Systems consolidation requires postlearning activation of NMDA receptors in the medial prefrontal cortex in trace eyeblink conditioning
Systems consolidation requires postlearning activation of NMDA receptors in the medial prefrontal cortex in trace eyeblink conditioning
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DOI：
10.1523/jneurosci.4381-05.2006
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发表时间：
2006-05-10
影响因子：
5.3
通讯作者：
Kirino, Yutaka
中科院分区：
文献类型：
--
作者：
Takehara-Nishiuchi, Kaori;Nakao, Kazuhito;Kirino, Yutaka
海马体在陈述性记忆中的重要性仅限于最近获得的记忆，而远程获得的记忆被认为存储在新皮质的某个地方。然而，记忆网络如何从海马体依赖性形式重组为新皮质依赖性形式仍然未知。我们之前报道过，内侧前额叶皮层（mPFC）对于大鼠踪迹眨眼条件反射中的新皮层依赖性远程记忆非常重要。在这里，我们研究了 mPFC 中 NMDA 受体在这种重组中的参与，并通过将拮抗剂长期输注到 mPFC 中来确定其贡献的时间窗口，特别是在学习后巩固期间。在学习后的前 1 或 2 周内阻断 mPFCNMDA 受体的大鼠在学习后 6 周测量时显示出记忆保留明显受损，但通过随后的调节重新学习正常。相比之下，如果在第三周至第四周或刚学习后的第一天进行同样的治疗，则没有效果。 NMDA 受体阻断的特异性通过这些大鼠海马-前额叶通路的长期增强作用的降低得到证实。这些结果表明，远程获得记忆的成功建立需要至少在学习后的最初一周激活 PFC 中的 NMDA 受体。这种 NMDA 受体依赖性过程可能会介导永久记忆存储基础的新皮质网络的成熟，并作为将记忆电路重组为新皮质依赖性形式的一种方式。
The importance of the hippocampus in declarative memory is limited to recently acquired memory, and remotely acquired memory is believed to be stored somewhere in the neocortex. However, it remains unknown how the memory network is reorganized from a hippocampus- dependent form into a neocortex- dependent one. We reported previously that the medial prefrontal cortex ( mPFC) is important for this neocortex- dependent remote memory in rat trace eyeblink conditioning. Here, we investigate the involvement of NMDA receptors in the mPFC in this reorganization and determine the time window of their contribution using chronic infusion of an antagonist into the mPFC, specifically during the postlearning consolidation period. The rats with blockade of the mPFCNMDA receptors during the first 1 or 2 weeks after learning showed a marked impairment in memory retention measured 6 weeks after learning, but relearned normally with subsequent conditioning. In contrast, the same treatment had no effect if it was performed during the third to fourth weeks or during the first day just after learning. The specificity of NMDA receptor blockade was confirmed by the reduced long- term potentiation in the hippocampal- prefrontal pathway in these rats. These results suggest that successful establishment of remotely acquired memory requires activation of NMDA receptors in them PFC during at least the initial week of the postlearning period. Such NMDA receptor- dependent processes may mediate the maturation of neocortical networks that underlies permanent memory storage and serve as a way to reorganize memory circuitry to the neocortex- dependent form.