# Development of a non-invasive method to monitor expression and function of optogenetic tools in non-human primates

> **NIH NIH R21** · EMORY UNIVERSITY · 2022 · $273,000

## Abstract

PROJECT SUMMARY
 Optogenetic methods have been used extensively to expand our knowledge of the normal and pathological
roles of the basal ganglia and related brain areas involved in Parkinson’s disease (PD). This revolutionary tech-
nology has, so far, been restricted to studies in rodent models of parkinsonism, while technical constraints have
largely limited the use of optogenetic experimentation in non-human primates (NHPs). The scarcity of optoge-
netics studies in NHPs is not limited to PD-related research. A critical limitation to the expansion of optogenetics
in primates is the lack of non-invasive methods to monitor opsin expression in vivo. Postmortem histology re-
mains the only reliable method to confirm the correct targeting of brain regions and level of opsin expression in
NHPs. Evidently, this method does not allow for in vivo corrections of experimental approaches.
 Expansion of the use of optogenetics in NHPs require the development of methods to monitor the temporal
course and level of opsin expression, so that insufficient expression levels can be detected and corrected in vivo,
thus avoiding costly experimental failures, and reducing the number of NHPs needed for research. We propose
a non-invasive approach to monitor opsin expression repeatedly in vivo, based on positron imaging tomography
(PET) imaging in NHPs. We will use an innovative version of the excitatory opsin channelrhodopsin-2 (ChR2),
in which the opsin is fused to the ligand binding domain of the human estrogen receptor alpha, creating the novel
opsin “ChRERa”. The radiolabeled fluorinated estradiol analog, [18F]-fluoroestradiol ([18F]-FES), binds strongly
to ChRERa, and the brain distribution of [18F]-FES can be visualized with PET. We will use ChRERa and re-
peated [18F]-FES PET scans to monitor opsin expression in Rhesus monkeys longitudinally. Using viral vectors,
we will express ChRERa in the motor portion of the striatum, and then conduct several [18F]-FES PET scans
over the next 12 months to describe the time course of PET detectable opsin expression. In parallel, we will
examine if the PET-identified pattern of ChRERa expression corresponds to the presence of functional opsins,
by conducting extracellular recordings during light activation. Finally, we will examine the correspondence be-
tween the opsin expression pattern found in the [18F]-FES PET scans and the opsin distribution identified with
post-mortem histology. These studies will establish a fundamental technology to evaluate in vivo the distribution
of opsins in the NHP. In alignment with the purpose of this FOA PA-21-219 (“Joint NINDS/NIMH Exploratory
Neuroscience Research Grant”), these studies have the long-term goal of using ChRERa and [18F]-FES PET
scans in our NHP optogenetic studies of the pathophysiology of parkinsonism. More broadly, validation of a
non-invasive in vivo method to monitor opsin expression could help accelerate reliable use of optogenetics for
the study of NHP models of neur...

## Key facts

- **NIH application ID:** 10451093
- **Project number:** 1R21NS123487-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Adriana Galvan
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $273,000
- **Award type:** 1
- **Project period:** 2022-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10451093

## Citation

> US National Institutes of Health, RePORTER application 10451093, Development of a non-invasive method to monitor expression and function of optogenetic tools in non-human primates (1R21NS123487-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10451093. Licensed CC0.

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