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

对潜在威胁的行为和神经内分泌反应的常见神经元通路

• 批准号: 10386575
• 负责人: Euphemia (Jena) Sabah Gewarges
• 金额: $ 3.82万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-02 至 2024-09-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10386575
• 关键词: Acute; Animal Model; Animals; Anterior; Anxiety Disorders; Area; Automobile Driving; Behavior; Behavioral; Calcium; Corticosterone; Data; Feedback; Glutamates; Goals; Hippocampus (Brain); Human; Hypothalamic structure; Immunohistochemistry; Individual; Individual Differences; Lesion; Measurement; Measures; Mediating; Mus; Neural Pathways; Neuroanatomy; Neurons; Neurosecretory Systems; Output; Pathway interactions; Phenotype; Plasma; Psychological Stress; Regulation; Research; Risk Assessment; Risk-Taking; Rodent; Role; Structure; Structure of terminal stria nuclei of preoptic region; Techniques; Testing; Training; Work; acute stress; arm; biological adaptation to stress; career; designer receptors exclusively activated by designer drugs; experimental study; hypothalamic-pituitary-adrenal axis; in vivo calcium imaging; neural circuit; novel; paraventricular nucleus; relating to nervous system; response

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.

项目概要/摘要： 面对潜在的威胁，冒险行为的个体差异往往伴随着 下丘脑-垂体-肾上腺（HPA）轴激活的相应差异。但是，底层 可能为行为和神经内分泌控制提供共同通路的神经回路， 被探索。这项研究的长期目标是确定提供这种共同作用的神经回路。 在应对潜在威胁时，调节行为和神经内分泌输出的途径。一 腹侧下托向前床的投射是提供这一共同通路的候选者 终纹核（aBNST）。该投射的神经解剖学包括直接的脑电活动， 投射从血管发送到aBNST，这反过来又将GABA能投射发送到 下丘脑的室旁核（PVN）是应激反应的主要发起者。先前 研究表明，VEGFR 2和BNST都与冒险行为和HPA轴抑制有关。该vanjiang 向PVN发送很少的投射，这表明它通过一个信号传递对HPA轴的抑制作用。 继电器结构，如BNST。事实上，PVN投射的aBNST神经元显示出在VEGF-C中激活减少。 提示aBNST可能是VEGF-C提供HPA轴的中继器 抑制作用此外，急性应激引起投射到aBNST的VEGFR 2神经元和PVN的激活 投射BNST神经元。鉴于这些数据，vSUB-aBNST投影可能提供一个共同的途径， 在潜在的威胁下，介导行为和神经内分泌控制，这是 这个提议。在第一个目标中，我们将确定vSUB-aBNST投射中的钙活性如何与 冒险行为和HPA轴活动的潜在威胁范例。在第二个目标中，我们将确定 在潜在威胁范例期间激活vSUB-alBNST投射是否改变冒险行为 HPA轴活性。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，可能揭示一种新的神经回路作为行为和神经内分泌的共同途径 调控