Collaborative Research: Cell signaling regulation of hormonally mediated auditory plasticity

合作研究：激素介导的听觉可塑性的细胞信号调节

• 批准号: 1932898
• 负责人: Allison Coffin
• 金额: $ 50.6万
• 依托单位: Washington State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1932898&HistoricalAwards=false
• 关键词: Collaborative; Research; Cell; signaling; regulation

Hormonal state can alter hearing capabilities in many animals, including humans, but it is not known how hormones affect the structure and function of the inner ear. This research uses plainfin midshipman fish to understand how hormones affect hearing. During the breeding season, male midshipman fish sing to attract mates, making acoustic communication vital for reproductive success. Female midshipman fish show seasonal, estrogen-dependent changes in hearing that make it easier for them to locate potential mates. This research asks how estrogen affects the production, survival, and function of sensory receptors involved in hearing to increase hearing sensitivity. This research has broader impact by increasing understanding of the natural world and providing insight into how hormones can influence the inner ear to modulate hearing – findings that can apply to many species, including humans. This research also impacts society by exposing high school teachers and their students to both the scientific method and cutting-edge scientific techniques. As part of the M.J. Murdock Charitable Trust Partners in Science program, high school teachers will work in university laboratories for two summers, gain valuable research skills, and present their work at national conferences. These teachers also work with the academic team to develop research-based lesson plans for the classroom. Members of the public can learn about this research through interactive museum demonstrations hosted by graduate students. In this way, non-scientists share the excitement of the science and students gain critical communication skills that they can use in the future.Hormonal modulation of sensory plasticity related to reproductive cycles is widespread among vertebrates, but the underlying molecular and genetic mechanisms responsible for these steroid-dependent changes remain poorly understood. This project takes an integrated molecular, anatomical, and physiological approach to determine the effects of gonadal steroids on the adaptive auditory plasticity for encoding socially relevant acoustic signals. The objective of this study is to determine how estrogen regulates cellular and molecular changes in the inner ear of the female plainfin midshipman, leading to seasonal, steroid-dependent changes in hearing that enhance intraspecific acoustic communication to facilitate reproduction. The central hypothesis is that estrogen upregulates inner ear gene networks for progenitor cell proliferation, hair cell differentiation, and cell survival, leading to increased hair cell addition and enhanced auditory sensitivity in reproductive female midshipman fish. The experiments use both in vitro and in vivo approaches to manipulate cellular signaling (Wnt, notch, and heat shock signaling pathways) in female midshipman from different reproductive states. Changes in gene expression are assessed with qRT-PCR, cell proliferation and survival with cell biology assays and fluorescent microscopy, and auditory function with electrophysiology. These studies allow to gain insight into neural and endocrine mechanisms that may act to enhance communication in all vertebrates.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.

激素状态可以改变包括人类在内的许多动物的听觉能力，但目前尚不清楚激素如何影响内耳的结构和功能。这项研究使用plainfin海军军官候补生鱼来了解激素如何影响听力。在繁殖季节，雄性海军军官学校的鱼会唱歌来吸引配偶，这使得声音交流对繁殖成功至关重要。雌性见习生鱼的听觉表现出季节性的、雌激素依赖性的变化，这使它们更容易找到潜在的配偶。这项研究探讨了雌激素如何影响与听力有关的感觉受体的产生、存活和功能，以提高听力灵敏度。这项研究通过增加对自然世界的了解，并深入了解激素如何影响内耳来调节听力，从而产生更广泛的影响-这些发现可以适用于许多物种，包括人类。这项研究还通过让高中教师和学生接触科学方法和尖端科学技术来影响社会。作为M. J.默多克慈善信托基金科学合作伙伴计划的一部分，高中教师将在大学实验室工作两个夏天，获得宝贵的研究技能，并在全国会议上介绍他们的工作。这些教师还与学术团队合作，为课堂制定基于研究的课程计划。公众可以通过研究生主持的互动博物馆演示了解这项研究。通过这种方式，非科学家分享科学的兴奋，学生获得他们可以在未来使用的关键沟通技巧。与生殖周期相关的感觉可塑性的激素调节在脊椎动物中广泛存在，但对这些类固醇依赖性变化的潜在分子和遗传机制仍然知之甚少。该项目采用综合的分子，解剖学和生理学方法来确定性腺类固醇对编码社会相关声学信号的自适应听觉可塑性的影响。本研究的目的是确定雌激素如何调节雌性plainfin海军军官候补生内耳的细胞和分子变化，导致听力的季节性，类固醇依赖性变化，增强种内声学通信，以促进生殖。核心假设是雌激素上调内耳基因网络的祖细胞增殖，毛细胞分化和细胞存活，导致增加的毛细胞增加和增强的听觉灵敏度在生殖女性见习生鱼。该实验使用体外和体内方法来操纵来自不同生殖状态的女性海军学员的细胞信号传导（Wnt，notch和热休克信号传导途径）。用qRT-PCR评估基因表达的变化，用细胞生物学测定和荧光显微镜评估细胞增殖和存活，用电生理学评估听觉功能。这些研究可以深入了解神经和内分泌机制，可能会采取行动，以加强所有脊椎动物的沟通。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。