Contextual fear conditioning is a form of Pavlovian learning during which an organism learns to fear previously neutral stimuli following their close temporal presentation with an aversive stimulus. In mouse models, freezing behavior is typically used to quantify learned fear. This dependent variable is the sum of multiple processes, including associative/configural learning, fear and anxiety, and general activity. To explore phenotypic constructs underlying contextual fear conditioning and correlated behaviors, as well as factors that may contribute to individual differences in learning and mental health, we tested BXD recombinant inbred strains previously found to show extreme contextual fear conditioning phenotypes and BXD parental strains, C57BL/6J and DBA/2J, in a series of tests including locomotor, anxiety, contextual/cued fear conditioning and non-associative hippocampus-dependent learning behaviors. Hippocampal expression of two previously identified candidate genes for contextual fear conditioning was also quantified. Behavioral and gene expression data were analyzed using exploratory factor analysis (EFA), which suggested five unique constructs representing activity/anxiety/exploration, associative fear learning, anxiety, post-shock freezing, and open field activity phenotypes. Associative fear learning and expression of one candidate gene, Hacd4, clustered as a construct within the factor analysis. Post-shock freezing during fear conditioning and expression of candidate gene Ptprd emerged as another unique construct, highlighting the independence of freezing after footshock from other fear conditioning variables in the current dataset. EFA results additionally suggest shared phenotypic variance in adaptive murine behaviors related to anxiety, general activity, and exploration. These findings inform understanding of fear learning and underlying biological mechanisms that may interact to produce individual differences in fear- and learning-related behaviors in mice.

情境恐惧条件反射是巴甫洛夫学习的一种形式，在此过程中，有机体在与厌恶刺激紧密相关的时间呈现后学会害怕先前的中性刺激。在小鼠模型中，冻结行为通常用于量化习得性恐惧。这个因变量是多个过程的总和，包括联想/配置学习、恐惧和焦虑以及一般活动。为了探索情境恐惧条件反射和相关行为的表型结构，以及可能导致学习和心理健康个体差异的因素，我们测试了先前发现显示极端情境恐惧条件表型的 BXD 重组近交系菌株和 BXD 亲本菌株 C57BL/ 6J 和 DBA/2J，进行一系列测试，包括运动、焦虑、情境/暗示恐惧条件反射和非联想海马依赖性学习行为。先前确定的两个用于背景恐惧调节的候选基因的海马表达也被量化。使用探索性因素分析（EFA）对行为和基因表达数据进行分析，提出了代表活动/焦虑/探索、联想恐惧学习、焦虑、电击后冻结和旷场活动表型的五种独特结构。一个候选基因Hacd4因子聚集 为一个构建体。恐惧条件反射期间的电击后冻结和候选基因Ptprd作为另一个独特的构造出现，强调了电击后冻结与当前数据集中其他恐惧条件变量的独立性EFA 结果还表明，与焦虑、一般活动和探索相关的适应性小鼠行为存在共同的表型差异。这些发现有助于理解恐惧学习和潜在的生物机制，这些机制可能相互作用，从而在小鼠的恐惧和学习相关行为中产生个体差异。