The Neuroendocrine Stress Axis in Amphibian Development and Physiology

动物在其生命周期的各个阶段都会做出关键的“决定”。这些决定在本质上是发展的、生理的和行为的，代表了对外部和内部因素的批判性评估。例如，变态、孵化或出生的时间可能取决于发育栖息地中生长机会和死亡风险之间的权衡。生理传感器计算这些权衡作为能量平衡和环境压力的函数，并且效应器启动对这些决定的生理、发育和行为响应。神经内分泌应激轴为动物提供了一种整合来自多种来源（内部和外部）的信息并相应地（行为，生理和发育）做出反应的手段。这些研究的目的是为理解神经内分泌应激系统中的信号传导提供一个机制基础。这些实验将利用一种强大的模式生物，南非爪蟾。拟议的研究将使用神经解剖学，生理学和分子方法来理解1）如何组织和调节中枢促肾上腺皮质激素释放激素（CRH）应激回路以应对环境应激，以及2）皮质类固醇（肾上腺应激激素）反馈和CRH结合蛋白如何调节CRH表达和作用。脊椎动物神经内分泌应激轴的基本组成和组织在进化的早期就出现了，这些通路的结构和功能是保守的。因此，青蛙的发现可能适用于其他脊椎动物物种。这些研究的结果应该提供一个更好的了解如何两栖动物应对环境压力，并考虑到最近记录的全球两栖动物种群下降，可以提供知识至关重要的野生动物保护工作。 这些研究的更广泛的影响包括高中和本科生参与前沿科学的机会，持续的国际合作，以及进一步确定环境压力对自然两栖动物种群健康的影响。

Animals make critical 'decisions' at all stages of their life cycles. These decisions are developmental, physiological and behavioral in nature, and represent a critical assessment of both external and internal factors. For example, the timing of metamorphosis, hatching, or birth may depend upon the tradeoffs between growth opportunity and mortality risk in the developmental habitat. Physiological sensors compute these tradeoffs as a function of energy balance and environmental stress, and effectors initiate physiological, developmental and behavioral responses to these determinations. The neuroendocrine stress axis provides a means for animals to integrate information from multiple sources (internal and external) and to respond accordingly (behaviorally, physiologically and developmentally). The objectives of the proposed studies are to provide a mechanistic basis for understanding signaling within the neuroendocrine stress system. These experiments will utilize a powerful model organism, the South African clawed frog Xenopus laevis. The proposed studies will use neuroanatomical, physiological and molecular approaches to understand 1) how central corticotropin-releasing hormone (CRH) stress circuits are organized and regulated in response to environmental stress, and 2) how corticosteroid (adrenal stress hormone) feedback and a CRH binding protein modulate CRH expression and action. The basic components and organization of the vertebrate neuroendocrine stress axis arose early in evolution, and the structure and function of these pathways are conserved. Thus, findings in the frog are likely to be applicable to other vertebrate species. Results of these studies should provide a better understanding of how amphibians respond to environmental stress, and, given recent documented global declines in amphibian populations, can provide knowledge vital to wildlife conservation efforts. The broader impacts of these studies include opportunities for high school and undergraduate students to participate in cutting edge science, continued international collaborations, and further identification of the consequences of environmental stress for the health of natural amphibian populations.