The mammalian target of rapamycin complex 1 (mTORC1), a transducer of local dendritic translation, participates in learning and memory processes as well as in mechanisms underlying alcohol-drinking behaviors. Using an unbiased RNA-seq approach, we identified Prosapip1 as a novel downstream target of mTORC1 whose translation and consequent synaptic protein expression are increased in the nucleus accumbens (NAc) of mice excessively consuming alcohol. We demonstrate that alcohol-dependent increases in Prosapip1 levels promote the formation of actin filaments, leading to changes in dendritic spine morphology of NAc medium spiny neurons (MSNs). We further demonstrate that Prosapip1 is required for alcohol-dependent synaptic localization of GluA2 lacking AMPA receptors in NAc shell MSNs. Finally, we present data implicating Prosapip1 in mechanisms underlying alcohol self-administration and reward. Together, these data suggest that Prosapip1 in the NAc is a molecular transducer of structural and synaptic alterations that drive and/or maintain excessive alcohol use.

中文翻译：

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Prosapip1依赖突触适应伏隔核驱动酒精摄入，寻求和奖励。

雷帕霉素复合物1（mTORC1）的哺乳动物靶标，是局部树突状翻译的转换器，参与学习和记忆过程以及饮酒行为的潜在机制。使用无偏RNA-seq方法，我们确定Prosapip1为mTORC1的新型下游靶标，其翻译和随后的突触蛋白表达在过量饮酒小鼠的伏隔核（NAc）中增加。我们证明Prosapip1水平的酒精依赖性增加会促进肌动蛋白丝的形成，从而导致NAc中棘神经元（MSNs）的树突棘形态改变。我们进一步证明Prosapip1是NAc壳MSNs中缺少AMPA受体的GluA2的酒精依赖性突触定位所必需的。最后，我们提出了有关Prosapip1参与酒精自我管理和奖励机制的数据。总之，这些数据表明，NAc中的Prosapip1是驱动和/或维持过量饮酒的结构和突触改变的分子传感器。