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Genetic Variation of the Serotonin 2a Receptor Affects Hippocampal Novelty Processing in Humans

Schott, BH; Seidenbecher, CI; Richter, S; Wustenberg, T; Debska-Vielhaber, G; Schubert, H; Heinze, HJ; ... Duzel, E; + view all (2011) Genetic Variation of the Serotonin 2a Receptor Affects Hippocampal Novelty Processing in Humans. PLOS ONE , 6 (1) , Article e15984. 10.1371/journal.pone.0015984. Green open access

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Abstract

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.

Type: Article
Title: Genetic Variation of the Serotonin 2a Receptor Affects Hippocampal Novelty Processing in Humans
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0015984
Publisher version: http://dx.doi.org/10.1371/journal.pone.0015984
Language: English
Additional information: © 2011 Schott et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This work was supported by Deutsche Forschungsgemeinschaft (DFG), SFB 779, TP A7 and A8 (http://www.dfg.de) and State of Saxony-Anhalt, State Research Award to Dr. Björn Schott (http://www.sachsen-anhalt.de/LPSA/index.​php?id=3564). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Keywords: EPISODIC MEMORY, 5-HT2A RECEPTOR, HIS452TYR POLYMORPHISM, INTERNEURONS, RETRIEVAL, AMPLITUDE, BRAIN, AGE
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Institute of Cognitive Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/1304527
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