Cortical mechanisms underlying hearing deficits in noisy backgrounds after noise trauma

About This Grant

Project Summary Noise-induced hearing loss (NIHL) is a major public health problem, affecting over 48 million adults in the United States and more than 430 million people worldwide. Individuals with NIHL often struggle to understand speech, follow conversations, and discriminate sounds in noisy environments. The World Health Organization has warned that more than one billion people are at risk of hearing loss due to noise overexposure. Despite the widespread burden, there are currently no FDA-approved pharmacological treatments for NIHL, and existing interventions are limited to hearing aids and cochlear implants. Because cochlear damage is irreversible, alternative strategies that leverage the brain’s capacity for plasticity are critically needed. The proposed research will investigate the cellular and circuit mechanisms within the primary auditory cortex (A1) that underlie impaired perception in noisy environments following NIHL. Our recent work has identified cell-type-specific plasticity in glutamatergic principal neurons (PNs) and inhibitory interneurons expressing parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal peptide (VIP) in A1, but these findings were limited to quiet conditions. The contributions of such plasticity to hearing deficits in noisy environments remain unknown. In Aim 1, we will use longitudinal in vivo two-photon Ca2⁺ imaging (2PCI) in awake mice to characterize the responses of A1 L2/3 PNs, PVs, SOMs, and VIPs to simple and complex auditory stimuli presented in noisy backgrounds after NIHL. In Aim 2, we will combine longitudinal 2PCI with an operant behavior assay to link perceptual tone detection performance to cell-type-specific activity in A1 during noisy conditions. In Aim 3, we will employ chemogenetic manipulation of A1 interneuron subtypes following NIHL and assess how modulating their activity influences both cortical dynamics and behavioral performance in noise. Together, these studies will reveal how specific excitatory and inhibitory neuron populations contribute to auditory perception in noise after NIHL and identify cortical targets for hearing rehabilitation. By defining neural mechanisms of perceptual deficits, this project has the potential to guide the development of novel therapeutic strategies for millions of individuals affected by NIHL.