Díaz-Mataix Lorenzo, Piper Walter T, Schiff Hillary C, Roberts Clark H, Campese Vincent D, Sears Robert M, LeDoux Joseph E
Center for Neural Science, New York University, New York, New York 10003, USA.
Emotional Brain Institute, Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA.
Learn Mem. 2017 Aug 16;24(9):432-439. doi: 10.1101/lm.044412.116. Print 2017 Sep.
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 β-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.
听觉威胁巴甫洛夫记忆的形成需要一个初始学习阶段，在此阶段，一个中性条件刺激（CS），如音调，与一个厌恶性刺激（US），如电击，配对。在这个阶段，CS获得了预测US发生的能力，因此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关联的形成来增强威胁记忆，但这种效应的本质尚未得到描述。在这里，我们表明，第一次条件试验的足部电击诱导的NE释放促进了随后学习的增强。因此，阻断NE传递会破坏多次试验但不会破坏单次试验的条件作用。我们进一步发现，增加条件试验之间的时间会消除NE的放大作用。同样，在条件作用之前立即在单独的环境中给予无信号的足部电击可以增强学习。这些结果有助于确定预期NE会改变或不会改变威胁处理的条件，并填补了在理解与应激和焦虑症病理生理学相关的神经过程方面的一个重要空白。
