title: A Deletion Variant of the α2b-Adrenoceptor Modulates the Stress-Induced Shift from "Cognitive" to "Habit" Memory.
abstract: Stress induces a shift from hippocampus-based "cognitive" toward dorsal striatum-based "habitual" learning and memory. This shift is thought to have important implications for stress-related psychopathologies, including post-traumatic stress disorder (PTSD). However, there is large individual variability in the stress-induced bias toward habit memory, and the factors underlying this variability are completely unknown. Here we hypothesized that a functional deletion variant of the gene encoding the α2b-adrenoceptor (ADRA2B), which has been linked to emotional memory processes and increased PTSD risk, modulates the stress-induced shift from cognitive toward habit memory. In two independent experimental studies, healthy humans were genotyped for theADRA2Bdeletion variant. After a stress or control manipulation, participants completed a dual-solution learning task while electroencephalographic (Study I) or fMRI measurements (Study II) were taken. Carriers compared with noncarriers of theADRA2Bdeletion variant exhibited a significantly reduced bias toward habit memory after stress. fMRI results indicated that, whereas noncarriers of theADRA2Bdeletion variant showed increased functional connectivity between amygdala and putamen after stress, this increase in connectivity was absent in carriers of the deletion variant, who instead showed overall enhanced connectivity between amygdala and entorhinal cortex. Our results indicate that a common genetic variation of the noradrenergic system modulates the impact of stress on the balance between cognitive and habitual memory systems, most likely via altered amygdala orchestration of these systems.SIGNIFICANCE STATEMENTStressful events have a powerful effect on human learning and memory. Specifically, accumulating evidence suggests that stress favors more rigid dorsal striatum-dependent habit memory, at the expense of flexible hippocampus-dependent cognitive memory. Although this shift may have important implications for understanding mental disorders, such as post-traumatic stress disorder, little is known about the source of individual differences in the sensitivity for the stress-induced bias toward habit memory. We report here that a common genetic variation of the noradrenergic system, a known risk factor for post-traumatic stress disorder, modulates the stress-induced shift from cognitive to habit memory, most likely through altered crosstalk between the hippocampus and dorsal striatum with the amygdala, a key structure in emotional memory.
authors.affiliation: Department of Cognitive Psychology and.
authors.forename: Lisa
authors.identifier: 0000-0002-2811-4080
authors.initials: L
authors.lastname: Wirz
authors.affiliation: Department of Differential Psychology, University of Hamburg, 20146 Hamburg, Germany, and.
authors.forename: Jan
authors.initials: J
authors.lastname: Wacker
authors.affiliation: Department of Differential and Biological Psychology, University of Bonn, 53111 Bonn, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Felten
authors.affiliation: Department of Differential and Biological Psychology, University of Bonn, 53111 Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Reuter
authors.affiliation: Department of Cognitive Psychology and Lars.Schwabe@uni-hamburg.de.
authors.forename: Lars
authors.initials: L
authors.lastname: Schwabe
mesh_terms: D000328:Adult; D001245:Association Learning / Q000502:physiology; D001288:Attention / Q000502:physiology; D001794:Blood Pressure / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging; D058256:Brain Waves / Q000235:genetics; D003071:Cognition / Q000502:physiology*; D005260:Female; D005838:Genotype; D006184:Habits; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008297:Male; D008568:Memory / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics* / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D017384:Sequence Deletion / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics* / Q000503:physiopathology*; D013997:Time Factors; D055815:Young Adult
chemical_list: D018341:Receptors, Adrenergic, alpha-2; D010100:Oxygen; D006854:Hydrocortisone
keywords: amygdala; dorsal striatum; hippocampus; memory; noradrenaline; stress