Department of Pharmacology & Physiology, Georgetown University, Washington, DC, USA.
Department of Neuroscience, Georgetown University, Washington, DC, USA.
Hippocampus. 2024 May;34(5):261-275. doi: 10.1002/hipo.23603. Epub 2024 Mar 22.
Decades of studies robustly support a critical role for the hippocampus in spatial memory across a wide range of species. Hippocampal damage produces clear and consistent deficits in allocentric spatial memory that requires navigating through space in rodents, non-human primates, and humans. By contrast, damage to the hippocampus spares performance in most non-navigational spatial memory tasks-which can typically be resolved using egocentric cues. We previously found that transient inactivation of the hippocampus impairs performance in the Hamilton Search Task (HST), a self-ordered non-navigational spatial search task. A key question, however, still needs to be addressed. Acute, reversible inactivation of the hippocampus may have resulted in an impairment in the HST because this approach does not allow for neuroplastic compensation, may prevent the development of an alternative learning strategy, and/or may produce network-based effects that disrupt performance. We compared learning and performance on the HST in male rhesus macaques (six unoperated control animals and six animals that underwent excitotoxic lesions of the hippocampus). We found a significant impairment in animals with hippocampal lesions. While control animals improved in performance over the course of 45 days of training, performance in animals with hippocampal lesions remained at chance levels. The HST thus represents a sensitive assay for probing the integrity of the hippocampus in non-human primates. These data provide evidence demonstrating that the hippocampus is critical for this type of non-navigational spatial memory, and help to reconcile the many null findings previously reported.
几十年来的研究有力地支持了海马体在各种物种的空间记忆中的关键作用。海马体损伤会导致明显而一致的空间记忆缺陷，这种缺陷需要啮齿动物、非人类灵长类动物和人类在空间中导航。相比之下，海马体的损伤不会影响大多数非导航空间记忆任务的表现，这些任务通常可以使用自我中心线索来解决。我们之前发现，海马体的短暂失活会损害 Hamilton 搜索任务（HST）的表现，这是一种自我有序的非导航空间搜索任务。然而，一个关键问题仍需要解决。急性、可逆性的海马体失活可能导致 HST 表现受损，因为这种方法不允许神经可塑性补偿，可能阻止替代学习策略的发展，和/或可能产生破坏表现的基于网络的效应。我们比较了雄性恒河猴（六只未手术的对照动物和六只接受海马体兴奋毒性损伤的动物）在 HST 上的学习和表现。我们发现海马体损伤的动物表现出明显的损伤。虽然对照动物在 45 天的训练过程中表现有所提高，但海马体损伤动物的表现仍保持在随机水平。因此，HST 代表了一种在非人类灵长类动物中探测海马体完整性的敏感测试。这些数据提供了证据，证明海马体对这种非导航空间记忆至关重要，并有助于解释以前报告的许多无效发现。
