Potentiometric monitoring of the redox state of brain structures of freely-moving rats in sleep-wake cycles

Variations of brain tissue redox state potential (E) of freely-moving white rats (300-350 g) in cycles of wakefulness (W), slow-wave sleep (SWS), and paradoxical sleep (PS) were measured by platinum electrodes symmetrically implanted into the frontal and occipital cortices and hippocampus. In addition, EMG of neck muscles and general motor activity of animals were recorded. The common reference electrode was implanted in the nasal bone. It was shown that in some brain sites (called active), episodes of W and PS were accompanied by a rise of E, and during transitions from W and PS to SWS, E dropped. The value of E varied in the range of 100 mV. It is suggested that transitions from W and PS to SWS are accompanied by shifts in the balance between the main energy sources. Oxidative phosphorylation prevails in W and PS, whereas aerobic glycolysis is the main source of energy during SWS. We think that this suggestion is supported both by a decrease in E in SWS and its oscillations typical of glucolytic processes [Aon et al., 1992]. Recent literature data [Bitter et al., 1996] suggest that astroglia is the main compartment for aerobic glycolysis.     

The modelling of the glycolytic oscillations in the potential of the oxidative-reductive status of the brain tissue in waking and anesthetized rats]

It was found that chemical hypoxia created by intraperitoneal injection of potassium cyanide (5-7 mg/kg) induced in both waking and anaesthetized (pentobarbital, 40 mg/kg) albino rats a significant decrease in the brain redox state potential (E) monitored with platinum electrodes. This decrease could be accompanied by a generation in some brain points of local chains of gradually damped quasisinusoidal E oscillations. Such oscillations were more expressed in waking than in anaesthetized animals. The frequency range of these oscillations was 4-7 cycles/min. This is the range of overlapping frequency ranges characteristic for the high level of vigilance (5-20 cycles/min) and slow-wave sleep and drowsiness (1.5-6 cycles/min). The amplitude of the observed oscillations was close to the maximal amplitude of the brain E oscillations characteristic for the high level of vigilance (up to several mV). The obtained evidence favors our suggestion that behavior-related E oscillations are formed by the oscillations in the redox balance of glycolysis. The similarity of the normal physiological oscillations and those simulated by us under abnormal conditions suggest a certain common mechanism of their generation.     

Changes in the rabbit brain cortex redox potential accompaning episodes of ECoG-arousal during slow-wave sleep

Local cortex E variations are well expressive indices of rate and peculiarities of energy metabolism. The brain E is determined by the ratio of processes occurring in two energy compartments in glycolysis, in whish glucose is split without oxygen utilization and in oxidative metabolism. In the present investigation, the brain cortex E changes were recorded with implanted platinum electrodes during slow wave sleep. Under such conditions, the E lowering detects acceleration in glycolytic compartment, whereas the E local rising shows acceleration in oxidative metabolism in the tissue surrounding the electrode. Earlier in rats, we have found that E significantly lowered in metabolic active cortical sites during episodes of SWS, and supposed that acceleration of glycolysis increased. Slow oscillations (a 20-40-sec prolongation of the amplitude up to several dozens millivolts) appeared at the same time. We considered these E slow oscillations to reflect changes in the rate in compartment of glycolysis. In this research, we have found the E slow oscillations to be created by regular episodes of ECoG-arousal which were accompanied by E decreases, i. e. by acceleration in glycolysis. We think the data presented show existence of functional system supporting a low level of arousal. As in any complex system with feed back connections, this system works in oscillatory regime.     

Rhythms of slow-wave sleep and wakefulness in fluctuations of the potential of the oxidative-reductive status of the cerebral cortex

A method of recording slow ROSP's changes of the brain in chronic animals was used. It has been shown that wakefulness was accompanied by quasisinusoidal oscillations of ROSP (periods--several seconds). During slow sleep, oscillations of ROSP became more complicated and their periods were longer. It is suggested that transitions from sleep to wakefulness and vice versa are connected with removal of maximums of oxidative metabolism tension between biochemical systems characterized by different rhythms of self-regulation. Rhythmic oscillations of ROSP reveal the possibility of separate functional system of the ROSP of the brain cortex to synchronize their oscillations in the brain tissue (biochemical synergism).     

Neuronal plasticity in thalamocortical networks during sleep and waking oscillations

Spontaneous brain oscillations during states of vigilance are associated with neuronal plasticity due to rhythmic spike bursts and spike trains fired by thalamic and neocortical neurons during low-frequency rhythms that characterize slow-wave sleep and fast rhythms occurring during waking and REM sleep. Intracellular recordings from thalamic and related cortical neurons in vivo demonstrate that, during natural slow-wave sleep oscillations or their experimental models, both thalamic and cortical neurons progressively enhance their responsiveness. This potentiation lasts for several minutes after the end of oscillatory periods. Cortical neurons display self-sustained activity, similar to responses evoked during previous epochs of stimulation, despite the fact that thalamic neurons remain under a powerful hyperpolarizing pressure. These data suggest that, far from being a quiescent state during which the cortex and subcortical structures are globally inhibited, slow-wave sleep may consolidate memory traces acquired during wakefulness in corticothalamic networks. Similar phenomena occur as a consequence of fast oscillations during brain-activated states.     

Spontaneous hemodynamic oscillations during human sleep and sleep stage transitions characterized with near-infrared spectroscopy

Understanding the interaction between the nervous system and cerebral vasculature is fundamental to forming a complete picture of the neurophysiology of sleep and its role in maintaining physiological homeostasis. However, the intrinsic hemodynamics of slow-wave sleep (SWS) are still poorly known. We carried out 30 all-night sleep measurements with combined near-infrared spectroscopy (NIRS) and polysomnography to investigate spontaneous hemodynamic behavior in SWS compared to light (LS) and rapid-eye-movement sleep (REM). In particular, we concentrated on slow oscillations (3-150 mHz) in oxy- and deoxyhemoglobin concentrations, heart rate, arterial oxygen saturation, and the pulsation amplitude of the photoplethysmographic signal. We also analyzed the behavior of these variables during sleep stage transitions. The results indicate that slow spontaneous cortical and systemic hemodynamic activity is reduced in SWS compared to LS, REM, and wakefulness. This behavior may be explained by neuronal synchronization observed in electrophysiological studies of SWS and a reduction in autonomic nervous system activity. Also, sleep stage transitions are asymmetric, so that the SWS-to-LS and LS-to-REM transitions, which are associated with an increase in the complexity of cortical electrophysiological activity, are characterized by more dramatic hemodynamic changes than the opposite transitions. Thus, it appears that while the onset of SWS and termination of REM occur only as gradual processes over time, the termination of SWS and onset of REM may be triggered more abruptly by a particular physiological event or condition. The results suggest that scalp hemodynamic changes should be considered alongside cortical hemodynamic changes in NIRS sleep studies to assess the interaction between the autonomic and central nervous systems.     

Dynamics of spontaneous activity in random networks with multiple neuron subtypes and synaptic noise

During slow-wave sleep, brain electrical activity is dominated by the slow (< 1 Hz) electroencephalogram (EEG) oscillations characterized by the periodic transitions between active (or Up) and silent (or Down) states in the membrane voltage of the cortical and thalamic neurons. Sleep slow oscillation is believed to play critical role in consolidation of recent memories. Past computational studies, based on the Hodgkin-Huxley type neuronal models, revealed possible intracellular and network mechanisms of the neuronal activity during sleep, however, they failed to explore the large-scale cortical network dynamics depending on collective behavior in the large populations of neurons. In this new study, we developed a novel class of reduced discrete time spiking neuron models for large-scale network simulations of wake and sleep dynamics. In addition to the spiking mechanism, the new model implemented nonlinearities capturing effects of the leak current, the Ca²⁺ dependent K⁺ current and the persistent Na⁺ current that were found to be critical for transitions between Up and Down states of the slow oscillation. We applied the new model to study large-scale two-dimensional cortical network activity during slow-wave sleep. Our study explained traveling wave dynamics and characteristic synchronization properties of transitions between Up and Down states of the slow oscillation as observed in vivo in recordings from cats. We further predict a critical role of synaptic noise and slow adaptive currents for spike sequence replay as found during sleep related memory consolidation.     

Sleep-Stage Correlates of Hippocampal Electroencephalogram in Primates

It has been demonstrated in the rodent hippocampus that rhythmic slow activity (theta) predominantly occurs during rapid eye movement (REM) sleep, while sharp waves and associated ripples occur mainly during non-REM sleep. However, evidence is lacking for correlates of sleep stages with electroencephalogram (EEG) in the hippocampus of monkeys. In the present study, we recorded hippocampal EEG from the dentate gyrus in monkeys overnight under conditions of polysomnographical monitoring. As result, the hippocampal EEG changed in a manner similar to that of the surface EEG: during wakefulness, the hippocampal EEG showed fast, desynchronized waves, which were partly replaced with slower waves of intermediate amplitudes during the shallow stages of non-REM sleep. During the deep stages of non-REM sleep, continuous, slower oscillations (0.5–8 Hz) with high amplitudes were predominant. During REM sleep, the hippocampal EEG again showed fast, desynchronized waves similar to those found during wakefulness. These results indicate that in the monkey, hippocampal rhythmic slow activity rarely occurs during REM sleep, which is in clear contrast to that of rodents. In addition, the increase in the slower oscillations of hippocampal EEG during non-REM sleep, which resembled that of the surface EEG, may at least partly reflect cortical inputs to the dentate gyrus during this behavioral state.     

Human gamma oscillations during slow wave sleep

Neocortical local field potentials have shown that gamma oscillations occur spontaneously during slow-wave sleep (SWS). At the macroscopic EEG level in the human brain, no evidences were reported so far. In this study, by using simultaneous scalp and intracranial EEG recordings in 20 epileptic subjects, we examined gamma oscillations in cerebral cortex during SWS. We report that gamma oscillations in low (30-50 Hz) and high (60-120 Hz) frequency bands recurrently emerged in all investigated regions and their amplitudes coincided with specific phases of the cortical slow wave. In most of the cases, multiple oscillatory bursts in different frequency bands from 30 to 120 Hz were correlated with positive peaks of scalp slow waves ("IN-phase" pattern), confirming previous animal findings. In addition, we report another gamma pattern that appears preferentially during the negative phase of the slow wave ("ANTI-phase" pattern). This new pattern presented dominant peaks in the high gamma range and was preferentially expressed in the temporal cortex. Finally, we found that the spatial coherence between cortical sites exhibiting gamma activities was local and fell off quickly when computed between distant sites. Overall, these results provide the first human evidences that gamma oscillations can be observed in macroscopic EEG recordings during sleep. They support the concept that these high-frequency activities might be associated with phasic increases of neural activity during slow oscillations. Such patterned activity in the sleeping brain could play a role in off-line processing of cortical networks.     

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.     

Modeling of Ca2+ flux in pancreatic beta-cells: role of the plasma membrane and intracellular stores

We have developed a detailed mathematical model of ionic flux in beta-cells that includes the most essential channels and pumps in the plasma membrane. This model is coupled to equations describing Ca2+, inositol 1,4,5-trisphosphate (IP3), ATP, and Na+ homeostasis, including the uptake and release of Ca2+ by the endoplasmic reticulum (ER). In our model, metabolically derived ATP activates inward Ca2+ flux by regulation of ATP-sensitive K+ channels and depolarization of the plasma membrane. Results from the simulations support the hypothesis that intracellular Na+ and Ca2+ in the ER can be the main variables driving both fast (2-7 osc/min) and slow intracellular Ca2+ concentration oscillations (0.3-0.9 osc/min) and that the effect of IP3 on Ca2+ leak from the ER contributes to the pattern of slow calcium oscillations. Simulations also show that filling the ER Ca2+ stores leads to faster electrical bursting and Ca2+ oscillations. Specific Ca2+ oscillations in isolated beta-cell lines can also be simulated.     

Slow Oscillation Amplitudes and Up-State Lengths Relate to Memory Improvement

There is growing evidence of the active involvement of sleep in memory consolidation. Besides hippocampal sharp wave-ripple complexes and sleep spindles, slow oscillations appear to play a key role in the process of sleep-associated memory consolidation. Furthermore, slow oscillation amplitude and spectral power increase during the night after learning declarative and procedural memory tasks. However, it is unresolved whether learning-induced changes specifically alter characteristics of individual slow oscillations, such as the slow oscillation up-state length and amplitude, which are believed to be important for neuronal replay. 24 subjects (12 men) aged between 20 and 30 years participated in a randomized, within-subject, multicenter study. Subjects slept on three occasions for a whole night in the sleep laboratory with full polysomnography. Whereas the first night only served for adaptation purposes, the two remaining nights were preceded by a declarative word-pair task or by a non-learning control task. Slow oscillations were detected in non-rapid eye movement sleep over electrode Fz. Results indicate positive correlations between the length of the up-state as well as the amplitude of both slow oscillation phases and changes in memory performance from pre to post sleep. We speculate that the prolonged slow oscillation up-state length might extend the timeframe for the transfer of initial hippocampal to long-term cortical memory representations, whereas the increase in slow oscillation amplitudes possibly reflects changes in the net synaptic strength of cortical networks.     

Sleep and wakefulness in Greenland seal pups

ECoG of both hemispheres, EOG, neck EMG and EKG were recorded in 2 white (age 10 days) and 2 gray pups (age 1 month) of harp seal. The active wakefulness occupied 23.4 +/- 3.8% of total recording time, the relaxed wakefulness--32.6 +/- 3.6%, drowsiness--4.8 +/- 1.1%, slow wave sleep--31.5 +/- 3.0%, paradoxical sleep--7.7 +/- 0.8%. The sleep cycle averaged 18.2 +/- 1.4 min. Interhemispheric asymmetry of the ECoG was not seen in all 4 pups. The respiration was fast and regular in the relaxed wakefulness, then long respiration pauses were alternated with episodes of hyperventilation during slow wave sleep and there was rare and irregular respiration in the paradoxical sleep. The heart rate was lowest during the paradoxical sleep. It is suggested that this pattern of sleep, allowing seals to delay their breathing during sleep for a long time may be considered as an adaptation to existence in freezing seas.     

Human plasma DSIP decreases at the initiation of sleep at different circadian times

Nocturnal plasma delta sleep-inducing peptide-like immunoreactivity (DSIP-LI) was determined serially in seven healthy male subjects. Time courses during nocturnal sleep (2300-0800 h), nocturnal sleep deprivation (2300-0500 h), and morning recovery sleep (0500–0800 h) after sleep deprivation were compared. A significant decrease in plasma DSIP-LI was found at the transition from wakefulness to sleep in both evening sleep (2300 h) and morning recovery sleep (0500 h). Time courses were accompanied by physiological changes in sleep electroencephalographic slow-wave activity, and in plasma concentrations of cortisol and human growth hormone. No sleep stage specificity was found. It is concluded that DSIP is influenced by the initiation of sleep.     

Vigilance state-dependent attenuation of hypercapnic chemoreflex and exaggerated sleep apnea in orexin knockout mice.

Exogenous administration of orexin can promote wakefulness and respiration. Here we examined whether intrinsic orexin participates in the control of breathing in a vigilance state-dependent manner. Ventilation was recorded together with electroencephalography and electromyography for 6 h during the daytime in prepro-orexin knockout mice (ORX-KO) and wild-type (WT) littermates. Respiratory parameters were separately determined during quiet wakefulness (QW), slow-wave sleep (SWS), or rapid eye movement (REM) sleep. Basal ventilation was normal in ORX-KO, irrespective of vigilance states. The hypercapnic ventilatory response during QW in ORX-KO (0.19 +/- 0.01 ml.min(-1).g(-1).%CO(2)(-1)) was significantly smaller than that in WT mice (0.38 +/- 0.04 ml.min(-1).g(-1).%CO(2)(-1)), whereas the responses during SWS and REM in ORX-KO were comparable to those in WT mice. Hypoxic responses during wake and sleep periods were not different between the genotypes. Spontaneous but not postsigh sleep apneas were more frequent in ORX-KO than in WT littermates during both SWS and REM sleep. Our findings suggest that orexin plays a crucial role both in CO(2) sensitivity during wakefulness and in preserving ventilation stability during sleep.     

Partitioning of inhaled ventilation between the nasal and oral routes during sleep in normal subjects.

The oral and nasal contributions to inhaled ventilation were simultaneously quantified during sleep in 10 healthy subjects (5 men, 5 women) aged 43 +/- 5 yr, with normal nasal resistance (mean 2.0 +/- 0.3 cmH(2)O. l(-1). s(-1)) by use of a divided oral and nasal mask. Minute ventilation awake (5.9 +/- 0.3 l/min) was higher than that during sleep (5.2 +/- 0.3 l/min; P < 0.0001), but there was no significant difference in minute ventilation between different sleep stages (P = 0.44): stage 2 5.3 +/- 0.3, slow-wave 5.2 +/- 0.2, and rapid-eye-movement sleep 5.2 +/- 0.2 l/min. The oral fraction of inhaled ventilation during wakefulness (7.6 +/- 4%) was not significantly different from that during sleep (4.3 +/- 2%; mean difference 3.3%, 95% confidence interval -2.1-8.8%, P = 0.19), and no significant difference (P = 0.14) in oral fraction was observed between different sleep stages: stage two 5.1 +/- 2.8, slow-wave 4.2 +/- 1.8, rapid-eye-movement 3.1 +/- 1.7%. Thus the inhaled oral fraction in normal subjects is small and does not change significantly with sleep stage.     

The Temporal Structure of Behaviour and Sleep Homeostasis

The amount and architecture of vigilance states are governed by two distinct processes, which occur at different time scales. The first, a slow one, is related to a wake/sleep dependent homeostatic Process S, which occurs on a time scale of hours, and is reflected in the dynamics of NREM sleep EEG slow-wave activity. The second, a fast one, is manifested in a regular alternation of two sleep states – NREM and REM sleep, which occur, in rodents, on a time scale of ∼5–10 minutes. Neither the mechanisms underlying the time constants of these two processes – the slow one and the fast one, nor their functional significance are understood. Notably, both processes are primarily apparent during sleep, while their potential manifestation during wakefulness is obscured by ongoing behaviour. Here, we find, in mice provided with running wheels, that the two sleep processes become clearly apparent also during waking at the level of behavior and brain activity. Specifically, the slow process was manifested in the total duration of waking periods starting from dark onset, while the fast process was apparent in a regular occurrence of running bouts during the waking periods. The dynamics of both processes were stable within individual animals, but showed large interindividual variability. Importantly, the two processes were not independent: the periodic structure of waking behaviour (fast process) appeared to be a strong predictor of the capacity to sustain continuous wakefulness (slow process). The data indicate that the temporal organization of vigilance states on both the fast and the slow time scales may arise from a common neurophysiologic mechanism.     

Dynamics of neuronal activity in the lateral preoptic area of hypothalamus in the course of sleep-waking cycle

Frequency and patterns of activity of 106 neurons in the lateral preoptic area of unanesthetized cats were studied under conditions of indolent head fixation. It was shown that this structure contains two somnogenic neuronal populations with different functions. Neurons increasing their discharge frequency during transition from active to quiet wakefulness and subsequent sleep development to the point of phasic stage of paradoxical sleep development are considered as elements of an anti-waking system, which is involved in the mechanisms of sleep onset and deepening by means of inactivation of the arousal system. Neurons displaying the highest firing rates during light slow-wave sleep and synchronization of discharges with sleep spindles are considered as elements of a slow-wave sleep network.     

An EEG study of different behavioral states of freely moving dolphins]

ECoG and EMG of neck and eye muscles of four free moving dolphins were recorded during sleep-wakefulness cycle through chronically implanted electrodes. Wakefulness is accompanied by desynchronized ECoG, and slow sleep by synchronized ECoG, including the sleep spindles and theta- and delta-waves. The standard EMG criteria do not allow the discrimination between fast sleep and wakefulness in dolphins. Behavioral observations alone do not inform about dolphin's sleep or wakefulness. The respiration of dolphins may be observed during bilateral ECoG synchronization in slow sleep without arousal. ECoG synchronization as well as desynchronization may be observed when the contralateral eye is open.