencephalogram (EEG), low spindle rate and frequent microarousals, and its duration proportionally increases with the preceding REM sleep duration. Using our model, we estimated the propensity for REM sleep at the transition from NREM to REM sleep and found that entering REM sleep with higher propensity resulted in longer REM sleep episodes with reduced EEG power. Compared with the light phase, the buildup of REM sleep propensity was slower during the dark phase. Our data-driven modeling approach uncovered basic principles underlying the timing and duration of REM sleep episodes in mice and provides a flexible framework to describe the ultradian regulation of REM sleep in health and disease.     

Circadian rhythms of slow-wave sleep and paradoxical sleep are in opposite phase in genetically hypoprolactinemic rats

In eleven genetically hypoprolactinemic rats (IPL nude rats) and five control rats (OFA), the sleep-waking cycle was continuously registered for 14 days at two ambient temperatures. At 23 degrees C, the slow wave sleep (SWS) duration of IPL rats was significantly higher (+6.8%, t = 5.4, p less than 0.001) than that of control rats, while the paradoxical sleep (PS) duration was lowered by 31.8% (t = 9.4, p less than 0.001). The circadian rhythm of PS disappeared while that of SWS persisted unchanged. At 30 degrees C, both sleep durations reached the level of control rats. The circadian rhythm of PS was however completely reversed: the PS acrophase was at 01 h while that of SWS was at 12 hrs. This first observation of spontaneous dissociation of the two states of sleep supports the hypothesis of two distinct circadian clocks, one for SWS, another for PS. It is suggested that hypothalamic prolactin and/or other still unknown genetic alterations might be responsible for the observed change in the PS circadian rhythm.     

Low-frequency rhythmic electrocutaneous hand stimulation during slow-wave night sleep: Physiological and therapeutic effects

Neocortical EEG slow wave activity (SWA) in the delta frequency band (0.5–4.0 Hz) is a hallmark of slow wave sleep (SWS) and its power is a function of prior wake duration and an indicator of a sleep need. SWS is considered the most important stage for realization of recovery functions of sleep. Possibility of impact on characteristics of a night sleep by rhythmic (0.8–1.2 Hz) subthreshold electocutaneous stimulation of a hand during SWS is shown: 1st night—adaptation, 2nd night—control, 3d and 4th nights—with stimulation during SWA stages of a SWS. Stimulation caused significant increase in average duration of SWS and EEG SWA power (in 11 of 16 subjects), and also well-being and mood improvement in subjects with lowered emotional tone. It is supposed that the received result is caused by functioning of a hypothetical mechanism directed on maintenance and deepening of SWS and counteracting activating, awakening influences of the afferent stimulation. The results can be of value both for understanding the physiological mechanisms of sleep homeostasis and for development of non-pharmacological therapy of sleep disorders.     

Diurnal and ultradian rhythms in human endocrine function: a minireview

Rapidly accumulating evidence indicates that every hypothalamo-pituitary axis is influenced by both sleep (irrespective of the time of day when it occurs) and circadian rhythmicity (irrespective of the sleep or wake condition). Circadian effects seem to be exerted by a modulation of the amplitude of secretory pulses. Sleep may affect pulse frequency. Recent studies indicate that this complex temporal organization is not limited to pituitary and pituitary-dependent hormones but also underlies glucose regulation and insulin secretion.     

Simulation study on dynamics transition in neuronal activity during sleep cycle by using asynchronous and symmetry neural network model

We have found that single neuronal activities in different regions in the brain commonly exhibit the distinct dynamics transition during sleep-waking cycle in cats. Especially, power spectral densities of single neuronal activities change their profiles from the white to the 1/f along with sleep cycle from slow wave sleep (SWS) to paradoxical sleep (PS). Each region has different neural network structure and physiological function. This suggests a globally working mechanism may be underlying the dynamics transition we concern. Pharmacological studies have shown that a change in a wide-spread serotonergic input to these regions possibly causes the neuronal dynamics transition during sleep cycle. In this paper, based on these experimental results, an asynchronous and symmetry neural network model including inhibitory input, which represents the role of the serotonergic system, is utilized to examine the reality of our idea that the inhibitory input level varying during sleep cycle induce that transition. Simulation results show that the globally applied inhibitory input can control the dynamics of single neuronal state evolution in the artificial neural network: 1/f-like power spectral density profiles result under weak inhibition, which possibly corresponds to PS, and white profiles under strong inhibition, which possibly corresponds to SWS. An asynchronous neural network is known to change its state according to its energy function. The geometrical structure of network energy function is thought to vary along with the change in inhibitory level, which is expected to cause the dynamics transition of neuronal state evolution in the network model. These simulation results support the possibility that the serotonergic system is essential for the dynamics transition of single neuronal activities during sleep cycle.