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Christen Crosta_Diversity Supplement: 1 R21 NS122159

Award Number: R21NS122159
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/18/2022
PERIOD OF PERFORMANCE END DATE: 10/31/2024

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Christen Crosta_Diversity Supplement: 1 R21 NS122159 - PROJECT SUMMARY Dendrite morphology determines many aspects of neuronal function, including action potential propagation and information processing. Although emerging evidence suggests that dendrite growth and branching is regulated locally, the lack of optimal measurements at local sites exists. Brain-derived neurotrophic factor (BDNF) is one of the most studied regulators of dendrite development, and we reported that BDNF exerts distinct local effects on the dendritic arbor depending on where on the arbor it is applied. BDNF triggers PKA activation to regulate dendrite branching, yet not much is known about how BDNF activates PKA to promote local dendrite branching. The proposed work aims to utilize cAMP-dependent protein kinase (PKA) activation sensors as part of a Fӧrster resonance energy transfer (FRET)-based imaging platform to study the spatiotemporal regulation of the dendritic arbor by PKA activation. First, we will locally apply PKA activator or inhibitor to the dendrite and show a functional relationship between PKA activity and dendrite branching. A microtubule targeted A-kinase activity reporter (tAKAR4α) that shows high sensitivity and dynamic range and is activated by neuromodulators will be expressed in cultured embryonic rat hippocampal neurons of both sexes. We will measure the time- dependent dynamic distribution of PKA in neurons as dendrites develop and branch over time. Second, it has been reported that nuclear signaling of activated PKA occurs and is highest after stimulation of secondary versus other order dendrites, regardless of distance from the soma. As such, we will construct a new PKA activation sensor, tAKAR4n, that will be targeted to the nucleus and use this new FRET sensor to determine whether nuclear PKA activity increases when secondary, but not other order, dendrites are stimulated with PKA activator. Third, we will use the tAKAR4a FRET sensor and nuclear-targeted AKAR4 probe to determine the mechanism by which BDNF locally regulates the arbor. These studies will shed light on mechanisms that shape neuronal morphology that can then be targeted for therapeutics to restore neuronal connectivity and circuitry after injury due to stroke or TBI or as a result of neurodegenerative diseases.


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 = $0 )
2025	2022	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/25/2025	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	12/15/2023	SUPPLEMENT FOR EXPANSION	$0
2024	2021	RUTGERS, THE STATE UNIVERSITY	3 RUTGERS PLZ	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/2/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	2/7/2023	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $92,699 )
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	1/18/2022	SUPPLEMENT FOR EXPANSION	$92,699
2022	2022	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	3/15/2022	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $92,699

Issue Date FY: 2021 ( Subtotal = $431,444 )
2021	2021	RUTGERS, THE STATE UNIVERSITY OF NEW JERSEY	3 RUTGERS PLZA	NEW BRUNSWICK	NJ	08901	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/27/2021	NEW	$431,444
														Subtotal = $431,444

Grand Total All Awards = $524,143

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Christen Crosta_Diversity Supplement: 1 R21 NS122159

Award Number: R21NS122159

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/18/2022

PERIOD OF PERFORMANCE END DATE: 10/31/2024

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