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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

PPN cell types manifesting P/Q-type channels only, N-type channels only, or N- and P/Q-type channels. PPN cells with only P/Q-type calcium channels numbered 20%, and are assumed to be “Wake-on” and modulated by CaMKII. PPN cells with both N- and P/Q-type calcium channels numbered 50%, and are assumed to be Wake/REM-on” and modulated by both CaMKII and cAMP/PKA metabolic pathways. PPN cells with only N-type calcium channels numbered 30%, and are assumed to be “REM-on” and modulated by the cAMP/PKA pathway. P/Q-only and N+P/Q cells thus are expected to be active during waking, while N-only and N+P/Q cells are active during REM sleep.
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f0010: PPN cell types manifesting P/Q-type channels only, N-type channels only, or N- and P/Q-type channels. PPN cells with only P/Q-type calcium channels numbered 20%, and are assumed to be “Wake-on” and modulated by CaMKII. PPN cells with both N- and P/Q-type calcium channels numbered 50%, and are assumed to be Wake/REM-on” and modulated by both CaMKII and cAMP/PKA metabolic pathways. PPN cells with only N-type calcium channels numbered 30%, and are assumed to be “REM-on” and modulated by the cAMP/PKA pathway. P/Q-only and N+P/Q cells thus are expected to be active during waking, while N-only and N+P/Q cells are active during REM sleep.

Mentions: We have breakthrough findings showing that in some PPN cells (50%), the N-type calcium channel blocker ω-conotoxin-GVIA (ω-CgTx) reduced gamma oscillation amplitude, while subsequent addition of the P/Q-type blocker ω-agatoxin-IVA (ω-Aga) blocked the remaining oscillations. Other PPN cells (20%) manifested gamma oscillations that were not significantly affected by the addition of ω-CgTx, however, ω-Aga blocked the remaining oscillations. In the rest of the cells (30%), ω-Aga had no effect on gamma oscillations, while ω-CgTx blocked them. Similar results were found during recordings of voltage-dependent calcium currents. These results confirm the presence of cells in the PPN that manifest gamma band oscillations through only N-type, only P/Q-type, and both N- and P/Q-type calcium channels [36,37]. This new cell type classification suggests that some PPN neurons fire only during REM sleep (“REM-on”, N-type only), only during waking (“Wake-on”, P/Q-type only), or during both waking and REM sleep (“Wake/REM-on”, N-type+P/Q-type) [36,37]. Fig. 1 shows the responses to depolarizing ramps in each of these cell types, with responses being mediated by both N- and P/Q-type calcium channels (partial block by each channel blocker), by N-type only (complete block by ω-CgTx), and by P/Q-type only (complete block by ω-Aga). Fig. 2 shows the distribution and main intracellular control pathways modulating the two channel types, and presumed in vivo firing patterns.


Pedunculopontine arousal system physiology - Implications for insomnia.

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

PPN cell types manifesting P/Q-type channels only, N-type channels only, or N- and P/Q-type channels. PPN cells with only P/Q-type calcium channels numbered 20%, and are assumed to be “Wake-on” and modulated by CaMKII. PPN cells with both N- and P/Q-type calcium channels numbered 50%, and are assumed to be Wake/REM-on” and modulated by both CaMKII and cAMP/PKA metabolic pathways. PPN cells with only N-type calcium channels numbered 30%, and are assumed to be “REM-on” and modulated by the cAMP/PKA pathway. P/Q-only and N+P/Q cells thus are expected to be active during waking, while N-only and N+P/Q cells are active during REM sleep.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0010: PPN cell types manifesting P/Q-type channels only, N-type channels only, or N- and P/Q-type channels. PPN cells with only P/Q-type calcium channels numbered 20%, and are assumed to be “Wake-on” and modulated by CaMKII. PPN cells with both N- and P/Q-type calcium channels numbered 50%, and are assumed to be Wake/REM-on” and modulated by both CaMKII and cAMP/PKA metabolic pathways. PPN cells with only N-type calcium channels numbered 30%, and are assumed to be “REM-on” and modulated by the cAMP/PKA pathway. P/Q-only and N+P/Q cells thus are expected to be active during waking, while N-only and N+P/Q cells are active during REM sleep.
Mentions: We have breakthrough findings showing that in some PPN cells (50%), the N-type calcium channel blocker ω-conotoxin-GVIA (ω-CgTx) reduced gamma oscillation amplitude, while subsequent addition of the P/Q-type blocker ω-agatoxin-IVA (ω-Aga) blocked the remaining oscillations. Other PPN cells (20%) manifested gamma oscillations that were not significantly affected by the addition of ω-CgTx, however, ω-Aga blocked the remaining oscillations. In the rest of the cells (30%), ω-Aga had no effect on gamma oscillations, while ω-CgTx blocked them. Similar results were found during recordings of voltage-dependent calcium currents. These results confirm the presence of cells in the PPN that manifest gamma band oscillations through only N-type, only P/Q-type, and both N- and P/Q-type calcium channels [36,37]. This new cell type classification suggests that some PPN neurons fire only during REM sleep (“REM-on”, N-type only), only during waking (“Wake-on”, P/Q-type only), or during both waking and REM sleep (“Wake/REM-on”, N-type+P/Q-type) [36,37]. Fig. 1 shows the responses to depolarizing ramps in each of these cell types, with responses being mediated by both N- and P/Q-type calcium channels (partial block by each channel blocker), by N-type only (complete block by ω-CgTx), and by P/Q-type only (complete block by ω-Aga). Fig. 2 shows the distribution and main intracellular control pathways modulating the two channel types, and presumed in vivo firing patterns.

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