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Development of Neuronal Circuits in the Auditory Systems

Award Number: R01DC004199
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The long-term goal of our research is to understand the cellular mechanisms by which precisely organized auditory networks become established and how this process is influenced by normal and abnormal neuronal activity. The proposed project is aimed at elucidating these mechanisms in a tonotopically organized, inhibitory sound localization pathway in the auditory brainstem. Specifically, we aim to shed light on the mechanisms by which the inhibitory connections from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO) become tonotopically organized and functionally fine-tuned. We recently demonstrated that formation of the tonotopic organization of the MMTB-LSO pathway involves specific functional elimination (silencing) and strengthening of GABA/glycinergic connections before hearing onset. We also found that during this period of reorganization, MNTB-LSO synapses can undergo activity- dependent long-term depression that involves cannabinoid signaling and, in addition to GABA and glycine, surprisingly also release glutamate as a third neurotransmitter. Building on these findings we are proposing experiments to a) illuminate the basic cellular and synaptic mechanisms by which MNTB-LSO connections become strengthened or eliminated during circuit reorganization and b) shed light on the seemingly paradoxical phenomenon of glutamate release from GABA/glycinergic MNTB-LSO synapses. To achieve these goals we will apply a variety of modern electrophysiological and imaging techniques, such as whole-cell and perforated patch clamp recordings, confocal calcium imaging, and mapping of functional connectivity with focal photolysis of caged glutamate, in auditory brainstem slices prepared from neonatal mice. The proposed research may provide new insights into the basic rules and activity-dependent mechanisms by which primary sound localization circuits in the mammalian brain become assembled and functionally fine- tuned. Detailed knowledge of these mechanisms is crucial for understanding the emergence of abnormal auditory circuits that result from early cochlea damage or malfunction and thus can help us to understand the cause of human communication disorders such as language perception, specific language impairment, and dyslexia that result from impaired auditory processing and that likely have developmental components.


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: 2022 ( Subtotal = -$871 )
2022	2020	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	22	7/13/2022	NON-COMPETING CONTINUATION	-$799
2022	2020	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	22	12/7/2021	NON-COMPETING CONTINUATION	-$72
2022	2009	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Trans-NIH Recovery Act Research Support	002	11	1/11/2022	SUPPLEMENT FOR EXPANSION	-$72
2022	2009	UNIVERSITY OF PITTSBURGH - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION	4200 FIFTH AVENUE	PITTSBURGH	PA	15260	ALLEGHENY	USA	Trans-NIH Recovery Act Research Support	000	11	12/7/2021	SUPPLEMENT FOR EXPANSION	$72
														Subtotal = -$871

Issue Date FY: 2020 ( Subtotal = $531,107 )
2020	2020	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	22	6/5/2020	NON-COMPETING CONTINUATION	$531,107
														Subtotal = $531,107

Issue Date FY: 2019 ( Subtotal = $531,107 )
2019	2019	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	21	6/5/2019	NON-COMPETING CONTINUATION	$531,107
														Subtotal = $531,107

Issue Date FY: 2018 ( Subtotal = $531,107 )
2018	2018	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	20	6/8/2018	NON-COMPETING CONTINUATION	$531,107
														Subtotal = $531,107

Issue Date FY: 2017 ( Subtotal = $527,713 )
2017	2017	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	002	19	6/13/2017	NON-COMPETING CONTINUATION	$527,713
2017	2016	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	18	12/5/2016	COMPETING CONTINUATION	$42,509
2017	2015	UNIVERSITY OF PITTSBURGH THE	3520 FIFTH AVE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	17	11/30/2016	NON-COMPETING CONTINUATION	-$42,509
														Subtotal = $527,713

Issue Date FY: 2016 ( Subtotal = $522,623 )
2016	2016	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	18	5/27/2016	COMPETING CONTINUATION	$522,623
														Subtotal = $522,623

Issue Date FY: 2015 ( Subtotal = $532,592 )
2015	2015	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	17	6/10/2015	NON-COMPETING CONTINUATION	$532,592
														Subtotal = $532,592

Issue Date FY: 2014 ( Subtotal = $537,973 )
2014	2014	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	16	6/3/2014	NON-COMPETING CONTINUATION	$537,973
														Subtotal = $537,973

Issue Date FY: 2013 ( Subtotal = $511,074 )
2013	2013	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	15	6/6/2013	NON-COMPETING CONTINUATION	$511,074
														Subtotal = $511,074

Issue Date FY: 2012 ( Subtotal = $537,973 )
2012	2012	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	14	5/10/2012	NON-COMPETING CONTINUATION	$537,973
														Subtotal = $537,973

Issue Date FY: 2011 ( Subtotal = $550,848 )
2011	2011	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	002	13	6/15/2011	COMPETING CONTINUATION	$550,848
2011	2010	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	12	6/15/2011	NON-COMPETING CONTINUATION	$0
2011	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Recovery Act Research Support	000	11	4/7/2011	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $550,848

Issue Date FY: 2010 ( Subtotal = $401,541 )
2010	2010	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	12	1/20/2010	NON-COMPETING CONTINUATION	$36,504
2010	2010	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	12	11/12/2009	NON-COMPETING CONTINUATION	$365,037
														Subtotal = $401,541

Issue Date FY: 2009 ( Subtotal = $677,493 )
2009	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	11	11/14/2008	NON-COMPETING CONTINUATION	$398,928
2009	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	11	3/16/2009	NON-COMPETING CONTINUATION	$44,325
2009	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Recovery Act Research Support	003	11	8/4/2009	SUPPLEMENT FOR EXPANSION	$2,546
2009	2009	UNIVERSITY OF PITTSBURGH	123 UNIVERSITY PLACE	PITTSBURGH	PA	15213	ALLEGHENY	USA	Trans-NIH Recovery Act Research Support	002	11	7/10/2009	SUPPLEMENT FOR EXPANSION	$231,694
														Subtotal = $677,493

Issue Date FY: 2008 ( Subtotal = $331,296 )
2008	2008	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	10	9/8/2008	SUPPLEMENT FOR EXPANSION	$37,392
2008	2008	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	10	11/20/2007	NON-COMPETING CONTINUATION	$293,904
														Subtotal = $331,296

Issue Date FY: 2007 ( Subtotal = $298,026 )
2007	2007	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	9	11/14/2006	NON-COMPETING CONTINUATION	$298,026
														Subtotal = $298,026

Issue Date FY: 2006 ( Subtotal = $306,838 )
2006	2006	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	001	8	1/6/2006	SUPPLEMENT FOR EXPANSION	$11,408
2006	2006	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	8	12/1/2005	COMPETING CONTINUATION	$295,430
														Subtotal = $306,838

Issue Date FY: 2005 ( Subtotal = $54,439 )
2005	2005	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	7	7/12/2005	NON-COMPETING CONTINUATION	$54,439
														Subtotal = $54,439

Issue Date FY: 2004 ( Subtotal = $211,416 )
2004	2004	UNIVERSITY OF PITTSBURGH	3017 CATHEDRAL OF LEARNING	PITTSBURGH	PA	15260	ALLEGHENY	USA	Research Related to Deafness and Communication Disorders	000	6	7/16/2004	NON-COMPETING CONTINUATION	$211,416
														Subtotal = $211,416

Issue Date FY: 2003 ( Subtotal = $254,938 ) (Continued on the next page)
Grand Total All Awards = $8,696,038

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Development of Neuronal Circuits in the Auditory Systems

Award Number: R01DC004199

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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