Role of the ventral subiculum in stress integration

The mammalian subiculum plays a prominent role in inhibition of the hypothalamo-pituitary-adrenocortical (HPA) axis. Lesion and stimulation studies indicate that the hippocampus, acting via output neurons of the ventral subiculum, acts to attenuate stress-induced glucocorticoid release. Lesions of the ventral subiculum enhance glucocorticoid secretion following psychogenic, but not systemic stressors, indicating that the influence of this structure on the HPA system is stressor-specific. Anatomical analyses fail to demonstrate direct interactions of the subiculum with principal stress-effector neurons in the paraventricular hypothalamus, consistent with a trans-synaptic mechanism of action. Accordingly, tracing data indicate that glutamatergic ventral subiculum neurons innervate GABAergic neurons in several paraventricular nucleus-projecting neurons in the hypothalamus and basal forebrain, suggesting that inhibition is mediated by glutamate-GABA relays. The subiculum also innervates several limbic forebrain structures that in turn have bisynaptic projections to paraventricular neurons, such as the prefrontal cortex, amygdala and lateral septum, suggesting that the subiculum may have a generalized up-stream influence on limbic stress integration. Finally, recent information suggests that the subiculum may also be stress excitatory under some circumstances, and that there may be substantial strain or individual differences in the net contribution of the subiculum, to stress integration. Overall, the present state of knowledge indicates that the role of the subiculum in stress integration is complex, and likely involves interactions of stress-relevant subicular output with limbic-hypothalamic stress-integrative circuits.