Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction
Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction
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DOI：
10.1523/jneurosci.3248-07.2008
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发表时间：
2008-01-09
影响因子：
5.3
通讯作者：
Quirk, Gregory J.
中科院分区：
文献类型：
--
作者：
Mueller, Devin;Porter, James T.;Quirk, Gregory J.
情绪唤起加强记忆。这在厌恶条件反射中最为明显，其中与压力相关的神经递质去甲肾上腺素（NE）增强了感觉刺激和恐惧诱发事件之间的联系。与条件反射相比，消失减少了恐惧反应，并被认为形成了新的记忆。然而，NE对于灭绝学习是否必要尚不清楚。先前的研究表明，边缘下前额叶皮层（IL）是一个消失巩固的部位。在这里，我们发现在灭绝训练之前阻断IL中的去甲肾上腺素能β受体会损害第二天对灭绝的检索，这与减弱的灭绝记忆一致。我们进一步发现β受体激活的后遗症，包括蛋白激酶A (PKA)， IL中的基因转录和翻译，是灭绝所必需的。为了确定这个级联的激活是否调节IL的兴奋性，我们测量了IL锥体神经元对注入电流的反应。NE以β受体和pka依赖的方式增加IL神经元的兴奋性。我们认为，在恐惧消退过程中，IL中释放的NE激活了pka介导的分子级联反应，从而增强了消退记忆。因此，由条件性恐惧引起的情绪唤醒矛盾地促进了随后恐惧的消除，从而确保了行为的灵活性。
Emotional arousal strengthens memory. This is most apparent in aversive conditioning, in which the stress-related neurotransmitter norepinephrine ( NE) enhances associations between sensory stimuli and fear-inducing events. In contrast to conditioning, extinction decreases fear responses, and is thought to form a new memory. It is not known, however, whether NE is necessary for extinction learning. Previous work has shown that the infralimbic prefrontal cortex (IL) is a site of extinction consolidation. Here, we show that blocking noradrenergic beta-receptors in IL before extinction training impaired retrieval of extinction the following day, consistent with a weakened extinction memory. We further found that the sequelae of beta-receptor activation, including protein kinase A (PKA), gene transcription and translation in IL, are necessary for extinction. To determine whether activation of this cascade modulates IL excitability, we measured the response of IL pyramidal neurons to injected current. NE increased the excitability of IL neurons in a beta-receptor- and PKA-dependent manner. We suggest that NE released in IL during fear extinction activates a PKA-mediated molecular cascade that strengthens extinction memory. Thus, emotional arousal evoked by conditioned fear paradoxically promotes the subsequent extinction of that fear, thereby ensuring behavioral flexibility.