Top-down and bottom-up control of stress-coping

Abstract

In this 30th anniversary issue review, we focus on the glucocorticoid modulation of limbic-prefrontocortical circuitry during stress-coping. This action of the stress hormone is mediated by mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) that are co-expressed abundantly in these higher brain regions. Via both receptor types, the glucocorticoids demonstrate, in various contexts, rapid nongenomic and slower genomic actions that coordinate consecutive stages of information processing. MR-mediated action optimises stress-coping, whereas, in a complementary fashion, the memory storage of the selected coping strategy is promoted via GR. We highlight the involvement of adipose tissue in the allocation of energy resources to central regulation of stress reactions, point to still poorly understood neuronal ensembles in the prefrontal cortex that underlie cognitive flexibility critical for effective coping, and evaluate the role of cortisol as a pleiotropic regulator in vulnerability to, and treatment of, trauma-related psychiatric disorders.

Keywords: PTSD; adipose tissue; brain; cognitive flexibility; glucocorticoid receptors; limbic-prefrontocortical circuitry; mineralocorticoid receptors.

Figure 1

The trajectory of information processing proceeds from mineralocorticoid receptor (MR)‐dominated signaling cascades that activate the circuits underlying appraisal processes and selection of an appropriate coping style, when encoding the experience for learning, which are all geared to protect the “self.” Then, glucocorticoid receptor (GR)‐mediated actions are engaged with recovery by dampening cellular stress reactions and activating executive functions aimed towards rationalisation and contextualisation of the experience.75 At the same time, GR‐mediated actions promote behavioural adaptation and memory consolidation and, by doing so, prime brain circuits to be prepared for future threats in similar contexts. In the case of a recurrent event, such GR‐mediated imprints provide the substrate for retrieval by a MR‐mediated mechanism, and so on. Initially, MR homodimers are involved but, by increasing glucocorticoid concentrations progressively, MR‐GR heterodimers, GR‐GR homodimers and complexes of MR/GR monomers with other transcription factors may be formed. Adapted from de Kloet et al10