Project Summary/Abstract: In the face of a potential threat, individual differences in risk-taking behaviors are often accompanied by corresponding differences in hypothalamic-pituitary-adrenal (HPA) axis activation. However, the underlying neural circuitry that may provide a common pathway for both behavioral and neuroendocrine control has not been explored. The long-term goal of this research is to identify the neural circuitry that provides this common pathway for mediating both behavioral and neuroendocrine outputs in response to a potential threat. One candidate for providing this shared pathway is the projection from ventral subiculum (vSUB) to anterior bed nucleus of the stria terminalis (aBNST). The neuroanatomy of this projection consists of direct glutamatergic projections sent from the vSUB to the aBNST, which in turn sends GABAergic projections to the paraventricular nucleus (PVN) of the hypothalamus, the primary initiator of the stress response. Previous studies have implicated both vSUB and BNST in risk-taking behavior and in HPA axis inhibition. The vSUB sends scant projections to the PVN, suggesting that it relays its inhibitory effects on the HPA axis through a relay structure such as BNST. Indeed, PVN projecting aBNST neurons show reduced activation in vSUB- lesioned animals, suggesting that the aBNST may be the relay through which the vSUB provides HPA axis inhibition. Furthermore, acute stress causes activation of vSUB neurons projecting to the aBNST and of PVN projecting BNST neurons. Given these data, the vSUB-aBNST projection may provide a common pathway that mediates both behavioral and neuroendocrine control under potential threat, which is the central hypothesis of this proposal. In the first Aim, we will determine how calcium activity in the vSUB-aBNST projection relates to risk-taking behavior and HPA axis activity in a potential threat paradigm. In the second Aim, we will determine whether activation of the vSUB-alBNST projection during a potential threat paradigm alters risk-taking behavior and HPA axis activity. The results will reveal the role of this projection in risk-taking behavior and HPA axis regulation, potentially revealing a novel neural circuit as a common pathway for behavior and neuroendocrine regulation.