Drosophila Neuroligin 4 Regulates Sleep through Modulating GABA Transmission
Drosophila Neuroligin 4 Regulates Sleep through Modulating GABA Transmission
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果蝇 Neuroligin 4 通过调节 GABA 传输来调节睡眠
DOI：
10.1523/jneurosci.0819-13.2013
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发表时间：
2013-09-25
影响因子：
5.3
通讯作者：
Han, Junhai
中科院分区：
文献类型：
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作者：
Li, Yi;Zhou, Zikai;Han, Junhai
睡眠是一种基本的、进化上保守的行为，与突触功能密切相关。神经素（Nlgs）是参与突触形成和突触传递的细胞粘附分子，是否参与睡眠尚不清楚。在这里，我们发现果蝇Nlg4 （DNlg4）在大腹侧侧时钟神经元（l-LNvs）中高度表达，并且l-LNvs衍生的DNlg4对睡眠调节至关重要。GABA在l-LNv突变体中传输受损，dnlg4突变体果蝇的睡眠缺陷可以通过GABA传输的遗传操作来修复。此外，dnlg4突变果蝇表现出GABAA受体RDL聚类的严重减少，并且dnlg4在体内与RDL相关。这些结果表明，DNlg4通过调节l-LNvs中的GABA传递来调节睡眠，这为果蝇突触粘附分子与睡眠之间提供了已知的第一个联系。
Sleep is an essential and evolutionarily conserved behavior that is closely related to synaptic function. However, whether neuroligins (Nlgs), which are cell adhesion molecules involved in synapse formation and synaptic transmission, are involved in sleep is not clear. Here, we show that Drosophila Nlg4 (DNlg4) is highly expressed in large ventral lateral clock neurons (l-LNvs) and that l-LNv-derived DNlg4 is essential for sleep regulation. GABA transmission is impaired in mutant l-LNv, and sleep defects in dnlg4 mutant flies can be rescued by genetic manipulation of GABA transmission. Furthermore, dnlg4 mutant flies exhibit a severe reduction in GABAA receptor RDL clustering, and DNlg4 associates with RDLs in vivo. These results demonstrate that DNlg4 regulates sleep through modulating GABA transmission in l-LNvs, which provides the first known link between a synaptic adhesion molecule and sleep in Drosophila.