Temporally Tuned Corticosteroid Feedback Regulation of the Stress Axis

Activity of the hypothalamic-pituitary-adrenal (HPA) axis is tuned by corticosteroid feedback. Corticosteroids regulate cellular function via genomic and nongenomic mechanisms, which operate over diverse time scales. This review summarizes recent advances in our understanding of how corticosteroid feedback regulates hypothalamic stress neuron function and output through synaptic plasticity, changes in intrinsic excitability, and modulation of neuropeptide production. The temporal kinetics of corticosteroid actions in the brain versus the pituitary have important implications for how organisms respond to stress. Furthermore, we will discuss, some of the technical limitations and missing links in the field, and the potential implications these may have on our interpretations of corticosteroid negative feedback experiments.