Auditory fear conditioning in rats is a widely used method to study learning, memory, and emotional responding. Despite procedural standardizations and optimizations, there is substantial interindividual variability in fear expression during test, notably in terms of fear expressed toward the testing context alone. To better understand which factors could explain this variation between subjects, we here explored whether behavior during training and expression of AMPA receptors (AMPARs) after long-term memory formation in the amygdala could predict freezing during test. We studied outbred male rats and found strong variation in fear generalization to a different context. Hierarchical clustering of these data identified two distinct groups of subjects that independently correlated with a specific pattern of behaviors expressed during initial training (i.e., rearing and freezing). The extent of fear generalization correlated positively with postsynaptic expression of GluA1-containing AMPA receptors in the basolateral nucleus of the amygdala. Our data thus identify candidate behavioral and molecular predictors of fear generalization that may inform our understanding of some anxiety-related disorders, such as posttraumatic stress disorder (PTSD), that are characterized by overgeneralized fear.

中文翻译：

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基底外侧杏仁核中 AMPA 受体在听觉恐惧调节过程中的特定行为和突触后表达预测雄性大鼠恐惧泛化的个体差异

大鼠听觉恐惧条件反射是一种广泛用于研究学习、记忆和情绪反应的方法。尽管程序标准化和优化，但在测试期间恐惧表达存在很大的个体差异，特别是在仅针对测试环境表达的恐惧方面。为了更好地了解哪些因素可以解释受试者之间的这种差异，我们在这里探讨了训练期间的行为和杏仁核中长期记忆形成后 AMPA 受体 (AMPAR) 的表达是否可以预测测试期间的冻结。我们研究了近亲交配的雄性大鼠，发现不同环境下的恐惧泛化存在很大差异。这些数据的层次聚类确定了两组不同的受试者，这两组受试者独立地与初始训练期间表达的特定行为模式相关（即，饲养和冻结）。恐惧泛化的程度与杏仁核基底外侧核中含有 GluA1 的 AMPA 受体的突触后表达呈正相关。因此，我们的数据确定了恐惧泛化的候选行为和分子预测因子，这些因子可能有助于我们理解一些与焦虑相关的疾病，例如创伤后应激障碍 (PTSD)，其特征是过度泛化恐惧。