Schafe G E, LeDoux J E
W. M. Keck Foundation Laboratory of Neurobiology, Center for Neural Science, New York University, New York, New York 10003, USA.
J Neurosci. 2000 Sep 15;20(18):RC96. doi: 10.1523/JNEUROSCI.20-18-j0003.2000.
Previous studies have shown that long-term potentiation (LTP) can be induced in the lateral nucleus of the amygdala (LA) after stimulation of central auditory pathways and that auditory fear conditioning modifies neural activity in the LA in a manner similar to LTP. The present experiments examined whether intra-LA administration of inhibitors of protein synthesis or protein kinase A (PKA) activity, treatments that block LTP in hippocampus, interfere with memory consolidation of fear conditioning. In the first series of experiments, rats received a single conditioning trial followed immediately by intra-LA infusions of anisomycin (a protein synthesis inhibitor) or Rp-cAMPS (an inhibitor of PKA activity) and were tested 24 hr later. Results indicated that immediate post-training infusion of either drug dose-dependently impaired fear memory retention, whereas infusions 6 hr after conditioning had no effect. Additional experiments showed that anisomycin and Rp-cAMPS interfered with long-term memory (LTM), but not short-term memory (STM), of fear and that the effect on LTM was specific to memory consolidation processes rather than to deficits in sensory or performance processes. Findings suggest that the LA is essential for memory consolidation of auditory fear conditioning and that this process is PKA and protein-synthesis dependent.
先前的研究表明，刺激中枢听觉通路后，杏仁核外侧核（LA）可诱导长时程增强（LTP），且听觉恐惧条件反射以类似于LTP的方式改变LA中的神经活动。本实验研究了在LA内注射蛋白质合成抑制剂或蛋白激酶A（PKA）活性抑制剂（这些处理可阻断海马体中的LTP）是否会干扰恐惧条件反射的记忆巩固。在第一组实验中，大鼠接受单次条件反射试验，随后立即在LA内注射茴香霉素（一种蛋白质合成抑制剂）或Rp-cAMPS（一种PKA活性抑制剂），并在24小时后进行测试。结果表明，训练后立即注射这两种药物中的任何一种都会剂量依赖性地损害恐惧记忆的保持，而在条件反射后6小时注射则没有效果。额外的实验表明，茴香霉素和Rp-cAMPS会干扰恐惧的长期记忆（LTM），但不会干扰短期记忆（STM），并且对LTM的影响特定于记忆巩固过程，而非感觉或行为过程中的缺陷。研究结果表明，LA对于听觉恐惧条件反射的记忆巩固至关重要，并且这一过程依赖于PKA和蛋白质合成。
