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Locus Ceruleus Control of Slow-Wave Homeostasis
Open accessAbstract
Sleep intensity is regulated by the duration of previous wakefulness, suggesting that waking results in the progressive accumulation of sleep need (Borbély and Achermann, 2000). In mammals, sleep intensity is reflected by slow-wave activity (SWA) in the nonrapid eye movement (NREM) sleep electroencephalogram, which increases in proportion to the time spent awake. However, the mechanisms responsible for the increase of NREM SWA after wakefulness remain unclear. According to a recent hypothesis (Tononi and Cirelli, 2003), the increase in SWA occurs because during wakefulness, many cortical circuits undergo synaptic potentiation, as evidenced by the widespread induction of long-term potentiation (LTP)-related genes in the brain of awake animals. A direct prediction of this hypothesis is that manipulations interfering with the induction of LTP-related genes should result in a blunted SWA response. Here, we examined SWA response in rats in which cortical norepinephrine (NA) was depleted, a manipulation that greatly reduces the induction of LTP-related genes during wakefulness (Cirelli and Tononi, 2004). We found that the homeostatic response of the lower-range SWA was markedly and specifically reduced after NA depletion. These data suggest that the wake-dependent accumulation of sleep need is causally related to cellular changes dependent on NA release, such as the induction of LTP-related genes, and support the hypothesis that sleep SWA homeostasis may be related to synaptic potentiation during wakefulness.
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“Suppressing expression of LTP-related genes in rats by chronic lesion of the noradrenergic system produced a strong reduction in the homeostatic SWA response (see, e.g., Refs.205 and 457, for similar results in flies).”
From About Sleep's Role in Memory (2013) · cites this paper as [205]
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“several studies show an increase in extracellular glutamate concentrations as well as molecular markers of LTP across wake periods and a decrease after sleep periods, particularly after SWS (204,205,207,257,457,607,940,1264)”
From About Sleep's Role in Memory (2013) · cites this paper as [205]
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“Both monoamines support synaptic remodeling via increasing activity of plasticity related immediate early genes (205,208,475).”
From About Sleep's Role in Memory (2013) · cites this paper as [205]
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Metadata
- Authors
- Cirelli, C., Huber, R., Gopalakrishnan, A., Southard, T. L., & Tononi, G.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2005-05-04
- Volume
- 25
- Issue
- 18
- Pages
- 4503-4511
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6725032
- OpenAlex
- W2007283165
- Cited by
- 119
- References
- 89
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 6 · 2023: 1 · 2022: 7 · 2021: 2 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 11 · 2016: 4 · 2015: 3 · 2014: 7 · 2013: 13 · 2012: 11
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- locus coeruleus, slow-wave activity, sleep homeostasis, norepinephrine depletion, synaptic potentiation, long-term potentiation, sleep need, wakefulness, NREM sleep, sleep-wake regulation
- MeSH terms
- Analysis of Variance, Animals, Behavior, Animal, Benzylamines, Brain, Brain Chemistry, Dopamine, Drug Interactions, Electroencephalography, Fluoxetine, Homeostasis, Locus Coeruleus, Male, Norepinephrine, Rats, Inbred WKY, Serotonin, Sleep Wake Disorders, Sleep Stages, Spectrum Analysis, Time Factors, Wakefulness, Selective Serotonin Reuptake Inhibitors, Rats
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