Norepinephrine and glucocorticoid effects on the brain mechanisms underlying memory accuracy and generalization

Stressful and emotionally arousing experiences activate hormonal and brain systems that create strong memories. Extensive evidence indicates that this strengthening effect involves the synergistic action of both norepinephrine and glucocorticoid hormones. This tight regulation of emotional memories is normally highly adaptive and pivotal for survival; yet, aberrant memory processing of stressful events is a major risk factor for the development of stress-related psychopathology. It remains unclear, however, to what extent these two stress hormone systems also affect the quality of such strengthened memories. In this Review, we discuss recent advances in the understanding of norepinephrine and glucocorticoid effects on the accuracy and generalization of contextual or episodic-like aspects of memory in rodents. We will argue that norepinephrine and glucocorticoids exert opposite effects on accuracy and generalization of memory through distinct effects on systems consolidation processes underlying the time-dependent reorganization of memory. Norepinephrine improves memory accuracy by boosting basolateral amygdala-hippocampal connectivity, hereby creating long-lasting hippocampus-dependent episodic-like memories. In contrast, glucocorticoids contribute to memory generalization by promoting integration of new memories into neocortical networks, decreasing hippocampal dependence. We discuss possible implications of these conceptual insights for understanding inter-individual differences in stress resilience and risk for psychopathology.