Neural Structures Mediating Expression and Extinction of Platform-Mediated Avoidance
Neural Structures Mediating Expression and Extinction of Platform-Mediated Avoidance
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DOI：
10.1523/jneurosci.0191-14.2014
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发表时间：
2014-07-16
影响因子：
5.3
通讯作者：
Quirk, Gregory J.
中科院分区：
文献类型：
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作者：
Bravo-Rivera, Christian;Roman-Ortiz, Ciorana;Quirk, Gregory J.
个人对环境威胁既有被动的防御反应，也有主动的防御反应。关于被动防御反应(例如，冻结)的神经回路我们知道得很多，但对主动防御反应(例如，回避)的底物却知之甚少。我们开发了一个主动回避任务，在这个任务中，老鼠通过踏上附近的平台来学习避免声音信号的脚击。这项任务的一个优点是减少了可能干扰回避的冻结，从而便于比较操纵对回避和冻结的影响。在10d的回避训练后，大鼠注入蝇草酚，以药物灭活大鼠的前额叶皮质(PL)、下缘皮质(IL)、腹侧纹状体(VS)或基底外侧杏仁核(BLA)。灭活PL、VS或BLA都会削弱回避表达，但这些区域在冰冻方面有所不同。失活的BLA减少了冰冻，与失去音调-电击联系一致，而失活的VS增加了冰冻，与丧失回避记忆一致。PL的灭活对冷冻无影响。IL的失活不会损害回避表达，但会损害回避消退。我们的发现表明，主动回避是由前额-纹状体回路介导的，在患有创伤相关障碍的个体中，这可能是过度活跃的。
Individuals use both passive and active defensive responses to environmental threats. Much is known about the neural circuits of passive defensive responses (e. g., freezing), but less is known about the substrates of active defensive responses (e. g., avoidance). We developed an active avoidance task in which rats learn to avoid a tone-signaled footshock by stepping onto a nearby platform. An advantage of this task is that freezing, which can interfere with avoidance, is reduced, thereby facilitating comparison of the effects of manipulations on avoidance versus freezing. After 10 d of avoidance training, rats were infused with muscimol to pharmacologically inactivate the prelimbic cortex (PL), infralimbic cortex (IL), ventral striatum (VS), or basolateral amygdala (BLA). Inactivating PL, VS, or BLA all impaired avoidance expression, but these areas differed with respect to freezing. Inactivating BLA decreased freezing consistent with loss of the tone-shock association, whereas inactivation of VS increased freezing consistent with loss of avoidance memory. Inactivation of PL had no effect on freezing. Inactivation of IL did not impair avoidance expression but did impair avoidance extinction. Our findings suggest that active avoidance is mediated by prefrontal-striatal circuits, which may be overactive in individuals suffering from trauma-related disorders.