A Common Neuronal Pathway for the Behavioral and Neuroendocrine Response to Potential Threat

项目摘要/摘要： 在面对潜在威胁时，个体冒险行为的差异往往伴随着 下丘脑-垂体-肾上腺(HPA)轴激活的相应差异。然而，潜在的 可能为行为和神经内分泌控制提供共同途径的神经回路尚未 已经被探索过了。这项研究的长期目标是确定提供这种共同的 调节行为和神经内分泌输出以应对潜在威胁的途径。一 从腹侧下丘(VSUB)到前床的投射是提供这种共同通路的候选神经。 终纹核(ABNST)。这一投射的神经解剖结构由直接谷氨酸能 从vSUB发送到aBNST的投影，aBNST又将GABA能投影发送到 下丘脑室旁核(PVN)，应激反应的主要发起者。上一首 研究表明vSUB和BNST都与冒险行为和HPA轴抑制有关。VSuB 向下丘脑室旁核发出微弱的投射，表明它通过一种 继电器结构，如BNST。事实上，PVN投射的aBNST神经元在vSuB- 提示aBNST可能是vSUB提供HPA轴的中继器 抑制力。此外，急性应激引起投射到aBNST和下丘脑室旁核的vsub神经元的激活。 投射BNST神经元。考虑到这些数据，vSUB-aBNST投影可能提供一条共同的途径， 在潜在威胁下调节行为和神经内分泌控制，这是 这项提议。在第一个目标中，我们将确定vSuB-aBNST投射中的钙活性与 潜在威胁范式中的冒险行为和HPA轴活动。在第二个目标中，我们将确定 潜在威胁范式期间vSUB-alBNST投影的激活是否会改变冒险行为 和HPA轴活动。研究结果将揭示这种投射在冒险行为和HPA轴中的作用。 调节，潜在地揭示了一种新的神经回路作为行为和神经内分泌的共同途径 监管。

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.