Pedunculopontine arousal system physiology - Implications for insomnia.
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.
Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Edgar
E
Garcia-Rill
Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Brennon
B
Luster
Center for Translational Neuroscience, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Susan
S
Mahaffey
IFIBYNE-CONICET and ININFA-CONICET, University of Buenos Aires, Argentina.
Veronica
V
Bisagno
IFIBYNE-CONICET and ININFA-CONICET, University of Buenos Aires, Argentina.
Francisco J
FJ
Urbano
CaMKII, calcium/calmodulin-dependent protein kinase; Calcium channels; EEG, electroencephalogram; Gamma band activity; KA, kainic acid; N-type calcium channel; NCS-1, neuronal calcium sensor protein 1; NMDA, n methyl d aspartic acid; Neuronal calcium sensor protein; P/Q-type calcium channel; PGO, ponto-geniculo-occipital; PPN, pedunculopontine nucleus; RAS, reticular activating system; REM, rapid eye movement; SWS, slow wave sleep; cAMP, cyclic adenosine monophosphate; ω-Aga, ω-agatoxin-IVA; ω-CgTx, ω-conotoxin-GVIA