Are early stress effects on cognitive processes mediated by the mineralocorticoid orglucocorticoid receptor?

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Stress affects several physiological and psychological domains and triggers a shift in information processing that is mediated by two separate neuroendocrine systems: the fast-responding catecholaminergic system and the slower glucocorticoid system. The glucocorticoid system is based on the hypothalamic-pituitary-adrenal axis, with cortisol as the main downstream glucocorticoid in humans. According to the network model of Hermans et al. (2014), two separate brain networks are implicated in the acute stress response. The salience network is responsible for exogenous attention, especially to potential threats, and the fast mobilization of energy. Resources are primarily allocated to this network immediately after the onset of the stressor until about one hour after stress exposure. In this early part of the stress response, the executive control network that mediates deliberate thinking and planned action is down-regulated. This process is initially driven by catecholaminergic activation, which sets in immediately within seconds with stress exposure. In addition and within minutes rapid non-genomic effects of cortisol appear on the scene and start to modulate the catecholaminergic effects. Cortisol can easily cross the blood-brain barrier and feeds back on the brain via two different receptor types: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR). While GRs are widely distributed in the brain, MRs are primarily located in limbic structures and the prefrontal cortex, which are areas critical for cognition and emotion. Several human and animal studies indicated a role for membrane-bound MRs in the early phase of the stress response and in rapid cortisol effects on emotional and cognitive processes. However, while rapid stress effects are often attributed to the MR, recent research in animals indicates a role of the - supposedly membrane bound and non-genomic - GR in rapid stress effects as well.These rapid effects are regionally and functionally specific and may differ between MRs and GRs. Overall, effects of GRs rather suppress, and those of MRs rather enhance neural excitability.In the proposed project, we plan to systematically disentangle MR vs. GR effects in the early stress response on emotional and cognitive processes that represent the salience network (attentional vigilance to emotional stimuli as determined by emotional dot-probe), the executive control network (working memory as assessed by n-back task) or both networks (risk taking as assessed by balloon analogue risk task). To our best knowledge, this would be the first project to investigate the differential contribution of both receptor systems on these cognitive domains in such a systematic manner.