In vitro Cortical Network Firing is Homeostatically Regulated: A Model for Sleep Regulation

Saberi-Moghadam, Sohrab; Simi, Alessandro; Setareh, Hesam; Mikhail, Cyril; Tafti, Mehdi

doi:10.1038/s41598-018-24339-6

Cited by 28 publications

(34 citation statements)

References 60 publications

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“…The synchronous slow oscillation appears to be the inherent property of cortical neuron assemblies because the oscillation can be found in ex vivo cortical slabs/slices ( Sanchez-Vives and McCormick, 2000 ; Timofeev et al, 2000 ). It was even shown that the cultured neurons exhibit a synchronous firing pattern similar to that of slow oscillation, and the synchronous firing pattern can be converted to asynchronous one by applying chemical(s) including excitatory neurotransmitters ( Hinard et al, 2012 ; Kaufman et al, 2014 ; Saberi-Moghadam et al, 2018 ). Overall, the synchronous slow oscillation of cortical neurons can be modulated through multiple layers of neurotransmitters, brain circuits, and neuronal networks.…”

Section: Hierarchical Organization Of Circadian Clocks and Sleep Homementioning

confidence: 99%

“…The role of mammalian ERK as a sleep-promoting kinase may lie in the control of gene expression associated with sleep-wake cycle. This notion was demonstrated through unique studies using cultured cortical neurons, which show electrophysiological activity similar to slow oscillation, together with the homeostatic recovery response to the administration of chemical/electrical stimulation ( Hinard et al, 2012 ; Saberi-Moghadam et al, 2018 ). The cortical neurons also show altered gene expression by chemical stimulation mimicking the awake state.…”

Section: Phosphorylation-dependent Control Of the Sleep-wake Cyclementioning

confidence: 99%

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Phosphorylation Hypothesis of Sleep

Ode

Ueda

2020

Front. Psychol.

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Sleep is a fundamental property conserved across species. The homeostatic induction of sleep indicates the presence of a mechanism that is progressively activated by the awake state and that induces sleep. Several lines of evidence support that such function, namely, sleep need, lies in the neuronal assemblies rather than specific brain regions and circuits. However, the molecular mechanism underlying the dynamics of sleep need is still unclear. This review aims to summarize recent studies mainly in rodents indicating that protein phosphorylation, especially at the synapses, could be the molecular entity associated with sleep need. Genetic studies in rodents have identified a set of kinases that promote sleep. The activity of sleep-promoting kinases appears to be elevated during the awake phase and in sleep deprivation. Furthermore, the proteomic analysis demonstrated that the phosphorylation status of synaptic protein is controlled by the sleep-wake cycle. Therefore, a plausible scenario may be that the awake-dependent activation of kinases modifies the phosphorylation status of synaptic proteins to promote sleep. We also discuss the possible importance of multisite phosphorylation on macromolecular protein complexes to achieve the slow dynamics and physiological functions of sleep in mammals.

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Section: Hierarchical Organization Of Circadian Clocks and Sleep Homementioning

confidence: 99%

Section: Phosphorylation-dependent Control Of the Sleep-wake Cyclementioning

confidence: 99%

Phosphorylation Hypothesis of Sleep

Ode

Ueda

2020

Front. Psychol.

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“…Lower spike firing generally typical of sleep is thought to be due, at least in part, to regular periods of widespread synchronous network silence, termed off periods, intruding on ongoing activity ( Steriade et al, 1993b ; Steriade et al, 2001 ; Sanchez-Vives and Mattia, 2014 ). Importantly, off periods in neural populations are thought to underpin slow wave dynamics at the level of the field potential ( Steriade et al, 1993a ; Massimini et al, 2004 ; Buzsáki et al, 2012 ), and it was shown that their properties reflect homeostatic sleep need ( Vyazovskiy et al, 2009 ; McKillop et al, 2018 ; Saberi-Moghadam et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Global sleep homeostasis reflects temporally and spatially integrated local cortical neuronal activity

Thomas

Guillaumin

McKillop

et al. 2020

eLife

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Sleep homeostasis manifests as a relative constancy of its daily amount and intensity. Theoretical descriptions define ‘Process S’, a variable with dynamics dependent on global sleep-wake history, and reflected in electroencephalogram (EEG) slow wave activity (SWA, 0.5–4 Hz) during sleep. The notion of sleep as a local, activity-dependent process suggests that activity history must be integrated to determine the dynamics of global Process S. Here, we developed novel mathematical models of Process S based on cortical activity recorded in freely behaving mice, describing local Process S as a function of the deviation of neuronal firing rates from a locally defined set-point, independent of global sleep-wake state. Averaging locally derived Processes S and their rate parameters yielded values resembling those obtained from EEG SWA and global vigilance states. We conclude that local Process S dynamics reflects neuronal activity integrated over time, and global Process S reflects local processes integrated over space.

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“…Previous studies have demonstrated that embryonic cortical neurons on MEA are able to recapitulate some essential features of sleep in a controllable way (I. Colombi et al, 2016; Hinard et al, 2012; Saberi-Moghadam, Simi, Setareh, Mikhail, & Tafti, 2018). Here, we treated cortical cultures with CCh to change the synchronized default sleep-like state, characterized by slow-wave oscillations typical of NREM sleep, into a theta-predominant state, which is typical of REM sleep.…”

Section: Discussionmentioning

confidence: 99%

The paternally imprinted geneSnord116regulates cortical neuronal activity

Pace

Colombi

Falappa

et al. 2019

Preprint

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words: 264; words count: 8047; figures: 5; Supplementary material: figures 4; table 6Conflict of Interest: each author discloses the absence of any conflicts of interest relative to the research covered in the submitted manuscript. AbstractPrader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by rapid eye movement (REM) sleep abnormalities. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in both humans and mice.Here, we further explore the processes of sleep regulation by studying the PWScr m+/pmouse line, which carries a paternal deletion of Snord116. We focused on microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles within NREM sleep. While the former are thought to contribute to neuronal network formation early in brain development, the latter are markers of thalamocortical processes. Both signals are often compromised in neurodevelopmental disorders and influence functional properties of cortical neurons. Thus, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array (MEA) studies.Our results indicate that the Snord116 gene in mice selectively influences REM sleep properties, such as theta rhythms and the organization of REM episodes throughout sleep-wake cycles. Moreover, sleep spindles present specific abnormalities in PWS model systems, indicating that these features of sleep may translate as potential biomarkers in human PWS. We observed abnormalities in the synchronization of cortical neuronal activity that are accounted for by high levels of norepinephrine.In conclusion, our results provide support for an important role of Snord116 in regulating brain activity during sleep and, in particular, cortical neuronal properties, thereby opening new avenues for developing interventions in PWS. Significance StatementWe found that the Snord116 gene, a major player in Prader-Willi syndrome (PWS), significantly impacts REM sleep and its regulation. Additionally, we found that sleep spindles, a subtle electroencephalography (EEG) marker that occurs during NREM sleep, are dysregulated in PWS mice that carry a paternal deletion of the Snord116 gene. Using a combination of in vivo and in vitro experiments, we identified sleep features at the network and molecular level that suggest that Snord116 is fundamental in the synchronization of neuronal networks. Our study also provides a new pre-clinical tool to investigate the pathophysiology of sleep in PWS.

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In vitro Cortical Network Firing is Homeostatically Regulated: A Model for Sleep Regulation

Cited by 28 publications

References 60 publications

Phosphorylation Hypothesis of Sleep

Phosphorylation Hypothesis of Sleep

Global sleep homeostasis reflects temporally and spatially integrated local cortical neuronal activity

The paternally imprinted geneSnord116regulates cortical neuronal activity

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