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Pedunculopontine arousal system physiology-Implications for schizophrenia.

Garcia-Rill E, D'Onofrio S, Mahaffey S, Bisagno V, Urbano FJ - Sleep Sci (2015)

Bottom Line: There is also dysregulation of gamma band activity, suggestive of disturbances in a host of arousal-related mechanisms.This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of the disease.Recent discoveries on the physiology of the pedunculopontine nucleus help explain many of these disorders of arousal in, and point to novel therapeutic avenues for, schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

ABSTRACT
Schizophrenia is characterized by major sleep/wake disturbances including increased vigilance and arousal, decreased slow wave sleep, and increased REM sleep drive. Other arousal-related symptoms include sensory gating deficits as exemplified by decreased habituation of the blink reflex. There is also dysregulation of gamma band activity, suggestive of disturbances in a host of arousal-related mechanisms. This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of the disease. Recent discoveries on the physiology of the pedunculopontine nucleus help explain many of these disorders of arousal in, and point to novel therapeutic avenues for, schizophrenia.

No MeSH data available.


Related in: MedlinePlus

Intracellular pathways mediating NCS-1 modulation of intracellular calcium and P/Q-type calcium channels. Representation of effects of acetylcholine (ACh) activation of a muscarinic 2 cholinergic receptor (M2R) acting through G protein coupling to phospholipase C (PLC), that in turn cleaves phospholipid phosphatidylinositol biphosphate (PIP2) into inositol triphosphate (IP3). IP3 is released and binds to IP3 receptors in the endoplasmic reticulum (ER) to release calcium (Ca2+). One of the intracellular pathways activated involves NCS-1, which stimulates (+) P/Q-type calcium channels and somewhat inhibits (−) N-type calcium channels. NCS-1 at low concentrations increases gamma oscillations while NCS-1 at high concentrations blocks them. In addition, NCS-1 over expression is inhibited (−) by lithium (Li+), removing the blockade of gamma oscillations and restoring the maintenance of gamma band activity in these cells.
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f0010: Intracellular pathways mediating NCS-1 modulation of intracellular calcium and P/Q-type calcium channels. Representation of effects of acetylcholine (ACh) activation of a muscarinic 2 cholinergic receptor (M2R) acting through G protein coupling to phospholipase C (PLC), that in turn cleaves phospholipid phosphatidylinositol biphosphate (PIP2) into inositol triphosphate (IP3). IP3 is released and binds to IP3 receptors in the endoplasmic reticulum (ER) to release calcium (Ca2+). One of the intracellular pathways activated involves NCS-1, which stimulates (+) P/Q-type calcium channels and somewhat inhibits (−) N-type calcium channels. NCS-1 at low concentrations increases gamma oscillations while NCS-1 at high concentrations blocks them. In addition, NCS-1 over expression is inhibited (−) by lithium (Li+), removing the blockade of gamma oscillations and restoring the maintenance of gamma band activity in these cells.

Mentions: We then carried out a study to determine the effects of NCS-1 concentration on PPN cell ramp-induced oscillations. When using 10 μM NCS-1, the oscillation amplitude immediately increased to four times the levels and but then gradually decreased until it was significantly reduced by 30 min. These effects suggest an immediate increase in amplitude by very high levels of NCS-1 that ultimately led to blockade. Based on these results, 1 μM NCS-1 seems to be the most critical concentration for promoting gamma oscillations, while 10 μM blocked oscillations, in keeping with the effects of NCS-1 over expression [89,99]. Fig. 2 is a diagram of the intracellular pathways at play, showing the NCS-1 may normally stimulate gamma oscillations through P/Q-type calcium channels.


Pedunculopontine arousal system physiology-Implications for schizophrenia.

Garcia-Rill E, D'Onofrio S, Mahaffey S, Bisagno V, Urbano FJ - Sleep Sci (2015)

Intracellular pathways mediating NCS-1 modulation of intracellular calcium and P/Q-type calcium channels. Representation of effects of acetylcholine (ACh) activation of a muscarinic 2 cholinergic receptor (M2R) acting through G protein coupling to phospholipase C (PLC), that in turn cleaves phospholipid phosphatidylinositol biphosphate (PIP2) into inositol triphosphate (IP3). IP3 is released and binds to IP3 receptors in the endoplasmic reticulum (ER) to release calcium (Ca2+). One of the intracellular pathways activated involves NCS-1, which stimulates (+) P/Q-type calcium channels and somewhat inhibits (−) N-type calcium channels. NCS-1 at low concentrations increases gamma oscillations while NCS-1 at high concentrations blocks them. In addition, NCS-1 over expression is inhibited (−) by lithium (Li+), removing the blockade of gamma oscillations and restoring the maintenance of gamma band activity in these cells.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608902&req=5

f0010: Intracellular pathways mediating NCS-1 modulation of intracellular calcium and P/Q-type calcium channels. Representation of effects of acetylcholine (ACh) activation of a muscarinic 2 cholinergic receptor (M2R) acting through G protein coupling to phospholipase C (PLC), that in turn cleaves phospholipid phosphatidylinositol biphosphate (PIP2) into inositol triphosphate (IP3). IP3 is released and binds to IP3 receptors in the endoplasmic reticulum (ER) to release calcium (Ca2+). One of the intracellular pathways activated involves NCS-1, which stimulates (+) P/Q-type calcium channels and somewhat inhibits (−) N-type calcium channels. NCS-1 at low concentrations increases gamma oscillations while NCS-1 at high concentrations blocks them. In addition, NCS-1 over expression is inhibited (−) by lithium (Li+), removing the blockade of gamma oscillations and restoring the maintenance of gamma band activity in these cells.
Mentions: We then carried out a study to determine the effects of NCS-1 concentration on PPN cell ramp-induced oscillations. When using 10 μM NCS-1, the oscillation amplitude immediately increased to four times the levels and but then gradually decreased until it was significantly reduced by 30 min. These effects suggest an immediate increase in amplitude by very high levels of NCS-1 that ultimately led to blockade. Based on these results, 1 μM NCS-1 seems to be the most critical concentration for promoting gamma oscillations, while 10 μM blocked oscillations, in keeping with the effects of NCS-1 over expression [89,99]. Fig. 2 is a diagram of the intracellular pathways at play, showing the NCS-1 may normally stimulate gamma oscillations through P/Q-type calcium channels.

Bottom Line: There is also dysregulation of gamma band activity, suggestive of disturbances in a host of arousal-related mechanisms.This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of the disease.Recent discoveries on the physiology of the pedunculopontine nucleus help explain many of these disorders of arousal in, and point to novel therapeutic avenues for, schizophrenia.

View Article: PubMed Central - PubMed

Affiliation: Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, United States.

ABSTRACT
Schizophrenia is characterized by major sleep/wake disturbances including increased vigilance and arousal, decreased slow wave sleep, and increased REM sleep drive. Other arousal-related symptoms include sensory gating deficits as exemplified by decreased habituation of the blink reflex. There is also dysregulation of gamma band activity, suggestive of disturbances in a host of arousal-related mechanisms. This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of the disease. Recent discoveries on the physiology of the pedunculopontine nucleus help explain many of these disorders of arousal in, and point to novel therapeutic avenues for, schizophrenia.

No MeSH data available.


Related in: MedlinePlus