Dataset Information

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

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 that MR gene 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 two MR SNPs associated with increased MR expression and transactivational activity (MR-2G/C C [rs2070951], MR-I180V A [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 the MR haplotype 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 in MR haplotype 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.

SUBMITTER: Wirz L

PROVIDER: S-EPMC5687596 | biostudies-literature | 2017 Nov-Dec

REPOSITORIES: biostudies-literature

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

Wirz Lisa L Reuter Martin M Wacker Jan J Felten Andrea A Schwabe Lars L

eNeuro 20171115 6

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 that <i>MR</i> gene variants contribute to these individual differences. In two experiments, healthy participants were genotyped, exposed to ...[more]

PMID: 29147678

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Project description: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 ?2b-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 the ADRA2B 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 ADRA2B deletion variant exhibited a significantly reduced bias toward habit memory after stress. fMRI results indicated that, whereas noncarriers 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.SIGNIFICANCE STATEMENT 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.

Project description:Horse training exposes horses to an array of cognitive and ethological challenges. Horses are routinely required to perform behaviours that are not aligned to aspects of their ethology, which may delay learning. While horses readily form habits during training, not all of these responses are considered desirable, resulting in the horse being subject to retraining. This is a form of cognitive flexibility and is critical to the extinction of habits and the learning of new responses. It is underpinned by complex neural processes which can be impaired by chronic or repeated stress. Domestic horses may be repeatedly exposed to multiples stressors. The potential contribution of stress impairments of cognitive flexibility to apparent training failures is not well understood, however research from neuroscience can be used to understand horses' responses to training. We trained horses to acquire habit-like responses in one of two industry-style aversive instrumental learning scenarios (moving away from the stimulus-instinctual or moving towards the stimulus-non-instinctual) and evaluated the effect of repeated stress exposures on their cognitive flexibility in a reversal task. We measured heart rate as a proxy for noradrenaline release, salivary cortisol and serum Brain Derived Neurotrophic Factor (BDNF) to infer possible neural correlates of the learning outcomes. The instinctual task which aligned with innate equine escape responses to aversive stimuli was acquired significantly faster than the non-instinctual task during both learning phases, however contrary to expectations, the repeated stress exposure did not impair the reversal learning. We report a preliminary finding that serum BDNF and salivary cortisol concentrations in horses are positively correlated. The ethological salience of training tasks and cognitive flexibility learning can significantly affect learning in horses and trainers should adapt their practices where such tasks challenge innate equine behaviour.

Dataset Information

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

Publications

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

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