Calcium-permeable AMPA receptor dynamics mediate fear memory erasure.

Calcium-permeable AMPA receptor dynamics mediate fear memory erasure.
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DOI:
10.1126/science.1195298
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发表时间:
2010-11-19
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Huganir RL
Huganir RL
中科院分区:
其他
文献类型:
--
作者:
Clem RL;Huganir RL

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创伤性恐惧记忆可以通过人类的行为疗法或啮齿动物模型的灭绝训练来抑制,但容易复发。然而,在某些情况下,这些治疗会对行为产生永久性的影响,这表明情绪记忆已经被擦除。这种不同结果的神经基础尚不清楚。我们发现,一个核心组成部分的干扰引起的擦除是突触的钙渗透性α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体(AMPAR)在外侧杏仁核的清除。这种形式的可塑性的瞬时上调,其中涉及AMPA受体的谷氨酸受体1亚基的磷酸化,定义了一个时间窗口,其中恐惧记忆可以被行为经验降解。这些结果揭示了消除恐惧和近期记忆相对不稳定的分子机制。
Traumatic fear memories can be inhibited by behavioral therapy for humans, or by extinction training in rodent models, but are prone to recur. Under some conditions, however, these treatments generate a permanent effect on behavior, which suggests that emotional memory erasure has occurred. The neural basis for such disparate outcomes is unknown. We found that a central component of extinction-induced erasure is the synaptic removal of calcium-permeable α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs) in the lateral amygdala. A transient up-regulation of this form of plasticity, which involves phosphorylation of the glutamate receptor 1 subunit of the AMPA receptor, defines a temporal window in which fear memory can be degraded by behavioral experience. These results reveal a molecular mechanism for fear erasure and the relative instability of recent memory.
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