# New approaches for chemical-genetic targeting of specific circuits and cell types in the mammalian brain

> **NIH NIH RF1** · SCRIPPS RESEARCH INSTITUTE, THE · 2020 · $2,666,892

## Abstract

The goal of this research is to establish new robust methods for manipulation of specific circuits and genetically
defined neuron types in brains of model organisms with small molecules. While several chemical-genetic
techniques are already available, these techniques have drawbacks that limit their utility. Our recent work
demonstrates that these obstacles can be overcome by using a strategy for acute control of function of proteins
of interest (POI) containing destabilizing domains (DD) with the inexpensive commercially available drug, TMP.
This compound efficiently crosses the blood-brain barrier, stabilizes DD-POIs with a rapid time course, and does
not produce undesired side effects by itself. Since DD tags can be attached to virtually any protein, TMP-inducible
stabilization is applicable to a broad spectrum of experimental paradigms. We propose to generate mouse alleles
and viral vectors encoding DD-POI fusions suitable for applications ranging from ultra-structural imaging to
assessment of complex behaviors. We will develop tools for TMP-dependent recombination of DNA and genome
editing (Aim1), acute labeling of behaviorally relevant neuron populations with a reporter compatible with optical
imaging and electron microscopy (Aim2), and cell-type-specific control of neurotransmitter secretion (Aim3). Our
collaborative team will demonstrate the advantages of these techniques by combining genomics, whole brain
imaging, serial electron microscopy, electrophysiology, optogenetics and behavior. New tools will be compared
side-by-side against existing technologies, and then distributed to the neuroscience community. We anticipate
that these efforts will significantly benefit future studies of the normal brain and mechanisms underlying
neurological diseases.

## Key facts

- **NIH application ID:** 10012597
- **Project number:** 1RF1MH123224-01
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** Anton Maximov
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,666,892
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10012597

## Citation

> US National Institutes of Health, RePORTER application 10012597, New approaches for chemical-genetic targeting of specific circuits and cell types in the mammalian brain (1RF1MH123224-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10012597. Licensed CC0.

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