Stress Induces a Shift Towards Striatum-Dependent Stimulus-Response Learning via the Mineralocorticoid Receptor

Abstract

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulusresponse learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

The stressed brain of humans and rodents

“…Thus, directly after a peak of cortisol, contextual memory and contextualization were found to be decreased, whereas more habitual forms of learning were enhanced . This was associated with an MR‐dependent switch from hippocampal to striatal activity . When subjects were tested several hours later, contextualization was improved in those who received hydrocortisone compared to placebo .…”

“…19,20 This was associated with an MR-dependent switch from hippocampal to striatal activity. 21,22 When subjects were tested several hours later, contextualization was improved in those who received hydrocortisone compared to placebo. 19 Overall, this leads to the notion (Figure 4) that shortly after a peak in cortisol, individuals are more focused on the "now," the "self," on emotional content; and select simple yet inflexible (spatial) solutions.…”

Lost in Time and Space: States of High Arousal Disrupt Implicit Acquisition of Spatial and Sequential Context Information

“…Stress produces a shift toward the use of “habit” memory by impairing hippocampus- and probably prefrontal cortex-dependent “cognitive” memory (Arnsten et al, 2012 ; Packard and Goodman, 2012 ; Schwabe and Wolf, 2013 ; Schwabe, 2013 , 2016 ; Gagnon and Wagner, 2016 ). Existing evidence fits in well with this notion, showing that stressful encounters decrease hippocampal activation (Pruessner et al, 2008 ; Henckens et al, 2009 ; Cousijn et al, 2012 ; Schwabe and Wolf, 2012 ) and thereby strengthen the dorsal striatum-dependent system (Poldrack and Packard, 2003 ; Vogel et al, 2015a , 2017 ), which then supports incremental strengthening of stimulus-response associations (Packard and Knowlton, 2002 ; Devan et al, 2011 ).…”

Dominant men are faster in decision-making situations and exhibit a distinct neural signal for promptness

“…Given previous work indicating that enhanced glucocorticoid levels can affect the activation of neural circuits ( Henckens et al 2011 , 2012 ; Vogel et al 2016 , 2017 ), we measured salivary cortisol at different time points of the experiment. We found no differences between the groups in cortisol levels throughout the experiment were (AUCg: F 1,19 = 0.23, p = 0.638, η 2 = 0.012, 95% CI [<0.001, 0.070]; AUCi: F 1,19 = 0.24, p = 0.633, η 2 = 0.012, 95% CI [<0.001, 0.072]).…”