Genetic dissection of the neuroendocrine and behavioral responses to stressful challenges

Dysregulation of the stress response is implicated in many psychopathologies. Data gathered over the past two decades have proposed a rather dualistic view of the central corticotropin-releasing factor (CRF)-urocortin system. Originally, it was thought that CRF/CRF receptor type 1 (CRFR1) signaling mediated stress-initiated effects and increased anxiety-like behavior, whereas activation of urocortins/CRFR2 ensured adequate recovery from stress and restoration of homeostasis. However, this view was based on data gained from genetically modified mouse models and pharmacological approaches; now, with the emergence of new and more specific biological tools, it has become clear that this is an over-simplistic proposal. It is becoming apparent that the function of the CRF-urocortin system’s components relies profoundly on the spatial and temporal patterns of activity of the CRF family members. Here, we provide an overview of recent work that proposes a more dynamic, modulatory role for the CRF system’s central pathways in the modulation of stress-linked behaviors. Recent findings suggest that the CRF system’s actions are brain-region specific and dependent on the type of neuronal cell involved.