scholarly journals From Physiology to Pathology of Cortico-Thalamo-Cortical Oscillations: Astroglia as a Target for Further Research

2021 ◽  
Vol 12 ◽  
Author(s):  
Davide Gobbo ◽  
Anja Scheller ◽  
Frank Kirchhoff

The electrographic hallmark of childhood absence epilepsy (CAE) and other idiopathic forms of epilepsy are 2.5–4 Hz spike and wave discharges (SWDs) originating from abnormal electrical oscillations of the cortico-thalamo-cortical network. SWDs are generally associated with sudden and brief non-convulsive epileptic events mostly generating impairment of consciousness and correlating with attention and learning as well as cognitive deficits. To date, SWDs are known to arise from locally restricted imbalances of excitation and inhibition in the deep layers of the primary somatosensory cortex. SWDs propagate to the mostly GABAergic nucleus reticularis thalami (NRT) and the somatosensory thalamic nuclei that project back to the cortex, leading to the typical generalized spike and wave oscillations. Given their shared anatomical basis, SWDs have been originally considered the pathological transition of 11–16 Hz bursts of neural oscillatory activity (the so-called sleep spindles) occurring during Non-Rapid Eye Movement (NREM) sleep, but more recent research revealed fundamental functional differences between sleep spindles and SWDs, suggesting the latter could be more closely related to the slow (<1 Hz) oscillations alternating active (Up) and silent (Down) cortical activity and concomitantly occurring during NREM. Indeed, several lines of evidence support the fact that SWDs impair sleep architecture as well as sleep/wake cycles and sleep pressure, which, in turn, affect seizure circadian frequency and distribution. Given the accumulating evidence on the role of astroglia in the field of epilepsy in the modulation of excitation and inhibition in the brain as well as on the development of aberrant synchronous network activity, we aim at pointing at putative contributions of astrocytes to the physiology of slow-wave sleep and to the pathology of SWDs. Particularly, we will address the astroglial functions known to be involved in the control of network excitability and synchronicity and so far mainly addressed in the context of convulsive seizures, namely (i) interstitial fluid homeostasis, (ii) K+ clearance and neurotransmitter uptake from the extracellular space and the synaptic cleft, (iii) gap junction mechanical and functional coupling as well as hemichannel function, (iv) gliotransmission, (v) astroglial Ca2+ signaling and downstream effectors, (vi) reactive astrogliosis and cytokine release.

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A35-A35
Author(s):  
E van Rijn ◽  
S A Walker ◽  
V C Knowland ◽  
S A Cairney ◽  
A D Gouws ◽  
...  

Abstract Introduction Memory for novel words benefits from sleep, particularly non-rapid eye movement (NREM) sleep and its features, such as sleep spindles and slow oscillations. This is consistent with systems consolidation models, in which sleep supports transfer from hippocampal to neocortical memory networks. Larger amounts of slow wave sleep in children has been proposed to account for enhanced consolidation effects, but such studies have typically focused on nocturnal sleep. We examined whether daytime naps benefit word retention in adults and children aged 10–12 years, and whether this relationship in children is affected by differences in white matter pathway microstructure. We hypothesized that the link between memory consolidation and structural brain connectivity will be mediated by the degree of sleep spindles during the nap. Methods Adults (N = 31; mean age = 20.91, SD = 1.55) and children (N = 38; mean age = 11.95, SD = 0.88) learned spoken novel words, followed by a 90-minute nap opportunity monitored with polysomnography. Memory for the words was tested pre- and post-nap. Children’s structural brain connectivity was measured using diffusion tensor imaging (DTI). Results Word memory was preserved following sleep in adults, while an adult wake control condition showed deterioration. Similarly, in children memory performance was stable over the nap, with wake control data currently being collected. Analyses relating behavioral changes over the nap to NREM sleep features and structural brain connectivity will be presented. Conclusion In line with sleep-dependent memory consolidation models, daytime naps protect novel words from forgetting in adults and children. Examining potential relationships between nap-based consolidation and structural integrity has important theoretical implications, given the increase in brain connectivity in language areas during childhood, as well as white matter alterations in developmental populations. Support This research was supported by the UK Economic and Social Research Council, grant no. ES/N009924/1.


2021 ◽  
Author(s):  
Thomas Schreiner ◽  
Elisabeth Kaufmann ◽  
Soheyl Noachtar ◽  
Jan-Hinnerk Mehrkens ◽  
Tobias Staudigl

A hallmark of non-rapid eye movement (NREM) sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used direct intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs, whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs. Furthermore, sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing the cardinal sleep rhythms in the neocortex and highlight the functional diversity of specific thalamic nuclei in humans. The concurrent coordination of sleep oscillations by the thalamus could have broad implications for the mechanisms underlying memory consolidation.


2019 ◽  
Vol 33 (1) ◽  
pp. 1-12 ◽  
Author(s):  
Elizabeth M. Stoakley ◽  
Karen J. Mathewson ◽  
Louis A. Schmidt ◽  
Kimberly A. Cote

Abstract. Resting respiratory sinus arrhythmia (RSA) is related to individual differences in waking affective style and self-regulation. However, little is known about the stability of RSA between sleep/wake stages or the relations between RSA during sleep and waking affective style. We examined resting RSA in 25 healthy undergraduates during the waking state and one night of sleep. Stability of cardiac variables across sleep/wake states was highly reliable within participants. As predicted, greater approach behavior and lower impulsivity were associated with higher RSA; these relations were evident in early night Non-REM (NREM) sleep, particularly in slow wave sleep (SWS). The current research extends previous findings by establishing stability of RSA within individuals between wake and sleep states, and by identifying SWS as an optimal period of measurement for relations between waking affective style and RSA.


Author(s):  
Michelle A. Frazer ◽  
Yesenia Cabrera ◽  
Rockelle S. Guthrie ◽  
Gina R. Poe

Abstract Purpose of review This paper reviews all optogenetic studies that directly test various sleep states, traits, and circuit-level activity profiles for the consolidation of different learning tasks. Recent findings Inhibiting or exciting neurons involved either in the production of sleep states or in the encoding and consolidation of memories reveals sleep states and traits that are essential for memory. REM sleep, NREM sleep, and the N2 transition to REM (characterized by sleep spindles) are integral to memory consolidation. Neural activity during sharp-wave ripples, slow oscillations, theta waves, and spindles are the mediators of this process. Summary These studies lend strong support to the hypothesis that sleep is essential to the consolidation of memories from the hippocampus and the consolidation of motor learning which does not necessarily involve the hippocampus. Future research can further probe the types of memory dependent on sleep-related traits and on the neurotransmitters and neuromodulators required.


2021 ◽  
Vol 22 (5) ◽  
pp. 2520
Author(s):  
Alba Bellot-Saez ◽  
Rebecca Stevenson ◽  
Orsolya Kékesi ◽  
Evgeniia Samokhina ◽  
Yuval Ben-Abu ◽  
...  

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.


2000 ◽  
Vol 89 (4) ◽  
pp. 1275-1282 ◽  
Author(s):  
Giora Pillar ◽  
Atul Malhotra ◽  
Robert B. Fogel ◽  
Josee Beauregard ◽  
David I. Slamowitz ◽  
...  

Although pharyngeal muscles respond robustly to increasing Pco 2 during wakefulness, the effect of hypercapnia on upper airway muscle activation during sleep has not been carefully assessed. This may be important, because it has been hypothesized that CO2-driven muscle activation may importantly stabilize the upper airway during stages 3 and 4 sleep. To test this hypothesis, we measured ventilation, airway resistance, genioglossus (GG) and tensor palatini (TP) electromyogram (EMG), plus end-tidal Pco 2(Pet CO2 ) in 18 subjects during wakefulness, stage 2, and slow-wave sleep (SWS). Responses of ventilation and muscle EMG to administered CO2(Pet CO2 = 6 Torr above the eupneic level) were also assessed during SWS ( n = 9) or stage 2 sleep ( n = 7). Pet CO2 increased spontaneously by 0.8 ± 0.1 Torr from stage 2 to SWS (from 43.3 ± 0.6 to 44.1 ± 0.5 Torr, P < 0.05), with no significant change in GG or TP EMG. Despite a significant increase in minute ventilation with induced hypercapnia (from 8.3 ± 0.1 to 11.9 ± 0.3 l/min in stage 2 and 8.6 ± 0.4 to 12.7 ± 0.4 l/min in SWS, P < 0.05 for both), there was no significant change in the GG or TP EMG. These data indicate that supraphysiological levels of Pet CO2 (50.4 ± 1.6 Torr in stage 2, and 50.4 ± 0.9 Torr in SWS) are not a major independent stimulus to pharyngeal dilator muscle activation during either SWS or stage 2 sleep. Thus hypercapnia-induced pharyngeal dilator muscle activation alone is unlikely to explain the paucity of sleep-disordered breathing events during SWS.


2018 ◽  
Author(s):  
KyoungBin Im

Parasomnias have long been recognized as part of sleep-related disorders or diseases in the mental disorders classification system such as Diagnostic and Statistical Manual of Mental Disorders. Nevertheless, many parasomnia symptoms are considered as a transient deviation from the norm in otherwise normal subjects due to disrupted status of consciousness. Sleep states are classified as rapid eye movement (REM) sleep and non-REM (NREM) sleep; similarly, parasomnias are classified as NREM-related parasomnias and REM-related parasomnias. NREM-related parasomnias share common pathophysiology of arousal-related phenomenon out of slow-wave sleep. Although listed as REM parasomnia disorders, nightmares and sleep paralysis are still considered comorbid symptoms or signs of other sleep disorders or mental disorders. Only REM sleep behavior disorder (RBD) is considered a relatively homogenous disease entity among all parasomnia diagnoses. Although RBD is the most newly added disorder entity in parasomnias, it is the most rigorously studied parasomnia such as RBD is strongly and clearly associated with concomitant or future developing neurodegenerative disease. This review contains 1 figure, 4 tables, and 18 references. Key Words: confusional arousals, dream enactment, pseudo-RBD, REM sleep behavior disorder, sleep-related eating, sleep terror, sleepwalking


2021 ◽  
Author(s):  
Felipe A. Torres ◽  
Patricio Orio ◽  
María-José Escobar

AbstractSlow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates to memory consolidation performance. However, little is known about the experimental protocol maximizing this effect, which could be induced by the power of slow-oscillation, the number of sleep spindles, or the timing of both events’ co-occurrence. Using a mean-field model of thalamocortical activity, we studied the effect of several stimulation protocols, varying the pulse shape, duration, amplitude, and frequency, as well as a target-phase using a closed-loop approach. We evaluated the effect of these parameters on slow-oscillations (SO) and sleep-spindles (SP), considering: (i) the power at the frequency bands of interest, (ii) the number of SO and SP, (iii) co-occurrences between SO and SP, and (iv) synchronization of SP with the up-peak of the SO. The first three targets are maximized using a decreasing ramp pulse with a pulse duration of 50 ms. Also, we observed a reduction in the number of SO when increasing the stimulus energy by rising its amplitude. To assess the target-phase parameter, we applied closed-loop stimulation at 0º, 45º, and 90º of the phase of the narrow-band filtered ongoing activity, at 0.85 Hz as central frequency. The 0º stimulation produces better results in the power and number of SO and SP than the rhythmic or aleatory stimulation. On the other hand, stimulating at 45º or 90º change the timing distribution of spindles centers but with fewer co-occurrences than rhythmic and 0º phase. Finally, we propose the application of closed-loop stimulation at the rising zero-cross point using pulses with a decreasing ramp shape and 50 ms of duration for future experimental work.Author summaryDuring the non-REM (NREM) phase of sleep, events that are known as slow oscillations (SO) and spindles (SP) can be detected by EEG. These events have been associated with the consolidation of declarative memories and learning. Thus, there is an ongoing interest in promoting them during sleep by non-invasive manipulations such as sensory stimulation. In this paper, we used a computational model of brain activity that generates SO and SP, to investigate which type of sensory stimulus –shape, amplitude, duration, periodicity– would be optimal for increasing the events’ frequency and their co-occurrence. We found that a decreasing ramp of 50 ms duration is the most effective. The effectiveness increases when the stimulus pulse is delivered in a closed-loop configuration triggering the pulse at a target phase of the ongoing SO activity. A desirable secondary effect is to promote SPs at the rising phase of the SO oscillation.


SLEEP ◽  
2021 ◽  
Author(s):  
Ullrich Bartsch ◽  
Laura J Corbin ◽  
Charlotte Hellmich ◽  
Michelle Taylor ◽  
Kayleigh E Easey ◽  
...  

Abstract The rs1344706 polymorphism in ZNF804A is robustly associated with schizophrenia and schizophrenia is, in turn, associated with abnormal non-rapid eye movement (NREM) sleep neurophysiology. To examine whether rs1344706 is associated with intermediate neurophysiological traits in the absence of disease, we assessed the relationship between genotype, sleep neurophysiology, and sleep-dependent memory consolidation in healthy participants. We recruited healthy adult males with no history of psychiatric disorder from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort. Participants were homozygous for either the schizophrenia-associated ‘A’ allele (N=22) or the alternative ‘C’ allele (N=18) at rs1344706. Actigraphy, polysomnography (PSG) and a motor sequence task (MST) were used to characterize daily activity patterns, sleep neurophysiology and sleep-dependent memory consolidation. Average MST learning and sleep-dependent performance improvements were similar across genotype groups, albeit more variable in the AA group. During sleep after learning, CC participants showed increased slow-wave (SW) and spindle amplitudes, plus augmented coupling of SW activity across recording electrodes. SW and spindles in those with the AA genotype were insensitive to learning, whilst SW coherence decreased following MST training. Accordingly, NREM neurophysiology robustly predicted the degree of overnight motor memory consolidation in CC carriers, but not in AA carriers. We describe evidence that rs1344706 polymorphism in ZNF804A is associated with changes in the coordinated neural network activity that supports offline information processing during sleep in a healthy population. These findings highlight the utility of sleep neurophysiology in mapping the impacts of schizophrenia-associated common genetic variants on neural circuit oscillations and function.


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