Indexed on: 25 Jan '17Published on: 25 Jan '17Published in: The Journal of neuroscience : the official journal of the Society for Neuroscience
Stress induces a shift from hippocampus-based 'cognitive' towards dorsal striatum-based 'habitual' learning and memory. This shift is thought to have important implications for stress-related psychopathologies, including posttraumatic stress disorder (PTSD). However, there is large individual variability in the stress-induced bias towards 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 towards habit memory. In two independent experimental studies, healthy humans were genotyped for the ADRA2B deletion variant. After a stress or control manipulation, participants completed a dual-solution learning task while electroencephalographic (study I) or functional magnetic resonance imaging (fMRI) measurements (study II) were taken. Carriers compared to non-carriers of the ADRA2B deletion variant exhibited a significantly reduced bias towards habit memory after stress. FMRI results indicated that whereas non-carriers of the ADRA2B deletion 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.Stressful 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 posttraumatic stress disorder (PTSD), little is known about the source of individual differences in the sensitivity for the stress-induced bias towards habit memory. We report here that a common genetic variation of the noradrenergic system, a known risk factor for PTSD, 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.