Department of Neuroscience, Brown University, Providence, Rhode Island 02912
Department of Biological Sciences, Southern Illinois University Edwardsville, Illinois 62026.
Genetics. 2020 May;215(1):103-116. doi: 10.1534/genetics.120.303101. Epub 2020 Mar 4.
Repeated alcohol experiences can produce long-lasting memories for sensory cues associated with intoxication. These memories can problematically trigger relapse in individuals recovering from alcohol use disorder (AUD). The molecular mechanisms by which ethanol changes memories to become long-lasting and inflexible remain unclear. New methods to analyze gene expression within precise neuronal cell types can provide further insight toward AUD prevention and treatment. Here, we used genetic tools in to investigate the lasting consequences of ethanol on transcription in memory-encoding neurons. rely on mushroom body (MB) neurons to make associative memories, including memories of ethanol-associated sensory cues. Differential expression analyses revealed that distinct transcripts, but not genes, in the MB were associated with experiencing ethanol alone compared to forming a memory of an odor cue associated with ethanol. Adult MB-specific knockdown of spliceosome-associated proteins demonstrated the necessity of RNA-processing in ethanol memory formation. These findings highlight the dynamic, context-specific regulation of transcription in cue-encoding neurons, and the lasting effect of ethanol on transcript usage during memory formation.
反复的酒精体验会对与醉酒相关的感觉线索产生持久的记忆。这些记忆可能会导致正在从酒精使用障碍（AUD）中恢复的个体复发。乙醇改变记忆以使其持久且僵化的分子机制尚不清楚。分析特定神经元细胞类型内基因表达的新方法可以为 AUD 的预防和治疗提供进一步的见解。在这里，我们使用 中的遗传工具来研究乙醇对记忆编码神经元中转录的持久影响。 依赖于蘑菇体（MB）神经元来形成联想记忆，包括与乙醇相关的感觉线索的记忆。差异表达分析显示，与形成与乙醇相关的气味线索的记忆相比，MB 中独特的转录本而不是基因与单独经历乙醇有关。成年 MB 特异性剪接体相关蛋白的敲低表明 RNA 处理在乙醇记忆形成中的必要性。这些发现强调了线索编码神经元中转录的动态、特定于上下文的调节，以及乙醇对记忆形成过程中转录物使用的持久影响。
