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Molecular mechanism of synapse assembly and function

Award Number: R01NS078179
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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The strength of synaptic connections plays a critical role in determining information flow within neural circuits and establishing how circuits can be modified in response to changing inputs. A key parameter of synaptic strength is the probability of neurotransmitter release from the presynaptic neuron. Neurotransmitter release depends on localized calcium influx triggering fusion of molecularly primed synaptic vesicles at specialized domains of presynaptic terminals called active zones. We and others have found that conserved proteins of the active zone cytomatrix regulate key determinants of release probability, including the number of release- ready synaptic vesicles, calcium channels clustering, and the spatial coupling of vesicles and channels. Presynaptic release properties vary considerably even between neighboring AZs of the same neuron. Yet, how proteins of the conserved AZ cytomatrix act locally to generate a diversity of synaptic strengths is not understood. Emerging observations, including our own preliminary data, indicate that AZ cytomatrix proteins are differentially deployed at functionally distinct synapses, suggesting a flexible strategy for achieving functional diversity. Here, we build on our advances in understanding local determinants of synaptic function to elucidate how active zones are organized to achieve synapse-specific neurotransmitter release properties (Aim 1), how synapses are reorganized during plasticity (Aim 2), and how functional heterogeneity interacts with plasticity to support circuit function in response to changing inputs (Aim 3).


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: 2023 ( Subtotal = $345,500 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	12/15/2022	NON-COMPETING CONTINUATION	$310,950
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	10	1/30/2023	NON-COMPETING CONTINUATION	$34,550
														Subtotal = $345,500

Issue Date FY: 2022 ( Subtotal = $345,500 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	9	4/22/2022	NON-COMPETING CONTINUATION	$34,551
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	9	12/31/2021	NON-COMPETING CONTINUATION	$310,949
														Subtotal = $345,500

Issue Date FY: 2021 ( Subtotal = $504,583 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	1/18/2021	NON-COMPETING CONTINUATION	$34,551
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	12/28/2020	NON-COMPETING CONTINUATION	$310,949
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	8	8/27/2021	SUPPLEMENT FOR EXPANSION	$159,083
														Subtotal = $504,583

Issue Date FY: 2020 ( Subtotal = $345,500 )
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	11/27/2019	NON-COMPETING CONTINUATION	$310,949
2020	2020	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	2/10/2020	NON-COMPETING CONTINUATION	$34,551
														Subtotal = $345,500

Issue Date FY: 2019 ( Subtotal = $359,172 )
2019	2019	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	6	1/9/2019	COMPETING CONTINUATION	$235,795
2019	2019	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	12/14/2018	COMPETING CONTINUATION	$359,172
2019	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/13/2018	NON-COMPETING CONTINUATION	$0
2019	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	1/9/2019	NON-COMPETING CONTINUATION	-$235,795
														Subtotal = $359,172

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	6/21/2018	NON-COMPETING CONTINUATION	$0
2018	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	5	8/3/2018	NON-COMPETING CONTINUATION	$0
2018	2016	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	6/13/2018	EXTENSION WITH OR WITHOUT FUNDS	$6,794
2018	2015	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	6/13/2018	NON-COMPETING CONTINUATION	-$6,794
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $325,684 )
2017	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/14/2017	NON-COMPETING CONTINUATION	$293,115
2017	2017	UNIVERSITY OF WISCONSIN SYSTEM	21 N PARK ST STE 6401	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	6/7/2017	NON-COMPETING CONTINUATION	$32,569
														Subtotal = $325,684

Issue Date FY: 2016 ( Subtotal = $325,684 )
2016	2016	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/21/2016	EXTENSION WITH OR WITHOUT FUNDS	$325,684
														Subtotal = $325,684

Issue Date FY: 2015 ( Subtotal = $344,843 )
2015	2015	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	4/29/2015	NON-COMPETING CONTINUATION	$344,843
														Subtotal = $344,843

Issue Date FY: 2014 ( Subtotal = $398,484 )
2014	2014	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/27/2014	SUPPLEMENT FOR EXPANSION	$19,159
2014	2014	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/24/2014	NON-COMPETING CONTINUATION	$379,325
														Subtotal = $398,484

Issue Date FY: 2013 ( Subtotal = $325,684 )
2013	2013	UNIVERSITY OF WISCONSIN SYSTEM/BOARD OF REGENTS	21 N PARK ST	MADISON	WI	53715	DANE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/29/2013	NEW	$325,684
														Subtotal = $325,684

Grand Total All Awards = $3,620,634

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Molecular mechanism of synapse assembly and function

Award Number: R01NS078179

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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