Thursday, November 21, 2024 11/21/2024

Role of SNARE Interactions in Central Synapse Function

Award Number: R01MH066198
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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View Award Abstract

Synaptic vesicles are distinct organelles that require multiple integral protein components to be functional. Despite this complexity, following exocytosis, synaptic vesicles are retrieved, recycled and reused swiftly within several seconds with high fidelity. The exact mechanisms that underlie this process remain poorly understood. In this renewal application, we propose to investigate mechanisms underlying synaptic vesicle exocytosis-endocytosis process by visualizing the fusion and retrieval of single synaptic vesicles using fluorescence imaging methodologies we developed in the last five years. In our hands, this imaging approach has become rather routine and versatile, amenable to molecular manipulations as well as multimodal imaging at physiological temperatures with high temporal resolution. Monitoring exo-endocytosis of single synaptic vesicles enables us to dissect permissive and instructive signals that regulate synaptic vesicle retrieval. Using this approach, our recent experiments suggested a limited role for the classical endocytosis machinery, while implying a critical role for the exocytotic fusion machinery, in regulation of quantal single vesicle endocytosis. In this renewal application, we will fully expand these initial findings and interrogate the mechanisms underlying single synaptic vesicle retrieval at physiological temperatures with high temporal resolution. To achieve this goal, we propose three specific aims. In the first aim, we will study the role of dynamins in single synaptic vesicle retrieval. The second aim will focus on the role of the SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) fusion machinery in single synaptic vesicle retrieval. Finally, the third aim will investigate the roles of endosomal SNAREs in spontaneous synaptic vesicle retrieval. Collectively, these complementary experiments will elucidate the molecular mechanisms ensuring the fidelity and the time course of synaptic vesicle retrieval in central synapses. Information attained from these studies will provide new insight to the synaptic substrates that may be affected by a number of in neuropsychiatric and neurological disorders including major depressive disorder, autism and schizophrenia.


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 = -$3,702 )
2025	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	21	10/10/2024	NON-COMPETING CONTINUATION	-$3,702
														Subtotal = -$3,702

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	21	3/1/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $506,253 )
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	21	2/7/2023	NON-COMPETING CONTINUATION	$50,625
2023	2023	VANDERBILT UNIVERSITY	110 21ST AVE S	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	21	12/1/2022	NON-COMPETING CONTINUATION	$455,628
														Subtotal = $506,253

Issue Date FY: 2022 ( Subtotal = $506,386 )
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	20	5/10/2022	NON-COMPETING CONTINUATION	$50,639
2022	2022	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	20	11/9/2021	NON-COMPETING CONTINUATION	$455,747
														Subtotal = $506,386

Issue Date FY: 2021 ( Subtotal = $506,516 )
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	19	4/7/2021	NON-COMPETING CONTINUATION	$50,652
2021	2021	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	19	11/10/2020	NON-COMPETING CONTINUATION	$455,864
														Subtotal = $506,516

Issue Date FY: 2020 ( Subtotal = $533,685 )
2020	2020	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	18	11/22/2019	NON-COMPETING CONTINUATION	$480,316
2020	2020	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	001	18	2/5/2020	NON-COMPETING CONTINUATION	$53,369
2020	2019	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	002	17	4/28/2020	COMPETING CONTINUATION	$1,455
2020	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	003	16	4/28/2020	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$1,455
														Subtotal = $533,685

Issue Date FY: 2019 ( Subtotal = $529,795 )
2019	2019	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	008	17	9/24/2019	COMPETING CONTINUATION	$0
2019	2019	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	006	17	4/30/2019	COMPETING CONTINUATION	$168,063
2019	2019	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	005	17	1/31/2019	COMPETING CONTINUATION	$534,295
2019	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	007	16	4/30/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$168,063
2019	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	003	15	1/7/2019	NON-COMPETING CONTINUATION	-$500
2019	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	001	15	11/13/2018	NON-COMPETING CONTINUATION	-$397,000
2019	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	000	16	11/12/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$392,500
2019	2018	VANDERBILT UNIVERSITY, THE	110 21ST AVENUE S STE 800	NASHVILLE	TN	37203	DAVIDSON	USA	Mental Health Research Grants	004	16	1/7/2019	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$23,848
2019	2017	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	002	14	1/7/2019	NON-COMPETING CONTINUATION	-$23,348
														Subtotal = $529,795

Issue Date FY: 2018 ( Subtotal = $397,500 )
2018	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	15	1/5/2018	NON-COMPETING CONTINUATION	$357,750
2018	2018	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	001	15	6/20/2018	NON-COMPETING CONTINUATION	$39,750
														Subtotal = $397,500

Issue Date FY: 2017 ( Subtotal = $397,500 )
2017	2017	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER, THE	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	001	14	6/20/2017	NON-COMPETING CONTINUATION	$39,750
2017	2017	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER	5323 HARRY HINES BLVD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	14	1/9/2017	NON-COMPETING CONTINUATION	$357,750
														Subtotal = $397,500

Issue Date FY: 2016 ( Subtotal = $397,500 )
2016	2016	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	13	1/25/2016	NON-COMPETING CONTINUATION	$397,500
														Subtotal = $397,500

Issue Date FY: 2015 ( Subtotal = $397,500 )
2015	2015	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	12	4/10/2015	NON-COMPETING CONTINUATION	$397,500
														Subtotal = $397,500

Issue Date FY: 2014 ( Subtotal = $397,500 )
2014	2014	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	11	4/11/2014	COMPETING CONTINUATION	$397,500
														Subtotal = $397,500

Issue Date FY: 2013 ( Subtotal = $373,032 )
2013	2013	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	10	5/8/2013	NON-COMPETING CONTINUATION	$373,032
														Subtotal = $373,032

Issue Date FY: 2012 ( Subtotal = $388,575 )
2012	2012	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	9	4/30/2012	NON-COMPETING CONTINUATION	$388,575
														Subtotal = $388,575

Issue Date FY: 2011 ( Subtotal = $388,575 )
2011	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	8	4/15/2011	NON-COMPETING CONTINUATION	$353,250
2011	2011	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	001	8	7/23/2011	NON-COMPETING CONTINUATION	$35,325
														Subtotal = $388,575

Issue Date FY: 2010 ( Subtotal = $392,500 )
2010	2010	UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CTR DALLAS	5323 HARRY HINES BOULEVARD	DALLAS	TX	75390	DALLAS	USA	Mental Health Research Grants	000	7	4/28/2010	NON-COMPETING CONTINUATION	$392,500
														Subtotal = $392,500

Issue Date FY: 2009 ( Subtotal = $392,500 ) (Continued on the next page)
Grand Total All Awards = $7,869,916

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Role of SNARE Interactions in Central Synapse Function

Award Number: R01MH066198

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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