Collaborative Research: Cell signaling regulation of hormonally mediated auditory plasticity

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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.