Noradrenergic Modulation of Fear Conditioning and Extinction.
Noradrenergic Modulation of Fear Conditioning and Extinction.
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DOI：
10.3389/fnbeh.2018.00043
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发表时间：
2018
影响因子：
3
通讯作者：
Maren S
中科院分区：
文献类型：
--
作者：
Giustino TF;Maren S
蓝斑去甲肾上腺素（LC-NE）系统在学习和记忆中起着广泛的作用。在此，我们开始以LC-NE系统的概述开始。然后，我们考虑如何直接和间接的操作LC-NE系统影响线索和上下文厌恶的学习和记忆。我们建议NE动态调节巴甫洛夫条件反射和消退，促进或损害学习厌恶过程下不同水平的行为唤醒。我们建议在高水平的压力下（例如，在恐惧条件反射期间/之后不久），蓝斑（LC）通过增强杏仁核功能同时钝化前额功能来促进线索恐惧学习。在低水平的唤醒下，LC促进PFC功能，以促进杏仁核的下游抑制，并促进线索恐惧的消退。因此，LC-NE对内侧前额叶皮层（mPFC）的作用可以用倒U函数来描述，这样它就可以根据唤醒状态来增强或阻碍学习。此外，LC-NE似乎对情境恐惧记忆的获得、巩固和消退特别重要。这可能是由于编码上下文信息的海马（HPC）中的密集肾上腺素受体表达以及NE调节长时程增强（LTP）的能力。此外，最近的工作表明，LC-NE功能的多样性，在厌恶性学习和记忆介导的LC神经元的功能异质性群体，由他们的投影目标定义。因此，LC-NE在学习和记忆中的功能是由伴随各种行为唤醒状态的投射特异性神经调节决定的。
The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning and memory. Here we begin with an overview of the LC-NE system. We then consider how both direct and indirect manipulations of the LC-NE system affect cued and contextual aversive learning and memory. We propose that NE dynamically modulates Pavlovian conditioning and extinction, either promoting or impairing learning aversive processes under different levels of behavioral arousal. We suggest that under high levels of stress (e.g., during/soon after fear conditioning) the locus coeruleus (LC) promotes cued fear learning by enhancing amygdala function while simultaneously blunting prefrontal function. Under low levels of arousal, the LC promotes PFC function to promote downstream inhibition of the amygdala and foster the extinction of cued fear. Thus, LC-NE action on the medial prefrontal cortex (mPFC) might be described by an inverted-U function such that it can either enhance or hinder learning depending on arousal states. In addition, LC-NE seems to be particularly important for the acquisition, consolidation and extinction of contextual fear memories. This may be due to dense adrenoceptor expression in the hippocampus (HPC) which encodes contextual information, and the ability of NE to regulate long-term potentiation (LTP). Moreover, recent work reveals that the diversity of LC-NE functions in aversive learning and memory are mediated by functionally heterogeneous populations of LC neurons that are defined by their projection targets. Hence, LC-NE function in learning and memory is determined by projection-specific neuromodulation that accompanies various states of behavioral arousal.
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