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Near Infrared Genetically Encoded Voltage Indicators (NIR-GEVIs) for All-Optical Electrophysiology (AOE)

Award Number: U01NS099573
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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Attaining effective optical modulation and readout of neuronal circuit activities has been a longstanding goal in neuroscience and is a key near-term aim of the BRAIN Initiative. Such neurotechnology is required to decipher how the brain’s electrical signals relate to perceptual, cognitive, emotional and motor functions. The idea to use light to modulate neuronal activities found its first broadly successful realization with the development of caged glutamate, but only since the use of genetically encoded (optogenetic) actuators such as channelrhodopsin, has this approach become overwhelmingly successful. The idea to use light to record electrical signals in the brain was conceptualized with the discovery of the first voltage-sensitive dyes more than half a century ago. Voltage imaging approaches have contributed much to our understanding of brain physiology, both at the cellular and systems levels, but the broad experimental use of these small molecule dyes suffers from several limitations including invasive staining procedures, pharmacological side effects, and blindness towards cellular diversity. These three limitations have been overcome by the recent invention of genetically-encoded voltage indicators (GEVIs). Although in many aspects superior to classical voltage sensitive dyes, GEVIs have not yet been satisfactorily optimized and their combination with optogenetic modulation has been difficult to achieve in practice. One major obstacle is the overlap of the spectral bands of light used to activate opsin-based actuators and at the same time excite and image available GEVIs. What is required to overcome this hurdle are well performing far red GEVIs that can be orthogonally combined with blue light-activated opsin-based actuators. We propose to use novel near-infrared (NIR) phytochrome-based fluorescent proteins (FPs) to generate a new class of GEVIs that are excited and fluoresce in the NIR spectrum, building on our expertise to generate GEVIs using GFP-like FPs. We plan to combine these NIR-GEVIs with blue-light activated excitatory and inhibitory opsins, to enable an optical approach that expands classical microelectrode-based intracellular single cell current-clamp recordings to large numbers of genetically defined neurons in awake mice. Transgenic mice in which this tool can be activated via Cre-recombinase expressing driver mouse lines will be one of our key deliverables.


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 = -$307,979 )
2023	2018	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE	FACULTY BUILDING SOUTH KENSINGTON C	LONDON				GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/8/2023	NON-COMPETING CONTINUATION	-$307,979
														Subtotal = -$307,979

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2018	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE	FACULTY BUILDING SOUTH KENSINGTON CAMPUS	LONDON				GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/19/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $0 )
2021	2018	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE	FACULTY BUILDING SOUTH KENSINGTON CAMPUS	LONDON				GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/23/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE	EXHIBITION ROAD SOUTH KENSINGTON CAMPUS	LONDON		SW7 2AZ		GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/16/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $924,034 )
2018	2018	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE	EXHIBITION ROAD	LONDON		SW7 2AZ		GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	7/2/2018	NON-COMPETING CONTINUATION	$924,034
														Subtotal = $924,034

Issue Date FY: 2017 ( Subtotal = $974,199 )
2017	2017	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE	EXHIBITION ROAD	LONDON		SW7 2AZ		GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/6/2017	NON-COMPETING CONTINUATION	$974,199
2017	2017	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE	EXHIBITION ROAD	LONDON		SW7 2AZ		GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	7/13/2017	NON-COMPETING CONTINUATION	$0
														Subtotal = $974,199

Issue Date FY: 2016 ( Subtotal = $1,047,790 )
2016	2016	IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY & MEDICINE	EXHIBITION ROAD	LONDON				GBR	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/21/2016	NEW	$1,047,790
														Subtotal = $1,047,790

Grand Total All Awards = $2,638,044

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Near Infrared Genetically Encoded Voltage Indicators (NIR-GEVIs) for All-Optical Electrophysiology (AOE)

Award Number: U01NS099573

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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