Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys
Memory loss in a nonnavigational spatial task after hippocampal inactivation in monkeys
复制标题
DOI：
10.1073/pnas.1320562111
复制
发表时间：
2014-03-18
影响因子：
11.1
通讯作者：
Malkova, Ludise
中科院分区：
文献类型：
--
作者：
Forcelli, Patrick A.;Palchik, Guillermo;Malkova, Ludise
海马在物种间的空间导航中有着广泛的作用，但它在非导航任务中的空间记忆中的作用尚不确定。特别是，当猴子在不需要导航的任务中进行测试时，空间记忆似乎不受海马体损伤的影响。然而，这些结果的解释是妥协的长期代偿性适应发生在病变后的几天和几周。为了验证海马体对于非导航空间记忆是必要的这一假设，我们选择了一种避免长期代偿性适应的技术。在测试时，我们通过微量输注谷氨酸受体拮抗剂犬尿氨酸短暂急性破坏海马功能。对动物进行自我排序空间记忆任务，即汉密尔顿搜索任务测试。在这项任务中，动物们会看到一个由八个盒子组成的阵列，每个盒子里都有一个食物盒;每次试验可以打开一个盒子，试验之间会有一个延迟。只有盒子的空间位置才能作为解决任务的线索。最佳策略是打开每个盒子一次，而不返回到以前访问过的位置。海马的短暂失活以延迟依赖的方式将性能降低到机会水平。相比之下，没有赤字时，看到盒子标记的非空间线索（颜色）。这些结果清楚地证明了猕猴海马在非导航空间记忆中的作用，并证明了该种属中该结构的药理学失活的功效。我们的数据使猴子海马体的作用与海马体功能的更广泛框架保持一致。
The hippocampus has a well-documented role for spatial navigation across species, but its role for spatial memory in nonnavigational tasks is uncertain. In particular, when monkeys are tested in tasks that do not require navigation, spatial memory seems unaffected by lesions of the hippocampus. However, the interpretation of these results is compromised by long-term compensatory adaptation occurring in the days and weeks after lesions. To test the hypothesis that hippocampus is necessary for nonnavigational spatial memory, we selected a technique that avoids long-term compensatory adaptation. We transiently disrupted hippocampal function acutely at the time of testing by microinfusion of the glutamate receptor antagonist kynurenate. Animals were tested on a self-ordered spatial memory task, the Hamilton Search Task. In the task, animals are presented with an array of eight boxes, each containing a food reinforcer; one box may be opened per trial, with trials separated by a delay. Only the spatial location of the boxes serves as a cue to solve the task. The optimal strategy is to open each box once without returning to previously visited locations. Transient inactivation of hippocampus reduced performance to chance levels in a delay-dependent manner. In contrast, no deficits were seen when boxes were marked with nonspatial cues (color). These results clearly document a role for hippocampus in nonnavigational spatial memory in macaques and demonstrate the efficacy of pharmacological inactivation of this structure in this species. Our data bring the role of the hippocampus in monkeys into alignment with the broader framework of hippocampal function.