Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory.
Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory.
复制标题
DOI：
10.1371/journal.pone.0027426
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Sutherland RJ
中科院分区：
文献类型：
--
作者：
Sparks FT;Lehmann H;Hernandez K;Sutherland RJ
使用兴奋性毒素N-甲基-D-天冬氨酸（NMDA）损伤海马（HPC）可导致背景恐惧记忆的逆行性遗忘。这种健忘症通常归因于HPC中细胞的丢失。然而，也已知NMDA在其注射后的数小时内引起强烈的神经元放电（癫痫发作活动）。这些癫痫发作可能会对记忆的恢复产生不利影响。在这里，我们评估逆行性遗忘是由于NMDA诱导的癫痫发作活动或细胞损伤本身的可能性。为了评估NMDA诱导的活动对背景记忆的影响，我们开发了一种损伤技术，该技术利用NMDA的神经毒性作用，同时抑制可能的相关癫痫发作活动。将NMDA和钠通道阻断剂河豚毒素（TTX）同时注入大鼠HPC，导致HPC广泛的双侧损伤。TTX与NMDA共输注抑制癫痫发作活动的传播。大鼠接受新环境与足部电击的配对，之后它们在最近（24小时）或远程（5周）时间点接受NMDA诱导、TTX+ NMDA诱导或无HPC损伤。恢复后，将大鼠置于休克环境中，并将冻结评分为恐惧记忆指数。在这两个时间点，具有完整HPC的大鼠表现出对厌恶背景的强大记忆，而接受NMDA或NMDA+TTX损伤的大鼠在最近和遥远的时间点表现出同等程度的习得性恐惧的显著减少。因此，在情境恐惧条件反射中观察到的逆行性遗忘不太可能是由于传播性癫痫发作活动破坏了非HPC网络。此外，在这两个时间点观察到的记忆缺陷提供了额外的证据，支持HPC在维持上下文记忆方面具有持续作用的主张。
Damage to the hippocampus (HPC) using the excitotoxin N-methyl-D-aspartate (NMDA) can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity) during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX), a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours) or remote (5 weeks) time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories.
登录
查看更多内容
影响因子：
3.5
作者：
Gaskin, S;Tremblay, A;Mumby, DG
通讯作者：
Mumby, DG
影响因子：
2
作者：
Epp, Jonathan;Keith, Julian R.;Sutherland, Robert J.
通讯作者：
Sutherland, Robert J.
影响因子：
5.3
作者：
KESNER, RP;DOTY, RW
通讯作者：
DOTY, RW
影响因子：
3.5
作者：
Clark, RE;Broadbent, NJ;Squire, LR
通讯作者：
Squire, LR
影响因子：
2
作者：
Lehmann, Hugo;Sparks, Fraser T.;Sutherland, Robert J.
通讯作者：
Sutherland, Robert J.