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Cited by 36Sleep and Wakefulness ResearchNeuroscience of respiration and sleepCircadian rhythm and melatonin

Calcium/Calmodulin Kinase II in the Pedunculopontine Tegmental Nucleus Modulates the Initiation and Maintenance of Wakefulness

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Datta, Subimal, O'Malley, Matthew W., Patterson, Elissa H.·2011·The Journal of Neuroscience
DOI 10.1523/jneurosci.3981-11.2011PMC PMC3229030
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Abstract

The pedunculopontine tegmentum nucleus (PPT) is critically involved in the regulation of wakefulness (W) and rapid eye movement (REM) sleep, but our understanding of the mechanisms of this regulation remains incomplete. The present study was designed to determine the role of PPT intracellular calcium/calmodulin kinase (CaMKII) signaling in the regulation of W and sleep. To achieve this aim, three different concentrations (0.5, 1.0, and 2.0 nmol) of the CaMKII activation inhibitor, KN-93, were microinjected bilaterally (100 nl/site) into the PPT of freely moving rats, and the effects on W, slow-wave sleep (SWS), REM sleep, and levels of phosphorylated CaMKII (pCaMKII) expression in the PPT were quantified. These effects, which were concentration-dependent and affected wake–sleep variables for 3 h, resulted in decreased W, due to reductions in the number and duration of W episodes; increased SWS and REM sleep, due to increases in episode duration; and decreased levels of pCaMKII expression in the PPT. Regression analyses revealed that PPT levels of pCaMKII were positively related with the total percentage of time spent in W (R2= 0.864;n= 28 rats;p< 0.001) and negatively related with the total percentage of time spent in sleep (R2= 0.863;p< 0.001). These data provide the first direct evidence that activation of intracellular CaMKII signaling in the PPT promotes W and suppresses sleep. These findings are relevant for designing a drug that could treat excessive sleepiness by promoting alertness.

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  • Like theta activity, PGO waves have been proposed as a mechanism supporting synaptic plasticity in the regions they reach.

    “Like theta activity, PGO waves have been proposed as a mechanism supporting synaptic plasticity in the regions they reach (258, 264).”

    From About Sleep's Role in Memory (2013) · cites this paper as [264]

    The Introduction and Discussion address PPT signaling in REM sleep and wakefulness, not a proposal that PGO waves support synaptic plasticity in the regions they reach. The References list other studies whose titles link pontine-wave generation to plasticity, but this paper does not itself state the attributed proposal (searched: PGO waves, pontine-wave plasticity, hippocampus and amygdala). (LLM, conf=0.73)

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Authors
Datta, S., O'Malley, M. W., & Patterson, E. H.
Affiliations
Boston University (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2011-11-23
Volume
31
Issue
47
Pages
17007-17016
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.3981-11.2011
PMC
PMC3229030
OpenAlex
W2048509568
Cited by
36
References
3
Citations by year
2026: 3 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 3 · 2017: 2 · 2016: 3 · 2015: 9 · 2014: 1 · 2013: 4 · 2012: 1
FWCI
0.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Mental Health (MH 59839, R01MH059839)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords
pedunculopontine nucleus, calcium/calmodulin-dependent protein kinase II, CaMKII signaling, wakefulness, REM sleep, slow-wave sleep, sleep regulation, KN-93, excessive sleepiness, alertness
MeSH terms
Benzenesulfonamides, Animals, Benzylamines, Male, Microinjections, Random Allocation, Sleep Stages, Sulfonamides, Wakefulness, Signal Transduction, Rats, Wistar, Pedunculopontine Tegmental Nucleus, Protein Kinase Inhibitors, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2

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