The Neuroendocrine Stress Axis in Amphibian Development and Physiology

动物在生命周期的各个阶段都会做出关键的“决定”。这些决定本质上是发育的、生理的和行为的，代表了对外部和内部因素的关键评估。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。生理传感器根据能量平衡和环境压力计算这些权衡，效应器根据这些决定启动生理、发育和行为反应。神经内分泌应激轴为动物整合来自多个来源（内部和外部）的信息并做出相应的反应（行为、生理和发育）提供了一种手段。本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了解1)中枢促肾上腺皮质激素释放激素（CRH）应激回路如何在响应环境应激时组织和调节，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的表达和作用。脊椎动物神经内分泌应激轴的基本组成和组织形成于进化早期，其结构和功能是保守的。因此，在青蛙身上的发现很可能适用于其他脊椎动物物种。这些研究的结果将有助于更好地理解两栖动物对环境压力的反应，并且，鉴于最近有记录的全球两栖动物数量下降，可以为野生动物保护工作提供至关重要的知识。这些研究的广泛影响包括为高中生和本科生提供参与前沿科学的机会，继续进行国际合作，并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.