Characterization of the amplificatory effect of norepinephrine in the acquisition of Pavlovian threat associations
Characterization of the amplificatory effect of norepinephrine in the acquisition of Pavlovian threat associations
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DOI：
10.1101/lm.044412.116
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发表时间：
2017-09-01
影响因子：
2
通讯作者：
LeDoux, Joseph E.
中科院分区：
文献类型：
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作者：
Diaz-Mataix, Lorenzo;Piper, Walter T.;LeDoux, Joseph E.
听觉威胁巴甫洛夫记忆的产生需要一个初始学习阶段，在这个阶段中，中性条件刺激（CS），如音调，与厌恶刺激（US），如电击配对。在这个阶段，CS获得了预测US发生的能力，从而引发条件性防御反应。去甲肾上腺素（NE）通过杏仁核中的β-肾上腺素能受体，通过促进CS-US关联的获得来增强威胁记忆，但这种作用的性质尚未被描述。在这里，我们表明，NE的释放，诱导的第一次条件反射试验的足电击，促进随后的增强学习。因此，阻断NE传递会破坏多次试验，但不会破坏一次试验条件反射。我们进一步发现，增加调节试验之间的时间消除了NE的放大效应。类似地，在条件反射之前立即在单独的上下文中传递无信号的电击足可以增强学习。这些结果有助于确定条件下，NE应该和不应该被期望改变威胁处理和填补一个重要的空白，在理解的神经过程相关的压力和焦虑症的病理生理。
The creation of auditory threat Pavlovian memory requires an initial learning stage in which a neutral conditioned stimulus (CS), such as a tone, is paired with an aversive one (US), such as a shock. In this phase, the CS acquires the capacity of predicting the occurrence of the US and therefore elicits conditioned defense responses. Norepinephrine (NE), through beta-adrenergic receptors in the amygdala, enhances threat memory by facilitating the acquisition of the CS-US association, but the nature of this effect has not been described. Here we show that NE release, induced by the footshock of the first conditioning trial, promotes the subsequent enhancement of learning. Consequently, blocking NE transmission disrupts multitrial but not one-trial conditioning. We further found that increasing the time between the conditioning trials eliminates the amplificatory effect of NE. Similarly, an unsignaled footshock delivered in a separate context immediately before conditioning can enhance learning. These results help define the conditions under which NE should and should not be expected to alter threat processing and fill an important gap in the understanding of the neural processes relevant to the pathophysiology of stress and anxiety disorders.