Pan-Neuronal Knockdown of Calcineurin Reduces Sleep in the Fruit Fly, Drosophila melanogaster
Pan-Neuronal Knockdown of Calcineurin Reduces Sleep in the Fruit Fly, Drosophila melanogaster
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DOI：
10.1523/jneurosci.5860-10.2011
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发表时间：
2011-09-14
影响因子：
5.3
通讯作者：
Kume, Kazuhiko
中科院分区：
文献类型：
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作者：
Tomita, Jun;Mitsuyoshi, Madoka;Kume, Kazuhiko
睡眠是一种独特的生理状态，它是由行为定义的，从哺乳动物到昆虫等无脊椎动物，各种物种都广泛保存着睡眠。由于各种新的动物模型提供了实验的可及性，包括果蝇，黑腹果蝇，在理解睡眠方面取得了重大进展。虽然睡眠的生理功能尚未完全阐明，但越来越多的证据表明，睡眠是维持神经元回路可塑性所必需的，因此在学习和记忆中也是必不可少的。钙调神经磷酸酶(CN)是一种由CNA和CNB亚基组成的异二聚体磷酸酶，在哺乳动物大脑中具有巩固记忆的功能，但其在果蝇中的神经功能尚不清楚。在这里，我们证明了CN是果蝇睡眠的重要调节因子。泛神经元RNA干扰介导的CN表达下调导致睡眠丧失，而CNA蛋白的成分活性形式的错误表达导致睡眠增加。此外，CNA基因敲除也损害了厌恶嗅觉记忆的保持。这些结果表明CN和钙依赖的信号转导在睡眠和记忆调节中的作用，并可能对它们之间的关系有更深入的了解。
Sleep is a unique physiological state, which is behaviorally defined, and is broadly conserved across species from mammals to invertebrates such as insects. Because of the experimental accessibility provided by various novel animal models including the fruit fly, Drosophila melanogaster, there have been significant advances in the understanding of sleep. Although the physiological functions of sleep have not been fully elucidated, accumulating evidence indicates that sleep is necessary to maintain the plasticity of neuronal circuits and, hence, is essential in learning and memory. Calcineurin (Cn) is a heterodimeric phosphatase composed of CnA and CnB subunits and known to function in memory consolidation in the mammalian brain, but its neurological functions in the fruit fly are largely unknown. Here, we show that Cn is an important regulator of sleep in Drosophila. A pan-neuronal RNA interference-mediated knockdown of Cn expression resulted in sleep loss, whereas misexpression of the constitutively active form of a CnA protein led to increased sleep. Furthermore, CnA knockdown also impaired the retention of aversive olfactory memory. These results indicate a role for Cn and calcium-dependent signal transduction in sleep and memory regulation and may bring insight into the relationship between them.