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Activity-dependent regulation of auditory nerve synapses in the cochlear nucleus

Award Number: R56DC023596
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/16/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2027

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Activity-dependent regulation of auditory nerve synapses in the cochlear nucleus - Project Summary Both noise exposure and conductive hearing loss can have long-term detrimental effects on hearing. Some of these effects result from long-lasting changes in the central auditory pathway, but these are not well understood. Changes early in the central auditory pathway could have consequences for all downstream sound processing. This proposal focuses on auditory nerve synapses, called endbulbs of Held, which are specialized to relay information from the periphery to binaural hearing circuits with high precision and fidelity. Previous work revealed that sound-driven activity leads to long-term changes in the properties of endbulbs and their postsynaptic targets, bushy cells in the cochlear nucleus. Just one week of increased activity due to environmental noise exposure increases the vesicle pool size and reduces synaptic depression through a pathway that appears to depend on nitric oxide. In addition, postsynaptic excitability increases. These changes contribute to enhancing synaptic fidelity. By contrast, after one week of conductive hearing loss, these synapses show deeper depression, smaller vesicle pool, and decreased postsynaptic excitability, with the consequence of reduced synaptic fidelity. Furthermore, synapses change in response to noise exposure for as little as 8 hr/day over the course of one week, which is similar to the experience of people in industrial occupations. This proposal will build on those results to identify the specific cellular mechanisms underlying this synaptic plasticity. Experiments of Aim #1 identify how nitric oxide drives changes in presynaptic depression and postsynaptic excitability. In Aim #2, modern 3D electron microscopy methods are used to identify ultrastructural rearrangements underlying changes in vesicle pool size. The experiments in Aim #3 examine the cumulative effects of intermittent noise exposure and the extent of recovery after exposure ceases. These experiments will substantially expand the understanding of activity-dependent synaptic changes occurring at the start of the central auditory pathway and provide insights into how to correct or avoid maladapted synapses following noise exposure or conductive hearing loss.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $355,850 )
2026	2026	THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK	520 LEE ENTRANCE STE 211	AMHERST	NY	14228	ERIE	USA	Research Related to Deafness and Communication Disorders	000	1	9/17/2026	NEW	$355,850
														Subtotal = $355,850

Grand Total All Awards = $355,850

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Activity-dependent regulation of auditory nerve synapses in the cochlear nucleus

Award Number: R56DC023596

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/16/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2027

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