Leibniz-Institute for Neurobiology, Magdeburg, Germany.
PLoS One. 2011 Jan 18;6(1):e15984. doi: 10.1371/journal.pone.0015984.
Serotonin (5-hydroxytryptamine, 5-HT) is an important neuromodulator in learning and memory processes. A functional genetic polymorphism of the 5-HT 2a receptor (5-HTR2a His452Tyr), which leads to blunted intracellular signaling, has previously been associated with explicit memory performance in several independent cohorts, but the underlying neural mechanisms are thus far unclear. The human hippocampus plays a critical role in memory, particularly in the detection and encoding of novel information. Here we investigated the relationship of 5-HTR2a His452Tyr and hippocampal novelty processing in 41 young, healthy subjects using functional magnetic resonance imaging (fMRI). Participants performed a novelty/familiarity task with complex scene stimuli, which was followed by a delayed recognition memory test 24 hours later. Compared to His homozygotes, Tyr carriers exhibited a diminished hippocampal response to novel stimuli and a higher tendency to judge novel stimuli as familiar during delayed recognition. Across the cohort, the false alarm rate during delayed recognition correlated negatively with the hippocampal novelty response. Our results suggest that previously reported effects of 5-HTR2a on explicit memory performance may, at least in part, be mediated by alterations of hippocampal novelty processing.
血清素（5-羟色胺，5-HT）是学习和记忆过程中的一种重要神经递质。5-HT2a 受体（5-HTR2a His452Tyr）的功能性遗传多态性导致细胞内信号转导减弱，先前已与几个独立队列的外显记忆表现相关，但目前尚不清楚其潜在的神经机制。人类海马体在记忆中起着至关重要的作用，特别是在检测和编码新信息方面。在这里，我们使用功能磁共振成像（fMRI）研究了 41 名年轻健康受试者中 5-HTR2a His452Tyr 与海马体新奇处理之间的关系。参与者使用复杂场景刺激进行新颖性/熟悉性任务，随后在 24 小时后进行延迟识别记忆测试。与 His 纯合子相比，Tyr 携带者在海马体对新刺激的反应减弱，并且在延迟识别中更倾向于将新刺激判断为熟悉。在整个队列中，延迟识别期间的错误警报率与海马体新奇反应呈负相关。我们的研究结果表明，先前报道的 5-HT2a 对外显记忆表现的影响可能至少部分是通过海马体新奇处理的改变介导的。
