Post-traumatic Stress Disorder: Evidence for Trauma-induced Brain Dysfunction Stress systems in the brain: molecules, nuclei and circuits

While the peripheral endocrine components of the stress-responsive systems are well known, the same cannot be said of the stress axis within the CNS itself. One relay point in brain is now clear the parvocellular subdivision of the paraventricular nucleus of the hypothalamus (mpPVN). Corticotropin releasing hormone (CRH) containing cells within this nucleus appears to be modulated by circuits responsive to stress. Earlier points in the stress circuit(s) in brain are currently only vaguely evident. We have divided the types of regulatory circuits involved in CNS control of stress into those which activate CRH cells and those which inhibit them. Here, data from a series of studies on the inhibito O' arm of the hypothalamo-pituitary-adrenal axis will be presented. A logical extension of this dichotomy is the presumption that among inhibitory circuits are those which respond to elevated circulating glucocorticoid levels and thereby provide 'negative feedback'. Among the studies discussed will be those involving hippocampus, glucocorticoid receptors, and subiculum connections to the bed nucleus of the stria terminalis and on to the mpPVN. A second set of studies is focused on the circuits which activate the PVN. These studies are rather new and take the view that many regions of CNS may be involved, with different areas mediating the responses to different classes of stressors. The ultimate goals of these studies are the identification of the activation and inhibition circuits and related neurochemistry involved in the control of the brain's response to stress.