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Understanding how glucocorticoids interact with neuromodulators to facilitate life-history transitions

了解糖皮质激素如何与神经调节剂相互作用以促进生活史转变

基本信息

批准号：
1755427
负责人：
Deborah Lutterschmidt
金额：
$ 70万
依托单位：
Portland State University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1755427&HistoricalAwards=false
关键词：
Understanding how glucocorticoids interact neuromodulators

项目摘要

All organisms must choose between investing resources in producing young or maintaining self through feeding, growth, and repair of tissues. Each time an organism makes this choice, it must also cope with the associated trade-offs that directly impact both its survival and reproductive fitness. Despite the critical importance of choosing between self-maintenance and reproduction, the mechanisms that shape these decision-making processes is not yet understood. In addition, it is not clear how resource availability, such as the quantity of body fat stores and the presence of mates and food, influences the motivation to pursue one opportunity over another. The goal of this project is to understand if and how glucocorticoid hormones interact with specific neuropeptides in the brain to regulate the behavioral switch between reproduction and feeding. This project provides outstanding opportunities for student involvement, with hands-on training in techniques that integrate neuroendocrine methods with behavioral analyses in the field. All project participants receive training in effective science communication techniques using a teaching module that includes participation in a community-based workshop on the "Neurobiology of Decision-Making." The proximate goal is to broaden the participation of diverse students in science education and community outreach. The researcher also incorporates project results into inquiry-based learning modules for use in the classroom, thereby exposing many more students to scientific discovery than is typically achievable in the laboratory. This project merges field and laboratory studies to better understand the neuroendocrine basis of decision-making. Because the decision to pursue reproductive versus foraging opportunities occurs on a short time scale (minutes to hours) in many animals, it is often difficult to disentangle the mechanisms that regulate both the individual behaviors and the transition between them. In this context, organisms that exhibit seasonal transitions between temporally distinct life-history stages can illuminate the mechanisms that regulate the underlying behaviors in all animals. Red-sided garter snakes (Thamnophis sirtalis) are a phenomenal vertebrate model in this regard because reproduction and foraging are relegated to temporally distinct life-history stages, and snakes undergo dramatic changes in hormone-brain-behavior relationships during the transition to foraging. Based on extensive preliminary data from the investigator's laboratory, this project tests a model in which glucocorticoids interact with the neuromodulators arginine vasotocin and neuropeptide Y to facilitate life-history transitions. The investigator uses a combination of pharmacological manipulation, immunohistochemistry, Western blot, and behavioral assays to achieve the following aims: (1) Determine the function of elevated glucocorticoids during life-history transitions; (2) Determine how glucocorticoids interact with neuromodulators to induce life-history transitions; and (3) Determine if and how neuromodulators are associated with altered sensitivity of the hypothalamus-pituitary-adrenal axis. Results from this project will provide a framework for understanding the neuroendocrine basis of decision-making and the mechanisms by which neuroendocrine signals reconfigure regulatory systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

所有生物体都必须在投入资源生产幼体和通过喂养、生长和修复组织来维持自身之间做出选择。每当生物体做出这种选择时，它还必须处理直接影响其生存和繁殖适应性的相关权衡。尽管在自我维持和繁殖之间做出选择至关重要，但形成这些决策过程的机制尚不清楚。此外，目前还不清楚资源的可用性，如身体脂肪储存的数量和配偶和食物的存在，是如何影响追求一个机会而不是另一个机会的动机的。该项目的目标是了解糖皮质激素是否以及如何与大脑中的特定神经肽相互作用，以调节繁殖和摄食之间的行为转换。该项目为学生参与提供了绝佳的机会，并提供了将神经内分泌方法与该领域行为分析相结合的技术实践培训。所有项目参与者都通过一个教学模块接受有效科学传播技术的培训，其中包括参加一个以社区为基础的“决策的神经生物学”讲习班。最近的目标是扩大不同学生对科学教育和社区外展的参与。研究人员还将项目结果纳入以探究为基础的学习模块，以便在课堂上使用，从而使更多的学生接触到科学发现，而不是通常在实验室中实现的。该项目结合了现场和实验室研究，以更好地了解决策的神经内分泌基础。因为在许多动物中，追求繁殖机会还是觅食机会的决定发生在很短的时间尺度上（几分钟到几小时），所以通常很难理清调节个体行为和它们之间转换的机制。在这种情况下，在时间上不同的生活史阶段之间表现出季节性转变的生物体可以阐明调节所有动物潜在行为的机制。在这方面，红边吊带蛇（Thamnophis sirtalis）是一个非凡的脊椎动物模型，因为繁殖和觅食在时间上是不同的生活史阶段，在向觅食过渡的过程中，蛇在激素-大脑-行为关系方面经历了巨大的变化。基于研究者实验室的大量初步数据，该项目测试了糖皮质激素与神经调节剂精氨酸缩宫素和神经肽Y相互作用以促进生活史转变的模型。研究者使用药理学操作、免疫组织化学、免疫印迹和行为分析相结合的方法来达到以下目的：(1)确定在生活史转变期间糖皮质激素升高的功能；(2)确定糖皮质激素如何与神经调节剂相互作用以诱导生活史转变；(3)确定神经调节剂是否以及如何与下丘脑-垂体-肾上腺轴的敏感性改变相关联。该项目的结果将为理解决策的神经内分泌基础和神经内分泌信号重新配置调节系统的机制提供一个框架。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。