Genetic variation of the serotonin 2a receptor affects hippocampal novelty processing in humans.
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.
Leibniz-Institute for Neurobiology, Magdeburg, Germany. bjoern.schott@med.ovgu.de
Björn H
BH
Schott
Constanze I
CI
Seidenbecher
Sylvia
S
Richter
Torsten
T
Wüstenberg
Grazyna
G
Debska-Vielhaber
Heike
H
Schubert
Hans-Jochen
HJ
Heinze
Alan
A
Richardson-Klavehn
Emrah
E
Düzel
D000328:Adult; D005838:Genotype; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D007858:Learning / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008568:Memory / Q000502:physiology; D020125:Mutation, Missense; D011110:Polymorphism, Genetic; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D021641:Recognition, Psychology / Q000502:physiology*; D055815:Young Adult
D044402:Receptor, Serotonin, 5-HT2A
Neuron. 2005 Jun 2;46(5):703-13
15924857
Int J Neuropsychopharmacol. 2008 Dec;11(8):1163-7
18611292
Am J Psychiatry. 2002 Mar;159(3):430-5
11870007
Annu Rev Psychol. 2002;53:1-25
11752477
Proc Natl Acad Sci U S A. 2006 Jan 24;103(4):1059-64
16418294
J Cogn Neurosci. 2000;12 Suppl 2:76-89
11506649
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8501-5
1700433
Acta Psychol (Amst). 2000 Dec;105(2-3):127-39
11194408
J Neurochem. 1997 May;68(5):2186-93
9109547
Ann Med. 2000 Apr;32(3):210-21
10821328
Science. 1997 Jul 18;277(5324):376-80
9219696
Nat Neurosci. 2003 Nov;6(11):1141-2
14566344
Eur J Hum Genet. 2006 Apr;14(4):443-9
16434999
Neuroscience. 1999 May;90(2):369-82
10215142
Brain Res. 1984 Oct 8;311(1):51-6
6488044
Cereb Cortex. 1996 Jan-Feb;6(1):71-9
8670640
Philos Trans R Soc Lond B Biol Sci. 2002 Aug 29;357(1424):1097-110
12217177
Neuroreport. 2005 May 31;16(8):839-42
15891581
Nat Rev Neurosci. 2003 Mar;4(3):193-202
12612632
Neurosci Biobehav Rev. 2010 Apr;34(5):660-9
19715723
Brain Res. 1998 Jan 1;779(1-2):309-13
9473706
Neuropsychopharmacology. 2010 May;35(6):1271-8
20072117
Neuroimage. 2005 May 1;25(4):1325-35
15850749
J Neurosci. 2006 Feb 1;26(5):1407-17
16452664
Neuron. 2006 Aug 3;51(3):369-79
16880131
Curr Med Chem. 2007;14(19):2053-69
17691947
Mol Pharmacol. 2004 Nov;66(5):1293-300
15496511
Annu Rev Neurosci. 2004;27:279-306
15217334