Division of Neurobiology and Zoology, University of Kaiserslautern, Kaiserslautern, Germany.
PLoS Biol. 2019 Aug 27;17(8):e3000400. doi: 10.1371/journal.pbio.3000400. eCollection 2019 Aug.
Adaptive decision-making depends on the formation of novel memories. In Drosophila, the mushroom body (MB) is the site of associative olfactory long-term memory (LTM) storage. However, due to the sparse and stochastic representation of olfactory information in Kenyon cells (KCs), genetic access to individual LTMs remains elusive. Here, we develop a cAMP response element (CRE)-activity-dependent memory engram label (CAMEL) tool that genetically tags KCs responding to the conditioned stimulus (CS). CAMEL activity depends on protein-synthesis-dependent aversive LTM conditioning and reflects the time course of CRE binding protein 2 (CREB2) activity during natural memory formation. We demonstrate that inhibition of LTM-induced CAMEL neurons reduces memory expression and that artificial optogenetic reactivation is sufficient to evoke aversive behavior phenocopying memory recall. Together, our data are consistent with CAMEL neurons marking a subset of engram KCs encoding individual memories. This study provides new insights into memory circuitry organization and an entry point towards cellular and molecular understanding of LTM storage.
自适应决策取决于新记忆的形成。在果蝇中，蘑菇体（MB）是与嗅觉相关的长期记忆（LTM）存储的部位。然而，由于感觉神经元（Kenyon 细胞，KCs）中嗅觉信息的稀疏和随机表示，对单个 LTM 的遗传访问仍然难以捉摸。在这里，我们开发了一种 cAMP 反应元件（CRE）-活性依赖性记忆印记标签（CAMEL）工具，该工具可对响应条件刺激（CS）的 KCs 进行遗传标记。CAMEL 活性依赖于蛋白质合成依赖性厌恶 LTM 条件作用，反映了在自然记忆形成过程中 CRE 结合蛋白 2（CREB2）活性的时间过程。我们证明，抑制 LTM 诱导的 CAMEL 神经元会降低记忆表达，而人工光遗传学再激活足以引起厌恶行为，模拟记忆召回。总的来说，我们的数据与 CAMEL 神经元标记编码单个记忆的一组特定的印迹 KCs 相一致。这项研究为记忆电路组织提供了新的见解，并为理解 LTM 存储的细胞和分子机制提供了切入点。
