Biology Department and Neuroscience and Behavior Program, Barnard College, New York, New York 10027, USA.
J Neurosci. 2012 Sep 26;32(39):13582-6. doi: 10.1523/JNEUROSCI.0809-12.2012.
L-type voltage-gated calcium channels (L-VGCCs) in the basolateral nucleus of the amygdala (BLA) are necessary for long-term memory of fear conditioning, where they are thought to drive the activation of protein kinases and to initiate gene transcription. However, their role in fear extinction learning is unclear given that systemic injections of VGCC antagonists induce a protracted stress response. Here we tested the effects of local infusions of the L-VGCC antagonists verapamil and nifedipine on both within-session extinction and fear extinction consolidation. Intra-BLA infusions of verapamil or nifedipine did not affect the expression of fear conditioning or the amount of within-session extinction but impaired extinction memory when rats were tested 24 h later drug-free. L-VGCC antagonists also prevented the increase in phosphorylated mitogen-activated protein kinase (MAPK) normally seen in the BLA following extinction learning. These results suggest that activation of L-VGCCs in the BLA at the time of fear extinction learning is necessary for the long-term retention of fear extinction via the MAPK pathway.
杏仁基底核（BLA）中的 L 型电压门控钙通道（L-VGCC）对于恐惧条件反射的长期记忆是必要的，它们被认为可以驱动蛋白激酶的激活并启动基因转录。然而，由于全身注射 VGCC 拮抗剂会引起持久的应激反应，因此它们在恐惧消退学习中的作用尚不清楚。在这里，我们测试了 L-VGCC 拮抗剂维拉帕米和硝苯地平局部输注对单次消退和恐惧消退巩固的影响。BLA 内注射维拉帕米或硝苯地平不会影响恐惧条件反射的表达或单次消退的量，但在无药物测试 24 小时后会损害消退记忆。L-VGCC 拮抗剂还阻止了在消退学习后 BLA 中通常观察到的磷酸化丝裂原激活蛋白激酶（MAPK）的增加。这些结果表明，在恐惧消退学习时激活 BLA 中的 L-VGCC 通过 MAPK 途径对于恐惧消退的长期保留是必要的。
