Abstract
The hippocampus and amygdala play major roles in the elaboration of stress responses to psychogenic stimuli. Damage to select regions of these structures substantially alters the HPA-response to stress: damage to the ventral subiculum enhances stress responsiveness, whereas medial amygdala lesions diminish stress-induced corticosterone secretion. Importantly, neither the ventral subiculum nor the medial amygdala directly innervate paraventricular nucleus (PVN) neurons controlling the stress response. Rather, regulatory information is relayed largely through cell populations in the bed nucleus of the stria terminalis (BST), medial preoptic area (mPOA), dorsomedial hypothalamus (DMH) and the peri-PVN region. Combined tract-tracing and in situ hybridization studies indicate that ventral subicular projections to BST, mPOA, DMH and peri-PVN are predominantly glutamatergic, whereas projections to the same regions from the medial amygdala are GABAergic. The data support the hypothesis that the hippocampus, via the subiculum, inhibits stress responses by glutamatergic excitation of GABAergic PVN-projecting neurons. In contrast, the amygdala, by way of the medial amygdaloiod nucleus, activates the stress response by disinhibition, involving GABAergic inhibition of GABA neurons that in turn project to the PVN. The data suggest that hippocampal and amygdaloid outflow is integrated by forebrain/hypothalamic structures prior to accessing the PVN, and affords an opportunity for limbic information to interface with hypothalamic homeostats prior to activating a stress response. Supported by NIMH grant MH49698. [Jpn J Physiol 54 Suppl:S27 (2004)]
