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BRAIN CONNECTS: Scalable Approaches for Bidirectional Brain-wide Trans-Neuronal Connectivity Mapping of Defined Cell Types

Award Number: U01NS136405
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: 08/15/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2027

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BRAIN CONNECTS: Scalable Approaches for Bidirectional Brain-wide Trans-Neuronal Connectivity Mapping of Defined Cell Types - PROJECT SUMMARY A major goal in modern neuroscience is to comprehensively map circuits of synaptically connected cell types throughout the mammalian brain. The key technological gap this proposal will address is the need for systematic, high-throughput methods to define neuronal wiring diagrams at the level of defined cell types. The overall objectives of this application are to establish a suite of tools that combine spatial transcriptomics and connectomics into scalable, high-throughput methods and analytical tools for linking the molecular identities of neural cell types to their synaptic connectivity. The rationale for the proposed work is that scalable, rapid means of unraveling circuit connectivity with cell type-specificity will accelerate efforts to unravel circuit structure and function throughout the brain. These goals will be pursued in three specific aims: 1) Establish and validate a spatial transcriptomic approach, TransA-MERFISH, for multiplexed, brain-wide mapping of the postsynaptic neurons of genetically defined starter cells; 2) Establish and validate a spatial transcriptomic approach, TransR- MERFISH, for multiplexed, brain-wide mapping of the presynaptic neurons of genetically defined starter cells; and 3) Establish computational platforms to decode the information gathered from TransA- and TransR- MERFISH. These collaborative experiments will draw on diverse expertise to merge connectomic methods developed by the applicants with spatial transcriptomic methods and analytical tools. These methods will be validated in the mouse brain, including multiple cortical and midbrain areas. The research proposed in this application is innovative because it establishes new tools to comprehensively map in situ synaptic inputs and outputs at the level of molecularly defined cell types. The proposed research will use commercial equipment to facilitate the easy adoption of these techniques by other labs. However, the approaches are also easily extensible to other spatial transcriptomics methods. The proposed research is significant because it is expected to yield a scalable, user-friendly, rapid means of unraveling circuit connectivity with cell type-specificity and defining circuit connectivity. Ultimately, the scalable tools developed here have the potential to accelerate investigations of neural circuit assembly and function in a variety of model organisms.


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: 2026 ( Subtotal = $0 )
2026	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/4/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $1,795,855 )
2025	2025	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	7/3/2025	NON-COMPETING CONTINUATION	$1,795,855
														Subtotal = $1,795,855

Issue Date FY: 2024 ( Subtotal = $2,347,750 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/8/2024	NEW	$2,347,750
														Subtotal = $2,347,750

Grand Total All Awards = $4,143,605

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BRAIN CONNECTS: Scalable Approaches for Bidirectional Brain-wide Trans-Neuronal Connectivity Mapping of Defined Cell Types

Award Number: U01NS136405

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: 08/15/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2027

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