Leake Jessica, Shvetcov Artur, Clemens Kelly J, Kershaw Kelly, Westbrook R Frederick, Holmes Nathan M
School of Psychology, University of New South Wales, Sydney, New South Wales 2052, Australia.
Department of Psychological Medicine, Sydney Children's Hospitals Network, Sydney, New South Wales 2145, Australia.
J Neurosci. 2025 Jun 18;45(25):e1087242025. doi: 10.1523/JNEUROSCI.1087-24.2025.
Rats quickly learn to fear a stimulus (e.g., a light) that signals brief but painful footshock. The consolidation of this first-order conditioned fear requires transcription and translation of specific genes in the basolateral amygdala complex (BLA). Rats also learn to fear the associates of first-order conditioned stimuli, such as a sound paired with the already-conditioned light. The consolidation of this second-order conditioned fear also requires transcriptional processes in the BLA, but unlike consolidation of first-order fear, it is unaffected by BLA infusions of the protein synthesis inhibitor, cycloheximide. Accordingly, this study sought to identify genes/pathways that regulate second-order conditioned fear in male rats. It focused on the involvement of immediate early genes, as these can be transcribed in the presence of protein synthesis inhibitors. In Experiment 1, we used a principal components analysis of PCR data and found that second-order fear conditioning involves region- and time-specific changes in a network of genes including the immediate early genes and In Experiments 2-4, we used BLA infusions of antisense oligonucleotides and found that is required for consolidation of both first- and second-order fears but is not required for reconsolidation of either and is not required for consolidation of first-order fear but is required for acquisition of second-order fear and reconsolidation of both types of fear. Hence, and regulate different aspects of first- and second-order fear conditioning in the BLA. These findings are discussed with respect to novel forms of information processing in the mammalian brain.
大鼠能迅速学会对一种刺激（如灯光）产生恐惧，这种刺激预示着短暂但会引起疼痛的足部电击。这种一阶条件性恐惧的巩固需要基底外侧杏仁核复合体（BLA）中特定基因的转录和翻译。大鼠还学会对一阶条件性刺激的关联物产生恐惧，比如与已经形成条件的灯光配对的声音。这种二阶条件性恐惧的巩固同样需要BLA中的转录过程，但与一阶恐惧的巩固不同的是，它不受向BLA注射蛋白质合成抑制剂环己酰亚胺的影响。因此，本研究旨在确定调节雄性大鼠二阶条件性恐惧的基因/通路。研究聚焦于即刻早期基因的参与情况，因为这些基因能在存在蛋白质合成抑制剂的情况下进行转录。在实验1中，我们对聚合酶链反应（PCR）数据进行主成分分析，发现二阶恐惧条件作用涉及一个基因网络中区域和时间特异性的变化，这些基因包括即刻早期基因 和 。在实验2 - 4中，我们向BLA注射反义寡核苷酸，发现 对于一阶和二阶恐惧的巩固都是必需的，但对于二者的重新巩固都不是必需的； 对于一阶恐惧的巩固不是必需的，但对于二阶恐惧的习得和两种类型恐惧的重新巩固是必需的。因此， 和 在BLA中调节一阶和二阶恐惧条件作用的不同方面。我们将结合哺乳动物大脑中信息处理的新形式来讨论这些发现。
