Paraventricular nucleus corticotropin-releasing hormone (CRH) neurons are activated by neural inputs from a number of possible sources (Figure 1). Stressors signaling homeostatic challenge (commonly referred to as systemic stressors) are mediated by neurocircuits providing direct excitation of paraventricular nucleus (PVN) neurons. For example, HPA-axis activation by blood loss (hemorrhage) is mediated by activation of brainstem norepinephrine neurons that project directly to the PVN. Activation of the HPA axis by fluid imbalance appears to be triggered by angiotensinergic neurons of the subfornical organ, which sense increases in circulating angiotensin II. Negative energy balance signals are relayed to the PVN by the arcuate nucleus, which activates CRH neurons by release of excitatory peptide messengers (such as neuropeptide Y and agouti-related peptide). Responses to systemic stress are thought to be reflexive, that is, they do not require the engagement of cognitive processes.
