arouser Reveals a Role for Synapse Number in the Regulation of Ethanol Sensitivity
arouser Reveals a Role for Synapse Number in the Regulation of Ethanol Sensitivity
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DOI：
10.1016/j.neuron.2011.03.030
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发表时间：
2011-06-09
期刊：
影响因子：
16.2
通讯作者：
Heberlein, Ulrike
中科院分区：
文献类型：
--
作者：
Eddison, Mark;Guarnieri, Douglas J.;Heberlein, Ulrike
对酒精镇静作用的敏感性降低是与酒精使用障碍（AUD）相关的特征。在果蝇中对乙醇镇静突变体进行的遗传筛选确定了arouser（aru），它在发育中的神经元中起作用，以降低乙醇敏感性。遗传学证据表明，aru通过Egfr/Erk信号转导激活和PI 3 K/Akt信号转导抑制来调节乙醇敏感性。aru突变体在果蝇幼虫和成虫中的突触末梢数量也有所增加。aru突变体增加的乙醇敏感性和突触数量在成年社会隔离后恢复，表明突触数量和乙醇敏感性之间存在因果关系。因此，我们表明，影响突触数量和乙醇敏感性的发育异常不是永久性的，可以通过操纵成年苍蝇的环境来逆转。
A reduced sensitivity to the sedating effects of alcohol is a characteristic associated with alcohol use disorders (AUDs). A genetic screen for ethanol sedation mutants in Drosophila identified arouser (aru), which functions in developing neurons to reduce ethanol sensitivity. Genetic evidence suggests that aru regulates ethanol sensitivity through its activation by Egfr/Erk signaling and its inhibition by PI3K/Akt signaling. The aru mutant also has an increased number of synaptic terminals in the larva and adult fly. Both the increased ethanol sensitivity and synapse number of the aru mutant are restored upon adult social isolation, suggesting a causal relationship between synapse number and ethanol sensitivity. We thus show that a developmental abnormality affecting synapse number and ethanol sensitivity is not permanent and can be reversed by manipulating the environment of the adult fly.