Marsh Jena S, Teixeira Cara, Gavade Swapnil, Johnston Colin, Baranwal Salisha, Snyder Christen N, Chang Chih-Lin, Yang Shany, Spencer-Segal Joanna L
Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA; Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, USA.
Michigan Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, USA.
Psychoneuroendocrinology. 2025 Jan;171:107229. doi: 10.1016/j.psyneuen.2024.107229. Epub 2024 Oct 30.
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.
回避或类似焦虑的行为伴随着下丘脑 - 垂体 - 肾上腺（HPA）轴激活的相应变化。这种协调的行为和神经内分泌控制的潜在神经回路尚未完全明确。先前的研究指出，从腹侧下托（vSub）到终纹床核（BNST）的神经投射可以抑制HPA轴对应激的反应。在这里，我们使用化学遗传学来研究vSub神经元及其向前侧终纹床核（aBNST）的投射在雄性和雌性小鼠回避行为及伴随的皮质酮反应中的作用。令人惊讶的是，我们发现腹侧下托神经元的化学遗传学激活增加了雄性和雌性小鼠对旷场试验的HPA轴反应，选择性激活投射到前侧终纹床核的vSub神经元（vSub - aBNST神经元）时也观察到了这种情况。另一方面，vSub神经元和vSub - aBNST神经元的激活对回避行为有不同影响，这表明vSub的行为作用是可变的，并且与其神经内分泌作用可分离。总之，我们的结果揭示了腹侧下托通过前侧终纹床核在HPA轴激活中出人意料的新作用。我们还表明，与腹侧海马一样，腹侧下托神经元根据其下游投射可增加或减少回避行为。
