Maren Stephen, Ferrario Carrie R, Corcoran Kevin A, Desmond Timothy J, Frey Kirk A
Department of Psychology, University of Michigan, 525 E. University Avenue, Ann Arbor, MI 48109-1109, USA.
Eur J Neurosci. 2003 Dec;18(11):3080-8. doi: 10.1111/j.1460-9568.2003.03063.x.
The amygdala is an essential neural substrate for Pavlovian fear conditioning. Nevertheless, long-term synaptic plasticity in amygdaloid afferents, such as the auditory thalamus, may contribute to the formation of fear memories. We therefore compared the influence of protein synthesis inhibition in the amygdala and the auditory thalamus on the consolidation of Pavlovian fear conditioning in Long-Evans rats. Rats received three tone-footshock trials in a novel conditioning chamber. Immediately after fear conditioning, rats were infused intra-cranially with the protein synthesis inhibitor, anisomycin. Conditional fear to the tone and conditioning context was assessed by measuring freezing behaviour in separate retention tests conducted at least 24 h following conditioning. Post-training infusion of anisomycin into the amygdala impaired conditional freezing to both the auditory and contextual stimuli associated with footshock. In contrast, intra-thalamic infusions of anisomycin or a broad-spectrum protein kinase inhibitor [1-(5'-isoquinolinesulphonyl)-2-methylpiperazine, H7] did not affect conditional freezing during the retention tests. Pre-training intra-thalamic infusion of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (APV), which blocks synaptic transmission in the auditory thalamus, produced a selective deficit in the acquisition of auditory fear conditioning. Autoradiographic assays of cerebral [14C]-leucine incorporation revealed similar levels of protein synthesis inhibition in the amygdala and thalamus following intra-cranial anisomycin infusions. These results reveal that the establishment of long-term fear memories requires protein synthesis in the amygdala, but not the thalamus, after auditory fear conditioning. Forms of synaptic plasticity that depend on protein synthesis, such as long-term potentiation, are likely candidates for the encoding and long-term storage of fear memories in the amygdala.
杏仁核是巴甫洛夫式恐惧条件反射的重要神经基础。然而，杏仁核传入神经（如听觉丘脑）中的长期突触可塑性可能有助于恐惧记忆的形成。因此，我们比较了杏仁核和听觉丘脑中蛋白质合成抑制对长 Evans 大鼠巴甫洛夫式恐惧条件反射巩固的影响。大鼠在一个新的条件反射箱中接受三次音调-足部电击试验。恐惧条件反射后，立即向大鼠颅内注射蛋白质合成抑制剂茴香霉素。通过在条件反射后至少 24 小时进行的单独保留试验中测量僵住行为，评估对音调的条件性恐惧和条件反射情境。训练后向杏仁核注射茴香霉素会损害对与足部电击相关的听觉和情境刺激的条件性僵住。相比之下，向丘脑内注射茴香霉素或一种广谱蛋白激酶抑制剂[1-(5'-异喹啉磺酰基)-2-甲基哌嗪，H7]在保留试验期间不影响条件性僵住。训练前向丘脑内注射 NMDA 受体拮抗剂 2-氨基-5-膦酰戊酸（APV），它会阻断听觉丘脑中的突触传递，在听觉恐惧条件反射的习得中产生选择性缺陷。对大脑[14C]-亮氨酸掺入的放射自显影分析显示，颅内注射茴香霉素后，杏仁核和丘脑中蛋白质合成抑制水平相似。这些结果表明，听觉恐惧条件反射后长期恐惧记忆的建立需要杏仁核而非丘脑中的蛋白质合成。依赖蛋白质合成的突触可塑性形式，如长时程增强，可能是杏仁核中恐惧记忆编码和长期存储的候选机制。
