Thalamic Cav3.1 T-type Ca2+ channel plays a crucial role in stabilizing sleep

Matthew P. Anderson, Takatoshi Mochizuki, Jinghui Xie, Walter Fischler, Jules P. Manger, Edmund M. Talley, Thomas E. Scammell, Susumu Tonegawa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

It has long been suspected that sensory signal transmission is inhibited in the mammalian brain during sleep. We hypothesized that Cav3.1 T-type Ca2+ channel currents inhibit thalamic sensory transmission to promote sleep. We found that T-type Ca2+ channel activation caused prolonged inhibition (>9 s) of action-potential firing in thalamic projection neurons of WT but not Cav3.1 knockout mice. Inhibition occurred with synaptic transmission blocked and required an increase of intracellular Ca 2+. Furthermore, focal deletion of the gene encoding Ca v3.1 from the rostral-midline thalamus by using Cre/IoxP recombination led to frequent and prolonged arousal, which fragmented and reduced sleep. Interestingly, sleep was not disturbed when Cav3.1 was deleted from cortical pyramidal neurons. These findings support the hypothesis that thalamic T-type Ca2+ channels are required to block transmission of arousal signals through the thalamus and to stabilize sleep.

Original languageEnglish
Pages (from-to)1743-1748
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number5
DOIs
StatePublished - 2005/02/01

Keywords

  • Arousal
  • Cre recombinase
  • Insomnia
  • Thalamus
  • α1G

ASJC Scopus subject areas

  • General

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