Redundant catecholamine signaling consolidates fear memory via phospholipase C.
Redundant catecholamine signaling consolidates fear memory via phospholipase C.
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DOI：
10.1523/jneurosci.5231-11.2012
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发表时间：
2012-02-08
期刊：
影响因子：
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通讯作者：
Thomas SA
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文献类型：
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作者：
Ouyang M;Young MB;Lestini MM;Schutsky K;Thomas SA
唤起情感的经历的记忆通常是生动和持久的。创伤后应激障碍（PTSD）中反复出现的创伤性记忆就是一个极端的例子。在情绪唤醒过程中释放的应激反应神经递质被认为可以增强恐惧记忆的巩固。这些递质可能包括去甲肾上腺素和肾上腺素（NE/E），因为在训练后不久刺激β-肾上腺素能受体可以增强记忆巩固。然而，缺乏NE/E的小鼠正常获得并巩固恐惧记忆。在这里，我们在小鼠和大鼠中使用药理学和遗传操作表明，NE/E对于经典恐惧记忆巩固不是必需的，因为β2-肾上腺素能受体的信号传导与D5-多巴胺能受体的多巴胺信号传导是多余的。由这些受体刺激以促进固结的细胞内信号传导利用不同的G蛋白来冗余地激活磷脂酶C。这些结果支持了最近的证据，表明在创伤后不久单独阻断β-肾上腺素能受体可能不足以预防PTSD。
Memories for emotionally arousing experiences are typically vivid and persistent. The recurrent, intrusive memories of traumatic events in post-traumatic stress disorder (PTSD) are an extreme example. Stress-responsive neurotransmitters released during emotional arousal are proposed to enhance the consolidation of fear memory. These transmitters may include norepinephrine and epinephrine (NE/E) because stimulating β-adrenergic receptors shortly after training can enhance memory consolidation. However, mice lacking NE/E acquire and consolidate fear memory normally. Here we show using pharmacologic and genetic manipulations in mice and rats that NE/E are not essential for Classical fear memory consolidation because signaling by the β2-adrenergic receptor is redundant with signaling by dopamine at the D5-dopaminergic receptor. The intracellular signaling that is stimulated by these receptors to promote consolidation utilizes distinct G proteins to redundantly activate phospholipase C. The results support recent evidence indicating that blocking β-adrenergic receptors alone shortly after trauma may not be sufficient to prevent PTSD.