Snyder Jason S, Cahill Shaina P, Frankland Paul W
Department of Psychology & Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, British Columbia, Canada.
Hospital for Sick Children, Program in Neurosciences & Mental Health, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada.
Hippocampus. 2017 Aug;27(8):871-882. doi: 10.1002/hipo.22737. Epub 2017 May 22.
Different memory systems offer distinct advantages to navigational behavior. The hippocampus forms complex associations between environmental stimuli, enabling flexible navigation through space. In contrast, the dorsal striatum associates discrete cues and favorable behavioral responses, enabling habit-like, automated navigation. While these two systems often complement one another, there are instances where striatal-dependent responses (e.g. approach a cue) conflict with hippocampal representations of spatial goals. In conflict situations, preference for spatial vs. response strategies varies across individuals and depends on previous experience, plasticity and the integrity of these two memory systems. Here, we investigated the role of adult hippocampal neurogenesis and exercise on mouse search strategies in a water maze task that can be solved with either a hippocampal-dependent place strategy or a striatal-dependent cue-response strategy. We predicted that inhibiting adult neurogenesis would impair hippocampal function and shift behavior towards striatal-dependent cue responses. However, blocking neurogenesis in a transgenic nestin-TK mouse did not affect strategy choice. We then investigated whether a pro-neurogenic stimulus, running, would bias mice towards hippocampal-dependent spatial strategies. While running indeed promoted spatial strategies, it did so even when neurogenesis was inhibited in nestin-TK mice. These findings indicate that exercise-induced increases in neurogenesis are not always required for enhanced cognitive function. Furthermore, our data identify exercise as a potentially useful strategy for promoting flexible, cognitive forms of memory in habit-related disorders that are characterized by excessive responding to discrete cues.
不同的记忆系统为导航行为提供了独特的优势。海马体在环境刺激之间形成复杂的关联，使动物能够在空间中灵活导航。相比之下，背侧纹状体将离散的线索与有利的行为反应联系起来，实现类似习惯的自动导航。虽然这两个系统通常相互补充，但在某些情况下，纹状体依赖的反应（如接近一个线索）与空间目标的海马体表征会发生冲突。在冲突情境中，对空间策略与反应策略的偏好因人而异，并取决于先前的经验、可塑性以及这两个记忆系统的完整性。在此，我们在水迷宫任务中研究了成年海马体神经发生和运动对小鼠搜索策略的作用，该任务既可以通过依赖海马体的位置策略，也可以通过依赖纹状体的线索-反应策略来解决。我们预测抑制成年神经发生会损害海马体功能，并使行为转向依赖纹状体的线索反应。然而，在转基因巢蛋白-TK小鼠中阻断神经发生并未影响策略选择。然后，我们研究了一种促进神经发生的刺激——跑步，是否会使小鼠偏向于依赖海马体的空间策略。虽然跑步确实促进了空间策略，但即使在巢蛋白-TK小鼠中神经发生受到抑制时也是如此。这些发现表明，运动诱导的神经发生增加并非增强认知功能所必需。此外，我们的数据确定运动是一种潜在有用的策略，可用于在以对离散线索过度反应为特征的习惯相关障碍中促进灵活的、认知形式的记忆。
