| Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold. | |
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MedLine Citation:
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PMID: 23035101 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Ralf D Wimmer; Simone Astori; Chris T Bond; Zita Rovó; Jean-Yves Chatton; John P Adelman; Paul Franken; Anita Lüthi |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of neuroscience : the official journal of the Society for Neuroscience Volume: 32 ISSN: 1529-2401 ISO Abbreviation: J. Neurosci. Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-04 Completed Date: 2013-01-17 Revised Date: 2013-04-10 |
Medline Journal Info:
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Nlm Unique ID: 8102140 Medline TA: J Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 13917-28 Citation Subset: IM |
Affiliation:
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Department of Fundamental Neuroscience, University of Lausanne, CH-1005 Lausanne, Switzerland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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, physiology Sleep Stages / physiology* Small-Conductance Calcium-Activated Potassium Channels / biosynthesis, genetics, physiology* Specific Pathogen-Free Organisms Thalamic Nuclei / cytology, physiology* Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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NS038880/NS/NINDS NIH HHS; R01 MH093599/MH/NIMH NIH HHS; R01 NS038880/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Kcnn2 protein, mouse; 0/Recombinant Fusion Proteins; 0/Small-Conductance Calcium-Activated Potassium Channels |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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