Document Detail


Sustaining sleep spindles through enhanced SK2-channel activity consolidates sleep and elevates arousal threshold.
MedLine Citation:
PMID:  23035101     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Ralf D Wimmer; Simone Astori; Chris T Bond; Zita Rovó; Jean-Yves Chatton; John P Adelman; Paul Franken; Anita Lüthi
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
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:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13917-28     Citation Subset:  IM    
Affiliation:
Department of Fundamental Neuroscience, University of Lausanne, CH-1005 Lausanne, Switzerland.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
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:
NS038880/NS/NINDS NIH HHS; R01 MH093599/MH/NIMH NIH HHS; R01 NS038880/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Kcnn2 protein, mouse; 0/Recombinant Fusion Proteins; 0/Small-Conductance Calcium-Activated Potassium Channels
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Microtubule plus-end tracking protein CLASP2 regulates neuronal polarity and synaptic function.
Next Document:  Biasing amacrine subtypes in the Atoh7 lineage through expression of Barhl2.