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BRAIN CONNECTS: Center for a pipeline of high throughput integrated volumetric electron microscopy for whole mouse brain connectomics

Award Number: UM1NS132253
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: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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BRAIN CONNECTS: Center for a pipeline of high throughput integrated volumetric electron microscopy for whole mouse brain connectomics - Project Summary: Center for whole mouse brain connectomics using high-throughput integrated volumetric electron microscopy (HIVE) Two fundamental components of the structural basis of brain function are cell type composition and the wiring diagram between those cells. Over the past decade there has been paradigm-shifting progress in understanding cell type composition of the brain. Now it’s time to systematically uncover the brain’s wiring diagram and place it into the context of cell types. Knowledge about the complete connectomes in C. elegans and Drosophila have revolutionized the understanding of cell types and circuit function in those systems. Transmission Electron Microscopy (TEM) has consistently led progress in that revolution and has the potential to scale up to the entire mouse brain with technical improvements in certain areas. During the IARPA MICrONS project, members of the HIVE team built a complete pipeline to section and image the mm3 and created the data processing, reconstruction and analysis infrastructure to make cells and connections analyzable. The result was a dataset with the largest EM level reconstructions of cells in any system, with neurons containing more than 14,000 inputs and 15,000 outputs. We accomplished this by applying a rigorous structured science process that is a hallmark of the Allen Institute’s team science approach. In this project we aim to improve our pipeline, developing critical technologies to tackle the challenges of scaling up to the whole mouse brain and linking to cell types. Our proposal will prepare and section an entire hemisphere, image it at 120 nm resolution, and image up to 10 mm3 at synaptic resolution within the Cortical Basal Ganglia Thalamic loop to provide key insights into circuit mechanisms within this circuit. To accomplish this, we will need to improve all individual aspects of the pipeline, while maintaining consistent integration tests that ensure that the pieces work together. We will standardize a whole mouse brain staining protocol and advance the automation of serial sectioning to collection of serial TEM sections across a whole mouse brain. Developments of serial section tilt TEM tomography will allow to scale EM imaging to a whole mouse brain at multiple scales, leveraging the re-imaging capacity of serial section TEM. We will develop open source data processing tools to bring down the cost of segmentation and while improving accuracy and integrating with a real-time globally accessible proofreading and analysis platform. Finally, we will integrate our data with full morphology reconstructions linked to gene expression, allowing us to create an integrated atlas of cell types and connectivity. Our dissemination strategy will further amplify our impact by democratizing access for both the scientific and educational community.


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 = $6,620,937 )
2025	2025	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/22/2025	NON-COMPETING CONTINUATION	$6,620,937
2025	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $6,620,937

Issue Date FY: 2024 ( Subtotal = $5,648,698 )
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	9/12/2024	NON-COMPETING CONTINUATION	$0
2024	2024	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	8/26/2024	NON-COMPETING CONTINUATION	$5,648,698
2024	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/4/2024	NEW	$0
2024	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	4/17/2024	NEW	$0
														Subtotal = $5,648,698

Issue Date FY: 2023 ( Subtotal = $6,132,469 )
2023	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	9/12/2023	NEW	$0
2023	2023	ALLEN INSTITUTE	615 WESTLAKE AVE N	SEATTLE	WA	98109	KING	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	8/31/2023	NEW	$6,132,469
														Subtotal = $6,132,469

Grand Total All Awards = $18,402,104

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BRAIN CONNECTS: Center for a pipeline of high throughput integrated volumetric electron microscopy for whole mouse brain connectomics

Award Number: UM1NS132253

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: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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