Somesthetic cortex reactivity during sleeping and waking in the rat

Summary The cortical S1 responsiveness was studied by unique and coupled stimuli of non-maximal intensity applied to somesthetic radiations. The reactivity is highest during sleep with slow waves, lowest during active waking, intermediate during non-active waking and rapid sleep. The recovery of responsiveness presents an exactly opposite form and begins at a long interstimulus delay (>150 msec).     

Neuroanatomy and neurochemistry of sleep

Sleep is regulated by homeostatic and circadian factors, and the regulation of sleep of mammals shares many molecular properties with the rest state of submammalian species. Several brain structures take part in waking: the basal forebrain, posterior and lateral hypothalamus, and nuclei in the tegmentum and pons. Active sleep mechanisms are located to the preoptic/anterior hypothalamic area. In addition to acetylcholine and monoamines, glutamate and hypocretin/orexin are important waking factors. Gamma-aminobutyric acid and several peptide factors, including cytokines, growth hormone-releasing hormone and prolactin, are related to sleep promotion. Adenosine is an important homeostatic sleep factor acting in basal forebrain and preoptic areas through A1 and A2A receptors. Prolonged waking activates inducible nitric oxide synthase in the basal forebrain, which through energy depletion causes adenosine release and recovery sleep. Numerous genes have been found differentially displayed in waking compared with sleep, and they relate to neural transmission, synaptic plasticity, energy metabolism and stress protection. The genetic background of a few sleep disorders has been solved.     

Human slow wave sleep: A review and appraisal of recent findings,with implications for sleep functions,and psychiatric illness

Recent findings concerning human slow wave sleep (hSWS-stages 3+4; delta EEG activity) are critically reviewed. Areas covered include the significance of the first hSWS cycle; hSWS in extended sleep; relationship between hSWS, prior wakefulness and sleep loss; hSWS influence on sleep length; problems with hSWS deprivation; influence of the circadian rhythm; individual differences in hSWS, especially, age, gender and constitutional variables such as physical fitness and body composition. Transient increases in hSWS can be produced by increasing both the quality and quantity of prior wakefulness, with an underlying mechanism perhaps relating to the waking level of brain metabolism. Whilst there may also be thermoregulatory influences on hSWS, hypotheses that energy conservation and brain cooling are major roles for hSWS are debatable. hSWS seems to offer some form of cerebral recovery, with the prefrontal cortex being particularly implicated. The hSWS characteristics of certain forms of major psychiatric disorders may well endorse this prefrontal link.     

Internal interactions within the human circadian system: the masking effect

Summary In the realm of human circadian rhythms, the masking effect is defined as the change in the course of deep body temperature induced by changes in the degree of physical activity, or by the alteration between sleep and wake. This effect is particularly obvious during internal desynchronization where the rhythms of deep body temperature, and the sleep-wake sleep-wake sleep cycle — i.e. one of the masking factors — run with different periods.Every sleep onset is accompanied by a rapid drop, and wake onset by a rapid rise in deep body temperature, each one with an overshoot of about 50% of the steady state variations. When rhythms are calculated, with the dominant temperature period as the screening period, exclusively from data obtained during sleep episodes, on the one hand, and from those obtained exclusively during wake, on the other, two average cycles emerge: the sleep temperature curve and the wake temperature curve. Both run in parallel but are separated by the masking effcct. As derived from many experiments, the mean masking effect amounts to 0.28±0.06°C. The masking effect also depends to some extent on the phase of the temperature rhtthm; it is larger than average around the temperature maximum and during the descending phase of the temperature cycle, where the alertness commonly is highest and the probability to sleep, in general, and the REM sleep propensity, in particular, are smaller than average. This also can be interpreted to indicate that the sleep temperature curve is phase advanced relative to the wake temperature curve; this, on the average, by 0.9±0.3 h.If the individually determined amount of masking is added to the temperature data obtained during sleep, or substracted from the temperature data obtained during wake, a temperature curve emerges that can be though of as being purified of the masking effect. Analyses of this artificial curve allow estimation of that part of the internal interactions uninfluenced by the masking effect. On the average, about half of the amount of interaction between the rhythm of sleep-wake and that of deep body temperature is explained by the masking effect, whereas the other half is oscillatory interaction. Both types of interaction are inherent and inseparable parts of the circadian clock mechanism, as can be deduced from model considerations.     

Seasonality in human sleep

The timing of sleep and sleep EEG parameters in 10 healthy male subjects were investigated in four seasons under controlled conditions. The phase of nocturnal sleep was delayed about one and a half hours in winter as compared to that in summer. The duration of stage 4 sleep decreased and REM sleep increased significantly in winter compared with summer. The seasonality in the timing of sleep can be explained by photoperiodic time cues, but the changes in sleep EEG parameters are diffucult to explain in terms of photoperiod.     

Changes in cAMP concentration in the rat preoptic area during synchronized and desynchronized sleep

Summary cAMP concentration was found to be significantly lower during desynchronized sleep than during synchronized sleep in the preoptic area of rats kept at normal laboratory temperature. No significant changes in cerebral cortex cAMP concentraion were observed in the same experimental conditions.This work was supported by grants from Consiglio Nazionale delle Ricerche and Ministero della Pubblica Istruzione.The authors wish to thank G. Mancinelli and L. Sabattini for technical assistance and M. Luppi for secretarial assistance.     

Long-term motor activity recording of dogs and the effect of sleep deprivation

Summary Motor activity of laboratory dogs was recorded for several weeks with an ambulatory monitoring device. The effect of 24 h sleep deprivation (SD) on motor activity during recovery was investigated. A clear rest-activity rhythm was established. The dogs exhibited a similar mean daily rest-activity pattern: 1) rest occurred mainly in the dark; 2) the amimals were most active after light onset; activity increased during the last two dark hours; 3) a rest period was found at noon and reduced activity during afternoon hours. There was a marked difference in total activity between individual dogs. Activity patterns varied as a function of the day of the week; this may have been a reflection of variations in the level of human activities in the laboratory. There was a significant reduction of motor activity during the 24-h period following SD. This was particularly evident in the first 6 h of the light period immediately following the deprivation.In addition, there was a significant increase in the number of episodes with activity 5 counts during recovery. The study confirms the possibility of measuring motor activity to assess compensatory mechanisms during recovery after SD. Sleep regulation, therefore, does not necessarily need to be exclusively examined by the invasive technique of EEG registration.     

The waking brain: an update

Wakefulness and consciousness depend on perturbation of the cortical soliloquy. Ascending activation of the cerebral cortex is characteristic for both waking and paradoxical (REM) sleep. These evolutionary conserved activating systems build a network in the brainstem, midbrain, and diencephalon that contains the neurotransmitters and neuromodulators glutamate, histamine, acetylcholine, the catecholamines, serotonin, and some neuropeptides orchestrating the different behavioral states. Inhibition of these waking systems by GABAergic neurons allows sleep. Over the past decades, a prominent role became evident for the histaminergic and the orexinergic neurons as a hypothalamic waking center.     

Memory processes during sleep: beyond the standard consolidation theory

Two-step theories of memory formation suggest that an initial encoding stage, during which transient neural assemblies are formed in the hippocampus, is followed by a second step called consolidation, which involves re-processing of activity patterns and is associated with an increasing involvement of the neocortex. Several studies in human subjects as well as in animals suggest that memory consolidation occurs predominantly during sleep (standard consolidation model). Alternatively, it has been suggested that consolidation may occur during waking state as well and that the role of sleep is rather to restore encoding capabilities of synaptic connections (synaptic downscaling theory). Here, we review the experimental evidence favoring and challenging these two views and suggest an integrative model of memory consolidation.     

Cyclic variation in the amplitude of a brain stem reflex during sleep and wakefulness

Zusammenfassung In frei beweglichen Katzen wurden Veränderungen des Reflexes zum Musculus massetericus während des Schlafes und im Wachzustand untersucht. Eine graduelle Abnahme der Amplitude des Reflexes wurde beobachtet, wenn die Tiere vom Wachzustand über eine «schläfrige Phase» (drowsy state) in die sogenannte «ruhige Schlafphase» (quiet sleep) gelangten. Während des paradoxalen Schlafes (active sleep) waren die Amplituden der Reflexpotentiale hochgradig herabgesetzt.

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This research was supported by a grant from the USPHS (MH-10083) and by the Veterans Administration.

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This work has received bibliographic aid from the UCLA Brain Information Service which is a part of the National Information Network of the NINDB, and supported under Contract No. PH-43-66-59.     

Sex differences in human circadian rhythms: Intrinsic periods and sleep fractions

Summary The period of freerunning circadian rhythms is significantly shorter and the fraction of sleep is significantly larger in human females than in males, as long as the rhythms run internally synchronized. The sex difference in the period could be a property either of the whole circadian system or of only one of the oscillators in a multi-oscillator system. The sex difference in the sleep fraction could be a fixed property of the sleep-wake rhythm or could depend on interactions in the multi-oscillator system. To investigate these questions, a sample of 33 long-term experiments, in which the rhythms ran internally synchronized in one section and internally desynchronized in another section, were analyzed. The periods of rhythms in rectal temperature were different in females and males during internal synchronization, but became identical during internal desynchronization. In contrast, sex differences in sleep-wake periods were more pronounced when the rhythms were desynchronized than when they were internally synchronized. This result provides evidence that the sex difference in periodicity is a property only of the sleep-wake rhythm; the intrinsic periods of temperature rhythms are identical in females and males, whereas those of sleep-wake rhythms are distinctly shorter in females than in males. In the state of internal synchronization, the joint period is a compromise between the intrinsic periods of the rhythms involved, and therefore it shows a small but significant sex difference. Moreover, the transition from internally synchronized to desynchronized rhythms is combined with a highly significant reduction in the sleep fraction, which is considerably greater in females than in males. These results suggest that the occurrence of internal desynchronization strongly affects the sleep-wake rhythm, and that the influence of rhythm disorders is considerably greater in females than in males.     

Human slow wave sleep: a review and appraisal of recent findings, with implications for sleep functions, and psychiatric illness.

Recent findings concerning human slow wave sleep (hSWS-stages 3 + 4; delta EEG activity) are critically reviewed. Areas covered include the significance of the first hSWS cycle; hSWS in extended sleep; relationship between hSWS, prior wakefulness and sleep loss; hSWS influence on sleep length; problems with hSWS deprivation; influence of the circadian rhythm; individual differences in hSWS, especially, age, gender and constitutional variables such as physical fitness and body composition. Transient increases in hSWS can be produced by increasing both the quality and quantity of prior wakefulness, with an underlying mechanism perhaps relating to the waking level of brain metabolism. Whilst there may also be thermoregulatory influences on hSWS, hypotheses that energy conservation and brain cooling are major roles for hSWS are debatable. hSWS seems to offer some form of cerebral recovery, with the prefrontal cortex being particularly implicated. The hSWS characteristics of certain forms of major psychiatric disorders may well endorse this prefrontal link.     

Regulation of cross-bridge detachment by Ca ions at high ionic strength in molluscan catch muscle

Summary Changes in the profile of equatorial intensities of X-ray diffraction from an intact, anterior byssal retractor muscle (ABRM) ofMytilus were examined at rest, during contracture brought about by acetylcholine (ACh) and a subsequent rigor-like contraction caused by raising the tonicity of the external solution, and after returning the tonicity to normal. The results suggest that the cross-bridges formed between thick and thin actin filaments during the ACh-contracture were maintained in the hypertonic solution and broken on decreasing the tonicity before the recovery of spacing of the actin filament lattice. A similar rigor-like contraction was induced in glycerinated ABRM by increasing salt concentration during active contraction. The rigor-like force declined rapidly when Ca⁺⁺ concentration decreased. The results suggest that the detachment of the cross-bridge from the actin filament is regulated by Ca⁺⁺ at high ionic strength in the ABRM.     

Sleep disturbance due to transportation noise: ear plugs vs oral drugs

Conclusion Sleep is not only the output of an EEG machine but a global phenomenon with unique physiological, environmental and psychological features occurring in a given individual. There is no question that statistical evaluation of noise-induced sleep disturbances in non homogeneous groups of subjects has resulted in the construction of a magnificent neurophysiological edifice by assembling a few individual bricks. In this respect, whether subjectively disturbed or not, we now know that when we sleep in noisy areas our delta sleep is reduced, our heart rate fails to habituate to individual noises, and we are more likely to develop psychic disturbances than residents in quiet areas. Data from these studies are however interspersed with results from a number of experiments during which the subject has been looked upon as nothing but a sleeper, i.e., experiments in which day-time stresses and noises were considered as irrelevant for the night-time study. It seems important therefore that future studies should gather more longitudinal data based on a limited number of subjects selected according to their day-time habits and psychological (e.g., extroverts/introverts) and physiological (e.g., short or long sleepers) characteristics. The knowledge about these situational factors and personality traits might provide new insights into individual biological strategies developed to cope with noise stress. The difficulties in assessing the effect of noise on sleep are particularly obvious if we consider another finding: deaf subjects spend significantly less time in delta sleep than do control subjects⁴⁷ and they present sleep pattern alterations remarkably similar to those which are most consistently described in noisy conditions.Research by the authors has been supported by grants from the Ministère de la Qualité de la Vie et de l'Environnement (France) and Commission of European Communities.     

Chronobiology of sleep in humans

Periodic circadian (24-h) cycles play an important role in daily hormonal and behavioural rhythms. Usually our sleep/wake cycle, temperature and melatonin rhythms are internally synchronized with a stable phase relationship. When there is a desynchrony between the sleep/wake cycle and circadian rhythm, sleep disorders such as advanced and delayed sleep phase syndrome can arise as well as transient chronobiologic disturbances, for example from jet lag and shift work. Appropriately timed bright light is effective in re-timing the circadian rhythm and sleep pattern to a more desired time, ameliorating these disturbances. Other less potent retiming effects may also be obtained from the judicious use of melatonin and exercise.     

Shivering during sleep: Relationship between muscle blood flow and fiber type composition

The present study considers in rabbit: i) the relationship between muscle blood flow (BF) increase and fiber-type composition during shivering; ii) the influence of the vigilance states (Quiet Wakefulness, QW; Synchronized Sleep, SS; Desynchronized Sleep, DS) on this relationship. The results show that muscle BF increase during shivering is proportional to the slow-twitch oxidative (SO) fiber component in QW and SS; in DS the proportionality is lost. This is in accordance with the disappearance of shivering, together with all thermoregulatory effector responses, in this sleep state. Another muscle circulation pattern occurring at low ambient temperature, the relationship between BF increase and muscle depth, also disappears in DS. This confirms that the integrative control of muscle circulation, like other integrative mechanisms, is impaired during DS.     

Hibernation at moderate temperatures: a continuation of slow wave sleep

Summary Golden-mantled ground squirrels (Citellus lateralis) displayed virtually continuous electrophysiological states of sleep when hibernating at moderate ambient temperatures (22°C). Rapid-eye-movement sleep progressively diminished with the fall in body temperature so that at a body temperature of 23°C it was completely absent. At this temperature hibernation was characterized by slow wave sleep isomorphic with slow wave sleep episodes at non-hibernating (euthermic) body temperatures.Supported by National Institute of Health grants GM 23694 awarded to R.J. Berger and GM 23695 awarded to H.C. Heller.     

Sleep in an Amazonian manatee,Trichechus inunguis

For the first time, sleep was studied in a representative of the order of Sirenia. Slow wave sleep occupied 27%, and paradoxical sleep 1% of the total recording time in the Amazonian manatee,Trichechus inunguis. The circadian rhythmicity of sleep was pronounced. During the sleep period, the manatee woke up for a short time for each respiratory act. Interhemispheric asynchrony of the electrocortical slow wave activity was found.     

EEG and sleep in aged hospitalized patients with senile dementia: 24-h recordings

Polygraphic recordings of wake and sleep were performed on 10 partly bed-ridden, severely deteriorated patients with senile dementia. Compared with healthy elderly persons these subjects showed less SWS (slow wave sleep, characterized by high amplitude, slow EEG waves), less REM sleep (rapid eye movement sleep, usually accompanied by dream activity) and poorly organized stage 2 sleep (no sleep spindles, i.e. phasic EEG activity with a frequency of 12-14 Hz). Six of the 10 patients had no dominant alpha rhythm during wakefulness; this seemed to be related to their more deteriorated clinical state, to still less SWS and REM sleep and more time spent in stage 2. The basic NREM-REM cycle of sleep, i.e. the regular alternation between non-REM- and REM-periods, could still be distinguished, however, and showed similar average temporal characteristics as in healthy old and younger people. Similarly, although sleep was severely fragmented in most patients and many sleep episodes occurred during the day, the day-night alternation of wakefulness and sleep was maintained in the sample as a whole.     

Technologies of sleep research

Sleep is investigated in many different ways, many different species and under many different circumstances. Modern sleep research is a multidisciplinary venture. Therefore, this review cannot give a complete overview of all techniques used in sleep research and sleep medicine. What it will try to do is to give an overview of widely applied techniques and exciting new developments. Electroencephalography has been the backbone of sleep research and sleep medicine since its first application in the 1930s. The electroencephalogram is still used but now combined with many different techniques monitoring body and brain temperature, changes in brain and blood chemistry, or changes in brain functioning. Animal research has been very important for progress in sleep research and sleep medicine. It provides opportunities to investigate the sleeping brain in ways not possible in healthy volunteers. Progress in genomics has brought new insights in sleep regulation, the best example being the discovery of hypocretin/orexin deficiency as the cause of narcolepsy. Gene manipulation holds great promise for the future since it is possible not only to investigate the functions of different genes under normal conditions, but also to mimic human pathology in much greater detail.