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: 1933166
• 负责人: Joseph Sisneros
• 金额: $ 76.6万
• 依托单位: University of Washington
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1933166&HistoricalAwards=false
• 关键词: Collaborative; Research; Cell; signaling; regulation; 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力能力，但尚不清楚骑马如何影响内耳的结构和功能。这项研究使用Plainfin Midshipman鱼来了解骑马的影响。在繁殖季节，男性中船员鱼唱歌以吸引伴侣，使声学交流对于生殖成功至关重要。雌性中型鱼类鱼类表现出季节性的雌激素依赖性听力变化，使他们更容易找到潜在的伴侣。这项研究询问雌激素如何影响听力涉及的感觉接收器的产生，生存和功能，以提高听力敏感性。这项研究通过增加对自然世界的理解并提供有关马匹如何影响内耳来调节听力的洞察力（可以适用于包括人类在内的许多物种的发现），从而产生了更广泛的影响。这项研究还通过使高中教师及其学生采用科学方法和尖端的科学技术来影响社会。作为M.J. Murdock慈善信托基金会的一部分，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，并在国家会议上介绍他们的工作。这些老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来了解这项研究。通过这种方式，非科学家分享了科学的兴奋，学生并获得了他们将来可以使用的关键沟通技巧。对与生殖周期相关的感觉可塑性的调节是脊椎动物中普遍存在的，但是基本的分子和遗传机制负责这些依赖于这些依赖于这些立体的变化。该项目采用综合分子，解剖和生理方法来确定性腺立体体对编码社会相关的声学信号的自适应听觉可塑性的影响。这项研究的目的是确定雌激素如何调节雌性平原中部船员内耳的细胞和分子变化，从而导致季节性的，类固醇依赖性的听力变化，从而增强了种内的声学通信以促进繁殖。中心假设是雌激素上调内耳网络网络，用于祖细胞增殖，毛细胞分化和细胞存活，从而导致毛细胞添加增加，并增强了生殖雌性中胎生鱼类的听觉敏感性。该实验都使用体外和体内方法来操纵来自不同生殖状态的女性中船员的细胞信号传导（Wnt，Notch和Head Shock Signal传导途径）。通过QRT-PCR，细胞增殖和细胞生物学测定法和荧光显微镜以及电生理学的听觉功能评估基因表达的变化。这些研究允许深入了解可能在所有脊椎动物中加强沟通的神经元和内分泌机制。该奖项反映了NSF的法定任务，并通过使用基金会的知识分子和更广泛的影响评估标准来评估，被认为是宝贵的支持。