Local sleep homeostasis in the avian brain: convergence of sleep function in mammals and birds?

The function of the brain activity that defines slow wave sleep (SWS) and rapid eye movement (REM) sleep in mammals is unknown. During SWS, the level of electroencephalogram slow wave activity (SWA or 0.5-4.5 Hz power density) increases and decreases as a function of prior time spent awake and asleep, respectively. Such dynamics occur in response to waking brain use, as SWA increases locally in brain regions used more extensively during prior wakefulness. Thus, SWA is thought to reflect homeostatically regulated processes potentially tied to maintaining optimal brain functioning. Interestingly, birds also engage in SWS and REM sleep, a similarity that arose via convergent evolution, as sleeping reptiles and amphibians do not show similar brain activity. Although birds deprived of sleep show global increases in SWA during subsequent sleep, it is unclear whether avian sleep is likewise regulated locally. Here, we provide, to our knowledge, the first electrophysiological evidence for local sleep homeostasis in the avian brain. After staying awake watching David Attenborough's The Life of Birds with only one eye, SWA and the slope of slow waves (a purported marker of synaptic strength) increased only in the hyperpallium--a primary visual processing region--neurologically connected to the stimulated eye. Asymmetries were specific to the hyperpallium, as the non-visual mesopallium showed a symmetric increase in SWA and wave slope. Thus, hypotheses for the function of mammalian SWS that rely on local sleep homeostasis may apply also to birds.     

Hippocampal memory consolidation during sleep: a comparison of mammals and birds

The transition from wakefulness to sleep is marked by pronounced changes in brain activity. The brain rhythms that characterize the two main types of mammalian sleep, slow‐wave sleep (SWS) and rapid eye movement (REM) sleep, are thought to be involved in the functions of sleep. In particular, recent theories suggest that the synchronous slow‐oscillation of neocortical neuronal membrane potentials, the defining feature of SWS, is involved in processing information acquired during wakefulness. According to the Standard Model of memory consolidation, during wakefulness the hippocampus receives input from neocortical regions involved in the initial encoding of an experience and binds this information into a coherent memory trace that is then transferred to the neocortex during SWS where it is stored and integrated within preexisting memory traces. Evidence suggests that this process selectively involves direct connections from the hippocampus to the prefrontal cortex (PFC), a multimodal, high‐order association region implicated in coordinating the storage and recall of remote memories in the neocortex. The slow‐oscillation is thought to orchestrate the transfer of information from the hippocampus by temporally coupling hippocampal sharp‐wave/ripples (SWRs) and thalamocortical spindles. SWRs are synchronous bursts of hippocampal activity, during which waking neuronal firing patterns are reactivated in the hippocampus and neocortex in a coordinated manner. Thalamocortical spindles are brief 7–14 Hz oscillations that may facilitate the encoding of information reactivated during SWRs. By temporally coupling the readout of information from the hippocampus with conditions conducive to encoding in the neocortex, the slow‐oscillation is thought to mediate the transfer of information from the hippocampus to the neocortex. Although several lines of evidence are consistent with this function for mammalian SWS, it is unclear whether SWS serves a similar function in birds, the only taxonomic group other than mammals to exhibit SWS and REM sleep. Based on our review of research on avian sleep, neuroanatomy, and memory, although involved in some forms of memory consolidation, avian sleep does not appear to be involved in transferring hippocampal memories to other brain regions. Despite exhibiting the slow‐oscillation, SWRs and spindles have not been found in birds. Moreover, although birds independently evolved a brain region—the caudolateral nidopallium (NCL)—involved in performing high‐order cognitive functions similar to those performed by the PFC, direct connections between the NCL and hippocampus have not been found in birds, and evidence for the transfer of information from the hippocampus to the NCL or other extra‐hippocampal regions is lacking. Although based on the absence of evidence for various traits, collectively, these findings suggest that unlike mammalian SWS, avian SWS may not be involved in transferring memories from the hippocampus. Furthermore, it suggests that the slow‐oscillation, the defining feature of mammalian and avian SWS, may serve a more general function independent of that related to coordinating the transfer of information from the hippocampus to the PFC in mammals. Given that SWS is homeostatically regulated (a process intimately related to the slow‐oscillation) in mammals and birds, functional hypotheses linked to this process may apply to both taxonomic groups.     

Basal forebrain acetylcholine release during REM sleep is significantly greater than during waking

Cholinergic neurons of the basal forebrain supply the neocortex with ACh and play a major role in regulating behavioral arousal and cortical electroencephalographic activation. Cortical ACh release is greatest during waking and rapid eye movement (REM) sleep and reduced during non-REM (NREM) sleep. Loss of basal forebrain cholinergic neurons contributes to sleep disruption and to the cognitive deficits of many neurological disorders. ACh release within the basal forebrain previously has not been quantified during sleep. This study used in vivo microdialysis to test the hypothesis that basal forebrain ACh release varies as a function of sleep and waking. Cats were trained to sleep in a head-stable position, and dialysis samples were collected during polygraphically defined states of waking, NREM sleep, and REM sleep. Results from 22 experiments in four animals demonstrated that means +/- SE ACh release (pmol/10 min) was greatest during REM sleep (0.77 +/- 0.07), intermediate during waking (0.58 +/- 0.03), and lowest during NREM sleep (0.34 +/- 0.01). The finding that, during REM sleep, basal forebrain ACh release is significantly elevated over waking levels suggests a differential role for basal forebrain ACh during REM sleep and waking.     

Neuronal Avalanches Differ from Wakefulness to Deep Sleep – Evidence from Intracranial Depth Recordings in Humans

Neuronal activity differs between wakefulness and sleep states. In contrast, an attractor state, called self-organized critical (SOC), was proposed to govern brain dynamics because it allows for optimal information coding. But is the human brain SOC for each vigilance state despite the variations in neuronal dynamics? We characterized neuronal avalanches – spatiotemporal waves of enhanced activity - from dense intracranial depth recordings in humans. We showed that avalanche distributions closely follow a power law – the hallmark feature of SOC - for each vigilance state. However, avalanches clearly differ with vigilance states: slow wave sleep (SWS) shows large avalanches, wakefulness intermediate, and rapid eye movement (REM) sleep small ones. Our SOC model, together with the data, suggested first that the differences are mediated by global but tiny changes in synaptic strength, and second, that the changes with vigilance states reflect small deviations from criticality to the subcritical regime, implying that the human brain does not operate at criticality proper but close to SOC. Independent of criticality, the analysis confirms that SWS shows increased correlations between cortical areas, and reveals that REM sleep shows more fragmented cortical dynamics.     

A phylogenetic analysis of sleep architecture in mammals: the integration of anatomy, physiology, and ecology

Among mammalian species, the time spent in the two main "architectural" states of sleep--slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep--varies greatly. Previous comparative studies of sleep architecture found that larger mammals, those with bigger brains, and those with higher absolute basal metabolic rates (BMR) tended to engage in less SWS and REM sleep. Species experiencing a greater risk of predation also exhibited less SWS and REM sleep. In all cases, however, these studies lacked a formal phylogenetic and theoretical framework and used mainly correlational analyses. Using independent contrasts and an updated data set, we extended existing approaches with path analysis to examine the integrated influence of anatomy, physiology, and ecology on sleep architecture. Path model structure was determined by nonmutually exclusive hypotheses for the function of sleep. We found that species with higher relative BMRs engage in less SWS, whereas species with larger relative brain masses engage in more REM sleep. REM sleep was the only sleep variable strongly influenced by predation risk; mammals sleeping in riskier environments engage in less REM sleep. Overall, we found support for some hypotheses for the function of sleep, such as facilitating memory consolidation or learning, but not others, such as energy conservation.     

Spontaneous Sleep-Like Brain State Alternations and Breathing Characteristics in Urethane Anesthetized Mice

Brain state alternations resembling those of sleep spontaneously occur in rats under urethane anesthesia and they are closely linked with sleep-like respiratory changes. Although rats are a common model for both sleep and respiratory physiology, we sought to determine if similar brain state and respiratory changes occur in mice under urethane. We made local field potential recordings from the hippocampus and measured respiratory activity by means of EMG recordings in intercostal, genioglossus, and abdominal muscles. Similar to results in adult rats, urethane anesthetized mice displayed quasi-periodic spontaneous forebrain state alternations between deactivated patterns resembling slow wave sleep (SWS) and activated patterns resembling rapid eye movement (REM) sleep. These alternations were associated with an increase in breathing rate, respiratory variability, a depression of inspiratory related activity in genioglossus muscle and an increase in expiratory-related abdominal muscle activity when comparing deactivated (SWS-like) to activated (REM-like) states. These results demonstrate that urethane anesthesia consistently induces sleep-like brain state alternations and correlated changes in respiratory activity across different rodent species. They open up the powerful possibility of utilizing transgenic mouse technology for the advancement and translation of knowledge regarding sleep cycle alternations and their impact on respiration.     

Differential Associations of Early- and Late-Night Sleep with Functional Brain States Promoting Insight to Abstract Task Regularity

Background

Solving a task with insight has been associated with occipital and right-hemisphere activations. The present study tested the hypothesis if sleep-related alterations in functional activation states modulate the probability of insight into a hidden abstract regularity of a task.

Methodology

State-dependent functional activation was measured by beta and alpha electroencephalographic (EEG) activity and spatial synchronization. Task-dependent functional activation was assessed by slow cortical potentials (SPs). EEG parameters during the performance of the Number Reduction Task (NRT) were compared between before sleep and after sleep sessions. In two different groups, the relevant sleep occurred either in the first or in the second half of the night, dominated by slow wave sleep (SWS) or by rapid eye movement (REM) sleep.

Principal Findings

Changes in EEG parameters only occurred in the early-night group, not in the late-night group and indicated occipital and right-hemisphere functional alterations. These changes were associated with off-line consolidation of implicit task representations and with the amount of SWS but they did not predict subsequent insight. The gain of insight was, however, independently associated with changes of spectral beta and alpha measures only in those subjects from the two sleep groups who would subsequently comprehend the hidden regularity of the task. Insight-related enhancement of right frontal asymmetry after sleep did not depend on sleep stages.

Significance

It is concluded that off-line restructuring of implicit information during sleep is accompanied by alterations of functional activation states after sleep. This mechanism is promoted by SWS but not by REM sleep and may contribute to attaining insight after sleep. Original neurophysiologic evidence is provided for alterations of the functional activation brain states after sleep. These alterations are associated with a decrease in controlled processing within the visual system and with an increase in the functional connectivity of the right hemisphere, and are supported by SWS in the first half of the night.     

The evolution and diversification of sleep

The evolutionary origins of sleep and its sub-states, rapid eye movement (REM) and non-REM (NREM) sleep, found in mammals and birds, remain a mystery. Although the discovery of a single type of sleep in jellyfish suggests that sleep evolved much earlier than previously thought, it is unclear when and why sleep diversified into multiple types of sleep. Intriguingly, multiple types of sleep have recently been found in animals ranging from non-avian reptiles to arthropods to cephalopods. Although there are similarities between these states and those found in mammals and birds, notable differences also exist. The diversity in the way sleep is expressed confounds attempts to trace the evolution of sleep states, but also serves as a rich resource for exploring the functions of sleep.     

Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia

Background

Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state.

Methodology/Principal Findings

Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame (∼11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane.

Conclusions/Significance

Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.     

The ontogeny and physiology confirms the dual nature of sleep states

In the Jouvet's laboratory, as early as 1960 the study of the ontogenesis of paradoxical sleep (PS) named "sleep 'with jerks" began in the kitten and led to the first publication in 1961. Then, several species were studied, lamb, rat, human neonates, etc. These works showed that at birth sleep with jerks was preponderant in altricial (immature) species (cat, rat) and the first to appear during the second half of gestation in precocious species (guinea pig). For Jouvet, sleep with jerks is a immature form of PS. Why PS is so important at birth? The maturation of the central nervous system, based on the myelinization, starts in the spinal cord then forwards to the brainstem and forebrain. So, PS mechanisms located in the brainstem are the first to mature and the only one to function. Then the slow wave sleep (SWS) and waking structures become mature. Phylogenetic studies showed that in mammals and birds PS was present even in marsupials and monotremes. Until now only the one exception is the dolphin with a voluntary breathing. To sleep and breath, dolphin has developed an unilateral sleep without classical PS. In other animals, reptiles, amphibians, fishes, PS was not observed with the parameters used in mammals. The study at birth (not yet done) of reptiles would allow perhaps the observation of a temporary PS. Based on these findings, a schematic model of the sleep regulation can be elaborated. Haeckel's aphorism "Ontogeny recapitulates phylogeny" seems true for PS which appears in birds and mammals i.e. at the end of evolution as it appears at the end of gestation when PS cerebral structures are present and mature.     

Potentiation of ketamine effects on the spiking activity in the lateral geniculate nucleus by rapid eye movement (REM) sleep deprivation.

In cats prepared for chronic recording of sleep, an investigation was made on the effects of an anaesthetic agent, ketamine [cl-581, 2-(O-chlorophenyl)-2-methylaminocyclohexamine HCl] and rapid eye movement (REM) sleep deprivation on spiking activity recorded from lateral geniculate (LGN) nucleus. In normal cats most of the LGN spikes occurring during sleep are found in REM sleep. Follwoing injection of 10 mg/kg of ketamine a substantial increase of slow wave sleep (SWS) spikes occurred. While selective REM sleep deprivation had the same effects, combined influences of ketamine and REM-sleep deprivation led to a marked potentiation of their individual effects probably by simultaneous stimulation of the neurone system which determines the endogenous electrical activity of LGN cells.     

Modeling the effect of sleep regulation on a neural mass model

In mammals, sleep is categorized by two main sleep stages, rapid eye movement (REM) and non-REM (NREM) sleep that are known to fulfill different functional roles, the most notable being the consolidation of memory. While REM sleep is characterized by brain activity similar to wakefulness, the EEG activity changes drastically with the emergence of K-complexes, sleep spindles and slow oscillations during NREM sleep. These changes are regulated by circadian and ultradian rhythms, which emerge from an intricate interplay between multiple neuronal populations in the brainstem, forebrain and hypothalamus and the resulting varying levels of neuromodulators. Recently, there has been progress in the understanding of those rhythms both from a physiological as well as theoretical perspective. However, how these neuromodulators affect the generation of the different EEG patterns and their temporal dynamics is poorly understood. Here, we build upon previous work on a neural mass model of the sleeping cortex and investigate the effect of those neuromodulators on the dynamics of the cortex and the corresponding transition between wakefulness and the different sleep stages. We show that our simplified model is sufficient to generate the essential features of human EEG over a full day. This approach builds a bridge between sleep regulatory networks and EEG generating neural mass models and provides a valuable tool for model validation.     

Sleep in brain development

With the discovery of rapid eye movement (REM) sleep, sleep was no longer considered a homogeneous state of passive rest for the brain. On the contrary, sleep, and especially REM sleep, appeared as an active condition of intense cerebral activity. The fact that we get large amounts of sleep in early life suggested that sleep may play a role in brain maturation. This idea has been investigated for many years through a large number of animal and human studies, but evidence remains fragmented. The hypothesis proposed was that REM sleep would provide an endogenous source of activation, possibly critical for structural maturation of the central nervous system. This proposal led to a series of experiments looking at the role of REM sleep in brain development. In particular, the influence of sleep in developing the visual system has been highlighted. More recently, non-REM (NREM) sleep state has become a major focus of attention. The current data underscore the importance of both REM sleep and NREM sleep states in normal synaptic development and lend support to their functional roles in brain maturation. Both sleep states appear to be important for neuronal development, but the corresponding contribution is likely to be different.     

A probabilistic framework for a physiological representation of dynamically evolving sleep state

This work presents a probabilistic method for mapping human sleep electroencephalogram (EEG) signals onto a state space based on a biologically plausible mathematical model of the cortex. From a noninvasive EEG signal, this method produces physiologically meaningful pathways of the cortical state over a night of sleep. We propose ways in which these pathways offer insights into sleep-related conditions, functions, and complex pathologies. To address explicitly the noisiness of the EEG signal and the stochastic nature of the mathematical model, we use a probabilistic Bayesian framework to map each EEG epoch to a distribution of likelihoods over all model sleep states. We show that the mapping produced from human data robustly separates rapid eye movement sleep (REM) from slow wave sleep (SWS). A Hidden Markov Model (HMM) is incorporated to improve the path results using the prior knowledge that cortical physiology has temporal continuity.     

Midlatency auditory evoked responses: Differential effects of sleep in the human

Middle latency responses (MLRs) in the 10–100 msec latency range, evoked by click stimuli, were studied in 14 adult volunteer subjects during sleep-wakefulness to determine whether such changes in state were reflected by any MLR component. Evoked potentials were collected in 500 trial averages during continuos presentation of 1/sec clicks during initial awake recordings and thereafter during a 2 h afternoon nap or all-night sleep session. Continuously recorded EEG, EOG and EMG were scored for wakefulness, stages 2–4 of slow wave sleep (SWS), and rapid eye movement (REM) sleep during each evoked potential epoch. The major components included in this study and their latency ranges, as determined by peak latency measurements from the awake records, were: ABR V, 5–8 msec, Pa, 30–40 msec, Nb, 45–55 msec, and P1, 55–80 msec. In agreement with previous reports, ABR V and Pa showed no amplitude changes from wakefulness to either SWS or REM. Not previously reported, however, was the dramatic decrease and disappearance of P1 during SWS and its reappearance during REM to an amplitude similar to that during wakefulness. This unique linkage between a particular evoked potential component and sleep-wakefulness indicates that its generator system must be functionally related to states of arousal. Relevant data from the cat model suggest that the generator substrate for P1 may be within the ascending reticular activating system.     

Muscle tone regulation during REM sleep: neural circuitry and clinical significance

Rapid eye movement (REM) sleep is a distinct behavioral state characterized by an activated cortical and hippocampal electroencephalogram (EEG) and concurrent muscle atonia. Research conducted over the past 50 years has revealed the neuronal circuits responsible for the generation and maintenance of REM sleep, as well as the pathways involved in generating the cardinal signs of REM sleep such as cortical activation and muscle atonia. The generation and maintenance of REM sleep appear to involve a widespread network in the pons and medulla. The caudal laterodorsal tegmental nucleus (cLDT) and sublaterodorsal nucleus (SLD) within the dorsolateral pons contain REM-on neurons, and the ventrolateral periaqueductal grey (vlPAG) contains REM-off neurons. The interaction between these structures is proposed to regulate REM sleep amounts. The cLDT-SLD neurons project to the basal forebrain via the parabrachial-precoeruleus (PB-PC) complex, and this pathway may be critical for the EEG activation seen during REM sleep. Descending SLD glutamatergic projections activate the ventromedial medulla, and spinal cord interneurons mediate muscle atonia and suppress phasic muscle twitches in spinal musculature. In contrast, phasic muscle twitches in the masseter muscles may be driven by glutamatergic neurons in the rostral parvicellular reticular nucleus (PCRt); however, the brain region responsible for generating phasic twitches in the other cranial muscles including facial muscles and tongue are not clear.     

Neostriatal administration of somatostatin:differential effect of small and large doses on behavior and motor control

The administration of small doses of somatostatin (SRIF) (0.01 and 0.1 microgram) into the neostriatal complex of unrestrained, freely moving rats induced general behavioral excitation associated with a variety of stereotyped movements, tremors, and a reduction of rapid eye movements (REM) and deep slow wave sleep (SWS). In contrast, the higher doses of SRIF (1.0 and 10.0 microgram) caused movements to be uncoordinated and frequently induced more severe difficulties in motor control such as contralateral hemiplegia-in-extension which restricted or completely prevented the expression of normal behavioral patterns. As a result, the animals appeared drowsy and inhibited. Analysis of the sleep-waking cycle revealed prolonged periods of a shallow SWS while REM sleep and deep SWS were markedly reduced; electroencephalogram recordings revealed periods of dissociation from behavior. The administration of endocrinologically inactive as well as the active analogues of SRIF failed to induce effects comparable with those observed after the administration of the same dose of the native hormone (10.0 microgram).     

Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep

Human dreaming occurs during rapid eye movement (REM) sleep. To investigate the structure of neural activity during REM sleep, we simultaneously recorded the activity of multiple neurons in the rat hippocampus during both sleep and awake behavior. We show that temporally sequenced ensemble firing rate patterns reflecting tens of seconds to minutes of behavioral experience are reproduced during REM episodes at an equivalent timescale. Furthermore, within such REM episodes behavior-dependent modulation of the subcortically driven theta rhythm is also reproduced. These results demonstrate that long temporal sequences of patterned multineuronal activity suggestive of episodic memory traces are reactivated during REM sleep. Such reactivation may be important for memory processing and provides a basis for the electrophysiological examination of the content of dream states.     

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.     

Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats.

The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats. The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc. )administration of PGE1, PGE2 and PGF2alpha increased wakefulness without a significant alteration of REM sleep. PGE1 administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep. The fact that previous administration of 5-hydroxytryptophane abolished the PGE1-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system.