ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity.
ADAR-mediated RNA editing suppresses sleep by acting as a brake on glutamatergic synaptic plasticity.
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DOI：
10.1038/ncomms10512
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发表时间：
2016-01-27
影响因子：
16.6
通讯作者：
Joiner WJ
中科院分区：
文献类型：
--
作者：
Robinson JE;Paluch J;Dickman DK;Joiner WJ
据推测，清醒时的突触增强可被睡眠期间净突触强度的稳态降低所抵消。然而，缺乏支持这一过程的分子机制。在这里，我们证明了由于果蝇谷氨酸能神经元的突触功能障碍，RNA编辑基因Adar的缺陷增加了睡眠。具体地说，囊泡谷氨酸转运体上调，导致NMDA受体过度激活，在Adar突变体中，谷氨酸能突触囊泡的储备池被选择性地扩大。总的来说，这些变化导致持续的神经递质释放，否则会导致突触抑制。我们认为，促进睡眠的神经元中的平衡从突触抑制向突触增强的转变是Adar缺陷动物睡眠压力增加的基础。我们的发现提供了一个可信的分子机制，将睡眠和突触可塑性联系起来。睡眠被认为是为了抵消在清醒过程中出现的净突触强度的增加。在这里，作者确定了RNA编辑基因Adar在调节谷氨酸能突触可塑性中的作用，并表明Adar表达的中断损害了果蝇的正常觉醒。
It has been postulated that synaptic potentiation during waking is offset by a homoeostatic reduction in net synaptic strength during sleep. However, molecular mechanisms to support such a process are lacking. Here we demonstrate that deficiencies in the RNA-editing gene Adar increase sleep due to synaptic dysfunction in glutamatergic neurons in Drosophila. Specifically, the vesicular glutamate transporter is upregulated, leading to over-activation of NMDA receptors, and the reserve pool of glutamatergic synaptic vesicles is selectively expanded in Adar mutants. Collectively these changes lead to sustained neurotransmitter release under conditions that would otherwise result in synaptic depression. We propose that a shift in the balance from synaptic depression towards synaptic potentiation in sleep-promoting neurons underlies the increased sleep pressure of Adar-deficient animals. Our findings provide a plausible molecular mechanism linking sleep and synaptic plasticity. Sleep is postulated to offset buildup in net synaptic strength that occurs during waking experience. Here, the authors identify a role for the RNA editing gene Adar in regulating glutamatergic synaptic plasticity and show that disruption in Adar expression impairs normal waking in flies.