Ventral subiculum control of avoidance behavior and hypothalamic-pituitary-adrenal axis reactivity via the bed nucleus of the stria terminalis in male and female mice - ISPNE 2024 Dirk Helhammer Award.

Avoidance or anxiety-like behavior is accompanied by corresponding changes in hypothalamic-pituitary-adrenal (HPA) axis activation. The underlying neural circuitry for this coordinated behavioral and neuroendocrine control is not well established. Prior studies pointed to a neural projection from the ventral subiculum (vSub) to the bed nucleus of the stria terminalis (BNST) that can inhibit the HPA axis response to stress. Here, we used chemogenetics to investigate the role of vSub neurons and their projection to the anterior BNST (aBNST) in avoidance behavior and the accompanying corticosterone response in male and female mice. Surprisingly, we found that chemogenetic activation of ventral subiculum neurons increased the HPA axis response to an open field test in male and female mice, which was also seen with selective activation of vSub neurons projecting to the anterior BNST (vSub-aBNST neurons). On the other hand, VSub neuron and vSub-aBNST neuron activation had different effects on avoidance behavior, suggesting that the behavioral role of the VSub is variable and is dissociable from its neuroendocrine effects. In conclusion, our results reveal a surprising and novel role for the ventral subiculum in HPA axis activation via the anterior BNST. We also show that, like the ventral hippocampus, ventral subiculum neurons can increase or decrease avoidance behavior depending on their downstream projection.