Neurophysiological analysis of the effects of partial paradoxical sleep deprivation

A neurophysiological study was made of the effects of partial and complete paradoxial sleep deprivation by substituting episodes of active wakefulness for spells of paradoxical sleep (PS) of the same duration in the sleep-wake cycle. Neither accumulated need for paradoxical sleep (culminating in increased onset of PS during deprivation), PS rebound during the post-deprivation period, nor dissociation of the stages of paradoxical sleep resulting in their intervening individually at unaccustomed points in the sleep-wake cycle were observed during our experimental procedure. The phenomenon of self-deprivation, increased heart rate, eye movements, and pontogeniculooccipital (PGO) action potentials also failed to occur during the post-deprivation period. It is postulated that PS requirement and the need for periods of wakefulness stem from the same neurochemical alterations.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 1, pp. 20–28, January–February, 1988.     

Reciprocal actions between sensory signals and sleep

To the best of our knowledge, there is no simple way to induce neural networks to shift from waking mode into sleeping mode. Our best guess is that a whole group of neurons would be involved and that the process would develop in a period of time and a sequence which are mostly unknown. The quasi-total sensory deprivation elicits a new behavioral state called somnolence. Auditory stimulation as well as total auditory deprivation alter sleep architecture. Auditory units exhibiting firing shifts on passing to sleep (augmenting or diminishing) are postulated to be locked to sleep-related networks. Those ( approximately 50%) that did not change during sleep are postulated to continue informing the brain as in wakefulness. A rhythmic functional plasticity of involved networks is postulated. A number of auditory and visual cells have demonstrated a firing phase locking to the hippocampal theta rhythm. This phase locking occurs both during wakefulness and sleep phases. The theta rhythm may act as an organizer of sensory information in visual and auditory systems, in all behavioral states adding a temporal dimension to the sensory processing. Sensory information from the environment and body continuously modulates the central nervous system activity, over which sleep phenomenology must develop. It also produces a basal tonus during wakefulness and sleep, determining changes in the networks that contribute to sleep development and maintenance and, eventually, it also leads to sleep interruption.     

Sleeping Dreams, Waking Hallucinations, and the Central Nervous System

Consciousness is now considered a primary function and activity of the brain itself. If so, consciousness is simply the brain's interpretation and integration of all the information made available to it at any given time. On the assumption that the brain is active across all states of being (wakefulness, REM sleep, and NREM sleep), this article proposes that dreaming and hallucinations represent variations on the same theme. Under usual circumstances during wakefulness, the brain ignores internally generated activity and attends to environmental sensory stimulation. During sleep, dreaming occurs because the brain attends to endogenously generated activity. In unusual settings, such as sleep-deprivation, sensory deprivation, or medication or drug ingestion, the brain attends to exogenous and endogenous activities simultaneously, resulting in hallucinations, or wakeful dreaming. This concept is supported by numerous neurologic conditions and syndromes that are associated with hallucinations.     

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.     

The influence of adrenergic and cholinergic blocking drugs on the glycogen content of the brain in rats deprived of paradoxical sleep

Recent studies have pointed out biochemical and pharmacological phenomena associated with the mechanism or mechanisms of sleep, especially in its paradoxical phase (Jouvet, 1964; Mandel, 1964). Our previous experiments have shown that paradoxical sleep (PS) deprivation leads to the fall of total glycogen content in certain regions of the brains of cats (Mr?ulja, Raki? and Radulova?ki, 1967; Mr?ulja and Raki?, 1968) and rats (Karad?i? and Mr?ulja, 1969). It was shown that changes of glycogen content correspond to PS deprivation and that PS deprivation is a specific stress to which the CNS responds selectively. Alterations in the glycogen concentration in a number of different brain structures lead us to conclude that neural areas affected by PS deprivation are widely distributed. Jouvet (1962) was one of the first to suggest that a neurohumoral mechanism may be concerned in the control of and characteristics of sleep. Experiments have shown that both cholinergic and adrenergic mechanisms may be involved in the initiation, maintenance and control of sleep. It has also been pointed out that paradoxical sleep can be started and maintained by cholinergic drugs (Matsuzaki, Okada and Shuto, 1967, 1968), blocked or reduced by anticholinergic compounds (Matsuzaki et al., 1968), and stimulated by noradrenaline or by its precursor, DOPA (Matsumoto and Jouvet, 1964). Bowers, Hartmann and Freedman (1966) showed that the ACh level of the rat telencephalon decreases with PS deprivation while the levels of norpinephrine and serotonin remain the same (Barchas and Freedman, 1963). More recently, Pujol, Mouret, Jouvet and Glowinski (1968) found the increased turnover of cerebral norepinephrine during rebound of PS in the rat. It is also of interest to point out that probably both adrenergic and cholinergic processes participate in the glycogenolytic effect of physostigmine (Mr?ulja, Terzi? and Varagi?, 1968). It was suggested that physostigmine initiates the cholinergic processes which then trigger off adrenergic processes. The aim in the present work was to determine the glycogen content in certain brain regions of rats which were subjected to PS deprivation lasting 72 hr and treated with some cholinergic or beta-adrenergic blocking agents, as well as with a catecholamine depleting drug.     

State-Dependent Changes in Auditory Sensory Gating in Different Cortical Areas in Rats

Sensory gating is a process in which the brain’s response to a repetitive stimulus is attenuated; it is thought to contribute to information processing by enabling organisms to filter extraneous sensory inputs from the environment. To date, sensory gating has typically been used to determine whether brain function is impaired, such as in individuals with schizophrenia or addiction. In healthy subjects, sensory gating is sensitive to a subject’s behavioral state, such as acute stress and attention. The cortical response to sensory stimulation significantly decreases during sleep; however, information processing continues throughout sleep, and an auditory evoked potential (AEP) can be elicited by sound. It is not known whether sensory gating changes during sleep. Sleep is a non-uniform process in the whole brain with regional differences in neural activities. Thus, another question arises concerning whether sensory gating changes are uniform in different brain areas from waking to sleep. To address these questions, we used the sound stimuli of a Conditioning-testing paradigm to examine sensory gating during waking, rapid eye movement (REM) sleep and Non-REM (NREM) sleep in different cortical areas in rats. We demonstrated the following: 1. Auditory sensory gating was affected by vigilant states in the frontal and parietal areas but not in the occipital areas. 2. Auditory sensory gating decreased in NREM sleep but not REM sleep from waking in the frontal and parietal areas. 3. The decreased sensory gating in the frontal and parietal areas during NREM sleep was the result of a significant increase in the test sound amplitude.     

睡眠剥夺对脑电活动相位相干性的影响研究

将小波变换和相位相干分析应用到事件相关电位实验的脑电信号中。在正常状态和一夜睡眠剥夺状态下提取12名受试者的视觉ERP,进行30～60Hz的小波变换,以此计算前额叶区域的导联内相位相干,以及枕叶和前额叶之间的相位相干性。发现睡眠剥夺引起前额叶的导联内相位相干活动减少和延迟,表明大脑维持完成任务的能力下降;枕叶与前额叶之间的gamma波段相位相干活动减少,表明功能区域之间的电活动传递效应减弱。基于小波变换的相位相干分析可以得到脑电的同步活动,为更好地理解睡眠的机制和评价睡眠剥夺对认知的影响提供了一条思路。     

Sleep, emotions, and visceral control

It is known that sleep is connected with sensory isolation of the brain, inactivation of the consciousness and reorganization of the electrical activity in all cerebral cortical areas. On the other hand, sleep deprivation leads to pathology in visceral organs and finally to the death of animals, while there are no obvious changes in the brain itself. It is still unclear how the changes in the brain activity during sleep could be connected with the visceral health. We assumed that the same brain areas and the same neurons that, in wakefulness, process exteroceptive information, switch, during sleep, to the processing of the interoceptive information. Thus, the central nervous system is involved in regulating the life support functions of the body during sleep. The results of our experiments supported this hypothesis, explained many observations obtained in somnology, and offered mechanisms of several pathological states connected with sleep. However, at the present level of the visceral sleep theory, there is no understanding of the well-known link between the emotional reactions of the body and transition from wakefulness to sleep, and sleep quality. In this study, an attempt is undertaken to combine the visceral theory of sleep with the need-informational theory of emotions proposed by P. Simonov. The visceral theory of sleep assumes that in living organisms there is a constant monitoring of the correspondence of the visceral parameters to the genetically determined values. Mismatch signals evoke the feeling of tiredness and the need of sleep. This sleep need enters the competition with other actual needs of the body. In accordance with the theory of Simonov, emotions connected with a particular need play an important role in their ranking for satisfaction. We propose that emotional estimation of the sleep need based on visceral signals occurs in the same brain structures which undertake this estimation for other behavioral needs in wakefulness. During sleep, the same brain structures involved in estimating emotions continue to rank visceral needs and define their order for processing in the cortical areas and in the highest centers of visceral integration. In the context of the proposed hypothesis, we discuss the results of the studies on the link between sleep and emotions.     

Tracking the Sleep Onset Process: An Empirical Model of Behavioral and Physiological Dynamics

The sleep onset process (SOP) is a dynamic process correlated with a multitude of behavioral and physiological markers. A principled analysis of the SOP can serve as a foundation for answering questions of fundamental importance in basic neuroscience and sleep medicine. Unfortunately, current methods for analyzing the SOP fail to account for the overwhelming evidence that the wake/sleep transition is governed by continuous, dynamic physiological processes. Instead, current practices coarsely discretize sleep both in terms of state, where it is viewed as a binary (wake or sleep) process, and in time, where it is viewed as a single time point derived from subjectively scored stages in 30-second epochs, effectively eliminating SOP dynamics from the analysis. These methods also fail to integrate information from both behavioral and physiological data. It is thus imperative to resolve the mismatch between the physiological evidence and analysis methodologies. In this paper, we develop a statistically and physiologically principled dynamic framework and empirical SOP model, combining simultaneously-recorded physiological measurements with behavioral data from a novel breathing task requiring no arousing external sensory stimuli. We fit the model using data from healthy subjects, and estimate the instantaneous probability that a subject is awake during the SOP. The model successfully tracked physiological and behavioral dynamics for individual nights, and significantly outperformed the instantaneous transition models implicit in clinical definitions of sleep onset. Our framework also provides a principled means for cross-subject data alignment as a function of wake probability, allowing us to characterize and compare SOP dynamics across different populations. This analysis enabled us to quantitatively compare the EEG of subjects showing reduced alpha power with the remaining subjects at identical response probabilities. Thus, by incorporating both physiological and behavioral dynamics into our model framework, the dynamics of our analyses can finally match those observed during the SOP.     

Auditory deprivation modifies biological rhythms in the golden hamster

To assess to what extent auditory sensory deprivation affects biological rhythmicity, sleep/wakefulness cycle and 24 h rhythm in locomotor activity were examined in golden hamsters after bilateral cochlear lesion. An increase in total sleep time as well as a decrease in wakefulness (W) were associated to an augmented number of W episodes, as well as of slow wave sleep (SWS) and paradoxical sleep (PS) episodes in deaf hamsters. The number of episodes of the three behavioural states and the percent duration of W and SWS increased significantly during the light phase of daily photoperiod only. Lower amplitudes of locomotor activity rhythm and a different phase angle as far as light off were found in deaf hamsters kept either under light-dark photoperiod or in constant darkness. Period of locomotor activity remained unchanged after cochlear lesions. The results indicate that auditory deprivation disturbs photic synchronization of rhythms with little effect on the clock timing mechanism itself.     

Quantitative physiologically based modeling of subjective fatigue during sleep deprivation

A quantitative physiologically based model of the sleep-wake switch is used to predict variations in subjective fatigue-related measures during total sleep deprivation. The model includes the mutual inhibition of the sleep-active neurons in the hypothalamic ventrolateral preoptic area (VLPO) and the wake-active monoaminergic brainstem populations (MA), as well as circadian and homeostatic drives. We simulate sleep deprivation by introducing a drive to the MA, which we call wake effort, to maintain the system in a wakeful state. Physiologically this drive is proposed to be afferent from the cortex or the orexin group of the lateral hypothalamus. It is hypothesized that the need to exert this effort to maintain wakefulness at high homeostatic sleep pressure correlates with subjective fatigue levels. The model's output indeed exhibits good agreement with existing clinical time series of subjective fatigue-related measures, supporting this hypothesis. Subjective fatigue, adrenaline, and body temperature variations during two 72 h sleep deprivation protocols are reproduced by the model. By distinguishing a motivation-dependent orexinergic contribution to the wake-effort drive, the model can be extended to interpret variation in performance levels during sleep deprivation in a way that is qualitatively consistent with existing, clinically derived results. The example of sleep deprivation thus demonstrates the ability of physiologically based sleep modeling to predict psychological measures from the underlying physiological interactions that produce them.     

Disruption of the structural organization of brain mitochondrial membranes during deprivation of the paradoxal sleep phase and correction for it using lithonite]

Interrelation between the structure-functional state of membranes of the brain mitochondria and intensity of metabolic processes in their lipid matrix has been studied during long-term deprivation of the paradoxic sleep and against a background of preventive administration of atypical tranquillizer, lithonite, a derivative of nicotinic acid. It is shown that sleep deprivation for four days is accompanied by expressed activation of lipids' oxidation by free radicals, inhibition of anti-oxidant system and inactivation of the marker enzymes of mitochondrial membranes. The character of binding and distribution of fluorescent probes 1-anilinonaphthalene-8-sulphonate (ANS) and N-phenyl-1-naphthalamine (PNA) in different layers of mitochondrial membranes is broken, which evidences for deep rearrangement of the lipid matrix. Sleep deprivation causes an increase in the relative volume and swelling of mitochondria but a decrease in the inner membrane area and the number of crusts. A course of lithonite administration exerts a selective membrane-protecting effect stabilizing structure-functional state of the brain mitochondria by non-specific protection of their lipid component and stimulation of the antioxidant system. An expediency to use lithonite for correction of other deadaptive processes induced by the membrane destruction is substantiated.     

Fluctuations and synchronizations of neural activities during sleep: Neural basis of possible sleep functions?

Physiological and psychological evidence have been accumulated concerning the function of sleep in development and learning/memory. Many conceptual ideas have been proposed to elucidate the mechanisms underlying them. Sleep consists of a wide variety of physiological processes. It has not yet been clarified which processes are involved in development and learning/memory processes. We have found that single neuronal activity exhibits a slowly fluctuating rate of discharge during rapid eye movement (REM) sleep and a random low discharge rate during non-rapid eye movement (NREM) sleep. It is suggested that a structural change of the neural network attractor underlies this neuronal dynamics-alternation by mathematical modeling. Functional interpretation of the neuronal dynamics-alternation was provided in combination with the phase locking of ponto-geniculo-occipital (PGO)/pontine (P) wave to the hippocampal theta wave, each of which is known to be involved in learning/memory processes. More directly, by the long-term sensory deprivation, the dynamics of neural activity during sleep was found to progressively change in a non-monotonic way. This finding reveals a possible interaction between sleep and reorganization of neural network in the matured brain. Here, in addition to the related findings, we described our idea about how sleep contributes to the learning/memory processes and reorganization of neural network of the matured brain through characteristic neural activities during sleep.

     

Rapid eye movement (rem) sleep deprivation: effect on acid mucopolysaccharides in rat brain.

The effect of rapid eye movement (REM) sleep deprivation on the total content and proportion of different mucopolysaccharides (AMPS) containing uronic acid in rat brain was studied. REM sleep deprivation was induced by the water tank methods. Five experimental groups of animals were used: control, stressed, REM sleep deprived, post-stress sleeping and post-deprivation sleeping rats. No changes of AMPS were observed in any of the experimental groups when the whole brain was analysed. A significant increase of AMPS was found in the cerebral hemispheres of stressed and REM deprived rats. A significant decrease of AMPS was observed in the cerebellum and brain stem. A further increase of AMPS was found in the cerebral hemispheres after the rebound of REM sleep following its deprivation, and after the recovery sleep following the stress. A significant increase of AMPS was found in the brain stem of rats allowed to recuperate after REM deprivation or stress as compared with the stressed and REM deprived animals. Recovery sleep induced a significant increase of AMPS in the cerebellum in previously stressed rats, while previously REM deprived rats exhibited a further decrease of AMPS from control values. The possible functional meaning of these results is discussed in relation to the role of REM sleep in protein synthesis and learning and memory processes. Intriguing, well-controlled positive findings and the fact that no experimental design is known where stress is minimal while REM deprivation is 100 per cent, justify and encourage continued efforts in studying the biochemical state of the brain during sleep and/or its alterations.     

Circadian and sleep-deprivation variations of monophosphorylated MAP-Kinase in hypothalamus and pons of rats

Behavior and physiological changes are under the influence of circadian and homeostatic variations. Temporal alignment regulates timing of neurobiological phenomena, such as protein phosphorylation. In the current report, we describe the circadian and sleep homeostatic phosphorylated mitogen-activated protein kinase (MAP-K) variations in hypothalamus and pons of rats across 24 h as well as after sleep deprivation. In the circadian study, MAP-K expression showed a building-up profile during the dark phase in hypothalamus, whereas an increase across the lights-on period was found in pons. On the other hand, that phosphorylation of MAP-K in hypothalamus and pons displayed a significant reduction after sleep rebound period. Data demonstrate that MAP-K phosphorylation undergoes circadian and sleep homeostatic variations in brain areas linked to sleep modulation.     

Tuberal Hypothalamic Neurons Secreting the Satiety Molecule Nesfatin-1 Are Critically Involved in Paradoxical (REM) Sleep Homeostasis

The recently discovered Nesfatin-1 plays a role in appetite regulation as a satiety factor through hypothalamic leptin-independent mechanisms. Nesfatin-1 is co-expressed with Melanin-Concentrating Hormone (MCH) in neurons from the tuberal hypothalamic area (THA) which are recruited during sleep states, especially paradoxical sleep (PS). To help decipher the contribution of this contingent of THA neurons to sleep regulatory mechanisms, we thus investigated in rats whether the co-factor Nesfatin-1 is also endowed with sleep-modulating properties. Here, we found that the disruption of the brain Nesfatin-1 signaling achieved by icv administration of Nesfatin-1 antiserum or antisense against the nucleobindin2 (NUCB2) prohormone suppressed PS with little, if any alteration of slow wave sleep (SWS). Further, the infusion of Nesfatin-1 antiserum after a selective PS deprivation, designed for elevating PS needs, severely prevented the ensuing expected PS recovery. Strengthening these pharmacological data, we finally demonstrated by using c-Fos as an index of neuronal activation that the recruitment of Nesfatin-1-immunoreactive neurons within THA is positively correlated to PS but not to SWS amounts experienced by rats prior to sacrifice. In conclusion, this work supports a functional contribution of the Nesfatin-1 signaling, operated by THA neurons, to PS regulatory mechanisms. We propose that these neurons, likely releasing MCH as a synergistic factor, constitute an appropriate lever by which the hypothalamus may integrate endogenous signals to adapt the ultradian rhythm and maintenance of PS in a manner dictated by homeostatic needs. This could be done through the inhibition of downstream targets comprised primarily of the local hypothalamic wake-active orexin- and histamine-containing neurons.     

Signals from the Brainstem Sleep/Wake Centers Regulate Behavioral Timing via the Circadian Clock

Sleep-wake cycling is controlled by the complex interplay between two brain systems, one which controls vigilance state, regulating the transition between sleep and wake, and the other circadian, which communicates time-of-day. Together, they align sleep appropriately with energetic need and the day-night cycle. Neural circuits connect brain stem sites that regulate vigilance state with the suprachiasmatic nucleus (SCN), the master circadian clock, but the function of these connections has been unknown. Coupling discrete stimulation of pontine nuclei controlling vigilance state with analytical chemical measurements of intra-SCN microdialysates in mouse, we found significant neurotransmitter release at the SCN and, concomitantly, resetting of behavioral circadian rhythms. Depending upon stimulus conditions and time-of-day, SCN acetylcholine and/or glutamate levels were augmented and generated shifts of behavioral rhythms. These results establish modes of neurochemical communication from brain regions controlling vigilance state to the central circadian clock, with behavioral consequences. They suggest a basis for dynamic integration across brain systems that regulate vigilance states, and a potential vulnerability to altered communication in sleep disorders.