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The Journal of Neuroscience, August 30, 2006, 26(35):8931-8942; doi:10.1523/JNEUROSCI.2173-06.2006

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Behavioral/Systems/Cognitive
Activation of Pedunculopontine Tegmental Protein Kinase A: A Mechanism for Rapid Eye Movement Sleep Generation in the Freely Moving Rat

Ram S. Bandyopadhya, Subimal Datta, and Subhash Saha

Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry, Boston University School of Medicine, Boston, Massachusetts 02118

Correspondence should be addressed to Dr. Subimal Datta, Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry, M-902, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118. Email: subimal{at}bu.edu

Cells in the pedunculopontine tegmentum (PPT) play a key role in the generation of rapid eye movement (REM) sleep, but its intracellular signaling mechanisms remain unknown. In the current studies, the role of PPT intracellular protein kinase A (PKA) in the regulation of REM sleep was evaluated by comparing PKA subunit [catalytic (PKA_C) and regulatory (PKA_RI, PKA_RII, and PKA_RII) types] expression and activity in the PPT at normal, high, and low REM sleep conditions. To compare anatomical specificity, REM sleep-dependent expressions of these PKA subunits were also measured in the medial pontine reticular formation (mPRF), medial prefrontal cortex (mPFC), and anterior hypothalamus (AHTh). The results of these PKA subunit expression and activity studies demonstrated that the expression of PKA_C and PKA activity in the PPT increased and decreased during high and low REM sleep, respectively. Conversely, PKA_C expression and PKA activity decreased with high REM sleep in the mPRF. Expression of PKA_C also decreased in the mPFC and remained unchanged in the AHTh with high REM sleep. These subunit expression and PKA activity data reveal a positive relationship between REM sleep and increased PKA activity in the PPT. To test this molecular evidence, localized activation of cAMP-dependent PKA activity was blocked using a pharmacological technique. The results of this pharmacological study demonstrated that the localized inhibition of cAMP-dependent PKA activation in the PPT dose-dependently suppressed REM sleep. Together, these results provide the first evidence that the activation of the PPT intracellular PKA system is involved in the generation of REM sleep.

Key words: REM sleep; signal transduction; pedunculopontine tegmentum; medial pontine reticular formation; medial prefrontal cortex; anterior hypothalamus

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Received Feb. 20, 2006; revised July 6, 2006; accepted July 25, 2006.

Correspondence should be addressed to Dr. Subimal Datta, Sleep and Cognitive Neuroscience Laboratory, Department of Psychiatry, M-902, Boston University School of Medicine, 85 East Newton Street, Boston, MA 02118. Email: subimal{at}bu.edu

This article has been cited by other articles:

				S. Datta Activation of Pedunculopontine Tegmental PKA Prevents GABAB Receptor Activation-Mediated Rapid Eye Movement Sleep Suppression in the Freely Moving Rat J Neurophysiol, June 1, 2007; 97(6): 3841 - 3850. [Abstract] [Full Text] [PDF]

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