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Articles, Behavioral/Systems/Cognitive

Sustaining Sleep Spindles through Enhanced SK2-Channel Activity Consolidates Sleep and Elevates Arousal Threshold

Ralf D. Wimmer, Simone Astori, Chris T. Bond, Zita Rovó, Jean-Yves Chatton, John P. Adelman, Paul Franken and Anita Lüthi
Journal of Neuroscience 3 October 2012, 32 (40) 13917-13928; DOI: https://doi.org/10.1523/JNEUROSCI.2313-12.2012
Ralf D. Wimmer
1Department of Fundamental Neuroscience, University of Lausanne, CH-1005 Lausanne, Switzerland,
3Center for Integrative Genomics, Génopode, University of Lausanne, CH-1015 Lausanne-Dorigny, Switzerland
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Simone Astori
1Department of Fundamental Neuroscience, University of Lausanne, CH-1005 Lausanne, Switzerland,
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Chris T. Bond
2Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, and
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Zita Rovó
1Department of Fundamental Neuroscience, University of Lausanne, CH-1005 Lausanne, Switzerland,
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Jean-Yves Chatton
1Department of Fundamental Neuroscience, University of Lausanne, CH-1005 Lausanne, Switzerland,
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John P. Adelman
2Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, and
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Paul Franken
3Center for Integrative Genomics, Génopode, University of Lausanne, CH-1015 Lausanne-Dorigny, Switzerland
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Anita Lüthi
1Department of Fundamental Neuroscience, University of Lausanne, CH-1005 Lausanne, Switzerland,
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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 Cav3.3-type Ca2+ channels and Ca2+-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.

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The Journal of Neuroscience: 32 (40)
Journal of Neuroscience
Vol. 32, Issue 40
3 Oct 2012
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Sustaining Sleep Spindles through Enhanced SK2-Channel Activity Consolidates Sleep and Elevates Arousal Threshold
Ralf D. Wimmer, Simone Astori, Chris T. Bond, Zita Rovó, Jean-Yves Chatton, John P. Adelman, Paul Franken, Anita Lüthi
Journal of Neuroscience 3 October 2012, 32 (40) 13917-13928; DOI: 10.1523/JNEUROSCI.2313-12.2012

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Sustaining Sleep Spindles through Enhanced SK2-Channel Activity Consolidates Sleep and Elevates Arousal Threshold
Ralf D. Wimmer, Simone Astori, Chris T. Bond, Zita Rovó, Jean-Yves Chatton, John P. Adelman, Paul Franken, Anita Lüthi
Journal of Neuroscience 3 October 2012, 32 (40) 13917-13928; DOI: 10.1523/JNEUROSCI.2313-12.2012
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