novel role for calcium/calmodulin kinase II within the brainstem pedunculopontine tegmentum for the regulation of wakefulness and rapid eye movement sleep

• Published in: Journal of neurochemistry Vol. 112; no. 1; pp. 271 - 281
• Main Authors: Stack, Edward C, Desarnaud, Frank, Siwek, Donald F, Datta, Subimal
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.01.2010; Blackwell Publishing Ltd; Wiley-Blackwell
• Subjects: Analytical, structural and metabolic biochemistry; Animals; ATF-2; Biological and medical sciences; Brain; Brain Stem; Brain Stem - enzymology; Calcium; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - genetics; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - physiology; CaMKII; Cell physiology; Enzymes and enzyme inhibitors; enzymology; Eye movements; Fundamental and applied biological sciences. Psychology; gene expression; genetics; Kinases; Male; Molecular and cellular biology; Neurosciences; Pedunculopontine Tegmental Nucleus; Pedunculopontine Tegmental Nucleus - enzymology; physiology; Rats; Rats, Wistar; REM sleep; RT-PCR; Signal transduction; Sleep, REM; Sleep, REM - physiology; Transferases; Wakefulness; Wakefulness - physiology; Phosphorylation; calmodulin-dependent protein kinase; ATF-2; Calcium; Enzyme; Transferases; Activation; Gene expression; Rapid eye movement sleep; REM sleep; Signal transduction; Neuron; CaMKII; Wakefulness; RT-PCR; Sleep wake cycle; Ca; Calmodulin
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.06452.x

Considerable evidence suggests that the brainstem pedunculopontine tegmentum (PPT) neurons are critically involved in the regulation of rapid eye movement (REM) sleep and wakefulness (W); however, the molecular mechanisms operating within the PPT to regulate these two behavioral states remain relatively unknown. Here we demonstrate that the levels of calcium/calmodulin kinase II (CaMKII) and phosphorylated CaMKII expression in the PPT decreased and increased with 'low W with high REM sleep' and 'high W/low REM sleep' periods, respectively. These state-specific expression changes were not observed in the cortex, or in the immediately adjacent medial pontine reticular formation. Next, we demonstrate that CaMKII activity in the PPT is negatively and positively correlated with the 'low W with high REM sleep' and 'high W/low REM sleep' periods, respectively. These differences in correlations were not seen in the medial pontine reticular formation CaMKII activity. Finally, we demonstrate that with increased PPT CaMKII activity observed during high W/low REM sleep, there were marked shifts in the expression of genes that are involved in components of various signal transduction pathways. Collectively, these results for the first time suggest that the increased CaMKII activity within PPT neurons is associated with increased W at the expense of REM sleep, and this process is accomplished through the activation of a specific gene expression profile.