Neuronal machinery of sleep homeostasis in Drosophila.

Neuronal machinery of sleep homeostasis in Drosophila.
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DOI:
10.1016/j.neuron.2013.12.013
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发表时间:
2014-02-19
期刊:
影响因子:
16.2
通讯作者:
Miesenböck G
Miesenböck G
中科院分区:
医学1区
文献类型:
--
作者:
Donlea JM;Pimentel D;Miesenböck G

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睡眠处于稳态控制之下,但感知睡眠需求和纠正睡眠不足的机制仍然未知。在这里,我们报告说,睡眠促进神经元与预测的背部扇形体(FB)形成的输出臂果蝇的睡眠稳态。稳态睡眠控制需要由crossveinless-c(cv-c)基因编码的Rho-GTdR激活蛋白,以将睡眠压力转化为背FB神经元的增加的电兴奋性。CV-C突变体表现出与睡眠丧失后相当的睡眠时间减少、睡眠反弹减少和记忆缺陷。靶向消融和抢救Cv-c的睡眠控制神经元的背FB损害和恢复,分别正常的睡眠模式。睡眠剥夺增加了背FB神经元的兴奋性,但这种自我平衡的调整是在短睡眠cv-c突变体中断。因此,睡眠压力通过以依赖于Cv-c的机制调节离子通道功能,使促进睡眠的神经元的输入-输出功能向更高的活性转移。背侧扇形体中的神经元传达睡眠稳态的输出睡眠需要增加这些睡眠控制神经元的电兴奋性睡眠稳态需要由crossveinless-c基因Cv-c编码的Rho-GAP调节睡眠控制神经元中的离子通道功能Donlea et al.发现睡眠稳态失调的突变果蝇:经过一整夜的工作,这些果蝇无法纠正累积的睡眠不足。这种突变影响了Rho-GT3激活蛋白,该蛋白调节促进睡眠的神经元的电兴奋性。
Sleep is under homeostatic control, but the mechanisms that sense sleep need and correct sleep deficits remain unknown. Here, we report that sleep-promoting neurons with projections to the dorsal fan-shaped body (FB) form the output arm of Drosophila’s sleep homeostat. Homeostatic sleep control requires the Rho-GTPase-activating protein encoded by the crossveinless-c (cv-c) gene in order to transduce sleep pressure into increased electrical excitability of dorsal FB neurons. cv-c mutants exhibit decreased sleep time, diminished sleep rebound, and memory deficits comparable to those after sleep loss. Targeted ablation and rescue of Cv-c in sleep-control neurons of the dorsal FB impair and restore, respectively, normal sleep patterns. Sleep deprivation increases the excitability of dorsal FB neurons, but this homeostatic adjustment is disrupted in short-sleeping cv-c mutants. Sleep pressure thus shifts the input-output function of sleep-promoting neurons toward heightened activity by modulating ion channel function in a mechanism dependent on Cv-c. Neurons in the dorsal fan-shaped body convey the output of the sleep homeostat Sleep need increases the electrical excitability of these sleep-control neurons Sleep homeostasis requires the Rho-GAP encoded by the crossveinless-c gene Cv-c modulates ion channel function in sleep-control neurons Donlea et al. discover mutant flies with a broken sleep homeostat: after an all-nighter, these flies are unable to correct the accumulated sleep deficit. The mutation affects a Rho-GTPase-activating protein that regulates the electrical excitability of sleep-promoting neurons.
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