# Cell-specific Targeting Approaches and Tools

> **NIH NIH U19** · COLD SPRING HARBOR LABORATORY · 2020 · $875,515

## Abstract

SUMMARY – Cell Tool Segment
A brain cell atlas is essential but not sufficient for understanding brain function. Armed with knowledge of the
cell census and wiring diagram of the brain, neuroscientists further need to be able to systematically observe
and manipulate the activity of defined cell types across many contexts. This requires reliable experimental
access to comprehensive sets of neuron types. The overall goal of the Cell Tool Segment is to leverage
molecular and anatomical information gained in the Molecular and Anatomical Research Segments to
establish experimental access to (1) a comprehensive set of forebrain projection neuron types and to (2) rare
and/or fragile populations of cells from the molecular whole-brain Atlas. In addition, we will generate reporter
lines and viral vectors that enable Cre / Flp labeling based on the intersection or subtraction of two driver
lines and/or anatomical (viral) labeling, enabling greater specificity in labeling through application of more
complex identifying criteria. We aim to generate a restricted but highly selected set of knock-in driver lines
that achieves maximal coverage of neuron types at high specificity. We will maximize coverage, specificity,
and impact through combinatorial use of Cre and FlpE alleles, anterograde and retrograde viral vectors,
and/or temporal regulation of recombinase activity to label neuron types based on intersecting criteria. Cell
populations captured by novel markers and driver lines will feed back into the Molecular and Anatomical
segments in an iterative process to refine cell type definition. In addition, these tools will allow the application
of a full range of modern techniques to defined cell populations to achieve concerted in-depth studies,
including physiological and functional studies during circuit operation and behavior. These genetic tools will
not only further our Center's goal of assembling a single-cell atlas of the brain, but also provide the field with
powerful, validated tools to enable systematic studies of brain network organization, function and
development.

## Key facts

- **NIH application ID:** 9937837
- **Project number:** 5U19MH114821-04
- **Recipient organization:** COLD SPRING HARBOR LABORATORY
- **Principal Investigator:** Z JOSH HUANG
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $875,515
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937837

## Citation

> US National Institutes of Health, RePORTER application 9937837, Cell-specific Targeting Approaches and Tools (5U19MH114821-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9937837. Licensed CC0.

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