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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

基本信息

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

项目摘要

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.

荷尔蒙状态可以改变包括人类在内的许多动物的听力，但目前尚不清楚荷尔蒙如何影响内耳的结构和功能。这项研究使用普莱芬恩学员鱼来了解荷尔蒙如何影响听力。在繁殖季节，雄性军校鱼歌唱以吸引配偶，这使得声音交流对繁殖成功至关重要。雌性军校鱼在听力上表现出季节性的、依赖雌激素的变化，这使它们更容易找到潜在的配偶。这项研究询问雌激素如何影响与听力有关的感官受体的产生、存活和功能，以提高听力敏感度。这项研究通过增加对自然界的了解，并提供对激素如何影响内耳以调节听力的洞察，产生了更广泛的影响--这些发现可以适用于包括人类在内的许多物种。这项研究还通过让高中教师和他们的学生接触科学方法和尖端科学技术来影响社会。作为M.J.默多克科学慈善信托伙伴计划的一部分，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，并在全国会议上展示他们的工作。这些教师还与学术团队合作，为课堂制定基于研究的教案。公众可以通过研究生主持的博物馆互动演示了解这项研究。通过这种方式，非科学家分享科学的兴奋，学生获得关键的沟通技能，他们可以在未来使用。与生殖周期相关的感觉可塑性的激素调节在脊椎动物中很普遍，但导致这些类固醇依赖变化的潜在分子和遗传机制仍然知之甚少。本项目采用分子、解剖学和生理学相结合的方法来确定性腺类固醇对编码社会相关声音信号的适应性听觉可塑性的影响。这项研究的目的是确定雌激素如何调节女性平原学员内耳的细胞和分子变化，导致季节性的类固醇依赖的听力变化，从而加强物种内的声学交流，以促进生殖。中心假设是雌激素上调内耳基因网络，促进祖细胞增殖、毛细胞分化和细胞存活，导致生殖雌性军校鱼毛细胞增加和听觉敏感度增强。这些实验使用体外和体内两种方法来操纵来自不同生殖状态的女性学员的细胞信号(Wnt、Noch和热休克信号通路)。基因表达变化用qRT-PCR检测，细胞增殖和存活用细胞生物学检测和荧光显微镜检测，听功能用电生理学检测。这些研究允许深入了解神经和内分泌机制，这些机制可能会增强所有脊椎动物的沟通。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。