The role of active zone protein Rab3 interacting molecule 1 alpha in the regulation of norepinephrine release, response to novelty, and sleep.
The role of active zone protein Rab3 interacting molecule 1 alpha in the regulation of norepinephrine release, response to novelty, and sleep.
复制标题
活性区蛋白 Rab3 相互作用分子 1 α 在调节去甲肾上腺素释放、对新奇事物的反应和睡眠中的作用。
DOI：
10.1016/j.neuroscience.2008.03.047
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发表时间：
2008
期刊：
影响因子：
3.3
通讯作者：
Sanford,LD
中科院分区：
文献类型：
--
作者：
Lonart,G;Tang,X;Simsek-Duran,F;Machida,M;Sanford,LD
睡眠机制和突触可塑性被认为是相互作用的，以调节稳态和记忆的形成。然而，介导突触可塑性的分子对睡眠的影响还不清楚。在这项研究中，我们证明了缺乏Rab3相互作用分子1 α（RIM1α）（Rim1αKO）的小鼠，一种突触活性区的蛋白质，是某些类型的突触可塑性和学习所必需的，与野生型同窝小鼠相比，基线快速眼动（REM）睡眠减少了53±5%。此外，与野生型同窝出生的小鼠相比，暴露于开阔的场地或新的物体诱导了更稳健和更持久的运动，表明习惯性改变。这种探索行为的差异与Rim 1 αKO小鼠的REM基因型特异性变化以及皮质和基底杏仁核中去甲肾上腺素释放失调相关。此外，中度睡眠剥夺（4小时），稳态睡眠反应的测试，诱导REM睡眠反弹与不同的时间过程中的Rim 1 αKO和他们的野生型同窝仔。由于去甲肾上腺素在调节觉醒和REM睡眠中起重要作用，我们的数据表明Rim 1 αKO动物中的去甲肾上腺素能缺乏影响探索行为和睡眠调节，并导致学习障碍。
Sleep mechanisms and synaptic plasticity are thought to interact to regulate homeostasis and memory formation. However, the influences of molecules that mediate synaptic plasticity on sleep are not well understood. In this study we demonstrate that mice lacking Rab3 interacting molecule 1 alpha (RIM1α) (Rim1αKO), a protein of the synaptic active zone required for certain types of synaptic plasticity and learning, had 53±5% less baseline rapid eye movement (REM) sleep compared with their wild type littermates. Also, compared with wild type littermates, exposure of the mice to an open field or to a novel object induced more robust and longer lasting locomotion suggesting altered habituation. This difference in exploratory behavior correlated with genotype specific changes in REM and deregulated release of norepinephrine in the cortex and basal amygdala of the Rim1αKO mice. Also, moderate sleep deprivation (4 h), a test of the homeostatic sleep response, induced REM sleep rebound with different time course in Rim1αKO and their wild type littermates. As norepinephrine plays an important role in regulating arousal and REM sleep, our data suggest that noradrenergic deficiency in Rim1αKO animals impacts exploratory behavior and sleep regulation and contributes to impairments in learning.