Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.

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Version: Author's accepted manuscript
Secondary document(s)
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State: Public
Version: Final published version
Serval ID
serval:BIB_078D7F363DB5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.
Journal
Journal of Neuroscience
Author(s)
Wimmer R.D., Astori S., Bond C.T., Rovó Z., Chatton J.Y., Adelman J.P., Franken P., Lüthi A.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
32
Number
40
Pages
13917-13928
Language
english
Abstract
Sleep spindles are synchronized 11-15 Hz electroencephalographic (EEG) oscillations predominant during nonrapid-eye-movement sleep (NREMS). Rhythmic bursting in the reticular thalamic nucleus (nRt), arising from interplay between Ca(v)3.3-type Ca(2+) channels and Ca(2+)-dependent small-conductance-type 2 (SK2) K(+) channels, underlies spindle generation. Correlative evidence indicates that spindles contribute to memory consolidation and protection against environmental noise in human NREMS. Here, we describe a molecular mechanism through which spindle power is selectively extended and we probed the actions of intensified spindling in the naturally sleeping mouse. Using electrophysiological recordings in acute brain slices from SK2 channel-overexpressing (SK2-OE) mice, we found that nRt bursting was potentiated and thalamic circuit oscillations were prolonged. Moreover, nRt cells showed greater resilience to transit from burst to tonic discharge in response to gradual depolarization, mimicking transitions out of NREMS. Compared with wild-type littermates, chronic EEG recordings of SK2-OE mice contained less fragmented NREMS, while the NREMS EEG power spectrum was conserved. Furthermore, EEG spindle activity was prolonged at NREMS exit. Finally, when exposed to white noise, SK2-OE mice needed stronger stimuli to arouse. Increased nRt bursting thus strengthens spindles and improves sleep quality through mechanisms independent of EEG slow waves (<4 Hz), suggesting SK2 signaling as a new potential therapeutic target for sleep disorders and for neuropsychiatric diseases accompanied by weakened sleep spindles.
Keywords
Action Potentials, Animals, Arousal/physiology, Auditory Threshold, Cells, Cultured/physiology, Electroencephalography, Female, Inhibitory Postsynaptic Potentials/physiology, Male, Mice, Mice, Inbred C57BL, Patch-Clamp Techniques, Polysomnography, Recombinant Fusion Proteins/biosynthesis, Recombinant Fusion Proteins/physiology, Sleep Stages/physiology, Small-Conductance Calcium-Activated Potassium Channels/biosynthesis, Small-Conductance Calcium-Activated Potassium Channels/genetics, Specific Pathogen-Free Organisms, Thalamic Nuclei/cytology, Thalamic Nuclei/physiology, Up-Regulation
Pubmed
Web of science
Open Access
Yes
Create date
31/10/2012 12:53
Last modification date
20/08/2019 12:29
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