Selective neurotoxic lesions of basolateral and central nuclei of the amygdala produce differential effects on fear conditioning
Selective neurotoxic lesions of basolateral and central nuclei of the amygdala produce differential effects on fear conditioning
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DOI：
10.1523/jneurosci.1644-04.2004
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发表时间：
2004-09-01
影响因子：
5.3
通讯作者：
Kim, JJ
中科院分区：
文献类型：
--
作者：
Koo, JW;Han, JS;Kim, JJ
在恐惧调节文献中，通常假设基底外侧杏仁核复合体（BLA）（外侧核和基底核）中的神经元支持条件性恐惧记忆的形成，并投射到中央核（CeA）中的神经元以表达条件性恐惧反应。根据这种串行处理-传输观点，BLA 或 CeA 的损伤会相应地破坏各种条件性恐惧反应的表达。在本研究中，我们通过同时评估冷冻和 22 kHz 超声波发声 (USV) 作为大鼠恐惧的依赖性测量，进一步研究了 BLA 和 CeA 在恐惧调节中的作用。选择性神经毒素，BLA 的 NMDA 和 CeA 的鹅膏菌酸，被用来破坏内在神经元（通过硫堇染料和 NeuN（神经元核）抗体染色证明）而不损坏通道纤维（通过髓磷脂染色证实）。在 10 次音调足部电击配对训练期间，BLA 损伤动物的电击后冻结和 USV 反应显着受损，而 CeA 损伤动物仅表现出轻微缺陷。同样，训练后 24 小时评估的条件性恐惧反应在 BLA 损伤的动物中严重减少，但在 CeA 损伤的动物中则没有。与 CeA 的鹅膏菌损伤相比，CeA 的小电解损伤强烈影响电击后、条件冷冻和 USV。总之，这些结果并不支持目前所支持的恐惧条件反射的 BLA-to-CeA 串行处理传输观点。相反，条件性恐惧的表达似乎主要涉及 BLA 投射，通过 CeA 到达下游恐惧反应结构。
In the fear conditioning literature, it is generally hypothesized that neurons in the basolateral amygdalar complex (BLA) (lateral and basal nuclei) support the formation of conditioned fear memory and project to neurons in the central nucleus (CeA) for the expression of conditioned fear responses. According to this serial processing-transmission view, damage to either BLA or CeA would comparably disrupt the expression of a variety of conditioned fear responses. In the present study, we further investigated the roles of BLA and CeA in fear conditioning by concurrently assessing freezing and 22 kHz ultrasonic vocalization (USV) as dependent measures of fear in rats. Selective neurotoxins, NMDA for the BLA and ibotenic acid for the CeA, were used to destroy intrinsic neurons [evidenced by thionin dye and NeuN (neuronal nuclei) antibody stainings] without damaging the fibers of passage (confirmed by myelin staining). During the 10 tone-footshock paired training, postshock freezing and USV responses were significantly impaired in BLA-lesioned animals, whereas CeA-lesioned animals exhibited only mild deficits. Similarly, conditioned fear responses assessed 24 hr after training were severely reduced in BLA-lesioned animals but not in CeA-lesioned animals. In contrast to ibotenic lesions of the CeA, small electrolytic lesions of the CeA strongly affected both postshock and conditioned freezing and USV. Together, these results do not support the currently espoused BLA-to-CeA serial processing-transmission view of fear conditioning. Instead, the expression of conditioned fear appears to primarily involve BLA projections that course through the CeA en route to downstream fear response structures.