Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning
Intra-amygdala blockade of the NR2B subunit of the NMDA receptor disrupts the acquisition but not the expression of fear conditioning
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DOI：
10.1523/jneurosci.21-17-06889.2001
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发表时间：
2001-09-01
影响因子：
5.3
通讯作者：
LeDoux, JE
中科院分区：
文献类型：
--
作者：
Rodrigues, SM;Schafe, GE;LeDoux, JE
杏仁核外侧核（LA）是巴甫洛夫恐惧条件反射神经回路的重要组成部分。尽管在训练前对LA和邻近区域的NMDA受体的阻断会破坏恐惧条件反射的获得，但在测试前的阻断也经常会破坏恐惧反应的表达。根据这种结果模式，不可能区分NMDA受体对可塑性的贡献和突触传递的作用。在过去的研究中，已经使用拮抗剂D， l -2-氨基-5-磷酸戊酸实现了NMDA的阻断，它阻断了整个异聚体受体复合物。本实验研究了使用选择性拮抗剂伊芬普罗地尔选择性阻断LA中NMDA受体NR2B亚基的作用。训练前全身注射伊芬普罗地尔导致听觉和情境恐惧条件反射习得的剂量依赖性损伤，而测试前注射则没有效果。杏仁核内注入伊芬普罗地尔也反映了这些结果，此外，研究还表明，这种效果是由于恐惧学习的中断，而不是记忆巩固的中断。因此，LA中的NMDA受体参与恐惧条件反射，NR2B亚基似乎对潜在的可塑性做出了独特的贡献。
The lateral nucleus of the amygdala (LA) is an essential component of the neural circuitry underlying Pavlovian fear conditioning. Although blockade of NMDA receptors in LA and adjacent areas before training disrupts the acquisition of fear conditioning, blockade before testing also often disrupts the expression of fear responses. With this pattern of results, it is not possible to distinguish a contribution of NMDA receptors to plasticity from a role in synaptic transmission. In past studies, NMDA blockade has been achieved using the antagonist D, L-2-amino-5-phosphovalerate, which blocks the entire heteromeric receptor complex. The present experiments examined the effects of selective blockade of the NR2B subunit of the NMDA receptor in LA using the selective antagonist ifenprodil. Systemic injections of ifenprodil before training led to a dose-dependent impairment in the acquisition of auditory and contextual fear conditioning, whereas injections before testing had no effect. Intra-amygdala infusions of ifenprodil mirrored these results and, in addition, showed that the effects are attributable to a disruption of fear learning rather than a disruption of memory consolidation. NMDA receptors in LA are thus involved in fear conditioning, and the NR2B subunit appears to make unique contributions to the underlying plasticity.