Investigating a Potential Mechanism of Noise-Induced Synaptopathy
Abstract
Noise is the most common cause of preventable hearing loss, affecting 31 million Americans. A less-studied subcategory of noise-induced hearing loss is known as hidden hearing loss, in which the synapses connecting inner ear hair cells to afferent ganglion neurons are damaged (termed synaptopathy). This damage is suspected to be caused by excess glutamate release in the synaptic cleft. However, the exact mechanism of synaptopathy remains unknown, and there is currently no FDA approved treatment. Here we investigate a potential mechanism of noise-induced synaptopathy. We hypothesize that excess glutamate release following noise damage will cause AMPA receptors lacking the GluA2 subunit to leak excess calcium into the ganglion cell, and that heterogenous distribution of this GluA2 subunit will be negatively correlated with calcium entry and damage to the ganglion cell. This hypothesis was tested by using noise to damage hair cells in the zebrafish lateral line – an established vertebrate model for studying noise-induced hearing loss. Following noise damage, GluA2 and GluA4 subunit distribution and intracellular calcium levels were determined. Synaptic integrity and ganglion cell death were also assessed at different time points after noise exposure. This research can shed light on the suspected mechanism of AMPA-receptor mediated synaptopathy following acoustic trauma, thus uncovering a potential pharmacological target. Given the absence of an FDA approved treatment and the inefficacy of hearing aids in mitigating hidden hearing loss, our research has the potential to fill a health care gap for a currently untreatable condition.
About the Presenter
Forrest Fearington
My name is Forrest, and I am a senior in the neuroscience program here at WSUV. My interest in research was sparked watching a documentary on 21st-century biomedical breakthroughs back in middle school. Since then (and even before then), witnessing several of my family members benefit from these breakthroughs fueled my initial interest in research as an undergrad. For the past year, my work in the Coffin lab has sought to understand the molecular mechanisms of noise-induced hearing loss with the goal of developing preventative therapies. I will soon be applying to medical school, and I am hoping to use this experience to further my research career as a medical student and physician. Outside of lab, I volunteer at the local free clinic and serve as an officer for the WSUV Pre-Health Club. During my free time, I closely follow professional baseball, tutor piano (suspended by COVID), and dabble in tennis, golf, and baseball with friends and family.