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 (), 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 the deletion 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 the deletion variant exhibited a significantly reduced bias toward habit memory after stress. fMRI results indicated that, whereas noncarriers of the 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 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.

Does Acute Stress Impact Declarative and Procedural Learning?

“…For example, although a psychosocial stress manipulation led to the use of procedural learning strategies in the study conducted by , participants' performance on the feedback-based learning task was not influenced by stress. This pattern of results was also observed in the study conducted by Wirz et al (2017), in which feedback timing was not manipulated experimentally but varied across studies due to changes in temporal resolution of the measured signals (two different methods, EEG vs. fMRI, were used to quantify brain activity during a probabilistic category learning task). Consistently, stimulus-response learning based on trial and error was not influenced by stress in the study conducted by Vogel and Schwabe (2018).…”

A Haplotype Associated with Enhanced Mineralocorticoid Receptor Expression Facilitates the Stress-Induced Shift from “Cognitive” to “Habit” Learning

“…Given the potential relevance of such effects in the face of different prevalences of stress-related mental disorders in men and women ( Bangasser and Valentino, 2014 ), determining whether there are significant differences in stress × MR genotype interactions on the use of multiple memory systems between men and women is an important challenge for future studies. Similarly, and in line with the finding that also genetic differences in the noradrenergic system modulate stress effects on multiple memory systems ( Wirz et al, 2017 ), it will be important for future research to investigate interactive effects of several genes, which will allow pooling of the relative small effects of individual polymorphisms.…”

“…Participants gave written informed consent and received a moderate monetary compensation of 25€ for their participation. This sample is part of a larger project on individual differences in stress effects on multiple memory systems ( Wirz et al, 2017 ).…”

“…Participants were assigned the strategy with the best fit score. If none of the scores for all possible strategies was <0.16, participants’ strategies were classified as “nonidentifiable” ( Gluck et al, 2002 ; Wirz et al, 2017 ). Independent of the experimental group, no strategy was identifiable in 20 participants (χ 2 (1) = 0.220, p = 0.639).…”

Analysis of the source of aggressiveness in gamecocks

“…We analysed the receptor genes (ADR) regulated by Epi or NE (Table 1) [36][37][38][39] . In both breeds, 54 amino acid mutation sites were confirmed in eight ADR genes (Shamo, 33 sites; Shaver Brown, 21 sites).…”