# An anatomical cell type atlas of gene expression, morphology and connectivity

> **NIH NIH U19** · ALLEN INSTITUTE · 2021 · $5,507,005

## Abstract

Project Summary (Research Segment 2)
The brain circuit is an intricately interconnected network of numerous cell types. To understand the principles
of information processing in the brain circuit, it is essential to determine a catalog of cell types, how they are
distributed throughout the brain, and how they are connected to each other. A cell's precise location within the
brain (where is it?), its specific dendritic and axonal morphology (what does it look like?), and its structural
connectivity with other cells in circuits and networks (who does it connect to?) are all critical anatomical factors
which contribute to the definition and accounting of different cell types. We will produce comprehensive
anatomical cell census data from brains of adult male and female mice, leveraging our existing mouse brain
reference and connectivity atlases, and employing three major scalable approaches. We will map the spatial
organization of transcriptomic cell types identified in Research Segment 1 using multiplexed error-robust
fluorescence in situ hybridization (MERFISH) with combinatorial marker gene sets identified in the single-cell
RNA-seq experiments. Furthermore, we will use MERFISH to determine the microenvironment, tissue
composition and ratio of various cell types. We will generate full neuronal morphologies of representative cell
types in major brain regions, using two different high-throughput and high-resolution whole-brain fluorescent
imaging approaches and semi-automated morphology reconstruction methods. These systematically collected
data will be used to discover rules underlying cell types as defined by their full dendritic and axonal
morphologies. We will use an optimized rabies tracing system to do monosynaptic, retrograde trans-synaptic
tracing to map whole-brain inputs to genetically-identified cell populations brain-wide. By combining this with
the Allen Institute's already created anterograde projectome, we will be able to generate a first iteration of the
mesoscale, input/output circuit wiring diagram. These different types of anatomical data will be integrated with
each other and with other cell type characterization data modalities in a variety of ways, including coupling
rabies tracing, full neuronal morphology, or in vivo functional imaging with multiplexed FISH, to derive an
integrated cell type classification scheme.

## Key facts

- **NIH application ID:** 10168632
- **Project number:** 5U19MH114830-05
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Hongkui Zeng
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $5,507,005
- **Award type:** 5
- **Project period:** 2017-09-20 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168632

## Citation

> US National Institutes of Health, RePORTER application 10168632, An anatomical cell type atlas of gene expression, morphology and connectivity (5U19MH114830-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168632. Licensed CC0.

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