Mineralocorticoid and glucocorticoid receptor balance in memory systems: Development and mechanism

An appropriate response to a stressor helps us to cope with that particular situation, for example by adapting our behavior. This is reflected by focused attention to the situation at hand and by enhanced memory formation of the event, which is relevant for future use of information in similar situations. Behavioral adaptation to a stressor is largely moderated by corticosteroid hormones which are released by the adrenal glands and which bind to mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the brain, but also dependent on environmental factors (such as early life experiences) and the genetic background of individuals. The objective of this thesis was to determine how differential and coordinated activation of MRs and GRs by stress hormones influence memory systems in rodents. Imbalanced activity of these receptors may be associated with vulnerability to develop various stress-related pathologies such as depression or posttraumatic stress disorder. We used mouse models with genetic modification of MR expression, manipulations of the early life environment (with possible consequences for MR and GR expression) and used pharmacological treatments influencing MR and GR activity in mice, rats and cell cultures. We conclude that MRs and GRs are critically involved in the processing of spatial information and stimulus-response learning, regulation of emotionality and neuronal activity in brain areas important for these processes. The effects depend on context and are affected by early life experiences.