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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

Proposed organization of cell ensembles in the PPN containing cells that express only N-type, only P/Q-type, or both calcium channels subtypes. Glutamatergic neurons are shown as red circles, cholinergic neurons as blue hexagons, and GABAergic cells as green ovals, some being electrically coupled (black bars). Groups of cells with a 5:3:2 ratio would all need to express the same channels subtype. Ensembles expressing only N-type channels would fire during REM sleep (REM-on), those expressing only P/Q-type channels would fire during waking (Wake-on), and those expressing both would fire during each state (Wake/REM-on).
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f0020: Proposed organization of cell ensembles in the PPN containing cells that express only N-type, only P/Q-type, or both calcium channels subtypes. Glutamatergic neurons are shown as red circles, cholinergic neurons as blue hexagons, and GABAergic cells as green ovals, some being electrically coupled (black bars). Groups of cells with a 5:3:2 ratio would all need to express the same channels subtype. Ensembles expressing only N-type channels would fire during REM sleep (REM-on), those expressing only P/Q-type channels would fire during waking (Wake-on), and those expressing both would fire during each state (Wake/REM-on).

Mentions: While there are three electrophysiological types of PPN cells in vitro, each of these is represented in the N-only, P/Q-only and N+P/Q cell groups, suggesting that all of the electrophysiological cell types are found in each cell ensemble. Anatomically, neurons in the PPN are scattered such that in the pars compacta there are glutamatergic (GLU), cholinergic (ACh), and GABAergic neurons in the ratio of 5:3:2, respectively [13]. Since all three electrophysiological types are included in the calcium channel segregation, it also means that all of the transmitter types are represented in the calcium channel segregation. This suggests that there are ensembles of N-only cells with glutamatergic, cholinergic, and GABAergic cells, and similarly for P/Q-only and N+P/Q cells. Studies using calcium imaging in the PPN pars compacta reveal an interesting anatomical organization within the nucleus. Pairs of PPN cells are labeled throughout the nucleus even in the control, unstimulated condition [48]. The spatial separation between couplets suggests that there are clusters of cells throughout the nucleus. Since electrically coupled neurons generally represent GABAergic neurons, we speculate that there are 5 GLU and 3 ACh neurons closely associated with each GABAergic pair. That is, there may be clusters of approximately 10 neurons scattered within the pars compacta that may create a functional subgroup. These functional subgroups may each bear a different combination of calcium channels. Much additional evidence is required to support this hypothesis, but it may be possible to dissect such an organization to determine how the nucleus as a whole generates coherent activity at specific frequencies. It is also important to determine how PPN neurons respond to sensory input and how that input generates coherent activity. Fig. 4 provides a proposed organization for these groups, each of which would includes each transmitter type, but all of the cells within the group would express one or both of the channels.


Pedunculopontine arousal system physiology - Implications for insomnia.

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

Proposed organization of cell ensembles in the PPN containing cells that express only N-type, only P/Q-type, or both calcium channels subtypes. Glutamatergic neurons are shown as red circles, cholinergic neurons as blue hexagons, and GABAergic cells as green ovals, some being electrically coupled (black bars). Groups of cells with a 5:3:2 ratio would all need to express the same channels subtype. Ensembles expressing only N-type channels would fire during REM sleep (REM-on), those expressing only P/Q-type channels would fire during waking (Wake-on), and those expressing both would fire during each state (Wake/REM-on).
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

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

f0020: Proposed organization of cell ensembles in the PPN containing cells that express only N-type, only P/Q-type, or both calcium channels subtypes. Glutamatergic neurons are shown as red circles, cholinergic neurons as blue hexagons, and GABAergic cells as green ovals, some being electrically coupled (black bars). Groups of cells with a 5:3:2 ratio would all need to express the same channels subtype. Ensembles expressing only N-type channels would fire during REM sleep (REM-on), those expressing only P/Q-type channels would fire during waking (Wake-on), and those expressing both would fire during each state (Wake/REM-on).
Mentions: While there are three electrophysiological types of PPN cells in vitro, each of these is represented in the N-only, P/Q-only and N+P/Q cell groups, suggesting that all of the electrophysiological cell types are found in each cell ensemble. Anatomically, neurons in the PPN are scattered such that in the pars compacta there are glutamatergic (GLU), cholinergic (ACh), and GABAergic neurons in the ratio of 5:3:2, respectively [13]. Since all three electrophysiological types are included in the calcium channel segregation, it also means that all of the transmitter types are represented in the calcium channel segregation. This suggests that there are ensembles of N-only cells with glutamatergic, cholinergic, and GABAergic cells, and similarly for P/Q-only and N+P/Q cells. Studies using calcium imaging in the PPN pars compacta reveal an interesting anatomical organization within the nucleus. Pairs of PPN cells are labeled throughout the nucleus even in the control, unstimulated condition [48]. The spatial separation between couplets suggests that there are clusters of cells throughout the nucleus. Since electrically coupled neurons generally represent GABAergic neurons, we speculate that there are 5 GLU and 3 ACh neurons closely associated with each GABAergic pair. That is, there may be clusters of approximately 10 neurons scattered within the pars compacta that may create a functional subgroup. These functional subgroups may each bear a different combination of calcium channels. Much additional evidence is required to support this hypothesis, but it may be possible to dissect such an organization to determine how the nucleus as a whole generates coherent activity at specific frequencies. It is also important to determine how PPN neurons respond to sensory input and how that input generates coherent activity. Fig. 4 provides a proposed organization for these groups, each of which would includes each transmitter type, but all of the cells within the group would express one or both of the channels.

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