NMDA receptors in retrosplenial cortex are necessary for retrieval of recent and remote context fear memory.
NMDA receptors in retrosplenial cortex are necessary for retrieval of recent and remote context fear memory.
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DOI：
10.1523/jneurosci.2107-11.2011
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发表时间：
2011-08-10
期刊：
影响因子：
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通讯作者：
Radulovic J
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文献类型：
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作者：
Corcoran KA;Donnan MD;Tronson NC;Guzmán YF;Gao C;Jovasevic V;Guedea AL;Radulovic J
随着时间的推移，记忆提取被认为是从海马体转移到新皮质部位的分布式网络。在这些部位中，压后皮层（RSC）在远程获得的情感记忆的提取过程中被强烈激活。然而，目前还不清楚RSC是否专门参与记忆储存或提取，以及哪些神经递质受体机制发挥其功能。我们解决了这些问题，通过抑制N-甲基-D-天冬氨酸受体（NMDAR）在RSC通过注射APV之前，在测试的上下文恐惧在雄性小鼠。前扣带皮层（ACC）和背侧海马（DH），这已经牵连在远程和最近的记忆检索，分别作为神经解剖控制。令人惊讶的是，APV只注入RSC，而不是ACC或DH，废除远程记忆的检索，所揭示的缺乏冻结的条件反射。APV注入RSC也损害了近期记忆的提取，但对条件反射或记忆储存没有影响。被试内实验证实，RSC在记忆提取中的作用是没有时间限制的。RSC依赖的背景恐惧记忆提取是由NR 2A介导的，而不是NR 2B，含有NMDAR亚基。总的来说，这些数据是第一次证明，RSC中的NMDAR是必要的远程和最近的记忆唤起恐惧的情况下检索。因此，RSC的功能障碍可能对创伤后应激障碍（PTSD）患者的创伤记忆的重新体验有显着贡献。
Over time, memory retrieval is thought to transfer from the hippocampus to a distributed network of neocortical sites. Of these sites, the retrosplenial cortex (RSC) is robustly activated during retrieval of remotely acquired, emotionally-valenced memories. It is unclear, however, whether RSC is specifically involved in memory storage or retrieval, and which neurotransmitter receptor mechanisms serve its function. We addressed these questions by inhibiting N-methyl-d-aspartate receptors (NMDAR) in RSC via infusions of APV prior to tests for context fear in male mice. Anterior cingulate cortex (ACC) and dorsal hippocampus (DH), which have been implicated in the retrieval of remote and recent memory, respectively, served as neuroanatomical controls. Surprisingly, infusion of APV only into RSC, but not ACC or DH, abolished retrieval of remote memory, as revealed by lack of freezing to the conditioning context. APV infused into RSC also impaired retrieval of recent memory, but had no effect on conditioning or memory storage. Within-subject experiments confirmed that the role of RSC in memory retrieval is not time-limited. RSC-dependent context fear memory retrieval was mediated by NR2A, but not NR2B, subunit-containing NMDAR. Collectively, these data are the first demonstration that NMDAR in RSC are necessary for the retrieval of remote and recent memories of fear-evoking contexts. Dysfunction of RSC may thereby contribute significantly to the re-experiencing of traumatic memories in patients with post-traumatic stress disorder (PTSD).