Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat

Datta, Subimal; Spoley, Eric E.; Patterson, Elissa H.

doi:10.1152/ajpregu.2001.280.3.r752

Cited by 129 publications

(119 citation statements)

References 55 publications

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“…Together, the PKA subunit expression, PKA activity, and cAMPdependent PKA activity inhibition data indicate that increased activation of the PPT intracellular PKA system is involved in the generation of REM sleep. These molecular and pharmacological findings are consistent with previous single-cell recordings and pharmacological stimulation studies that have shown that activation of PPT cells is critical for the generation of REM sleep (ElMansari et al, 1989;Datta, 1995;Datta et al, 2001;Datta and Siwek, 2002;Ulloor et al, 2004).…”

Section: Discussionsupporting

confidence: 91%

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

Bandyopadhya¹,

Datta²,

Saha³

2006

J. Neurosci.

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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.

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Section: Discussionsupporting

confidence: 91%

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

Bandyopadhya¹,

Datta²,

Saha³

2006

J. Neurosci.

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“…PPT/LDT activation (Lydic et al, 1991;Lydic and Baghdoyan, 1993), whereas glutamatergic stimulation of PPT increases REM sleep up to 6 h after injection (Datta et al, 2001). These results mirror the parameters of the UII-induced increase in REM state.…”

Section: Discussionsupporting

confidence: 62%

“…Glutamatergic stimulation of the PPT in rats reduces REM sleep latency and increases REM sleep because of an increase in both duration and number of episodes of REM sleep (Datta et al, 2001). We did not observe significant changes in the latency or duration of REM sleep episodes in the animals treated with UII, suggesting that UII produces a stimulation that is different from the glutamatergic stimulation of the mesopontine cholinergic neurons.…”

Section: Discussionmentioning

confidence: 99%

Urotensin II Modulates Rapid Eye Movement Sleep through Activation of Brainstem Cholinergic Neurons

Huitrón‐Reséndiz

Kristensen²,

Sanchez‐Alavez³

et al. 2005

Journal of Neuroscience

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Urotensin II (UII) is a cyclic neuropeptide with strong vasoconstrictive activity in the peripheral vasculature. UII receptor mRNA is also expressed in the CNS, in particular in cholinergic neurons located in the mesopontine tegmental area, including the pedunculopontine tegmental (PPT) and lateral dorsal tegmental nuclei. This distribution suggests that the UII system is involved in functions regulated by acetylcholine, such as the sleep-wake cycle. Here, we tested the hypothesis that UII influences cholinergic PPT neuron activity and alters rapid eye movement (REM) sleep patterns in rats. Local administration of UII into the PPT nucleus increases REM sleep without inducing changes in the cortical blood flow. Intracerebroventricular injection of UII enhances both REM sleep and wakefulness and reduces slow-wave sleep 2. Intracerebroventricular, but not local, administration of UII increases cortical blood flow. Moreover, whole-cell recordings from rat-brain slices show that UII selectively excites cholinergic PPT neurons via an inward current and membrane depolarization that were accompanied by membrane conductance decreases. This effect does not depend on action potential generation or fast synaptic transmission because it persisted in the presence of TTX and antagonists of ionotropic glutamate, GABA, and glycine receptors. Collectively, these results suggest that UII plays a role in the regulation of REM sleep independently of its cerebrovascular actions by directly activating cholinergic brainstem neurons.

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“…To record the behavioral states of vigilance, cortical electroencephalogram (EEG), dorsal neck muscle electromyogram (EMG), electrooculogram (EOG), hippocampal EEG (to record theta wave), and pontine EEG (to record P-wave) recording electrodes were chronically implanted, as described previously (Datta, 2000(Datta, , 2002Datta et al, 2001). In addition, a stainless steel guide tube (26 gauge) with an equal length stylet inside was stereotaxically implanted 2 mm above the P-wave recording electrodes for the microinjection of control saline or carbachol solution into the P-wave generator (in relation to stereotaxic "0": posterior, 0.80; lateral, 1.3; horizontal, 2.0) of freely moving rats as described previously .…”

Section: Methodsmentioning

confidence: 99%

“…and perfused transcardially with heparinized cold phosphate buffer (0.1 M, pH 7.4) followed by 4% paraformaldehyde in 0.1 M phosphate buffer. The brains were then removed and processed for staining and histological localization of injection sites as described previously (Datta et al, 2001;.…”

Section: Methodsmentioning

confidence: 99%

Activation of Phasic Pontine-Wave Generator Prevents Rapid Eye Movement Sleep Deprivation-Induced Learning Impairment in the Rat: A Mechanism for Sleep-Dependent Plasticity

Datta¹,

Mavanji²,

Ulloor³

et al. 2004

J. Neurosci.

150

167

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Animal and human studies of sleep and learning have demonstrated that training on various tasks increases subsequent rapid eye movement (REM) sleep and phasic pontine-wave (P-wave) activity, followed by improvement in performance on the learned task. It is well documented that REM sleep deprivation after learning trials blocks the expected improvement in performance on subsequent retesting. Our aim was to test whether experimentally induced P-wave generator activation could eliminate the learning impairment produced by post-training REM sleep deprivation. Rats were trained on a two-way active avoidance-learning task. Immediately thereafter, two groups of those rats received a control vehicle (100 nl saline) microinjection and one group received a carbachol (50 ng in 100 nl saline) microinjection into the P-wave generator. The carbachol-injected group and one of the two control saline microinjected groups were selectively deprived of REM sleep during a 6 hr polygraphic recording session. All rats were then tested on the avoidance-learning task. The rats that received both the control saline injection and REM sleep deprivation showed learning deficits compared with the control saline-injected rats that were allowed to sleep normally. In contrast, the rats that received the carbachol microinjection and REM sleep deprivation demonstrated normal learning. These results demonstrate, for the first time, that carbachol-induced activation of the P-wave generator prevents the memory-impairing effects of post-training REM sleep deprivation. This evidence supports our hypothesis that the activation of the P-wave generator during REM sleep deprivation enhances a physiological process of memory, which occurs naturally during post-training REM sleep.

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Microinjection of glutamate into the pedunculopontine tegmentum induces REM sleep and wakefulness in the rat

Cited by 129 publications

References 55 publications

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

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

Urotensin II Modulates Rapid Eye Movement Sleep through Activation of Brainstem Cholinergic Neurons

Activation of Phasic Pontine-Wave Generator Prevents Rapid Eye Movement Sleep Deprivation-Induced Learning Impairment in the Rat: A Mechanism for Sleep-Dependent Plasticity

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