Calcium/calmodulin kinase II in the pedunculopontine tegmental nucleus modulates the initiation and maintenance of wakefulness

Subimal Datta, Matthew W. O'Malley, Elissa H. Patterson

Research output: Contribution to journalArticle

18 Citations (Scopus)

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 ofWand 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 thenumberand duration ofWepisodes; increasedSWSandREMsleep, 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 timespentinW(R 2=0.864;n=28rats;p<0.001)andnegativelyrelatedwiththetotalpercentageoftimespentinsleep(R 2=0.863;p<0.001). These data provide the first direct evidence that activation of intracellularCaMKIIsignaling in thePPTpromotesWand suppresses sleep. These findings are relevant for designing a drug that could treat excessive sleepiness by promoting alertness.

Original languageEnglish (US)
Pages (from-to)17007-17016
Number of pages10
JournalJournal of Neuroscience
Volume31
Issue number47
DOIs
StatePublished - Nov 23 2011

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Pedunculopontine Tegmental Nucleus
Calcium-Calmodulin-Dependent Protein Kinases
Wakefulness
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Sleep
Maintenance
Calcium
REM Sleep
Regression Analysis
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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Calcium/calmodulin kinase II in the pedunculopontine tegmental nucleus modulates the initiation and maintenance of wakefulness. / Datta, Subimal; O'Malley, Matthew W.; Patterson, Elissa H.

In: Journal of Neuroscience, Vol. 31, No. 47, 23.11.2011, p. 17007-17016.

Research output: Contribution to journalArticle

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