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. 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 tenfold lower affinity. Principal cells in limbic structures contain gluco- 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. 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 via MRs in the plasma membrane are thought to enhance excitability, in concert with other stress hormones. This will promote the appraisal and most likely the first stages of encoding of the stressful situation. At the same time, GRs are activated which several hours later - through delayed genomic pathways - restore excitability and preserve earlier encoded information. While brief activation of GRs in the context of a stressful situation leads to adaptive responses, the pleiotropic hormone effects can become a vulnerability factor when the circuit is exposed to additional challenges, for example, during ischemia, or when GRs are repeatedly activated such as during chronic stress.