3.07 – Corticosteroid Actions on Electrical Activity in the Limbic Brain

Corticosteroid hormones easily enter the brain and bind to receptors that translocate to the nucleus, where they regulate transcription of responsive genes. It has become evident that corticosteroid receptors can also mediate rapid nongenomic actions. Within the brain corticosterone binds with high affinity to mineralocorticoid receptors (MRs) that have a restricted distribution. Glucocorticoid receptors (GRs), which are much more widespread, display a 10-fold lower affinity. Principal cells in many limbic structures contain GRs as well as MRs. Electrophysiological studies over the past decades have addressed the role of these two receptor types in information transfer through limbic areas, most notably the hippocampus, amygdala, and prefrontal cortex. The current view is that intracellular MRs serve to maintain steady electrical activity and optimal viability in neurons under nonstress conditions. Following stress exposure, rapid nongenomic effects primarily via MRs are thought to enhance excitability, in concert with other stress hormones. This is thought to promote the appraisal of stressful situations and the selection of an adequate strategy. At the same time, GRs are activated which several hours later – through delayed genomic pathways – restore excitability, preserve earlier encoded information, and allow contextualization and rationalization of the event. While brief activation of MRs and GRs in the context of a stressful situation leads to adaptive responses, the pleiotropic hormone effects can become a vulnerability factor when GRs are repeatedly activated such as during chronic stress.