Considerable work demonstrates that Pavlovian fear conditioning depends on N-methyl-D-aspartate (NMDA) receptor-dependent plasticity within the amygdala. In addition, the bed nucleus of the stria terminalis (BNST) has also been implicated in fear conditioning, particularly in the expression of fear to poor predictors of threat. We recently found that the expression of backward (BW) fear conditioning, in which an auditory conditioned stimulus (CS) follows a footshock unconditioned stimulus (US), requires the BNST; the expression of forward (FW) fear conditioning was not disrupted by BNST inactivation. However, whether NMDA receptors within the BNST contribute to the acquisition of fear conditioning is unknown. Moreover, the central nucleus of the amygdala (CeA), which has extensive connections with the BNST, is critically involved in FW conditioning, however whether it participates in BW conditioning has not been explored. Here we test the specific hypothesis that the CeA and the BNST mediate the acquisition of FW and BW fear conditioning, respectively. Adult female and male rats were randomly assigned to receive bilateral infusions of the NMDA receptor antagonist, D,L-2-amino-5-phosphonovalerate (APV), into the CeA or BNST prior to FW or BW fear conditioning. We found that intra-CeA APV impaired the acquisition of both FW and BW conditioning, whereas intra-BNST APV produced selective deficits in BW conditioning. Moreover, APV in the BNST significantly reduced contextual freezing, whereas CeA NMDA receptor antagonism impeded early but not long-lasting contextual fear. Collectively, these data reveal that CeA and BNST NMDA receptors have unique roles in fear conditioning.

相当多的工作表明巴甫洛夫恐惧条件依赖于N杏仁核内的-甲基-D-天冬氨酸（NMDA）受体依赖性可塑性。此外，纹状体的床核 (BNST) 也与恐惧条件反射有关，特别是在对威胁的不良预测因子的恐惧表达中。我们最近发现向后 (BW) 恐惧条件反射的表达，其中听觉条件刺激 (CS) 跟随足震无条件刺激 (US)，需要 BNST；BNST 失活不会干扰前向 (FW) 恐惧条件反射的表达。然而，BNST 内的 NMDA 受体是否有助于获得恐惧条件是未知的。此外，与 BNST 有广泛联系的杏仁核中央核 (CeA) 与 FW 条件反射密切相关，但尚未探讨它是否参与 BW 条件反射。在这里，我们测试了特定假设，即 CeA 和 BNST 分别介导 FW 和 BW 恐惧条件反射的获得。在 FW 或 BW 恐惧条件反射之前，成年雌性和雄性大鼠被随机分配接受 NMDA 受体拮抗剂 D,L-2-amino-5-phosphonovalerate (APV) 双侧输注到 CeA 或 BNST。我们发现，CeA 内 APV 削弱了 FW 和 BW 调节的获得，而 BNST 内 APV 在 BW 调节中产生了选择性缺陷。此外，BNST 中的 APV 显着减少了上下文冻结，而 CeA NMDA 受体拮抗作用阻止了早期但不是持久的上下文恐惧。总的来说，这些数据表明 CeA 和 BNST NMDA 受体在恐惧条件反射中具有独特的作用。