Noise-induced hearing loss alters efferent control of central auditory hyperactivity

The National Institute on Deafness and Other Communication Disorders awarded Creighton University $161,405 on July 1, 2026, under the Research Related to Deafness and Communication Disorders program (CFDA 93.173) to investigate how noise-induced hearing loss alters the auditory efferent system and contributes to central auditory hyperactivity.

The research examines lateral olivocochlear neurons, the most abundant efferent neurons responsible for brain-to-ear feedback and hearing protection after noise exposure. Two specific aims guide the work: determining how noise-induced hearing loss alters gene expression and LOC neuron activity, and assessing how noise-induced LOC alterations contribute to central hyperactivity. The investigator predicts that noise-induced increases in neuropeptide expression correspond to altered burst firing and calcium channel gene expression in LOC neurons. Patch-seq methodology will correlate gene expression with electrophysiological properties at the single-cell level to test whether elevated LOC activity plays a compensatory role following noise-induced hearing loss.

Performance runs through June 30, 2029, with work conducted in Omaha, Nebraska. The project grant funds direct and indirect research costs including salaries, equipment, supplies, and travel.

Abstract

Hearing loss affects ~20% of the global population, altering both peripheral and central auditory systems. IT is closely linked to auditory disorders such as tinnitus and hyperacusis. While extensive research has examined cochlear and ascending pathway dysfunction, the auditory efferent system - responsible for brain-to-ear feedback - remains underexplored. Lateral olivocochlear (LOC) neurons, the most abundant efferent neurons, promote hearing protection and recovery after noise exposure. This function may be related to their increased neurotransmitter and neuropeptide expression following noise-induced hearing loss (nihl). However, how these changes influence cochlear function depends on electrophysiological properties of LOC neurons, which remain poorly understood. Whether LOC system changes are adaptive or pathological for auditory function is also unknown. This proposal addresses these gaps by: (aim 1) determining how nihl alters gene expression and LOC neuron activity, and (aim 2) assessing how nihl-induced LOC alterations contribute to central hyperactivity. The central hypothesis is that nihl elevates LOC activity and drives correlated changes in gene expression, with the two processes acting interdependently to drive compensatory adjustments in cochlear output and mitigate central hyperactivity. Recently, i discovered a unique infra-slow burst firing pattern of electrical activity in LOC neurons, driven by CA2+ channels, which may regulate neuropeptide release onto spiral ganglion neuron dendrites. Hence, i predict that nihl-induced neuropeptide expression increase corresponds to altered burst firing and CA2+ channel gene expression in LOC neurons. To test this, patch-SEQ will correlate gene expression with electrophysiological properties at the single-cell level. If elevated LOC activity plays a compensatory role following nihl, loss of such activity could exacerbate the central consequences of nihl. To test this, in vivo single-unit recordings from the inferior colliculus (IC) will assess central hyperactivity in young adult mice with intact or ablated LOC systems, taking advantage of recently-developed GATA3FLPO; ucncre; ROSA26FLTG; maptds-DTR mice that allows selective ablation of LOC neurons by diphtheria toxin (DTX) treatment without affecting hearing thresholds. I predict that LOC-ablated mice will show higher spontaneous IC firing following nihl compared to LOC-intact mice. An additional benefit of this approach is the ability to assess LOC function in regulating central gain without nihl; IC recordings in ablated mice are also expected to show elevated baseline firing rates. This project will uncover the cellular mechanisms driving altered efferent activity in pathological conditions, establishing the role of efferents in connecting hearing loss to hyperactivity-related disorders like tinnitus and hyperacusis, and guiding novel strategies for functional recovery.