Daytime micro-naps in a nocturnal migrant: an EEG analysis

Many species of typically diurnal songbirds experience sleep loss during the migratory seasons owing to their nocturnal migrations. However, despite substantial loss of sleep, nocturnally migrating songbirds continue to function normally with no observable effect on their behaviour. It is unclear if and how avian migrants compensate for sleep loss. Recent behavioural evidence suggests that some species may compensate for lost night-time sleep with short, uni- and bilateral 'micro-naps' during the day. We provide electrophysiological evidence that short episodes of sleep-like daytime behaviour (approx. 12s) are accompanied by sleep-like changes in brain activity in an avian migrant. Furthermore, we present evidence that part of this physiological brain response manifests itself as unihemispheric sleep, a state during which one brain hemisphere is asleep while the other hemisphere remains essentially awake. Episodes of daytime sleep may represent a potent adaptation to the challenges of avian migration and offer a plausible explanation for the resilience to sleep loss in nocturnal migrants.     

Sleep in birds: lying on the continuum of activity and rest

Abstract

Sleep is highly organized activity which is associated with decreased muscular activity and reduced response to environmental stimuli. The sleep is regulated by both, circadian and homeostatic mechanisms. Sleep patterns can be studied by behavioral assays by observing different sleep behaviors or by neuronal activity such as EEG (electroencephalogram), EOG (electro-oculogram), and EMG (electromyogram). Sleep is organized into non-rapid eye movement (NREM) and rapid eye movement. The sleep pattern in birds are similar to that in mammals, however, few differences such as existence of unihemispheric sleep (UHS) in almost all birds compared to few marine mammals do exist. The UHS results in asymmetry of the brain function measured as slow wave activity (SWA). Several migrants exhibit sleeplessness and they compensate it by NREM. They employ UHS during their migratory flight to remain alert while sleeping and maintain the balance while flying which is advantageous for these birds. Thus, sleep is of fundamental significance for the animal as it lies on the continuum of activity and rest. The present review focuses on some of above mentioned facts about sleep in higher vertebrates particularly in birds.     

Searching for sleep mutants of Drosophila melanogaster

The functions of sleep are still unknown, but are probably related to cellular and molecular aspects of neural function. To better understand the benefits that sleep may bring at the cellular level, recent studies have employed Drosophila melanogaster as a model system and shown that fruit flies share the fundamental features of mammalian sleep. As in mammals, sleep in Drosophila is characterized by increased arousal threshold and by changes in brain electrical activity. Fly sleep is homeostatically regulated independent of the circadian clock, is modulated by stimulants and hypnotics, and is affected by age. Also, fly sleep is associated with changes in brain gene expression similar to those observed in mammals. While Drosophila neurobiology is sufficiently complex to permit meaningful generalizations to mammals and humans, Drosophila genetics is simple enough to allow a rapid mutagenesis screening. An ongoing mutagenesis study has screened approximately 5000 mutant Drosophila lines and found that sleep amount, sleep pattern, and the homeostatic regulation of sleep are highly conserved phenotypes in flies. So far, this study has identified 10 short sleeper lines and 4 lines that show no sleep rebound after sleep deprivation. Ultimately, the characterization of these lines should help identifying crucial cellular pathways involved in the regulatory mechanisms of sleep and its functional consequences.     

Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback

This mini-review article presents the remarkable progress that has been made in the past decade in our understanding of the neural circuitry underlying the regulation of sleep-wake states and circadian control of behaviors. Following a brief introduction to sleep architecture and physiology, the authors describe the neural circuitry and neurotransmitters that regulate sleep and cortical arousal (i.e., wakefulness). They next examine how sleep and wakefulness are regulated by mutual inhibition between sleep-and arousal-promoting circuitry and how this interaction functions analogously to an electronic "flip-flop" switch that ensures behavioral state stability. The authors then discuss the role of circadian and homeostatic processes in the consolidation of sleep, including the physiologic basis of homeostatic sleep drive (i.e., wake-dependent increase in sleep propensity) and the role of the SCN in the circadian regulation of sleep-wake cycles. Finally, they describe the hypothalamic circuitry for the integration of photic and nonphotic environmental time cues and how this integration allows organisms to sculpt patterns of rest-activity and sleep-wake cycles that are optimally adaptive.     

The human connectome: A structural description of the human brain

The connection matrix of the human brain (the human "connectome") represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact.     

Mathematical Models for Sleep-Wake Dynamics: Comparison of the Two-Process Model and a Mutual Inhibition Neuronal Model

Sleep is essential for the maintenance of the brain and the body, yet many features of sleep are poorly understood and mathematical models are an important tool for probing proposed biological mechanisms. The most well-known mathematical model of sleep regulation, the two-process model, models the sleep-wake cycle by two oscillators: a circadian oscillator and a homeostatic oscillator. An alternative, more recent, model considers the mutual inhibition of sleep promoting neurons and the ascending arousal system regulated by homeostatic and circadian processes. Here we show there are fundamental similarities between these two models. The implications are illustrated with two important sleep-wake phenomena. Firstly, we show that in the two-process model, transitions between different numbers of daily sleep episodes can be classified as grazing bifurcations. This provides the theoretical underpinning for numerical results showing that the sleep patterns of many mammals can be explained by the mutual inhibition model. Secondly, we show that when sleep deprivation disrupts the sleep-wake cycle, ostensibly different measures of sleepiness in the two models are closely related. The demonstration of the mathematical similarities of the two models is valuable because not only does it allow some features of the two-process model to be interpreted physiologically but it also means that knowledge gained from study of the two-process model can be used to inform understanding of the behaviour of the mutual inhibition model. This is important because the mutual inhibition model and its extensions are increasingly being used as a tool to understand a diverse range of sleep-wake phenomena such as the design of optimal shift-patterns, yet the values it uses for parameters associated with the circadian and homeostatic processes are very different from those that have been experimentally measured in the context of the two-process model.     

Does Sleep Play a Role in Memory Consolidation? A Comparative Test

Sleep is a pervasive characteristic of mammalian species, yet its purpose remains obscure. It is often proposed that ‘sleep is for the brain’, a view that is supported by experimental studies showing that sleep improves cognitive processes such as memory consolidation. Some comparative studies have also reported that mammalian sleep durations are higher among more encephalized species. However, no study has assessed the relationship between sleep and the brain structures that are implicated in specific cognitive processes across species. The hippocampus, neocortex and amygdala are important for memory consolidation and learning and are also in a highly actived state during sleep. We therefore investigated the evolutionary relationship between mammalian sleep and the size of these brain structures using phylogenetic comparative methods. We found that evolutionary increases in the size of the amygdala are associated with corresponding increases in NREM sleep durations. These results are consistent with the hypothesis that NREM sleep is functionally linked with specializations of the amygdala, including perhaps memory processing.     

Sleep deprivation in a quantitative physiologically based model of the ascending arousal system

A physiologically based quantitative model of the human ascending arousal system is used to study sleep deprivation after being calibrated on a small set of experimentally based criteria. The model includes the sleep-wake switch of mutual inhibition between nuclei which use monoaminergic neuromodulators, and the ventrolateral preoptic area. The system is driven by the circadian rhythm and sleep homeostasis. We use a small number of experimentally derived criteria to calibrate the model for sleep deprivation, then investigate model predictions for other experiments, demonstrating the scope of application. Calibration gives an improved parameter set, in which the form of the homeostatic drive is better constrained, and its weighting relative to the circadian drive is increased. Within the newly constrained parameter ranges, the model predicts repayment of sleep debt consistent with experiment in both quantity and distribution, asymptoting to a maximum repayment for very long deprivations. Recovery is found to depend on circadian phase, and the model predicts that it is most efficient to recover during normal sleeping phases of the circadian cycle, in terms of the amount of recovery sleep required. The form of the homeostatic drive suggests that periods of wake during recovery from sleep deprivation are phases of relative recovery, in the sense that the homeostatic drive continues to converge toward baseline levels. This undermines the concept of sleep debt, and is in agreement with experimentally restricted recovery protocols. Finally, we compare our model to the two-process model, and demonstrate the power of physiologically based modeling by correctly predicting sleep latency times following deprivation from experimental data.     

Control of REM sleep: an aspect of the regulation of physiological homeostasis.

Since REM sleep is characterized by a suspension of the hypothalamic integration of homeostatic regulations, it has been assumed that the duration of both REM sleep episodes and of the time interval between the end of one episode and the beginning of the following episode may be regulated according to sleep related processes and the homeostatic needs of the organism. A series of studies performed on the rat has shown that REM sleep episodes occur as two basic types: single REM sleep episodes, that are separated by intervals > 3 min and sequential episodes, that are separated by intervals < or = 3 min and appear in a cluster. Moreover, it has been observed that, in this species, a change in REM sleep occurrence is caused by a modification in the number of episodes and not in their duration. With respect to this, sleep deprivation and recovery are characterized by a decrease and an increase, respectively, in the number of sequential REM sleep episodes, but the number of single episodes tends to be kept constant. The central aspects of this kind of regulation have been examined biochemically in the preoptic-anterior hypothalamus, an area involved in the control of autonomic and sleep related processes. The results show that the accumulation of adenosine 3':5'-cyclic monophosphate (cAMP) is impaired, in this region, during sleep deprivation and appears to return to the control levels, during the recovery, with a rate inversely related to the degree of the previous deprivation. Moreover, it has been observed that the systemic administration of DL-propranolol and LiCl reduces cAMP accumulation mainly in the preoptic-anterior hypothalamus; this condition is concomitant with a reduction in REM sleep occurrence.     

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.     

An examination of cetacean brain structure with a novel hypothesis correlating thermogenesis to the evolution of a big brain

This review examines aspects of cetacean brain structure related to behaviour and evolution. Major considerations include cetacean brain-body allometry, structure of the cerebral cortex, the hippocampal formation, specialisations of the cetacean brain related to vocalisations and sleep phenomenology, paleoneurology, and brain-body allometry during cetacean evolution. These data are assimilated to demonstrate that there is no neural basis for the often-asserted high intellectual abilities of cetaceans. Despite this, the cetaceans do have volumetrically large brains. A novel hypothesis regarding the evolution of large brain size in cetaceans is put forward. It is shown that a combination of an unusually high number of glial cells and unihemispheric sleep phenomenology make the cetacean brain an efficient thermogenetic organ, which is needed to counteract heat loss to the water. It is demonstrated that water temperature is the major selection pressure driving an altered scaling of brain and body size and an increased actual brain size in cetaceans. A point in the evolutionary history of cetaceans is identified as the moment in which water temperature became a significant selection pressure in cetacean brain evolution. This occurred at the Archaeoceti - modern cetacean faunal transition. The size, structure and scaling of the cetacean brain continues to be shaped by water temperature in extant cetaceans. The alterations in cetacean brain structure, function and scaling, combined with the imperative of producing offspring that can withstand the rate of heat loss experienced in water, within the genetic confines of eutherian mammal reproductive constraints, provides an explanation for the evolution of the large size of the cetacean brain. These observations provide an alternative to the widely held belief of a correlation between brain size and intelligence in cetaceans.     

Dynamical properties of the two-process model for sleep-wake cycles in infantile autism

The two-process model is a scheme for the timing of sleep that consists of homeostatic (Process S) and circadian (Process C) variables. The two-process model exhibits abnormal sleep patterns such as internal desynchronization or sleep fragmentation. Early infants with autism often experience sleep difficulties. Large day-by-day changes are found in the sleep onset and waking times in autistic children. Frequent night waking is a prominent property of their sleep. Further, the sleep duration of autistic children is often fragmented. These sleep patterns in infants with autism are not fully understood yet. In the present study, the sleep patterns in autistic children were reproduced by a modified two-process model using nonlinear analysis. A nap term was introduced into the original two-process model to reproduce the sleep patterns in early infants. The nap term and the time course of Process S are mentioned in the present study. Those parameters led to bifurcation of the sleep-wake cycle in the modified two-process model. In a certain range of these parameter sets, a small external noise was amplified, and an irregular sleep-wake cycle appeared. The short duration of sleep led to another irregular sleep onset or waking. Consequently, an irregular sleep-wake cycle appeared in early infantile autism.     

Dolphins Can Maintain Vigilant Behavior through Echolocation for 15 Days without Interruption or Cognitive Impairment

In dolphins, natural selection has developed unihemispheric sleep where alternating hemispheres of their brain stay awake. This allows dolphins to maintain consciousness in response to respiratory demands of the ocean. Unihemispheric sleep may also allow dolphins to maintain vigilant states over long periods of time. Because of the relatively poor visibility in the ocean, dolphins use echolocation to interrogate their environment. During echolocation, dolphin produce clicks and listen to returning echoes to determine the location and identity of objects. The extent to which individual dolphins are able to maintain continuous vigilance through this active sense is unknown. Here we show that dolphins may continuously echolocate and accurately report the presence of targets for at least 15 days without interruption. During a total of three sessions, each lasting five days, two dolphins maintained echolocation behaviors while successfully detecting and reporting targets. Overall performance was between 75 to 86% correct for one dolphin and 97 to 99% correct for a second dolphin. Both animals demonstrated diel patterns in echolocation behavior. A 15-day testing session with one dolphin resulted in near perfect performance with no significant decrement over time. Our results demonstrate that dolphins can continuously monitor their environment and maintain long-term vigilant behavior through echolocation.     

Network Self-Organization Explains the Statistics and Dynamics of Synaptic Connection Strengths in Cortex

The information processing abilities of neural circuits arise from their synaptic connection patterns. Understanding the laws governing these connectivity patterns is essential for understanding brain function. The overall distribution of synaptic strengths of local excitatory connections in cortex and hippocampus is long-tailed, exhibiting a small number of synaptic connections of very large efficacy. At the same time, new synaptic connections are constantly being created and individual synaptic connection strengths show substantial fluctuations across time. It remains unclear through what mechanisms these properties of neural circuits arise and how they contribute to learning and memory. In this study we show that fundamental characteristics of excitatory synaptic connections in cortex and hippocampus can be explained as a consequence of self-organization in a recurrent network combining spike-timing-dependent plasticity (STDP), structural plasticity and different forms of homeostatic plasticity. In the network, associative synaptic plasticity in the form of STDP induces a rich-get-richer dynamics among synapses, while homeostatic mechanisms induce competition. Under distinctly different initial conditions, the ensuing self-organization produces long-tailed synaptic strength distributions matching experimental findings. We show that this self-organization can take place with a purely additive STDP mechanism and that multiplicative weight dynamics emerge as a consequence of network interactions. The observed patterns of fluctuation of synaptic strengths, including elimination and generation of synaptic connections and long-term persistence of strong connections, are consistent with the dynamics of dendritic spines found in rat hippocampus. Beyond this, the model predicts an approximately power-law scaling of the lifetimes of newly established synaptic connection strengths during development. Our results suggest that the combined action of multiple forms of neuronal plasticity plays an essential role in the formation and maintenance of cortical circuits.     

Awakening to the behavioral analysis of sleep in Drosophila

Perhaps the most observable of the many circadian oscillations that have been described in both vertebrate and invertebrate animals is the daily alterations in periods of rest and activity. Recent studies in the fruit fly Drosophila melanogaster suggest that these periods of inactivity are not simply rest but share many of the fundamental components that define mammalian sleep. Thus, quiescent episodes are characterized by reduced awareness of the environment and are homeostatically regulated. Although this field is in its infancy, recent studies have focused on the interaction between circadian and homeostatic processes. These results indicate that components of the circadian clock may play a substantial role in mechanisms underlying sleep homeostasis at the molecular level. In this article, the author reviews recent advances obtained using Drosophila as a model system to elucidate fundamental components of sleep regulation.     

Spectral EEG indicator of pressure to enter into deep sleep: its responsiveness to closing the eyes for just a few minutes exhibits a pure exponential buildup during sleep deprivation

According to the two-process model of sleep–wake regulation, a homeostatic sleep pressure, i.e. a pressure to enter into deep non-rapid eyes movement (NREM) sleep, must exhibit a purely exponential buildup during prolonged wakefulness. However, this pressure is usually measured indirectly, i.e. during the following episode of actual deep NREM sleep. The purpose of this paper was to show that, despite a prominent circadian modulation of time course of any waking EEG index, the model-postulated purely exponential buildup of the homeostatic sleep pressure can be directly confirmed. During two days of sleep deprivation experiments, the EEG of healthy adults (N = 30) was recorded every other hour throughout 5-min eyes closed relaxation. Sixteen ln-transformed single-Hz power densities (from 1 to 16 Hz) were computed for each of 5 one-min intervals. Differences between these densities obtained for the first and the following intervals were calculated and averaged. The obtained 16 values were used as the frequency weighting curve for weighting densities of each set of 16 single-Hz power densities. Summing-up of these weighted densities provided a single measure that was found to co-vary with self-rated sleepiness throughout two-day interval of sleep deprivation, thus reflecting the joint influence of the circadian and homeostatic processes. However, two-day time course of responsiveness of this measure to closing the eyes for just a few minutes exhibited a purely exponential buildup. It was concluded that this result provided a direct experimental confirmation of the model-predicted exponential buildup of the homeostatic sleep pressure across prolonged episode of wakefulness.     

Rest in Drosophila is a sleep-like state

To facilitate the genetic study of sleep, we documented that rest behavior in Drosophila melanogaster is a sleep-like state. The animals choose a preferred location, become immobile for periods of up to 157 min at a particular time in the circadian day, and are relatively unresponsive to sensory stimuli. Rest is affected by both homeostatic and circadian influences: when rest is prevented, the flies increasingly tend to rest despite stimulation and then exhibit a rest rebound. Drugs acting on a mammalian adenosine receptor alter rest as they do sleep, suggesting conserved neural mechanisms. Finally, normal homeostatic regulation depends on the timeless but not the period central clock gene. Understanding the molecular features of Drosophila rest should shed new light on the mechanisms and function of sleep.     

Diversity and noise effects in a model of homeostatic regulation of the sleep-wake cycle

Recent advances in sleep neurobiology have allowed development of physiologically based mathematical models of sleep regulation that account for the neuronal dynamics responsible for the regulation of sleep-wake cycles and allow detailed examination of the underlying mechanisms. Neuronal systems in general, and those involved in sleep regulation in particular, are noisy and heterogeneous by their nature. It has been shown in various systems that certain levels of noise and diversity can significantly improve signal encoding. However, these phenomena, especially the effects of diversity, are rarely considered in the models of sleep regulation. The present paper is focused on a neuron-based physiologically motivated model of sleep-wake cycles that proposes a novel mechanism of the homeostatic regulation of sleep based on the dynamics of a wake-promoting neuropeptide orexin. Here this model is generalized by the introduction of intrinsic diversity and noise in the orexin-producing neurons, in order to study the effect of their presence on the sleep-wake cycle. A simple quantitative measure of the quality of a sleep-wake cycle is introduced and used to systematically study the generalized model for different levels of noise and diversity. The model is shown to exhibit a clear diversity-induced resonance: that is, the best wake-sleep cycle turns out to correspond to an intermediate level of diversity at the synapses of the orexin-producing neurons. On the other hand, only a mild evidence of stochastic resonance is found, when the level of noise is varied. These results show that disorder, especially in the form of quenched diversity, can be a key-element for an efficient or optimal functioning of the homeostatic regulation of the sleep-wake cycle. Furthermore, this study provides an example of a constructive role of diversity in a neuronal system that can be extended beyond the system studied here.     

Endocrine Effects of the Mammalian Pineal

The current status of knowledge concerning the mammalian pineal'sendocrine effects and the possible mechanisms for their mediationis reviewed and discussed. The diversity, physiological relations,and variability of the pineal's peripheral effects, and theconstancy, rapidity, and homeostatic nature of its central andbehavioral effects are consistent with the view that the pineal'sprimary action is on brain tissue. It remains probable thaton a seasonal basis, the pineal's vegetative and homeostaticeffects may contribute to the adaptive physiological changesin particular mammalian species under the influence of changesin photoperiod and possibly other environmental factors.