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Multi-color optical voltage imaging of neural activity in behaving animals

Award Number: U01NS120822
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/15/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2025

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Multi-color optical voltage imaging of neural activity in behaving animals - Abstract Groundbreaking work within the NIH BRAIN Initiative has revealed many new types of neurons and their genetic signatures. The dividends from this research will include sophisticated tools allowing selective genetic access to these cell-types, such as for imaging, optogenetic or tracing studies. To complement these powerful genetic tools, it will be equally important to have new imaging techniques that can reveal how multiple neuron- types work together in the live brain to support information-processing and construct different brain states. To address this challenge, Stanford University and The John B. Pierce Laboratory at Yale University will create optical techniques for imaging the concurrent voltage dynamics of up to 4 separate neuron-types in behaving animals. First, we will combine machine learning methods and an automated, high-throughput protein screening platform to engineer 4 different categories of genetically encoded fluorescent optical indicators of neuronal transmembrane voltage. We will then innovate several types of optical instruments tailored to work in conjunction with the new voltage indicators. These instruments will enable unprecedented studies of voltage rhythms and spiking dynamics in 2–4 genetically identified neuron-types in superficial and deep brain areas of awake behaving animals. One instrument will allow us to track the concurrent, population voltage oscillations of 2 neuron-types in freely behaving rodents. Another instrument, an optical mesoscope, will enable imaging studies of voltage waves and oscillations across the entire neocortical surface of behaving mice. A third device will be a high-speed miniature microscope for tracking neural dynamics at single cell-, single spike-resolution in freely behaving mice. Lastly, we will develop the capability to image with millisecond-scale precision the simultaneous spiking dynamics of 4 targeted neuron-types in either cortical or deep brain areas. Five external beta-tester labs will evaluate all these innovations in live mice and flies and provide critical user-feedback. If our work succeeds, it will be a ‘game-changer’ for studies of brain dynamics, yielding vital knowledge about how different neuron-types synergize their dynamics to shape animal behavior and the brain’s global states in health and disease. To facilitate this outcome, we plan a 5-fold strategy for resource sharing: (i) All voltage-indicator constructs, viral vectors, transgenic flies, software and screening data will be deposited at public repositories for open distribution; (ii) All instrument designs will be published in extensive detail to facilitate replication; (iii) Our novel imaging devices will be integrated into an existing NIH-supported, publicly accessible facility for brain-imaging in rodents; (iv) In project years 2–4, we will conduct 4 training workshops for 40 visiting scientists per year (120 in total) to learn the new technologies firsthand. These visitors will also provide extensive user-feedback; (v) We will license our imaging instruments for commercial distribution. Overall, we expect our project will lead to major conceptual advances in brain science and multiple new technologies that will reshape the practice of mammalian brain imaging.


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 = $742,050 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/23/2024	NON-COMPETING CONTINUATION	$742,050
														Subtotal = $742,050

Issue Date FY: 2024 ( Subtotal = $789,034 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	7/26/2024	NON-COMPETING CONTINUATION	$0
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/28/2023	NON-COMPETING CONTINUATION	$789,034
														Subtotal = $789,034

Issue Date FY: 2023 ( Subtotal = $889,939 )
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	7/26/2023	NON-COMPETING CONTINUATION	$0
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/24/2023	NON-COMPETING CONTINUATION	$889,939
2023	2023	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	6/8/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $889,939

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/21/2021	NEW	$0
2022	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/7/2022	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $875,437 )
2021	2021	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	6/2/2021	NEW	$875,437
														Subtotal = $875,437

Grand Total All Awards = $3,296,460

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Multi-color optical voltage imaging of neural activity in behaving animals

Award Number: U01NS120822

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

PERIOD OF PERFORMANCE START DATE: 06/15/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2025

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