Memory consolidation of auditory Pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala
Memory consolidation of auditory Pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala
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DOI：
10.1523/jneurosci.20-18-j0003.2000
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发表时间：
2000-09-15
影响因子：
5.3
通讯作者：
LeDoux, JE
中科院分区：
文献类型：
--
作者：
Schafe, GE;LeDoux, JE
以往的研究表明，长时程增强（LTP）可以在杏仁核（LA）的中央听觉通路的刺激后，听觉恐惧条件化修改在LA的神经活动类似的方式。本实验研究是否内LA管理的蛋白质合成或蛋白激酶A（PKA）活性的抑制剂，治疗，阻止LTP在海马，干扰记忆巩固恐惧条件反射。在第一系列实验中，大鼠接受单次条件试验，随后立即进行茴香霉素（蛋白质合成抑制剂）或Rp-cAMPS（PKA活性抑制剂）的LA内输注，并在24小时后进行测试。结果表明，训练后立即输注任何一种药物剂量依赖性损害恐惧记忆的保留，而输注后6小时条件反射没有影响。其他实验表明，茴香霉素和Rp-cAMPS干扰恐惧的长期记忆（LTM），但不是短期记忆（STM），并且对LTM的影响是特定于记忆巩固过程，而不是感觉或表现过程的缺陷。研究结果表明，LA是必不可少的听觉恐惧条件反射的记忆巩固，这一过程是PKA和蛋白质合成依赖。
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.