# BRAIN CONNECTS: A Center for High-throughput Integrative Mouse Connectomics

> **NIH NIH UM1** · HARVARD UNIVERSITY · 2024 · $3,335,651

## Abstract

Project Summary/Abstract
The proposed project will demonstrate the feasibility of generating a complete synapse-level brain map
(connectome) by developing a serial-section electron microscopy pipeline that could scale to a whole mouse
brain. This work will image 10 cubic millimeters, itself an unprecedentedly large dataset that may exceed tens
of petabytes. Yet the mouse brain is 50 times larger. Reaching this ambitious goal will require advances in
whole-brain staining, imaging, image-processing, analysis, and dissemination tools. We will scale and test
these tools by producing a connectome of the hippocampal formation, a critical brain region for memory and
spatial navigation. Specifically, we will define our volume of interest via microCT scanning of a whole brain.
Then we will cut it into semithin serial sections and image them with multibeam scanning electron microscopy
and ion beam milling. This technique images a thin layer of tissue and then removes it to reveal the next layer
until each section is fully imaged, minimizing distortions caused by previous ultra-thin sectioning approaches.
 The imaging data will be processed by an improved version of our state-of-the-art pipeline. After quality
monitoring and image compression, our automated system will assemble the full volume from imaged slices
and then label tissue elements: neurons, glia, blood vessels, myelin, cell bodies, and synapses. This
reconstruction will then be proofread and registered to the Allen Institute brain atlas, allowing us to relate our
data to other types of data. Our analysis will identify cell types by region and layer, and reveal the detailed
connectivity of hippocampal formation circuits. Using custom software, we will integrate these structural results
on cell types with other approaches based on light microscopy and single-cell gene expression, allowing us to
relate our results to the extensive literature on hippocampal formation structure and function. To promote
diverse perspectives, we will involve undergraduates from underrepresented backgrounds in the proofreading
and scientific discovery phases of our work, offering them mentoring as well as research experience.
 We will turn these data into a lasting resource for the scientific community and the public by scaling up
free access via online sharing tools to allow any interested party to render, proofread, or otherwise analyze the
cells and circuits in this volume. To illustrate how this resource can be combined with other discoveries, we will
define cell types based on their morphology and connectivity, characterize the relationship between these
assignments and transcriptomic-based classifications, and integrate this information with previous work.
Finally, we will define local and long-range microcircuit motifs in our data and use it to identify circuit principles
and mechanisms of memory and spatial cognition, by testing and improving models of the hippocampal
formation. Throughout the project, we will m...

## Key facts

- **NIH application ID:** 10923921
- **Project number:** 5UM1NS132250-02
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Jeff W Lichtman
- **Activity code:** UM1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $3,335,651
- **Award type:** 5
- **Project period:** 2023-09-08 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10923921

## Citation

> US National Institutes of Health, RePORTER application 10923921, BRAIN CONNECTS: A Center for High-throughput Integrative Mouse Connectomics (5UM1NS132250-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10923921. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*