Locus Ceruleus Control of State-Dependent Gene Expression

Cirelli, C.

doi:10.1523/jneurosci.0949-04.2004

Cited by 103Sleep and Wakefulness ResearchCircadian rhythm and melatoninNeurotransmitter Receptor Influence on Behavior

Locus Ceruleus Control of State-Dependent Gene Expression

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Cirelli, C.·2004·Journal of Neuroscience

DOI 10.1523/jneurosci.0949-04.2004PMC PMC6729294

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Abstract

Wakefulness and sleep are accompanied by changes in behavior and neural activity, as well as by the upregulation of different functional categories of genes. However, the mechanisms responsible for such state-dependent changes in gene expression are unknown. Here we investigate to what extent state-dependent changes in gene expression depend on the central noradrenergic (NA) system, which is active in wakefulness and reduces its firing during sleep. We measured the levels of approximately 5000 transcripts expressed in the cerebral cortex of control rats and in rats pretreated with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], a neurotoxin that removes the noradrenergic innervation of the cortex. We found that NA depletion reduces the expression of approximately 20% of known wakefulness-related transcripts. Most of these transcripts are involved in synaptic plasticity and in the cellular response to stress. In contrast, NA depletion increased the expression of the sleep-related gene encoding the translation elongation factor 2. These results indicate that the activity of the central NA system during wakefulness modulates neuronal transcription to favor synaptic potentiation and counteract cellular stress, whereas its inactivity during sleep may play a permissive role to enhance brain protein synthesis.

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Both monoamines support synaptic remodeling via increasing activity of plasticity related immediate early genes.
“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 [208]
The ‘Norepinephrine and plasticity’ section says norepinephrine positively modulates plasticity-related genes involved in synaptic structure and function. But ‘Other effects of norepinephrine depletion on gene expression’ reports that an almost complete serotonergic lesion did not affect several of the same genes. The paper therefore does not support the claim that both monoamines act through this mechanism; page numbers are unavailable in our copy. (LLM, conf=0.88)
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Tononi G, Cirelli C, Shaw PJ (2000) The molecular correlates of sleep, wak- ing, and sleep deprivation. Human Frontier Workshop VIII, The regula- tion of sleep, (Borbely AA, Hayaishi O, Seinowski TJ, Altman JS, eds), pp 155-168. Strasbourg, France: HFSP.

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Authors: Cirelli, C.
Affiliations: University of Wisconsin–Madison (US)
Corresponding author: Cirelli, C.
ORCID: Cirelli, C.
Venue: Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2004-06-09
Volume: 24
Issue: 23
Pages: 5410-5419
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.0949-04.2004
PMC: PMC6729294
OpenAlex: W2076224262
Cited by: 103
References: 67
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 3 · 2013: 6 · 2012: 7
FWCI: 4.88
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Defense
National Institute of Mental Health
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: locus coeruleus, noradrenergic system, wakefulness, sleep, synaptic plasticity, stress response, elongation factor 2, brain protein synthesis, norepinephrine depletion
MeSH terms: Animals, Brain Chemistry, Circadian Rhythm, Dopamine, Gene Expression Regulation, Locus Coeruleus, Male, Neuronal Plasticity, Norepinephrine, Rats, Inbred WKY, Serotonin, Sleep, Sleep Stages, Synapses, Transcription, Genetic, Wakefulness, DNA, Complementary, Oligonucleotide Array Sequence Analysis, Peptide Elongation Factor 2, Rats

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Locus Ceruleus Control of State-Dependent Gene Expression

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