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Pedunculopontine arousal system physiology - Implications for insomnia.

Garcia-Rill E, Luster B, Mahaffey S, Bisagno V, Urbano FJ - Sleep Sci (2015)

Bottom Line: This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of insomnia, mainly representing an overactive waking drive.We determined that high frequency activity during waking and REM sleep is controlled by two different intracellular pathways and channel types in PPN cells.We found three different PPN cell types that have one or both channels and may be active during waking only, REM sleep only, or both.

View Article: PubMed Central - PubMed

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

ABSTRACT
We consider insomnia a disorder of waking rather than a disorder of sleep. This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of insomnia, mainly representing an overactive waking drive. We determined that high frequency activity during waking and REM sleep is controlled by two different intracellular pathways and channel types in PPN cells. We found three different PPN cell types that have one or both channels and may be active during waking only, REM sleep only, or both. These discoveries point to a specific mechanism and novel therapeutic avenues for insomnia.

No MeSH data available.


Related in: MedlinePlus

Intracellular pathways modulated by different glutamatergic receptors that drive independent calcium channel types. As discussed above, a wealth of information is available to suggest that NMDA promotes waking in the PPN and that this effect is mediated by CaMKII, and that kainic acid promotes REM sleep and that this effect is mediated by cAMP/PKA. Both of these pathways interact with the release of calcium from the endoplasmic reticulum (ER) induced by inositol phosphate 3 (IP3) release from the membrane and binding to the IP3 receptor. In addition, P/Q-type channels are modulated by CaMKII while N-type channels are modulated by cAMP/PKA. This points to a selective participation of P/Q-type channels in generating gamma band activity during waking, and N-type channels generating gamma band activity during REM sleep.
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f0015: Intracellular pathways modulated by different glutamatergic receptors that drive independent calcium channel types. As discussed above, a wealth of information is available to suggest that NMDA promotes waking in the PPN and that this effect is mediated by CaMKII, and that kainic acid promotes REM sleep and that this effect is mediated by cAMP/PKA. Both of these pathways interact with the release of calcium from the endoplasmic reticulum (ER) induced by inositol phosphate 3 (IP3) release from the membrane and binding to the IP3 receptor. In addition, P/Q-type channels are modulated by CaMKII while N-type channels are modulated by cAMP/PKA. This points to a selective participation of P/Q-type channels in generating gamma band activity during waking, and N-type channels generating gamma band activity during REM sleep.

Mentions: Interestingly, PPN cells with N-type channels only manifested oscillations in the 50 Hz range, while cells with P/Q-type channels only exhibited oscillations in the 45 Hz range, while cells with both N- and P/Q-type channels showed oscillations in the 37 Hz range. These results suggest that each channel type may have a preferred oscillation frequency, but when channels coexist they may manifest lower frequencies, perhaps due to competition and/or differential location along dendrites [27]. Fig. 3 provides a diagram of the intracellular “waking” pathway and the “REM sleep” pathway, and their modulation of different calcium channel types by separate glutamatergic receptor types. With this information, we can now attempt to selectively modulate waking by affecting P/Q-type calcium channels and/or the CaMKII pathway, or modulate REM sleep by affecting the N-type calcium channels and/or the cAMP/PK pathway.


Pedunculopontine arousal system physiology - Implications for insomnia.

Garcia-Rill E, Luster B, Mahaffey S, Bisagno V, Urbano FJ - Sleep Sci (2015)

Intracellular pathways modulated by different glutamatergic receptors that drive independent calcium channel types. As discussed above, a wealth of information is available to suggest that NMDA promotes waking in the PPN and that this effect is mediated by CaMKII, and that kainic acid promotes REM sleep and that this effect is mediated by cAMP/PKA. Both of these pathways interact with the release of calcium from the endoplasmic reticulum (ER) induced by inositol phosphate 3 (IP3) release from the membrane and binding to the IP3 receptor. In addition, P/Q-type channels are modulated by CaMKII while N-type channels are modulated by cAMP/PKA. This points to a selective participation of P/Q-type channels in generating gamma band activity during waking, and N-type channels generating gamma band activity during REM sleep.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608886&req=5

f0015: Intracellular pathways modulated by different glutamatergic receptors that drive independent calcium channel types. As discussed above, a wealth of information is available to suggest that NMDA promotes waking in the PPN and that this effect is mediated by CaMKII, and that kainic acid promotes REM sleep and that this effect is mediated by cAMP/PKA. Both of these pathways interact with the release of calcium from the endoplasmic reticulum (ER) induced by inositol phosphate 3 (IP3) release from the membrane and binding to the IP3 receptor. In addition, P/Q-type channels are modulated by CaMKII while N-type channels are modulated by cAMP/PKA. This points to a selective participation of P/Q-type channels in generating gamma band activity during waking, and N-type channels generating gamma band activity during REM sleep.
Mentions: Interestingly, PPN cells with N-type channels only manifested oscillations in the 50 Hz range, while cells with P/Q-type channels only exhibited oscillations in the 45 Hz range, while cells with both N- and P/Q-type channels showed oscillations in the 37 Hz range. These results suggest that each channel type may have a preferred oscillation frequency, but when channels coexist they may manifest lower frequencies, perhaps due to competition and/or differential location along dendrites [27]. Fig. 3 provides a diagram of the intracellular “waking” pathway and the “REM sleep” pathway, and their modulation of different calcium channel types by separate glutamatergic receptor types. With this information, we can now attempt to selectively modulate waking by affecting P/Q-type calcium channels and/or the CaMKII pathway, or modulate REM sleep by affecting the N-type calcium channels and/or the cAMP/PK pathway.

Bottom Line: This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of insomnia, mainly representing an overactive waking drive.We determined that high frequency activity during waking and REM sleep is controlled by two different intracellular pathways and channel types in PPN cells.We found three different PPN cell types that have one or both channels and may be active during waking only, REM sleep only, or both.

View Article: PubMed Central - PubMed

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

ABSTRACT
We consider insomnia a disorder of waking rather than a disorder of sleep. This review examines the role of the reticular activating system, especially the pedunculopontine nucleus, in the symptoms of insomnia, mainly representing an overactive waking drive. We determined that high frequency activity during waking and REM sleep is controlled by two different intracellular pathways and channel types in PPN cells. We found three different PPN cell types that have one or both channels and may be active during waking only, REM sleep only, or both. These discoveries point to a specific mechanism and novel therapeutic avenues for insomnia.

No MeSH data available.


Related in: MedlinePlus