Calcineurin is a central regulator of process S and governs sleep homeostasis in locus coeruleus
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE256499 | GEO | 2025/02/28
REPOSITORIES: GEO
Similar Datasets
Project description:This a model from the article:
Sleep deprivation in a quantitative physiologically based model of the ascending
arousal system.
Phillips AJ, Robinson PA. J Theor Biol
2008 Dec 21;255(4):413-23 18805427
,
Abstract:
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.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Phillips AJ, Robinson PA. (2008) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230110 | BioModels
Project description:This a model from the article:
Sleep deprivation in a quantitative physiologically based model of the ascending
arousal system.
Phillips AJ, Robinson PA. J Theor Biol
2008 Dec 21;255(4):413-23 18805427
,
Abstract:
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.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Phillips AJ, Robinson PA. (2008) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230115 | BioModels
Project description:Every day, we sleep for a third of the day. Sleep is important for cognition, brain waste clearance, metabolism, and immune responses. Homeostatic regulation of sleep is maintained by progressively rising sleep need during wakefulness, which then dissipates during sleep. The molecular mechanisms governing sleep are largely unknown. Here, we used a combination of single-cell RNA sequencing and cell-type specific proteomics to interrogate the molecular and functional underpinnings of sleep. Different cell-types in the brain regions show similar transcriptional response to sleep need whereas sleep deprivation changes overall expression indicative of altered antigen processing, synaptic transmission and cellular metabolism in brainstem, cortex and hypothalamus, respectively. Increased sleep need enhances expression of transcription factor Sox2, Mafb, and Zic1 in brainstem; Hlf, Cebpb and Sox9 in cortex, and Atf3, Fosb and Mef2c in hypothalamus. Results from cell-type proteome analysis suggest that sleep deprivation changes abundance of proteins in cortical neurons indicative of altered synaptic vesicle cycles and glucose metabolism whereas in astrocytes it alters the abundance of proteins associated with fatty acid degradation. Similarly, phosphoproteomics of each cell type demonstrates large shifts in site-specific protein phosphorylation in neurons and astrocytes of sleep deprived mice. Our results indicate that sleep deprivation regulates transcriptional, translational and post-translational responses in a cell-specific manner and advances our understanding of the cellular and molecular mechanisms that govern sleep-wake homeostasis in mammals.
2022-10-13 | PXD018334 | Pride
Project description:The preoptic area of hypothalamus plays an important role in sleep homeostasis. We used snRNA-seq to identify neurons involved in homeostatic sleep response.
2024-04-01 | GSE243489 | GEO
Project description:Homeostatic scaling is a global form of synaptic plasticity used by neurons to adjust overall synaptic weight and maintain neuronal firing rates while protecting information coding. While homeostatic scaling has been demonstrated in vitro, a clear physiological function of this plasticity type has not been defined. Sleep is an essential process that modifies synapses to support cognitive functions such as learning and memory. Evidence suggests that information coding during wake drives synapse strengthening which is offset by weakening of synapses during sleep .Here we use biochemical fractionation, proteomics and in vivo two-photon imaging to characterize wide-spread changes in synapse composition in mice through the wake/sleep cycle. We find that during the sleep phase, synapses are weakened through dephosphorylation and removal of synaptic AMPA-type glutamate receptors (AMPARs) driven by the immediate early gene Homer1a and signaling from group I metabotropic glutamate receptors (mGluR1/5), consistent with known mechanisms of homeostatic scaling-down in vitro. Further, we find that these changes are important in the consolidation of contextual memories. While Homer1a gene expression is driven by neuronal activity during wake, Homer1a protein targeting to synapses serves as an integrator of arousal and sleep need through signaling by the wake-promoting neuromodulator noradrenaline (NA) and sleep-promoting modulator adenosine. During sleep or periods of increased sleep need Homer1a enters synapses where it remodels mGluR1/5 signaling complexes to promote AMPAR removal. Thus, we have characterized widespread changes occurring at synapses through the wake/sleep cycle and demonstrated that known mechanisms of homeostatic scaling-down previously demonstrated only in vitro are active in the brain during sleep to remodel synapses, contributing to memory consolidation.
2017-02-13 | PXD004537 | Pride
Project description:To gain insight into the molecular changes of sleep need, this study addresses gene expression changes in a subpopulation of neurons selectively activated by sleep deprivation. Whole brain expression analyses after 6h sleep deprivation clearly indicate that Homer1a is the best index of sleep need, consistently in all mouse strains analyzed. Transgenic mice expressing a FLAG-tagged poly(A)-binding protein (PABP) under the control of Homer1a promoter were generated. Because PABP binds the poly(A) tails of mRNA, affinity purification of FLAG-tagged PABP proteins from whole brain lysates, is expected to co-precipitate all mRNAs from neurons expressing Homer1a. Three other activity-induced genes (Ptgs2, Jph3, and Nptx2) were identified by this technique to be over-expressed after sleep loss. All four genes play a role in recovery from glutamate-induced neuronal hyperactivity. The consistent activation of Homer1a suggests a role for sleep in intracellular calcium homeostasis for protecting and recovering from the neuronal activation imposed by wakefulness. Keywords: sleep deprivation, neuronal subpopulation transcriptome
2007-12-07 | GSE9443 | GEO
Project description:In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) M-NM-8 power during wakefulness and M-NM-4 power during sleep, were greater in the Per35/5 mice. During recovery, the Per35/5 mice fully compensated for the SD-induced deficit in M-NM-4 power, but the Per34/4 and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism. Mice recievied 12 hours of sleep restriction during the 12 hours of light in the light-dark cycle Boxhill represents Per35/5 mice and Coach represents Per34/4 mice. A total of 48 samples comprising 24 mice
2014-03-11 | E-GEOD-55494 | biostudies-arrayexpress
Project description:In humans, a primate-specific variable-number tandem-repeat (VNTR) polymorphism (4 or 5 repeats 54 nt in length) in the circadian gene PER3 is associated with differences in sleep timing and homeostatic responses to sleep loss. We investigated the effects of this polymorphism on circadian rhythmicity and sleep homeostasis by introducing the polymorphism into mice and assessing circadian and sleep parameters at baseline and during and after 12 h of sleep deprivation (SD). Microarray analysis was used to measure hypothalamic and cortical gene expression. Circadian behavior and sleep were normal at baseline. The response to SD of 2 electrophysiological markers of sleep homeostasis, electroencephalography (EEG) M-NM-8 power during wakefulness and M-NM-4 power during sleep, were greater in the Per35/5 mice. During recovery, the Per35/5 mice fully compensated for the SD-induced deficit in M-NM-4 power, but the Per34/4 and wild-type mice did not. Sleep homeostasis-related transcripts (e.g., Homer1, Ptgs2, and Kcna2) were differentially expressed between the humanized mice, but circadian clock genes were not. These data are in accordance with the hypothesis derived from human data that the PER3 VNTR polymorphism modifies the sleep homeostatic response without significantly influencing circadian parameters.-Hasan, S., van der Veen, D. R., Winsky-Sommerer, R., Hogben, A., Laing, E. E., Koentgen, F., Dijk, D.-J., Archer, S. N. A human sleep homeostasis phenotype in mice expressing a primate-specific PER3 variable-number tandem-repeat coding-region polymorphism. Mice were kept under 3.5h light- 3.5 hours dark cycles and samples were collected in the 17th light cycle Boxhill represents Per35/5 mice and Coach represents Per34/4 mice. A total of 30 samples comprizing 30 mice
2014-03-11 | E-GEOD-55495 | biostudies-arrayexpress
Project description:In mice and humans, sleep quantity of individuals are governed by genetic factors and exhibit age-dependent variations. However, the core molecular pathways and effector mechanisms that regulate sleep time in mammals remain unclear. Here, we characterize a major signaling pathway for transcriptional regulation of sleep quantity in mice by adeno-associated virus-mediated somatic genetics analysis. Adult brain chimeric-knockout of LKB1 kinase, an activator of AMPK-related protein kinase SIK3/SLEEPY, markedly reduces non-rapid eye movement sleep (NREMS) amount and delta power–a measure of sleep depth. Downstream of LKB1-SIK3 pathway, gain or loss-of-function of histone deacetylases HDAC4/5 in adult brain neurons causes bidirectional changes of NREMS amount and delta power. Phosphorylation of HDAC4/5 is regulated in relation to sleep need, and HDAC4 specifically regulates sleep amount in posterior hypothalamus. Genetic and transcriptomic studies reveal that HDAC4 cooperates with CREB in both transcriptional and sleep regulation. These findings introduce the concept of signaling pathways targeting transcription modulators to regulate daily sleep amount and demonstrate utility of somatic genetics in mouse sleep research.
2022-09-18 | GSE182907 | GEO
Project description:Quantitative proteomic/phosphoproteomic studies of homeostatic sleep need mice models.
2017-12-23 | MSV000081865 | MassIVE