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

Year: 2017

Type: article

Abstract: Stress induces a shift from hippocampus-dependent “cognitive” toward dorsal striatum-dependent “habit” memory. However, not all individuals are susceptible to this shift under stress. Based on pharmacological studies indicating a critical role of the mineralocorticoid receptor (MR) in the stress-induced bias toward dorsal striatal learning, we hypothesized thatMRgene variants contribute to these individual differences. In two experiments, healthy participants were genotyped, exposed to a stressor or control manipulation and performed a learning task that can be solved using hippocampal or dorsal striatal systems, while electroencephalography (EEG; Experiment I) or functional magnetic resonance imaging (fMRI; Experiment II) measurements were taken. Stress led to a shift from hippocampal to dorsal striatal learning which was more pronounced in homo- and heterozygous carriers of a six single nucleotide polymorphisms (SNPs)-comprising haplotype containing the alleles of twoMR SNPsassociated with increased MR expression and transactivational activity (MR-2G/CC[rs2070951],MR-I180VA[rs5522]). This stress-induced shift toward habit memory was paralleled by an increased feedback-related negativity (FRN), which may reflect striatal processing, and increased caudate activation. Carriers of theMRhaplotype showed a reduced P3a, an event-related potential thought to indicate cognitive processing, and reduced hippocampal activity after stress. Moreover, stress resulted in reduced amygdala-hippocampus connectivity and the decrease in amygdala connectivity to the parahippocampal cortex was particularly pronounced inMRhaplotype carriers. Our findings indicate that genetic variants associated with enhanced MR expression facilitate a stress-induced shift from hippocampal toward dorsal striatal learning, most likely via impaired hippocampal processing and reduced amygdala-hippocampus cross talk, allowing the dorsal striatum to guide behavior under stress.

Source: eNeuro

DOI: 10.1523/eneuro.0359-17.2017

Authors: Lisa Wirz, Martin Reuter, Jan Wacker, Andrea Felten, Lars Schwabe

Institutions: Universität Hamburg, University of Bonn

Language: English

Topic: Stress Responses and Cortisol

Subfield: Behavioral Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,925