Emotion enhances learning via norepinephrine regulation of AMPA-Receptor trafficking
Emotion enhances learning via norepinephrine regulation of AMPA-Receptor trafficking
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DOI：
10.1016/j.cell.2007.09.017
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发表时间：
2007-10-05
期刊：
影响因子：
64.5
通讯作者：
Malinow, Roberto
中科院分区：
文献类型：
--
作者：
Hu, Hailan;Real, Eleonore;Malinow, Roberto
情绪增强了我们对甚至是微不足道的事件形成生动记忆的能力。去甲肾上腺素（NE）是情绪唤醒时释放的一种神经调质，在记忆的情绪调节中起着重要作用。然而，潜在的分子机制仍然难以捉摸。为此，我们研究了NE在上下文记忆形成中的作用，以及在长时程增强（LTP）过程中含GluR 1的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体的突触传递中的作用，LTP是学习的候选突触机制。我们发现，NE，以及情绪压力，诱导磷酸化的GluR 1在其突触传递的关键网站。这些位点的磷酸化是必要的，足以降低LTP期间GluR 1突触掺入的阈值。在行为实验中，NE可以降低野生型小鼠的记忆形成阈值，但在GluR 1磷酸化位点携带突变的小鼠中则不然。我们的研究结果表明，NE驱动的GluR 1磷酸化促进了含GluR 1的AMPAR的突触传递，降低了LTP的阈值，从而为情绪如何增强学习和记忆提供了分子机制。
Emotion enhances our ability to form vivid memories of even trivial events. Norepinephrine ( NE), a neuromodulator released during emotional arousal, plays a central role in the emotional regulation of memory. However, the underlying molecular mechanism remains elusive. Toward this aim, we have examined the role of NE in contextual memory formation and in the synaptic delivery of GluR1-containing alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid ( AMPA)-type glutamate receptors during longterm potentiation (LTP), a candidate synaptic mechanism for learning. We found that NE, as well as emotional stress, induces phosphorylation of GluR1 at sites critical for its synaptic delivery. Phosphorylation at these sites is necessary and sufficient to lower the threshold for GluR1 synaptic incorporation during LTP. In behavioral experiments, NE can lower the threshold for memory formation in wild-type mice but not in mice carrying mutations in the GluR1 phosphorylation sites. Our results indicate that NE-driven phosphorylation of GluR1 facilitates the synaptic delivery of GluR1-containing AMPARs, lowering the threshold for LTP, thereby providing a molecular mechanism for how emotion enhances learning and memory.