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Mechanisms of hypersensitivity to sound-induced cochlear damage

Award Number: R01DC013048
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: 03/01/2013
PERIOD OF PERFORMANCE END DATE: 01/31/2030

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Mechanisms of hypersensitivity to sound-induced cochlear damage - Project Summary Sexually mature females have enhanced auditory nerve encoding of loud sounds compared to males. While there is evidence that this sex difference is mediated by gonad-derived hormones, there has been little progress in the field to understand mechanistically how these hormones mediate their effects. Our published and preliminary data in mice show sex differences in hearing sensitivity in adolescence. Also, in adolescence, we find structural sex differences in the maturation of cochlear afferent synapses. Adolescence is a critical period in humans and other mammals where distinct structural and functional changes coincide with behavioral maturation. In fact, long-lasting behavioral deficits in response to diminished adolescent sensory experience occur in rodents. We will use state-of-the-art anatomical approaches at the light and electron microscopy (EM) levels, including serial EM-tomography, Xenium in situ hybridization, confocal imaging, and electrophysiological studies to determine underlying sex differences in adolescents. Aim 1 will test the hypothesis of a distinct structural and molecular refinement of cochlear ribbon synapses in adolescent females and males. These studies will increase our understanding of why females exhibit greater discharge synchrony or are better protected from noise- induced hearing loss than males, especially before menopause. In Aim 2, we will test that gonad-derived estradiol and androgens refine the relative ratios of Type I spiral ganglion neuron (SGN) subtypes by regulating the expression of genes relating to cell excitability. With these studies, we will begin understanding the role of sex hormones on SGN synchrony via the classical genomic effects of steroids. Studies in Aim 3 will test that reduced sensory experience in adolescence differentially alters key pre- and post-synaptic structural and molecular features of modiolar and pillar-side cochlear ribbon synapses in females and males. These studies will increase our understanding of sex differences in cochlear adaptation to sensory experience from adolescence to adulthood. This project will provide unique information to understand the sex-specific cellular and molecular mechanisms underlying sound coding's temporal precision in normal and hearing-impaired adolescent mice, which are still largely unknown.


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 = $672,058 )
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	12	1/13/2026	NON-COMPETING CONTINUATION	$604,853
2026	2026	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	12	2/10/2026	NON-COMPETING CONTINUATION	$67,205
														Subtotal = $672,058

Issue Date FY: 2025 ( Subtotal = $706,738 )
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	11	1/21/2025	COMPETING CONTINUATION	$706,738
2025	2025	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	003	11	9/3/2025	COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	002	10	8/7/2025	NON-COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	10	1/21/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $706,738

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	10	6/28/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $579,113 )
2023	2023	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	10	6/27/2023	NON-COMPETING CONTINUATION	$579,113
2023	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	9	10/20/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $579,113

Issue Date FY: 2022 ( Subtotal = $579,113 )
2022	2022	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	9	7/25/2022	NON-COMPETING CONTINUATION	$579,113
														Subtotal = $579,113

Issue Date FY: 2021 ( Subtotal = $589,359 )
2021	2021	UNIVERSITY OF PITTSBURGH, THE	4200 5TH AVE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	8	7/1/2021	NON-COMPETING CONTINUATION	$589,359
														Subtotal = $589,359

Issue Date FY: 2020 ( Subtotal = $663,804 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	002	7	6/23/2020	NON-COMPETING CONTINUATION	$589,322
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	6	2/5/2020	COMPETING CONTINUATION	$0
2020	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	6	1/7/2020	COMPETING CONTINUATION	$74,482
														Subtotal = $663,804

Issue Date FY: 2019 ( Subtotal = $603,217 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	6	4/12/2019	COMPETING CONTINUATION	$603,217
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	6	4/17/2019	COMPETING CONTINUATION	$0
														Subtotal = $603,217

Issue Date FY: 2018 ( Subtotal = -$8 )
2018	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	5	7/17/2018	NON-COMPETING CONTINUATION	$0
2018	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	5	9/10/2018	NON-COMPETING CONTINUATION	-$8
														Subtotal = -$8

Issue Date FY: 2017 ( Subtotal = $472,124 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	5	2/9/2017	NON-COMPETING CONTINUATION	$424,910
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	5	5/24/2017	NON-COMPETING CONTINUATION	$47,214
														Subtotal = $472,124

Issue Date FY: 2016 ( Subtotal = $468,851 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	4	1/19/2016	EXTENSION WITH OR WITHOUT FUNDS	$468,851
														Subtotal = $468,851

Issue Date FY: 2015 ( Subtotal = $551,387 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	3	2/5/2015	NON-COMPETING CONTINUATION	$551,387
														Subtotal = $551,387

Issue Date FY: 2014 ( Subtotal = $557,676 )
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	2	2/24/2014	SUPPLEMENT FOR EXPANSION	$88,472
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	2	2/12/2014	NON-COMPETING CONTINUATION	$469,204
														Subtotal = $557,676

Issue Date FY: 2013 ( Subtotal = $470,656 )
2013	2013	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	1	2/15/2013	NEW	$470,656
														Subtotal = $470,656

Grand Total All Awards = $6,914,088

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Mechanisms of hypersensitivity to sound-induced cochlear damage

Award Number: R01DC013048

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: 03/01/2013

PERIOD OF PERFORMANCE END DATE: 01/31/2030

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