Contextual fear conditioning (CFC) in rodents is the most widely used behavioural paradigm in neuroscience research to elucidate the neurobiological mechanisms underlying learning and memory. It is based on the pairing of an aversive unconditioned stimulus (US; e.g. mild footshock) with a neutral conditioned stimulus (CS; e.g. context of the test chamber) in order to acquire associative long-term memory (LTM), which persists for days and even months. Using genome-wide analysis, several studies have generated lists of genes modulated in response to CFC in an attempt to identify the “memory genes”, which orchestrate memory formation. Yet, most studies use naïve animals as a baseline for assessing gene-expression changes, while only few studies have examined the effect of the US alone, without pairing to context, using genome-wide analysis of gene-expression. Herein, using the ribosome profiling methodology, we show that in male mice an immediate shock, which does not lead to LTM formation, elicits pervasive translational and transcriptional changes in the expression of Immediate Early Genes (IEGs) in dorsal hippocampus (such as Fos and Arc), a fact which has been disregarded by the majority of CFC studies. By removing the effect of the immediate shock, we identify and validate a new set of genes, which are translationally and transcriptionally responsive to the association of context-to-footshock in CFC, and thus constitute salient “memory genes”.

啮齿动物的情境恐惧条件反射 (CFC) 是神经科学研究中最广泛使用的行为范式，用于阐明学习和记忆的神经生物学机制。它基于厌恶的无条件刺激（美国；例如轻度足震）与中性条件刺激（CS；例如测试室的背景）的配对，以获得持续数天的联想长期记忆（LTM）甚至几个月。使用全基因组分析，几项研究已经生成了响应 CFC 调节的基因列表，以试图识别协调记忆形成的“记忆基因”。然而，大多数研究使用幼稚动物作为评估基因表达变化的基线，而只有少数研究单独检查了美国的影响，而没有与背景配对，使用基因表达的全基因组分析。在此，我们使用核糖体分析方法表明，在雄性小鼠中，立即电击不会导致 LTM 形成，引起背海马中即时早期基因 (IEG) 表达的普遍翻译和转录变化（例如Fos和Arc），这一事实已被大多数 CFC 研究忽视。通过消除即时电击的影响，我们识别并验证了一组新的基因，这些基因在翻译和转录上对 CFC 中上下文与足部电击的关联有反应，因此构成了显着的“记忆基因”。