# Dendritome mapping of genetically-defined and sparsely-labeled cortical and striatal projection neurons

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $837,445

## Abstract

PROJECT SUMMARY
 Integrating molecular, morphological, and connectomic properties is critical for unbiased
classification of neuronal cell types in the mammalian brain. Here we propose a novel approach to
classify neuronal cell types by brainwide comprehensive profiling of the dendritic morphology of
genetically-defined neurons in the mouse brain. We have developed an innovative mouse genetic tool,
called Mosaicism with Repeat Frameshift (or MORF), which enables sparsely and stochastically labeling
of genetically-defined neurons in mice. MORF reporter mice can label in exquisite detail single neurons from
dendrite and spines to axons and axonal terminals at a labeling frequency of 1-5% of a given neuronal
population. We propose to cross our new MORF lines with Cre mouse lines for striatal medium spiny neurons
(MSNs) of direct- and indirect pathways, and for cortical pyramidal neurons of distinct cortical layers (i.e.
L2/3/4, L5 and L6). Each MORF/Cre mouse will allow us to image the detailed dendritic morphology for
thousands of genetically-defined striatal and cortical neurons (i.e. dendritome). We have also developed and
streamlined imaging and computational tools to acquire and register brainwide single neuron
morphological data onto a standard reference mouse brain atlas. We will digitally reconstruct hundreds of
thousands of MORF-labeled neurons using our novel program called G-Cut. Reconstructed neurons will
subsequently used for morphology based clustering to define new morphological subtypes, which in turn
can be analyzed for the expression of novel molecular markers neuronal cell types (e.g. from single cell
RNA-sequencing). Finally, we will disseminate the data to the Brain Cell Data Center (BCDC) for data
integration with those from other BRAIN Initiative Cell Census Network (BICCN) and for data access by
the broader neuroscience research community.
 In addition to dendritome data generation and analyses, we will further advance our MORF
method by generating new MORF reporter mouse lines with logarithmic fold decrease in the Cre-
dependent labeling frequencies, which will permit imaging of the complete, brainwide morphology of
genetically-defined single neurons that include both dendritic and axonal arborization. Such tool should
greatly facilitate the neuronal morphology based cell type classification. Finally, we will develop
integrated computer hardware and software for domain-specific computing for automated image
processing and neuronal reconstruction, a major bottleneck in analyzing large bioimage datasets.
Altogether we will provide rich dendritome information to enable unbiased, morphology-based neuronal
cell type classification, and novel mouse genetic tools and computer software and hardware to advance
the field of large-scale neuronal morphological imaging and analyses for the comprehensive study of the
mammalian brain.

## Key facts

- **NIH application ID:** 10407481
- **Project number:** 5U01MH117079-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Hong-Wei Dong
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $837,445
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10407481

## Citation

> US National Institutes of Health, RePORTER application 10407481, Dendritome mapping of genetically-defined and sparsely-labeled cortical and striatal projection neurons (5U01MH117079-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10407481. Licensed CC0.

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