Wednesday, January 22, 2025 1/22/2025

Multiplex interrogation of neuromodulatory signaling in behaving animals with enhanced depth and resolution

Award Number: U01NS120820
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary The dynamic adaptability of the mammalian brain to environmental changes is remarkable, as it is the complexity of the networks of neurons underlying the operations that allow for such adaptations. Although we have some understanding of the anatomical and functional basis of this, we are still lacking a detailed picture of how the modulation of neuronal activity works. What is the timing and locations of these neuromodulator release and relationship with excitatory/inhibitory circuits? How does the neuromodulators circuitry accomplish the regulation of firing and synaptic properties of targeted neurons? Filling these gaps in knowledge would advance our understanding of all aspects of neuromodulator biology and allow discovery of new therapeutic strategies. To help close this gap, we have used creative approaches to the development of genetically encoded to directly report behaviorally triggered and modulated neuromodulator release including serotonin (5-HT), dopamine (DA) and norepinephrine (NE). We have disseminated these indicators to the neuroscience community and spurred major discoveries of novel mechanisms regulating neuromodulator release underlying motivation and addiction. Build on this initial success, we propose to further expand the effectiveness of this toolbox of NM sensors to enable imaging sparse release at depth and subcellular resolution. Our specific goals are to (1) improve the sensitivity of our current sensors to enable robust imaging of sparse neuromodulator release, push their spatial resolution to the subcellular level and increase linearity of response at lower concentrations; (2) expand their spectral range to red/far-red to enhance imaging depth, SNR and in vivo multiplex measurement and manipulation of multiple circuit components using two or three distinct colors, and (3) characterize the possible interference of current sensors with endogenous signaling and systematically validate emerging sensors with a wide-ranging microscopy approaches in vivo. Our strategy relies on a dynamic collaboration between the sensor design team and end users to obtain continuous feedback to implement efficient improvements to the sensors. It is our goal to rapidly disseminate a wide range of well-characterized, highly sensitive indicators for the neuroscience community to be employed to study behaving mice, fish, flies and worms, to enrich our knowledge on the functional roles of neuromodulators in the brain circuitry.


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: 2024 ( Subtotal = $883,967 )
2024	2024	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	8/20/2024	NON-COMPETING CONTINUATION	$883,967
2024	2023	MAX PLANCK FLORIDA CORP	1 MAX PLANCK WAY	JUPITER	FL	33458	PALM BEACH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	2/16/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$570,101
2024	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	2/16/2024	NON-COMPETING CONTINUATION	-$570,101
														Subtotal = $883,967

Issue Date FY: 2023 ( Subtotal = $863,544 )
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/7/2023	NON-COMPETING CONTINUATION	$863,544
2023	2023	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	3	8/10/2023	NON-COMPETING CONTINUATION	$0
2023	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	6/23/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $863,544

Issue Date FY: 2022 ( Subtotal = $863,993 )
2022	2022	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	8/8/2022	NON-COMPETING CONTINUATION	$863,993
2022	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/28/2022	NEW	$0
														Subtotal = $863,993

Issue Date FY: 2021 ( Subtotal = $869,559 )
2021	2021	UNIVERSITY OF CALIFORNIA, DAVIS	1850 RESEARCH PARK DR, STE 300	DAVIS	CA	95618	YOLO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/30/2021	NEW	$869,559
														Subtotal = $869,559

Grand Total All Awards = $3,481,063

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Multiplex interrogation of neuromodulatory signaling in behaving animals with enhanced depth and resolution

Award Number: U01NS120820

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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