The Ca v3.3 calcium channel is the major sleep spindle pacemaker in thalamus

Simone Astori, Ralf D. Wimmer, Haydn M. Prosser, Corrado Corti, Mauro Corsi, Nicolas Liaudet, Andrea Volterra, Paul Franken, John P. Adelman, Anita Lüthi

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107 Scopus citations

Abstract

Low-threshold (T-type) Ca 2+ channels encoded by the Ca V3 genes endow neurons with oscillatory properties that underlie slow waves characteristic of the non-rapid eye movement (NREM) sleep EEG. Three Ca V3 channel subtypes are expressed in the thalamocortical (TC) system, but their respective roles for the sleep EEG are unclear. Ca V3.3 protein is expressed abundantly in the nucleus reticularis thalami (nRt), an essential oscillatory burst generator. We report the characterization of a transgenic Ca V3.3 -/- mouse line and demonstrate that Ca V3.3 channels are indispensable for nRt function and for sleep spindles, a hallmark of natural sleep. The absence of Ca V3.3 channels prevented oscillatory bursting in the lowfrequency (4-10 Hz) range in nRt cells but spared tonic discharge. In contrast, adjacent TC neurons expressing Ca V3.1 channels retained low-threshold bursts. Nevertheless, the generation of synchronized thalamic network oscillations underlying sleep-spindle waves was weakened markedly because of the reduced inhibition of TC neurons via nRt cells. T currents in Ca V3.3 -/- mice were <30% compared with those in WT mice, and the remaining current, carried by Ca V3.2 channels, generated dendritic [Ca 2+] i signals insufficient to provoke oscillatory bursting that arises from interplay with Ca 2+-dependent small conductance-type 2 K + channels. Finally, naturally sleeping Ca V3.3 -/- mice showed a selective reduction in the power density of the σ frequency band (10-12 Hz) at transitions from NREM to REM sleep, with other EEG waves remaining unaltered. Together, these data identify a central role for Ca V3.3 channels in the rhythmogenic properties of the sleep-spindle generator and provide a molecular target to elucidate the roles of sleep spindles for brain function and development.

Original languageEnglish (US)
Pages (from-to)13823-13828
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number33
DOIs
StatePublished - Aug 16 2011

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Keywords

  • Alpha1i
  • Cacna1i
  • Inhibition
  • Ion channel
  • Synchrony

ASJC Scopus subject areas

  • General

Cite this

Astori, S., Wimmer, R. D., Prosser, H. M., Corti, C., Corsi, M., Liaudet, N., Volterra, A., Franken, P., Adelman, J. P., & Lüthi, A. (2011). The Ca v3.3 calcium channel is the major sleep spindle pacemaker in thalamus. Proceedings of the National Academy of Sciences of the United States of America, 108(33), 13823-13828. https://doi.org/10.1073/pnas.1105115108