# Photoactivatable systems for controlling transcription and ablating synapses.

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $2,135,623

## Abstract

The advent of optogenetic tools for controlling neuronal function with light has led to dramatic
advances in the understanding of the anatomy and function of neural circuits. Optogenetic tools
for controlling transcription and modifying neuronal connectivity could also be extremely useful
for interrogating neuronal circuits. However, these tools are based on photo-activatable
complexes, and all current versions of such complexes, which depend on photo-isomerization,
have a small amount of background activation in the dark, which makes them difficult to
implement in vivo. The experiments in this grant use a novel photo-activation complex based on
the intrinsically photo-cleavable protein, PhoCl, which displays virtually no activation in the dark,
and thus is appropriate for use in vivo. We will use this complex to develop novel light-
activatable systems for mediating transcription and for ablating excitatory or inhibitory synapses.
The latter application is based on novel technology that we previously developed that uses E3
ligases targeted to synaptic scaffolding proteins to mediate degradation of the scaffolding
proteins. In turn, this results in the structural and functional ablation of synapses that they
support. The final aim of the grant is to optimize the structure of PhoCl so that it can be cleaved
faster and more efficiently with two photon light.

## Key facts

- **NIH application ID:** 9927247
- **Project number:** 1R01NS115610-01
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** DONALD B ARNOLD
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,135,623
- **Award type:** 1
- **Project period:** 2020-09-30 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9927247

## Citation

> US National Institutes of Health, RePORTER application 9927247, Photoactivatable systems for controlling transcription and ablating synapses. (1R01NS115610-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9927247. Licensed CC0.

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