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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要/摘要：面对潜在威胁，冒险行为的个体差异通常伴随着下丘脑 - 垂体 - 肾上腺（HPA）轴激活的相应差异。但是，基础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被探索了。这项研究的长期目标是确定提供这种常见的神经回路响应潜在威胁，介导行为和神经内分泌产量的途径。一提供此共享途径的候选人是从腹侧底部（VSUB）到前床的投影质末端的核（abnst）。该投影的神经解剖学由直接谷氨酸能从VSUB发送到ABNST的预测又将GABA能预测发送给下丘脑的副核核（PVN），应力反应的主要启动因子。以前的研究已将VSUB和BNST涉及冒险行为和HPA轴抑制作用。 VSUB 向PVN发送很少的预测，表明它通过A对HPA轴的抑制作用进行了继电器结构，例如BNST。实际上，PVN投射ABNST神经元在VSUB- 病变的动物，表明ABNST可能是VSUB提供HPA轴的继电器抑制。此外，急性应激会导致投射到ABNST和PVN的VSUB神经元的激活投影双胞胎神经元。鉴于这些数据，vsub-abn的投影可能会提供一个共同的途径在潜在威胁下介导行为和神经内分泌的控制，这是这个建议。在第一个目标中，我们将确定VSUB-ABNST投影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，我们将确定在潜在威胁范式中激活VSUB-ALBNST投影是否会改变冒险行为和HPA轴活动。结果将揭示该预测在冒险行为和HPA轴上的作用调节，有可能揭示新的神经回路是行为和神经内分泌的常见途径规定。