The Relationship between Acute Glucocorticoid Levels and Hippocampal Function Depends upon Task Aversiveness and Memory Processing Stage

This review evaluates the effects of glucocorticoids (GCs), the adrenal steroids released in response to stress, on memory functions requiring the hippocampus in animals and humans. The data support the hypothesis that the learning function between GCs and hippocampal-dependent memory is modulated by 1) the aversive nature of the learning paradigm and 2) stage of memory processing (acquisition, consolidation, retrieval). When tasks are minimally aversive, the glucocorticoid receptor (GR) mediates an inverted U-shaped relationship between GC levels and hippocampal function, while the mineralocorticoid receptor (MR) mediates attentional processes and/or reaction to novelty. This inverted U-shaped relationship during minimally aversive training paradigms describes GC-mediated memory processing at both acquisition and consolidation. In contrast, highly aversive paradigms activate the amygdala and elevate GCs as part of the training procedure, revealing a nonlinear inverted U-shaped relationship during acquisition and a positive linear function during consolidation. Thus, highly aversive tasks that activate the amygdala shift the memory function from an inverted U-shaped curve to a linear representation between GC levels and memory consolidation