Department of Biology, University of Fribourg, Fribourg, Switzerland.
Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics, University of Bern, Bern, Switzerland.
PLoS Genet. 2023 Jun 12;19(6):e1010802. doi: 10.1371/journal.pgen.1010802. eCollection 2023 Jun.
The formation of long-term memories requires changes in the transcriptional program and de novo protein synthesis. One of the critical regulators for long-term memory (LTM) formation and maintenance is the transcription factor CREB. Genetic studies have dissected the requirement of CREB activity within memory circuits, however less is known about the genetic mechanisms acting downstream of CREB and how they may contribute defining LTM phases. To better understand the downstream mechanisms, we here used a targeted DamID approach (TaDa). We generated a CREB-Dam fusion protein using the fruit fly Drosophila melanogaster as model. Expressing CREB-Dam in the mushroom bodies (MBs), a brain center implicated in olfactory memory formation, we identified genes that are differentially expressed between paired and unpaired appetitive training paradigm. Of those genes we selected candidates for an RNAi screen in which we identified genes causing increased or decreased LTM.
长期记忆的形成需要转录程序和新蛋白质合成的改变。转录因子 CREB 是长时记忆 (LTM) 形成和维持的关键调节因子之一。遗传研究已经剖析了记忆回路中 CREB 活性的要求,但是对于 CREB 下游的遗传机制以及它们如何有助于定义 LTM 阶段知之甚少。为了更好地理解下游机制,我们在这里使用了靶向 DamID 方法 (TaDa)。我们使用果蝇 Drosophila melanogaster 作为模型生成了 CREB-Dam 融合蛋白。在蘑菇体 (MBs) 中表达 CREB-Dam,MBs 是参与嗅觉记忆形成的大脑中心,我们鉴定了在配对和非配对食欲训练范式之间差异表达的基因。在那些基因中,我们选择了 RNAi 筛选的候选基因,其中我们鉴定了导致 LTM 增加或减少的基因。