Dynamics of neuronal activity in the posterior hypothalamus during alternating phases of the sleep-wake cycle

The dynamics of neuronal activity in the posterior hypothalamus in different phases of the sleep-wake cycle were investigated during experiments on free-ranging cats. The highest frequency discharges were found to occur in 89.3% of neurons belonging to this region during the stages of active wakefulness and emotionally influenced paradoxical sleep. These neurons become less active during restful wakefulness and the unemotional stage of paradoxical sleep; this reduced activity can be most clearly observed in the context of slow-wave sleep. It was found that 7.1% of test neurons discharged at the highest rate during the stage of active wakefulness. They did not achieve an activity level characteristic of active wakefulness during the period of paradoxical sleep, although activity level was higher than during other states. Only 3.6% of neurons followed the opposite pattern, with discharges succeeding more frequently in slow-wave sleep and activity reduced to an equal degree during wakefulness and paradoxical sleep. The neurophysiological mechanisms governing the sleep-wake cycle and how the posterior hypothalamus contributes to these mechanisms are discussed.I. S. Beritashvili Institute of Physiology, Academy of Sciences of Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 160–167, March–April, 1988.     

Neuronal activity in the amygdaloid structure during the sleep-wake cycle of the rat

The pattern of neuronal spike activity in the amygdaloid structure was studied in the sleep-wake cycle during experiments on unrestrained rats. It was shown that most neurons of the dorsomedial portion of the amygdala display greater spike activity during active wakefulness (80%) and paradoxical sleep (66.7%) than during slow-wave sleep. Most neurons of the basolateral amygdaloid region discharged at high frequency during active wakefulness (84.6%) and during paradoxial sleep (38.4%) compared with the frequency of firing during slow-wave sleep. Some neurons were found whose rate of discharge rose during slow-wave sleep in comparison with a similar period of paradoxical sleep (38.4%) and of active wakefulness (7.7%). Our findings show how the pattern of neuronal activity in the dosromedial and basolateral regions of the amygdaloid structure differs at various stages of the sleep-wake cycle. It is postulated that this structure serves mainly to regulate emotionally motivated processes rather than helping to govern the basic mechanisms of the sleep-wake cycle.Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 17, No. 6, pp. 747–756, November–December, 1985.     

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.     

Electrical activity of the limbic structures of the dog brain during simultaneous stimulation of the cingulate gyrus and hypothalamus]

Simultaneous electrical stimulation of the anterior part of the cingulate gyrus and the anterior-lateral part of the hypothalamus in the dog brought about EEG synchronization in the limbic system structures and increased correlation coefficients between them. The animal's behaviour exhibited positive emotionally reactions (licking, sniffing, wagging the tail), attended with slowing of the heart rate. The indicated changes directly depend on the degree of emotional stress (the changes are more pronounced in hungry than in sated animals). Simultaneous stimulation of the anterior part of the cingulate gyrus and the anterior-lateral part of the hypothalamus apparently activates a system which reduces the level of emotional stress.     

Daily rhythms of the sleep-wake cycle

ABSTRACT: The amount and timing of sleep and sleep architecture (sleep stages) are determined by several factors, important among which are the environment, circadian rhythms and time awake. Separating the roles played by these factors requires specific protocols, including the constant routine and altered sleep-wake schedules. Results from such protocols have led to the discovery of the factors that determine the amounts and distribution of slow wave and rapid eye movement sleep as well as to the development of models to determine the amount and timing of sleep. One successful model postulates two processes. The first is process S, which is due to sleep pressure (and increases with time awake) and is attributed to a 'sleep homeostat'. Process S reverses during slow wave sleep (when it is called process S'). The second is process C, which shows a daily rhythm that is parallel to the rhythm of core temperature. Processes S and C combine approximately additively to determine the times of sleep onset and waking. The model has proved useful in describing normal sleep in adults. Current work aims to identify the detailed nature of processes S and C. The model can also be applied to circumstances when the sleep-wake cycle is different from the norm in some way. These circumstances include: those who are poor sleepers or short sleepers; the role an individual's chronotype (a measure of how the timing of the individual's preferred sleep-wake cycle compares with the average for a population); and changes in the sleep-wake cycle with age, particularly in adolescence and aging, since individuals tend to prefer to go to sleep later during adolescence and earlier in old age. In all circumstances, the evidence that sleep times and architecture are altered and the possible causes of these changes (including altered S, S' and C processes) are examined.     

Pain and emotion interactions in subregions of the cingulate gyrus

Acute pain and emotion are processed in two forebrain networks, and the cingulate cortex is involved in both. Although Brodmann's cingulate gyrus had two divisions and was not based on any functional criteria, functional imaging studies still use this model. However, recent cytoarchitectural studies of the cingulate gyrus support a four-region model, with subregions, that is based on connections and qualitatively unique functions. Although the activity evoked by pain and emotion has been widely reported, some view them as emergent products of the brain rather than of small aggregates of neurons. Here, we assess pain and emotion in each cingulate subregion, and assess whether pain is co-localized with negative affect. Amazingly, these activation patterns do not simply overlap.     

月经周期对女性睡眠-觉醒和静息-活动的影响

目前有关月经周期对睡眠影响的研究结果并不一致,而对月经周期中昼夜睡眠-觉醒及静息-活动节律尚缺乏系统性的研究.本研究旨在观察正常育龄期女性月经周期中睡眠-觉醒及静息-活动昼夜节律的变化.我们采用静息-活动监测仪(actigraphy)和睡眠日志,调查了12个自然生活状态下健康育龄期妇女在月经周期不同阶段,即行经期、围排卵期、黄体早期及黄体晚期中睡眠与活动节律的变化.结果显示,睡眠-觉醒节律参数在四期之间无统计学显著差异;而静息-活动节律方面,所有受试女性静息-活动节律的平均日周期长度为(24.01±0.29)h,并且四期之间无显著性差异.行经期日间稳定系数(interdaily stability,IS)比黄体早期显著增加(P＜0.05).黄体早期日间活动开始时间明显较黄体晚期提前(P＜0.05);黄体早期的活动峰值时相比围排卵期显著提前(P＜0.05).月经周期可以影响静息-活动昼夜节律时相.而总体静息-活动数量与质量未发生显著变化;健康育龄期妇女在月经周期的各阶段中睡眠-觉醒节律亦无明显变异.     

Dynamics of behaviour during neuronal morphogenesis in culture

We report a developmental sequence in the type and frequency of behaviours of neurons differentiating in vitro. We characterised these changes with extensive analysis of time-lapse sequences from both the continuing cell line pheochromocytoma PC12 and primary mixed cell culture of cat and mouse central nervous system. PC12 cells activated by nerve growth factor (NGF) differentiate in a uniform and synchronous manner. This allowed the first quantification of changes in different neuron behaviours during morphogenesis. Shortly after NGF activation, PC12 cells are highly labile in morphology and exhibit a large variety of morphological behaviours. During the first week of differentiation, the frequency of these behaviours declines, and gross morphology becomes more stable. The frequency of neurite initiation after 1 week in NGF is one-seventh what it was after 2 days in NGF. Over the same period, neurite retraction declines to one-third, and somal migration ceases altogether. Growth-cone activity does not decline during development. These behaviour changes correlate with published data on the differentiation of the neurite cytoskeleton. A qualitatively similar ontogeny was noted in the differentiation of CNS neurons in mixed cell culture. Major differences occur in the relative timing of changes in behaviours. Mature, stable morphology is not detected in these cultures until 7 weeks in vitro.     

Seasonal variations in sleep-wake cycle inMicrocebus murinus

Seasonal variations in the sleep-wake cycle of four captiveMicrocebus murinus were studied, using electroencephalography. TheMicrocebus were maintained under artificial light which reproduced the day-night cycle at the latitude of Paris, France (49°). Microcebus spends from three fourths to two thirds of the 24-hr cycle in sleep phase from September to January, whereas sleep phase constitutes only a half of the daily cycle in summer. The REM-S duration is relatively constant throughout the year, although being notably lengthened in September. Quiet wakefulness constitutes the major part of the time spent awake during the first part of the annual rest season (October to December). These patterns are similar to those seen during the prehibernation state in hibernating mammals.     

Neurocognitive processing of esophageal central sensitization in the insula and cingulate gyrus

The cingulate and insular cortices are parts of the limbic system that process and modulate gastrointestinal sensory signals. We hypothesized that sensitization of these two limbic area may operate in esophageal sensitization. Thus the objective of the study was to elucidate the neurocognitive processing in the cingulate and insular cortices to mechanical stimulation of the proximal esophagus following infusion of acid or phosphate buffer solution (PBS) into the esophagus. Twenty-six studies (14 to acid and 12 to PBS infusion) were performed in 20 healthy subjects (18-35 yr) using high-resolution (2.5 x 2.5 x 2.5 mm(3) voxel size) functional MRI (fMRI). Paradigm-driven, 2-min fMRI scans were performed during randomly timed 15-s intervals of proximal esophageal barostatically controlled distentions and rest, before and after 30-min of distal esophageal acid or PBS perfusion (0.1 N HCl or 0.1 M PBS at 1 ml/min). Following distal esophageal acid infusion, at subliminal and liminal levels of proximal esophageal distentions, the number of activated voxels in both cingulate and insular cortices showed a significant increase compared with before acid infusion (P < 0.05). No statistically significant change in cortical activity was noted following PBS infusion. We conclude that 1) acid stimulation of the esophagus results in sensitization of the cingulate and insular cortices to subliminal and liminal nonpainful mechanical stimulations, and 2) these findings can have ramifications with regard to the mechanisms of some esophageal symptoms attributed to reflux disease.     

Role of septal and entorhinal inputs in the generation of hippocampal electrical activity in the cat sleep-wake cycle

The effects of septal lesion and entorhinal cortex section on hippocampal electrical activity during the cat sleep-wake cycle were investigated in chronic experiments. The medial portion of the septum only was found to participate in generation of this activity. Complete suppression of hippocampal theta rhythm during active wakefulness and paradoxical sleep were the main effects of septal lesion. In slow-wave sleep, the effects of septal lesion manifested in a slight attenuation of the intensity of the dominant frequency (of 1 Hz). Widespread septal lesion does not add to the changes occurring when the medial portion of the septum is so isolated. Section of the entorhinal cortex produces a sharp increase in hippocampal theta rhythm during waking and paradoxical sleep. Clearcut attenuation of delta and subdelta rhythm intensities were observed in slowwave sleep. It is postulated that under normal conditions hippocampal entorhinal input exerts a modulating effect on the genesis of hippocampal theta rhythm.I. S. Beritashvili Institute of Physiology, Academy of Sciences of the Georgian SSR, Tbilisi. Translated from Neirofiziologiya, Vol. 19, No. 5, pp. 622–630, September–October, 1987.     

Characterization of a H-arginine-vasopressin binding site in the cingulate gyrus of the rat pup

Autoradiographic analysis of 1, 8, 16 and 26-day-old rat brains showed ³H-arginine⁸-vasopressin (³H-AVP) binding to the cingulate gyrus-dorsal hippocampus (CG) only in the 8-day-old rat brain. Saturation analysis of CG membranes prepared from pups (7–10 days) and adults (90 days) revealed a small but significant increase in binding site concentration in adults compared to pups. However, the K_d of the ³H-AVP binding site increased significantly with age. The K_d of ³H-AVP binding to pup CG membranes was 0.9±0.1 nM, while the adult CG was 5.7±1.0 nM. The pharmacological specificity of ³H-AVP binding sites in the pup and adult CG was similar, but differed markedly from the profile observed in adult septal membranes. The primary specificity difference between the pup CG and septum was the reduced potency of certain V₁ receptor antagonists. In competition experiments the CG binding site showed a reduced affinity for the V₁ antagonist, [d(CH₂)₅, Tyr(Me)]AVP. This reduced affinity for the V₁ antagonist was also documented autoradiographically using ³H-[d(CH₂)₅, Tyr(Me)]AVP. The data suggest that the ³H-AVP binding site expressed in the pup CG is not identical to the V₁ type receptor present in the periphery and brain of the adult rat.     

Dynamic changes in the immunoreactivity of neuropeptide systems of the suprachiasmatic nuclei in golden hamsters during the sleep-wake cycle

The sleep-wake cycle is virtually the most prominent circadian rhythm in mammals. In the timing system of sleep and wakefulness, the intrinsic neuropeptide systems of the suprachiasmatic nuclei (SCN) may play an important role. To elucidate this possible influence in the golden hamster, the immunoreactivity patterns of the suprachiasmatic gastrin-releasing peptide (GRP), vasoactive intestinal polypeptide (VIP), and arginine-vasopressin (AVP) systems were investigated in relation to the day-night and sleep-wake cycle by use of immunocytochemistry combined with semiquantitative planimetric analysis. For the GRP system, the highest level of immunoreactivity (expressed as area density) was observed in sleeping hamsters. Intermediate levels were found in awake, motorically active evening animals, whereas the lowest levels of immunoreactivity were detected in awake, motorically inactive hamsters studied in the morning. The immunoreactivity of the VIP system showed a completely opposite pattern, indicating highest area density in awake morning, intermediate area density in awake evening and lowest area density in sleeping golden hamsters. The immunoreactivity pattern of the AVP system, displaying highest levels in sleeping individuals, was virtually identical to that of the GRP system. Together with the related signs of neuronal activity, the present results favor an important role of these neuropeptide systems for the integration of central nervous information related to the sleep-wake cycle with photic information of the retinal input.     

Dynamics of relative chromosome position during the cell cycle

The position of chromosomal neighborhoods in living cells was followed using three different methods for marking chromosomal domains occupying arbitrary locations in the nucleus; photobleaching of GFP-labeled histone H2B, local UV-marked DNA, and photobleaching of fluorescently labeled DNA. All methods revealed that global chromosomal organization can be reestablished through one cell division from mother to daughters. By simultaneously monitoring cell cycle stage in the cells in which relative chromosomal domain positions were tracked, we observed that chromosomal neighborhood organization is apparently lost in the early G1 phase of the cell cycle. However, the daughter cells eventually regain the general chromosomal organization pattern of their mothers, suggesting an active mechanism could be at play to reestablish chromosomal neighborhoods.     

Spike avalanches exhibit universal dynamics across the sleep-wake cycle

Background

Scale-invariant neuronal avalanches have been observed in cell cultures and slices as well as anesthetized and awake brains, suggesting that the brain operates near criticality, i.e. within a narrow margin between avalanche propagation and extinction. In theory, criticality provides many desirable features for the behaving brain, optimizing computational capabilities, information transmission, sensitivity to sensory stimuli and size of memory repertoires. However, a thorough characterization of neuronal avalanches in freely-behaving (FB) animals is still missing, thus raising doubts about their relevance for brain function.

Methodology/Principal Findings

To address this issue, we employed chronically implanted multielectrode arrays (MEA) to record avalanches of action potentials (spikes) from the cerebral cortex and hippocampus of 14 rats, as they spontaneously traversed the wake-sleep cycle, explored novel objects or were subjected to anesthesia (AN). We then modeled spike avalanches to evaluate the impact of sparse MEA sampling on their statistics. We found that the size distribution of spike avalanches are well fit by lognormal distributions in FB animals, and by truncated power laws in the AN group. FB data surrogation markedly decreases the tail of the distribution, i.e. spike shuffling destroys the largest avalanches. The FB data are also characterized by multiple key features compatible with criticality in the temporal domain, such as 1/f spectra and long-term correlations as measured by detrended fluctuation analysis. These signatures are very stable across waking, slow-wave sleep and rapid-eye-movement sleep, but collapse during anesthesia. Likewise, waiting time distributions obey a single scaling function during all natural behavioral states, but not during anesthesia. Results are equivalent for neuronal ensembles recorded from visual and tactile areas of the cerebral cortex, as well as the hippocampus.

Conclusions/Significance

Altogether, the data provide a comprehensive link between behavior and brain criticality, revealing a unique scale-invariant regime of spike avalanches across all major behaviors.     

Dynamics of Cdk1 substrate specificity during the cell cycle

Cdk specificity is determined by the intrinsic selectivity of the active site and by substrate docking sites on the cyclin subunit. There is a long-standing debate about the relative importance of these factors in the timing of Cdk1 substrate phosphorylation. We analyzed major budding yeast cyclins (the G1/S-cyclin Cln2, S-cyclin Clb5, G2/M-cyclin Clb3, and M-cyclin Clb2) and found that the activity of Cdk1 toward the consensus motif increased gradually in the sequence Cln2-Clb5-Clb3-Clb2, in parallel with cell cycle progression. Further, we identified a docking element that compensates for the weak intrinsic specificity of Cln2 toward G1-specific targets. In addition, Cln2-Cdk1 showed distinct consensus site specificity, suggesting that cyclins do not merely activate Cdk1 but also modulate its active-site specificity. Finally, we identified several Cln2-, Clb3-, and Clb2-specific Cdk1 targets. We propose that robust timing and ordering of cell cycle events depend on gradual changes in the substrate specificity of Cdk1.