Thursday, November 21, 2024 11/21/2024

Developmental Determination of Central Auditory Physiology by the Inner Ear

Award Number: U01DC018537
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary: A longstanding and fundamental question of neural development in sensory pathways is: What is the role of the organization of the sensory epithelium in establishing central topographic organization? In the auditory system a direct approach to addressing this question has been elusive because it has not been possible to manipulate the input to the brain from the auditory periphery without either complete ablation of the inner ear or induction of hearing dysfunction. The proposed experiments will establish for the first time, a model of repatterned frequency representation in the chick inner ear by utilizing a new genetic manipulation in embryos. This manipulation takes advantage of the known genetic factors that establish the organization of the ear at a very early developmental stage that precedes the auditory nerve innervation of the central nervous system. By overexpressing one of these factors, bone morphogenic protein 7 (BMP7), inner ears develop almost exclusively low frequency hair cell phenotypes. In the first brain structure to receive auditory nerve input, the cochlear nucleus, neurons express a number of well characterized biophysical and morphological specializations for processing sound in specific frequencies. Frequency specific tuning is topographically mapped in both the ear and auditory brain regions, a feature known as 'tonotopy.' Thus, neural specialization occurs along an orderly tonotopic map in the cochlear nucleus. The central hypothesis of this proposal is that tonotopic refinement of specializations in the cochlear nucleus is developmentally determined by patterned input from the inner ear, and is not independently induced by local cues in the developing brain. This hypothesis is now testable using animals with tonotopically altered inner ears. The first aim of this proposal is to examine whether the BMP7 manipulation indeed induces repatterning of hair cell tuning mechanism in the inner ear. The second aim investigates the electrical input response properties of cochlear nucleus neurons in animals that have developed with tonotopically altered inner ears. Finally, the third aim will investigate the dependence of cochlear nucleus structure on normal topographic innervation from the auditory nerve. These research objectives, if successful, will provide new insights into the mechanisms that establish the functional organization of auditory structures. Revelation of these mechanisms may be informative to optimization strategies for therapeutic interventions in early deafness or hearing loss that aim to preserve normal function and capacity in auditory circuitry.


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: 2024 ( Subtotal = $384,712 )
2024	2024	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Research Related to Deafness and Communication Disorders	000	3	4/17/2024	NON-COMPETING CONTINUATION	$384,712
														Subtotal = $384,712

Issue Date FY: 2023 ( Subtotal = $376,002 )
2023	2023	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Research Related to Deafness and Communication Disorders	000	2	5/3/2023	NON-COMPETING CONTINUATION	$376,002
2023	2023	LEHIGH UNIVERSITY	526 BRODHEAD AVE	BETHLEHEM	PA	18015	NORTHAMPTON	USA	Research Related to Deafness and Communication Disorders	001	2	5/9/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $376,002

Grand Total All Awards = $760,714

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Developmental Determination of Central Auditory Physiology by the Inner Ear

Award Number: U01DC018537

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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