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

被引:157
作者
Anderson, MP
Mochizuki, T
Xie, J
Fischler, W
Manger, JP
Talley, EM
Scammell, TE
Tonegawa, S
机构
[1] MIT, Picower Ctr Learning & Memory, Howard Hughes Med Inst, Cambridge, MA 02139 USA
[2] MIT, InsT Phys & Chem Res RIKEN, Neurosci Res Ctr, Ctr Canc Res,Dept Biol, Cambridge, MA 02139 USA
[3] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA
[4] Harvard Univ, Sch Med, Mol Neuropathol Lab, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA
[6] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA
关键词
insomnia; alpha; 1G; thalamus; arousal; Cre recombinase;
D O I
10.1073/pnas.0409644102
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
it has long been suspected that sensory signal transmission is inhibited in the mammalian brain during sleep. We hypothesized that Ca(v)3.1 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 Ca(v)3.1 knockout mice. Inhibition occurred with synaptic transmission blocked and required an increase of intracellular Ca2+. Furthermore, focal deletion of the gene encoding Ca(v)3.1 from the rostral-midline thalamus by using Cre/loxP recombination led to frequent and prolonged arousal, which fragmented and reduced sleep. Interestingly, sleep was not disturbed when Ca(v)3.1 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.
引用
收藏
页码:1743 / 1748
页数:6
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