Institute of Cognitive Neuroscience, University College London, London, WC1N 3AR, United Kingdom.
J Neurosci. 2012 Oct 10;32(41):14193-204. doi: 10.1523/JNEUROSCI.1278-12.2012.
Activation of the hippocampus is required to encode memories for new events (or episodes). Observations from animal studies suggest that, for these memories to persist beyond 4-6 h, a release of dopamine generated by strong hippocampal activation is needed. This predicts that dopaminergic enhancement should improve human episodic memory persistence also for events encoded with weak hippocampal activation. Here, using pharmacological functional MRI (fMRI) in an elderly population in which there is a loss of dopamine neurons as part of normal aging, we show this very effect. The dopamine precursor levodopa led to a dose-dependent (inverted U-shape) persistent episodic memory benefit for images of scenes when tested after 6 h, independent of whether encoding-related hippocampal fMRI activity was weak or strong (U-shaped dose-response relationship). This lasting improvement even for weakly encoded events supports a role for dopamine in human episodic memory consolidation, albeit operating within a narrow dose range.
海马体的激活对于编码新事件（或情节）的记忆是必需的。动物研究的观察结果表明，为了使这些记忆持续超过 4-6 小时，需要由强烈的海马体激活产生的多巴胺释放。这预示着多巴胺能增强应该也能改善人类情节记忆的持久性，即使是对弱海马体激活编码的事件也是如此。在这里，我们在老年人群中使用药理学功能磁共振成像（fMRI），这些人群的多巴胺神经元随着正常衰老而丢失，结果表明这种情况确实存在。多巴胺前体左旋多巴导致 6 小时后测试时的场景图像的持续情节记忆受益呈剂量依赖性（倒 U 形），与编码相关的海马体 fMRI 活动强弱无关（U 形剂量反应关系）。即使对于弱编码的事件，这种持久的改善也支持多巴胺在人类情节记忆巩固中的作用，尽管它在狭窄的剂量范围内起作用。
