# Methods for anterograde tracing of active circuits

> **NIH MH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2026 · $668,587

## Abstract

Project Summary
A central yet unrealized goal of modern neuroscience is to map all the neural circuits within the brain and the
changes that occur during development, learning, aging, and in disease states. Towards this end, we recently
developed a rationally designed method for anterograde transsynaptic tracing from excitatory presynaptic
neurons that is monosynaptic, activity-dependent, and non-toxic and provides genetic access to postsynaptic
cells. This rational approach has many advantages over traditional methods based on viruses' intrinsic
transsynaptic labeling capabilities. We have shown that in our method, the tracer is released presynaptically
and binds to a postsynaptic protein before being taken up by the postsynaptic cell. The tracer can be fused to
Cre or other recombinases, allowing genetic labeling and access to the postsynaptic cell. Here, using a similar
approach, we will develop a new method for anterograde tracing from inhibitory neurons. This will represent
the first method capable of tracing from genetically determined inhibitory starter cells in an anterograde
direction, monosynaptically, and without retrograde transmission or toxicity. This method will be particularly
valuable because other methods of anterograde tracing that depend on bulk labeling or electrophysiological
activation of postsynaptic cells cannot be used for tracing circuits that originate from inhibitory neurons. In
addition, we will develop an analogous tracer for cholinergic circuits, which cannot currently be efficiently
traced by viruses either in the anterograde or retrograde directions. Finally, we will develop a method for
labeling and providing genetic access to cells that have been either excited or inhibited by specific presynaptic
neurons over a prescribed time period. This application takes advantage of the unique activity dependence of
the transsynaptic labeling techniques that we have developed.

## Key facts

- **NIH application ID:** 11312740
- **Project number:** 5R01MH139680-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** DONALD B ARNOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** MH
- **Fiscal year:** 2026
- **Award amount:** $668,587
- **Award type:** 5
- **Project period:** 2025-04-04T00:00:00 → 2030-02-28T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11312740

## Citation

> US National Institutes of Health, RePORTER application 11312740, Methods for anterograde tracing of active circuits (5R01MH139680-02). Retrieved via AI Analytics 2026-07-03 from https://api.ai-analytics.org/grant/nih/11312740. Licensed CC0.

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