With respect to extrahypothalamic regulation of the HPA axis, lesion studies have clearly demonstrated the importance of both forebrain and hindbrain regions for regulation of the HPA axis under both basal and stress conditions (Herman et al., 2003; Pecoraro et al., 2006). In response to stress, these regions appear to be differentially involved in activation of the HPA axis such that neural inputs to the PVN that originate from hindbrain structures are involved in activating the HPA axis following a physiological stressor (e.g., internal, physiological disturbances in homeostasis, such as fluid loss or immune challenge (Herman et al., 2003; Pecoraro et al., 2006)), while those originating in the forebrain are involved in HPA axis activation following psychological stressors (e.g., external, psychological disturbances, such as threat signals (Ulrich-Lai and Herman, 2009)). Taken together, the HPA axis is an intricate system which exhibits both simple and complex means of regulation and exerts both rapid and delayed effects on neuronal function.
