Hormone-Mediated Plasticity within Central Auditory Circuits

PROJECT SUMMARY/ABSTRACT This proposal will causally test how hormones affect the development and activation of the neural circuitry that drives auditory processing. In humans and other vertebrates, major life transitional events such as development and reproduction are driven by changes in levels of circulating hormones which can impact hearing. Sex steroids like estrogen and testosterone have been shown to have differential effects on hearing sensitivity in adults, while thyroid hormone and glucocorticoids affect infant development and hearing loss in children. Hormone systems are thus becoming targets of therapeutic interventions aimed at improving the quality of life for the approximately 1 in 4 humans that have some level of hearing loss. These therapies can be used to enhance peripheral auditory system function, but their direct impacts on central auditory processing neural circuits is less clear. Understanding the mechanisms through which neuroendocrine systems shape plasticity in auditory function during development and reproduction will provide crucial insights into hormone-mediated hearing loss. The proposed research combines molecular and electrophysiological approaches to examine the basis of neuroendocrine modulation of auditory processing during reproduction and development. Harnessing the well characterized sex-specific acoustically-guided behaviors of one of nature’s acoustic specialists, the frog, this proposal sets out to test the central hypothesis that plasticity in auditory processing is driven by neuroendocrine systems that acutely modulate molecular and neuronal function. My overall objective is to gain essential knowledge and skills to establish an independent research program that advances our understanding of how the brain organizes and integrates auditory cues across biological timescales. During the K99 phase, I will use Tag-Based-RNA-Sequencing (TagSeq) and multiunit electrophysiology techniques to characterize the molecular profile and neural activity patterns of central auditory processing regions pre- and post-reproduction. During the R00 phase, I will implement the techniques acquired in the mentored phase to examine plasticity within the auditory system over development. These experiments will not only test fundamental hypotheses about hormonal regulation of gene expression and neural circuit activity but will help discover novel molecular mechanisms that are important for reorganizing auditory systems in times of drastic and acute physiological change. This research will serve as a launching point to develop a larger research program that investigates how hormones modulate plasticity of auditory function during development. Investigations into the factors, neural circuits, and genes that regulate auditory processing will provide insights into how hormone signaling impacts, and could potentially help ameliorate, hearing-related disorders.