Canadian Centre for Behavioural Neuroscience, Department of Neuroscience, University of Lethbridge, 4401 University Dr., Lethbridge, Alberta T1K 3M4, Canada.
Neurobiol Learn Mem. 2013 Nov;106:309-15. doi: 10.1016/j.nlm.2013.05.008. Epub 2013 Jun 7.
There are still basic uncertainties concerning the role of the hippocampus (HPC) in maintaining long-term context memories. All experiments examining the effects of extensive HPC damage on context memory for a single learning episode find that damage soon after learning results in robust retrograde amnesia. Some experiments find that if the learning-to-damage interval is extended, remote context memories are spared. In contrast, other experiments fail to find spared remote context memory. One possible explanation for inconsistency might be the potency of the context memory conditioning procedure, as the experiments showing spared remote memory used a greater number of context-shock pairings, likely creating a stronger context fear memory. We designed an experiment to directly test the question: does increasing the number of context-shock pairings result in sparing of remote context memory after HPC damage? Six independent groups of rats received either 3 or 12 context-shock pairings during a single conditioning session and then either received extensive HPC damage or Control surgery at 1-week, 2-months, or 4-months after conditioning. 10 days after surgery rats were tested for memory of the shock context. Consistent with all relevant studies, HPC damage at the shortest training-surgery interval produced robust retrograde amnesia for both 3- and 12-shock groups whereas the Control rats expressed significantly high levels of memory. At the longer training-surgery interval, HPC damage produced similarly robust retrograde amnesia in the rats in both the 3- and 12-shock groups. These results clearly demonstrate that increasing the number of context-shock pairings within a single learning session does not change the dependence of the memory on the HPC. Current evidence from our group on retrograde amnesia has now shown that partial damage, dorsal vs. ventral damage, discrete cue+context conditioning, time after training, and number of context-shock pairings do not affect HPC dependence of context fear memories. When taken together, the evidence strongly supports a permanent role of the HPC in context memory.
关于海马体（HPC）在维持长期情境记忆中的作用，仍存在基本的不确定性。所有研究广泛的 HPC 损伤对单次学习事件的情境记忆影响的实验都发现，学习后不久的损伤会导致严重的逆行性遗忘。一些实验发现，如果延长学习到损伤的间隔，远程情境记忆就会被保留下来。相比之下，其他实验则没有发现远程情境记忆被保留。不一致的一个可能解释可能是情境记忆条件作用程序的效力，因为显示保留远程记忆的实验使用了更多的情境-电击配对，可能会产生更强的情境恐惧记忆。我们设计了一个实验来直接检验这个问题：在 HPC 损伤后，增加情境-电击配对的数量是否会导致远程情境记忆的保留？六组独立的大鼠在单次条件作用过程中接受 3 或 12 次情境-电击配对，然后在条件作用后 1 周、2 个月或 4 个月接受广泛的 HPC 损伤或对照手术。手术后 10 天，大鼠接受关于电击情境记忆的测试。与所有相关研究一致，在最短的训练-手术间隔内，HPC 损伤对 3 次和 12 次电击组都产生了严重的逆行性遗忘，而对照组大鼠则表现出明显较高的记忆水平。在较长的训练-手术间隔内，3 次和 12 次电击组的 HPC 损伤都产生了类似的严重逆行性遗忘。这些结果清楚地表明，在单次学习过程中增加情境-电击配对的数量并不会改变记忆对 HPC 的依赖性。我们小组目前关于逆行性遗忘的证据表明，部分损伤、背侧与腹侧损伤、离散线索+情境条件作用、训练后时间和情境-电击配对的数量都不会影响 HPC 对情境恐惧记忆的依赖性。综合来看，这些证据强烈支持 HPC 在情境记忆中的永久性作用。
