Double dissociation of the requirement for GluN2B- and GluN2A-containing NMDA receptors in the destabilization and restabilization of a reconsolidating memory.
Double dissociation of the requirement for GluN2B- and GluN2A-containing NMDA receptors in the destabilization and restabilization of a reconsolidating memory.
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DOI：
10.1523/jneurosci.3273-12.2013
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发表时间：
2013-01-16
期刊：
影响因子：
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通讯作者：
Everitt BJ
中科院分区：
文献类型：
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作者：
Milton AL;Merlo E;Ratano P;Gregory BL;Dumbreck JK;Everitt BJ
已知NMDAR(NMDAR)上的信号对记忆再巩固很重要，但尽管大多数研究表明NMDAR拮抗剂阻止记忆再稳定并导致健忘症，但其他研究表明，GluN2B选择性NMDAR拮抗剂防止记忆失稳，保护记忆。这些明显自相矛盾、相互矛盾的数据提供了一个机会，可以更准确地定义记忆再巩固机制中不同NMDAR亚型的要求，并进一步了解谷氨酸能信号在这一过程中的作用。在这里，使用完全巩固的巴甫洛夫听觉恐惧记忆的大鼠，我们证明了在记忆失稳和再稳定过程中，杏仁基底外侧核中含有GluN2B和GluN2A的NMDAR的需求分别是双重分离的。我们进一步表明，记忆提取和记忆失稳的机制存在双重分离，因为AMPAR拮抗阻止了记忆提取，同时仍然允许记忆失稳过程发生。这些数据表明，杏仁基底外侧核内的谷氨酸能信号机制以不同和分离的方式介导了先前巩固的恐惧记忆的恢复、失稳和再稳定。
Signaling at NMDA receptors (NMDARs) is known to be important for memory reconsolidation, but while most studies show that NMDAR antagonists prevent memory restabilization and produce amnesia, others have shown that GluN2B-selective NMDAR antagonists prevent memory destabilization, protecting the memory. These apparently paradoxical, conflicting data provide an opportunity to define more precisely the requirement for different NMDAR subtypes in the mechanisms underlying memory reconsolidation, and to further understand the contribution of glutamatergic signaling to this process. Here, using rats with fully consolidated pavlovian auditory fear memories, we demonstrate a double dissociation in the requirement for GluN2B-containing and GluN2A-containing NMDARs within the basolateral amygdala in the memory destabilization and restabilization processes, respectively. We further show a double dissociation in the mechanisms underlying memory retrieval and memory destabilization, since AMPAR antagonism prevented memory retrieval while still allowing the destabilization process to occur. These data demonstrate that glutamatergic signaling mechanisms within the basolateral amygdala differentially and dissociably mediate the retrieval, destabilization and restabilization of previously consolidated fear memories.