NEUROCIRCUITRY OF STRESS - CENTRAL CONTROL OF THE HYPOTHALAMO-PITUITARY-ADRENOCORTICAL AXIS

Integration of the hypothalamo-pituitary-adrenal stress response occur s by way of interactions between stress-sensitive brain circuitry and neuroendocrine neurons of the hypothalamic paraventricular nucleus (PV N). Stressors involving an immediate physiologic threat ('systemic' st ressors) are relayed directly to the PVN, probably via brainstem catec holaminergic projections. By contrast, stressors requiring interpretat ion by higher brain structures ('processive' stressors) appear to be c hanneled through limbic forebrain circuits. Forebrain limbic sites con nect with the PVN via interactions with GABA-containing neurons in the bed nucleus of the stria terminalis, preoptic area and hypothalamus. Thus, final elaboration of processive stress responses is likely to in volve modulation of PVN GABAergic tone. The functional and neuroanatom ical data obtained suggest that disease processes involving inappropri ate stress control involve dysfunction of processive stress pathways.