Actin is highly enriched at dendritic spines, and actin remodeling plays an essential role in structural plasticity. The mammalian target of rapamycin complex 2 (mTORC2) is a regulator of actin polymerization. Here, we report that alcohol consumption increases F-actin content in the dorsomedial striatum (DMS) of mice, thereby altering dendritic spine morphology in a mechanism that requires mTORC2. Specifically, we found that excessive alcohol consumption increases mTORC2 activity in the DMS, and that knockdown of Rictor, an essential component of mTORC2 signaling, reduces actin polymerization, and attenuates the alcohol-dependent alterations in spine head size and the number of mushroom spines. Finally, we show that knockdown of Rictor in the DMS reduces alcohol consumption, whereas intra-DMS infusion of the mTORC2 activator, A-443654, increases alcohol intake. Together, these results suggest that mTORC2 in the DMS facilitates the formation of F-actin, which in turn induces changes in spine structure to promote and/or maintain excessive alcohol intake.

中文翻译：

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小鼠背部纹状体中的mTORC2有助于酒精依赖性F-肌动蛋白的聚合，结构修饰和消耗。

肌动蛋白在树突棘中高度富集，肌动蛋白重塑在结构可塑性中起着至关重要的作用。雷帕霉素复合物2（mTORC2）的哺乳动物靶标是肌动蛋白聚合反应的调节剂。在这里，我们报告饮酒会增加小鼠背部纹状体（DMS）中F-肌动蛋白的含量，从而在需要mTORC2的机制中改变树突棘的形态。具体来说，我们发现过量的酒精消耗会增加DMS中的mTORC2活性，而敲除Rictor（mTORC2信号的必不可少的成分）会降低肌动蛋白的聚合反应，并减弱酒精依赖的脊柱头部大小和蘑菇棘数目的变化。最后，我们证明了在DMS中敲除Rictor可以减少酒精消耗，而在DMS内注入mTORC2激活剂A-443654，增加酒精摄入量。总之，这些结果表明，DMS中的mTORC2促进了F-肌动蛋白的形成，进而诱导了脊柱结构的改变，从而促进和/或维持了过量的酒精摄入。