# Trans-synaptic optogenetics: reversible temporal control of activity at defined synaptic connections

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2020 · $177,188

## Abstract

Project Summary/Abstract
The introduction of optogenetic methods for controlling activity in defined subsets of neurons has enabled new
insights into the functional roles of anatomically distinct brain regions implicated in drug addiction. However,
limitations with existing optogenetic tools have made it difficult to address how local connections within a given
brain region enable it to integrate and process multiple inputs from other regions. Here we propose to generate
a fundamentally unique type of optogenetic tool for silencing defined sets of synapses within local microcircuits,
to ultimately understand how they control addiction-related behaviors. Our approach leverages the ability of
presynaptic G protein coupled receptors (GPCRs) to inhibit synaptic transmission. In contrast to existing
approaches that use direct optical activation of light-sensing GPCRs, our approach involves optical activation of
a separate construct on the postsynaptic side of the synaptic cleft, which in turn activates the presynaptic GPCR.
In our two aims, we will develop optogenetic tools capable of trans-cellular GPCR activation using high
throughput assays in cell lines, and then use experiments in neurons to refine these tools to enable trans-synaptic
control of GPCR activation. We will combine optogenetics with electrophysiological readouts in primary neuronal
cultures and brain slices to validate their ability to reversibly inhibit synaptic transmission. Successful completion
of the proposal will establish new tools with unprecedented synaptic-resolution control over neurotransmission.
This technology will enable new experiments to dissect how key brain regions involved in addiction, like the
nucleus accumbens, ventral tegmenetal area, and prefrontal cortex, locally integrate information received from
diverse brain regions.

## Key facts

- **NIH application ID:** 9975126
- **Project number:** 5R21DA049569-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Bryan Copits
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,188
- **Award type:** 5
- **Project period:** 2019-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975126

## Citation

> US National Institutes of Health, RePORTER application 9975126, Trans-synaptic optogenetics: reversible temporal control of activity at defined synaptic connections (5R21DA049569-02). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9975126. Licensed CC0.

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