Dopamine receptor 4 promoter polymorphism modulates memory and neuronal responses to salience

• Published in: NeuroImage (Orlando, Fla.) Vol. 84; pp. 922 - 931
• Main Authors: Strange, B.A., Gartmann, N., Brenninkmeyer, J., Haaker, J., Reif, A., Kalisch, R., Büchel, C.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.01.2014; Elsevier; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Brain - physiology; Dopamine; Dopamine - genetics; Dopamine - metabolism; DRD4 promoter polymorphism; fMRI; Fundamental and applied biological sciences. Psychology; Genotype; Hippocampus; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Memory; Memory - physiology; Middle Aged; Novelty; Personality traits; Polymorphism, Single Nucleotide; Promoter Regions, Genetic - genetics; Receptors, Dopamine D4 - genetics; Rodents; Vertebrates: nervous system and sense organs; Young Adult; fMRI; Dopamine; Memory; Hippocampus; DRD4 promoter polymorphism; Novelty; Dopamine receptor; Central nervous system; Catecholamine; Nuclear magnetic resonance imaging; Encephalon; Neurotransmitter; Functional imaging; Polymorphism
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2013.09.065

Animal models and human functional imaging data implicate the dopamine system in mediating enhanced encoding of novel stimuli into human memory. A separate line of investigation suggests an association between a functional polymorphism in the promoter region for the human dopamine 4 receptor gene (DRD4) and sensitivity to novelty. We demonstrate, in two independent samples, that the −521C>T DRD4 promoter polymorphism determines the magnitude of human memory enhancement for contextually novel, perceptual oddball stimuli in an allele dose-dependent manner. The genotype-dependent memory enhancement conferred by the C allele is associated with increased neuronal responses during successful encoding of perceptual oddballs in the ventral striatum, an effect which is again allele dose-dependent. Furthermore, with repeated presentations of oddball stimuli, this memory advantage decreases, an effect mirrored by adaptation of activation in the hippocampus and substantia nigra/ventral tegmental area in C carriers only. Thus, a dynamic modulation of human memory enhancement for perceptually salient stimuli is associated with activation of a dopaminergic–hippocampal system, which is critically dependent on a functional polymorphism in the DRD4 promoter region. •Dopamine critical for enhanced memory for novelty, yet mechanism in humans unknown•C allele of human DRD4 promoter SNP augments perceptual oddball memory enhancement•Memory effects parallel C allele-dependent striatal, SN/VTA, hippocampal activation•Memory increase and neuronal responses are dynamic showing adaptation in C carriers