Department of Neurobiology, Faculty of Natural Sciences, University of Haifa, Haifa 31905, Israel.
Hippocampus. 2012 Mar;22(3):494-500. doi: 10.1002/hipo.20915. Epub 2011 Jan 14.
Extinction learning is associated with a decline of the conditioned fear response (CR). However, re-exposure to the unconditioned stimulus (US, shock) is associated with the return of the fear response. This study aimed to study the role of protein synthesis and actin rearrangement in the CA1 hippocampal subregion and the basolateral amygdala (BLA) in acquisition and reacquisition of contextual fear conditioning. To that end, we trained rats on contextual fear conditioning and extinction, and on the last extinction training session we reconditioned the animals by re-exposure to the US. Immediately after, rats were microinfused with the protein synthesis inhibitor anisomycin or the actin rearrangement inhibitor cytochalasin D into either the BLA or the CA1. The results of this study show differential involvement of anisomycin and cytochalasin D in the acquisition and reacquisition of contextual fear conditioning. Specifically, while the microinfusion of anisomycin into the BLA or the CA1 immediately after reconditioning of fear did not inhibit the return of fear, the microinfusion of cytochalsin D into either the BLA or the CA1 attenuated fear responses. Interestingly, the initial acquisition of contextual fear memory is dependent on intra-BLA and CA1 protein synthesis and cytoskeletal rearrangement, since the microinfusion of these drugs blocked the formation of long-term fear memory. The results suggest that the two processes of acquisition and reacquisition of fear are not identical and they engage different mechanisms.
灭绝学习与条件性恐惧反应 (CR) 的下降有关。然而，重新暴露于非条件刺激 (US，电击) 会导致恐惧反应的恢复。本研究旨在研究蛋白质合成和肌动蛋白重排在 CA1 海马亚区和外侧杏仁核 (BLA) 中在获得和重新获得情境性恐惧条件反射中的作用。为此，我们对大鼠进行了情境性恐惧条件反射和灭绝训练，并在最后一次灭绝训练中，通过重新暴露于 US 来重新训练动物。之后，立即将蛋白质合成抑制剂放线菌酮或肌动蛋白重排抑制剂细胞松弛素 D 微注入 BLA 或 CA1。这项研究的结果表明，放线菌酮和细胞松弛素 D 在获得和重新获得情境性恐惧条件反射中的作用不同。具体来说，虽然在重新训练恐惧后立即将放线菌酮微注入 BLA 或 CA1 中不会抑制恐惧的恢复，但将细胞松弛素 D 微注入 BLA 或 CA1 会减弱恐惧反应。有趣的是，情境性恐惧记忆的初始获得依赖于 BLA 和 CA1 内的蛋白质合成和细胞骨架重排，因为这些药物的微注入阻断了长期恐惧记忆的形成。结果表明，恐惧的获得和重新获得这两个过程并不相同，它们涉及不同的机制。
