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Measuring and Modeling the Cochlear Organ-of-Corti Motions Responsible for Inner-and Outer-Hair-Cell Drives and Amplification

Award Number: R01DC007910
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: 02/05/2007
PERIOD OF PERFORMANCE END DATE: 06/30/2028

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Measuring and Modeling the Cochlear Organ-of-Corti Motions Responsible for Inner-and Outer-Hair-Cell Drives and Amplification - Project Summary/Abstract Our knowledge of cochlear organ-of-Corti (OoC) mechanics is undergoing major rethinking. Recent findings show that the reticular lamina (RL) moves much more than the basilar membrane (BM) and with a different phase than previously thought. Our high-resolution optical-coherence-tomography (OCT) imaging and vibrometry measurements in the gerbil high-frequency basal region reveal that the RL at outer-hair-cell (OHC) row 3 (RL3) moves significantly more than at OHC row 1 (RL1). This new discovery suggests that the RL’s mosaic structure, comprised of the cuticular plates of the basally tilted OHCs and apically tilted phalangeal processes (PhPs) is not stiff, but rather bends and/or stretches. Our central hypothesis is that the PhP extensions of the Deiters’ cells (DCs) influence radial and longitudinal motion of the RL mosaic to provide the motion phase and/or magnitude at each OHC row required for cochlear amplification, and sensitive hearing. This hypothesis will be tested by measurements and models to determine if: (1) RL3 motion has a bigger radial component that increases the drive to the OHC3 stereocilia; (2) cytoarchitectural differences below the RL mosaic (e.g., the radial and longitudinal PhP angles) cause the radial and longitudinal motions to differ across the three OHC rows; (3) the outer-tunnel (OT) fluid space is part of a resonant system that has a substantial effect on RL radial motion; and (4) the OoC area changes the pressure in the scala media to produce amplification, and (5) how these motions influence the drive to inner-hair-cell (IHC) stereocilium bundles. A high-resolution, high-framerate OCT system (approx. 2.3-µm axial resolution) will be used to image and measure motions of the OoC in gerbils and mice. We will measure the transverse and radial motions and/or the radial and longitudinal motions of the BM, OHC–DC junctions, RL, OT, and tectorial membrane (TM) in response to acoustic stimulation at multiple sound levels; and will do so at cochlear locations corresponding approximately to 0.5-kHz (apical), 2-kHz (middle), and 45-kHz (basal) locations in gerbil, and 10-kHz (apical), 20-kHz (middle), and 60-kHz (basal) locations in mouse, to determine the applicability of our hypotheses. The measurements from the middle and apical turns in these two species will span much of the 0.02–20 kHz frequency range of human hearing. To translate the measured OoC motions into a detailed understanding of the mechanisms responsible for OHC and IHC stimulation, we will use our OCT images and measurements to build and test passive and active 3D finite-element models of gerbil and mouse cochleae. The models will incorporate, in a viscous-fluid environment, the detailed OoC microanatomy, including the radial and longitudinal PhP angles across the three rows, pillar cells, IHCs, and TM. The models will allow clear relationships to be established between cochlear function and the structure and material properties of the OoC. This work will combine experimental and modeling efforts to deepen our understanding of the complex mechanical interactions within the cochlea that produce amplification and sound transduction.


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: 2025 ( Subtotal = $696,198 )
2025	2025	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	17	5/28/2025	NON-COMPETING CONTINUATION	$696,198
														Subtotal = $696,198

Issue Date FY: 2024 ( Subtotal = $696,198 )
2024	2024	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	16	6/14/2024	NON-COMPETING CONTINUATION	$696,198
2024	2022	MASSACHUSETTS EYE AND EAR INFIRMARY	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	14	6/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $696,198

Issue Date FY: 2023 ( Subtotal = $701,481 )
2023	2023	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	003	15	7/5/2023	COMPETING CONTINUATION	$701,481
2023	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	002	14	6/27/2023	NON-COMPETING CONTINUATION	$0
2023	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	14	4/12/2023	SUPPLEMENT FOR EXPANSION	$0
2023	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	14	4/12/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $701,481

Issue Date FY: 2022 ( Subtotal = $660,043 )
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	14	4/20/2022	NON-COMPETING CONTINUATION	$54,291
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	14	12/15/2021	NON-COMPETING CONTINUATION	$488,619
2022	2022	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	002	14	5/12/2022	SUPPLEMENT FOR EXPANSION	$117,133
														Subtotal = $660,043

Issue Date FY: 2021 ( Subtotal = $545,800 )
2021	2021	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	13	12/15/2020	NON-COMPETING CONTINUATION	$491,220
2021	2021	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	13	1/8/2021	NON-COMPETING CONTINUATION	$54,580
														Subtotal = $545,800

Issue Date FY: 2020 ( Subtotal = $545,800 )
2020	2020	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	12	12/4/2019	NON-COMPETING CONTINUATION	$491,220
2020	2020	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	001	12	1/16/2020	NON-COMPETING CONTINUATION	$54,580
														Subtotal = $545,800

Issue Date FY: 2019 ( Subtotal = $540,156 )
2019	2019	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	11	12/14/2018	NON-COMPETING CONTINUATION	$540,156
														Subtotal = $540,156

Issue Date FY: 2018 ( Subtotal = $556,456 )
2018	2018	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	002	10	3/26/2018	COMPETING CONTINUATION	$1,756
2018	2018	MASSACHUSETTS EYE AND EAR INFIRMARY & PHYSICIAN STAFF, INC.	243 CHARLES ST	BOSTON	MA	02114	SUFFOLK	USA	Research Related to Deafness and Communication Disorders	000	10	2/5/2018	COMPETING CONTINUATION	$556,456
2018	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	9	3/26/2018	EXTENSION WITH OR WITHOUT FUNDS	-$1,756
														Subtotal = $556,456

Issue Date FY: 2017 ( Subtotal = $0 )
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	004	9	8/16/2017	EXTENSION WITH OR WITHOUT FUNDS	$0
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	003	9	7/25/2017	EXTENSION WITH OR WITHOUT FUNDS	$3,974
2017	2016	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	9	11/18/2016	EXTENSION WITH OR WITHOUT FUNDS	$154,669
2017	2015	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	002	8	7/25/2017	NON-COMPETING CONTINUATION	-$3,974
2017	2015	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 SERRA MALL	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	8	11/18/2016	NON-COMPETING CONTINUATION	-$154,669
														Subtotal = $0

Issue Date FY: 2016 ( Subtotal = $546,473 )
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	9	9/2/2016	EXTENSION WITH OR WITHOUT FUNDS	$546,474
2016	2016	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	9	9/15/2016	EXTENSION WITH OR WITHOUT FUNDS	-$1
														Subtotal = $546,473

Issue Date FY: 2015 ( Subtotal = $546,214 )
2015	2015	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	8	7/15/2015	NON-COMPETING CONTINUATION	$546,214
														Subtotal = $546,214

Issue Date FY: 2014 ( Subtotal = $561,480 )
2014	2014	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	7	8/18/2014	NON-COMPETING CONTINUATION	$561,480
														Subtotal = $561,480

Issue Date FY: 2013 ( Subtotal = $536,115 )
2013	2013	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	6	6/18/2013	NON-COMPETING CONTINUATION	$536,115
														Subtotal = $536,115

Issue Date FY: 2012 ( Subtotal = $494,374 )
2012	2012	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	5	6/15/2012	COMPETING CONTINUATION	$494,374
2012	2010	STANFORD UNIVERSITY	616 SERRA STREET	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	4	1/26/2012	NON-COMPETING CONTINUATION	$0
														Subtotal = $494,374

Issue Date FY: 2010 ( Subtotal = $257,432 )
2010	2010	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	4	1/15/2010	NON-COMPETING CONTINUATION	$257,432
														Subtotal = $257,432

Issue Date FY: 2009 ( Subtotal = $259,596 )
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	001	3	3/18/2009	NON-COMPETING CONTINUATION	$25,960
2009	2009	STANFORD UNIVERSITY	651 SERRA STREET, ROOM 110	STANFORD	CA	94305	SANTA CLARA	USA	Research Related to Deafness and Communication Disorders	000	3	1/13/2009	NON-COMPETING CONTINUATION	$233,636
														Subtotal = $259,596

Issue Date FY: 2008 ( Subtotal = $259,695 ) (Continued on the next page)
Grand Total All Awards = $8,666,194

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Measuring and Modeling the Cochlear Organ-of-Corti Motions Responsible for Inner-and Outer-Hair-Cell Drives and Amplification

Award Number: R01DC007910

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: 02/05/2007

PERIOD OF PERFORMANCE END DATE: 06/30/2028

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